gebhart/patrepeval huggingface dataset:
ClinVar: public archive of interpretations of clinically relevant variants (2015)

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) at the National Center for Biotechnology Information (NCBI) is a freely available archive for interpretations of clinical significance of variants for reported conditions. The database includes germline and somatic variants of any size, type or genomic location. Interpretations are submitted by clinical testing laboratories, research laboratories, locus-specific databases, OMIM®, GeneReviews™, UniProt, expert panels and practice guidelines. In NCBI's Variation submission portal, submitters upload batch submissions or use the Submission Wizard for single submissions. Each submitted interpretation is assigned an accession number prefixed with SCV. ClinVar staff review validation reports with data types such as HGVS (Human Genome Variation Society) expressions; however, clinical significance is reported directly from submitters. Interpretations are aggregated by variant-condition combination and assigned an accession number prefixed with RCV. Clinical significance is calculated for the aggregate record, indicating consensus or conflict in the submitted interpretations. ClinVar uses data standards, such as HGVS nomenclature for variants and MedGen identifiers for conditions. The data are available on the web as variant-specific views; the entire data set can be downloaded via ftp. Programmatic access for ClinVar records is available through NCBI's E-utilities. Future development includes providing a variant-centric XML archive and a web page for details of SCV submissions.
Enhancement and suppression of thermal emission by a three-dimensional photonic crystal (2000)

The emission and detection of electromagnetic radiation are essential optical processes that govern performance of lasers, detectors and solar cells. Through light-photonic crystal interaction, a three-dimensional (3D) photonic crystal offers a way to alter such optical processes. Experimental realization is done by building a thin slab of 3D photonic crystal onto a silicon material. The 3D crystal structure is found to be highly effective in suppressing silicon thermal radiation in the photonic band gap spectral regime. Emission is also enhanced in the photonic passbands. At passband resonant frequencies, a thin slab of 3D photonic crystal actually acts like a planar blackbody.
Intrinsic disorder in the androgen receptor: identification, characterisation and drugability (2011)

The androgen receptor (AR) regulates networks of genes in response to the steroid hormones testosterone and dihydrotestosterone. The receptor protein is made up of both stably folded globular domains, involved in hormone and DNA binding, and regions of intrinsic disorder, including the N-terminal domain (NTD). The AR-NTD has a modular activation function (termed AF1) and is important for gene regulation, participating in multiple protein-protein interactions. Biophysical studies have revealed that AR-NTD/AF1 has limited stable secondary structure and conforms to a 'collapsed disordered' conformation. The AR-NTD/AF1 has the propensity to adopt an α-helical conformation in response to a natural osmolyte or a co-regulatory binding partner. The AR is a key drug target in the management of advanced prostate cancer and recently a small molecule inhibitor was identified that interacts with the NTD/AF1 and impairs protein-protein interactions and recruitment of the receptor to target genes. In this review the role of intrinsic disorder in AR function is discussed along with the potential to develop new drugs that will target the structurally plastic NTD.
Expression profiling predicts outcome in breast cancer (2002)

Gruvberger et al. postulate, in their commentary published&#13;\nin this issue of Breast Cancer Research, that our&#13;\n“prognostic gene set may not be broadly applicable to&#13;\nother breast tumor cohorts”, and they suggest that “it may&#13;\nbe important to define prognostic expression profiles separately&#13;\nin estrogen receptor (ER) positive and negative&#13;\ntumors”. This is based on two observations derived from&#13;\nour gene expression profiling data in breast cancer: the&#13;\noverlap between reporter genes for prognosis and ER&#13;\nstatus, and Gruvberger et al.’s inability to confirm the&#13;\nprognosis prediction using a nonoptimal selection of 58 of&#13;\nour 231 prognosis reporter genes.
Unilateral Neglect (2013)

