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1
Brophy, Justin. "The Spike Milligan Public Speaking Competition." Psychiatric Bulletin 27, no. 07 (July 2003): 273. http://dx.doi.org/10.1017/s0955603600002580.
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The Spike Milligan Public Speaking Competition is a series of events conducted by the Irish Division of The Royal College of Psychiatrists' Public Education Committee. The initiative began as a local project, as part of the Changing Minds campaign. It is aimed at developing lifelong positive attitudes towards mental illness by doctors in training, and at redressing some of the stigma and negativity towards mental illness prevalent among trained doctors. It also aims to provide them with a positive experience of public speaking, in particular on mental health topics, and to enhance skills in communication with the public.
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Brophy, Justin. "The Spike Milligan Public Speaking Competition." Psychiatric Bulletin 27, no. 7 (June 2003): 273. http://dx.doi.org/10.1192/pb.27.7.273.
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The Spike Milligan Public Speaking Competition is a series of events conducted by the Irish Division of The Royal College of Psychiatrists' Public Education Committee. The initiative began as a local project, as part of the Changing Minds campaign. It is aimed at developing lifelong positive attitudes towards mental illness by doctors in training, and at redressing some of the stigma and negativity towards mental illness prevalent among trained doctors. It also aims to provide them with a positive experience of public speaking, in particular on mental health topics, and to enhance skills in communication with the public.
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Barnes, Peter. "‘An Uncooked Army Boot’: Spike Milligan, 1918–2002." New Theatre Quarterly 18, no. 3 (August 2002): 205–10. http://dx.doi.org/10.1017/s0266464x02000295.
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Allen, David, and Fanny Hercouet. "La Bile noire et son humour : fin du monde, l’être déchet et la ligue de domination mondiale." psychologie clinique, no. 45 (2018): 7–19. http://dx.doi.org/10.1051/psyc/201845007.
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L’étude pose la question de l’humour noir et son rapport à la mélancolie clinique. Les witz d’Hamlet sont étudiés comme une possible date de naissance de l’humour noir. Les écrits de Spike Milligan et Peter Cook concernant la fin du monde sont étudiés en tant qu’expression de l’humour mélancolique. Ainsi l’humour noir semble être le terrain sur lequel le mélancolique peut faire le procès de l’homme post Auschwitz, post Hiroshima, une forme de critique encore disponible au sujet moderne.
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Graham, Philip. "Peter Wilson." Child Psychology and Psychiatry Review 4, no. 4 (November 1999): 183–84. http://dx.doi.org/10.1017/s1360641799002075.
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For a relatively new organisation (it was founded only 10 years ago), Young Minds has already made a major impact on the CAMHS field. Its magazine contains lively articles by writers such as Susie Orbach and Adam Phillips and is widely read. It runs a well-used information service for parents concerned about the mental health of their children, and a consultancy service for professionals. High profile personalities such as Spike Milligan, John Bird, John Fortune and Nick Hornby have given their services to its fund-raising events. Who can take the major credit for the success of Young Minds? Stand up, Peter Wilson, the subject of this profile. He was initially Chair of the organisation and has been Director since April 1992.
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Pavía Cogollos, José. "Capítulo 5. «And now for something completely different». A propósito de Monty Python’s Flying Circus." Espejo de Monografías de Comunicación Social, no. 1 (November 19, 2018): 93–112. http://dx.doi.org/10.52495/c5.emcs.1.c37.
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El cinco de octubre de 1969, los cimientos de la BBC se tambalearon con la explosión de una forma radicalmente nueva de hacer comedia: Monty Python Flying Circus. La serie que iba a estar en antena durante cinco años ininterrumpidos, el último episodio se emitió el 5 de diciembre de 1974, se convirtió con gran rapidez en un éxito clamoroso. Los Python recogieron el legado del mítico The Goon Show o las comedias de la Ealing, así como de figuras tan relevantes con Spike Milligan, Peter Sellers o Richard Lester que cristaliza en un irreverente programa dispuesto a cuestionar inmisericordemente las formas televisivas y las convenciones culturales. La serie resultó ser un espacio abonado a la experimentación estilística y temática mediante la utilización de una compleja forma de comedia que hizo estragos no sólo con el aparato cinematográfico sino también con la cultura contemporánea.Palabras clave: Comedia, Monty Python, Flying Circus, Televisión Británica.
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Bebber, Brett. "The Short Life ofCurry and Chips: Racial Comedy on British Television in the 1960s." Journal of British Cinema and Television 11, no. 2-3 (July 2014): 213–35. http://dx.doi.org/10.3366/jbctv.2014.0204.
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This article analyses Curry and Chips (ITV, 1969), a situation comedy that relied heavily on racial humour to satisfy its audiences. Like other sitcoms during this era in British television, it capitalised on extant anxieties about the increasing migration of formerly colonised subjects to Britain. Johnny Speight and Spike Milligan, the programme's creators, believed that forwarding vulgar racial epithets and bigoted humour put English attitudes to immigration under examination. But the programme proved popular because of its appeal to white workers, who viewed depictions of the challenges of integrating non-white workers in a comedic context with some pleasure. Under the thin guise of political satire, the programme recirculated ethnic stereotypes and racist discourses to make its humour apparent. Audience research and letters of complaint also reveal that Curry and Chips appealed to audiences sympathetic to the racist attitudes forwarded by the programme's characters and failed to change white Britons’ perspectives on migration and integration. Because of the debate it caused about the appropriateness of its humour, Curry and Chips lasted only a single series before being banned by the Independent Television Authority. Like other forms of racial humour, the comedy resonated with working-class anxieties but negated the programme's utility as progressive parody.
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Jacobs, Donna. "Me depressed? Don't make me laugh! A guide to overcoming depressionNick Torrens (Researcher, Writer, Director) & Spike Milligan (Presenter). (1996). [Video]. Sydney: Monkey See Productions. 45 minutes; $95 + $5 p&h." Behaviour Change 15, no. 1 (March 1998): 63. http://dx.doi.org/10.1017/s0813483900005921.
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Hewitt, G. F. "John Gordon Collier, F.R.Eng. 22 January 1935 — 18 November 1995." Biographical Memoirs of Fellows of the Royal Society 45 (January 1999): 67–75. http://dx.doi.org/10.1098/rsbm.1999.0006.
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John Collier was a chemical engineer who, in his earlier career, was a specialist in two–phase flow and heat transfer. He was formerly Chairman of the UK Atomic Energy Authority (UKAEA) and was Chairman of Nuclear Electric plc when he died on 18 November 1995. John Collier was born in London on 22 January 1935. His father, Jack Collier, was a musician who was one of the country's leading double–bass players. Jack had turned down the job of lead bass with the Hallé Orchestra at the age of 20 and set out to see the world. While playing in the ship's band on a transatlantic trip he met John's mother (Edith Georgina de Ville, a passenger on the same ship) and married her soon afterwards, in 1925. John was their only child and his infant years were spent in prewar London, his father making a name for himself playing music of a wide variety. During the war, Jack Collier became a member of ENSA, the Forces' entertainment service. His attempts to protect his wife and child against the bombing seemed to be relatively unsuccessful; he moved them to Southampton, Coventry and Manchester in turn! The young John Collier, at the age of six, was actually machinegunned by a German fighter plane flying down a Southampton street. John and his mother finally returned to London just in time for the start of the V1 (flying bomb) raids. All these moves meant that John attended nine different schools during the war years–a very disruptive experience. The family was reunited again after the war but their happiness was short–lived; John's mother (Edith) had a recurrence of the cancer she had suffered towards the end of the war and died in 1948. In 1951, Jack Collier married Guinevere (Jean) Olga Northcote. By this time, he was working freelance, playing with the major London orchestras; he was much in demand. He still did some work with lighter music, particularly on the radio where he played in such programmes as ITMA (Tommy Handley) and The Goon Show (Spike Milligan, Harry Secombe and Peter Sellers), and he later played on television shows such as The Morecombe and Wise Show.
