gebhart/patrepeval huggingface dataset:
Coronavirus Non-Structural Protein 1 Is a Major Pathogenicity Factor: Implications for the Rational Design of Coronavirus Vaccines (2007)

Attenuated viral vaccines can be generated by targeting essential pathogenicity factors. We report here the rational design of an attenuated recombinant coronavirus vaccine based on a deletion in the coding sequence of the non-structural protein 1 (nsp1). In cell culture, nsp1 of mouse hepatitis virus (MHV), like its SARS-coronavirus homolog, strongly reduced cellular gene expression. The effect of nsp1 on MHV replication in vitro and in vivo was analyzed using a recombinant MHV encoding a deletion in the nsp1-coding sequence. The recombinant MHV nsp1 mutant grew normally in tissue culture, but was severely attenuated in vivo. Replication and spread of the nsp1 mutant virus was restored almost to wild-type levels in type I interferon (IFN) receptor-deficient mice, indicating that nsp1 interferes efficiently with the type I IFN system. Importantly, replication of nsp1 mutant virus in professional antigen-presenting cells such as conventional dendritic cells and macrophages, and induction of type I IFN in plasmacytoid dendritic cells, was not impaired. Furthermore, even low doses of nsp1 mutant MHV elicited potent cytotoxic T cell responses and protected mice against homologous and heterologous virus challenge. Taken together, the presented attenuation strategy provides a paradigm for the development of highly efficient coronavirus vaccines.
Masking generates contiguous segments of metal-coated and bare DNA for scanning tunneling microscope imaging. (1993)

To date, no microscopic methods are available to confirm scanning tunneling microscope (STM) images of DNA. The difficulties encountered in repeating these images may be attributed to inadequate distribution of molecules on the substrate, poor adhesion to the substrate, or the low conductivity of the molecules. However, these factors are difficult to assess in an STM experiment where they may act simultaneously. A method to isolate these factors involves partly masking the deposited molecules before coating them with a conductive film to produce adjacent segments of coated and bare DNA after the mask is removed. The coated DNA segments are conductive and mechanically stable to allow easy identification of DNA by the STM. Furthermore, the path of a molecule can be traced from a coated to an uncoated region to test STM imaging of bare DNA. Masked preparations of DNA deposited on platinum/carbon-coated mica and highly oriented pyrolytic graphite were examined with a tunneling current 1000 times lower than the usual nanoamps. The tip apparently displaces molecules adsorbed to graphite to preclude imaging whereas more stably bound DNA on platinum/carbon-coated mica appears in reversed contrast.
Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice. (1994)

A recombinant protein corresponding to the Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) and synthetic 15-mer peptides of the whole MOG molecule with eight amino acid overlaps were screened for their ability to induce experimental allergic encephalomyelitis (EAE) in Biozzi AB/H (H-2dq1) and SJL (H-2S) mice. Clinical and histologic evidence of EAE developed after sensitization with the recombinant MOG protein in both AB/H and SJL mice. In AB/H mice at least three MOG epitopes within residues 1-22, 43-57, and 134-148 induced clinical and histologic EAE, whereas only the sequence 92-106 was encephalitogenic in SJL mice. Histologically, the inflammatory response in the central nervous system consisted of perivascular accumulations of CD5+ T cells and F4/80+ macrophage/microglia cells equally distributed in the brain and spinal cord. The subpial/meningeal infiltration, characteristic of mouse EAE induced with spinal cord homogenate, was only observed in cases of severe clinical disease in SJL mice in which the cellular infiltrates predominated in the spinal cord. In spite of the presence of histologic lesions in AB/H mice immunized with MOG, clinical disease either rapidly resolved or was clinically silent. In contrast to immunization of SJL mice with recombinant MOG, sensitization to MOG 92-106 induced severe clinical paralysis. After recovery these animals relapsed and exhibited demyelinated lesions. This study is the first to describe encephalitogenic epitopes of MOG that induce both clinical and histologic signs of EAE in mice. These and previous findings implicating MOG as a target Ag for Ab-mediated attack in EAE suggest that such autoreactivity to MOG may be significant in the development of human demyelinating diseases such as multiple sclerosis.
Dealing with the Evolutionary Downside of CRISPR Immunity: Bacteria and Beneficial Plasmids (2013)

