gebhart/patrepeval huggingface dataset:
Transgenic mice carrying the dominant rhodopsin mutation P347S: Evidence for defective vectorial transport of rhodopsin to the outer segments (1996)

To explore the pathogenic mechanism of dominant mutations affecting the carboxyl terminus of rhodopsin that cause retinitis pigmentosa, we generated five lines of transgenic mice carrying the proline-347 to serine (P347S) mutation. The severity of photoreceptor degeneration correlated with the levels of transgene expression in these lines. Visual function as measured by the electroretinogram was approximately normal at an early age when there was little histologic evidence of photoreceptor degeneration, but it deteriorated as photoreceptors degenerated. Immunocytochemical staining showed the mutant rhodopsin predominantly in the outer segments prior to histologically evident degeneration, a finding supported by quantitation of signal intensities in different regions of the photoreceptor cells by confocal microscopy. A distinct histopathologic abnormality was the accumulation of submicrometer-sized vesicles extracellularly near the junction between inner and outer segments. The extracellular vesicles were bound by a single membrane that apparently contained rhodopsin as revealed by ultrastructural immunocytochemical staining with anti-rhodopsin antibodies. The outer segments, although shortened, contained well-packed discs. Proliferation of the endoplasmic reticulum as reported in Drosophila expressing dominant rhodopsin mutations was not observed. The accumulation of rhodopsinladen vesicles likely represents aberrant transport of rhodopsin from the inner segments to the nascent disc membranes of the outer segments. It is possible that photoreceptor degeneration occurs because of a failure to renew outer segments at a normal rate, thereby leading to a progressive shortening of outer segments, or because of the loss of cellular contents to the extracellular space, or because of both.
Microemulsion for Intradermal Delivery Of Cetyl Alcohol and Octyl Dimethyl PABA (1990)

A water-in-oil microemulsion was prepared to deliver cetyl alchohol [I] octyl dimethyl PABA or Padimate-O [II] in vitro using human and hairless mouse skin. A standard Franz diffusion cell and a microsectiong cryostat microtome were used to quantify the rate and the depth of penetration and the results were compared in the percent does penetrated for this microemulsion and two macroemulsion formulations, namely a cream and a lotion. It appeared that the microemulsion had the ability to deliver [I] into the skin 2-6 times faster and at least twice as much as that with the other two formulations. Furthermore, the absorption of [I] from the cream or lotion product could bel enhanced by as much as 50-250% if the skin had been pretreated with microemulsion prior to product application. The advantage of using a microemulison to acheieve deeper and faster penetratin of the permeating compunds was clearly demonstreated in this study.
The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies (2007)

Serotonin Transporter (5HTT or SLC6A4) mRNA transcription is regulated by both genetic and epigenetic mechanisms. Unfortunately, despite intense scrutiny, the exact identity and contribution of each of these regulatory mechanisms, and their relationship to behavioral illness remain unknown. This lack of knowledge is critical because alterations in SLC6A4 function are posited to be central to a wide variety of CNS disorders. In order to address this shortcoming, we quantified 5HTTLPR genotype, SLC6A4 mRNA production and CpG methylation using biomaterial from 192 lymphoblast cell lines derived from subjects who participated in the latest wave of the Iowa Adoption Studies. We then analyzed the resulting data with respect to clinical characteristics. We confirmed prior findings that the short (s) 5HTTLPR allele is associated with lower amounts of mRNA transcription, but there was no significant effect of the "Long G" allele on mRNA transcription. We also found that CpG methylation was higher (P < 0.0008) and mRNA production (P < 0.0001) was lower in females as compared to males. Those subjects with a lifetime history of Alcohol Dependence had higher levels of SLC6A4 mRNA. There was a trend for an association of increased overall methylation with lifetime history of major depression. Finally, we confirm our prior findings that the exact levels of 5HTT mRNA expression are dependent on how it is measured. We conclude that both genetic variation and epigenetic modifications contribute to the regulation of SLC6A4 function and that more in-depth studies of the molecular mechanisms controlling gene activity and the relationship of these mechanisms to behavioral illness are indicated.
PB1-F2 Influenza A Virus Protein Adopts a β-Sheet Conformation and Forms Amyloid Fibers in Membrane Environments (2010)

