gebhart/patrepeval huggingface dataset:
Neuroprotective possibilities for Huntington’s disease (2001)

Huntington's disease (HD) is a devastating genetic disorder. Despite the absence of effective therapy, there has been an explosion in interest for developing treatment strategies aimed at lessening or preventing the neuronal death that occurs in this disease. In large part, the renewed interest in neuroprotective strategies has been spurred by our increasing understanding of the genetic and molecular events that drive the underlying neuropathology of HD. This escalating understanding of the biological underpinnings of HD is derived from several convergent sources represented by investigators with clinical, genetic, molecular, physiological and neurobehavioural backgrounds. The diversity of data being generated has, in turn, produced a unique time in HD research where an impressive number of potential therapeutics are coming to the forefront. This review outlines several of these possibilities including the use of intracerebrally delivered neurotrophic factors, pharmacologically altering cellular energy production, the use of antiglutamatergic drugs, the use of caspase inhibitors and inhibitors of protein aggregation. This review also touches on the interesting possibility of whether or not the neurodegeneration in HD is at least partially reversible in nature. All of these possibilities are highlighted in the context that HD is a neurodegenerative disorder in which genetic detection provides a clear and unequivocal opportunity for neuroprotection.
Endoplasmic reticulum HSP90b1 (gp96, grp94) optimizes B-cell function via chaperoning integrin and TLR but not immunoglobulin (2008)

Endoplasmic reticulum (ER) unfolded protein response (UPR) plays pivotal roles in both early B-cell development and plasma cell differentiation. As a major ER chaperone to mediate the UPR and a master chaperone for Toll-like receptors (TLRs), HSP90b1 (grp94, gp96) has long been implicated to facilitate the assembly of immunoglobulin. We hereby critically and comprehensively examine the roles of HSP90b1 in B-cell biology in vivo using B-cell-specific HSP90b1-null mice. We found that knockout B cells developed normally. There were no apparent problems with plasma cell differentiation, Ig assembly, class-switching, and Ig production. Strikingly, although both mutant conventional and innatelike B cells failed to compartmentalize properly due to loss of select but not all integrins, HSP90b1 was required for neither germinal center formation nor memory antibody responses in vivo. The only significant defect associated with HSP90b1 ablation in B cells was an attenuated antibody production in the context of TLR stimulation. Thus, our study has resolved the long-standing question regarding HSP90b1 in B-cell biology: HSP90b1 optimizes the function of B cells by chaperoning TLRs and integrins but not immunoglobulin. This study also has important implications in resolving the controversial roles of TLR in B-cell biology.
Point-of-care urinary pneumococcal antigen test in the emergency department for community acquired pneumonia (2008)

PNAG diagnosis of pneumococcal pneumonia can be accurately performed as a point-of-care test by emergency department clinical staff. Without specific efforts to achieve early urine collection, the timeframe of testing will frequently fall outside the 4-hour patient stay of a UK emergency department and may be more appropriately considered as a test for the medical admissions unit in this setting. Sensitivity is at least equal to conventional culture methods and the result is available rapidly enough to potentially influence treatment decisions, a strategy that warrants further investigation.
Handheld high-throughput plasmonic biosensor using computational on-chip imaging (2014)

We demonstrate a handheld on-chip biosensing technology that employs plasmonic microarrays coupled with a lens-free computational imaging system towards multiplexed and high-throughput screening of biomolecular interactions for point-of-care applications and resource-limited settings. This lightweight and field-portable biosensing device, weighing 60 g and 7.5 cm tall, utilizes a compact optoelectronic sensor array to record the diffraction patterns of plasmonic nanostructures under uniform illumination by a single-light emitting diode tuned to the plasmonic mode of the nanoapertures. Employing a sensitive plasmonic array design that is combined with lens-free computational imaging, we demonstrate label-free and quantitative detection of biomolecules with a protein layer thickness down to 3 nm. Integrating large-scale plasmonic microarrays, our on-chip imaging platform enables simultaneous detection of protein mono- and bilayers on the same platform over a wide range of biomolecule concentrations. In this handheld device, we also employ an iterative phase retrieval-based image reconstruction method, which offers the ability to digitally image a highly multiplexed array of sensors on the same plasmonic chip, making this approach especially suitable for high-throughput diagnostic applications in field settings. A handheld biosensor that employs lens-free imaging on a plasmonic chip could simplify high-throughput protein detection. The device, developed by Arif Cetin and co-workers at Boston University and the University of California at Los Angeles in the USA, promises label-free quantitative detection of large variety of proteins on the same sensor chip. The unit, which is battery-powered, 7.5 cm tall and just 60 g in weight, operates by transmitting light from an LED through a functionalized plasmonic chip containing an array of periodic nanoholes in a gold film. The diffraction pattern of the nanoapertures is recorded by a CMOS image sensor. The presence of a protein monolayer as thin as 3 nm that binds to the plasmonic chip induces a dramatic change in the diffraction pattern sampled by the image sensor chip.
50 Years of Computer Simulation of the Human Thermoregulatory System (2013)

