gebhart/patrepeval huggingface dataset:
Familial Amyotrophic Lateral Sclerosis Mutants of Copper/Zinc Superoxide Dismutase Are Susceptible to Disulfide Reduction (2003)

We observed that 14 biologically metallated mutants of copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis all exhibited aberrantly accelerated mobility during partially denaturing PAGE and increased sensitivity to proteolytic digestion compared with wild type SOD1. Decreased metal binding site occupancy and exposure to the disulfide-reducing agents dithiothreitol, Tris(2-carboxyethyl)phosphine (TCEP), or reduced glutathione increased the fraction of anomalously migrating mutant SOD1 proteins. Furthermore, the incubation of mutant SOD1s with TCEP increased the accessibility to iodoacetamide of cysteine residues that normally participate in the formation of the intrasubunit disulfide bond (Cys-57 to Cys-146) or are buried within the core of the beta-barrel (Cys-6). SOD1 enzymes in spinal cord lysates from G85R and G93A mutant but not wild type SOD1 transgenic mice also exhibited abnormal vulnerability to TCEP, which exposed normally inaccessible cysteine residues to modification by maleimide conjugated to polyethylene glycol. These results implicate SOD1 destabilization under cellular disulfide-reducing conditions at physiological pH and temperature as a shared property that may be relevant to amyotrophic lateral sclerosis mutant neurotoxicity.
Concentration Dependence of a Poly-Leucine Surfactant Protein C Analogue on in vitro and in vivo Surfactant Activity (2007)

These data suggest that SP-C33 is similarly efficient as the native peptide in improving surface properties of phospholipids mixtures and in increasing lung compliance in surfactant-deficient states, but that other components are needed to maintain alveolar stability at low airway pressures.
Specification and estimation of hedonic housing price models (1992)

Alternative traditional and spatial autoregressive hedonic urban housing price models are offered corresponding to different conceptualizations of the housing price determination process. Some methodological issues relevant to their estimation are addressed that draw upon recent developments from spatial econometrics. These include the selection of the appropriate estimation strategy; the application of diagnostic tests for the detection of spatial dependence and heterogeneity; and the use of robust methods in the presence of heteroskedasticity.
Clinical comparison of the AutoMicrobic system gram-positive identification card, API Staph-Ident, and conventional methods in the identification of coagulase-negative Staphylococcus spp (1983)

In an effort to rapidly identify coagulase-negative staphylococci (CNS), a clinical comparison was conducted with the AutoMicrobic system Gram-Positive Identification Card (GPI) (Vitek Systems, Inc.), the API Staph-Ident (Analytab Products), and the conventional methods of W. E. Kloos and K. H. Schleifer (W. E. Kloos and K. H. Schleifer, J. Clin. Microbiol. 1:82-88, 1975). CNS isolates tested included 157 from blood and 33 from urine in pure culture at greater than 10(5) CFU/ml. S. epidermidis accounted for 79.6 and 60.6% of the isolates from blood and urine, respectively. S. saprophyticus was the next most frequent urine isolate (27.4%). Other CNS species were isolated from blood and urine specimens with frequencies of less than 5%. Overall, the GPI correctly identified 158 (83.2%) of the 190 CNS, whereas the Staph-Ident identified 124 (65.3%) without further testing. This resulted in the GPI and Staph-Ident correctly identifying 95.9 and 74.5% of the S. epidermidis and 100 and 33% of the S. saprophyticus, respectively. The GPI misidentified 8 (47%) of the S. hominis and S. warneri isolates as S. saprophyticus, indicating the need for novobiocin testing. These data suggest that the GPI is a more definitive method for the rapid identification of S. epidermidis than the Staph-Ident and that both systems require additional testing to identify S. saprophyticus.
Germline viral “fossils” guide in silico reconstruction of a mid-Cenozoic era marsupial adeno-associated virus (2016)

