gebhart/patrepeval huggingface dataset:
CRF 1 receptor-dependent increases in irritability-like behavior during abstinence from chronic intermittent ethanol vapor exposure (2017)

Abstract Background In humans, emotional and physical signs of withdrawal from ethanol are commonly seen. Many of these symptoms, including anxiety-like and depression-like behavior, have been characterized in animal models of ethanol dependence. One issue with several current behavioral tests measuring withdrawal in animal models is they are often not repeatable within subjects over time. Additionally, irritability, one of the most common symptoms of ethanol withdrawal in humans, has not been well characterized in animal models. The corticotropinreleasing factor (CRF)-CRF 1 receptor system has been suggested to be critical for the emergence of anxiety-like behavior in ethanol dependence, but the role of this system in irritability-like behavior has not been characterized. Methods The present study compared the effects of chronic intermittent ethanol vapor exposure (CIE)-induced ethanol dependence on irritabilitylike behavior in rats using the bottle-brush test during acute withdrawal and protracted abstinence. Rats were trained to self-administer ethanol in operant chambers and then either left in a nondependent state or made dependent via CIE. Naive, nondependent, and dependent rats were tested for irritability-like behavior in the bottle-brush test 8 h and 2 weeks into abstinence from ethanol. A separate cohort of dependent rats was used to examine the effect of the specific CRF 1 receptor antagonist R121919 on irritability-like behavior. Results Dependent rats exhibited escalated ethanol intake compared with their own pre-CIE baseline and nondependent rats. At both time-points of abstinence, ethanol-dependent rats exhibited increased aggressive-like responses compared with naive and nondependent rats. R121919 blocked the increased irritability-like behavior in dependent rats. Conclusions The effect of R121919 to block increased irritability-like behavior suggests that CRF plays an important role in this behavior, similar to other negative emotional withdrawal symptoms. Quantifying and understanding the molecular basis of irritability-like behavior may yield new insights into withdrawal from ethanol and other drugs of abuse.
Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study (2016)

Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer. Dusquetide reduced the duration of OM in mouse and hamster models by approximately 50%, which was recapitulated by the 50% reduction of severe OM (SOM) in the Phase 2 trial. A reduction in the clinical rate of infection was also observed, consistent with previously reported preclinical studies. In aggregate, these results not only demonstrate the safety and efficacy of dusquetide in addressing this unmet medical need, but also provide proof of concept for the translation of dusquetide action between animal models and the human clinical setting, and further support the contention that innate immunity is an important driver for the initiation and continued impact of OM.
Faculty Opinions recommendation of Time-resolved electrochemical quantification of azanone (HNO) at low nanomolar level. (2013)

Azanone (HNO, nitroxyl) is a highly reactive and short-lived compound with intriguing and highly relevant properties. It has been proposed to be a reaction intermediate in several chemical reactions and an in vivo, endogenously produced key metabolite and/or signaling molecule. In addition, its donors have important pharmacological properties. Therefore, given its relevance and elusive nature (it reacts with itself very quickly), the development of reliable analytical methods for quantitative HNO detection is in high demand for the advancement of future research in this area. During the past few years, several methods were developed that rely on chemical reactions followed by mass spectrometry, high-performance liquid chromatography, UV–vis, or fluorescence-trapping-based methodologies. In this work, our recently developed HNO-sensing electrode, based on the covalent attachment of cobalt(II) 5,10,15,20-tetrakis[3-(p-acetylthiopropoxy)phenyl] porphyrin [Co(P)] to a gold electrode, has been thoroughly characterized in terms of sensibility, accuracy, time-resolved detection, and compatibility with complex biologically compatible media. Our results show that the Co(P) electrode: (i) allows time-resolved detection and kinetic analysis of the electrode response (the underlying HNO-producing reactions can be characterized) (ii) is able to selectively detect and reliably quantify HNO in the 1–1000 nM range, and (iii) has good biological media compatibility (including cell culture), displaying a lack of spurious signals due to the presence of O2, NO, and other reactive nitrogen and oxygen species. In summary, the Co(P) electrode is to our knowledge the best prospect for use in studies investigating HNO-related chemical and biological reactions.
Adenosine analogs inhibit the guanine‐7‐methylation of mRNA cap structures (1993)

The adenosine analogs neplanocin A and deazaneplanocin A were observed to inhibit the in vivo guanine-7-methylation of mRNA cap structure using a new assay for hypomethylated RNA. Treatment of cultured mammalian cells with these adenosine analogs resulted in the same extent of hypomethylation of cap structure as did ethionine injection in mice. Neplanocin A and its non-metabolizable analog 3-deazaneplanocin A show the same maximal level of inhibition of methylation suggesting that these adenosine analogs exert their effects by elevating S-adenosylhomocysteine levels rather than by conversion to other inhibitory compounds.
Double-monoclonal immunofluorometric assays for pregnancy-associated plasma protein A/proeosinophil major basic protein (PAPP-A/proMBP) complex in first-trimester maternal serum screening for Down syndrome (1997)

