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Kumbhari, Vivek, Pietro Familiari, Niels Bjerregaard, Mathieu Pioche, Edward Jones, Weon Ko, Bu Hayee, et al. "Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case–control study." Endoscopy 49, no. 07 (May 4, 2017): 634–42. http://dx.doi.org/10.1055/s-0043-105485.
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Abstract Background and study aims The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER. Patients and methods All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal [GI] endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of < 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI). Results A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m2) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 – 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 – 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %. Conclusion Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.
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Baker, H. V. "Glycolytic gene expression in Saccharomyces cerevisiae: nucleotide sequence of GCR1, null mutants, and evidence for expression." Molecular and Cellular Biology 6, no. 11 (November 1986): 3774–84. http://dx.doi.org/10.1128/mcb.6.11.3774.
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In Saccharomyces cerevisiae, the gcr mutation is known to have a profound effect on the levels of most glycolytic enzymes, reducing them to 5% of normal or less in growth on noncarbohydrates. Here I report the preparation of chromosomal gcr insertion and deletion mutations. The null mutations were recessive, were not lethal, and caused a pattern of glycolytic enzyme deficiency similar to that seen earlier for the gcr1-1 allele, including the partial inducibility by glucose of the residual enzyme activities. DNA sequence analysis showed that GCR1 encoded a protein of molecular weight 94,414, with a very low codon bias index, characteristic of several S. cerevisiae regulatory genes; adjacent 5' and 3' sequences contained elements suggesting that it was transcribed, polyadenylated, and translated. RNA gel transfer hybridization experiments with purified polyadenylated RNA and a probe complementary to the 5' portion of the open reading frame showed that Ger was expressed as a polyadenylated transcript. Together with previous work, the present results suggest that the Gcr product may be a transcriptional factor necessary specifically for the high-level transcription of a limited set of genes whose products, the enzymes of glycolysis, constitute a substantial fraction of cell proteins and are responsible for the primary metabolic flux in many cells.
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Baker, H. V. "Glycolytic gene expression in Saccharomyces cerevisiae: nucleotide sequence of GCR1, null mutants, and evidence for expression." Molecular and Cellular Biology 6, no. 11 (November 1986): 3774–84. http://dx.doi.org/10.1128/mcb.6.11.3774-3784.1986.
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In Saccharomyces cerevisiae, the gcr mutation is known to have a profound effect on the levels of most glycolytic enzymes, reducing them to 5% of normal or less in growth on noncarbohydrates. Here I report the preparation of chromosomal gcr insertion and deletion mutations. The null mutations were recessive, were not lethal, and caused a pattern of glycolytic enzyme deficiency similar to that seen earlier for the gcr1-1 allele, including the partial inducibility by glucose of the residual enzyme activities. DNA sequence analysis showed that GCR1 encoded a protein of molecular weight 94,414, with a very low codon bias index, characteristic of several S. cerevisiae regulatory genes; adjacent 5' and 3' sequences contained elements suggesting that it was transcribed, polyadenylated, and translated. RNA gel transfer hybridization experiments with purified polyadenylated RNA and a probe complementary to the 5' portion of the open reading frame showed that Ger was expressed as a polyadenylated transcript. Together with previous work, the present results suggest that the Gcr product may be a transcriptional factor necessary specifically for the high-level transcription of a limited set of genes whose products, the enzymes of glycolysis, constitute a substantial fraction of cell proteins and are responsible for the primary metabolic flux in many cells.
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Kumar, Manik, Nicky Naincy, and Rahul Ranjan. "Elementary Education in India in the Era of Universalization of Education: Instrument of Access or the Perpetuation of Inequality." Emerging Economy Studies 4, no. 2 (September 13, 2018): 218–31. http://dx.doi.org/10.1177/2394901518795073.
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Sixty years of policymaking in the arena of elementary educational reforms in India and global focus through the Millennium Development Goals (MDGs) have seen progress along with persisting inequality in access to education especially for socioeconomic and marginalized sections across the regions. This article focuses on analysis of two goals of MDGs which is related to universalization of education and reducing gender inequality in access to elementary education after introduction of policy interventions such as Sarva Shiksha Abhiyan (SSA) and Right to Education (RTE) Act in India through Gender Equity Index (GEI) and Disparity Index (DI) in Gross Enrollment Ratio (GER). Results are still consistent with the fact that even after incentives such as SSA and RTE, the scenario of elementary education has not changed much for the deprived sections, even it has shown a declining trend after 2009 for Scheduled Tribes (ST) children. The social reproduction of inequality is being manifested now in the quality of elementary education in India.
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Kulkarni, Bhushan V., Kathleen LaSance, Joyce E. Sorrell, Lisa Lemen, Stephen C. Woods, Randy J. Seeley, and Darleen Sandoval. "The role of proximal versus distal stomach resection in the weight loss seen after vertical sleeve gastrectomy." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 311, no. 5 (November 1, 2016): R979—R987. http://dx.doi.org/10.1152/ajpregu.00125.2016.
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The mechanisms involved in the weight loss seen after vertical sleeve gastrectomy (VSG) are not clear. The rat stomach has two morphologically and functionally distinct proximal and distal parts. The rat model for VSG involves complete removal of the proximal part and 80% removal of the distal part along the greater curvature. The purpose of this study was to understand the potential independent contributions of removal of these distinct gastric sections to VSG outcomes. We prepared four surgical groups of male Long-Evans rats: VSG, sham surgery (control), selective proximal section removal (PR), and selective distal section removal (DR). Gastric emptying rate (GER) was highest after VSG compared with all other groups. However, PR, in turn, had significantly greater GER compared with both DR and sham groups. The surgery-induced weight loss followed the same pattern with VSG causing the greatest weight loss and PR having greater weight loss compared with DR and sham groups. The results were robust for rats fed regular chow or a high-fat diet. Body mass analysis revealed that the weight loss was due to the loss of fat mass, and there was no change in lean mass after the surgeries. In conclusion, removal of the proximal stomach contributes to most, but not all, of the physiological impact of VSG.
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Cresi, Francesco, Elena Maggiora, Alice Pirra, Paola Tonetto, Carlotta Rubino, Laura Cavallarin, Marzia Giribaldi, Guido E. Moro, Chiara Peila, and Alessandra Coscia. "Effects on Gastroesophageal Reflux of Donkey Milk-Derived Human Milk Fortifier Versus Standard Fortifier in Preterm Newborns: Additional Data from the FortiLat Study." Nutrients 12, no. 7 (July 18, 2020): 2142. http://dx.doi.org/10.3390/nu12072142.
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Background: Feeding intolerance is a frequent diagnosis in very preterm infants. As seen in the FortiLat trial, human milk fortification with the new donkey milk-derived human milk fortifier (DF) seems to improve feeding tolerance in these infants. The aim of this study was to evaluate the effects of using the DF compared with bovine milk-derived fortifier (BF) on gastroesophageal reflux (GER) in very low birth weight (VLBW) infants. Methods: Over a total of 156 preterm infants were enrolled into the FortiLat trial (GA <32 weeks and birth weight <1500 g) and randomized into the BF arm or DF arm, and we selected all infants with clinical signs of GER and cardiorespiratory (CR) symptoms. All the infants underwent CR and multichannel intraluminal impedance and pH (MII/pH) monitoring associated with gastric ultrasound to evaluate GER and gastric emptying time. Results: 10 infants were enrolled, and 5 were in the DF arm. At MII/pH, infants enrolled into the DF arm showed a lower GER frequency than BF arm infants (p = 0.036). Half gastric emptying time was similar in DF and BF arm infants (p = 0.744). Conclusion: The use of donkey-derived human milk fortifier reduced the GER frequency and consequently should be recommended in infants with feeding intolerance.
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Mercier, Guy. "La région et l'État selon Friedrich Ratzel et Paul Vidal de la Blache." Annales de Géographie 104, no. 583 (1995): 211–35. http://dx.doi.org/10.3406/geo.1995.13886.
