gebhart/patrepeval huggingface dataset:
Sufficiency Revisited: Rethinking Statistical Algorithms in the Big Data Era (2016)

The big data era demands new statistical analysis paradigms, since traditional methods often break down when datasets are too large to fit on a single desktop computer. Divide and Recombine (D&R) is becoming a popular approach for big data analysis, where results are combined over subanalyses performed in separate data subsets. In this article, we consider situations where unit record data cannot be made available by data custodians due to privacy concerns, and explore the concept of statistical sufficiency and summary statistics for model fitting. The resulting approach represents a type of D&R strategy, which we refer to as summary statistics D&R; as opposed to the standard approach, which we refer to as horizontal D&R. We demonstrate the concept via an extended Gamma–Poisson model, where summary statistics are extracted from different databases and incorporated directly into the fitting algorithm without having to combine unit record data. By exploiting the natural hierarchy of data, our approach has major benefits in terms of privacy protection. Incorporating the proposed modelling framework into data extraction tools such as TableBuilder by the Australian Bureau of Statistics allows for potential analysis at a finer geographical level, which we illustrate with a multilevel analysis of the Australian unemployment data. Supplementary materials for this article are available online.
Human telomeres contain at least three types of G–rich repeat distributed non-randomly (1989)

Using a combination of different oligonucleotides and restriction enzymes we have examined the gross organisation of repeats within the most distal region of human chromosomes. We demonstrate here that human telomeres do not contain a pure uniform 6 base pair repeat unit but that there are at least three types of repeat. These three types of repeat are present at the ends of most or all human chromosomes. The distribution of each type of repeat appears to be non-random. Each human telomere has a similar arrangement of these repeats relative to the ends of the chromosome. This could reflect differences in the functions that they perform, or might result from the mutation and correction processes occurring at human telomeres. The number of repeat units, the repeat types and arrangement differs at mouse telomeres. Analysing the change in length of the telomeric repeat region between an individuals blood and germline DNA reveals that this is due to variable amounts of the TTAGGG repeat and not the other repeat types. This organization of repeat units at human telomeres will only be confirmed upon the isolation and sequencing of full length (10-15 kb), intact human telomeres.
A WRKY Gene from Creosote Bush Encodes an Activator of the Abscisic Acid Signaling Pathway (2004)

The creosote bush (Larrea tridentata) is a xerophytic evergreen C3 shrub thriving in vast arid areas of North America. As the first step toward understanding the molecular mechanisms controlling the drought tolerance of this desert plant, we have isolated a dozen genes encoding transcription factors, including LtWRKY21 that encodes a protein of 314 amino acid residues. Transient expression studies with the GFP-LtWRKY21 fusion construct indicate that the LtWRKY21 protein is localized in the nucleus and is able to activate the promoter of an abscisic acid (ABA)-inducible gene, HVA22, in a dosage-dependent manner. The transactivating activity of LtWRKY21 relies on the C-terminal sequence containing the WRKY domain and a N-terminal motif that is essential for the repression activity of some regulators in ethylene signaling. LtWRKY21 interacts synergistically with ABA and transcriptional activators VP1 and ABI5 to control the expression of the HVA22 promoter. Co-expression of VP1, ABI5, and LtWRKY21 leads to a much higher expression of the HVA22 promoter than does the ABA treatment alone. In contrast, the Lt-WRKY21-mediated transactivation is inhibited by two known negative regulators of ABA signaling: 1-butanol, an inhibitor of phospholipase D, and abi1-1, a dominant negative mutant protein phosphatase. Interestingly, abi1-1 does not block the synergistic effect of LtWRKY21, VP1, and ABI5 co-expression, indicating that LtWRKY21, VP1, and ABI5 may form a complex that functions downstream of ABI1 to control ABA-regulated expression of genes.
Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study (1996)

CA 125 is a powerful index of risk of ovarian and fallopian tube cancer in asymptomatic postmenopausal women.
Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study (2017)