The immune systems that protect organisms from infectious agents invariably have a cost for the host. In bacteria and archaea CRISPR-Cas loci can serve as adaptive immune systems that protect these microbes from infectiously transmitted DNAs. When those DNAs are borne by lytic viruses (phages), this protection can provide a considerable advantage. CRISPR-Cas immunity can also prevent cells from acquiring plasmids and free DNA bearing genes that increase their fitness. Here, we use a combination of experiments and mathematical-computer simulation models to explore this downside of CRISPR-Cas immunity and its implications for the maintenance of CRISPR-Cas loci in microbial populations. We analyzed the conjugational transfer of the staphylococcal plasmid pG0400 into Staphylococcus epidermidis RP62a recipients that bear a CRISPR-Cas locus targeting this plasmid. Contrary to what is anticipated for lytic phages, which evade CRISPR by mutations in the target region, the evasion of CRISPR immunity by plasmids occurs at the level of the host through loss of functional CRISPR-Cas immunity. The results of our experiments and models indicate that more than 10(-4) of the cells in CRISPR-Cas positive populations are defective or deleted for the CRISPR-Cas region and thereby able to receive and carry the plasmid. Most intriguingly, the loss of CRISPR function even by large deletions can have little or no fitness cost in vitro. These theoretical and experimental results can account for the considerable variation in the existence, number and function of CRISPR-Cas loci within and between bacterial species. We postulate that as a consequence of the opposing positive and negative selection for immunity, CRISPR-Cas systems are in a continuous state of flux. They are lost when they bear immunity to laterally transferred beneficial genes, re-acquired by horizontal gene transfer, and ascend in environments where phage are a major source of mortality.
Nucleosides I. A New Synthesis of 1-β-D-Arabinofuranosyl Pyrimidine Nucleosides (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleosides I. A New Synthesis of 1-β-D-Arabinofuranosyl Pyrimidine NucleosidesT. Y. Shen, H. M. Lewis, and W. V. RuyleCite this: J. Org. Chem. 1965, 30, 3, 835–838Publication Date (Print):March 1, 1965Publication History Published online1 May 2002Published inissue 1 March 1965https://pubs.acs.org/doi/10.1021/jo01014a043https://doi.org/10.1021/jo01014a043research-articleACS PublicationsRequest reuse permissionsArticle Views322Altmetric-Citations39LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Stepwise assembly of metal–organic framework based on a metal–organic polyhedron precursor for drug delivery (2011)

A 12-connected network with fcu topology was firstly reported focusing on using predesigned metal-organic polyhedron (MOP) as the precursor, and its adsorption and delivery of the drug 5-fluorouracil (5-FU) was also determined.
Induction of mucosal tolerance in Peyer‘s patch—deficient, ligated small bowel loops (2005)

To explore the requirement for M cells and the Peyer's patch (PP) in induction of oral tolerance and address the potential in vivo role of intestinal epithelial cells as nonprofessional APCs, we have attempted to induce tolerance in mice with ligated small bowel loops without M cells and Peyer's patches. A 2-centimeter section of vascularized small bowel was spliced away from the gut without disruption of the mesenteric attachments. We introduced OVA directly into the lumen of the loop prior to footpad immunization. By excising segments of bowel that contain PPs in some mice and segments without patches in others, we could study the necessity of the M cell and the underlying patch versus epithelial cells in induction of mucosal tolerance. We show that OVA-specific T cell proliferation and serum antibody responses are reduced in mice that have previously been given OVA both in PP-containing loops and in loops without patches. Furthermore, both high- and low-dose tolerance could be induced in the absence of PPs. Low-dose tolerance is associated with bystander suppression and requires IL-10, which indicates active suppression and the induction of regulatory cells. These data suggest that there is a critical role for components of the mucosal immune system other than PPs in antigen sampling and induction of oral tolerance.
Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab (2006)