This paper presents an updated and augmented version of the Wissler human thermoregulation model that has been developed continuously over the past 50 years. The existing Fortran code is translated into C with extensive embedded commentary. A graphical user interface (GUI) has been developed in Python to facilitate convenient user designation of input and output variables and formatting of data presentation. Use of the code with the GUI is described and demonstrated. New physiological elements were added to the model to represent the hands and feet, including the unique vascular structures adapted for heat transfer associated with glabrous skin. The heat transfer function and efficacy of glabrous skin is unique within the entire body based on the capacity for a very high rate of blood perfusion and the novel capability for dynamic regulation of blood flow. The model was applied to quantify the absolute and relative contributions of glabrous skin flow to thermoregulation for varying levels of blood perfusion. The model also was used to demonstrate how the unique features of glabrous skin blood flow may be recruited to implement thermal therapeutic procedures. We have developed proprietary methods to manipulate the control of glabrous skin blood flow in conjunction with therapeutic devices and simulated the effect of these methods with the model.
Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic (2009)

Asenapine sublingual tablets are a new option for the treatment of acute episodes of schizophrenia and for the treatment of acute manic or mixed episodes of bipolar I disorder. Although there is no evidence for asenapine's efficacy to be superior to currently available agents, asenapine's favourable weight and metabolic profile are of clinical interest. A caveat is that the data reviewed regarding asenapine are from its manufacturer. No independent studies of asenapine's efficacy or safety are available. Obstacles to the use of asenapine are the recommendations for twice daily dosing and the need to avoid food or liquids for 10 min after administration. As asenapine's bioavailability is very low if ingested, asenapine is unique among the antipsychotics, in that it needs to be swallowed to be covertly 'cheeked'.
Science, medicine, and the future: osteoporosis (1997)

Efficient processing of incoming sensory input is essential for an organism9s survival. A growing body of evidence suggests that sensory systems have developed coding strategies that are constrained by the statistics of the natural environment. Consequently, it is necessary to first characterize neural responses to natural stimuli to uncover the coding strategies used by a given sensory system. Here we report for the first time the statistics of vestibular rotational and translational stimuli experienced by rhesus monkeys during natural (e.g., walking, grooming) behaviors. We find that these stimuli can reach intensities as high as 1500 deg/s and 8 G. Recordings from afferents during naturalistic rotational and linear motion further revealed strongly nonlinear responses in the form of rectification and saturation, which could not be accurately predicted by traditional linear models of vestibular processing. Accordingly, we used linear–nonlinear cascade models and found that these could accurately predict responses to naturalistic stimuli. Finally, we tested whether the statistics of natural vestibular signals constrain the neural coding strategies used by peripheral afferents. We found that both irregular otolith and semicircular canal afferents, because of their higher sensitivities, were more optimized for processing natural vestibular stimuli as compared with their regular counterparts. Our results therefore provide the first evidence supporting the hypothesis that the neural coding strategies used by the vestibular system are matched to the statistics of natural stimuli.
Interventions for alopecia areata (2008)

Few treatments for alopecia areata have been well evaluated in randomised trials. We found no RCTs on the use of diphencyprone, dinitrochlorobenzene, intralesional corticosteroids or dithranol although they are commonly used for the treatment of alopecia areata. Similarly although topical steroids and minoxidil are widely prescribed and appear to be safe, there is no convincing evidence that they are beneficial in the long-term. Most trials have been reported poorly and are so small that any important clinical benefits are inconclusive. There is a desperate need for large well conducted studies that evaluate long-term effects of therapies on quality of life. Considering the possibility of spontaneous remission especially for those in the early stages of the disease, the options of not being treated therapeutically or, depending on individual preference wearing a wig may be alternative ways of dealing with this condition.
Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma (2001)

