gebhart/patrepeval huggingface dataset:
Anti-phospholipid antibodies and CD5+ B cells in HIV infection (1999)

This cross-sectional study evaluates the correlation between anti-phospholipid antibodies and CD5+ B cells in 110 patients infected with HIV-1. There were 89.1% of the patients who had IgG antibodies against cardiolipin and phosphatidylserine. The prevalence of IgM and IgA antibodies was < 22%. AIDS was associated with lower frequencies of IgM antibodies against cardiolipin (P = 0.05) and IgG-antibodies against cardiolipin and phosphatidylserine (P = 0.011). Drug users had higher IgM antibodies against phospholipids than patients from other risk groups (P = 0.02). A history of thromboembolic events was not accompanied by higher levels of anti-phospholipid antibodies (P > 0.2). No correlation between anti-phospholipid antibodies and CD5+ B cells was detected. Percentage part of CD5+ B lymphocytes was elevated in all patients and absolute CD4+ T lymphocyte counts and HIV p24 antigen were inversely correlated. In advanced disease a significant reduction of anti-phospholipid antibodies was contrasted with persistent elevation of CD5+ B lymphocytes. These observations may reflect immunological dysfunction involving apoptosis and endothelial damage rather than polyclonal B cell hyperstimulation. A possible explanation would be that in HIV infection an increased rate of spontaneous apoptosis in peripheral blood lymphocytes is accompanied by functional and structural changes of mitochondria. Therefore, structurally altered mitochondrial phospholipids could serve as antigen to induce specific humoral immune responses.
Image recognition with an adiabatic quantum computer I. Mapping to quadratic unconstrained binary optimization (2008)

Many artificial intelligence (AI) problems naturally map to NP-hard optimization problems. This has the interesting consequence that enabling human-level capability in machines often requires systems that can handle formally intractable problems. This issue can sometimes (but possibly not always) be resolved by building special-purpose heuristic algorithms, tailored to the problem in question. Because of the continued difficulties in automating certain tasks that are natural for humans, there remains a strong motivation for AI researchers to investigate and apply new algorithms and techniques to hard AI problems. Recently a novel class of relevant algorithms that require quantum mechanical hardware have been proposed. These algorithms, referred to as quantum adiabatic algorithms, represent a new approach to designing both complete and heuristic solvers for NP-hard optimization problems. In this work we describe how to formulate image recognition, which is a canonical NP-hard AI problem, as a Quadratic Unconstrained Binary Optimization (QUBO) problem. The QUBO format corresponds to the input format required for D-Wave superconducting adiabatic quantum computing (AQC) processors.
Evaluation of bone turnover in postmenopausal patients with type 2 diabetes mellitus using biochemical markers and bone mineral density measurements (2003)

Although osteoporosis is reported as a potential complication of type 1 diabetes mellitus (DM), the effects of type 2 DM on bone mass are conflicting. Most of the studies conducted in recent years reveal that bone mineral density (BMD) values of type 2 DM patients are not decreased and even increased when compared with healthy control groups. In this study we evaluated bone turnover in 57 postmenopausal type 2 DM patients utilizing biochemical markers for bone formation and resorption, and BMD measurements. We found that BMD values in diabetic patients (0.91 +/- 0.11 g/cm(2) for lumbar region, 0.89 +/- 0.14 g/cm(2) for hip region) were higher than healthy postmenopausal control group (0.81 +/- 0.12 g/cm(2) for lumbar region, 0.76 +/- 0.10 g/cm(2) for hip region). Serum alkaline phosphatase values were similar to the control group, whereas serum osteocalcin and N-telopeptide/creatinine (NTx/Cr) values were significantly lower than the control group (osteocalcin: 8.82 +/- 4.03 ng/ml, NTx/Cr: 122.70 +/- 81.76 nMBCE/mMCr) in diabetic patients (osteocalcin: 4.44 +/- 3.53 ng/ml, NTx/Cr: 42.24 +/- 29.97 nMBCE/mMCr). Also a significant correlation was observed between body mass index and BMD values. Our findings suggested that the bone turnover rate is remarkably lower in type 2 DM patients compared to healthy postmenopausal patients.
Amino Acid Ester Prodrugs of Acyclovir (1992)

