gebhart/patrepeval huggingface dataset:
Lamin A/C mutations associated with familial and sporadic cases of dilated cardiomyopathy in Koreans (2007)

Dilated cardiomyopathy (DCM) is characterized by cardiac dilation and systolic dysfunction. So far sixteen genes have been shown to cause autosomal dominant familial dilated cardiomyopathy (FDC). We identified a large Korean family from the Jeju island showing a clear Mendelian inheritance of FDC. A genomewide linkage scan at 9 cM marker density identified a peak multipoint LOD score of 2.82 at D1S195. Haplotyping of the region with 15 additional markers defined a candidate interval that included a known candidate gene encoding the lamin A/C (LMNA). Sequencing of the LMNA exons revealed one missense mutation at C568T (Arg190Trp) in the alpha-helical rod domain of the LMNA gene co-segregating with FDC with conduction-system disease. The same mutation was found in patients of another Korean family with FDC without conduction-system disease. Upon screening 14 sporadic DCM cases, we found three LMNA mutations including a case having a previously described (Glu161Lys) mutation and two having novel mutations (Glu53Val and Glu186Lys). Our results suggest that variable genotypes of laminopathy are implicated in not only familial but also considerable proportion of sporadic DCM.
Far infrared polarizing grids for use at cryogenic temperatures (1989)

A technique is presented for constructing free-standing wire grids for use as far-IR polarizers. The grids are reliable under repeated cycling between room temperature and 1.5 K.
Progenitor and Terminal Subsets of CD8 + T Cells Cooperate to Contain Chronic Viral Infection (2012)

Chronic infections strain the regenerative capacity of antiviral T lymphocyte populations, leading to failure in long-term immunity. The cellular and molecular events controlling this regenerative capacity, however, are unknown. We found that two distinct states of virus-specific CD8(+) T cells exist in chronically infected mice and humans. Differential expression of the T-box transcription factors T-bet and Eomesodermin (Eomes) facilitated the cooperative maintenance of the pool of antiviral CD8(+) T cells during chronic viral infection. T-bet(hi) cells displayed low intrinsic turnover but proliferated in response to persisting antigen, giving rise to Eomes(hi) terminal progeny. Genetic elimination of either subset resulted in failure to control chronic infection, which suggests that an imbalance in differentiation and renewal could underlie the collapse of immunity in humans with chronic infections.
An Immunotolerant HER-2/neuTransgenic Mouse Model of Metastatic Breast Cancer (2008)

The model closely recapitulates the pattern of metastatic spread in breast cancer. This immunotolerant metastatic model is a novel addition to existing breast cancer models and coupling the model with in vivo imaging greatly facilitates the evaluation of targeted immunotherapies of metastasis.
Ultra‐long‐acting insulin degludec has a flat and stable glucose‐lowering effect in type 2 diabetes (2012)

IDeg has a flat and consistent glucose-lowering effect in people with type 2 diabetes.
Association of Sex Hormones and Adiposity with Plasma Levels of Fibrinogen and PAI-1 in Postmenopausal Women (1996)

Blood levels of the clotting factor fibrinogen and tissue plasminogen activator inhibitor-1 (PAI-1), a primary inhibitor of fibrinolysis, have been positively linked to risk of coronary heart disease. The authors have reported previously that plasma fibrinogen appears to rise after menopause and to be reduced with use of postmenopausal hormonal therapy. There is also evidence to suggest that sex hormones may influence PAI-1. To examine whether plasma fibrinogen and PAI-1 antigen levels differ among older postmenopausal women according to use of hormone therapy and by blood level of estrogen and androgens, these variables were assessed among 277 healthy women aged 65-82 years, one half of whom were receiving therapy. The study population was drawn from the Study of Osteoporotic Fractures, Pittsburgh, Pennsylvania, during 1986-1988. Overall, results showed median PAI-1 levels to be lower on average with oral and transdermal use of hormone therapy (25.0 vs. 33.5 ng/ml, p < 0.01) and mean fibrinogen levels to be lower (279 vs. 295 mg/dl, p < 0.02) with use of oral estrogen (but not transdermal) therapy compared with women not receiving therapy. Among women not receiving therapy, PAI-1 and fibrinogen levels were not related to endogenous sex hormone levels, with the exception of a modest positive relation between PAI-1 and serum estrone concentrations (rs = 0.29). In addition, a markedly higher PAI-1 level was found for women with a preponderance of upper body fat, independent of obesity. In sum, results showed that older women receiving postmenopausal hormone therapy had more favorable plasma levels of the hemostatic factors PAI-1 and fibrinogen than did those not receiving therapy, which can be explained in large part by differences between the two groups in obesity and body fat distribution.
Targeted disruption of Bcl-2 alpha beta in mice: occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. (1994)