Purpose The clinical activity observed in a phase I dose-escalation study of concurrent therapy with nivolumab (NIVO) and ipilimumab (IPI) in patients with previously treated or untreated advanced melanoma led to subsequent clinical development, including randomized trials. Here, we report long-term follow-up data from study CA209-004, including 3-year overall survival (OS). Patients and Methods Concurrent cohorts 1, 2, 2a, and 3 received escalating doses of NIVO plus IPI once every 3 weeks for four doses, followed by NIVO once every 3 weeks for four doses, then NIVO plus IPI once every 12 weeks for eight doses. An expansion cohort (cohort 8) received concurrent NIVO 1 mg/kg plus IPI 3 mg/kg once every 3 weeks for four doses, followed by NIVO 3 mg/kg once every 2 weeks, which is the dose and schedule used in phase II and III studies and now approved for patients with unresectable or metastatic melanoma. Results Among all concurrent cohorts (N = 94) at a follow-up of 30.3 to 55.0 months, the 3-year OS rate was 63% and median OS had not been reached. Objective response rate by modified WHO criteria was 42%, and median duration of response was 22.3 months. Incidence of grade 3 and 4 treatment-related adverse events was 59%. The most common grade 3 and 4 treatment-related adverse events were increases in lipase (15%), alanine aminotransferase (12%), and aspartate aminotransferase (11%). One treatment-related death (1.1%) occurred in a patient who had multiorgan failure 70 days after the last dose of NIVO plus IPI. Conclusion This is the longest follow-up for NIVO plus IPI combination therapy in patients with advanced melanoma. The 3-year OS rate of 63% is the highest observed for this patient population and provides additional evidence for the durable clinical activity of immune checkpoint inhibitors in the treatment of advanced melanoma.
An outline of the Romanian special education approach. New attitudes for a new perspective (2004)

Romanian special education finds its beginnings in the second half of the nineteenth century at the same time as the constitution of the modern state and the efforts of gradual opening to new Europ...
MAFFT version 5: improvement in accuracy of multiple sequence alignment (2005)

The accuracy of multiple sequence alignment program MAFFT has been improved. The new version (5.3) of MAFFT offers new iterative refinement options, H-INS-i, F-INS-i and G-INS-i, in which pairwise alignment information are incorporated into objective function. These new options of MAFFT showed higher accuracy than currently available methods including TCoffee version 2 and CLUSTAL W in benchmark tests consisting of alignments of >50 sequences. Like the previously available options, the new options of MAFFT can handle hundreds of sequences on a standard desktop computer. We also examined the effect of the number of homologues included in an alignment. For a multiple alignment consisting of approximately 8 sequences with low similarity, the accuracy was improved (2-10 percentage points) when the sequences were aligned together with dozens of their close homologues (E-value < 10(-5)-10(-20)) collected from a database. Such improvement was generally observed for most methods, but remarkably large for the new options of MAFFT proposed here. Thus, we made a Ruby script, mafftE.rb, which aligns the input sequences together with their close homologues collected from SwissProt using NCBI-BLAST.
Fluoroquinolones (1991)

Fluoroquinolones are the newest antibiotics for treatment of some infections caused by highly resistant bacteria (eg, Pseudomonas aeruginosa). Clinically sound indications for these drugs include resistant infections of the urinary, intestinal, and respiratory tracts; otitis externa; osteomyelitis; foot infections in diabetic patients; and late infections complicating burns. Fluoroquinolone therapy is not indicated in children younger than 12 years old and patients with foreign bodies, abscesses, pelvic inflammatory disease, or infections requiring a prophylactic antibiotic. Drug interactions with antacids or theophylline may occur.
RelE, a global inhibitor of translation, is activated during nutritional stress (2001)

The stringent response is defined as the physiological changes elicited by amino acid starvation. Many of these changes depend on the regulatory nucleotide ppGpp (guanosine tetraphosphate) synthesized by RelA (ppGpp synthetase I), the relA-encoded protein. The second rel locus of Escherichia coli is called relBE and encodes RelE cytotoxin and RelB antitoxin. RelB counteracts the toxic effect of RelE. In addition, RelB is an autorepressor of relBE transcription. Here we reveal a ppGpp-independent mechanism that reduces the level of translation during amino acid starvation. Artificial overexpression of RelE severely inhibited translation. During amino acid starvation, the presence of relBE caused a significant reduction in the poststarvation level of translation. Concomitantly, relBE transcription was rapidly and strongly induced. Induction of transcription occurred independently of relA and spoT (encoding ppGpp synthetase II), but instead depended on Lon protease. Consistently, Lon was required for degradation of RelB. Replacement of the relBE promoter with a LacI-regulated promoter indicated that strong and ongoing transcription of relBE is required to maintain a proper RelB:RelE ratio during starvation. Thus relBE may be regarded as a previously uncharacterized type of stress-response element that reduces the global level of translation during nutritional stress.
Palladium-catalyzed reaction of allyl halides with α-diazocarbonyl compounds (2008)