Section A: is Neglect? P. Halligan, J. Marshall, The Nature and Natural History of Neglect. G. Valler, The Anatomical Basis of Spatial Hemineglect in Humans. Section B: Neuropsychological Processes Underlying Neglect. G. Gainotti, The Role of Spontaneous Eye Movements in Orienting Attention and in Unilateral Neglect. G. Rizzolatti, A. Berti, Neural Mechanisms of Spatial Neglect. M. Kinsbourne, Orientational Bias Model of Unilateral Neglect: Evidence from Attentional Gradients within Hemispace. M.J. Farah, M.A. Wallace, S.P. Vecera, What and Where in Visual Attention: Evidence from the Neglect Syndrome. G.W. Humphries, M.J. Riddoch, Interactive Attentional Systems and Unilateral Visual Neglect. I. Robertson, The Relationship between Lateralised and Non-Lateralised Attentional Deficits in Unilateral Left Neglect. L.C. Robertson, M. Eglin, Attentional Search in Unilateral Visual Neglect. E. Ladevas, Shifts of Attention in Patients with Visual Neglect. R. Werth, Shifts and Omissions in Spatial Reference in Unilateral Neglect. A.W. Ellis, A.W. Young, B.M. Flude, Neglect and Visual Language. J. Marshall, P. Halligan, I. Robertson, A Critical Review of Contemporary Theories. Section C: Rehabilitation of Neglect. L. Diller, The Behavioural Management of Neglect. I. Robertson, P. Halligan, J. Marshall, Prospects for the Rehabilitation of Unilateral Neglect.
Enrichment and Site Mapping of O-Linked N-Acetylglucosamine by a Combination of Chemical/Enzymatic Tagging, Photochemical Cleavage, and Electron Transfer Dissociation Mass Spectrometry (2009)

Numerous cellular processes are regulated by the reversible addition of either phosphate or O-linked beta-N-acetylglucosamine (O-GlcNAc) to nuclear and cytoplasmic proteins. Although sensitive methods exist for the enrichment and identification of protein phosphorylation sites, those for the enrichment of O-GlcNAc-containing peptides are lacking. Reported here is highly efficient methodology for the enrichment and characterization of O-GlcNAc sites from complex samples. In this method, O-GlcNAc-modified peptides are tagged with a novel biotinylation reagent, enriched by affinity chromatography, released from the solid support by photochemical cleavage, and analyzed by electron transfer dissociation mass spectrometry. Using this strategy, eight O-GlcNAc sites were mapped from a tau-enriched sample from rat brain. Sites of GlcNAcylation were characterized on important neuronal proteins such as tau, synucleins, and methyl CpG-binding protein 2.
Treatment of glioblastoma multiforme cells with temozolomide-BioShuttle ligated by the inverse Diels-Alder ligation chemistry (2009)

Recurrent glioblastoma multiforme (GBM), insensitive against most therapeutic interventions, has low response and survival rates. Temozolomide (TMZ) was approved for second-line therapy of recurrent anaplastic astrocytoma. However, TMZ therapy in GBM patients reveals properties such as reduced tolerability and inauspicious hemogram. The solution addressed here concerning GBM therapy consolidates and uses the potential of organic and peptide chemistry with molecular medicine. We enhanced the pharmacologic potency with simultaneous reduction of unwanted adverse reactions of the highly efficient chemotherapeutic TMZ. The TMZ connection to transporter molecules (TMZ-BioShuttle) was investigated, resulting in a much higher pharmacological effect in glioma cell lines and also with reduced dose rate. From this result we can conclude that a suitable chemistry could realize the ligation of pharmacologically active, but sensitive and highly unstable pharmaceutical ingredients without functional deprivation. The TMZ-BioShuttle dramatically enhanced the potential of TMZ for the treatment of brain tumors and is an attractive drug for combination chemotherapy.
Structural basis for isoform-specific inhibition of human CTPS1 (2021)