Eighteen amino acid esters of the antiherpetic drug, acyclovir, were synthesized as potential prodrugs for oral administration. The esters were examined for in vitro antiviral activity against herpes simplex virus Type 1 (HSV-1). They were found to have less potency than the parent compound. Their efficiencies as prodrugs were evaluated in rats by measuring the urinary recovery of acyclovir. Ten prodrugs produced greater amounts of the parent drug in the urine. The L-amino acid esters were better prodrugs than the corresponding D- or D, L-isomers, suggesting the involvement of a stereoselective transporter. The L-valyl ester, 256U87, was the best prodrug. Sixty three per cent of its administered dose was excreted as acyclovir in the urine, a considerable improvement over acyclovir itself, for which this value was 19%. Since 256U87 was stable in aqueous solutions, its conversion to acyclovir in vivo was probably enzyme catalyzed. This L-valyl ester prodrug of acyclovir is now undergoing clinical evaluation.
Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy (2009)

We report the development of a previously undescribed gold nanoparticle bio-barcode assay probe for the detection of prostate specific antigen (PSA) at 330 fg/mL, automation of the assay, and the results of a clinical pilot study designed to assess the ability of the assay to detect PSA in the serum of 18 men who have undergone radical prostatectomy for prostate cancer. Due to a lack of sensitivity, available PSA immunoassays are often not capable of detecting PSA in the serum of men after radical prostatectomy. This new bio-barcode PSA assay is approximately 300 times more sensitive than commercial immunoassays. Significantly, with the barcode assay, every patient in this cohort had a measurable serum PSA level after radical prostatectomy. Patients were separated into categories based on PSA levels as a function of time. One group of patients showed low levels of PSA with no significant increase with time and did not recur. Others showed, at some point postprostatectomy, rising PSA levels. The majority recurred. Therefore, this new ultrasensitive assay points to significant possible outcomes: (i) The ability to tell patients, who have undetectable PSA levels with conventional assays, but detectable and nonrising levels with the barcode assay, that their cancer will not recur. (ii) The ability to assign recurrence earlier because of the ability to measure increasing levels of PSA before conventional tools can make such assignments. (iii) The ability to use PSA levels that are not detectable with conventional assays to follow the response of patients to adjuvant or salvage therapies.
IL-4 in the Brain: A Cytokine To Remember (2012)

IL-4 has been extensively studied in the context of its role in immunity. Accumulating evidence indicates, however, that it also plays a critical role in higher functions of the normal brain, such as memory and learning. In this review, we summarize current knowledge of the basic immunology of IL-4, describe how and where this cytokine appears to operate in normal brain function, and propose a hypothesis concerning its potential role in neurological pathologies.
Germline competence of mouse ES and iPS cell lines: Chimera technologies and genetic background (2009)

In mice, gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics. This strategy allows precise location of the site of transgene integration and is most commonly used to ablate gene expression ("knock-out"), or to introduce mutant or modified alleles at the locus of interest ("knock-in"). The efficacy of producing live, transgenic mice challenges our understanding of this complex process, and of the factors which influence germline competence of embryonic stem cell lines. Increasingly, evidence indicates that culture conditions and in vitro manipulation can affect the germline-competence of Embryonic Stem cell (ES cell) lines by accumulation of chromosome abnormalities and/or epigenetic alterations of the ES cell genome. The effectiveness of ES cell derivation is greatly strain-dependent and it may also influence the germline transmission capability. Recent technical improvements in the production of germline chimeras have been focused on means of generating ES cells lines with a higher germline potential. There are a number of options for generating chimeras from ES cells (ES chimera mice); however, each method has its advantages and disadvantages. Recent developments in induced pluripotent stem (iPS) cell technology have opened new avenues for generation of animals from genetically modified somatic cells by means of chimera technologies. The aim of this review is to give a brief account of how the factors mentioned above are influencing the germline transmission capacity and the developmental potential of mouse pluripotent stem cell lines. The most recent methods for generating specifically ES and iPS chimera mice, including the advantages and disadvantages of each method are also discussed.
Adaptive Evolution of Human Immunodeficiency Virus-Type 1 During the Natural Course of Infection (1996)