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Catenacci, Daniel V. T., Haeseong Park, A. Craig Lockhart, Philip Jordan Gold, Peter C. Enzinger, Jeffrey L. Nordstrom, Sam Hong, et al. "Phase 1b/2 study of margetuximab (M) plus pembrolizumab (P) in advanced HER2+ gastroesophageal junction (GEJ) or gastric (G) adenocarcinoma (GEA)." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 140. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.140.
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140 Background: Trastuzumab (T) + chemotherapy (ctx) is standard for 1st line advanced HER2+ GEA, yet subsequent targeted options are lacking. M is an anti-Her 2 monoclonal antibody with an optimized Fc domain to increase affinity for activating CD16A Fc-receptors (FcR) on NK cells. Outcomes for T-treated patients (pts) carrying the low-affinity CD16A-F allele are generally worse than pts homozygous for the high-affinity V allele. M is designed to be FcR genotype independent. Evidence of clinical activity of M alone has been seen in HER2+ GEA pts post T, while P has demonstrated durable activity. Loss of HER2 amplification may occur after T failure in a subset of initially HER2+ GEA pts. Preclinical studies suggest that engagement of innate and adaptive immunity with the combination of anti-HER-2 antibodies and T-cell checkpoint inhibition could achieve greater antitumor activity than either agent alone. Methods: Advanced HER2+, PD-L1-unselected GEA pts post T failure were eligible. Dose escalation evaluated 10 and 15 mg/kg M and 200 mg P for 2nd line or higher pts. Cohort expansion evaluates safety and objective response rate (ORR) by RECIST v1.1 in 2nd line pts. M + P is given every 21 days; response assessed every 6 weeks. HER2 amplification status was assessed in a subset of pts by plasma circulating tumor (ct) DNA analysis prior to Cycle 1 of M+P. Results: Dose escalation enrolled 9 pts; cohort expansion 48 pts at 15 mg/kg M: 30 in North America (NA) and 18 in Asia (A). Treatment was well tolerated, with 1 drug-related serious adverse event. Of 38 evaluable pts to date in expansion (24 NA and 14 A), the best overall responses include 7 pts (18.4%) with PR (4 confirmed and 3 unconfirmed) and 11 (28.9%) with SD. Higher ORR trends were observed in A vs NA (35.7% vs 8.3%) and G vs GEJ (31.6% vs 5.3%). Of 25 pts with ctDNA results, HER2 amplification detection was higher in GC than GEJ (80% vs 53%). Responses were independent of FcR genotype; CD16A genotype for evaluable pts with PR: 1 V/V, 2 V/F, 2 F/F with similar allelic distribution among non-responders. Conclusions: M+P is a well-tolerated ctx-free regimen that has shown preliminary antitumor activity in 2nd line pts with advanced/metastatic GEA. Clinical trial information: NCT02689284.
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Alcindor, Thierry, Touhid Opu, Arielle Elkrief, Farzin Khosrow-Khavar, Carmen L. Mueller, Jonathan Cools-Lartigue, Marc Hickeson, et al. "Phase II trial of perioperative chemotherapy + avelumab in locally advanced gastroesophageal adenocarcinoma: Preliminary results." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 4046. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4046.
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4046 Background: Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of avelumab to perioperative chemotherapy will increase the major pathologic response (MPR) rate in comparison with historical controls. Methods: Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, M0, WHO PS 0-1. Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II gastroesophageal junction (GEJ) tumors. Aim of the study: MPR as defined as tumor regression grades 0-1 (modified Ryan scheme); as per hypothesis, this experimental regimen will result in a 20% rate of MPR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 MPR are seen in the first 16 patients, the study will be closed. The study hypothesis cannot be rejected if at least 6 MPR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle. Survival rates are calculated with Kaplan-Meier method. Preliminary results are presented since the study has met its primary endpoint. Results: Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: GEJ (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Biomarkers expression: mismatch repair (MMR) protein loss (3/28); PD-L1(clone 73-10) expression in 1% (TPS) or more of tumor cells seen in 12/28 samples, and >10% in 6 patients. Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show MPR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions. No correlation was seen between MMR proteins or PD-L1 expression and tumor regression. With a median follow-up of 1.5 years (range 0.4-2.5), the disease-free survival rate is projected to be 0.92 (95% CI 0.83-1.00) at 12 months and 0.77 (95% CI 0.58-1.00) at 24 months. Conclusions: The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment. Clinical trial information: NCT03288350.
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SMITH, JENNIE. "Silver Lining Seen in Failed Trial of Anti-HIV Gel." Internal Medicine News 43, no. 17 (October 2010): 28. http://dx.doi.org/10.1016/s1097-8690(10)70879-9.
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Lin, Chao, Yu Jie Hou, Qing Long Zeng, Hai Gong, Ling Nie, and Hua Qiu. "The Design and Experiment of Oval Bevel Gear." Applied Mechanics and Materials 86 (August 2011): 297–300. http://dx.doi.org/10.4028/www.scientific.net/amm.86.297.
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Aiming at the complex design and analysis methods of noncircular bevel gear, combining the gear space engagement theory and the generating method of tooth profile, the profile generating process was seen as the pure rolling between the pitch line of virtual processing tool and pitch curve of oval bevel gear based on the virtual generating method. The blank parameters and relation equation between tool parameters and procedure parameters of generating method were deduced. General parametric solid models of oval bevel gear were founded. Based on experimental result of oval bevel gear transmission, the design profile of oval bevel gear which was obtained according to generating method was verified.
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Unwin, P. Tim H. "The viticultural geography of France in the 17th century according to John Locke//La géographie viticole de la France au XVIIe siècle selon John Locke." Annales de Géographie 109, no. 614 (2000): 395–414. http://dx.doi.org/10.3406/geo.2000.1842.
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JANCIN, BRUCE. "Duac Gel Advantageous in Acne; Prevents Drying Seen in BP Alone." Family Practice News 36, no. 12 (June 2006): 39. http://dx.doi.org/10.1016/s0300-7073(06)73387-4.
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Luan, Zhen Hui, Chao Wang, and Wei Peng Gao. "Analysis of Pitch Curve of Internal-Curved Planet Gear Pump." Advanced Materials Research 787 (September 2013): 782–85. http://dx.doi.org/10.4028/www.scientific.net/amr.787.782.
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Non-circular gear can be seen as a variant of circular gear, whose rolling circle become non-circular rather than circular of circular gear and such kind of non-circular rolling circle is called Pitch Curve. When designing of non-circular gear, one has to decide the Pitch Curve according to given conditions before determines other parameters. Generally, there are two kinds of situations as to determine the Pitch Curve. 1).Determine the Pitch Curve according to deputy drive ratio function of non-circular gear. 2).Determine the Pitch Curve according to deputy position function. This context has been to deal with the propose of an internal-curved planet gear pump, theories of how center wheel and annular gear are designed and the design as well as the calculation of the Pitch Curve.
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Boxma, Onno, Andreas Löpker, and Michel Mandjes. "On two classes of reflected autoregressive processes." Journal of Applied Probability 57, no. 2 (June 2020): 657–78. http://dx.doi.org/10.1017/jpr.2020.6.
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AbstractWe introduce two general classes of reflected autoregressive processes, INGAR+ and GAR+. Here, INGAR+ can be seen as the counterpart of INAR(1) with general thinning and reflection being imposed to keep the process non-negative; GAR+ relates to AR(1) in an analogous manner. The two processes INGAR+ and GAR+ are shown to be connected via a duality relation. We proceed by presenting a detailed analysis of the time-dependent and stationary behavior of the INGAR+ process, and then exploit the duality relation to obtain the time-dependent and stationary behavior of the GAR+ process.
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Kayaoglu, Eren, Ozlem Salman, and Adem Candas. "Study on Stress and Deformation of an Elevator Safety Gear Brake Block Using Experimental and FEA Methods." Advanced Materials Research 308-310 (August 2011): 1513–18. http://dx.doi.org/10.4028/www.scientific.net/amr.308-310.1513.