Mice carrying ablated coding regions of the bcl-2 alpha and bcl-2 beta transcripts have been made. bcl-2-/- mutants are smaller but viable, although about half of them die by 6 weeks of age. As shown earlier with somatic bcl-2 gene-targeted mice, the number of lymphocytes markedly decreased within few weeks after birth while other hematopoietic lineages remained unaffected. Among lymphocytes, CD8+ T cells disappeared most quickly followed by CD4+ T cells, whereas B cells were least affected. bcl-2-/- lymphocytes, however, could respond normally to various stimuli including anti-CD3, Con A, phorbol 12-myristate 13-acetate plus ionomycin, interleukin 2, lipopolysaccharide, and anti-IgM antibody. Abnormalities among nonlymphoid organs include smaller auricles, hair color turning gray at 4-5 weeks of age, and polycystic kidney disease-like change of renal tubules. These results suggest that Bcl-2 may be involved during morphogenesis where inductive interactions between epithelium and mesenchyme are important such as in the kidneys, hair follicles, and perichondrium of auricles. Surprisingly, the nervous system, intestines, and skin appear normal despite the fact that these organs show high levels of endogenous Bcl-2 expression in normal mice.
Imaging individual microRNAs in single mammalian cells in situ (2009)

MicroRNAs (miRNAs) are potent negative regulators of gene expression that have been implicated in most major cellular processes. Despite rapid advances in our understanding of miRNA biogenesis and mechanism, many fundamental questions still remain regarding miRNA function and their influence on cell cycle control. Considering recent reports on the impact of cell-to-cell fluctuations in gene expression on phenotypic diversity, it is likely that looking at the average miRNA expression of cell populations could result in the loss of important information connecting miRNA expression and cell function. Currently, however, there are no efficient techniques to quantify miRNA expression at the single-cell level. Here, a method is described for the detection of individual miRNA molecules in cancer cells using fluorescence in situ hybridization. The method combines the unique recognition properties of locked nucleic acid probes with enzyme-labeled fluorescence. Using this approach, individual miRNAs are identified as bright, photostable fluorescent spots. In this study, miR-15a was quantified in MDA-MB-231 and HeLa cells, while miR-155 was quantified in MCF-7 cells. The dynamic range was found to span over three orders of magnitude and the average miRNA copy number per cell was within 17.5% of measurements acquired by quantitative RT-PCR.
A Transition Metal Complex of D-Glucose (2001)

The most important monosaccharide-and not a single structurally characterized transition metal complex. That is the actual situation regarding basis data for understanding or designing metal-catalyzed reactions of D-glucose. This oversight is remedied with a palladium(II) complex and a structural analysis (see picture, en=ethylenediamine).
UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells (2007)

Epigenetic inheritance in mammals relies in part on robust propagation of DNA methylation patterns throughout development. We show that the protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1), also known as NP95 in mouse and ICBP90 in human, is required for maintaining DNA methylation. UHRF1 colocalizes with the maintenance DNA methyltransferase protein DNMT1 throughout S phase. UHRF1 appears to tether DNMT1 to chromatin through its direct interaction with DNMT1. Furthermore UHRF1 contains a methyl DNA binding domain, the SRA (SET and RING associated) domain, that shows strong preferential binding to hemimethylated CG sites, the physiological substrate for DNMT1. These data suggest that UHRF1 may help recruit DNMT1 to hemimethylated DNA to facilitate faithful maintenance of DNA methylation.
Isolation and Characterization of a Cell Line from the Epithelial Cells of the Human Fetal Pancreas (1997)