The Pd(OAc)(2)-catalyzed reaction between alpha-diazocarbonyl compounds and allyl bromides or chlorides leads to the formation of 1,3-diene derivatives.
Deep Networks for Image Super-Resolution with Sparse Prior (2015)

Deep learning techniques have been successfully applied in many areas of computer vision, including low-level image restoration problems. For image super-resolution, several models based on deep neural networks have been recently proposed and attained superior performance that overshadows all previous handcrafted models. The question then arises whether large-capacity and data-driven models have become the dominant solution to the ill-posed super-resolution problem. In this paper, we argue that domain expertise represented by the conventional sparse coding model is still valuable, and it can be combined with the key ingredients of deep learning to achieve further improved results. We show that a sparse coding model particularly designed for super-resolution can be incarnated as a neural network, and trained in a cascaded structure from end to end. The interpretation of the network based on sparse coding leads to much more efficient and effective training, as well as a reduced model size. Our model is evaluated on a wide range of images, and shows clear advantage over existing state-of-the-art methods in terms of both restoration accuracy and human subjective quality.
Molecular mechanisms of cellular mechanics (2006)

Mechanical forces play an essential role in cellular processes as input, output, and signals. Various protein complexes in the cell are designed to handle, transform and use such forces. For instance, proteins of muscle and the extracellular matrix can withstand considerable stretching forces, hearing-related and mechanosensory proteins can transform weak mechanical stimuli into electrical signals, and regulatory proteins are suited to forcing DNA into loops to control gene expression. Here we review the structure-function relationship of four protein complexes with well defined and representative mechanical functions. The first example is titin, a protein that confers passive elasticity on muscle. The second system is the elastic extracellular matrix protein, fibronectin, and its cellular receptor integrin. The third protein system is the transduction apparatus in hearing and other mechanical senses, likely containing cadherin and ankyrin repeats. The last system is the lac repressor protein, which regulates gene expression by looping DNA. This review focuses on atomic level descriptions of the physical mechanisms underlying the various mechanical functions of the stated proteins.
Chemical Modification to Reduce Renal Uptake of Disulfide-Bonded Variable Region Fragment of Anti-Tac Monoclonal Antibody Labeled with 99mTc (1999)

The anti-Tac disulfide-bonded variable region fragment (dsFv) is a genetically engineered, 25 kDa, murine monoclonal antibody fragment that recognizes the alpha subunit of the interleukin-2 receptor (IL-2Ralpha). The dsFv radiolabeled with the tetrafluorophenyl ester (TFP) of [99mTc]mercaptoacetyltriglycine ([99mTc]MAG3-TFP) showed rapid tumor uptake and fast blood clearance in mice, resulting in high tumor-to-nontumor background ratios. However, its high renal uptake was a problem. In this study, we tested the effect of lowering the isoelectric point (pI) of dsFv to <9.3 on renal and tumor uptake. To lower the pI, dsFv was acylated simultaneously with both [99mTc]MAG3-TFP and TFP-glycolate. The acylation of dsFv decreased its pI and its immunoreactivity inversely proportional to the molar ratio of TFP-glycolate to dsFv, whereas the conjugation of [99mTc]MAG3-TFP alone did not. When biodistribution studies were performed in nude mice, the effect of the lowered pI was reflected primarily in decreased kidney uptake and whole-body retention, with its highest effect seen at the earliest time point (15 min) after injection. In tumor-bearing nude mice, glycolated [99mTc]MAG3-dsFv with a pI range of 4.9 to 6.5 accumulated selectively into IL-2 receptor-positive SP2/Tac tumor similar to that of the control [125I]dsFv labeled by the Iodo-Gen method, whereas its renal uptake was 25% of [125I]dsFv at 15 min. At 90 min, the ratios of tumor to receptor-negative SP2/0 tumor, liver, kidney, stomach, and blood had peaked at 10.9, 8.5, 0.3, 5.0, and 6.2, respectively, for the glycolated [99mTc]MAG3-dsFv. The corresponding ratios for [125I]dsFv were 3.7, 5.0, 0.1, 1.5, and 2.1, respectively.
P-glycoprotein expression in human retinal pigment epithelium. (2002)