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Hadjizacharia, Pantelis, Peter Rhee, Viraj Pandit, Hassan Aziz, Donald Green, and Bellal Joseph. "Blunt Assault: ‘Million Dollar Baby’." American Surgeon 80, no. 1 (January 2014): 72–75. http://dx.doi.org/10.1177/000313481408000127.
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Contrasting reports exist in the literature regarding the management of patients with blunt assault to the head, neck, and face and more importantly for clearing the cervical spine. The purpose of our study was to determine the risk of cervical spine injuries after blunt assault to the head, neck, and face and its association with other injuries. We performed a retrospective case review of all blunt assault trauma admissions to the head, neck, and face at our Level I trauma center. We identified all patients who were assaulted with hands and feet and blunt instruments. A total of 3286 patients with blunt assault to the head, neck, and face were identified of whom 11 (0.003%) were found to have a cervical spine fracture or cervical spine subluxation. None of the patients had a cervical spinal cord injury. The 11 patients composed our study population with a mean age of 39 ± 7.8 years, 100 per cent were male, and the mean Injury Severity Score was 12 ± 7.9. Five (45%) patients required surgery for stabilization of the cervical spine. Mortality was reported in only one patient who had a C7 transverse process fracture. Cervical spine injury after blunt assault is rare but does occur and encompasses significant injuries requiring surgical intervention. However, these injuries are the result of direct blows to the cervical spine and we suggest that assaulted patients with no direct trauma to the neck do not require an exhaustive evaluation of the cervical spine.
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Alkhudaydi, Tahani, Daniel Reynolds, Simon Griffiths, Ji Zhou, and Beatriz de la Iglesia. "An Exploration of Deep-Learning Based Phenotypic Analysis to Detect Spike Regions in Field Conditions for UK Bread Wheat." Plant Phenomics 2019 (July 31, 2019): 1–17. http://dx.doi.org/10.34133/2019/7368761.
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Wheat is one of the major crops in the world, with a global demand expected to reach 850 million tons by 2050 that is clearly outpacing current supply. The continual pressure to sustain wheat yield due to the world’s growing population under fluctuating climate conditions requires breeders to increase yield and yield stability across environments. We are working to integrate deep learning into field-based phenotypic analysis to assist breeders in this endeavour. We have utilised wheat images collected by distributed CropQuant phenotyping workstations deployed for multiyear field experiments of UK bread wheat varieties. Based on these image series, we have developed a deep-learning based analysis pipeline to segment spike regions from complicated backgrounds. As a first step towards robust measurement of key yield traits in the field, we present a promising approach that employ Fully Convolutional Network (FCN) to perform semantic segmentation of images to segment wheat spike regions. We also demonstrate the benefits of transfer learning through the use of parameters obtained from other image datasets. We found that the FCN architecture had achieved a Mean classification Accuracy (MA) >82% on validation data and >76% on test data and Mean Intersection over Union value (MIoU) >73% on validation data and and >64% on test datasets. Through this phenomics research, we trust our attempt is likely to form a sound foundation for extracting key yield-related traits such as spikes per unit area and spikelet number per spike, which can be used to assist yield-focused wheat breeding objectives in near future.
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Pace, Christopher M., Joseph R. Donnelly, Jeffrey L. Jeter, William C. Brumley, and G. Wayne Sovocool. "Determination of Aromatic Amines in Soils." Journal of AOAC INTERNATIONAL 79, no. 3 (May 1, 1996): 777–83. http://dx.doi.org/10.1093/jaoac/79.3.777.
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Abstract A rapid liquid chromatographic (LC) method with ultraviolet (UV) or fluorescence detection was developed for parts-per-billion levels of aromatic amines in soils. 2,4-Diaminotoluene, pyridine, aniline, 2-pi-coline, 2-toluidine, 5-nitro-2-toluidine, 2-methyl-6-ethylaniline, 4-aminobiphenyl, 4-nitroaniline, 1-naphthyl-amine, 2-methoxyaniline, and 2-naphthyiamine were tested. The method involves extraction by sonication with 1% ammonium hydroxide–acetonitrile and analysis by LC using gradient elution with aqueous 0.01 M ammonium acetate–0.0005% triethylamine and acetonitrile. Recoveries of 67–106% (9.2 and 34% for 1-and 2-naphthylamines, respectively) were obtained from sand and organic-containing soils spiked in the parts-per-million range. Recoveries from sand spiked at 8.5–25 ppb were 88–105%. Recoveries from organic soil varied from nondetectable to 86% at spikes of 85–500 ppb. Detection limits ranged from 0.5 ppb for highly fluorescent 2-naphthyiamine (by fluorescence detection) to 0.5 ppm for nonfluorescing pyridines (by UV detection).
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Pillay, Tahir S. "Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein." Journal of Clinical Pathology 73, no. 7 (May 6, 2020): 366–69. http://dx.doi.org/10.1136/jclinpath-2020-206658.
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The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called COVID-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be ‘preactivated’ and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV-2 spike protein S.
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Marks, Paul. "Swipe for 5 million filters to spice up your selfies." New Scientist 227, no. 3036 (August 2015): 19. http://dx.doi.org/10.1016/s0262-4079(15)31069-1.
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Ehsan, Muhammad Ali, Safyan Akram Khan, and Abdul Rehman. "Screen-Printed Graphene/Carbon Electrodes on Paper Substrates as Impedance Sensors for Detection of Coronavirus in Nasopharyngeal Fluid Samples." Diagnostics 11, no. 6 (June 3, 2021): 1030. http://dx.doi.org/10.3390/diagnostics11061030.
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Severe acute respiratory syndrome (SARS-CoV-2), the causative agent of the global pandemic, which has resulted in more than one million deaths with tens of millions reported cases, requires a fast, accurate, and portable testing mechanism operable in the field environment. Electrochemical sensors, based on paper substrates with portable electrochemical devices, can prove an excellent alternative in mitigating the economic and public health effects of the disease. Herein, we present an impedance biosensor for the detection of the SARS-CoV-2 spike protein utilizing the IgG anti-SARS-CoV-2 spike antibody. This label-free platform utilizing screen-printed electrodes works on the principle of redox reaction impedance of a probe and can detect antigen spikes directly in nasopharyngeal fluid as well as virus samples collected in the universal transport medium (UTM). High conductivity graphene/carbon ink is used for this purpose so as to have a small background impedance that leads to a wider dynamic range of detection. Antibody immobilization onto the electrode surface was conducted through a chemical entity or a biological entity to see their effect; where a biological immobilization can enhance the antibody loading and thereby the sensitivity. In both cases, we were able to have a very low limit of quantification (i.e., 0.25 fg/mL), however, the linear range was 3 orders of magnitude wider for the biological entity-based immobilization. The specificity of the sensor was also tested against high concentrations of H1N1 flu antigens with no appreciable response. The most optimized sensors are used to identify negative and positive COVID-19 samples with great accuracy and precision.
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Gyrka, A. D., O. O. Pedash, I. O. Kulyk, O. O. Viniukov, and V. A. Ischenko. "ПРОДУКТИВНІСТЬ ПШЕНИЦІ ОЗИМОЇ ЗАЛЕЖНО ВІД СТРОКУ СІВБИ ТА НОРМИ ВИСІВУ ПІСЛЯ РІПАКУ ОЗИМОГО В УМОВАХ СТЕПУ." Ukrainian Journal of Ecology 7, no. 1 (March 18, 2017): 30–36. http://dx.doi.org/10.15421/20173.