This revision will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.
Topical Treatment of Experimental Herpes Simplex Keratouveitis With 2′-O-glycylacyclovir (1984)

2'-O-glycylacyclovir, a water-soluble ester derivative of acyclovir, has proved efficacious in the topical treatment of epithelial and stromal herpes simplex keratitis, and iritis therewith associated, when administered as a 1% eyedrop formulation to rabbits.
Expression of Cyclooxygenase-1 and Cyclooxygenase-2 in Human Breast Cancer (1998)

Our results suggest that overexpression of COX may not be unique to colon cancer and may be a feature common to other epithelial tumors.
A hybrid ribonuclease H. A novel RNA cleaving enzyme with sequence-specific recognition. (1992)

A hybrid enzyme which site-specifically hydrolyzes RNA was created by covalently linking an oligodeoxyribonucleotide to Escherichia coli ribonuclease HI, an enzyme which specifically cleaves RNA moiety of DNA/RNA hybrids. A cysteine residue was substituted for Glu135 by site-directed mutagenesis in the mutant enzyme, in which all 3 free cysteine residues were replaced by alanine (Kanaya, S., Kimura, S., Katsuda, C., and Ikehara, M. (1990) Biochem. J. 271, 59-66), and coupled with a maleimide group, which is attached to the 5' terminus of the nonadeoxyribonucleotide (5'-GTCATCTCC-3') with a flexible tether. The resulting hybrid enzyme, d9-C135/RNase H, cleaved the phosphodiester bond between the fifth and sixth residues of the complementary nonaribonucleotide, without addition of the oligodeoxyribonucleotide. The nonaribonucleotide is cleaved by the wild-type or unmodified mutant enzyme only when the complementary oligodeoxyribonucleotide is present. When the kinetic parameters of the hybrid enzyme for the hydrolysis of the nonaribonucleotide were compared with those of the unmodified mutant enzyme for the hydrolysis of the nonanucleotide duplex, the hybrid enzyme exhibited a 7- and 4-fold decreases in the Km and kcat values, respectively, indicating that it performs multiple turnovers and has a sufficiently high hydrolytic activity. Hybrid ribonucleases H with various oligodeoxyribonucleotides in size and sequence, therefore, might be used as excellent tools for structural and functional studies of RNA.
Prognostic role and correlation of CA9, CD31, CD68 and CD20 with the desmoplastic stroma in pancreatic ductal adenocarcinoma (2016)

We assessed the prognostic value of hypoxia (carbonic anhydrase 9; CA9), vessel density (CD31), with macrophages (CD68) and B cells (CD20) that can interact and lead to immune suppression and disease progression using scanning and histological mapping of whole-mount FFPE pancreatectomy tissue sections from 141 primarily resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with surgery and adjuvant chemotherapy. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin). The median OS was 21 months after a mean follow-up of 20 months (range, 2-69 months). The median tumor surface area positive for CA9 and CD31 was 7.8% and 8.1%, respectively. Although total expression of these markers lacked prognostic value in the entire cohort, nevertheless, high tumor compartment CD68 expression correlated with worse PFS (p = 0.033) and DMFS (p = 0.047). Also, high CD31 expression predicted for worse OS (p = 0.004), PFS (p = 0.008), LPFS (p = 0.014) and DMFS (p = 0.004) in patients with moderate density stroma. High stromal and peripheral compartment CD68 expression predicted for significantly worse outcome in patients with loose and moderate stroma density, respectively. Altogether, in contrast to the current notion, hypoxia levels in PDAC appear to be comparable to other malignancies. CD31 and CD68 constitute prognostic markers in patient subgroups that vary according to tumor compartment and stromal density. Our study provides important insight on the pathophysiology of PDAC and should be exploited for future treatments.
Minimap2: pairwise alignment for nucleotide sequences (2018)

Supplementary data are available at Bioinformatics online.
Study of progesterone release mechanisms from a silicone matrix by a new analytical method (2004)