Human RPE, not exposed to inducer treatment, expresses P-glycoprotein with localization to both apical and basal cell surfaces. Basolateral P-glycoprotein could serve a protective function for the neural retina helping to clear unwanted substances from subretinal space. The finding that P-glycoprotein is also on the apical surface suggests possible additional roles for P-glycoprotein in the RPE.
The Speciation of Silver Nanoparticles in Antimicrobial Fabric Before and After Exposure to a Hypochlorite/Detergent Solution (2009)

Because of their antibacterial properties, silver nanoparticles are often used in consumer products. To assess environmental and/or human health risks from these nanoparticles, there is a need to identify the chemical transformations that silver nanoparticles undergo in different environments. Thus an antimicrobial sock material containing Ag nanoparticles was examined by X-ray absorption spectroscopy to identify the speciation of Ag. The material was exposed to a hypochlorite/detergent solution and subjected to agitation. An elemental Ag nanopowder was also exposed to the hypochlorite/detergent solution or to a 1 mol L(-1) NaCl solution. Results showed that the sock material nanoparticles consisted of elemental Ag. After exposure to the hypochlorite/detergent solution, a significant portion (more than 50%) of the sock nanoparticles were converted, in situ, to AgCl. Results from exposures to elemental Ag nanopowder suggest that an oxidation step is necessary for the elemental Ag nanoparticles to transform into AgCl as there was no evidence of AgCl formation in the presence of chloride alone. As a result, if Ag ions leach from consumer products, any chloride present may quickly scavenge the ions. In addition, the efficacy of Ag, as an antimicrobial agent in fabrics, may be limited, or even negated, after washing in solutions containing oxidizers as AgCl is much less reactive than Ag ion.
Antibody-Mediated Disruption of the Annexin-V Antithrombotic Shield: A New Mechanism for Thrombosis in the Antiphospholipid Syndrome (1999)

Introduction The antiphospholipid (aPL) syndrome is a condition that manifests in patients as vascular thromboembolism or recurrent pregnancy loss together with laboratory evidence for the presence of antibodies against anionic phospholipid-protein complexes. For a recent comprehensive review, the reader is referred to Hughes et al.1 The syndrome was first proposed to be a distinct entity, called anticardiolipin syndrome, in 1985,2 and was later renamed antiphospholipid syndrome.3 The disorder was classified as “primary” in the absence of a concurrent autoimmune condition, such as systemic lupus erythematosus, or “secondary” in the presence of another such autoimmune disorder. Antiphospholipid antibodies are detected by their reactivity to anionic phospholipids (or protein-phospholipid complexes) in solid phase immunoassays, or by their inhibition of phospholipid-dependent coagulation reactions, known as the “lupus anticoagulant” effect. The ever-expanding, yet still insufficiently integrated, knowledge of this enigmatic disorder makes this area an intriguing subject for investigation. The pathophysiologic mechanism of this syndrome has remained obscure, resulting from the apparent multiplicity of antigenic determinants recognized by the antibodies. In addition, a large number of effects1 have been described for the antibodies in vitro and in cell culture systems. These effects, which include the paradoxical lupus anticoagulant (LAC) phenomenon, are a consequence of the numerous roles played by phospholipids in the hemostasis system and in a multitude of biologic processes. The purpose of this review is to introduce the reader to the current state of knowledge of the role of annexin-V in this disorder.
The Monoclonal Antibody 11G7 Recognizes a Novel Differentiation Antigen Expressed on Hemopoietic Precursor Cells (1991)

A monoclonal antibody (11G7) detecting a novel antigen on human hemopoietic progenitor cells (named 11G7R = 11G7 receptor) was raised by immunization of a Balb/c mouse with the leukemic blasts of a patient suffering from chronic myelogenous leukemia blast crisis (CML-BC). The antigen is expressed on most of MHC class II bearing peripheral blood leucocytes (PBL) and on a subpopulation of bone marrow mononuclear cells (BMMNC). By FACS-sorting and colony assays, it could be demonstrated that 11G7R is expressed on myelo-monocytic and myelo-granulocytic bone marrow precursor cells (GM-CFC, G-CFC, M-CFC) but is absent from erythroid precursor cells (BFU-E) and on cells exhibiting the capacity to form mixed colonies (GEMM-CFC). Double-fluorescence analysis on BMMNC revealed that 11G7R is expressed on a subset of B-cells, myeloid cells and cells carrying the HPCA-1 antigen (CD34). It has a similar distribution pattern to the myeloid antigens CD13 and CD33. However, in contrast to these antigens, 11G7R is also expressed on the blasts of several lymphoid leukemias (4/9 B-ALL, 1/2 T-ALL) and therefore it is not restricted to the myeloid lineage.
The effect of vitamin E on granulocyte function in patients with recurrent infections. (1991)