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<p>The effect of sowing time and seeding rate on productivity of winter wheat after unusual predecessor – winter rape was investigated. Results of studies indicates, that number of plants per unit area, their productive tillering, grain weight per spike, number of grains per spike had higher values at the optimum sowing time, which in our experiments was on September, 20. Delay in planting until September, 30, and even more, till October, 10 negatively impacted primarily the stand density of plants, their productive tillering, grain content per spike, grain weight per spike and 1000 grain weight. During the research, the highest yield of winter wheat (5.23 t/ha) was obtained in plots where sowing was carried out on September, 20 with seeding rate at 5 and 6 million/ha. The sowing in earlier (September, 10) and later (September, 30) period led to decrease of crop yields at 0.41 and 0.49 t/ha respectively.</p>
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Casalino, Lorenzo, Abigail C. Dommer, Zied Gaieb, Emilia P. Barros, Terra Sztain, Surl-Hee Ahn, Anda Trifan, et al. "AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics." International Journal of High Performance Computing Applications 35, no. 5 (April 20, 2021): 432–51. http://dx.doi.org/10.1177/10943420211006452.
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We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spike’s full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems.
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Amalova, Akerke, Saule Abugalieva, Adylkhan Babkenov, Sandukash Babkenova, and Yerlan Turuspekov. "Genome-wide association study of yield components in spring wheat collection harvested under two water regimes in Northern Kazakhstan." PeerJ 9 (July 27, 2021): e11857. http://dx.doi.org/10.7717/peerj.11857.
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Background Bread wheat is the most important cereal in Kazakhstan, where it is grown on over 12 million hectares. One of the major constraints affecting wheat grain yield is drought due to the limited water supply. Hence, the development of drought-resistant cultivars is critical for ensuring food security in this country. Therefore, identifying quantitative trait loci (QTLs) associated with drought tolerance as an essential step in modern breeding activities, which rely on a marker-assisted selection approach. Methods A collection of 179 spring wheat accessions was tested under irrigated and rainfed conditions in Northern Kazakhstan over three years (2018, 2019, and 2020), during which data was collected on nine traits: heading date (HD), seed maturity date (SMD), plant height (PH), peduncle length (PL), number of productive spikes (NPS), spike length (SL), number of kernels per spike (NKS), thousand kernel weight (TKW), and kernels yield per m2 (YM2). The collection was genotyped using a 20,000 (20K) Illumina iSelect SNP array, and 8,662 polymorphic SNP markers were selected for a genome-wide association study (GWAS) to identify QTLs for targeted agronomic traits. Results Out of the total of 237 discovered QTLs, 50 were identified as being stable QTLs for irrigated and rainfed conditions in the Akmola region, Northern Kazakhstan; the identified QTLs were associated with all the studied traits except PH. The results indicate that nine QTLs for HD and 11 QTLs for SMD are presumably novel genetic factors identified in the irrigated and rainfed conditions of Northern Kazakhstan. The identified SNP markers of the QTLs for targeted traits in rainfed conditions can be applied to develop new competitive spring wheat cultivars in arid zones using a marker-assisted selection approach.
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Vernet, Rémi, Emily Charrier, Julien Grogg, and Nicolas Mach. "A Quantitative ELISA Protocol for Detection of Specific Human IgG against the SARS-CoV-2 Spike Protein." Vaccines 9, no. 7 (July 9, 2021): 770. http://dx.doi.org/10.3390/vaccines9070770.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with at least 3.8 million deaths to date. For that reason, finding an efficient vaccine for this virus quickly became a global priority. The majority of vaccines now marketed are based on the SARS-CoV-2 spike protein that has been described as the keystone for optimal immunization. In order to monitor SARS-CoV-2 spike-specific humoral responses generated by immunization or infection, we have developed a robust and reproducible enzyme-linked immunosorbent assay (ELISA) protocol. This protocol describes a method for quantitative detection of IgG antibodies against the SARS-CoV-2 spike protein using antigen-coated microtiter plates. Results showed that antibodies could be quantified between the range of 1.953 ng/mL to 500 ng/mL with limited inter- and intra-assay variability.
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George, Santosh, Anasuya Chattopadhyay Pal, Jacqueline Gagnon, Sushma Timalsina, Pallavi Singh, Pratap Vydyam, Muhammad Munshi, et al. "Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients." Kidney360 2, no. 6 (April 14, 2021): 924–36. http://dx.doi.org/10.34067/kid.0002172021.
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AbstractBackgroundSARS-CoV-2 infection has, as of April 2021, affected >133 million people worldwide, causing >2.5 million deaths. Because the large majority of individuals infected with SARS-CoV-2 are asymptomatic, major concerns have been raised about possible long-term consequences of the infection.MethodsWedeveloped an antigen capture assay to detect SARS-CoV-2 spike protein in urine samples from patients with COVID-19whose diagnosis was confirmed by positive PCR results from nasopharyngeal swabs (NP-PCR+) forSARS-CoV-2. We used a collection of 233 urine samples from 132 participants from Yale New Haven Hospital and the Children’s Hospital of Philadelphia that were obtained during the pandemic (106 NP-PCR+ and 26 NP-PCR−), and a collection of 20 urine samples from 20 individuals collected before the pandemic.ResultsOur analysis identified 23 out of 91 (25%) NP-PCR+ adult participants with SARS-CoV-2 spike S1 protein in urine (Ur-S+). Interestingly, although all NP-PCR+ children were Ur-S−, one child who was NP-PCR− was found to be positive for spike protein in their urine. Of the 23 adults who were Ur-S+, only one individual showed detectable viral RNA in urine. Our analysis further showed that 24% and 21% of adults who were NP-PCR+ had high levels of albumin and cystatin C, respectively, in their urine. Among individuals with albuminuria (>0.3 mg/mg of creatinine), statistical correlation could be found between albumin and spike protein in urine.ConclusionsTogether, our data showed that one of four individuals infected with SARS-CoV-2 develop renal abnormalities, such as albuminuria. Awareness about the long-term effect of these findings is warranted.
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Prompetchara, Eakachai, Chutitorn Ketloy, Kittipan Tharakhet, Papatsara Kaewpang, Supranee Buranapraditkun, Teerasit Techawiwattanaboon, Suwitra Sathean-anan-kun, et al. "DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice." PLOS ONE 16, no. 3 (March 22, 2021): e0248007. http://dx.doi.org/10.1371/journal.pone.0248007.
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More than 65 million people have been confirmed infection with SARS-CoV-2 and more than 1 million have died from COVID-19 and this pandemic remains critical worldwide. Effective vaccines are one of the most important strategies to limit the pandemic. Here, we report a construction strategy of DNA vaccine candidates expressing full length wild type SARS-CoV-2 spike (S) protein, S1 or S2 region and their immunogenicity in mice. All DNA vaccine constructs of pCMVkan-S, -S1 and -S2 induced high levels of specific binding IgG that showed a balance of IgG1/IgG2a response. However, only the sera from mice vaccinated with pCMKkan-S or -S1 DNA vaccines could inhibit viral RBD and ACE2 interaction. The highest neutralizing antibody (NAb) titer was found in pCMVkan-S group, followed by -S1, while -S2 showed the lowest PRNT50 titers. The geometric mean titers (GMTs) were 2,551, 1,005 and 291 for pCMVkan-S, -S1 and -S2, respectively. pCMVkan-S construct vaccine also induced the highest magnitude and breadth of T cells response. Analysis of IFN-γ positive cells after stimulation with SARS-CoV-2 spike peptide pools were 2,991, 1,376 and 1,885 SFC/106 splenocytes for pCMVkan-S, -S1 and -S2, respectively. Our findings highlighted that full-length S antigen is more potent than the truncated spike (S1 or S2) in inducing of neutralizing antibody and robust T cell responses.