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It has been seen that Cylindrical Type Instantaneous Safety Gear, which is one of the most important element of an elevator system, during safety gear operation is being exposed to high stresses and brake accelerations. The stress and deformation distribution of a cylindrical type safety gear’s brake block was investigated using finite elements and experimental methods. Results found with FEM by using ABAQUS/CAE software were compared to experimental results. It is clearly seen that the element type and boundary conditions used in finite element modelling give satisfactory results.
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Shi, Zhaoyao, Jihua Ren, Zhipeng Feng, and Jing Li. "Key Technology and Experimental Study of Unequal Pitches Meshing between Metal Worm and Plastic Helical Gears." Applied Sciences 11, no. 1 (December 31, 2020): 333. http://dx.doi.org/10.3390/app11010333.
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In traditional gear design, the design theory is based on a rigid hypothesis and is popularly adopted in the preparation of metal gear. Plastic gear designing lacks a mature design theory. Hence, scholars still follow the traditional gear design theory. There is a marked difference in the rigidity and stiffness between the conventional gear design and plastic gear features. In traditional design theory, the deformation is 0.2% (Note: To assess the material yield, conditional yield strength is calculated). Designing deformation can exceed 2% for plastic gears, and the difference can sometimes be more than tenfold. The traditional design theory cannot match the gear strength and precision in the design of plastic gear. In the case of plastic gear, due to numerous meshing teeth, the 2% deformation seen cannot be neglected and should be taken into account in the presence and absence of loading to improve the meshing condition. Improvement in the gear loading ability and reduction in the meshing noise can thus be achieved. Herein, we propose an unequal pitch design theory. The results of Finite Element Analysis (FEA) and experimental verification showed that the strength could be increased by 24% for unequal pitch design theory.
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Millar, Russell B. "Reliability of size-selectivity estimates from paired-trawl and covered-codend experiments." ICES Journal of Marine Science 67, no. 3 (December 10, 2009): 530–36. http://dx.doi.org/10.1093/icesjms/fsp266.
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Abstract Millar, R. B. 2010. Reliability of size-selectivity estimates from paired-trawl and covered-codend experiments. – ICES Journal of Marine Science, 67: 530–536. To determine the size selectivity of a trawl codend from sea trials, the researcher must choose between using paired (experimental and control) and covered-codend gears. The paired-gear method has the advantage that the experimental codend can be deployed without modification, but has the disadvantage of a more complex statistical analysis. It has previously been claimed that this analysis is inherently biased regardless of sampling effort. This claim is shown to be erroneous, and it is seen that both methods produce estimators that have negligible bias under typical experimental conditions. However, paired-gear analyses were seen to produce estimators having greater statistical variability than the covered-codend analyses. Over the range of simulations employed herein, it was found that the paired-gear method generally had moderately higher (ratio of 1.3–1.9) statistical error for estimation of the length of 50% retention, when fished with equal sampling effort as the covered-codend gear. Paired-gear estimates of the selection range could have considerably higher standard error than covered-codend estimates (ratio of 1.6–4.2), with the highest ratio being for a scenario where the selection curve was asymmetric and sampling effort consisted of ten replicate deployments where the number of measured fish was restricted to 250.
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Suizu, Rie, Akito Iwasaki, Yoshiaki Shuku, and Kunio Awaga. "Spatially inhomogeneous, stepwise phase transitions in a thiazyl diradical: a structural mismatch induced by lattice transformation." Journal of Materials Chemistry C 3, no. 30 (2015): 7968–77. http://dx.doi.org/10.1039/c5tc01410g.
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Klempner, Samuel Jacob, Russell Madison, Jeffrey S. Ross, Vincent A. Miller, Siraj Mahamed Ali, Alexa Betzig Schrock, Jeeyun Lee, Seung Tae Kim, and Joseph Chao. "FGFR2-altered gastroesophageal adenocarcinomas (GEA) are a rare clinicopathologic entity with a distinct genomic landscape." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 72. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.72.
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72 Background: Therapies directed at receptor tyrosine kinases (RTKs) in GEA have met with limited success. The small molecule FGFR2 inhibitor AZD4547 failed in a phase II biomarker-selected trial, though activity has been seen with FGFR2-directed strategies, including monoclonal antibodies. Despite observed activity, very little is known about the genomic landscape of FGFR2-altered GEA. Using a large genomic database, we sought to examine the classes of FGFR2 alterations and frequency of co-occurring alterations in GEA. Methods: 6,667 tissue specimens from unique patients with advanced GEA were assayed using hybrid capture-based comprehensive genomic profiling (CGP). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 95 or 114 loci. Descriptive statistics were used to compare among subgroups. Results: We identified a total of 269 (4.0%) FGFR2-altered cases consisting of FGFR2 amplified (amp; 209, 78% of FGFR2-altered), FGFR2 mutated (mut; 40, 15%) and FGFR2 rearranged (re, 37, 14%). There was a female predominance in FGFR2-altered cases (M:F = 1.6:1) vs FGFR wild-type (WT) (2.8:1). Cases with FGFR2amp and FGFR2re were exclusively MS-stable. The most common fusion partner was TACC2 (22%). FGFR2amp GEA had higher rates of TP53 mutation versus either FGFR2re of FGFR2mut cases (p = 4.4E-6). Co-occurring alterations in the other GEA RTK targets including ERBB2 (10%) , EGFR (8%) and MET (3%) were observed in all types of FGFR2-altered GEA. Co-occurring downstream alterations in MYC (17%), KRAS (10%) and PIK3CA (5.6%) were observed frequently in each class of FGFR2-altered GEA. The median TMB for FGFR2-altered GEA was 3.6 mut/mb, which was not significantly different from a median of 4.3 mut/mb seen in FGFR2 WT samples (p = 0.53). Conclusions: FGFR2-altered GEA is a heterogenous subgroup with approximately 20% of FGFR2-altered samples harboring concurrent RTK alterations. Putative co-occurring modifiers of FGFR2 directed therapy including oncogenic MYC, KRAS, PIK3CA alterations were also frequent, suggesting that pre-treatment CGP and combination approaches may be needed to optimize patient selection.
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Shaker, Reza, Eytan Bardan, Chengming Gu, Benson T. Massey, Thomas Sanders, Mark K. Kern, Raymond G. Hoffmann, and Walter J. Hogan. "Effect of lower esophageal sphincter tone and crural diaphragm contraction on distensibility of the gastroesophageal junction in humans." American Journal of Physiology-Gastrointestinal and Liver Physiology 287, no. 4 (October 2004): G815—G821. http://dx.doi.org/10.1152/ajpgi.00120.2004.
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Previous studies of distensibility of the gastroesophageal junction (GEJ) in humans have not tried to distinguish between the effects of muscle action and passive elastic tissue properties of the GEJ. We studied 15 healthy subjects (ages 23–67 yr, 11 men/4 women) by using a catheter with a highly complaint bag positioned manometrically at the GEJ. The bag was distended with air at a rate of 20 ml/min while intrabag pressure was recorded. Distensions were performed during normal breathing, with breath held at maximum inspiration (MI) to activate the diaphragmatic crura, and with midesophageal balloon distension (BD) to relax the lower esophageal sphincter. In 10 subjects, distensions were performed after atropine injection (12 μg/kg iv). Pressure-volume curves and incremental distensibility values were calculated and compared among the different conditions. Both MI and BD significantly altered the slopes of the pressure-volume curves, whereas no effect was seen with atropine. Maximum distensibility was seen at the volume increment of 5–10 ml and was reduced with larger volumes. Distensibility measurements for the various test conditions tended to converge at the largest volume increment, suggesting that distensibility at this degree of distension was more related to the passive elastic properties of the GEJ. On the basis of these findings, we conclude that there can be significant active muscular contributions to recordings of distensibility at the GEJ, variations that must be controlled for during different study conditions.
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Sun, Jian Dong, E. Tian, Hong Lei, Zi Ping Liu, and Wen Yu Fu. "The Impact of Helical Gear Parameters Based on Axial Meshing Transmission on Swash Plate Pulse CVT Characteristics." Applied Mechanics and Materials 101-102 (September 2011): 224–27. http://dx.doi.org/10.4028/www.scientific.net/amm.101-102.224.