The study aimed to investigate whether polymorphisms in genes of the EGFR signaling pathway are associated with clinical outcome in advanced colorectal cancer (CRC) patients treated with single-agent Cetuximab. Polymorphisms of interest in the EGFR pathway include: cyclin D1 (CCND1) A870G, cyclooxygenase 2 (Cox-2) G-765C, epidermal growth factor (EGF) A61G, epidermal growth factor receptor (EGFR) codon R497 K, EGFR CA dinucleotide repeat in intron 1, interleukin (IL)-8 T-251A and vascular endothelial growth factor (VEGF) C936 T gene polymorphisms. Thirty-nine metastatic CRC patients were enrolled in the IMCL-0144 trial and treated with single-agent Cetuximab. Using the polymerase chain reaction-restriction fragment length polymorphism method, gene polymorphisms of CCND1, COX-2, EGF, EGFR, IL-8 and VEGF were assessed from genomic DNA extracted from blood samples. A significant association was found between the CCND1 A870G polymorphism and overall survival in our 39 CRC subjects. Patients with the AA homozygous genotype survived for a median of 2.3 months [95% confidence interval (CI)=2.1-5.7], whereas those with any G allele (AG, GG genotype) survived for a median of 8.7 months (95% CI=4.4-13.5) (P=0.019, log-rank test). When we analysed the cyclin D1 and EGF polymorphisms together, patients with favourable genotypes (EGF any A allele and CCND1 any G allele) showed a median survival time of 12 months (95% CI=4.8-15.2), whereas patients with any two unfavourable genotypes (EGF GG or CCND1 AA) showed a median survived time of 4.4 months (95% CI=2.1-5.7) (P=0.004, log-rank test). The findings of this pilot study suggest that the cyclin D1 A870G and the EGF A61G polymorphisms may be useful molecular markers for predicting clinical outcome in CRC patients treated with single-agent Cetuximab.
Mitochondrial fission and fusion (2010)

Mitochondria are highly dynamic cellular organelles, with the ability to change size, shape and position over the course of a few seconds. Many of these changes are related to the ability of mitochondria to undergo the highly co-ordinated processes of fission (division of a single organelle into two or more independent structures) or fusion (the opposing reaction). These actions occur simultaneously and continuously in many cell types, and the balance between them regulates the overall morphology of mitochondria within any given cell. Fission and fusion are active processes which require many specialized proteins, including mechanical enzymes that physically alter mitochondrial membranes, and adaptor proteins that regulate the interaction of these mechanical proteins with organelles. Although not fully understood, alterations in mitochondrial morphology appear to be involved in several activities that are crucial to the health of cells. In the present chapter we discuss the mechanisms behind mitochondrial fission and fusion, and discuss the implications of changes in organelle morphology during the life of a cell.
Face Masks and Respirators in the Fight Against the COVID-19 Pandemic: A Review of Current Materials, Advances and Future Perspectives (2020)

The outbreak of COVID-19 has spread rapidly across the globe, greatly affecting how humans as a whole interact, work and go about their daily life. One of the key pieces of personal protective equipment (PPE) that is being utilised to return to the norm is the face mask or respirator. In this review we aim to examine face masks and respirators, looking at the current materials in use and possible future innovations that will enhance their protection against SARS-CoV-2. Previous studies concluded that cotton, natural silk and chiffon could provide above 50% efficiency. In addition, it was found that cotton quilt with a highly tangled fibrous nature provides efficient filtration in the small particle size range. Novel designs by employing various filter materials such as nanofibres, silver nanoparticles, and nano-webs on the filter surfaces to induce antimicrobial properties are also discussed in detail. Modification of N95/N99 masks to provide additional filtration of air and to deactivate the pathogens using various technologies such as low- temperature plasma is reviewed. Legislative guidelines for selecting and wearing facial protection are also discussed. The feasibility of reusing these masks will be examined as well as a discussion on the modelling of mask use and the impact wearing them can have. The use of Artificial Intelligence (AI) models and its applications to minimise or prevent the spread of the virus using face masks and respirators is also addressed. It is concluded that a significant amount of research is required for the development of highly efficient, reusable, anti-viral and thermally regulated face masks and respirators.
Detection of anti‐D in D– recipients transfused with D+ red blood cells (2007)

The 22 percent rate of anti-D alloimmunization in patients requiring urgent RBC transfusion was intermediate between the rates previously reported for D- oncology patients transfused with D+ RBCs and that in immunocompetent volunteer recipients.
Liquid chromatography at the critical point of adsorption — A new technique for polymer characterization (1996)