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Zha, Lisha, Xinyue Chang, Hongxin Zhao, Mona O. Mohsen, Liang Hong, Yuhang Zhou, Hongquan Chen, et al. "Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles." Vaccines 9, no. 4 (April 16, 2021): 395. http://dx.doi.org/10.3390/vaccines9040395.
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The ongoing coronavirus disease (COVID-19) pandemic is caused by a new coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) first reported in Wuhan City, China. From there, it has been rapidly spreading to many cities inside and outside China. Nowadays, more than 110 million cases with deaths surpassing 2 million have been recorded worldwide, thus representing a major health and economic issues. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here, we demonstrated that the recombinantly expressed receptor-binding domain (RBD) of the spike protein can be coupled to immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMVTT). The RBD displayed CuMVTT bound to ACE2, the viral receptor, demonstrating proper folding of RBD. Furthermore, a highly repetitive display of the RBD on CuMVTT resulted in a vaccine candidate that induced high levels of specific antibodies in mice, which were able to block binding of the spike protein to ACE2 and potently neutralize SARS-CoV-2 virus in vitro.
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Ebrahimpour, Adel, Mohammadreza Chehrassan, Mehrdad Sadighi, Mehdi Azizmohammad Looha, Amin Karimi, Alireza Raeisi, Alireza Zali, and Mohammad Esmaeil Akbari. "Mobile Spine Osseous Sarcoma: Descriptive Epidemiological Analysis Based on a National Population-Based Study." Archives of Iranian Medicine 24, no. 8 (August 1, 2021): 629–35. http://dx.doi.org/10.34172/aim.2021.89.
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Background: Primary osseous sarcomas of the mobile spine are rare bony tumors. Ewing sarcoma, chondrosarcoma, chordoma and osteosarcoma constitute the majority of primary bone sarcomas of the spine; however, other rare sarcoma tumors may also affect the spine. In order to perform an epidemiological study of theses tumors, national registries may help to evaluate data for populations with similar characteristics. Methods: A population-based study was designed based on data from the Iran National Cancer Registry (INCR). All morphology codes (M-Code) of primary osseous sarcomas of the mobile spine (C-code 41.2) were derived and analyzed. Results: Among 186 patients with primary osseous sarcomas of the mobile spine, 67.2% were men and 32.8% were women. The median (IQR) age was 37.0 (20.0–59.0) years and the age-standardized incidence rate (ASIR) was 0.37 per million. The majority of cases of Ewing sarcoma (29.5%) were observed in the age group 20–25 years. Among male patients with chondrosarcoma, the median age was 39.0 (30.0–50.0), while females showed a median age of 56.0 (50.0–59.0). The median age of patients with chordoma was 54.0 (47.0–63.0) years. The crude incidence rate of mobile spine osteosarcoma was 0.04 per million. Conclusion: Ewing sarcoma was the most frequent primary osseous sarcoma of the mobile spine. A male predilection was observed among all major sarcomas of the mobile spine. Ewing sarcoma in Iran affects the mobile spine in slightly older ages compared to other studies. Myxoid chondrosarcoma is the most frequent subtype of the mobile spine chondrosarcoma. Chordoma affects male in older ages compared to females. In contrast with other studies which showed a bimodal distribution of osteosarcoma of the spine including young adult and older age groups, 86% of cases in Iran were in the age group of 10–40 years.
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Salleh, Mohd Zulkifli, Jeremy P. Derrick, and Zakuan Zainy Deris. "Structural Evaluation of the Spike Glycoprotein Variants on SARS-CoV-2 Transmission and Immune Evasion." International Journal of Molecular Sciences 22, no. 14 (July 10, 2021): 7425. http://dx.doi.org/10.3390/ijms22147425.
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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents significant social, economic and political challenges worldwide. SARS-CoV-2 has caused over 3.5 million deaths since late 2019. Mutations in the spike (S) glycoprotein are of particular concern because it harbours the domain which recognises the angiotensin-converting enzyme 2 (ACE2) receptor and is the target for neutralising antibodies. Mutations in the S protein may induce alterations in the surface spike structures, changing the conformational B-cell epitopes and leading to a potential reduction in vaccine efficacy. Here, we summarise how the more important variants of SARS-CoV-2, which include cluster 5, lineages B.1.1.7 (Alpha variant), B.1.351 (Beta), P.1 (B.1.1.28/Gamma), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota) and B.1.617.2 (Delta) confer mutations in their respective spike proteins which enhance viral fitness by improving binding affinity to the ACE2 receptor and lead to an increase in infectivity and transmission. We further discuss how these spike protein mutations provide resistance against immune responses, either acquired naturally or induced by vaccination. This information will be valuable in guiding the development of vaccines and other therapeutics for protection against the ongoing coronavirus disease 2019 (COVID-19) pandemic.
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Santra, Sourav, Sasti Gopal Das, Suman Kumar Halder, Kuntal Ghosh, Amrita Banerjee, Amiya Kumar Panda, and Keshab Chandra Mondal. "Structure-based assortment of herbal analogues against spike protein to restrict COVID-19 entry through hACE2 receptor: An in-silico approach." Acta Biologica Szegediensis 64, no. 2 (April 10, 2021): 159–71. http://dx.doi.org/10.14232/abs.2020.2.159-171.
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On-going global pandemic COVID-19 has spread all over the world and has led to more than 1.97 million deaths till date. Natural compounds may be useful to protecting health in this perilous condition. Mechanism of shuttle entry of SARS-COV-2 virus is by interaction with viral spike protein with human angiotensin-converting enzyme-2 (ACE-2) receptor. To explore potential natural therapeutics, 213 important phytochemi-cals of nine medicinal plants Aconitum heterophyllum, Cassia angustifolia, Cymbopogon flexuosus, Cymbopogon martinii, Nux vomica, Phyllanthus urinaria, Swertia chirayita, Justicia adhatoda, Vetiveria zizanioides were selected for in-silico molecular docking against the spike protein of SARS-COV-2 and compared with recently prescribed drug chloroquine, ramdesivir, lopinavir and hydroxychloroquine. Results revealed that rhamnocitrin of P. urinaria, 1,5-dihydroxy-3,8-dimethoxyxanthone of S. chirayita and laevojunenol of V. zizanioides potentially binds with the receptor binding site of SARS-COV-2 spike glycoprotein and more robustly destabilized the RBD-ACE-2 binding over chloroquine, ramdesivir, lopinavir and hydroxychloroquine. It was also found that laevojunenol, rhamnocitrin, and 1,5-dihydroxy-3,8-dimethoxyxanthone qualified the criteria for drug-likeness as per Lipinski rule. After attachment of the selected phytochemical with the spike protein the affinity of the later towards ACE-2 was minimized and the effect of 1,5-dihydroxy-3,8-dimethoxyxanthone and laevojunenol was superior. Hence, rhamnocitrin of P. urinaria, 1,5-dihydroxy-3,8-dimethoxyxanthone of S. chirayita and laevojunenol of V. zizanioides, are potential therapeutic molecules for SARS-COV-2, which upon binding with spike protein changes the affinity of the spike towards ACE-2 and therefore restrict the entry of the virus into a human cell. Subsequent clinical validation is needed to confirm these phytochemicals as drugs to combat COVID-19.
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Pramanik, Avijit, Ye Gao, Shamily Patibandla, Dipanwita Mitra, Martin G. McCandless, Lauren A. Fassero, Kalein Gates, Ritesh Tandon, and Paresh Chandra Ray. "The rapid diagnosis and effective inhibition of coronavirus using spike antibody attached gold nanoparticles." Nanoscale Advances 3, no. 6 (2021): 1588–96. http://dx.doi.org/10.1039/d0na01007c.
