gebhart/patrepeval huggingface dataset:
Hidden Hearing Loss: A Disorder with Multiple Etiologies and Mechanisms (2019)

Hidden hearing loss (HHL), a recently described auditory disorder, has been proposed to affect auditory neural processing and hearing acuity in subjects with normal audiometric thresholds, particularly in noisy environments. In contrast to central auditory processing disorders, HHL is caused by defects in the cochlea, the peripheral auditory organ. Noise exposure, aging, ototoxic drugs, and peripheral neuropathies are some of the known risk factors for HHL. Our knowledge of the causes and mechanisms of HHL are based primarily on animal models. However, recent clinical studies have also shed light on the etiology and prevalence of this cochlear disorder and how it may affect auditory perception in humans. Here, we review the current knowledge regarding the causes and cellular mechanisms of HHL, summarize information on available noninvasive tests for differential diagnosis, and discuss potential therapeutic approaches for treatment of HHL.
Crystallization Kinetics of Barium and Strontium Aluminosilicate Glasses of Feldspar Composition (1994)

Crystallization kinetics of BaO.Al2O3.2SiO2 (BAS) and SrO.Al2O3.2SiO2 (SAS) glasses in bulk and powder forms have been studied by non-isothermal differential scanning calorimetry (DSC). The crystal growth activation energies were evaluated to be 473 and 451 kJ/mol for bulk samples and 560 and 534 kJ/mol for powder specimens in BAS and SAS glasses, respectively. Development of crystalline phases on thermal treatments of glasses at various temperatures has been followed by powder x-ray diffraction. Powder samples crystallized at lower temperatures than the bulk and the crystallization temperature was lower for SAS glass than BAS. Crystallization in both glasses appeared to be surface nucleated. The high temperature phase hexacelsian, MAl2Si2O8 (M = Ba or Sr), crystallized first by nucleating preferentially on the glass surface. Also, monoclinic celsian does not nucleate directly in the glass, but is formed at higher temperatures from the transformation of the metastable hexagonal phase. In SAS the transformation to monoclinic celsian occurred rapidly after 1 h at 1100 C. In contrast, in BAS this transformation is sluggish and difficult and did not go to completion even after 10 h heat treatment at 1400 C. The crystal growth morphologies in the glasses have been observed by optical microscopy. Some of the physical properties of the two glasses are also reported.
Organization of Two Cortico–Basal Ganglia Loop Circuits That Arise from Distinct Sectors of the Monkey Dorsal Premotor Cortex (2013)

© 2012 Takada et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Organization of Two Cortico–Basal Ganglia Loop Circuits That Arise from Distinct Sectors of the Monkey Dorsal Premotor Cortex
A 2-D Convolver Architecture For Real-Time Image Processing (1989)

This paper presents a novel architecture for two VLSI ICs, an 8-bit and 12-bit version, which execute real-time 3x3 kernel image convolutions at rates exceeding 10 ms per 512x512 pixel frame (at a 30 MHz external clock rate). The ICs are capable of performing &quot;on-the-fly&quot; convolutions of images without any need for external input image buffers. Both symmetric and asymmetric coefficient kernels are supported, with coefficient precision up to 12 bits. Nine on-chip multiplier-accumulators maintain double-precision accuracy for maximum precision of the results and minimum roundoff noise. In addition, an on-chip ALU can be switched into the pixel datapath to perform simultaneous pixel-point operations on the incoming data. Thus, operations such as thresholding, inversion, shifts, and double frame arithmetic can be performed on the pixels with no extra speed penalty. Flexible internal datapaths of the processors provide easy means for cascadability of several devices if larger image arrays need to be processed. Moreover, larger convolution kernels, such as 6x6, can easily be supported with no speed penalty by employing two or more convolvers. On-chip delay buffers can be programmed to any desired raster line width up to 1024 pixels. The delay buffers may also be bypassed when direct &quot;Sum-Of-Products&quot; operation of the multipliers is required; such as when external frame buffer address sequencing is desired. These features make the convolvers suitable for applications such as affine and bilinear interpolation, one-dimensional convolution (FIR filtration), and matrix operations. Several examples of applications illustrating stand-alone and cascade mode operation of the ICs will be discussed.
Role of the iron transporter OsNRAMP1 in cadmium uptake and accumulation in rice (2011)

The heavy metal cadmium (Cd) is toxic to humans, and its accumulation in rice grains is a major agricultural problem. Rice has seven putative metal transporter NRAMP genes, but microarray analysis showed that only OsNRAMP1 is highly up-regulated by iron (Fe) deficiency. OsNRAMP1 localized to the plasma membrane and transported Cd as well as Fe. OsNRAMP1 expression was observed mainly in roots and was higher in the roots of a high-Cd-accumulating cultivar (Habataki) than in those of a low-Cd-accumulating cultivar (Sasanishiki). The amino acid sequence of OsNRAMP1 in the Sasanishiki and Habataki cultivars was found to be 100% identical. These results suggest that OsNRAMP1 participates in cellular Cd uptake and that the differences observed in Cd accumulation among cultivars are because of differences in OsNRAMP1 expression levels in roots.
Minimization of fixed pattern noise in photon event counting imaging (2002)