The influenza A virus PB1-F2 protein, encoded by an alternative reading frame in the PB1 polymerase gene, displays a high sequence polymorphism and is reported to contribute to viral pathogenesis in a sequence-specific manner. To gain insights into the functions of PB1-F2, the molecular structure of several PB1-F2 variants produced in Escherichia coli was investigated in different environments. Circular dichroism spectroscopy shows that all variants have a random coil secondary structure in aqueous solution. When incubated in trifluoroethanol polar solvent, all PB1-F2 variants adopt an alpha-helix-rich structure, whereas incubated in acetonitrile, a solvent of medium polarity mimicking the membrane environment, they display beta-sheet secondary structures. Incubated with asolectin liposomes and SDS micelles, PB1-F2 variants also acquire a beta-sheet structure. Dynamic light scattering revealed that the presence of beta-sheets is correlated with an oligomerization/aggregation of PB1-F2. Electron microscopy showed that PB1-F2 forms amorphous aggregates in acetonitrile. In contrast, at low concentrations of SDS, PB1-F2 variants exhibited various abilities to form fibers that were evidenced as amyloid fibers in a thioflavin T assay. Using a recombinant virus and its PB1-F2 knock-out mutant, we show that PB1-F2 also forms amyloid structures in infected cells. Functional membrane permeabilization assays revealed that the PB1-F2 variants can perforate membranes at nanomolar concentrations but with activities found to be sequence-dependent and not obviously correlated with their differential ability to form amyloid fibers. All of these observations suggest that PB1-F2 could be involved in physiological processes through different pathways, permeabilization of cellular membranes, and amyloid fiber formation.
Near‐infrared Raman spectroscopy for the classification of epithelial pre‐cancers and cancers (2002)

Abstract The use of near‐infrared Raman spectroscopy to interrogate epithelial tissue biochemistry and hence distinguish between normal and abnormal tissues was investigated. Six different epithelial tissues from the larynx, tonsil, oesophagus, stomach, bladder and prostate were measured. Spectral diagnostic models were constructed using multivariate statistical analysis of the spectra to classify samples of epithelial cancers and pre‐cancers. Tissues were selected for clinical significance and to include those which develop into carcinoma from squamous, transitional or columnar epithelial cells. Rigorous histopathological protocols were followed and mixed pathology tissue samples were discarded from the study. Principal component fed linear discriminant models demonstrated excellent group separation, when tested by cross‐validation. Larynx samples, with squamous epithelial tissue, were separated into three distinct groups with sensitivities ranging from 86 to 90% and specificities from 87 to 95%. Bladder specimens, containing transitional epithelial tissue, were separated into five distinct groups with sensitivities of between 78 and 98% and specificities between 96 and 99%. Oesophagus tissue can contain both squamous and columnar cell carcinomas. A three group model discriminated the columnar cell pathological groups with sensitivities of 84–97% and specificities of 93–99%, and an eight group model combining both columnar and squamous tissues in the oesophagus was able to discriminate pathologies with sensitivities of 73–100% and specificities of 92–100%. It is likely that any overlap between pathology group predictions will have been due to a combination of the difficulty in histologically distinguishing between pre‐cancerous states and the fact that there is no biochemical boundary from one pathological group to the next, i.e. there is believed to be a continuum of progression from the normal to the diseased state. Copyright © 2002 John Wiley &amp; Sons, Ltd.
Pharmacokinetics of zidovudine in cats (2004)

Cats had slower clearance of zidovudine, compared with other species. Plasma concentrations of zidovudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.07 microM [0.019 microg/mL] for wild-type FIV clinical isolate) for at least 12 hours after i.v., i.g., or p.o. administration.
Coverage in sensor networks via persistent homology (2007)