Germline endogenous viral elements (EVEs) genetically preserve viral nucleotide sequences useful to the study of viral evolution, gene mutation, and the phylogenetic relationships among host organisms. Here, we describe a lineage-specific, adeno-associated virus (AAV)-derived endogenous viral element (mAAV-EVE1) found within the germline of numerous closely related marsupial species. Molecular screening of a marsupial DNA panel indicated that mAAV-EVE1 occurs specifically within the marsupial suborder Macropodiformes (present-day kangaroos, wallabies, and related macropodoids), to the exclusion of other Diprotodontian lineages. Orthologous mAAV-EVE1 locus sequences from sixteen macropodoid species, representing a speciation history spanning an estimated 30 million years, facilitated compilation of an inferred ancestral sequence that recapitulates the genome of an ancient marsupial AAV that circulated among Australian metatherian fauna sometime during the late Eocene to early Oligocene. In silico gene reconstruction and molecular modelling indicate remarkable conservation of viral structure over a geologic timescale. Characterisation of AAV-EVE loci among disparate species affords insight into AAV evolution and, in the case of macropodoid species, may offer an additional genetic basis for assignment of phylogenetic relationships among the Macropodoidea. From an applied perspective, the identified AAV "fossils" provide novel capsid sequences for use in translational research and clinical applications.
Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer (2012)

Glutamate carboxypeptidase II (GCPII) is a membrane-bound binuclear zinc metallopeptidase with the highest expression levels found in the nervous and prostatic tissue. Throughout the nervous system, glia-bound GCPII is intimately involved in the neuron-neuron and neuron-glia signaling via the hydrolysis of N-acetylaspartylglutamate (NAAG), the most abundant mammalian peptidic neurotransmitter. The inhibition of the GCPII-controlled NAAG catabolism has been shown to attenuate neurotoxicity associated with enhanced glutamate transmission and GCPII-specific inhibitors demonstrate efficacy in multiple preclinical models including traumatic brain injury, stroke, neuropathic and inflammatory pain, amyotrophic lateral sclerosis, and schizophrenia. The second major area of pharmacological interventions targeting GCPII focuses on prostate carcinoma; GCPII expression levels are highly increased in androgen-independent and metastatic disease. Consequently, the enzyme serves as a potential target for imaging and therapy. This review offers a summary of GCPII structure, physiological functions in healthy tissues, and its association with various pathologies. The review also outlines the development of GCPII-specific small-molecule compounds and their use in preclinical and clinical settings.
Preparation and analysis of cSNP chip on hepatocellular carcinoma-related genes. (2005)

The cSNP chip of hepatocellular carcinoma-related genes can accelerate the discovery of polymorphic markers on hepatocellular carcinoma.
HIF isoforms in the skin differentially regulate systemic arterial pressure (2013)

Vascular flow through tissues is regulated via a number of homeostatic mechanisms. Localized control of tissue blood flow, or autoregulation, is a key factor in regulating tissue perfusion and oxygenation. We show here that the net balance between two hypoxia-inducible factor (HIF) transcription factor isoforms, HIF-1α and HIF-2α, is an essential mechanism regulating both local and systemic blood flow in the skin of mice. We also show that balance of HIF isoforms in keratinocyte-specific mutant mice affects thermal adaptation, exercise capacity, and systemic arterial pressure. The two primary HIF isoforms achieve these effects in opposing ways that are associated with HIF isoform regulation of nitric oxide production. We also show that a correlation exists between altered levels of HIF isoforms in the skin and the degree of idiopathic hypertension in human subjects. Thus, the balance between HIF-1α and HIF-2α expression in keratinocytes is a control element of both tissue perfusion and systemic arterial pressure, with potential implications in human hypertension.
JKanji: wavelet-based interactive kanji completion (2002)

JKanji is an interactive character completion system that provides stroke-order-independent recognition of complex handwritten glyphs such as Japanese kanji or Chinese hanzi. As the user enters each stroke, JKanji offers a menu of likely completions, generated from a robust multiscale matching algorithm augmented with a statistical language model. Unlike many existing systems, JKanji can incrementally incorporate new training examples, either to adapt to the idiosyncrasies of a particular user, or to increase its vocabulary. On a kanji input task with a vocabulary of 6369 kanji and English characters, JKanji has demonstrated 93%-96% recognition accuracy and up to 80% reduction in the number of input strokes. JKanji is computationally efficient, processing images at 5-10 Hz on an inexpensive portable computer and is well-suited for integration into personal digital assistants as an input method. JKanji's recognition system also processes low-quality digital camera images.
Observation of the Spin Hall Effect in Semiconductors (2004)