Abstract The release behavior of progesterone from a silicone matrix to release media containing 60% (v/v) alcohol and water was investigated and kinetically evaluated. For this purpose, samples containing 5, 10, or 15% (w/w) micronized progesterone were prepared through the mixing of two‐component silicone and the drug in a thermomixer. The discs were cured with compression molding. Then, the release from a controlled surface area was experimentally determined by a high‐performance thin‐layer chromatography technique, a new method for progesterone analysis. With Higuchi's model, the drug‐release behavior of the dispersion systems was determined by a partition‐controlled process (the relationship between the accumulated amount of the drug released and the time) and a matrix‐controlled process (the relationship between the accumulated amount of the drug released and the square root of time). The release profile determined by experimental data was in good agreement with Higuchi's model. Moreover, the product of the solubility and diffusivity of progesterone in the polymer matrix was evaluated and found to be 8.1 × 10 −7 mg/cm/s. Finally, the effects of fillers on the release behavior were studied. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 3040–3044, 2004
Auctioning the Airwaves: The Contest for Broadband pcs Spectrum (1995)

The House and Senate of the United States Congress recently passed legislation that directs the FCC to establish a system for using auctions to allocate the use of radio spectrum for personal communications services. There is a unique and unprecedented set of issues that arise in this context, which are of interest to economists, industry analysts, regulators, and policymakers. We discuss these issues and evaluate their likely impact on the outcome of the spectrum auctions. In addition, we argue that there may be pitfalls in the auction procedure adopted by the FCC, and we discuss possible alternative procedures.
Experimental results and modeling techniques for substrate noise in mixed-signal integrated circuits (1993)

An experimental technique is described for observing the effects of switching transients in digital MOS circuits that perturb analog circuits integrated on the same die by means of coupling through the substrate. Various approaches to reducing substrate crosstalk (the use of physical separation of analog and digital circuits, guard rings, and a low-inductance substrate bias) are evaluated experimentally for a CMOS technology with a substrate comprising an epitaxial layer grown on a heavily doped bulk wafer. Observations indicate that reducing the inductance in the substrate bias is the most effective. Device simulations are used to show how crosstalk propagates via the heavily doped bulk and to predict the nature of substrate crosstalk in CMOS technologies integrated in uniform, lightly doped bulk substrates, showing that in such cases the substrate noise is highly dependent on layout geometry. A method of including substrate effects in SPICE simulations for circuits fabricated on epitaxial, heavily doped substrates is developed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The genetics of sugary enhancer (se), an independent modifier of sweet corn (su) (1978)

The high sugar content of the sweet corn line, IL677a, was found to be due to the effects of an independent recessive modifier of the su genotype. This new mutant is not one of 12 previously reported endosperm mutants. The gene can be bred readily into other su lines, but to obtain the full effects of the high sugary trait in F1 hybrids, both su parents should be homozygous for the gene. The gene symbol Se (sugary enhancer) is recommended for the new mutant.
Development of a tail vein transection bleeding model in fully anaesthetized haemophilia A mice – characterization of two novel FVIII molecules (2016)

The optimized tail vein transection bleeding model is sensitive to standard as well as half-life prolonged FVIII molecules and should be a valuable alternative to both the tail tip bleeding model, enhancing sensitivity to pharmacological intervention, as well as to the previously used tail vein transection survival model, avoiding death or near-death as endpoint.
The Distribution and Characteristics of ‘와(wa)’ Complement in Korean (2006)

이 글은 술어적 기능을 하는 어휘범주와의 관계에 있어서 필수 성분으로 나타나는 ‘와’ 보충어를 연구 대상으로 한다. ‘와’ 보충어를 요구하는 술어적 어휘범주의 유형에 초점을 맞추어서, ‘와’ 보충어가 이들 어휘범주에 의해 도입된다는 사실을 실제 말뭉치에서의 ‘와’ 보충어의 분포를 통해서 드러내 보일 것이다. 지금까지의 보충어에 대한 연구는 기본적으로 동사 혹은 형용사가 가지는 필수 성분의 수와 그 통사ㆍ의미적 특성을 규명하는 것이 중심이 되어 왔다. 그렇지만, 이 글에서는 ‘와’ 보충어를 요구하는 술어적 요소가 기존의 연구에서 주로 다루어져 왔던 이른바 대칭용언뿐만 아니라, 일련의 명사(구), 부사, 혹은 동사구로 확대되어야 함을 밝히고자 한다. 아울러 ‘와’ 보충어를 취하는 용언 이외의 어휘범주의 분포 및 통사적 특징을 살펴보도록 한다.<BR> 이 글에 사용된 말뭉치는 ‘21세기 세종계획 현대국어 말뭉치’이며, 이중 문어 말뭉치 약 900만 어절을 토대로 표본 추출(sampling)의 방식을 적용하여 90만여 어절의 연구용 말뭉치를 구성하였다. 이 연구용 말뭉치를 대상으로 ‘와’ 보충어가 술어적 어휘범주와의 관계에 있어 필수 성분으로 해석되는 3,624개의 용례를 추출하였다. ‘와’ 보충어를 취하는 어휘범주의 분포는 ‘동사(33.1%) 〉형용사(20.0%) 〉부사(19.1%) 〉명사(구)(16.7%) 〉동사구(10.8%) 〉수량사(0.2%)’의 순으로 나타났다.
Interferon‐γ‐inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin‐12 for interferon‐γ production (1996)