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A new structure of mechanical pulse CVT –rotational swash plate pulse CVT was put forward. This paper analyzed the impact of helical gear parameters on swash plate pulse CVT characteristics, it can be seen that the angular velocity of output shaft is proportional to the angle between Swash plate surface and vertical cross section of the input shaft and the swash plate surface, the gear modulus has no effect on the transmission ratio, the guide rod pitch diameter is the major factor contacting gear tooth Strength, when the other parameters unchanged, ( is the pitch helix angle)is proportional to the output torque, and is inversely proportional to the output torque.
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Meng, Rui, Neng Gang Xie, and Xiao Jing Han. "Multi-Objective Optimization Design of the Helical Gear Transmission Based on Coalition Cooperative Game Theory." Applied Mechanics and Materials 44-47 (December 2010): 1525–32. http://dx.doi.org/10.4028/www.scientific.net/amm.44-47.1525.
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Considering helical gear transmission's economic performance and drive reliability, construct multi-objective optimization model of the helical gear transmission with taking normal module, teeth number of small helical gear, helix angle and the gear width coefficient as design variables and taking the volume of small and large helical gear and opposite number of overlap ratio as objective functions. Propose multi-objective optimization design method based on coalition cooperative game theory where the two design goals are seen as two game players. By calculating the impact factor of design variables to objective functions and fuzzy clustering, the design variables are divided into strategy space of game players. Each game player takes its own revenue function as target and does single objective optimization in its own strategy space in order to get its own best strategy. The best strategies of all players form a combination of one round game and the optimal solution can be obtained through several game rounds. Example results show the effectiveness of game method.
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Xu, Shu Bo, Cai Nian Jing, Ke Ke Sun, Guo Cheng Ren, and Gui Qing Wang. "Finite Element Analysis and Optimization of Deformation Behavior for Spur Gear Warm Forging Process." Advanced Materials Research 148-149 (October 2010): 854–58. http://dx.doi.org/10.4028/www.scientific.net/amr.148-149.854.
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Recent years have therefore seen growing interest in gear precision forging to net-shape form of forge bevel, spur and helical gears, as an alternative to conventional manufacturing. In this paper, gear precision forging processes are simulated by using metal forming finite element code DEFORM-3D. The investigations of gear precision forging processes are conducted with perform forging and final forging processes. The processes of completely closed-die forging, moving-die forging and central divided flow forging processes are investigated for spur gears. The effect of different processes on the distribution of effective stress in the workpieces and forging loads are given. The purpose of this study is to introduce a new method, a so-called floating-relief method which applied to the forging of spur gears. It indicated that the flowing properties of the gear billet have a higher improve than that of conventional forging process. And the forging load obtained by using this new precision forging technology is decline sharply. The floating-relief method for gear precision forging is a sound process in the practical application.
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MacLennan, David N. "Reflections on technology and science in fishery research." ICES Journal of Marine Science 74, no. 8 (April 7, 2017): 2069–75. http://dx.doi.org/10.1093/icesjms/fsx045.
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Abstract In the latter part of the 20th century, fishery research expanded from its original biological base to include new areas, notably investigations of fishing-gear performance and fish-detection by sonar. The past 50 years have seen huge advances in technology and the combination of physical and biological insights in fishery research. Fishing-gear investigations initially focussed on the economics of commercial fishing, but in the 1970s energy consumption in fishing became a major issue. Thereafter, the objectives changed to support for fishery management through gear innovations and research, giving a better understanding of exploitation patterns. During this period, fishery acoustics advanced from crude beginnings in the 1960s to the powerful stock-assessment tool it is today. Progress in these fields has depended on multi-disciplinary research involving both the physical and biological sciences. There have been failures along the way, but there is now good understanding of how technology as well as science can make a positive contribution to fishery management. This essay describes these developments as seen from my personal involvement over the past half century. It concludes with some pointers to the future, and practical advice to young researchers considering a career in fishery research.
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Puyo, Jean-yves. "La science forestière vue par les géographes français, ou la confrontation de deux sciences «diagonales» (1870-1914)//The science of Forestry as seen by French geographers : the encounter of two «transverse» sciences (1870-1914)." Annales de Géographie 108, no. 609 (1999): 615–34. http://dx.doi.org/10.3406/geo.1999.2071.
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Masuda, Takahiro, Balazs Kovacs, Ross Bremner, and Sumeet Mittal. "PS01.009: COMPREHENSIVE CLASSIFICATION FOR ANTIREFLUX FUNCTION OF THE ESOPHAGOGASTRIC JUNCTION BASED ON HIGH-RESOLUTION MANOMETRY." Diseases of the Esophagus 31, Supplement_1 (September 1, 2018): 52. http://dx.doi.org/10.1093/dote/doy089.ps01.009.
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Abstract Background The anatomical configuration of the esophagogastric junction (EGJ) and the thoracoabdominal pressure gradient (TAPG) affect gastric content backflow into the esophagus. A comprehensive antireflux function assessment is needed to identify underlying derangements in patients with gastroesophageal reflux (GER). Herein we propose an objective scoring system for grading EGJ function. Methods We analyzed patients who underwent 24-hour pH study and high-resolution manometry in 2017 at our institution. We assessed three factors: EGJ morphology, lower esophageal sphincter pressure integral, and TAPG. Each factor was scored on a scale of 0–2, and a cumulative score was calculated (Table 1). Patients were divided into 3 groups based on cumulative score: 0, competent EGJ function (Grade I); 1–3, moderate incompetency (Grade II); 4–6, poor competency (Grade III). Results In total, 140 patients were studied. The mean age was 58.6 years, 75 patients (53.6%) were men, and the mean body mass index was 28.6 kg/m2. Fifty-one patients (36.4%) had an abnormal DeMeester score (ie, > 14.72). A significant, progressive increase was seen in number of reflux episodes (I-25.7, II-36.4, III-50.5, rs = 0.207, P = 0.015), total acid exposure time (I-1.0%, II-2.1%, III-5.0%, rs = 0.312, P < 0.001) and prevalence of abnormal pH score (I-13.0%, II-32.0%, III-57.1%, rs = 0.314, P < 0.001) from Grade I to III. Conclusion The proposed grading of the EGJ based on a cumulative score of individual parameters has a good correlation with GER. Disclosure All authors have declared no conflicts of interest.
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Johnson-Glenberg, Mina C., David A. Birchfield, Colleen Megowan-Romanowicz, and Erica L. Snow. "If the Gear Fits, Spin It!" International Journal of Gaming and Computer-Mediated Simulations 7, no. 4 (October 2015): 40–65. http://dx.doi.org/10.4018/ijgcms.2015100103.
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Two embodied gears games were created. Better learners should use fewer gear switches to reflect their knowledge. Twenty–three 7th graders, playing as dyads, used gestures to manipulate virtual gears. The Kinect sensor tracked arm-spinning movements and switched gear diameters. Knowledge tests were administered. Statistically significant knowledge gains were seen. For Game 1 (gear spun one direction), switching significantly predicted only pretest knowledge. For Game 2 (gear spun two directions) switching was also negatively correlated with both tests. For game 2, those who used fewer switches during gameplay understood the construct better scoring higher on both tests. Dyadic analyses revealed the winner used significantly fewer switches. In-process data can provide a window onto knowledge as it is being encoded. However, games should stay within the learner's ZPD, because if the game is too easy (Game 1), meaningful data may be difficult to gather. The use of in ludo data from games with high sensitivity may attenuate the need for repetitive traditional, post-intervention tests.
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Rahbari, Mohammad, Mathieu Pecqueux, Daniela Aust, Holger Stephan, Oliver Tiebel, Antonios Chatzigeorgiou, Torsten Tonn, et al. "Expression of Glypican 3 Is an Independent Prognostic Biomarker in Primary Gastro-Esophageal Adenocarcinoma and Corresponding Serum Exosomes." Journal of Clinical Medicine 8, no. 5 (May 16, 2019): 696. http://dx.doi.org/10.3390/jcm8050696.
