gebhart/patrepeval huggingface dataset:
Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in Humans (2011)

Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.
Key Compounds of the Hydropyrolysis of Glucose in Supercritical Water in the Presence of K2CO3 (2003)

Hydropyrolysis of glucose as a model compound for cellulose in hot compressed water in the presence of K2CO3 at temperatures of 400 and 500 °C and pressures of 30 and 50 MPa in the range of 1.8−16.3 min reaction time is conducted to characterize key compounds of the thermochemical conversion {phenols (phenol and cresols), furfurals [methylfurfural and (hydroxymethyl)furfural], organic acids, aldehydes}. To compare the effect of alkali salts on the pyrolysis of glucose and biomass, the experiments are conducted in the presence of K2CO3, while biomass includes usually alkali salts. Hydrothermolysis of glucose in the presence of K2CO3 increases the hydrogen yield and the amount of phenols under these conditions. The formation and the degradation pathways of phenols and the other compounds that are identified are discussed. A simplified reaction scheme for glucose decomposition is given and used to discuss the role of these compounds. The effect of varying properties of supercritical water such as density, dielectric constant, and ion product on the reaction pathways is also reported.
Migraine pathogenesis and state of pharmacological treatment options (2009)

Migraine is a largely inherited disorder of the brain characterized by a complex, but stereotypical, dysfunction of sensory processing. Often the most obvious clinical symptom is head pain, but non-headache symptoms such as photophobia, phonophobia and nausea are clearly part of the typical presentation. This review discusses the current pathophysiological concepts of migraine and migraine aura, such as a possible brainstem dysfunction and cortical spreading depression. Acute and preventive migraine treatment approaches are briefly covered with a focus on shortcomings of the currently available treatment options. A number of different receptors, such as calcitonin gene-related peptide (CGRP), TRPV1 and glutamate receptors, are currently being targeted by potential novel migraine therapeutics. The prospects of this research are exciting and are likely to improve patient care.
A precomputed polynomial representation for interactive BRDF editing with global illumination (2008)

The ability to interactively edit BRDFs in their final placement within a computer graphics scene is vital to making informed choices for material properties. We significantly extend previous work on BRDF editing for static scenes (with fixed lighting and view) by developing a precomputed polynomial representation that enables interactive BRDF editing with global illumination. Unlike previous precomputation-based rendering techniques, the image is not linear in the BRDF when considering interreflections. We introduce a framework for precomputing a multibounce tensor of polynomial coefficients that encapsulates the nonlinear nature of the task. Significant reductions in complexity are achieved by leveraging the low-frequency nature of indirect light. We use a high-quality representation for the BRDFs at the first bounce from the eye and lower-frequency (often diffuse) versions for further bounces. This approximation correctly captures the general global illumination in a scene, including color-bleeding, near-field object reflections, and even caustics. We adapt Monte Carlo path tracing for precomputing the tensor of coefficients for BRDF basis functions. At runtime, the high-dimensional tensors can be reduced to a simple dot product at each pixel for rendering. We present a number of examples of editing BRDFs in complex scenes with interactive feedback rendered with global illumination.
Low-mode conformational search elucidated: Application to C39H80 and flexible docking of 9-deazaguanine inhibitors into PNP (1999)

We previously described a new conformational search method, termed low-mode search (LMOD), and discussed its utility for conformational searches performed on cycloalkanes and a cyclic penta-peptide.1 In this report, we discuss a rigorous implementation of mode following (c-LMOD) for conformational searching, and we demonstrate that for a conformational search involving cycloheptadecane, this rigorous implementation is capable of finding all of the previously known structures. To the best of our knowledge, this is the first computational proof that mode following can be used for conformational searches conducted on a complex molecular system. We show, however, that, as expected, it is generally inefficient to perform a conformational search in this manner. Nonetheless, c-LMOD has been shown to be an excellent method for conducting conformational analyses involving conformational interconversions, where the location of saddle points is important. We also describe refinement to our original LMOD procedure (l-LMOD) and discuss its utility for a difficult conformational search problem, namely locating the global minimum energy conformation of C39H80. For this search, l-LMOD combined with limited torsional Monte Carlo movement was able to locate the lowest energy structures yet reported, and significantly outperformed a pure torsional Monte Carlo and a genetic algorithm-based search. Furthermore, we also demonstrate the utility of l-LMOD combined with random translation/rotation of a ligand for the extremely difficult problem of docking flexible ligands into flexible protein binding sites on a system that includes 9-deaza-guanine-based inhibitors docked into the flexible biding site of PNP. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1671–1684, 1999
Particles for Multiplexed Analysis in Solution:  Detection and Identification of Striped Metallic Particles Using Optical Microscopy (2002)