Electrically induced electron-spin polarization near the edges of a semiconductor channel was detected and imaged with the use of Kerr rotation microscopy. The polarization is out-of-plane and has opposite sign for the two edges, consistent with the predictions of the spin Hall effect. Measurements of unstrained gallium arsenide and strained indium gallium arsenide samples reveal that strain modifies spin accumulation at zero magnetic field. A weak dependence on crystal orientation for the strained samples suggests that the mechanism is the extrinsic spin Hall effect.
Reentrant polygon clipping (1974)

A new family of clipping algorithms is described. These algorithms are able to clip polygons against irregular convex plane-faced volumes in three dimensions, removing the parts of the polygon which lie outside the volume. In two dimensions the algorithms permit clipping against irregular convex windows. Polygons to be clipped are represented as an ordered sequence of vertices without repetition of first and last, in marked contrast to representation as a collection of edges as was heretofore the common procedure. Output polygons have an identical format, with new vertices introduced in sequence to describe any newly-cut edge or edges. The algorithms easily handle the particularly difficult problem of detecting that a new vertex may be required at a corner of the clipping window. The algorithms described achieve considerable simplicity by clipping separately against each clipping plane or window boundary. Code capable of clipping the polygon against a single boundary is reentered to clip against subsequent boundaries. Each such reentrant stage of clipping need store only two vertex values and may begin its processing as soon as the first output vertex from the preceeding stage is ready. Because the same code is reentered for clipping against subsequent boundaries, clipping against very complex window shapes is practical. For perspective applications in three dimensions, a six-plane truncated pyramid is chosen as the clipping volume. The two additional planes parallel to the projection screen serve to limit the range of depth preserved through the projection. A perspective projection method which provides for arbitrary view angles and depth of field in spite of simple fixed clipping planes is described. This method is ideal for subsequent hidden-surface computations.
Coronaviruses disease 2019 (COVID-19): Causative agent, mental health concerns, and potential management options (2020)

Coronavirus disease-2019 (COVID-19) pandemic started from Wuhan, China has infected more than 6.7 million individuals and killed more than 390,000 individuals globally. Due to the higher transmissibility and infectiousness, asymptomatic infection, and lack of effective treatment options and vaccine, fatalities and morbidities are increasing day by day globally. Despite physical health consequences, COVID-19 pandemic has created stress and anxiety, as result there is an increased risk of mental illnesses both in the infected and normal individuals. To eradicate these risks, it is necessary to determine the COVID-19 zoonotic source of transmission to humans and clinical manifestations in infected individuals. Although, identification or development of the highly effective therapeutic agents is necessary, however, development of protective strategies against the COVID-19 by enhancing immune responses will be an asset in the current scenarios of the COVID-19 pandemic. In this paper, we discuss the transmission, health consequences, and potential management (therapeutic and preventive) options for COVID-19 disease.
Identification of Aim-1 as the underwhiteMouse Mutant and Its Transcriptional Regulation by MITF (2002)

Animal pigmentation mutants have provided rich models for the identification of genes modulating pathways from melanocyte development to melanoma. One mouse model is the underwhite locus, alleles of which manifest altered pigmentation of both eye and fur, sometimes in an age-dependent fashion. Here we show that the mouse homolog of a recently identified gene whose mutation produces Japanese gold-colored fish, medaka b, maps to the mouse underwhite locus. We identify distinct mutations of this gene, known as Aim-1, in three underwhite mouse alleles and find that structure/function differences correlate with recessive versus dominant inheritance. The human ortholog of AIM-1 was originally identified as a melanocyte-restricted antigen that is recognized by autologous T cells from a patient with melanoma. We also provide evidence that AIM-1 is transcriptionally modulated by MITF, a melanocyte-specific transcription factor essential to pigmentation and a clinical diagnostic marker in human melanoma. Although AIM-1 appears to reside downstream of MITF, chromatin immunoprecipitations do not reveal binding of MITF to a 5'-flanking region containing histone 3 acetylation, indicating that MITF either acts indirectly on AIM-1 or it binds to a remote regulatory sequence. Nevertheless, MITF links AIM-1 expression and the underwhite phenotype to a transcriptional network central to pigmentation in mammals.
Calicheamicin θ: A Rationally Designed Molecule with Extremely Potent and Selective DNA Cleaving Properties and Apoptosis Inducing Activity (1994)