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Exosomes are nano-sized membranous vesicles of endosomal origin that carry nucleic acids, lipids and proteins. The cargo of exosomes is cell origin specific and the release of these exosomes and uptake by an acceptor cell is seen as a vital element of cell-cell communication. Here, we sought to investigate the diagnostic and prognostic value of the expression of glypican 3 (GPC3) on primary gastro-esophageal adenocarcinoma (GEA) tissue (tGPC3) and corresponding serum exosomes (eGPC3). Circulating exosomes were extracted from serum samples of 49 patients with GEA and 56 controls. Extracted exosomes were subjected to flow cytometry for the expression of eGPC3 and GPC3 expression on primary GEA tissue samples was determined by immunohistochemistry and correlated to clinicopathological parameters. We found decreased eGPC3 levels in GEA patients compared to healthy controls (p < 0.0001) and high tGPC3 expression. This was significantly associated with poor overall survival (high vs. low eGPC3: 87.40 vs. 60.93 months, p = 0.041, high vs. low tGPC3: 58.03 vs. 84.70 months, p = 0.044). Cox regressional analysis confirmed tGPC3 as an independent prognostic biomarker for GEA (p = 0.02) and tGPC3 expression was validated in two independent cohorts. Our findings demonstrate that eGPC3 and tGPC3 can be used as potential diagnostic and prognostic biomarkers for GEA.
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Idrees, Ghazala, and Abid Ghafoor Chaudhry. "Precursors of Pollen Allergies: An Anthropo-Economic Perspective." Global Economics Review V, no. II (June 30, 2020): 17–28. http://dx.doi.org/10.31703/ger.2020(v-ii).02.
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This explanatory study is intended to determine precursors of pollen allergies, an anthropo-economic perspective. In a nutshell, it deals with how pollen allergy is produced, circulated and dealt with in the setting of twin cities; Islamabad and Rawalpindi. Medically, allergies can be prevented but not cured. The cultural means of prevention and care are always preferred by the needs of the body, health, age and disease accordingly. The word anthropo is inconsistently used in a way human deal socio-culturally with the issue. Objective: The paper attempts to examine some environmental and socio-cultural determinants of pollen allergies in Rawalpindi and Islamabad. Materials and Methods: Socio-Economic Survey Form, FGD checklist, interview guide and life histories were prepared to collect data in order to unveil the cultural mythology on pollen allergies. The study reveals that �the livings of pollen patients have seen under the lenses of cultural economy�.
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Wieck, Hans-Georg. "The GDR—As Seen by the Federal German Foreign Intelligence Agency (BND) 1985–1990." Journal of Intelligence History 6, no. 1 (June 2006): 85–103. http://dx.doi.org/10.1080/16161262.2006.10555126.
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Angermund, Ralf, W. Knauf, M. Freund, M. R. Nowrousian, H. Einsele, H. Goldschmidt, W. E. Berdel, et al. "Role of Bortezomib in the Treatment of Multiple Myeloma - First Results from a Representative Multicentre Treatment Survey in Germany (GER)." Blood 106, no. 11 (November 16, 2005): 5156. http://dx.doi.org/10.1182/blood.v106.11.5156.5156.
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Abstract Background: Over the past decade new treatment options and drugs significantly altered the treatment paradigm and treatment guidelines for patients with Multiple Myeloma have been established (e.g. ASCO). Bortezomib (Velcade®) (Vel) was first approved in GER for Multiple Myeloma in April 2004 based on phase II data in treatment after 2nd relapse. A representative multicentre treatment survey was performed to detect treatment behaviour in GER. The survey performed in 4th quarter 2004, based on data of 3rd quarter 2004 was done about one quarter after approval of Vel in GER. As an example of how a new treatment option is integrated into clinical practice, we describe the use of Vel at this certain time point. Methods: The methods of this representative analysis was provided elsewhere (Freund et al). The data presented here are a subset of this analysis based on 59 sites and 500 patients. Results: 278 male and 222 female patients, 56% at the time of analysis for decision on primary therapy, 25% for secondary treatment and 19% for further treatment were included in this analysis. The centres participating were 15% university hospitals (UH), 27% non-university hospitals with specialized (SH) and 19% without specialized (NSH) haematology department, and 39% office-based haematologists (OBH). Vel was selected as therapy in 10.4% of patients in total, (14% UH, 52% SH, 2% NSH and 32% OBH) mainly for treatment of > 3rd relapse (21%), followed by 2nd relapse (15%) and 1st relapse (8%). No use of Vel was detected as primary treatment. Within treatment ≥ 3rd relapse, Vel was the 2nd most frequently used drug after dexamethasone (dex) (21% and 47% respectively). Vel was most frequently planned as next therapy (53%) followed by dex (23%) and thalidomide (thal) (12%). Only 5% of this population was treated within a clinical study. After 2nd relapse (approved label at that time), Vel was used as 7th most frequent drug (15%) after dex, cyclophosphamide, melphalan, thal, adriamycine and vincristine. Planned further therapy for these patients was most frequently Vel (51%) followed by dex (19%), thal (20%) and bendamustine (14%). According to multivariate analysis Vel was mostly used by OBH following thal, cyclophosphamide and dex treatment. After 1st relapse (not approved at time of survey), Vel played a minor role (8% of chemotherapy used, ranked 10th) mainly in SH in younger patients below age 40 yrs. with concurrent diseases not qualifying for high dose chemotherapy after melphalan treatment. Conclusion: New treatment options like Vel are quickly integrated into treatment behaviour in GER, mainly by use in OBH and within approved indication. According to planned treatment, Vel was seen at this early time point as most frequently planned further therapy in ≥ 2nd relapse indicating this drug’s possibility to become a future treatment standard in heavily pretreated patients. In order to detect the dynamic of change of treatment of Multiple Myeloma, a comparable survey is worth to be repeated in an adequate time period.
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Li, Chao Feng, Shi Hua Zhou, and Jie Liu. "Numerical Simulation of a Bending-Torsion Coupling Gear Transmission System." Applied Mechanics and Materials 448-453 (October 2013): 3403–7. http://dx.doi.org/10.4028/www.scientific.net/amm.448-453.3403.
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Based on the establishment of angular contact ball bearing mechanical model, a nonlinear coupled lateral, torsional and axial dynamic model of helical gear-rotor-bearing system is established, and the dynamic differential equations of the coupled lateral-torsional-axial nonlinear vibration are deduced for imbalance rotors. The investigations are systematically carried out by oscillograms and spectrograms with rotating speed, taking into account eccentricity and nonlinear supporting by rolling bearing. The results show that the rotation frequency of the driven shaft appears in the driving shaft. In addition, the rotation frequencies and meshing frequency appear obviously in torsional direction. It can be seen that the lateral, torsional and axial response characteristics of driving and driven shafts obvious differences are due to the effects of the gear assembly characteristic, gear geometry parameters and the angular contact ball bearings characteristics. As a result, not only appear the rotational frequency and stiffness frequency, but also yield the bearing variable stiffness frequency and conbined frequency in lateral directions. However, the theory of the helical gear-rotor-bearing system still needs further research.
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Yin, Minghu, Yahui Cui, Xiangjun Meng, Jinzhong Zuo, and Yuhao Qi. "Dynamic analysis of double-helical gear system considering effect of oil film among meshing teeth." Advances in Mechanical Engineering 12, no. 5 (May 2020): 168781402092011. http://dx.doi.org/10.1177/1687814020920117.
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The oil film among meshing teeth is just like a spring-damping element, and it can dominate the friction and meshing characteristics of the gear pair and influence its dynamic performances further. Thus, this article focuses on a double-helical gear system and makes efforts to consider the effect of the oil film among meshing teeth more deeply, which can enhance the precision of dynamic analysis for the gear system. First, based on the elasto-hydrodynamic lubrication theory and “microtomy” method, the models of friction and meshing characteristics are developed including the friction state and spring-damping effect of the oil film among meshing teeth; then, the dynamic models of the double-helical gear system with the effect of the oil film among meshing teeth are established, and finally, the experiments are carried out to verify the value of the models developed in this article. According to the theoretical and experimental analyses, it can be seen that the dynamic model considering the effect of the oil film among the meshing teeth is more precise and practical, and the effect of the oil film should be considered in the dynamic analysis of the gear system, especially at the condition with heavy load or high speed.