In this report, we present data demonstrating that cylindrical metallic particles, with various submicrometer striping patterns, may be readily distinguished in an optical microscope. Accurate particle identification is discussed relative to synthesis reproducibility and the limitations of optical microscopes. Results from a library of these particles, of which over 100 different striping patterns have been produced, are presented. For these particles, made with Au and Ag stripes, more than 70 patterns may be identified with greater than 90% accuracy. The ability to chemically modify the surface of these particles, making them useful for bioanalytical measurements, is also demonstrated. Finally, we discuss improvements in our manufacturing and identification processes that will lead to both larger numbers of striping patterns and improved identification accuracy.
Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin–Pinoline Hybrids (2015)

6-Methoxy-1,2,3,4-tetrahydro-β-carboline (pinoline) and N-acetyl-5-methoxytryptamine (melatonin) are both structurally related to 5-hydroxytryptamine (serotonin). Here we describe the design, synthesis, and characterization of a series of melatonin rigid analogues resulting from the hybridization of both pinoline and melatonin structures. The pharmacological evaluation of melatonin-pinoline hybrids comprises serotonergic and melatonergic receptors, metabolic enzymes (monoamine oxidases), antioxidant potential, the in vitro blood-brain barrier permeability, and neurogenic studies. Pinoline at trace concentrations and 2-acetyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline (2) were able to stimulate early neurogenesis and neuronal maturation in an in vitro model of neural stem cells isolated from the adult rat subventricular zone. Such effects are presumably mediated via serotonergic and melatonergic stimulation, respectively.
Calcific Uremic Arteriolopathy: Pathophysiology, Reactive Oxygen Species and Therapeutic Approaches (2010)

Calcific uremic arteriolopathy (CUA)/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone, and hyperphosphatemia with consequent increases in the calcium x phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species - oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFkappaB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.
Synthesis and Pharmacoclogical Activity of a Pyrido[3',4':5,4]pyrrolo[1,2-c][1,4]benzodiazepine-3,10-dione, a New Benzodiazepine-b-carboline Type Hybrid Molecule (1989)

Diethyl 2.3-dihydro-6-azaindoline-2.5-dicarboxylate 9 was synthesized and used as starting material in the preparation of a novel benzodiazepine-p-carboline type hybrid molecule (3aR,S)-ethyl 3.10dioxo-2,3,3a,4-tetrahydr~-1OH-pyrido[3',4':5,4lpyrrolo[l,2-cl11,41b e n z o d i a z e p i n e -6 -c a h y l a t e z.The benzodiazepine receptor binding affinities of this compound and its precursors were found to be very modest & D. These results confirm our previously proposed model of the configuration of the benzodiazepine and 8-carboline binding sites on the receptor as represented by the configuration of these two moieties in the high affinity hybrid 1.This paper is dedicated to Professor Sir Derek Barton on the occasion of his 70th birthday.The benzodiazepine receptor of the m a l i a n central nervous system is known to mediate the anticonvulsant, anxiolytic and sedative properties of 1,4-ben~odiaze~ines (e.g.flunitrazeparn, la, Scheme 1 ) . -This receptor also binds compounds of the 3-cerboxy-0-carboline class (e.g.ethyl 0-carboline-3carboxylata or 0-CCE. 2 ) with high affinity.2Based on the hypothesis that 1.4-benzodiaeepines and 3-carboxy-0-carboline.occupy separate but adjacent (or partly overlapping) sites on the receptor protein, we have recently described the synthesis and high binding affinity of a hybrid molecule 2 which combines structural features of both and 2 in a single m~lecule.~This hybrid may thus presumably occupy simultaneously both types of sites on the receptor.In this paper, we present the synthesis and receptor affinity of another type of hybrid molecule in which the 1.4-beneodiazepinedione moiety (B) is this time fused to the 1.2 positions of 5-ethoxycarbonyl-6-amindoline (9).The latter constitutes the reduced form of the 6-azaindole h, the essential phamacophore of active 0-carbalines of type 2.The preparation of dicarboxylic 6-azaindolen of type 4 has not previously been described.Prydman et al.4 were able to synthesize 2-ethoxycarbonyl-5-rnethoxy-6-azaindole by condensation of diethyl oxalata with 2-methaxy-4-methyl-5-nitropyridine followed by reductive cyclizetion of the resulting pyruvatr.This methodology was adapted for the synthesis of starting from 2,4-lutidins @, Scheme 2 ) .
The Voltage-dependent Anion Channel Is the Target for a New Class of Inhibitors of the Mitochondrial Permeability Transition Pore (2003)