Cytidine triphosphate synthase 1 (CTPS1) is necessary for an effective immune response, as revealed by severe immunodeficiency in CTPS1-deficient individuals [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]). CTPS1 expression is up-regulated in activated lymphocytes to expand CTP pools [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]), satisfying increased demand for nucleic acid and lipid synthesis [L. D. Fairbanks, M. Bofill, K. Ruckemann, H. A. Simmonds], [<i>J. Biol. Chem.</i> ] [270], [29682-29689] ([1995]). Demand for CTP in other tissues is met by the CTPS2 isoform and nucleoside salvage pathways [E. Martin <i>et al</i>], [<i>Nature</i>] [510], [288-292] ([2014]). Selective inhibition of the proliferative CTPS1 isoform is therefore desirable in the treatment of immune disorders and lymphocyte cancers, but little is known about differences in regulation of the isoforms or mechanisms of known inhibitors. We show that CTP regulates both isoforms by binding in two sites that clash with substrates. CTPS1 is less sensitive to CTP feedback inhibition, consistent with its role in increasing CTP levels in proliferation. We also characterize recently reported small-molecule inhibitors, both CTPS1 selective and nonselective. Cryo-electron microscopy (cryo-EM) structures reveal these inhibitors mimic CTP binding in one inhibitory site, where a single amino acid substitution explains selectivity for CTPS1. The inhibitors bind to CTPS assembled into large-scale filaments, which for CTPS1 normally represents a hyperactive form of the enzyme [E. M. Lynch <i>et al</i>], [<i>Nat. Struct. Mol. Biol.</i>] [24], [507-514] ([2017]). This highlights the utility of cryo-EM in drug discovery, particularly for cases in which targets form large multimeric assemblies not amenable to structure determination by other techniques. Both inhibitors also inhibit the proliferation of human primary T cells. The mechanisms of selective inhibition of CTPS1 lay the foundation for the design of immunosuppressive therapies.
Pacifier Cleaning Practices and Risk of Allergy Development (2013)

Parental sucking of their infant's pacifier may reduce the risk of allergy development, possibly via immune stimulation by microbes transferred to the infant via the parent's saliva.
Use of recombinant factor IX in subjects with haemophilia B undergoing surgery (2002)

Recombinant human FIX (rFIX) was evaluated in 28 subjects, including 26 with mild, moderate, or severe haemophilia B and two haemophilia B carriers undergoing 36 surgical procedures. Preoperative rFIX dose was highly correlated with postinfusion FIX activity, r=0.61, P=0.0158. Peri- and post-operative estimated blood loss was similar to that expected in non-haemophilic individuals, and haemostasis was rated as excellent or good in 34 of 35 (97.1%) of the operative procedures. Transfusions were required in five of 36 (13.9%) procedures, including one liver transplantation, and three knee and one hip arthroplasties. Adverse events occurred in 15 of 28 (53.6%) subjects, but there were no perioperative haemorrhages, thromboembolic events, coagulation activation, viral transmission, or inhibitor formation. A transient low-responding FIX inhibitor developed in one subject preoperatively, but required no change in treatment and resolved 15 months later. Thus, rFIX was found to be safe and effective in achieving haemostasis in subjects with FIX deficiency undergoing surgery.
Analysis of Seed Loss and Pulmonary Seed Migration in Patients Treated With Virtual Needle Guidance and Robotic Seed Delivery (2010)

Our pulmonary seed migration and total seed loss rates are comparable to the ones reported in the literature. Virtual needle guidance and automated seed delivery system are in our hand as accurate as the manual technique.
A phase I/II study of telomerase peptide vaccination of patients with non-small cell lung cancer (2005)

2580 Background: A phase I/II study was conducted to investigate the safety, tolerability and clinical response to vaccination with a combination of telomerase peptides GV1001 (hTERT: 611–626) and HR2822 (hTERT: 540–548).Methods: Twenty-six patients with non-small cell lung cancerreceived intradermal administrations of either 112 μg or 560 μg GV1001 in combination with 68.4 μg HR2822 and granulocyte macrophage-colony stimulating factor. The treatment period was ten weeks. Booster vaccinations with 560 μg GV1001 were offered as follow-up. Monitoring of blood samples, clinical examination and radiological staging were performed regularly. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T-cell proliferation. Bone marrow function was monitored in long time survivors. Our regional medical research ethics committee has approved the study and signed informed consent was obtained in all subjects. Results: The treatment was well tolerated with minor side effects. Immune responses against GV1001 were detected in 11 of 24 evaluable patients during the primary regimen and in an additional two patients following booster injections. Two patients responded to HR2822. Cloned GV1001-specific CD4+ T cells displayed a Th1 cytokine profile and recognized autologous antigen presenting cells pulsed with recombinant telomerase protein. No bone marrow toxicities were observed in long time survivors with immune responses. A complete tumor response was observed in one patient who developed GV1001-specific cytotoxic T cells that could be cloned from peripheral blood. Conclusions: Telomerase vaccination of patients with advanced treatment resistant NSCL cancer is feasible and results in potentially beneficial immune responses in about 50% of vaccinated patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GemVax GemVax
Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria (2006)