Pancreatic cell lines are useful for basic studies of pancreatic biology and for possible application to cell transplantation therapies for diabetes. A retroviral vector expressing simian virus 40 (SV40) T antigen and H-ras val12 was used to infect a monolayer culture of epithelial cells from an 18-wk human fetal pancreas. Infected cells gave rise to a clonal epithelial cell line, designated TRM-1. This cell line expresses epithelial markers as well as glut2 and small amounts of insulin and glucagon. TRM-1 is the first cell line to be generated from the human fetal pancreas and also the first cell line derived directly from the fetal pancreas of any species. The approach that we have used to develop TRM-1 should be applicable to isolating cell lines from other stages of human pancreatic development. Copyright © 1997 Elsevier Science, Inc.
Progressive effects of the interaction of Sodium nitrite and sunset yellow on different physiological parameters in albino rats (2001)

It has been noticed that the Egyptian children usually eat and drink food containing both food preservative and food colourants at the same time . This has attracted the attention to study the interaction between one of food preservatives (sodium nitrite) and a food coloring agent (sunset yellow). The mixture of the two agents at the limited dose of each was found to be a lethal dose. So, 1/10th of this dose was used daily for 30 days. Animals were devided into three groups. The first group served as a control, while the second group was orally administered a mixture of 10mg sod. nitrite (NaNO3)/kg and 0.5 mg/ kg /day sun set yellow (S.S.Y)/. The third group received selenium (5 mcg/kg) in addition to the above mentioned mixture. After 30 days of treatment, half of the animals from each group were decapitated. The other half of animals was left for another 15 days without treatment for recovery. Ingestion of the mixture of (NaNO3 and S.S.Y) significantly decreased rat body weight, R B C and WBC counts, Hb %. , Hct %. Serum inorganic phosphorus, serum protein and serum albumin. Significant increases were observed in serum glucose, T3, T4, calcium, GGT, LDH, Cpk, ALK.ph and cholesterol. Also cholesterol of brain, liver and heart were significantly elevated. No changes were recorded for organ/ body weight, respiratory rate, heart beats, rectal temperature, AST and ALT activities of serum and tissues, acid phosphatase activity, total lipids of serum and tissues, cholesterol of muscle and kidney and serum triglycerides A complete recovery from the abnormalities of most biochemical and haematological parameters was observed after 15 days recovery or when selenium was administered This draws attention to the dangers of interactions of such preservatives and colorants. The present study showed that even the permitted doses of colourants and food preservatives may be harmful.
Identification of Chimeric Antigen Receptors That Mediate Constitutive or Inducible Proliferation of T Cells (2015)

This study compared second-generation chimeric antigen receptors (CAR) encoding signaling domains composed of CD28, ICOS, and 4-1BB (TNFRSF9). Here, we report that certain CARs endow T cells with the ability to undergo long-term autonomous proliferation. Transduction of primary human T cells with lentiviral vectors encoding some of the CARs resulted in sustained proliferation for up to 3 months following a single stimulation through the T-cell receptor (TCR). Sustained numeric expansion was independent of cognate antigen and did not require the addition of exogenous cytokines or feeder cells after a single stimulation of the TCR and CD28. Results from gene array and functional assays linked sustained cytokine secretion and expression of T-bet (TBX21), EOMES, and GATA-3 to the effect. Sustained expression of the endogenous IL2 locus has not been reported in primary T cells. Sustained proliferation was dependent on CAR structure and high expression, the latter of which was necessary but not sufficient. The mechanism involves constitutive signaling through NF-κB, AKT, ERK, and NFAT. The propagated CAR T cells retained a diverse TCR repertoire, and cellular transformation was not observed. The CARs with a constitutive growth phenotype displayed inferior antitumor effects and engraftment in vivo. Therefore, the design of CARs that have a nonconstitutive growth phenotype may be a strategy to improve efficacy and engraftment of CAR T cells. The identification of CARs that confer constitutive or nonconstitutive growth patterns may explain observations that CAR T cells have differential survival patterns in clinical trials.
Heterosynaptic plasticity in the neocortex (2009)

Ongoing learning continuously shapes the distribution of neurons' synaptic weights in a system with plastic synapses. Plasticity may change the weights of synapses that were active during the induction-homosynaptic changes, but also may change synapses not active during the induction-heterosynaptic changes. Here we will argue, that heterosynaptic and homosynaptic plasticity are complementary processes, and that heterosynaptic plasticity might accompany homosynaptic plasticity induced by typical pairing protocols. Synapses are not uniform in their susceptibility for plastic changes, but have predispositions to undergo potentiation or depression, or not to change. Predisposition is one of the factors determining the direction and magnitude of homo- and heterosynaptic changes. Heterosynaptic changes which take place according to predispositions for plasticity may provide a useful mechanism(s) for homeostasis of neurons' synaptic weights and extending the lifetime of memory traces during ongoing learning in neuronal networks.
[Distal cutaneous necrosis, an unusual etiology: hyperhomocysteinemia]. (1999)