The rate of progression to disease varies considerably among individuals infected with human immunodeficiency virus-type 1 (HIV-1). Analyses of semiannual blood samples obtained from six infected men showed that a rapid rate of CD4 T cell loss was associated with relative evolutionary stasis of the HIV-1 quasispecies virus population. More moderate rates of CD4 T cell loss correlated with genetic evolution within three of four subjects. Consistent with selection by the immune constraints of these subjects, amino acid changes were apparent within the appropriate epitopes of human leukocyte antigen class I-restricted cytotoxic T lymphocytes. Thus, the evolutionary dynamics exhibited by the HIV-1 quasispecies virus populations under natural selection are compatible with adaptive evolution.
Enrichment and Detection of Rare Proteins with Aptamer-Conjugated Gold Nanorods (2012)

Rare protein enrichment and sensitive detection hold great potential in biomedical studies and clinical practice. This work describes the use of aptamer-conjugated gold nanorods for the efficient enrichment of rare proteins from buffer solutions and human plasma. Gold nanorod (AuNR) surfaces were modified with a long PEG chain and a 15-mer thrombin aptamer for protein enrichment and detection. Studies of the effect of surface modification on enrichment efficiency of thrombin showed that a change of only one EG(6) linker unit, i.e., from 2EG(6) to 3EG(6), could increase thrombin protein capture efficiency by up to 47%. Furthermore, a 1 ppm sample of thrombin in buffer could be enriched with around 90% efficiency using a low concentration (0.19 nM) of gold nanorod probe modified with 3EG(6) spacer, and with the same probe, effective capture was achieved down to 10 ppb (1 ng) thrombin in plasma samples. In addition to α-thrombin enrichment, prothrombin was also efficiently captured from plasma samples via gold nanorods conjugated with 15-mer thrombin aptamer. Our work demonstrates efficient enrichment of rare proteins using aptamer-modified nanomaterials, which can be used in biomarker discovery studies.
Immunological benefits of antiretroviral therapy in very early stages of asymptomatic chronic HIV-1 infection (2000)

Initiating highly active antiretroviral therapy at very early stages of chronic HIV-1 infection allows rapid and almost complete normalization of T cell subsets and preservation of T cell functions. These early-treated patients could be excellent candidates for receiving additional HIV-specific immune-based therapies, which might be essential for the control of HIV infection.
An Oncogenic Role for ETV1 in Melanoma (2010)

Copy gains involving chromosome 7p represent one of the most common genomic alterations found in melanomas, suggesting the presence of "driver" cancer genes. We identified several tumor samples that harbored focal amplifications situated at the peak of common chromosome 7p gains, in which the minimal common overlapping region spanned the ETV1 oncogene. Fluorescence in situ hybridization analysis revealed copy gains spanning the ETV1 locus in >40% of cases, with ETV1 amplification (>6 copies/cell) present in 13% of primary and 18% of metastatic melanomas. Melanoma cell lines, including those with ETV1 amplification, exhibited dependency on ETV1 expression for proliferation and anchorage-independent growth. Moreover, overexpression of ETV1 in combination with oncogenic NRAS(G12D) transformed primary melanocytes and promoted tumor formation in mice. ETV1 overexpression elevated microphthalmia-associated transcription factor expression in immortalized melanocytes, which was necessary for ETV1-dependent oncogenicity. These observations implicate deregulated ETV1 in melanoma genesis and suggest a pivotal lineage dependency mediated by oncogenic ETS transcription factors in this malignancy.
Tat-Conjugated Synthetic Macromolecules Facilitate Cytoplasmic Drug Delivery To Human Ovarian Carcinoma Cells (2002)

We have synthesized N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cell penetrating peptide Tat conjugates and evaluated their subcellular distribution in A2780 human ovarian carcinoma cells by confocal fluorescence microscopy and subcellular fractionation. Our data indicate the transport of these conjugates by a single Tat molecule to both the cytoplasm and nucleus via a nonendocytotic and concentration independent process. The uptake was observed to occur within 3 min, as confirmed by live cell microscopy. In contrast, HPMA copolymers lacking the Tat peptide were internalized solely by endocytosis. For the first time, Tat-mediated cytoplasmic delivery of a polymer bound anticancer drug, doxorubicin, was also demonstrated. These findings establish the feasibility of overcoming major cellular and subcellular obstacles to intracellular macromolecular delivery and hold great promise for the development of polymer-based systems for the cytoplasmic delivery of therapeutic molecules.
Acute arterial thrombosis after escalated-dose methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy with recombinant granulocyte colony-stimulating factor: A possible new recombinant granulocyte colony-stimulating factor toxicity (1992)