Abstract The novel cytokine interferon‐γ‐inducing factor (IGIF) augments natural killer (NK) cell activity in cultures of human peripheral blood mononuclear cells (PBMC), similarly to the structurally unrelated cytokine interleukin (IL)‐12. IGIF has been found to enhance the production of interferon‐γ (IFN‐γ) and granulocyte/macrophage colony‐stimulating factor (GM‐CSF) while inhibiting the production of IL‐10 in concanavalin A (Con A)‐stimulated PBMC. In this study, when anti‐CD3 monoclonal antibody (mAb)‐stimulated human enriched T cells were exposed to IGIF, the cytokine dose‐dependently enhanced the proliferation of the cells and this could be completely inhibited by a neutralizing antibody against IL‐2 at lower concentrations of IGIF. Neutralizing antibody against IFN‐γ had only insignificant inhibitory effects on T cell proliferation at higher concentrations of IGIF. Enzyme‐linked immunosorbent assays (ELISA) revealed that, like PBMC, T cells exposed to IGIF produced large amounts of IFN‐γ; however, changes in the production of IL‐4 and IL‐10 were minimal. IGIF, but not IL‐12, significantly enhanced IL‐2 and GM‐CSF production in T cell cultures, as determined by CTLL‐2 bioassay and ELISA, respectively; however, both IGIF and IL‐12 enhanced IFN‐γ production by the T cells. When T cells were exposed to a combination of IGIF and IL‐12, a synergistic effect was observed on the production of IFN‐γ, but not on production of IL‐2 and GM‐CSF. In conclusion, IGIF enhances T cell proliferation apparently through an IL‐2‐dependent pathway and enhances Th1 cytokine production in vitro and exhibits synergism when combined with IL‐12 in terms of enhanced IFN‐γ production but not IL‐2 and GM‐CSF production. Based on structural and functional differences from any known cytokines, it was recently proposed that this cytokine be designated interleukin‐18.
Detection of rheumatoid factors of different isotypes and of circulating immune complexes in patients with inflammatory bowel disease. (1990)

The behaviour of some serological aspects of autoimmunity was studied in patients with inflammatory bowel disease (IBD) by determining the incidence and levels of serum IgM, IgG and IgA rheumatoid factors (RF) and of circulating immune-complexes (IC) in 67 patients suffering from ulcerative colitis (UC) and 53 from Crohn's disease (CD). Sera from 40 young healthy subjects were included as controls. RF were detected by an enzyme linked immuno-assay (ELISA) and IC by the CIC-conglutinin and the CIC-C1q assays. ELISA detected a higher incidence of IgM RF in both UC and CD groups than the routine agglutination tests, although the mean levels were non significantly higher than in controls. Mean IgG RF levels were significantly above normal in UC and CD patients, the latter showing a greater incidence of elevated values and higher mean levels. IgA RF were significantly elevated only in CD patients; mean values for the UC group were within the normal range. The CIC-conglutinin test did not detect a significant incidence or high mean levels of IC and the CIC-C1q assay turned up a sizeable number of positive samples only in the CD group. Although still only preliminary, these overall findings suggest that RF activity is somehow present in patients with IBD. The greater prevalence of IC in CD patients, together with the patterns of IgG and IgA RF support the concept that this disease possibly involves autoimmune phenomena more than ulcerative colitis.