The attack of a thiolate ion on the trisulfide unit of natural calicheamicin γ (1) activates it to form a diradical, which then attacks DNA. Thioacetate 2 is even more readily activated—under mildly basic conditions caused by OH- ions—and likewise exhibits extremely interesting biological properties.
Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97 (2015)

Exploratory SAR studies of a new phenyl indole chemotype for p97 inhibition revealed C-5 indole substituent effects in the ADPGlo assay that did not fully correlate with either electronic or steric factors. A focused series of methoxy-, trifluoromethoxy-, methyl-, trifluoromethyl-, pentafluorosulfanyl-, and nitro-analogues was found to exhibit IC50s from low nanomolar to double-digit micromolar. Surprisingly, we found that the trifluoromethoxy-analogue was biochemically a better match of the trifluoromethyl-substituted lead structure than a pentafluorosulfanyl-analogue. Moreover, in spite of their almost equivalent strongly electron-depleting effect on the indole core, pentafluorosulfanyl- and nitro-derivatives were found to exhibit a 430-fold difference in p97 inhibitory activities. Conversely, the electronically divergent C-5 methyl- and nitro-analogues both showed low nanomolar activities.
Simultaneous and Rapid Analysis of Cyclosporin A and Creatinine in Finger Prick Blood Samples Using Liquid Chromatography Tandem Mass Spectrometry and Its Application in C2 Monitoring (2002)

A simple and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous analysis of cyclosporin A (CsA) and creatinine using capillary blood has been developed. Venous and capillary blood samples were taken predose and at C2 from 65 heart and lung transplant recipients (65 x 4 samples). For comparisons, serum creatinine and blood CsA concentrations were measured by the Jaffe and EMIT methods, respectively, using an Olympus AU600 analyzer. For the LC-MS/MS assay, samples were prepared in a 96 x 700-microL well block by adding 10 microL of blood (or serum) to 40 microL of 0.1 mol/L zinc sulphate solution containing deuterated creatinine internal standard. Proteins were precipitated by adding 100 microL acetonitrile containing ascomycin internal standard. After vigorous mixing and centrifugation, 5 microL of the supernatant was injected into the LC-MS/MS system. A Waters 2795 high-performance liquid chromatography (HPLC) system was used to elute a C18 cartridge (3 mm x 4 mm) at 0.6 mL/min with a step gradient of 50-100% methanol containing 2 mmol/L ammonium acetate and 0.1% (v/v) formic acid. The column was maintained at 55 degrees C, and the retention times were creatinine, 0.4 minutes; ascomycin, 0.98 minutes; and CsA, 1.2 minutes. Cycle time was 2.5 minutes, injection to injection. The analytes were monitored using a Quattro microtandem mass spectrometer operated in multiple reaction monitoring mode using the following transitions: creatinine, m/z 114>44; d3-creatinine (IS), m/z 117>47; ascomycin (IS), m/z 809>756; and CsA, m/z 1,220>1,203. Assay characteristics were CsA intraassay CV, 3.6-3.0% (33-1,500 microg/L); CsA interassay CV, 6.7-2.5% (10-5,000 microg/L); LC-MS/MS capillary [CsA] = 0.99 x LC-MS/MS venous [CsA] - 4.2, R = 0.98; and LC-MS/MS venous [CsA] = 0.93 x EMIT venous [CsA] + 2.9, R = 0.98. Creatinine intraassay CV, 6.6-2.5% (20-720 micromol/L); interassay CV, 5.7-3.3% (80-590 micromol/L); LC-MS/MS capillary [creatinine] = 0.99 Jaffe plasma [creatinine] -42.6, R = 0.87. Total time for the preparation and analysis of 30 samples was approximately 2 hours. This assay will provide a flexible, robust, and cost-effective solution for the monitoring of CsA and creatinine in transplant recipients with potential applications in pediatric medicine and pharmacokinetic studies, in which frequent sampling is required.
The Arabidopsis hrl1 mutation reveals novel overlapping roles for salicylic acid, jasmonic acid and ethylene signalling in cell death and defence against pathogens (2002)