Combination chemotherapy with a regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) has produced long-term survival times in a significant proportion of patients with advanced nodal and metastatic urothelial tumors. The availability of the colony-stimulating factors has spurred interest in studies evaluating escalated dosing schedules of M-VAC in an attempt to improve major response rates and overall survival. More frequent use of the colony-stimulating factors, however, in this and other settings may be associated with unrecognized side effects. The authors report a case of arterial thrombosis in a 69-year-old man receiving recombinant granulocyte colony-stimulating factor (rhG-CSF) and escalated-dose M-VAC for treatment of a transitional cell carcinoma of the bladder. Incidents of venous thrombosis have been reported previously with the use of colony-stimulating factors, but, to the knowledge of the authors, this case represents the first report of an arterial thrombosis occurring in a patient receiving rhG-CSF.
HtrA1 Inhibits Mineral Deposition by Osteoblasts (2007)

HtrA1 is a secreted multidomain protein with serine protease activity. In light of increasing evidence implicating this protein in the regulation of skeletal development and pathology, we investigated the role of HtrA1 in osteoblast mineralization and identified domains essential for this activity. We demonstrate increased HtrA1 expression in differentiating 2T3 osteoblasts prior to the appearance of mineralization. HtrA1 is subsequently down-regulated in fully mineralized cultures. The functional role of HtrA1 in matrix calcification was investigated using three complementary approaches. First, we transfected a full-length HtrA1 expression plasmid into 2T3 cells and showed that overexpression of HtrA1 delayed mineralization, reduced expression of Cbfa1 and collagen type I mRNA, and prevented BMP-2-induced mineralization. Second, knocking down HtrA1 expression using short interfering RNA induced mineral deposition by 2T3 cells. Third, by expressing a series of recombinant HtrA1 proteins, we demonstrated that the protease domain and the PDZ domain are essential for the inhibitory effect of HtrA1 on osteoblast mineralization. Finally, we tested whether HtrA1 cleaves specific matrix proteins that are known to regulate osteoblast differentiation, mineralization, and/or BMP-2 activity. Full-length recombinant HtrA1 cleaved recombinant decorin, fibronectin, and matrix Gla protein. Both the protease domain and the PDZ domain were necessary for the cleavage of matrix Gla protein, whereas the PDZ domain was not required for the cleavage of decorin or fibronectin. Type I collagen was not cleaved by recombinant HtrA1. These results suggest that HtrA1 may regulate matrix calcification via the inhibition of BMP-2 signaling, modulating osteoblast gene expression, and/or via the degradation of specific matrix proteins.
Marine natural product antifoulants: Status and potential (1996)

This overview attempts to bring together a widely scattered and disparate literature on marine natural product antifoulants. In particular, studies that have focused on the screening of secondary metabolites are reviewed in the context of the development of new antifouling coatings. Despite considerable progress towards characterising compounds that inhibit settlement of micro‐ and/or macrofouling, evidence for an ecological role for these compounds is poor. Even if broad spectrum antifoulants of sufficient promise are discovered, major hurdles must be overcome before they can be commercially exploited. Not least are the need to procure sufficient material and the cost of registration. Given these constraints and the relatively small size of the marine coatings market, industrial investment in product research and development appears low. Notwithstanding these problems, some marine organisms are able to maintain a surface that is essentially free of epibionts. Fundamental research on natural antifouling mechanisms is now required. The information gained, in addition to ascertaining the relative importance of physical versus chemical defences to marine organisms, would provide a conceptual framework for the development of novel, and ideally nontoxic, coatings.
A novel locus of Yersinia enterocolitica serotype O:3 involved in lipopolysaccharide outer core biosynthesis (1995)