We introduce a topological approach to a problem of covering a region in Euclidean space by balls of fixed radius at unknown locations (this problem being motivated by sensor networks with minimal sensing capabilities). In particular, we give a homological criterion to rigorously guarantee that a collection of balls covers a bounded domain based on the homology of a certain simplicial pair. This pair of (Vietoris-Rips) complexes is derived from graphs representing a coarse form of distance estimation between nodes and a proximity sensor for the boundary of the domain. The methods we introduce come from persistent homology theory and are applicable to nonlocalized sensor networks with ad hoc wireless communications.
Replication and single-cycle delivery of SARS-CoV-2 replicons (2021)

Molecular virology tools are critical for basic studies of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. Experimental systems that do not rely on viruses capable of spread are needed for potential use in lower-containment settings. In this work, we use a yeast-based reverse genetics system to develop spike-deleted SARS-CoV-2 self-replicating RNAs. These noninfectious self-replicating RNAs, or replicons, can be trans-complemented with viral glycoproteins to generate replicon delivery particles for single-cycle delivery into a range of cell types. This SARS-CoV-2 replicon system represents a convenient and versatile platform for antiviral drug screening, neutralization assays, host factor validation, and viral variant characterization.
FET‐Based Biosensors for The Direct Detection of Organophosphate Neurotoxins (2004)

Abstract Recent world‐wide terrorist events associated with the threat of hazardous chemical agent proliferation, and outbreaks of chemical contamination in the food supply has demonstrated an urgent need for sensors that can directly detect the presence of dangerous chemical toxins. Such sensors must enable real‐time detection and accurate identification of different classes of pesticides (e.g., carbamates and organophosphates) but must especially discriminate between widely used organophosphate (OP) pesticides and G‐ and V‐type organophosphate chemical warfare nerve agents. Present field analytic sensors are bulky with limited specificity, require specially‐trained personnel, and, in some cases, depend upon lengthy analysis time and specialized facilities. Most bioanalytical based systems are biomimetic. These sensors utilize sensitive enzyme recognition elements that are the in‐vivo target of the neurotoxic agents which the sensor is attempting to detect. The strategy is well founded; if you want to detect cholinesterase toxins use cholinesterase receptors. However, this approach has multiple limitations. Cholinesterase receptors are sensitive to a wide range of non‐related compounds and require lengthy incubation time. Cholinesterase sensors are inherently inhibition mode and therefore require baseline testing followed by sample exposure, retest and comparison to baseline. Finally, due to the irreversible nature of enzyme‐ligand interactions, inhibition‐mode sensors cannot be reused without regeneration of enzyme activity, which in many cases is inefficient and time‐consuming. In 1996, we pioneered a new “kinetic” approach for the direct detection of OP neurotoxins based on agent hydrolysis by the enzyme organophosphate hydrolase (OPH; EC 3.1.8.2; phosphotriesterase) and further identified a novel multi‐enzyme strategy for discrimination between different classes of neurotoxins. The major advantage of this sensor strategy is it allows direct and continuous measurement of OP agents using a reversible biorecognition element. We also investigated incorporation of enzymes with variations in substrate specificity (e.g., native OPH, site‐directed mutants of OPH, and OPAA (EC 3.1.8.1), based upon preferential hydrolysis of PO, PF and PS bonds to enable discrimination among chemically diverse OP compounds. Organophosphate hydrolase enzymes were integrated with several different transduction platforms including conventional pH electrodes, fluoride ion‐sensitive electrodes, and pH‐responsive fluorescent dyes. Detection limit for most systems was in the low ppm concentration range. This article reviews our integration of organophosphate hydrolase enzymes with pH sensitive field effect transistors (FETs) for OP detection.
<title>Fuzzy logic approach to object recognition</title> (1993)