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Shah, Manish A. "Unanswered Questions in the Management of Gastroesophageal Junction Adenocarcinoma: An Overview from the Medical Oncologist's Perspective." American Society of Clinical Oncology Educational Book, no. 33 (May 2013): e155-e159. http://dx.doi.org/10.14694/edbook_am.2013.33.e155.
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Patients with gastroesophageal junction (GEJ) adenocarcinoma have multiple treatment options; however, are victims of lack of consensus and wide variation in treatment, sometimes within the same hospital. While there is a consensus that surgery alone is inadequate for locally advanced disease, locoregional treatment has become the point for debate. Only in 2010 was the reclassification of GEJ cancers as esophageal cancers. Treatment options remain as varied as the classification of GEJ cancers: preoperative chemoradiotherapy, definitive chemoradiation, perioperative chemotherapy, and resection followed by postoperative chemoradiation. Several studies have examined the varying treatment paradigms; however, many fall short due to methodology or sample size. The MAGIC study determined perioperative chemotherapy to be an acceptable standard treatment option for patients with gastric cancer, althouth a significant portion of enrolled patients had distal esophageal and GEJ adenocarcinoma. The CROSS study concluded combination chemotherapy and radiation before resection beneficial. Preoperative therapy in cases of GEJ is beneficial for survival, but not as much impact is seen as in esophageal SCC, which exhibits an increased sensitivity to CRT. There is concurrence with two phase III studies from Japan and Korea on the role of adjuvant chemotherapy for gastric cancer. However, the applicability of these studies to GEJ adenocarcinoma remains a question, especially with the significantly different epidemiology of increased proximal and GEJ tumors in the West compared to Asia. To move forward with this increasingly prevalent disease, we will need to do more than understand the multiple treatment paradigms—we will need to select a strategy and examine it.
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Alter, D. M., and Tsu-Chin Tsao. "Stability of Turning Processes with Actively Controlled Linear Motor Feed Drives." Journal of Engineering for Industry 116, no. 3 (August 1, 1994): 298–307. http://dx.doi.org/10.1115/1.2901945.
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Using linear motors as machine tool feed drives has the potential of enhancing machining performance by eliminating gear related mechanical problems and increasing speed and accuracy, but introduces a stability concern due to a strong dynamic feedback interaction between the machining process and the drives. This paper investigates the stability aspect of this dynamic interaction and the use of active damping to achieve machining stability in turning. Various necessary and sufficient conditions for stability at all cutting speeds are derived, and have been used to study the effect of damping and gear reduction in system stability. The interaction of the cutting process with the tool servo loop is seen to have significant instability consequences in systems with small drive gear reductions. Both theoretical stability and experimental cutting results are presented for PD and PID regulation. Results show that actively controlled linear motors can provide sufficient dynamic stiffness for stable turning operation.
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Haasnoot, Tim, Marloes Kraan, and Simon R. Bush. "Fishing gear transitions: lessons from the Dutch flatfish pulse trawl." ICES Journal of Marine Science 73, no. 4 (February 1, 2016): 1235–43. http://dx.doi.org/10.1093/icesjms/fsw002.
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Abstract This paper focuses on the transition in the Dutch cutter fleet-targeting flatfish, from the conventional beam trawl to the pulse trawl fishing gear. In doing so, we explore the process of gear transition, presenting the challenges that fishers and policy-makers face. The pulse trawl technique represents a particularly controversial gear transition as it makes use of electricity, which has been banned by the European Union since 1988. However, it is seen by those developing it in the Netherlands as an important alternative fishing gear to the conventional beam trawl technique, which is becoming increasingly inefficient with rising fuel prices and well-documented impact on benthic habitats. By using a multi-level perspective on socio-technical transitions as the analytical framework, we explore the development of the pulse trawl and the interaction between different levels. We also discuss the influence of technology-push on its transition into practice and regulation. This paper demonstrates the importance of social dimensions in the adoption of new fishing gears and in doing so contributes to our knowledge on how technological transitions in fisheries can be managed.
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Stokes, Raymond G. "Autarky, Ideology, and Technological Lag: The Case of the East German Chemical Industry, 1945–1964." Central European History 28, no. 1 (March 1995): 29–45. http://dx.doi.org/10.1017/s0008938900011237.
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The ignominious and total collapse of the German Democratic Republic (GDR) in 1989/90 revealed all too clearly the disastrous state of the country's economy, especially in comparison to the Federal Republic of Germany (FRG). This fact must not, however, be seen in isolation from another, apparently contradictory one: From the beginning to the end of its existence, the GDR was the shining economic and technological star in the communist firmament in Eastern Europe. GDR electronics and optics were crucial to the Soviet space program and to East-bloc military production, which counted among communism's few technological successes. Its chemical and automobile industries were also well regarded in the Eastern bloc and in many developing countries. The GDR's technological prowess—especially when combined with its favored and very lucrative relationship with the FRG—made for a reasonably high standard of living, not just in relation to other countries in the Soviet bloc, but in relation to other industrialized countries as well.
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Woolridge, Katherine, and Deirdre Hooper. "Complications of gel manicures." Our Dermatology Online 12, e (August 27, 2021): e75-e75. http://dx.doi.org/10.7241/ourd.2021e.75.
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Green nail syndrome is a nail disorder mostly seen in the elderly and those frequently exposed to water. Gel nail polish has become a very popular alternative to regular nail polish received during manicures. This popularity has allowed potential adverse effects to surface. We present a unique case of green nail syndrome in a healthy 50 year old healthy female after the removal of gel nail polish after a few weeks. The case raises awareness to potential complications and further consequences of gel manicures.
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Hembrough, Todd A., Les Henderson, Brittany Rambo, Wei-Li Liao, Sheeno Thyparambil, Kathleen Bangali, Jamar Uzzell, et al. "Quantification of HER2 from gastroesophageal cancer (GEC) FFPE tissue by mass spectrometry (MS)." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 17. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.17.
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17 Background: Trastuzumab had a survival benefit in ‘HER2 positive’ GEC, determined by IHC/FISH. These companion diagnostics have limitations. IHC is semi-quantitative, subjective, and sensitive to antigen instability in FFPE; FISH is laborious, expensive, and subjective. Gene amplification may not correlate to protein expression. Moreover these are low throughput assays. There is increased recognition of profound interpatient molecular heterogeneity with several putative biomarkers, and only scarce tissue to assess for each one. We sought to evaluate our MS platform on GEC FFPE tissues for HER2 status compared to IHC/FISH. We also applied the “GEC-plex” of 11 other potentially predictive/prognostic markers for GEC. Methods: We utilized trypsin digestion mapping of rHER2 to identify unique peptides for SRM development. Stable isotope-labeled peptides were synthesized as internal standards, and standard curves were generated in a complex eukaryotic matrix (PC3 cells) to determine LOD, LLOQ, accuracy, precision and linearity of the assays. The assay was run on 17 GEC cell lines, in parallel with FISH/IHC, and expression thresholds were established for HER2+/HER2-; the sensitivity/specificity of the established cutoffs were then tested prospectively in FFPE GEC tissues on 10uM FFPE LCM slides (n=121). HER2 stability from FFPE sections was assessed by assaying 33 freshly cut FFPE samples; the adjacent sections were processed one year later. Results: The HER2 peptide chosen (ELVSEFSR) had a LOD of 100 amol and CV<20%. HER2 MS on GEC cell lines revealed concordance with FISH (HER2:CEP17) ratio (R2=0.96). The analysis suggested HER2 expression > 750 amol/ug was indicative of HER2 amplification. The assay was stable in archival FFPE sections (R2=0.76). For GEC FFPE cases, ‘any’ HER2 expression was seen in 69.4% of cases; 8.2% showed HER2 > 750 amol (10/121) - all were HER2 amplified. No cases <550 amol/ug were HER2 amplified. IHC/FISH results for cases with 550-750 amol/ug demonstrated a heterogeneous ‘equivocal’ zone, not unlike ‘IHC 2+’, which may require FISH confirmatory testing. Conclusions: ‘GEC-plex’ has a quantitative, sensitive, and specific HER2 assay that can be multiplexed along with other GEC biomarkers.