Four double-monoclonal time-resolved immunofluorometric assays (TrIFMAs) have been developed for the specific determination of pregnancy-associated plasma protein A/proeosinophil major basic protein (PAPP-A/ proMBP) complex in first-trimester maternal serum samples. The assays have a functional sensitivity of < 4 mIU/L and a working range from 4 to 1000 mIU/L. These 4 assays, together with a polyclonal sandwich TrIFMA, were compared for their ability to discriminate between normal pregnancies (n = 149) and pregnancies carrying a Down syndrome fetus (n = 36) in maternal serum screening samples from gestational weeks 4-13. In 26 Down syndrome pregnancies from gestational weeks 7-12, the median PAPP-A multiples of the median concentration in controls (MoMs) determined by monoclonal antibody combinations 234-3/234-2*, 234-4/234-2*, 234-4/234-5*, and 234-5/234-6* were 0.35, 0.37, 0.42, and 0.44, respectively, whereas the median MoM determined by the polyclonal assay was 0.56. ROC curve analysis also showed that better overall diagnostic accuracy and detection rates were achieved by the monoclonal TrIFMAs than by the polyclonal TrIFMA. This report is the first to describe assays that specifically measure PAPP-A/proMBP complex without possible interference from other proMBP-containing complexes.
III. Asymmetry in plasma membrane signal transduction: lessons from brush-border Na+/H+exchangers (1998)

Signal transduction in epithelial cells adds another level of complexity to the signaling that occurs in symmetrical cells, in the form of the need to coordinate and keep separate signals at the apical and basolateral membranes. Regulation by protein kinases of ileal NaCl absorption and its component brush-border Na+/H+ exchanger are used as an example of how signaling in epithelial cells must deal with spatial localization of signals, protein-protein interactions, signaling molecules, and the involvement of the transport protein being regulated in collecting and focusing the signals generated at the receptor and beyond.
Supplemental Data from A Bifunctional MAPK/PI3K Antagonist for Inhibition of Tumor Growth and Metastasis (2023)

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A rat brain cDNA encoding the neurotransmitter transporter with an unusual structure (1993)

A rat cDNA clone encoding the novel membrane protein of the neurotransmitter transporters family was cloned and sequenced. The cDNA was identified as a transcript of the gene NTT4 of which a partial genomic clone was previously sequenced. Alignment of the amino acid sequence of NTT4 with other members of the neurotransmitter transporter family revealed a marked deviation from the conserved structure of all other members of the family. The largest extracellular loop with a potential glycosylation site was identified between membrane segments 7 and 8. The protein retains the common glycosylated loop between transmembrane helices 3 and 4 in all members of the family. The transcript of NTT4 was found exclusively in the central nervous system and is more abundant in the cerebellum and the cerebral cortex.
Pulmonary carcinoids. Immunohistochemical demonstration of brain-gut peptides (1983)

Antisera raised against serotonin, gastrin, somatostastin, motilin, bombesin, calcitonin, secretin, glucagon, ACTH, neurotensin, and pancreatic polypeptide carboxyterminal hexapeptide were employed to immunohistochemically stain seven pulmonary carcinoids. Argentaffin and argyrophil stains were also performed on all cases. Serotonin-like immunoreactivity was present in four tumors, pancreatic polypeptide-like immunoreactivity in four tumors, bombesin-like immunoreactivity in two tumors and ACTH-like immunoreactivity in one tumor. The cells shown to contain neuroendocrine products constituted a minority cell population in all tumors except the ACTH-immunoreactive tumor. This study suggests that pulmonary carcinoids, like their abdominal counterparts, contain a variety of neuroendocrine products, and may produce more than one neuroendocrine product. Serotonin and pancreatic polypeptide-like immunoreactivity were the most prevalent neuroendocrine products demonstrable in this study.
Identification of an immunodominant type‐II collagen peptide recognized by T cells in H‐2q mice: self tolerance at the level of determinant selection (1992)