In this paper, a linguistic approach to the problem of object recognition is outlined and fuzzy logic solution is given for this formulation. The problem under investigation is divided into two sub-problems: (1) feature extraction from a digitized image, and (2) matching features extracted against a set of pre-defined objects. Using linguistic approach, solving the problem of feature extraction yields a set of linguistic descriptions of an object from a particular digitized image. These descriptions will be matched with known patterns to derive a decision on the shape of the object. The use of fuzzy logic in matching patterns has been shown to provide satisfactory results in Monte Carlo simulations, especially in the case that there is ambiguity in the pictures. This ambiguity is often caused by a lack of extracted features in matching a pattern resulted from some viewpoint at the object or from a picture of poor quality.
Architecture for a Web-based clinical information system that keeps the design open and the access closed. (1998)

We are developing the Patient Clinical Information System (PatCIS) project at Columbia-Presbyterian Medical Center to provide patients with access to health information, including their own medical records (permitting them to contribute selected aspects to the record), educational materials and automated decision support. The architecture of the system allows for multiple, independent components which make use of central services for managing security and usage logging functions. The design accommodates a variety of data entry, data display and decision support tools and provides facilities for tracking system usage and questionnaires. The user interface minimizes hypertext-related disorientation and cognitive overload; our success in this regard is the subject of on-going evaluation.
Roles of Thiol-Redox Pathways in Bacteria (2001)

Disulfide bonds in proteins play various important roles. They are either formed as structural features to stabilize the protein or are found only transiently as part of a catalytic or regulatory cycle. In vivo, the formation and reduction of disulfide bonds is catalyzed by specialized thiol-disulfide exchanging enzymes that contain an active site with the sequence motif Cys-X-X-Cys. These proteins have structurally evolved to catalyze predominantly either oxidative reactions or reductive steps. There is mounting evidence that, in addition to the thiol redox potential, the spatial distribution within different cell compartments and the overall redox state of the cell are equally important. In the cytoplasm, multiple pathways play overlapping roles in the reduction of disulfide bonds and additionally, the expression of several components of thiol-redox pathways was shown to respond to the changes in the cellular thiol-redox equilibrium. In the periplasm, two systems coexist, one catalyzing thiol oxidation and the other disulfide reduction. Recent results suggest that two different mechanisms are used to translocate reducing power from the cytoplasm or to dissipate the electrons after oxidation.
Identification of p53 as a Sequence-Specific DNA-Binding Protein (1991)

The tumor-suppressor gene p53 is altered by missense mutation in numerous human malignancies. However, the biochemical properties of p53 and the effect of mutation on these properties are unclear. A human DNA sequence was identified that binds specifically to wild-type human p53 protein in vitro. As few as 33 base pairs were sufficient to confer specific binding. Certain guanines within this 33-base pair region were critical, as methylation of these guanines or their substitution with thymine-abrogated binding. Human p53 proteins containing either of two missense mutations commonly found in human tumors were unable to bind significantly to this sequence. These data suggest that a function of p53 may be mediated by its ability to bind to specific DNA sequences in the human genome, and that this activity is altered by mutations that occur in human tumors.
Major Advances in Determining Appropriate Selection Goals (2006)