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Stein, Matthew K., Joanne Xiu, Michael Gary Martin, Axel Grothey, Philippe Prouet, Jeffrey Owsley, Forrest W. Williard, et al. "Molecular comparison between peritoneal metastases (PM) and primary gastric (GC) and gastroesophageal junction (GEJ) cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 4053. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.4053.
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4053 Background: PM from GC or GEJ portend a poor prognosis and molecular differences are ill defined. Methods: We compared genomic profiles of primary (P) GC and GEJ with PM patients (pts) and other metastases (OM) sent to Caris Life Sciences. Testing comprised immunohistochemistry (IHC) including programmed death ligand 1 (PD-L1) combined positive score (CPS), copy number alterations (CNA), 592-gene next-generation sequencing (NGS), microsatellite instability (MSI) and tumor mutational burden (TMB). Results: 1366 cases were identified: 1041 GC (707 P, 98 PM, 236 OM) and 325 GEJ (248 P, 5 PM, 72 OM). PM were increased in GC versus GEJ (9% v. 2%, p < 0.0001). 91% GC and 93% GEJ were adenocarcinoma (AD); GC were more likely signet ring (SR) histology versus GEJ (11% v. 3%, p < 0.0001) and GC PM were more likely SR versus other OM or P (13% v. 12% v. 7%, p = 0.067). The mean age of PM pts (57 years) was younger than primary GC (63, p = 0.002) and OM (61; p = 0.044). More PM GC pts were female than P or OM (48% v. 35% v. 34%, p = 0.03). No molecular profiling differences were seen between GEJ and GC pts and they were combined for analysis; findings from 1246 AD pts are shown below (see Table). OM (9%, p = 0.041) had more CNA in CCNE1 than PM (2%, p = 0.041) or P (5%, p = 0.002). Conclusions: Compared to P and OM GC, PM pts were younger, more likely female and had a higher incidence of SR histology. PD-L1, HER2 IHC and ERBB2 CNA were reduced in PM versus P, suggesting novel therapeutic targets are needed. [Table: see text]
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Abrass, C. K., and A. K. Berfield. "Phenotypic modulation of rat glomerular visceral epithelial cells by culture substratum." Journal of the American Society of Nephrology 5, no. 8 (February 1995): 1591–99. http://dx.doi.org/10.1681/asn.v581591.
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The interaction of cells with their supporting extracellular matrix influences cellular phenotype, cellular proliferation, protein synthetic profile, and specific gene activation. To examine the ability of culture substratum to modulate the phenotype expressed by glomerular epithelial cells (GEC) in culture, GEC were grown on plastic culture plates coated with collagen gels (Type I collagen, Vitrogen) or a complex matrix from the Englebreth-Holm-Swarm tumor (Matrigel). Cultures were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). On untreated plastic, GEC grew in a random pattern. Cells were flat and thin with many filamentous processes. When grown on collagen I gels, GEC grew to confluence as a tight monolayer with typical cobblestone appearance. These cells demonstrated surface microvilli and a central cilium. TEM showed an epithelial appearance with tight junctions. When plated on the surface of Matrigel, GEC formed nests of cells that gradually burrowed into the gel. Proliferation on this matrix was extremely slow. TEM demonstrated that there are surface projections that abut the matrix and that the nests of cells are hollow with a central lumen. SEM demonstrated nests of cells that formed a sphere. Surface microvilli were not as abundant as cells grown on Vitrogen, and cilia were not seen. Cells could be removed from one surface, plated onto another, and would shift phenotype to that observed for subcultures primarily plated onto that surface. Cells on each complex substrate, as well as GEC plated on tissue culture plates coated with individual matrix proteins were biosynthetically labeled with (35S)methionine. The profile and rate of protein synthesis were modified by the plating substrate. These observations demonstrate that rat GEC can be induced to display variable phenotypes in culture that are determined by the plating substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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Alkindi, Mohammed, Sundar Ramalingam, Osama Alghamdi, Omar Mohamed Alomran, Mohammed Awadh Binsalah, and Mohammed Badwelan. "Guided bone regeneration with osteoconductive grafts and PDGF: A tissue engineering option for segmental bone defect reconstruction." Journal of Applied Biomaterials & Functional Materials 19 (January 2021): 228080002098740. http://dx.doi.org/10.1177/2280800020987405.
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Regeneration and reconstruction of segmental bone defects (SBD) is a clinical challenge in maxillofacial surgery and orthopedics. The present study evaluated efficacy of guided bone-regeneration (GBR) of rat femoral SBD using osteoconductive equine-bone (EB) and beta-tricalcium phosphate (beta-TCP) grafts, either with or without platelet-derived growth-factor (PDGF). Following ethical-approval, 50 male Wistar-Albino rats (aged ~12–15 months and weighing ~450–500 g) were included. A 5 mm femoral critical-size SBD was created and animals were divided into five groups depending on the graft material used for GBR (EB, EB + PDGF, Autograft, beta-TCP, beta-TCP + PDGF; n = 10/group). Following 12-weeks of healing, animals were sacrificed and femur specimens were analyzed through qualitative histology and quantitative histomorphometry. There was new bone bridging femoral SBD in all groups and qualitatively, better bone formation was seen in autograft and EB + PDGF groups. Histomorphometric bone-area (BA %) was significantly high in autograft group, followed by EB + PDGF, beta-TCP + PDGF, EB, and beta-TCP groups. Addition of PDGF to EB and beta-TCP during GBR resulted in significantly higher BA%. After 12-weeks of healing, EB + PDGF for GBR of rat femoral segmental defects resulted in new bone formation similar to that of autograft. Based on this study, GBR with EB and adjunct PDGF could be a potential clinical alternative for reconstruction and regeneration of segmental bone defects.
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Lee, Steven P., Jill M. Brooks, Hatim Al-Jarrah, Wendy A. Thomas, Tracey A. Haigh, Graham S. Taylor, Sibille Humme, et al. "CD8 T Cell Recognition of Endogenously Expressed Epstein-Barr Virus Nuclear Antigen 1." Journal of Experimental Medicine 199, no. 10 (May 17, 2004): 1409–20. http://dx.doi.org/10.1084/jem.20040121.
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The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the antigen from proteasomal breakdown and, as measured in cytotoxicity assays, from major histocompatibility complex (MHC) class I–restricted presentation to CD8+ T cells. This led to the concept of EBNA1 as an immunologically silent protein that although unique in being expressed in all EBV malignancies, could not be exploited as a CD8 target. Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream of the GAr domain and assaying recognition by interferon γ release, we show that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines (LCLs) is in fact presented to CD8+ T cells via a proteasome/peptide transporter–dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although slightly lower than seen with paired lines expressing a GAr-deleted EBNA1 protein, leads to strong and specific inhibition of LCL outgrowth in vitro. Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway despite GAr-mediated stabilization of the mature protein. We infer that EBNA1-specific CD8+ T cells do play a role in control of EBV infection in vivo and might be exploitable in the control of EBV+ malignancies.
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Khine, Hnin, David L. Goldman, and Jeffrey R. Avner. "Management of Fever in Postpneumococcal Vaccine Era: Comparison of Management Practices by Pediatric Emergency Medicine and General Emergency Medicine Physicians." Emergency Medicine International 2014 (2014): 1–5. http://dx.doi.org/10.1155/2014/702053.