Defence against pathogens in Arabidopsis is orchestrated by at least three signalling molecules: salicylic acid (SA), jasmonic acid (JA) and ethylene (ET). The hrl1 (hypersensitive response-like lesions 1) mutant of Arabidopsis is characterized by spontaneous necrotic lesions, accumulation of reactive oxygen species, constitutive expression of SA- and ET/JA-responsive defence genes, and enhanced resistance to virulent bacterial and oomycete pathogens. Epistasis analyses of hrl1 with npr1, etr1, coi1 and SA-depleted nahG plants revealed novel interactions between SA and ET/JA signalling pathways in regulating defence gene expression and cell death. RNA gel-blot analysis of RNA isolated separately from the lesion+ and the lesion- leaves of double mutants of hrl1 revealed different signalling requirements for the expression of defence genes in these tissues. Expression of the ET/JA-responsive PDF1.2 gene was markedly reduced in hrl1 npr1 and in SA-depleted hrl1 nahG plants. In hrl1 nahG plants, expression of PDF1.2 was regulated by benzathiadiazole in a concentration-dependent manner: induced at low concentration and suppressed at high concentration. The hrl1 etr1 plants lacked systemic PR-1 expression, and exhibited compromised resistance to virulent Pseudomonas syringae and Peronospora parasitica. Inhibiting JA responses in hrl1 coi1 plants lead to exaggerated cell death and severe stunting of plants. Finally, the hrl1 mutation lead to elevated expression of AtrbohD, which encodes a major subunit of the NADPH oxidase complex. Our results indicate that defence gene expression and resistance against pathogens in hrl1 is regulated synergistically by SA and ET/JA defence pathways.
Carbon nanotube acoustic and optical sensors for volatile organic compound detection (2005)

Carbon nanotube coated acoustic and optical sensors have been successfully studied for volatile organic compound (VOC) sensing applications, at room temperature. Here, Langmuir–Blodgett (LB) films consisting of tangled bundles of single-walled carbon nanotubes (SWCNTs) have been transferred onto different transducing sensors by using a linker–buffer LB multilayered material of cadmium arachidate pre-deposited on the sensor surface to promote adhesion of SWCNTs. Two different kinds of sensors have been designed, fabricated and utilized: quartz crystal microbalance 10 MHz AT-cut quartz resonators and standard silica optical fibre sensors based on light reflectometry at a wavelength of 1310 nm. The proposed detection techniques are focused on two key parameters in gas sensing applications: mass and refractive index, and their changes induced by gas molecule absorption. The results indicate high sensitivity, good repeatability and reversibility. Signals from each sensor type have been analysed and processed by using pattern recognition techniques such as principal component analysis and use of artificial neural networks. The recognition of the hybrid system is successfully performed, improving the data fusion from acoustic and optical sensors with SWCNT-functionalized sensors that are highly discriminating. To our knowledge, this is the first reported study of combined hybrid integration of acoustic sensors with optical fibre sensors using nanostructured materials as single-walled carbon nanotubes for VOC detection, at room temperature.
Evaporation-Induced Self-Assembly of Hybrid Bridged Silsesquioxane Film and Particulate Mesophases with Integral Organic Functionality (2000)

We report an evaporation-induced self-assembly procedure to prepare poly(bridged silsesquioxane) thin-film and particulate mesophases that incorporate organic moieties (1−3) into periodic, mesostructured frameworks as molecularly dispersed bridging ligands. Capacitance−voltage measurements along with a variety of structural characterization procedures were performed to begin to elucidate structure−property relationships of this new class of surfactant-templated mesophases. We observed a consistent trend of increasing modulus and hardness and decreasing dielectric constant with substitution of the bridged silsesquioxane (⋮Si(CH2)2Si⋮) for siloxane (⋮SiOSi⋮) in the framework. This preliminary evidence suggests that the introduction of integral organic groups into the frameworks of mesoporous materials can result in synergistic properties, promising an unprecedented ability to tune properties and function.
Generation of Tumor-Specific Cytotoxic T Lymphocytes and Memory T Cells by Immunization with Tumor-Derived Heat Shock Protein gp96 (1998)

Tumor-derived heat shock proteins have been shown previously to elicit specific prophylactic immunity to cognate tumors. Here we establish that administration of gp96 results in generation of tumor-specific cytotoxic T lymphocyte response in addition to protective immunity. In one instance, gp96 preparations are shown to elicit an immune response against a tumor, where intact tumor cells are unable to do so. Finally, our results indicate that gp96 preparations elicit a memory T cell response that is capable of being recalled.