Different diagnoses could be possible for cases associating an inflammatory venous disease and stage IV arteritis. Latent hyperhomocysteinemia was diagnosed in this case on the basis of the methionine loading test and identification of the heterozygous form of cystathionine ss. Patients with latent hyperhomocysteinemia have an increased risk of both thrombosis and arteritis. Our case emphasizes the importance of searching for hyperhomocysteinemia in patients with early arterial and/or venous thromboembolism, either as repeated episodes or occurring in an unusual territory.
Quantitative imaging of nanoscale mechanical properties using hybrid nanoindentation and force modulation (2001)

In this article, we present a quantitative stiffness imaging technique and demonstrate its use to directly map the dynamic mechanical properties of materials with nanometer-scale lateral resolution. For the experiments, we use a “hybrid” nanoindenter, coupling depth-sensing nanoindentation with scanning probe imaging capabilities. Force modulation electronics have been added, enhancing instrument sensitivity and enabling measurements of time dependent materials properties (e.g., loss modulus and damping coefficient) not readily obtained with quasi-static indentation techniques. Tip–sample interaction stiffness images are acquired by superimposing a sinusoidal force (∼1 μN) onto the quasi-static imaging force (1.5–2 μN), and recording the displacement amplitude and phase as the surface is scanned. Combining a dynamic model of the indenter (having known mass, damping coefficient, spring stiffness, resonance frequency, and modulation frequency) with the response of the tip–surface interaction, creates maps of complex stiffness. We demonstrate the use of this approach to obtain quantitative storage and loss stiffness images of a fiber-epoxy composite, as well as directly determine the loss and storage moduli from the images using Hertzian contact mechanics. Moduli differences as small as 20% were resolved in the images at loads two orders of magnitude lower than with indentation, and were consistent with measurements made using conventional quasi-static depth-sensing indentation techniques.
Oligomeric Modeling and Electrostatic Analysis of the gp120 Envelope Glycoprotein of Human Immunodeficiency Virus (2000)

The human immunodeficiency virus envelope glycoproteins, gp120 and gp41, function in cell entry by binding to CD4 and a chemokine receptor on the cell surface and orchestrating the direct fusion of the viral and target cell membranes. On the virion surface, three gp120 molecules associate noncovalently with the ectodomain of the gp41 trimer to form the envelope oligomer. Although an atomic-level structure of a monomeric gp120 core has been determined, the structure of the oligomer is unknown. Here, the orientation of gp120 in the oligomer is modeled by using quantifiable criteria of carbohydrate exposure, occlusion of conserved residues, and steric considerations with regard to the binding of the neutralizing antibody 17b. Applying similar modeling techniques to influenza virus hemagglutinin suggests a rotational accuracy for the oriented gp120 of better than 10 degrees. The model shows that CD4 binds obliquely, such that multiple CD4 molecules bound to the same oligomer have their membrane-spanning portions separated by at least 190 A. The chemokine receptor, in contrast, binds to a sterically restricted surface close to the trimer axis. Electrostatic analyses reveal a basic region which faces away from the virus, toward the target cell membrane, and is conserved on core gp120. The electrostatic potentials of this region are strongly influenced by the overall charge, but not the precise structure, of the third variable (V3) loop. This dependence on charge and not structure may make electrostatic interactions between this basic region and the cell difficult to target therapeutically and may also provide a means of viral escape from immune system surveillance.
Distribution of merosin, a laminin-related tissue-specific basement membrane protein, in human Schwann cell neoplasms. (1989)