The relevance of the mitochondrial permeability transition pore (PTP) in Ca2+ homeostasis and cell death has gained wide attention. Yet, despite detailed functional characterization, the structure of this channel remains elusive. Here we report on a new class of inhibitors of the PTP and on the identification of their molecular target. The most potent among the compounds prepared, Ro 68-3400, inhibited PTP with a potency comparable to that of cyclosporin A. Since Ro 68-3400 has a reactive moiety capable of covalent modification of proteins, [3H]Ro 68-3400 was used as an affinity label for the identification of its protein target. In intact mitochondria isolated from rodent brain and liver and in SH-SY5Y human neuroblastoma cells, [3H]Ro 68-3400 predominantly labeled a protein of approximately 32 kDa. This protein was identified as the isoform 1 of the voltage-dependent anion channel (VDAC). Both functional and affinity labeling experiments indicated that VDAC might correspond to the site for the PTP inhibitor ubiquinone0, whereas other known PTP modulators acted at distinct sites. While Ro 68-3400 represents a new useful tool for the study of the structure and function of VDAC and the PTP, the results obtained provide direct evidence that VDAC1 is a component of this mitochondrial pore.
Species‐specific variation in signal peptide design Implications for protein secretion in foreign hosts (1989)

Secretory signal peptides from individual prokaryotic and eukaryotic species have been analyzed, and the lengths and amino acid compositions of the positively charged amino-terminal region, the central hydrophobic region, and the carboxy-terminal cleavage-region have been compared. We find distinct differences between species in all three regions. Implications for protein secretion in foreign hosts are discussed.
Characterization of a Key Neutralizing Epitope on Pertussis Toxin Recognized by Monoclonal Antibody 1B7 (2009)

Despite more than five decades of research and vaccination, infection by Bordetella pertussis remains a serious disease with no specific treatments or validated correlates of protective immunity. Of the numerous monoclonal antibodies binding pertussis toxin (PTx) that have been produced and characterized, murine IgG2a monoclonal antibody 1B7 is uniquely neutralizing in all in vitro assays and in vivo murine models of infection. 1B7 binds an epitope on the enzymatically active S1 subunit of PTx (PTx-S1) with some linear elements, but previous work with S1 scanning peptides, phage-displayed peptide libraries, and S1 truncation/deletion variants was unable to more precisely define the epitope. Using computational docking algorithms, alanine scanning mutagenesis, and surface plasmon resonance, we characterize the epitope bound by 1B7 on PTx-S1 in molecular detail and define energetically important interactions between residues at the interface. Six residues on PTx-S1 and six residues on 1B7 were identified that, when altered to alanine, resulted in variants with significantly reduced affinity for the native partner. Using this information, a model of the 1B7-S1 interaction was developed, indicating a predominantly conformational epitope located on the base of S1 near S4. The location of this epitope is consistent with previous data and is shown to be conserved across several naturally occurring strain variants, including PTx-S1A, -B (Tohama-I), -D, and -E (18-323) in addition to the catalytically inactive 9K/129G variant. This highly neutralizing but poorly immunogenic epitope may represent an important target for next-generation vaccine development, identification of immune correlates, and passive immunization strategies for pertussis.
Combatting bacterial infections by killing persister cells with mitomycin C (2015)