Efflux pump genes and proteins are present in both antibiotic-susceptible and antibiotic-resistant bacteria. Pumps may be specific for one substrate or may transport a range of structurally dissimilar compounds (including antibiotics of multiple classes); such pumps can be associated with multiple drug (antibiotic) resistance (MDR). However, the clinical relevance of efflux-mediated resistance is species, drug, and infection dependent. This review focuses on chromosomally encoded pumps in bacteria that cause infections in humans. Recent structural data provide valuable insights into the mechanisms of drug transport. MDR efflux pumps contribute to antibiotic resistance in bacteria in several ways: (i) inherent resistance to an entire class of agents, (ii) inherent resistance to specific agents, and (iii) resistance conferred by overexpression of an efflux pump. Enhanced efflux can be mediated by mutations in (i) the local repressor gene, (ii) a global regulatory gene, (iii) the promoter region of the transporter gene, or (iv) insertion elements upstream of the transporter gene. Some data suggest that resistance nodulation division systems are important in pathogenicity and/or survival in a particular ecological niche. Inhibitors of various efflux pump systems have been described; typically these are plant alkaloids, but as yet no product has been marketed.
The Cavity and Pore Helices in the KcsA K + Channel: Electrostatic Stabilization of Monovalent Cations (1999)

The electrostatic influence of the central cavity and pore alpha helices in the potassium ion channel from Streptomyces lividans (KcsA K+ channel) was analyzed by solving the finite difference Poisson equation. The cavity and helices overcome the destabilizing influence of the membrane and stabilize a cation at the membrane center. The electrostatic effect of the pore helices is large compared to that described for water-soluble proteins because of the low dielectric membrane environment. The combined contributions of the ion self-energy and the helix electrostatic field give rise to selectivity for monovalent cations in the water-filled cavity. Thus, the K+ channel uses simple electrostatic principles to solve the fundamental problem of ion destabilization by the cell membrane lipid bilayer.
Suppressor Function of Umbilical Cord Blood-Derived CD4+CD25+ T-Regulatory Cells Exposed to Graft-versus-Host Disease Drugs (2006)

These data indicate a general resistance of expanded UCB Treg cells to GVHD immune suppressive agents and support trials to test UCB Treg infusions under the cover of GVHD prophylactic drugs in hematopoietic cell transplantation.
Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics (2002)

Quantitative proteomics has traditionally been performed by two-dimensional gel electrophoresis, but recently, mass spectrometric methods based on stable isotope quantitation have shown great promise for the simultaneous and automated identification and quantitation of complex protein mixtures. Here we describe a method, termed SILAC, for stable isotope labeling by amino acids in cell culture, for the in vivo incorporation of specific amino acids into all mammalian proteins. Mammalian cell lines are grown in media lacking a standard essential amino acid but supplemented with a non-radioactive, isotopically labeled form of that amino acid, in this case deuterated leucine (Leu-d3). We find that growth of cells maintained in these media is no different from growth in normal media as evidenced by cell morphology, doubling time, and ability to differentiate. Complete incorporation of Leu-d3 occurred after five doublings in the cell lines and proteins studied. Protein populations from experimental and control samples are mixed directly after harvesting, and mass spectrometric identification is straightforward as every leucine-containing peptide incorporates either all normal leucine or all Leu-d3. We have applied this technique to the relative quantitation of changes in protein expression during the process of muscle cell differentiation. Proteins that were found to be up-regulated during this process include glyceraldehyde-3-phosphate dehydrogenase, fibronectin, and pyruvate kinase M2. SILAC is a simple, inexpensive, and accurate procedure that can be used as a quantitative proteomic approach in any cell culture system.
Catalytic Properties and Specificity of the Extracellular Nuclease of Staphylococcus aureus (1967)