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Background. The primary objective of this study was to compare management practices of general emergency physicians (GEMPs) and pediatric emergency medicine physicians (PEMPs) for well-appearing young febrile children.Methods. We retrospectively reviewed the charts of well-appearing febrile children aged 3–36 months who presented to a large urban children’s hospital (PED), staffed by PEMPs, or a large urban general emergency department (GED), staffed by GEMPs. Demographics, immunization status, laboratory tests ordered, antibiotic usage, and final diagnoses were collected.Results. 224 cases from the PED and 237 cases from the GED were reviewed. Children seen by PEMPs had significantly less CXRs (23 (10.3%) versus 51 (21.5%),P=0.001) and more rapid viral testing done (102 (45%) versus 40 (17%),P<0.0001). A diagnosis of a viral infection was more common in the PED, while a diagnosis of bacterial infection (including otitis media) was more common in the GED. More GED patients were prescribed antibiotics (41% versus 27%,P=0.002), while more PED patients were treated with oseltamivir (6.7% versus 0.4%,P< 0.001).Conclusions. Our findings identify important differences in the care of the young, well-appearing febrile child by PEMPs and GEMPs and highlight the need for standardization of care.
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Popkonstantinović, Branislav, Ratko Obradović, Miša Stojićević, Zorana Jeli, Ivana Cvetković, Ivana Vasiljević, and Zoran Milojević. "The Design and Simulation of an Astronomical Clock." Applied Sciences 11, no. 9 (April 28, 2021): 3989. http://dx.doi.org/10.3390/app11093989.
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This paper describes and explains the synthesis of an astronomical clock mechanism which displays the mean position of the Sun, the Moon, the lunar node and zodiac circle as well as the Moon phases and their motion during the year as seen from the Earth. The clock face represents the stereographic projection of the celestial equator, celestial tropics, zodiac circle (ecliptic) and horizon for the latitude of Belgrade from the north celestial pole to the equator plane. The observed motions of celestial objects are realized by a set of clock gear trains with properly calculated gear ratios. The method of continued fraction is applied in the computation of proper and practically applicable gear ratios of the clock gear trains. The fully operational 3D model of the astronomical clock is created and the motion study of its operation is accomplished by using the SolidWorks 2016 application. The simulation results are compared with the ephemeris data and the detected differences are used to evaluate the long-term accuracy of the astronomical clock operation. The presented methods of the clock mechanism synthesis can be useful for the design, maintenance and conservation of large-scale city astronomical clocks since these clocks represent a precious historical and cultural heritage of European civilization.
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Almugbel, Fahad, Laith Al-Showbaki, Husam Alqaisi, Chihiro Suzuki, Osvaldo Espin-Garcia, Marta Honório, Raymond Woo-Jun Jang, Shabbir M. H. Alibhai, and Elena Elimova. "Impact of age on outcomes and symptoms in patients with advanced gastroesophageal cancer (GEC)." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 193. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.193.
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193 Background: Although age is a non-modifiable risk factor for most cancers, alone it is not very helpful in deciding on the best treatment for patients. Insufficient data exist in the oldest old ( > 75 years) compared to young-old (65-75 years) and to younger ( < 65 years) patients with de novo metastatic GEC regarding which factors influence response and outcomes. Methods: We retrospectively assessed all patients with de novo metastatic GEC seen from 2006-2015 at the Princess Margaret Cancer Center in Toronto-Ontario, Canada. We used Kaplan-Meier plots and Cox proportional hazards analyses to examine factors associated with progression-free survival (PFS) and overall survival (OS). To examine patient-reported outcomes we used the Edmonton Symptom Assessment System (ESAS) in the first six months of therapy using cross-sectional and longitudinal analyses. Results: A total of 580 de novo metastatic GEC patients were seen between 2006 and 2015. Of these (14%) were oldest old, (31%) were young-old (age 65-75) and 54% were younger ( < 65 years). Most patients (67-80%) were male. Median OS for the entire cohort was 9.1 mo. (95% confidence interval (CI) 8.0 – 10.1); the shortest OS was in the oldest old group at 4.5 mo. compared to 8.7 mo. in young-old and 9.8 mo. in younger group, p < 0.001. PFS was also significantly different among the age groups (4.4 mo., 6.1 mo., and 6.5 mo., respectively), p = 0.0145. In a multivariate model predictors for OS were age (young-old group), number of metastasis, and Eastern Cooperative Oncology Group (ECOG) performance scale (PS). Similar predictors were found for PFS; however, age was not a significant factor. Of the 55 patients who provided ESAS data, 58% were < 65 and 42% were age≥ 65. The most common symptoms at presentation were fatigue, appetite, and well-being. There were no differences by age group (all p > 0.05). Conclusions: Patients age > 75 have poorer OS compared to younger age groups but PFS does not differ, suggesting similar benefits with treatment in appropriately selected older adults with advanced GEC. Symptom profiles were similar with age. Further comprehensive care is needed for older patients with advanced GEC to improve their survival.
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Sauter, Claude, Bernard Lorber, and Richard Giegé. "Towards atomic resolution with crystals grown in gel: The case of thaumatin seen at room temperature." Proteins: Structure, Function, and Bioinformatics 48, no. 2 (August 1, 2002): 146–50. http://dx.doi.org/10.1002/prot.10125.
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Ding, Jian Jun, Zhuang De Jiang, Bing Li, and Jun Jie Guo. "Study on the Composite Measuring Method for Small Module Gears." Key Engineering Materials 381-382 (June 2008): 83–86. http://dx.doi.org/10.4028/www.scientific.net/kem.381-382.83.
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The detection technique of small module gears has a very important research and application value. In this paper, a composite measuring method is presented based on combining traditional mechanical contact measurement with optical image non-contact measurement. First of all, this paper analyzes the basic principle of composite probe composed of optical fiber stylus and CCD imaging system. The tail-end of the stylus is shaped into a micro-sphere, where a small refection mirror is designed. When the laser is transmitted through the fiber, a round facula can be seen from the CCD camera. The micro-sphere is kept contact with the surface of the measured gear at the time of measuring and the error of the measured gear will be reflected by the offset of the facula center. Meanwhile, the sub-pixel extraction algorithm for the center of facula image is presented. Then the calibration principle and method of probe system is analyzed in detail. Finally, the data processing principle of the presented method is discussed for gear measurement.
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Beisser, Patrick S., Gert Grauls, Cathrien A. Bruggeman, and Cornelis Vink. "Deletion of the R78 G Protein-Coupled Receptor Gene from Rat Cytomegalovirus Results in an Attenuated, Syncytium-Inducing Mutant Strain." Journal of Virology 73, no. 9 (September 1, 1999): 7218–30. http://dx.doi.org/10.1128/jvi.73.9.7218-7230.1999.
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ABSTRACT The rat cytomegalovirus (RCMV) R78 gene belongs to an uncharacterized class of viral G protein-coupled receptor (GCR) genes. The predicted amino acid sequence of the R78 open reading frame (ORF) shows 25 and 20% similarity with the gene products of murine cytomegalovirus M78 and human cytomegalovirus UL78, respectively. The R78 gene is transcribed throughout the early and late phases of infection in rat embryo fibroblasts (REF) in vitro. Transcription of R78 was found to result in three different mRNAs: (i) a 1.8-kb mRNA containing the R78 sequence, (ii) a 3.7-kb mRNA containing both R77 and R78 sequences, and (iii) a 5.7-kb mRNA containing at least ORF R77 and ORF R78 sequences. To investigate the function of the R78 gene, we generated two different recombinant virus strains: an RCMV R78 null mutant (RCMVΔR78a) and an RCMV mutant encoding a GCR from which the putative intracellular C terminus has been deleted (RCMVΔR78c). These recombinant viruses replicated with a 10- to 100-fold-lower efficiency than wild-type (wt) virus in vitro. Interestingly, unlike wt virus-infected REF, REF infected with the recombinants develop a syncytium-like appearance. A striking difference between wt and recombinant viruses was also seen in vivo: a considerably higher survival was seen among recombinant virus-infected rats than among RCMV-infected rats. We conclude that the RCMV R78 gene encodes a novel GCR-like polypeptide that plays an important role in both RCMV replication in vitro and the pathogenesis of viral infection in vivo.