Substantial increases of 3,500 kg of milk, 130 kg of fat, and 100 kg of protein per cow per lactation have resulted from improvements in genetics, nutrition, and management during the past 20 yr. At the same time, the interval from calving to conception increased (unfavorable) by 24 d. Genetics has accounted for about 55% of gains in the yield traits and about one-third of the change in interval to conception. Genetic gains in the yield traits and productive life have accumulated to around 1.7 and 1.2 genetic standard deviations since 1980. Unfavorable genetic changes in conception interval since 1980 and somatic cell score since 1990 have accumulated to 1.0 and 0.12 genetic standard deviations. The most important advance in selection indexes has been the introduction of nonyield traits. Advances in selection indexes have gone hand in hand with advances in data collection and genetic evaluation. As new traits were recorded in dairy management databases and as genetic evaluations were developed for these traits, they were incorporated into selection indexes. Until 1994, when somatic cell score and productive life were introduced, selection indexes provided by USDA included only yield traits. In 2000, composite type indexes for udder, feet and legs, and body size were added. Daughter pregnancy rate and service sire- and daughter-calving ease were included in 2003. The lifetime merit indexes introduced in 2003 have, for the first time, resulted in theoretical selection responses in the desired direction for all traits. During this time, the percentage relative economic weights in selection indexes increased from 0 to 45% for the nonyield traits. Selection emphasis on nonyield traits should continue to increase as additional traits (e.g., calf survival, metabolic disease, and male fertility) are introduced in the future. Wide variation exists among countries in traits included in selection indexes and in relative economic weights. Molecular genetic studies have identified many chromosome regions with potentially important major genes for economic traits. Use of DNA markers for genetic improvement is currently limited by lack of precision in marker location. Discovery of major genes will be accelerated by the availability of the bovine genome sequence, comparative genome maps and genome sequences across species, and increased use of breed crosses in molecular studies. As major genes are identified, their effects will be incorporated into genetic evaluations and selection indexes.
Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use (2012)

In spontaneously breathing patients with ACF, high cIVC values (>40%) are usually associated with fluid responsiveness while low values (< 40%) do not exclude fluid responsiveness.
PCS antenna measurement (2002)

The accurate measurement of the radiation performances of an antenna small compared to the wavelength is far from trivial, as in most cases the results are disturbed by the spurious currents flowing on the connecting cables. In this contribution, we present a measurement technique which avoids this problem and gives excellent results for both gain and eficiency measurements.
A Healing Vision (1996)

novels of the young adult writer Chris Crutcher tells us about hope and love. Wve known Chris Crutcher for nearly 30 years. I knew him not only before his beard was gray; I knew him before the beard. I knew him when he weighed 160, when he enlarged beyond 200, and I saw him get back to 160 and stay there. I knew him before Running Loose (1983, New York: Greenwillow Books). I remember the night I turned the last page of that manuscript and had to call him in Berkeley and wake him up to say he'd-by God!-done it. I knew him when he was
49.4: High‐definition Top‐emitting AMOLED Display with Highly Reliable Oxide Semiconductor Field Effect Transistors (2011)

Abstract We have developed a highly efficient top‐emitting white OLED by employing a stable reflective anode structure and a p‐doped buffer layer. Furthermore, combining the white OLED with color filters, we succeeded in fabricating a prototype of a high‐definition AMOLED display having highly reliable OS‐FETs as the backplane.
Stress Analysis of a Novel MEMS Microphone Chip Using Finite Element Analysis (2005)

Residual stress produces major challenges in the fabrication of MEMS devices. This is particularly true in the development of MEMS microphones since the response of the thin sound-sensitive diaphragm is strongly affected by stress. It is important to predict the effects of fabrication stress on the microphone chip and identify the failure modes to ensure a satisfactory fabrication yield. In this study, a finite element model of the microphone chip is developed to analyze the laminated structure under different fabrication stresses. The model of the microphone chip includes the diaphragm, backplate and sacrificial oxide layers on top of the silicon substrate. Fabrication stresses are included through the use of an equivalent thermal stress. The stresses in the different layers have been estimated based on measurements performed on fabricated test structures. The estimated stresses are simulated in the finite element model. An important factor in determining the process reliability is the compressive stress of the low temperature sacrificial oxide layer (LTO). A variety of stress combinations between different layers with the low temperature oxide layer are investigated. It is found that an adequate level of tensile stress in the backplate is crucial to ensure the fabrication yield. In the designs considered here, silicon nitride in combination with a thin conductive layer is identified as a favorable material for the backplate considering its high modulus and tensile stress in ‘as deposited’ film. In addition, the presence of a LTO layer on the backside of the wafer turns out to be very helpful in reducing the deflection of the unreleased chip and the stress in the diaphragm. In the case where there is a net compressive stress in the laminate, the failure mode is identified by nonlinear analysis. This analysis provides a guideline to select robust materials and tune the fabrication process to ensure a satisfactory fabrication yield.