Abstract The T cell recognition of type‐II collagen (CII) in H‐2 q mice, susceptible to CII‐induced arthritis, was analyzed. With the use of T cell hybridomas derived from rat CII‐immunized mice, a peptide corresponding to amino acids 245–270 on chick CII was found to harbor a T cell epitope which is present on heterologous CII (chick, rat, human, and bovine CII) but not on autologous CII. It was shown that this epitope was located within amino acids 260–270, although flanking regions in either direction were necessary for proper recognition. A peptide corresponding to human CII (256–270) was used for further studies. A single amino acid difference at position 266 between mouse CII (aspartic acid) and heterologous CII (glutamic acid) strongly influenced recognition of this peptide. No response towards the mouse peptide was seen with any of the T cell hybridomas. Inhibition studies revealed that the mouse peptide did not bind as well to major histocompatibility complex as the corresponding heterologous peptide. Both peptides gave rise to a T cell response after immunization. However, immunization with the heterologous peptide resulted in a response strictly directed to rat CII and the immunogen while immunization with the autologous peptide elicited T cells which reacted in a heteroclitic fashion, with a stronger response to the heterologous peptide than to the autologous peptide, and did respond to rat CII but not to mouse CII. We suggest that aspartic acid in position 266 results in a cryptic determinant in mouse CII which is neither recognized after CII immunization nor capable of tolerance induction. A glutamic acid at position 266, however, gives rise to an immunodominant epitope which is recognized by a large proportion of the T cells activated after immunization with heterologous CII.
A computer-aided method for the evaluation of fusional reserves with objective control of fusion break (2010)

A method for evaluating the fusional reserves has been developed and tested. The method employs an interactive computer program permitting the checking of the subject’s report at the moment of fusion failure during an artificial increase in the convergence or divergence of the visual axes in the course of measurement. The control is based on the use of purely binocular stimuli (random-dot stereograms, RDSs) and dynamic markers, which are added to the test object (TO) in a random order during the measurement procedure and changes in the shape of the TO. The TO with a marker encoded in the stereogram is only perceived owing to binocular mechanisms, and it becomes invisible if fusion has been disturbed. Its disappearance allows the subject to determine the moment of fusion failure, and the shape of the object with the marker before this moment allows the experimenter to check the subject’s report. Statistical analysis of the results of the primary and secondary measurements of the fusional reserves of 72 subjects has confirmed that the method is sufficiently reliable.
Molecular and Biocompatibility Characterization of Red Blood Cell Membrane Targeted and Cell-Penetrating-Peptide-Modified Polymeric Nanoparticles (2017)

Red blood cells (RBCs) express a variety of immunomodulatory markers that enable the body to recognize them as self. We have shown that RBC membrane glycophorin A (GPA) receptor can mediate membrane attachment of protein therapeutics. A critical knowledge gap is whether attaching drug-encapsulated nanoparticles (NPs) to GPA and modification with cell-penetrating peptide (CPP) will impact binding, oxygenation, and the induction of cellular stress. The objective of this study was to formulate copolymer-based NPs containing model fluorescent-tagged bovine serum albumin (BSA) with GPA-specific targeting ligands such as ERY1 (ENPs), single-chain variable antibody (scFv TER-119, SNPs), and low-molecular-weight protamine-based CPP (LNPs) and to determine their biocompatibility using a variety of complementary high-throughput in vitro assays. Experiments were conducted by coincubating NPs with RBCs at body temperature, and biocompatibility was evaluated by Raman spectroscopy, hemolysis, complement lysis, and oxidative stress assays. Data suggested that LNPs effectively targeted RBCs, conferring 2-fold greater uptake in RBCs compared to ENPs and SNPs. Raman spectroscopy results indicated no adverse effect of NP attachment or internalization on the oxygenation status of RBCs. Cellular stress markers such as glutathione, malondialdehyde, and catalase were within normal limits, and complement-mediated lysis due to NPs was negligible in RBCs. Under the conditions tested, our data demonstrates that molecular targeting of the RBC membrane is a feasible translational strategy for improving drug pharmacokinetics and that the proposed high-throughput assays can prescreen diverse NPs for preclinical and clinical biocompatibility.
On the Importance of Volatile Agents Devoid of Anesthetic Action (1994)

*Department of Anesthesia, Massachusetts General Hospital and Departments of Anaesthesia, Harvard Medical School, Boston, Massachusetts †Department of Anesthesia, Massachusetts General Hospital and Departments of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts Address correspondence and reprint requests to Keith W. Miller, DPhil, Department of Anesthesia, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114. Accepted for publication July 29, 1994.
Second generation large area microchannel plate flat panel phototubes (2016)