A spectrophotometric assay is described for staphylococcal nuclease, based on the increase in absorbance at 260 mµ which accompanies deoxyribonucleic acid and RNA hydrolysis. Initial velocities are proportional to enzyme concentration over a 70-fold range. The enzyme has greater affinity for DNA than for RNA, and activity is greater with heat-denatured DNA than with native DNA. No inhibitory products accumulate during the reaction. The enzyme is stable at pH values as low as 0.1, and in a concentration of 0.15 mg per ml there is no loss of activity after boiling (20 min). Dilute solutions are protected from heat inactivation by a mixture of albumin and Ca++ as well as by denatured DNA. The optimum pH for RNase and DNase activities is between 9 and 10, depending on the Ca++ concentration. At higher pH values, less Ca++ is required. The inhibitory effect of high Ca++ concentrations is more pronounced at higher pH values. Considerable DNase but no RNase activity results if Ca++ is replaced by Sr++, while Fe++ and Cu++ cause minimal activation. A number of heavy metal cations inhibit DNase and RNase activities competitively with Ca++; Hg++, Zn++, and Cd++ are the most potent of these. Activities resulting from combinations of DNA and RNA with Ca++ or Sr++ suggest that these substrates are hydrolyzed by the same or closely related regions on the enzyme. Enzyme activity toward DNA and RNA is strongly inhibited by 5'-phosphoryl (not by 2'- or 3'-phosphoryl) derivatives of deoxyadenylic, adenylic, and deoxythymidylic acids, and deoxythymidine 3',5'-diphosphate is the most potent inhibitor. High activity is obtained with polyadenylic acid compared to polyuridylic acid, polycytidylic acid, and RNA. These findings are consistent with the known action of the enzyme (cleavage of the 5'-phosphoryl ester bond), and suggest that the differential activity toward DNA and RNA results at least in part from differences in the affinity toward the constituent bases of these nucleic acids.
Amplification of residual DNA sequences in sterile bronchoscopes leading to false-positive PCR results (1996)

PCR has been used successfully for the direct detection of Mycobacterium tuberculosis in uncultured patient samples. Its potential is hindered by the risk of false-positive results as a result of either amplicon carryover of cross-contamination between patient samples. In the present study, we investigated whether residual amplifiable human or M. tuberculosis DNA could remain in sterile bronchoscopes and potentially be a cause of false-positive PCR results in subsequent patient samples. Sterilized bronchoscopes were flushed with sterile saline, and the collected eluate was submitted for PCR amplification of IS6110 sequences and exon 8 of the human p53 gene. Of a total of 55 washes of sterile bronchoscopes from two institutions, 2 (3.6%) contained amplifiable M. tuberculosis DNA and 11 (20%) contained residual human DNA. These findings indicate that residual DNA can remain in sterilized bronchoscopes and can be a source of false-positive PCR results.
Ethanol Reduces Expression of the Nerve Growth Factor Receptor, But Not Nerve Growth Factor Protein Levels in the Neonatal Rat Cerebellum (1997)

The cerebellum is especially vulnerable to ethanol's neurotoxic effects during development, and ethanol exposure during the brain growth spurt will deplete cerebellar neurons. The mechanisms underlying this neuronal cell loss remain elusive. Nerve growth factor (NGF) is a neurotrophin that promotes cell survival in various brain areas, and there is evidence that NGF may play a role in the developing cerebellum. This study examined whether ethanol exposure of the neonatal rat cerebellum altered the levels of either NGF or the expression of p75 and trkA, which are two components of the NGF receptor. Ethanol exposure had no effect on NGF levels in the neonatal cerebellum, as determined by an NGF-specific ELISA. Immunohistochemical labeling techniques indicated that both the p75 and trkA NGF receptors were expressed on Purkinje cell dendrites in the developing cerebellum, with posterior lobules expressing higher levels of p75 and trkA NGF receptor, compared with anterior lobules. Ethanol exposure of neonatal rats reduced the expression of both p75 and trkA NGF receptors on the Purkinje cell dendrites. These results suggest that ethanol could interfere with neurotrophic support of Purkinje cells by reducing the levels of available NGF receptor.
Phase II Trial of Taxol in Patients with Metastatic Renal Cell Carcinoma (1991)

Based on results of previous Phase I studies, 18 patients with documented metastatic renal cell carcinoma received Taxol 250 mg/m2 as a 24-h infusion, repeated every 21 days in this Phase II study. All patients received premedication with dexamethasone, diphenhydramine, and cimetidine. There were no responses in the 18 patients treated.
Quantitative myocardial infarction on delayed enhancement MRI. Part I: Animal validation of an automated feature analysis and combined thresholding infarct sizing algorithm (2006)

Clinically relevant overestimation of MI can occur in visual interpretation and in human manual contouring, particularly with respect to extent of infarction on a regional basis.