The influence of vit. E treatment on metabolic and bactericidal granulocyte activity in patients with recurrent infections was studied by chemiluminescence and phagocytosis assays. Vit. E serum level was significantly diminished before therapy. Six weeks supplementation with 200-300 mg/day of vit. E resulted in improvement of clinical status and normalisation of alpha-tocopherol serum level. Bactericidal activity of granulocytes was lower in patients than in the respective controls and it slightly rose after vit. E therapy. Before, therapy, patients granulocytes showed metabolic activity above or within the control range. Vit. E treatment increased, had no effect or decreased granulocyte metabolic activity, but never below the control range.
Subverting ER-Stress towards Apoptosis by Nelfinavir and Curcumin Coexposure Augments Docetaxel Efficacy in Castration Resistant Prostate Cancer Cells (2014)

Despite its side-effects, docetaxel (DTX) remains a first-line treatment against castration resistant prostate cancer (CRPC). Therefore, strategies to increase its anti-tumor efficacy and decrease its side effects are critically needed. Targeting of the constitutive endoplasmic reticulum (ER) stress in cancer cells is being investigated as a chemosensitization approach. We hypothesized that the simultaneous induction of ER-stress and suppression of PI3K/AKT survival pathway will be a more effective approach. In a CRPC cell line, C4-2B, we observed significant (p<0.005) enhancement of DTX-induced cytotoxicity following coexposure to thapsigargin and an AKT-inhibitor. However, since these two agents are not clinically approved, we investigated whether a combination of nelfinavir (NFR) and curcumin (CUR), known to target both these metabolic pathways, can similarly increase DTX cytotoxicity in CRPC cells. Within 24 hrs post-exposure to physiologic concentrations of NFR (5 µM) and CUR (5 µM) a significantly (p<0.005) enhanced cytotoxicity was evident with low concentration of DTX (10 nM). This 3-drug combination rapidly increased apoptosis in aggressive C4-2B cells, but not in RWPE-1 cells or in primary prostate epithelial cells (PrEC). Comparative molecular studies revealed that this 3-drug combination caused a more pronounced suppression of phosphorylated-AKT and higher induction in phosphorylated-eIF2α in C4-2B cells, as compared to RWPE-1 cells. Acute exposure (3-9 hrs) to this 3-drug combination intensified ER-stress induced pro-apoptotic markers, i.e. ATF4, CHOP, and TRIB3. At much lower concentrations, chronic (3 wks) exposures to these three agents drastically reduced colony forming units (CFU) by C4-2B cells. In vivo studies using mice containing C4-2B tumor xenografts showed significant (p<0.05) enhancement of DTX's (10 mg/kg) anti-tumor efficacy following coexposure to NFR (20 mg/kg) & CUR (100 mg/kg). Immunohistochemical (IHC) analyses of tumor sections indicated decreased Ki-67 staining and increased TUNEL intensity in mice exposed to the 3-drug combination. Therefore, subverting ER-stress towards apoptosis using adjuvant therapy with NFR and CUR can chemosensitize the CRPC cells to DTX therapy.
Recombinant Human Interleukin-2, Recombinant Human Interferon Alfa-2a, or Both in Metastatic Renal-Cell Carcinoma (1998)

Cytokines are active in a few patients with metastatic renal-cell carcinoma. The higher response rate and longer event-free survival obtained with a combination of cytokines must be balanced against the toxicity of such treatment.
Photoacid-Induced Fluorescence Quenching: A New Strategy for Fluorescent Imaging in Polymer Films (2000)

Fluorescent images can be photochemically generated in thin films of the copolymer 1. This fluorescent copolymer has been designed in such a way that interaction with a photochemically formed acid HA, leading to the protonated species, quenches the fluorescence. When this quenching occurs in selected areas patterned images are obtained.
High-throughput minor histocompatibility antigen prediction (2009)

http://www.peptidecheck.org.