Full textAbstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease that began in 2019 (COVID-19), has been responsible for 1.4 million deaths worldwide as of 13 November 2020.
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Mladenov, Velimir, Miodrag Dimitrijevic, Sofija Petrovic, Jan Bocanski, Borislav Banjac, Ankica Kondic-Spika, and Dragana Trkulja. "Genetic analysis of spike length in wheat." Genetika 51, no. 1 (2019): 167–78. http://dx.doi.org/10.2298/gensr1901167m.
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The permanent need for efficient plant breeding comes from the increment of human population, which is projected to reach 9.7 million by 2050. Novel approaches could be used to reach these goals more rapidly, raising the question of efficiency, as well. Spike length is one of the important components of grain yield formation in wheat. The influence of individual plan traits is getting more important to grain yield formation per area unit in stressful growing conditions, which are increasingly present due to global climate changes. The objectives of the present research were three-fold: (i) to determine the influence of a genotype, environment and their interaction on spike length and to evaluate stability of the trait; (ii) to present cause-causing links on a graphical example; (iii) to transform a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components. Samples were obtained from 96 winter wheat cultivars grown in 2011/12 and 2012/13 on two locations. The wheat genotype population was profiled with 28 microsatellites. The ANOVA of the total phenotypic variation of the experiment shows that genotypes took the largest portion, followed by the influence of the GE interaction. Additional analysis of the GE interaction using the PCA analysis shows a statistical significance of the first two main components. In the conducted research, the dispersion of the points represents two subpopulations, but the geographical origin could not explain the grouping of genotypes within the same, so the division into two groups was done on the basis of their lines of descent.
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Sikora, Mateusz, Sören von Bülow, Florian E. C. Blanc, Michael Gecht, Roberto Covino, and Gerhard Hummer. "Computational epitope map of SARS-CoV-2 spike protein." PLOS Computational Biology 17, no. 4 (April 1, 2021): e1008790. http://dx.doi.org/10.1371/journal.pcbi.1008790.
Full textAbstract:
The primary immunological target of COVID-19 vaccines is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface and mediates viral entry into the host cell. To identify possible antibody binding sites, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation, and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for structure-based vaccine design. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics. The protective glycan shield and the high flexibility of its hinges give the stalk overall low epitope scores. Our computational epitope-mapping procedure is general and should thus prove useful for other viral envelope proteins whose structures have been characterized.
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Winsor, Matthew S. "Bridging the Language Barrier in Mathematics." Mathematics Teacher 101, no. 5 (December 2007): 372–78. http://dx.doi.org/10.5951/mt.101.5.0372.
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Teaching mathematics to English Language Learners (ELL students) has become a challenge faced by an increasing number of U.S. teachers. Between 1979 and 2004, the number of K–12 students who spoke a language other than English at home increased from 3.8 million to 9.9 million. During that same time, the number of K–12 students who had difficulty speaking English increased from 1.3 million to 2.8 million (U.S. Department of Education 2006). Even teachers who may speak a second language still face the daunting task of teaching mathematics effectively to ELL students. I was one of those teachers. From 1995 to 1999, I taught at a high school in Southern California where the student population was 56 percent Hispanic. I spoke Spanish and was hired in part to teach mathematics to ELL students. I taught my classes in English. My school had no materials for use in an ELL class with Spanish speakers, and I could not find a textbook company that offered such materials. I was also not eager to spend enormous amounts of time trying to translate mathematics texts.
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Filler, Aaron G. "Emergence and optimization of upright posture among hominiform hominoids and the evolutionary pathophysiology of back pain." Neurosurgical Focus 23, no. 1 (July 2007): 1–6. http://dx.doi.org/10.3171/foc-07/07/e4.
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✓The lordotic region of the lumbar spine is a significant focus of pain and dysfunction in the human body, and its susceptibility to disorders may reflect its substantial reconfiguration during the course of human evolution. The basic anatomy of the lumbar vertebra in Old World Monkeys and Early Miocene apes, or proconsulids, retains typical mammalian architecture. The lumbar vertebra in humans is different in the repositioning of the lumbar transverse process dorsal to the vertebral body rather than originating on the body itself and in the loss of the styloid process that is adjacent to the facets in other primates. These two features appeared in Morotopithecus bishopi 21.6 million years ago, suggesting that this ape is the founder of an upright hominiform lineage. The iliocostalis lumborum muscles migrated onto the iliac crest approximately 18 million years ago, becoming a powerful lateral flexor muscle of the trunk. The posterior superior iliac spine shifted far dorsal to the longissimus insertion in the genus Homo between 1 and 2 million years ago, making this muscle a powerful extensor of the lumbar spine. Functionally, the establishment of strong muscular flexors and extensors adds dynamic compressive stresses to the lumbar disks and also makes these muscles susceptible to strain.
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Wajnberg, Ania, Fatima Amanat, Adolfo Firpo, Deena R. Altman, Mark J. Bailey, Mayce Mansour, Meagan McMahon, et al. "Robust neutralizing antibodies to SARS-CoV-2 infection persist for months." Science 370, no. 6521 (October 28, 2020): 1227–30. http://dx.doi.org/10.1126/science.abd7728.
Full textAbstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection.
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Badraoui, Riadh, Mohd Adnan, Fevzi Bardakci, and Mousa M. Alreshidi. "Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism." Molecules 26, no. 3 (January 28, 2021): 673. http://dx.doi.org/10.3390/molecules26030673.
Full textAbstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inducing coronavirus disease 2019 (COVID-19) is still an ongoing challenge. To date, more than 95.4 million have been infected and more than two million deaths have been officially reported by the WHO. Angiotensin-converting enzyme (ACE) plays a key role in the disease pathogenesis. In this computational study, seventeen coding variants were found to be important for ACE2 binding with the coronavirus spike protein. The frequencies of these allele variants range from 3.88 × 10−3 to 5.47 × 10−6 for rs4646116 (K26R) and rs1238146879 (P426A), respectively. Chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are mainly used to prevent and treat malaria and rheumatic diseases. They are also used in several countries to treat SARS-CoV-2 infection inducing COVID-19. Both CQ and HCQ were found to interact differently with the various ACE2 domains reported to bind with coronavirus spike protein. A molecular docking approach revealed that intermolecular interactions of both CQ and HCQ exhibited mediation by ACE2 polymorphism. Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies, particularly their use in the absence of specific vaccines or drugs.
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Blobel, Gerd A., Chris C. S. Hsiung, Peng Huang, Cheryl Keller, Paul Ginart, Kristen Jahn, Caroline Bartman, et al. "A Hyperactive Transcriptional State Marks Genome Reactivation during Mitotic Exit." Blood 126, no. 23 (December 3, 2015): 48. http://dx.doi.org/10.1182/blood.v126.23.48.48.
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Abstract The tremendous proliferative capacity of erythroid precursor cells underlies the production of over a million red blood cells per second in adult humans. During every mitosis the mammalian nucleus is disassembled and transcriptionally silent. Genome reactivation after mitosis is a key step in the propagation of transcriptional programs through cell generations, yet how this occurs remains largely unexplored. We carried out the first genome wide survey of transcription in cells emerging from mitosis using RNA polymerase II ChIP seq in purified populations at various post-mitotic time points. Using unsupervised approaches, we discover and classify genome reactivation patterns among genes. A surprisingly large fraction of genes (~25%) displays a post-mitotic spike in transcription. This spike represents the first complete round of transcription and accounts for the greatest gene-to-gene variance in temporal patterns of transcription in G1 phase. Another notable and contrasting pattern is gene activation late in the G1 phase. Single-molecule RNA FISH imaging demonstrates that the post-mitotic transcriptional spike represents the highest activity throughout the cell cycle and results in an increase in mature mRNAs, indicating that the phenomenon has the capacity to alter gene expression. Surprisingly, the post-mitotic transcriptional spike occurs independent of enhancer action and can be recapitulated with promoter sequences ectopically integrated into the genome. In contrast, late-G1 gene reactivation is distinct and requires enhancer function. Our findings uncover novel modes of transcriptional control during exit from mitosis with implications for our understanding of transitions in gene expression states in dividing cells. Disclosures No relevant conflicts of interest to declare.