Abstract Liquid chromatography at the critical point of adsorption (CC) is a versatile method for the determination of different types of molecular heterogeneity in polymers. Operating at the transition point of size‐exclusion and adsorption modes of liquid chromatography, this method is capable of separating polymers according to their functionality. At the critical point of adsorption the polymer chain behaves like an invisible part of the macromolecule and only the heterogeneities (functional groups, blocks, grafts) manifest themselves chromatographically. The application of this method to the determination of the chemical heterogeneity of block copolymers and the composition of polymer blends is demonstrated. Block copolymers can be analysed with respect to the block lengths of the individual blocks. A complete description of their molecular heterogeneity is possible using two‐dimensional chromatography CC vs. SEC. Binary polymer blends are separated with respect to the components regardless of their individual molar masses under experimental conditions, where one component elutes at the critical point of adsorption.
Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes (2000)

A technique is presented that allows neonatal rat cardiac myocytes to form spontaneously and coherently beating 3-dimensional engineered heart tissue (EHT) in vitro, either as a plane biconcaval matrix anchored at both sides on Velcro-coated silicone tubes or as a ring. Contractile activity was monitored in standard organ baths or continuously in a CO(2) incubator for up to 18 days (=26 days after casting). Long-term measurements showed an increase in force between days 8 and 18 after casting and stable forces thereafter. At day 10, the twitch amplitude (TA) of electrically paced EHTs (average length x width x thickness, 11 x 6 x 0.4 mm) was 0.51 mN at length of maximal force development (L(max)) and a maximally effective calcium concentration. EHTs showed typical features of neonatal rat heart: a positive force-length and a negative force-frequency relation, high sensitivity to calcium (EC(50) 0.24 mM), modest positive inotropic (increase in TA by 46%) and pronounced positive lusitropic effect of isoprenaline (decrease in twitch duration by 21%). Both effects of isoprenaline were sensitive to the muscarinic receptor agonist carbachol in a pertussis toxin-sensitive manner. Adenovirus-mediated gene transfer of beta-galactosidase into EHTs reached 100% efficiency. In summary, EHTs retain many of the physiological characteristics of rat cardiac tissue and allow efficient gene transfer with subsequent force measurement.
Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain (2007)

The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging. Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Beyond the "flight-or-fight" response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body ("allostatic load"). Yet, hormones associated with stress protect the body in the short-run and promote adaptation ("allostasis"). The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course. Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.
How bad are the symptoms and bowel dysfunction of patients with the irritable bowel syndrome? A prospective, controlled study with emphasis on stool form. (1991)

Since it is not known whether the symptoms and bowel function of patients with the irritable bowel syndrome are truly abnormal we used diaries and frequent telephone interviews over a 31 day period to assess symptoms, defecation, and stool types in 26 unselected female hospital patients with the irritable bowel syndrome, 27 women who admitted to recurrent colonic pain but had not consulted a doctor (non-complainers), and 27 healthy control subjects. Unexpectedly, abdominal pain and bloating occurred in most of the control subjects. Pain, however, was six times more frequent in the patients and was more often considered severe. Bloating occurred three times more often. Defecation was more frequent, more erratic in timing and stool form, and more likely to produce stools of extreme forms, indicating rapid fluctuations in intestinal transit time. Urgency was four times more prevalent in patients than control subjects. Straining to finish defecating was nine times more prevalent and was often accompanied by feelings of incomplete evacuation--a combination which could lead to the misdiagnosis of constipation. The normal relation between stool form and the above symptoms was distorted, possibly due to rectal irritability. Non-complainers were intermediate between patients and control subjects in almost every parameter but were closer to control subjects than to patients. Patients with the irritable bowel syndrome have real cause for complaint and their bowel function is truly abnormal.
Concurrent bimanual stylus interaction: a study of non-preferred hand mode manipulation (2006)

Pen/Stylus input systems are constrained by the limited input capacity of the electronic stylus. Stylus modes, which allow multiple interpretations of the same input, lift capacity limits, but confront the user with possible cognitive and motor costs associated with switching modes. This paper examines the costs of bimanual mode switching, in which the non-preferred hand performs actions that change modes while the preferred hand executes gestures that provide input. We examine three variants to control mode of a stylus gesture: pre-gesture mediation, post-gesture mediation, and mediation that occurs concurrently with stylus gesturing. The results show that concurrent mode-switching is faster than the alternatives, and, in one trial, marginally outperforms the control condition, un-moded drawing. These results demonstrate an instance in which suitably designed mode-switching offers minimal cost to the user. The implications of this result for the design of stylus input systems are highlighted.