The expression of merosin and laminin was studied in human schwannomas, plexiform neurofibromas, and malignant schwannomas immunohistochemically using monoclonal antibodies. Merosin is a unique novel tissue-specific basement membrane protein found in basement membranes of trophoblast, striated muscle, and Schwann cells. Merosin is related to laminin, another basement membrane protein with which it shows a homologous C terminal domain. In schwannomas, merosin was only found in areas where tumor cells were in contact with stromal or vascular tissue. Laminin, however, was present in all tumor cell basement membranes. In plexiform neurofibromas large amounts of both merosin and laminin were seen in Schwann cell basement membranes. Very little of either protein was found in malignant schwannomas. Thus merosin is present almost exclusively in highly differentiated Schwann cell neoplasms, and its distribution is more restricted than that of laminin. The expression of merosin in plexiform neurofibromas and in the schwannoma cells juxtaposed to the mesenchymal cells suggests that this protein is induced epigenetically in well-differentiated cells in contact with connective tissue or vascular components.
The First Structure of UDP-Glucose Dehydrogenase Reveals the Catalytic Residues Necessary for the Two-fold Oxidation, (2000)

Bacterial UDP-glucose dehydrogenase (UDPGlcDH) is essential for formation of the antiphagocytic capsule that protects many virulent bacteria such as Streptococcus pyogenes and Streptococcus pneumoniae type 3 from the host's immune system. We have determined the X-ray structures of both native and Cys260Ser UDPGlcDH from S. pyogenes (74% similarity to S. pneumoniae) in ternary complexes with UDP-xylose/NAD+ and UDP-glucuronic acid/NAD(H), respectively. The 402 residue homodimeric UDPGlcDH is composed of an N-terminal NAD+ dinucleotide binding domain and a C-terminal UDP-sugar binding domain connected by a long (48 Å) central α-helix. The first 290 residues of UDPGlcDH share structural homology with 6-phosphogluconate dehydrogenase, including conservation of an active site lysine and asparagine that are implicated in the enzyme mechanism. Also proposed to participate in the catalytic mechanism are a threonine and a glutamate that hydrogen bond to a conserved active site water molecule suitably positioned for general acid/base catalysis.
Monoclonal Antibodies Specific for Rat IgG1, IgG2a, and IgG2b Subclasses, and Kappa Chain Monotypic and Allotypic Determinants: Reagents for Use with Rat Monoclonal Antibodies (1982)

Mouse monoclonal antibodies to rat IgG were obtained by fusion of immune SJL mouse spleen cells to NSI myeloma cells. Seven monoclonal antibodies have been labeled with 125I and studied as to specificity and avidity by using a panel of rat monoclonal antibodies both as inhibitors and target antigens in soft well plate and indirect cell binding assays. All MAb were selected for high avidity of 4 X 10(7) to greater than or equal to 2 X 10(9) M-1. Four MAb were subclass-specific. RG11/39, RG7/1, and RG7/11 were absolutely specific for the Fc' region of IgG1, IgG2a, and IgG2b, respectively. RG9/6 showed specificity for the Fab' region of IgG2a but crossreacted with lower avidity with IgG2c. Three MAb reacted with rat kappa chains. RG7/9 defined a monotypic (common) kappa chain determinant. RG11/15 and RG7/7 were specific for allelic kappa 1a and kappa 1b determinants, respectively. The monotypic and kappa 1a allotypic determinants are topographically separated. The antibodies can be used as screening reagents in indirect cell binding assays. They have sensitivity similar to affinity-purified rabbit anti-rat IgG and more defined specificity. They do not crossreact with mouse or human IgG, making them particularly suitable companion reagents for rat anti-mouse or anti-human MAb. One Mab, RG7/7, strongly crossreacts with Syrian hamster IgG.
β Blocker treatment and other prognostic variables in patients with clinical evidence of heart failure after acute myocardial infarction: evidence from the AIRE study (1999)

beta Blocker treatment is associated with improved outcomes in patients with clinical evidence of mild to moderate heart failure after myocardial infarction. Most importantly, high risk patients with persistent heart failure appear to benefit at least as much as lower risk patients with transient heart failure.
Carbapenem antibiotics for serious infections (2012)

An 81 year old woman with a long term, indwelling urinary catheter is admitted with fever and hypotension thought to be due to septicaemia secondary to urinary tract infection. She is treated empirically with intravenous cefotaxime and gentamicin, but her condition deteriorates over 24 hours, with increasing hypotension and continuing fever. For broader spectrum coverage, her empirical antibiotic treatment is changed to intravenous meropenem. The next day, urine and blood cultures grow an Escherichia coli producing an extended spectrum β lactamase (ESBL), conferring resistance to cefotaxime and gentamicin but not to meropenem. The meropenem is continued for seven days, with clinical and bacteriological resolution of the patient’s infection.