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Donier, J., and J. Bonart. "A Million Metaorder Analysis of Market Impact on the Bitcoin." Market Microstructure and Liquidity 01, no. 02 (December 2015): 1550008. http://dx.doi.org/10.1142/s2382626615500082.
Full textAbstract:
We present a thorough empirical analysis of market impact on the Bitcoin/USD exchange market using a complete dataset that allows us to reconstruct more than one million metaorders. We empirically confirm the “square-root law” for market impact, which holds on four decades in spite of the quasi-absence of statistical arbitrage and market marking strategies. We show that the square-root impact holds during the whole trajectory of a metaorder and not only for the final execution price. We also attempt to decompose the order flow into an “informed” and “uninformed” component, the latter leading to an almost complete long-term decay of impact. This study sheds light on the hypotheses and predictions of several market impact models recently proposed in the literature and promotes heterogeneous agent models as promising candidates to explain price impact on the Bitcoin market — and, we believe, on other markets as well.
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Pedachenko, Eugene G., Ievgenii I. Slynko, Oleksii S. Nekhlopochyn, Anna N. Nikiforova, Viacheslav S. Botev, and Tetyana A. Yovenko. "Epidemiology of tumors of the spinal cord and spine in Ukraine in 2000-2019." Ukrainian Neurosurgical Journal 27, no. 1 (March 29, 2021): 11–20. http://dx.doi.org/10.25305/unj.217283.
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Objective. To determine the dynamics and state of neurosurgical care for tumors of the spinal cord and spine (TSCS) in Ukraine. Materials and methods. The work is based on the analysis of hospitalizations and surgical treatment of patients with TSCS in neurosurgical departments of Ukraine in 2000-2019. Results. In 2019, 1,325 patients with TSCS were hospitalized in neurosurgical departments of Ukraine, which is 2,3 times more than in 2000 (567), per 1 million population - almost 3 times (34,7 vs. 11, 6 ). Over 20 years, the number of operated patients increased 2,8 times (from 385 to 1079), per 1 million population - 3,6 times (from 7,9 to 28,3), there was an increase in surgical activity by 20% (from 67,9 to 81,4%), a decrease in the general and postoperative mortality - twice (from 2,6 to 1,2% and from 2,6 to 1,3% respectively). Patients with TSCS account for 1,5% of all patients hospitalized in neurosurgical departments of Ukraine, 12,8% of all CNS neoplasms and 5,2% of all spinal pathology. Vertebral tumors account for 42,64% of all TSCS and extramedullary tumors have an incidence rate similar to vertebral tumors (42,64%), intramedullary tumors account for 14,72%. In 2019, 74.4% more patients with extramedullary tumors were hospitalized than in 2000 (565 and 324 respectively), and 84.5% more were operated on (463 and 251 respectively). The rate of increase is even higher per 1 million population. In 2019, there were 14.8 hospitalizations per 1 million population for extramedullary tumors, which is 2.2 times greater than in 2000 (6,6 hospitalizations), and 12,1 operations, which is 2,4 times greater than in 2000 (5,1 operations). In 2019, patients with intramedullary tumors were hospitalized 2,2 times more than in 2000. (195 and 89 respectively), were operated 2,5 times more (151 and 61 respectively). The rate of increase is even 4higher per 1 million population. In 2019, there were 5,1 hospitalizations for intramedullary tumors per 1 million population, which is 2,8 times greater than in 2000 (1,8 hospitalizations), and 4,0 operations, which is 3,2 times greater than in 2000 (1,2 operations). In 2019, patients with vertebral tumors were hospitalized 3.7 times more than in 2000 (565 and 154 respectively), were operated 6,4 times more (465 and 73 respectively). The rate of increase is even higher per 1 million population. In 2019, there were 14,8 hospitalizations per 1 million population for vertebral tumors, which is 4,7 greater than in 2000 (3,1 hospitalizations), and 12,2 surgeries, which is 8,2 greater than in 2000 (1,5 operations). Сonclusions. The introduction of modern neuroimaging methods and advanced treatment methods into clinical practice has contributed to an increase in the number of hospitalizations and surgical interventions in TSCS.
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&NA;. "The Total Number of Spine Operations in the United States Approaches Half a Million Annually." Back Letter 10, no. 5 (May 1995): 52. http://dx.doi.org/10.1097/00130561-199505000-00005.
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Nguyen, Dung, Donal Skelly, and Niluka Goonawardane. "A Novel Immunofluorescence Assay for the Rapid Serological Detection of SARS-CoV-2 Infection." Viruses 13, no. 5 (April 24, 2021): 747. http://dx.doi.org/10.3390/v13050747.
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As of April 2021, the COVID-19 pandemic has swept through 213 countries and infected more than 132 million individuals globally, posing an unprecedented threat to human health. There are currently no specific antiviral treatments for COVID-19 and vaccination programmes, whilst promising, remain in their infancy. A key to restricting the pandemic is the ability to minimize human–human transmission and to predict the infection status of the population in the face of emerging SARS-CoV-2 variants. Success in this area is dependent on the rapid detection of COVID-19 positive individuals with current/previous SARS-CoV-2 infection status. In this regard, the ability to detect antibodies directed against the SARS-CoV-Spike protein in patient sera represents a powerful biomarker for confirmation of infection. Here, we report the design of a proof-of-concept cell–based fluorescent serology assay (termed C19-S-I-IFA) to detect SARS-CoV-2 infection. The assay is based on the capture of IgG antibodies in the serum of COVID-19-positive patients using cells exogenously expressing SARS-CoV-2-Spike and their subsequent fluorescent detection. We validate the assay in 30 blood samples collected in Oxford, UK, in 2020 during the height of the pandemic. Importantly, the assay can be modified to express emerging Spike-variants to permit assessments of the cross-reactivity of patient sera to emerging SARS-CoV-2 strains.
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Bugembe, Daniel Lule, My V. T. Phan, Isaac Ssewanyana, Patrick Semanda, Hellen Nansumba, Beatrice Dhaala, Susan Nabadda, et al. "Emergence and spread of a SARS-CoV-2 lineage A variant (A.23.1) with altered spike protein in Uganda." Nature Microbiology 6, no. 8 (June 23, 2021): 1094–101. http://dx.doi.org/10.1038/s41564-021-00933-9.
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AbstractHere, we report SARS-CoV-2 genomic surveillance from March 2020 until January 2021 in Uganda, a landlocked East African country with a population of approximately 40 million people. We report 322 full SARS-CoV-2 genomes from 39,424 reported SARS-CoV-2 infections, thus representing 0.8% of the reported cases. Phylogenetic analyses of these sequences revealed the emergence of lineage A.23.1 from lineage A.23. Lineage A.23.1 represented 88% of the genomes observed in December 2020, then 100% of the genomes observed in January 2021. The A.23.1 lineage was also reported in 26 other countries. Although the precise changes in A.23.1 differ from those reported in the first three SARS-CoV-2 variants of concern (VOCs), the A.23.1 spike-protein-coding region has changes similar to VOCs including a change at position 613, a change in the furin cleavage site that extends the basic amino acid motif and multiple changes in the immunogenic N-terminal domain. In addition, the A.23.1 lineage has changes in non-spike proteins including nsp6, ORF8 and ORF9 that are also altered in other VOCs. The clinical impact of the A.23.1 variant is not yet clear and it has not been designated as a VOC. However, our findings of emergence and spread of this variant indicate that careful monitoring of this variant, together with assessment of the consequences of the spike protein changes for COVID-19 vaccine performance, are advisable.