Yersinia enterocolitica serotype O:3 strain 6471/76-c (YeO3-c) was sensitive to bacteriophage phi R1-37 when grown at 37 degrees C but not when grown at 22 degrees C because of steric hindrance by abundant lipopolysaccharide (LPS) O-side chain (O-antigen) expressed at 22 degrees C. The transposon library of YeO3-c was grown at 37 degrees C and screened for phage phi R1-37-resistant transposon insertion mutants. Three types of mutant were isolated: (i) phage receptor mutants expressing O-antigen (LPS-smooth), (ii) phage receptor mutants not expressing O-antigen (LPS-rough), and (iii) LPS-smooth mutants with the phage receptor constitutively sterically blocked. Mutant type (i) was characterized in detail; the transposon insertion inactivates an operon, named the trs operon. The main findings based on this mutant are: (i) the frs operon is involved in the biosynthesis of the LPS outer core in YeO3-c; the nucleotide sequence of the trs operon revealed eight novel genes showing similarly to known polysaccharide biosynthetic genes of various Gram-negative bacteria as well as to capsule biosynthesis genes of Staphylococcus aureus; (ii) the biosynthesis of the core of YeO3-c involves at least two genetic loci; (iii) the trs operon is required for the biosynthesis of the bacteriophage phi R1-37 receptor structures; (iv) the homopolymeric O-antigen of YeO3-c is ligated to the inner core in Y. enterocolitica O:3; (v) the trs operon is located between the adk-hemH and galE-gsk gene pairs in the Y. enterocolitica chromosome; and (vi) the phage phi R1-37 receptor is present in many but not in all Y. enterocolitica serotypes. The results also allow us to speculate that the trs operon is a relic of the ancestral rfb region of Y. enterocolitica O:3 carrying genes indispensable for the completion of the core polysaccharide biosynthesis.
Studies of Electrochemical Synthesis of Ultrathin ZnO Nanorod/Nanobelt Arrays on Zn Substrates in Alkaline Solutions of Amine−Alcohol Mixtures (2007)

The electrode reactions and pathways involved in the electrochemical fabrication of highly ordered ultrathin ZnO nanorod/nanobelt arrays in alkaline solutions of amine−alcohol mixtures are systematically studied and revealed. These include electrochemical surface oxidation of the Zn cathode to Zn(OH)42−, simultaneous in situ nucleation of ZnO from the Zn(OH)42− ions on the cathode, and subsequent amine-capped growth into the ZnO nanobelt/nanorod arrays. It is shown that the growth step can also be supported by the Zn(OH)42− source from the anodic oxidation, and the growth from this source actually yields much more uniform and smooth nanobelt/nanorod arrays than those from only the cathodic source. Furthermore, the strategy has been successfully applied to the fabrication of a ZnO nanorod array on an ITO substrate covered with a Zn film, which promises exciting applications in solar cell and sensor devices.
Context-dependent optimal substitution matrices (1995)

Substitution matrices are a key tool in important applications such as identifying sequence homologies, creating sequence alignments and more recently using evolutionary patterns for the prediction of protein structure. We have derived a novel approach to the derivation of these matrices that utilizes not only multiple sequence alignments, but also the associated evolutionary trees. The key to our method is the use of a Bayesian formalism to calculate the probability that a given substitution matrix fits the tree structures and multiple sequence alignment data. Using this procedure, we can determine optimal substitution matrices for various local environments, depending on parameters such as secondary structure and surface accessibility.
Sodium Channel Inactivation: Molecular Determinants and Modulation (2005)

Voltage-gated sodium channels open (activate) when the membrane is depolarized and close on repolarization (deactivate) but also on continuing depolarization by a process termed inactivation, which leaves the channel refractory, i.e., unable to open again for a period of time. In the "classical" fast inactivation, this time is of the millisecond range, but it can last much longer (up to seconds) in a different slow type of inactivation. These two types of inactivation have different mechanisms located in different parts of the channel molecule: the fast inactivation at the cytoplasmic pore opening which can be closed by a hinged lid, the slow inactivation in other parts involving conformational changes of the pore. Fast inactivation is highly vulnerable and affected by many chemical agents, toxins, and proteolytic enzymes but also by the presence of beta-subunits of the channel molecule. Systematic studies of these modulating factors and of the effects of point mutations (experimental and in hereditary diseases) in the channel molecule have yielded a fairly consistent picture of the molecular background of fast inactivation, which for the slow inactivation is still lacking.