Persister cells are a multi-drug tolerant subpopulation of bacteria that contribute to chronic and recalcitrant clinical infections such as cystic fibrosis and tuberculosis. Persisters are metabolically dormant, so they are highly tolerant to all traditional antibiotics which are mainly effective against actively growing cells. Here, we show that the FDA-approved anti-cancer drug mitomycin C (MMC) eradicates persister cells through a growth-independent mechanism. MMC is passively transported and bioreductively activated, leading to spontaneous cross-linking of DNA, which we verify in both active and dormant cells. We find MMC effectively eradicates cells grown in numerous different growth states (e.g. planktonic cultures and highly robust biofilm cultures) in both rich and minimal media. Additionally, MMC is a potent bactericide for a broad range of bacterial persisters, including commensal Escherichia coli K-12 as well as pathogenic species of E. coli, Staphylococcus aureus and Pseudomonas aeruginosa. We also demonstrate the efficacy of MMC in an animal model and a wound model, substantiating the clinical applicability of MMC against bacterial infections. Therefore, MMC is the first broad-spectrum compound capable of eliminating persister cells, meriting investigation as a new approach for the treatment of recalcitrant infections.
Comparison of Defects Created by Plasma-Based Ion Implantation and Conventional Implantation of Hydrogen in Germanium (2007)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Allele-specific Expression of the Murine Ren-1 Genes (1989)

Inbred strains of mice carry either one of two alleles for the Ren-1 gene on chromosome 1; Ren-1c or Ren-1d. The Ren-1d allele is found in association with a tightly linked duplicated locus, Ren-2. The relative accumulations of renin transcripts derived from each locus were found to differ between mice with one or two renin loci in three extra renal tissues, the adrenal gland, testis, and sex accessory gland tissue. We find that the two Ren-1 alleles exhibit characteristic expression patterns in these tissues. Using genetic analyses and an allele-specific dideoxynucleotide primer extension assay we have further characterized the expression differences in these tissues. The results suggest that the allele-specific expression patterns observed for the Ren-1 genes are regulated by closely associated sequences in cis.
Metal-Free Alternating Copolymerization of CO2 with Epoxides: Fulfilling “Green” Synthesis and Activity (2016)

Polycarbonates were successfully synthesized for the first time through the anionic copolymerization of epoxides with CO2, under metal-free conditions. Using an approach based on the activation of epoxides by Lewis acids and of CO2 by appropriate cations, well-defined alternating copolymers made of CO2 and propylene oxide (PO) or cyclohexene oxide (CHO) were indeed obtained. Triethyl borane was the Lewis acid chosen to activate the epoxides, and onium halides or onium alkoxides involving either ammonium, phosphonium, or phosphazenium cations were selected to initiate the copolymerization. In the case of PO, the carbonate content of the poly(propylene carbonate) formed was in the range of 92-99% and turnover numbers (TON) were close to 500; in the case of CHO perfectly alternating poly(cyclohexene carbonate) were obtained and TON values were close to 4000. The advantages of such a copolymerization system are manifold: (i) no need for multistep catalyst/ligand synthesis as in previous works; (ii) no transition metal involved in the copolymer synthesis and therefore no coloration of the samples isolated; and (iii) no necessity for postsynthesis purification.
The Relationship between Standard Automated Perimetry and GDx VCC Measurements (2004)

GDx VCC measurements of the peripapillary RNFL relate well with functional loss in glaucoma. Based on the observed relationships between function and structure, patients with mild to moderate visual field loss in glaucoma may be better monitored with the GDx VCC and patients who have severe loss, with SAP.
Severe combined immunodeficiency (SCID) in the mouse. Pathology, reconstitution, neoplasms. (1985)

Histologic findings in mice with severe combined immunodeficiency (SCID) were remarkably uniform, consisting of lymphopenia, a rudimentary thymic medulla without cortex, relatively empty splenic follicles and lymph nodes, and undeveloped bronchial and gastrointestinal lymphocytic foci. Fluorescence-activated cell sorter studies revealed a few T cells (apparently nonfunctional) in thymus and spleen; interestingly, these cells seemed highly disposed to neoplasia, because thymic T-cell lymphomas were observed in 41 of 269 mice. No pre-B or B cells could be identified. Cells of the myeloid lineage appeared normal. Reconstitution of lymphoid tissues was achieved after intravenous injection of histocompatible bone marrow cells.
A novel approach to robust speech endpoint detection in car environments (2002)

In the process of speech recognition, it is especially crucial to precisely locate endpoints of the input utterance to be free of non-speech regions. This paper proposes a novel approach that finds robust features for endpoint detection in a noisy in-car environment. In the proposed method, we integrate both the widely used energy and entropy to form a new feature that possesses advantages of each individual while compensating for the drawback of each other. By monitoring the transition of the extracted new features, more precise endpoints could be found. Experiments in a real noisy environment, inside a Honda Civic car with background radio music and free chat, reveal an accuracy improvement which reached over 10% higher compared with a pure energy-based algorithm.