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Osorio-González, D., V. J. Muñiz-Orozco, C. P. González, M. Fuentes-Acosta, J. Mulia-Rodríguez, and L. A. Mandujano-Rosas. "Receptor Binding Domain (RBD) Structural Susceptibility in the SARS-CoV-2 Virus Spike Protein Exposed to a Pulsed Electric Field." Journal of Nuclear Physics, Material Sciences, Radiation and Applications 8, no. 2 (February 10, 2021): 177–82. http://dx.doi.org/10.15415/jnp.2021.82023.
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SARS-CoV-2 is responsible for causing the Coronavirus disease 2019 (COVID-19) pandemic, which has so far infected more than thirty million people and caused almost a million deaths. For this reason, it has been a priority to stop the transmission of the outbreak through preventive measures, such as surface disinfection, and to establish bases for the design of an effective disinfection technique without chemical components. In this study, we performed in silico analysis to identify the conformational alterations of the SARS-CoV-2 Spike Receptor Binding Domain (RBD) caused by the effect of a pulsed electric field at two different intensities. We found that both stimuli, especially the one with the highest angular frequency and amplitude, modified the electrical charge distribution in the RBD surface and the number of hydrogen bonds. Moreover, the secondary structure was significantly affected, with a decrease of the structured regions, particularly the regions with residues involved in recognizing and interacting with the receptor ACE2. Since many regions suffered conformational changes, we calculated RMSF and ΔRMSF to identify the regions and residues with larger fluctuations and higher flexibility. We found that regions conformed by 353-372, 453-464, and 470-490 amino acid residues fluctuate the most, where the first is considered a therapeutic target, and the last has alreadybeen characterized for its flexibility. Our results indicate that a pulsed electric field can cause loss of stability in the Spike-RBD, and we were able to identify the vulnerable sites to be used as a starting point for the development of viral inhibition or inactivation mechanisms.
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Danziger, Ron, Christina Tan, Leonid Churilov, Peter Mitchell, Richard Dowling, Steven Bush, and Bernard Yan. "Intrinsic hospital factors: overlooked cause for variations in delay to transfer for endovascular thrombectomy." Journal of NeuroInterventional Surgery 13, no. 10 (February 16, 2021): 968–73. http://dx.doi.org/10.1136/neurintsurg-2020-016836.
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BackgroundIntrinsic hospital factors leading to time delay to inter-hospital transfer for endovascular thrombectomy (EVT) have not been adequately investigated, leading to uncertainty in generalizability of hub and spoke EVT services. We investigated the contribution of intrinsic hospital factors to variations in time delay in a multicenter, retrospective study.MethodsThe setting was a hub and spoke EVT state-wide system for a population of 6.3 million and 34 spoke hospitals. We collected data on acute large vessel occlusion strokes transferred from spoke to hub for consideration of EVT between January 2016 and December 2018. The primary endpoint was the proportion of variability in delay-time in transfer cases contributed to by intrinsic hospital factors estimated through variance component analysis implemented as a mixed-effect linear regression model with hospitals as random effects.ResultsWe included 434 patients. The median age was 72 years (IQR 62–79), 44% were female, and the median baseline National Institutes of Health Stroke Scale (NIHSS) was 16 (IQR 11–20). The median onset to CT time was 100 mins (IQR 69–157) at the spoke hospitals and CT acquisition at the spoke hospital to time of transfer was 93 min (IQR 70–132). 53% of the observed variability in time from CT acquisition at the spoke hospital to transfer to the EVT center was explained by intrinsic hospital factors, as opposed to patient-related factors.ConclusionsIntrinsic hospital factors explained more than half of the observed variability in time from CT acquisition at the spoke hospital to departure for transfer. We recommend that the design of hub and spoke EVT services should account for intrinsic hospital factors to minimize hospital transfer delay.
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Hong, Junping, Qian Wang, Qian Wu, Junyu Chen, Xijing Wang, Yingbin Wang, Yixin Chen, and Ningshao Xia. "Rabbit Monoclonal Antibody Specifically Recognizing a Linear Epitope in the RBD of SARS-CoV-2 Spike Protein." Vaccines 9, no. 8 (July 28, 2021): 829. http://dx.doi.org/10.3390/vaccines9080829.
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To date, SARS-CoV-2 pandemic has caused more than 188 million infections and 4.06 million deaths worldwide. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein has been regarded as an important target for vaccine and therapeutics development because it plays a key role in binding the human cell receptor ACE2 that is required for viral entry. However, it is not easy to detect RBD in Western blot using polyclonal antibody, suggesting that RBD may form a complicated conformation under native condition and bear rare linear epitope. So far, no linear epitope on RBD is reported. Thus, a monoclonal antibody (mAb) that recognizes linear epitope on RBD will become valuable. In the present study, an RBD-specific rabbit antibody named 9E1 was isolated from peripheral blood mononuclear cells (PBMC) of immunized rabbit by RBD-specific single B cell sorting and mapped to a highly conserved linear epitope within twelve amino acids 480CNGVEGFNCYFP491 on RBD. 9E1 works well in Western blot on S protein and immunohistochemistry on the SARS-CoV-2 infected tissue sections. The results demonstrated that 9E1 can be used as a useful tool for pathological and functional studies of SARS-CoV-2.
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Carlson, Kyle, Joshua Kim, Annamaria Lusardi, and Colin F. Camerer. "Bankruptcy Rates among NFL Players with Short-Lived Income Spikes." American Economic Review 105, no. 5 (May 1, 2015): 381–84. http://dx.doi.org/10.1257/aer.p20151038.
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We test for consumption smoothing using bankruptcy data on players in the National Football League (NFL), who typically earn several million dollars during an income spike that lasts a few years. The life-cycle hypothesis predicts that players should save substantially while playing and then have little risk of bankruptcy post-NFL. However, players in our sample begin to file for bankruptcy soon after they stop playing and continue filing at a high rate through at least the first 12 years of retirement. Players' total earnings and career lengths have surprisingly little effect on the risk of bankruptcy.
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Hälvä, Seija. "Consumption and production of herbs in Finland." Agricultural and Food Science 57, no. 4 (December 1, 1985): 231–37. http://dx.doi.org/10.23986/afsci.72209.
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A study on the consumption and production of spice and medicinal herbs in Finland was carried out in 1983. There are approximately 150 commercial herb plant growers in Finland. Most of the farmers grow leafy herbs; only ten percent grow seed (botanically also fruit) spices e.g. caraway and mustard. The total cultivation area for leafy herbs is 30 hectares; for dill 14 and for parsley 12 hectares. Seed spices are grown on 130 hectares, most of this is devoted to mustard. Finland is almost self sufficient for fresh dill and parsley, but dry herbs are mostly imported. Self-sufficiency of caraway is 40 % and mustard 20 % while the other herbs and spices are also mostly imported. The total herb and spice import in 1982 was approximately 30 million Finnmarks, half of which was for the import of the so-called exotic spices. The total import of those herbs that could be cultivated in Finland was 17 million FIM. The most promising of these being mustard, garlic, chamomile, mints, dill and parsley.
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Rodrigues, João P. G. L. M., Susana Barrera-Vilarmau, João M. C. Teixeira, Marija Sorokina, Elizabeth Seckel, Panagiotis L. Kastritis, and Michael Levitt. "Insights on cross-species transmission of SARS-CoV-2 from structural modeling." PLOS Computational Biology 16, no. 12 (December 3, 2020): e1008449. http://dx.doi.org/10.1371/journal.pcbi.1008449.