Very large (20 cm × 20 cm) flat panel phototubes are being developed which employ novel microchannel plates (MCPs). The MCPs are manufactured using borosilicate microcapillary arrays which are functionalized by the application of resistive and secondary emissive layers using atomic layer deposition (ALD). This allows the operational parameters to be set by tailoring sequential ALD deposition processes. The borosilicate substrates are robust, including the ability to be produced in large formats (20 cm square). ALD MCPs have performance characteristics (gain, pulse amplitude distributions, and imaging) that are equivalent or better than conventional MCPs. They have low intrinsic background (0.045 events cm<sup>-2</sup> sec<sup>-1</sup>)., high open area ratios (74% for the latest generation of borosilicate substrates), and stable gain during &gt;7 C cm<sup>-2</sup> charge extraction after preconditioning (vacuum bake and burn-in). The tube assemblies use a pair of 20 cm × 20 cm ALD MCPs comprised of a borosilicate entrance window, a proximity focused bialkali photocathode, and a strip-line readout anode. The second generation design employs an all glass body with a hot indium seal and a transfer photocathode. We have achieved &gt;20% quantum efficiency and good gain uniformity over the 400 cm<sup>2</sup> field of view, spatial resolution of &lt;1 cm and obtained event timing accuracy of close to 100 ps FWHM.
Glucagon-Like Peptide-1 Protects β-Cells Against Apoptosis by Increasing the Activity of an Igf-2/Igf-1 Receptor Autocrine Loop (2009)

An IGF-2/IGF-1 receptor autocrine loop operates in beta-cells. GLP-1 increases its activity by augmenting IGF-1 receptor expression and by stimulating secretion; this mechanism is required for GLP-1-induced protection against apoptosis. These findings may lead to novel ways of preventing beta-cell loss in the pathogenesis of diabetes.
Conceptual design of a device to measure hand swelling in a micro-gravity environment (1993)

In the design of pressurized suits for use by astronauts in space, proper fit is an important consideration. One particularly difficult aspect of the suit design is the design of the gloves. If the gloves of the suit do not fit properly, the grip strength of the astronaut can be decreased by as much as fifty percent. These gloves are designed using an iterative process and can cost over 1.5 million dollars. Glove design is further complicated by the way the body behaves in a micro-gravity environment. In a micro-gravity setting, fluid from the lower body tends to move into the upper body. Some of this fluid collects in the hands and causes the hands to swell. Therefore, a pair of gloves that fit well on earth may not fit well when they are used in space. The conceptual design process for a device which can measure the swelling that occurs in the hands in a micro-gravity environment is described. This process involves developing a specifications list and function structure for the device and generating solution variants for each of the sub functions. The solution variants are then filtered, with the variants that violate any of the specifications being discarded. After acceptable solution variants are obtained, they are combined to form design concepts. These design concepts are evaluated against a set of criteria and the design concepts are ranked in order of preference. Through this process, the two most plausible design concepts were an ultrasonic imaging technique and a laser mapping technique. Both of these methods create a three dimensional model of the hand, from which the amount of swelling can be determined. In order to determine which of the two solutions will actually work best, a further analysis will need to be performed.
Optimizing Survival Predictions of Hypopharynx Cancer: Development of a Clinical Prediction Model (2019)

4 Laryngoscope, 130:2166-2172, 2020.
ChemInform Abstract: Synthesis and Reactions of Chloroazodienes: A New and General Synthesis of Pyridazines. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The color stability of silorane- and methacrylate-based resin composites (2012)

The purpose of this study were to evaluate the discoloration of a silorane-based resin and two methacrylated-based resin composites upon exposure to different staining solutions coffee, red wine, porcine liver esterase and distilled water for 7 days. The colors of all specimens before and after storage in the solutions were measured by a spectrophotometer based on CIE Lab system, and the color differences thereby calculated. Data were statistically analyzed by ANOVA and Scheffe's test. For coffee and red wine, the mean color change in silorane-based resin was significantly lower than that in methacylate-based resin composites (p<0.05). For porcine liver esterase and distilled water, there was no significant difference in the mean values of color change between silorane- and methacrylate-based resin composites (p>0.05). In conclusion, the silorane-based resin composites exhibited better color stability (less ΔE) after exposure to the colored staining solutions.
A Multiple-Input Digitally Controlled Buck Converter for Envelope Tracking Applications in Radiofrequency Power Amplifiers (2009)

Wireless communication transmitters have very low efficiencies due to the use of linear radiofrequency power amplifiers. Several techniques have been proposed over the years to improve the efficiency of these systems. One of the most promising is called the envelope tracking technique, which is based on using a fast switching mode power supply to provide a varying voltage to the power amplifier that tracks the envelope of the transmitted signal. The amplifier can, thus, operate continuously near its theoretical maximum efficiency, greatly improving the overall efficiency of the communication system. This paper proposes a multilevel digitally controlled power supply suitable for this application. It is shown to perform very well, achieving very high efficiency, high-output power capability and tracking bandwidths above 50 kHz. This paper also shows that the proposed system is able to produce a 15% overall increase in efficiency in a complete envelope tracking system.