Full textAbstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 31 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic and confirmed cases of cross-species transmission, the question of the extent to which this transmission is possible emerges, as well as what molecular features distinguish susceptible from non-susceptible animal species. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also allow us to predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.
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Kafle, Prakash, Babita Khanal, Dipak Kumar Yadav, Deepak Poudel, and Iype Cherian. "Spinal cord injury, Clinical Profile and its Management at Tertiary Care Center in Nepal." Journal of Nobel Medical College 8, no. 1 (June 14, 2019): 16–21. http://dx.doi.org/10.3126/jonmc.v8i1.24450.
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Background: Spinal cord injury causes serious disability among patients. More than 40 million people worldwide suffer from Spinal cord injury every year. Most of them are young men. More than10% of trauma victims sustain spine injury and have higher mortality than other injuries.
Materials and Methods: This is a prospective observational hospital based study of traumatic spine injury cases admitted at Nobel Medical College Teaching Hospital, Biratanagr, Nepal from November 2017 to October2018.
Results: Total of 352 cases were observed and 36 cases who meet the inclusion criteria for surgical intervention were analyzed. Most common affected age group was between 31-40 years with mean age of 40 years. Out of total cases, 81% were male. Most common cause for spine injury was road traffic accident. Cervical spine was the most common injury (66.7%) and C5- C6subluxation being common radiological diagnosis. ASIA-C neurology status (41.7%) on presentation being most common neurological status. Head injury was the most common associated injury. Anterior cervical discectomy and fusion was the most common surgical procedure performed. Superficial surgical site infections were observed in two cases and hardware failure was seen in one case.
Conclusion: The epidemiology of traumatic spine injuries in eastern region of Nepal is similar with other developing countries. In present study, most common cause of spine injury was motor vehicle accidents followed by fall injuries and seen in male. Prevention of road traffic accident might decrease the incidence of spine injury there by reducing the national burden.
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McCallum, Matthew, Alexandra C. Walls, John E. Bowen, Davide Corti, and David Veesler. "Structure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation." Nature Structural & Molecular Biology 27, no. 10 (August 4, 2020): 942–49. http://dx.doi.org/10.1038/s41594-020-0483-8.
Full textAbstract:
Abstract SARS-CoV-2 is the causative agent of the COVID-19 pandemic, with 10 million infections and more than 500,000 fatalities by June 2020. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface and fusion of the viral and host membranes. Prefusion SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design. However, its limited stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a construct corresponding to the prefusion SARS-CoV-2 S ectodomain trimer, covalently stabilized by a disulfide bond in the closed conformation. Structural and antigenicity analyses show we successfully shut S in the closed state without otherwise altering its architecture. We demonstrate that this strategy is applicable to other β-coronaviruses, such as SARS-CoV and MERS-CoV, and might become an important tool for structural biology, serology, vaccine design and immunology studies.
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Georgiou, Eliza (Eleni-Zacharoula), Savvina Prapiadou, and Helen Kourea. "Spine ABC, A Multidimensional Case Report from A to Z: Aneurysmal Bone Cyst of the Spine." International Journal of Medical Students 7, no. 2 (August 31, 2019): 33–37. http://dx.doi.org/10.5195/ijms.2019.407.
Full textAbstract:
Background: Aneurysmal bone cysts (ABC) are uncommon entities which cause expansile and destructive bone lesions and are characterized by reactive proliferation of connective tissue. They usually grow rapidly with hypervascularity. ABC’s incidence on the spine is 1.5 in 10 million. Most cases present with pain of unexplained origin.
The Case: Presented in this paper is an ABC case in the spinous process of the L2 vertebra of a 20-year-old Greek female patient. The main symptom was persistent back pain, without neurological symptoms, of four years’ duration. Treatment consisted of surgical curettage of the lesion. In this case report, we tried to describe not only the pathology of this disease but also the subsequent psychosocial symptoms that accompany it. We managed to accomplish that by exploiting the knowledge of an experienced pathologist, the help of the physicians responsible for this case, the interest of some sensitized medical students, and of course, the experience of the patient herself since the patient is also the lead author.
Conclusion: The focal point of this article is that even though ABCs might lead to excruciating pain, this pain can be alleviated with the proper treatment, especially if the communication between physician and patient is optimal.
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Zadnik, Patricia, Rachel Sarabia-Estrada, Mari L. Groves, Camilo Molina, Christopher Jackson, Edward McCarthy, Ziya L. Gokaslan, et al. "A novel animal model of human breast cancer metastasis to the spine: a pilot study using intracardiac injection and luciferase-expressing cells." Journal of Neurosurgery: Spine 18, no. 3 (March 2013): 217–25. http://dx.doi.org/10.3171/2012.11.spine12325.
Full textAbstract:
Object Metastatic spine disease is prevalent in cancer victims; 10%–30% of the 1.2 million new patients diagnosed with cancer in the US exhibit spinal metastases. Unfortunately, treatments are limited for these patients, as disseminated disease is often refractory to chemotherapy and is difficult to treat with surgical intervention alone. New animal models that accurately recapitulate the human disease process are needed to study the behavior of metastases in real time. Methods In this study the authors report on a cell line that reliably generates bony metastases following intracardiac injection and can be tracked in real time using optical bioluminescence imaging. This line, RBC3, was derived from a metastatic breast adenocarcinoma lesion arising in the osseous spine of a rat following intracardiac injection of MDA-231 human breast cancer cells. Results Upon culture and reinjection of RBC3, a statistically significantly increased systemic burden of metastatic tumor was noted. The resultant spine lesions were osteolytic, as demonstrated by small animal CT scanning. Conclusions This cell line generates spinal metastases that can be tracked in real time and may serve as a useful tool in the study of metastatic disease in the spine.
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Cazzato, Gerardo, Giulia Mazzia, Antonietta Cimmino, Anna Colagrande, Sara Sablone, Teresa Lettini, Roberta Rossi, et al. "SARS-CoV-2 and Skin: The Pathologist’s Point of View." Biomolecules 11, no. 6 (June 4, 2021): 838. http://dx.doi.org/10.3390/biom11060838.
Full textAbstract:
The SARS-CoV-2 pandemic has dramatically changed our lives and habits. In just a few months, the most advanced and efficient health systems in the world have been overwhelmed by an infectious disease that has caused 3.26 million deaths and more than 156 million cases worldwide. Although the lung is the most frequently affected organ, the skin has also resulted in being a target body district, so much so as to suggest it may be a real “sentinel” of COVID-19 disease. Here we present 17 cases of skin manifestations studied and analyzed in recent months in our Department; immunohistochemical investigations were carried out on samples for the S1 spike-protein of SARS-CoV-2, as well as electron microscopy investigations showing evidence of virions within the constituent cells of the eccrine sweat glands and the endothelium of small blood vessels. Finally, we conduct a brief review of the COVID-related skin manifestations, confirmed by immunohistochemistry and/or electron microscopy, described in the literature.
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Crandall, JoAnn (Jodi). "Content-Centered Learning in the U.S." Annual Review of Applied Linguistics 13 (March 1992): 110–26. http://dx.doi.org/10.1017/s0267190500002427.
Full textAbstract:
Although estimates of the number of language minority students in U.S. schools vary, there is consensus that the numbers are increasing dramatically. In 1980, there were 24 million language minority individuals living in the United States, including nearly 8 million school-age children and 2.6 million children under age five, one or both of whose parents spoke a language other than English at home (Waggoner 1992). Of the school age children, an estimated 3–5 million had limited English proficiency. Between 1980 and 1990, according to the U.S. Census, the Asian-American population more than doubled and the Hispanic-American population increased by more than 50 percent. Many major metro-politan school districts report a student population speaking more than 60 or 70 different languages, and in one of these, Los Angeles, more than 50 percent of the school age population is language minority.