Low light-level ultraviolet and optical imaging with a photon counting image intensifier coupled to a charge coupled device camera generally results in varying levels of fixed pattern noise in the image. Here, we demonstrate that this can be minimized by the appropriate choice of photon event centroiding algorithm. We compare the fixed pattern noise generated by a center of gravity centroiding algorithm, a Gaussian centroiding algorithm, and a hybrid centroiding algorithm which uses center of gravity centroiding when one wing is zero, and Gaussian centroiding otherwise. This approach yields the best image quality with a lower fixed pattern noise parameter (9.99%) than the sole use of Gaussian centroiding (16.4%), and there is no need for a look-up table correction. In addition, the hybrid algorithm also yields maximum detective quantum efficiency by overcoming small pulse centroiding failure associated with Gaussian centroiding. The digitization error when recording the events is modeled with a Monte Carlo simulation and discussed. It is found that a center of gravity algorithm produces not only significant fixed pattern noise, but also pulse height dependent x̄ positions. For a Gaussian centroiding algorithm the x̄ positions are independent of the pulse height, the fixed pattern noise is low and the digitization error only yields a small increase of the fixed pattern noise parameter. This shows that while there is a limit to centroiding accuracy due to the digitization error, the appropriate choice of centroiding algorithm is a much more important factor to minimize fixed pattern noise.
Novel Mechanisms of Antiprogestin Action (1996)

Endocrine therapy used either prophylactically or therapeutically for the treatment of locally advanced or metastatic breast cancers offers many advantages to patients whose tumors contain functional estrogen (ER) and progesterone (PR) receptors. The range of treatments defined as endocrine include surgical ablation of endocrine glands, administration of pharmacologic doses of steroid hormones, chemical blockade of steroid hormone biosynthesis, and inhibition of endogenous steroid hormone action at the tumor with synthetic antagonists. The last of these approaches is the most widely used, making the antiestrogen tamoxifen the preferred first-line therapeutic agent for treatment of hormone-dependent metastatic breast cancer. The wide-spread use of tamoxifen reflects its efficacy and low toxicity, and the fact that it makes good physiological sense to block the local proliferative effects of estrogens directly at the breast. But are estrogens the only hormones with a proliferative impact on the breast and on breast cancers? This chapter focuses on evidence that progesterone also has proliferative actions in the breast; on preliminary data showing that progesterone antagonists may be new tools for the management of metastatic breast cancer; and on recent data suggesting that antiprogestin-occupied PR have novel mechanisms of action that bear on tissue specificity and development of hormone resistance.
Discovery of MK-6169, a Potent Pan-Genotype Hepatitis C Virus NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Substitutions (2018)

We describe the discovery of MK-6169, a potent and pan-genotype hepatitis C virus NS5A inhibitor with optimized activity against common resistance-associated substitutions. SAR studies around the combination of changes to both the valine and aminal carbon region of elbasvir led to the discovery of a series of compounds with substantially improved potency against common resistance-associated substitutions in the major genotypes, as well as good pharmacokinetics in both rat and dog. Through further optimization of key leads from this effort, MK-6169 (21) was discovered as a preclinical candidate for further development.
Rhenium and Technetium Complexes with TridentateN-[(N′′,N′′-Dialkylamino)(thiocarbonyl)]-N′-substituted Benzamidine Ligands (2008)

N-[(Dialkylamino)(thiocarbonyl)]benzimidoyl chlorides react with functionalized amines such as 2-aminophenol, 2-methylaminopyridine, and 2-aminobenzoic acid in clean and high-yield procedures with the formation of the novel tridentate N-[(N'', N''-dialkylamino)(thiocarbonyl)]- N'-substituted benzamidine ligands H2L1, HL2, and H2L3. By starting from (NBu4)[MOCl4] (M = Re, Tc) or [ReOCl3(PPh3)2] and H2L1, a series of oxorhenium(V) and oxotechnetium(V) complexes of the composition [MOCl(L1)] were synthesized and characterized by spectroscopic methods and X-ray crystallography. The monomeric, five-coordinate compounds are air-stable and bind (L1)(2-) tridentate in the equatorial coordination sphere. Dimeric products of the compositions [(ReOCl(L2))2O] and [ReOCl(L3)]2 were isolated during reactions with HL2 and H2L3. While dimerization in [(ReOCl(L2))2O] is established via an oxo bridge, the metal atoms in [ReOCl(L3)]2 are connected by the carboxylic group of the ligand, and the product represents the first example of a high-oxidation state rhenium complex displaying such a bonding feature.
beta-globin YAC transgenes exhibit uniform expression levels but position effect variegation in mice (2000)

Expression of a construct integrated at different genomic locations often varies because of position effects that have been subcategorized as stable (decreased level of expression) and variegating (decreased proportion of expressing cells). It is well established that locus control regions (LCRs) generally overcome position effects in transgenes. However, whether stable and variegated position effects are equally overcome by an intact LCR has not been determined. We report that single-copy yeast artificial chromosome transgenes containing an unmodified human beta -globin locus were not subject to detectable stable position effects but did undergo mild to severe variegating position effects at three of the four non-centromeric integration sites tested. We also find that, at a given integration site, the distance and the orientation of the LCR relative to the regulated gene contributes to the likelihood of variegating position effects, and can affect the magnitude of its transcriptional enhancement. DNase I hypersensitive site (HSS) formation varies with the proportion of expressing cells, not the level of gene expression, suggesting that silencing of the transgene is associated with a lack of HSS formation in the LCR region. We conclude that transcriptional enhancement and variegating position effects are caused by fundamentally different but inter-dependent mechanisms.
Placement and Routing Methods Based on Mixed Wiring of JTLs and PTLs for RSFQ circuits (2019)

We propose placement and routing methods integrated in automated layout design flow for rapid single-flux-quantum (RSFQ) circuits. In order to realize small circuit area and low latency, both Josephson transmission lines (JTLs) and passive transmission lines (PTLs) are used for interconnects. Placement and routing are performed considering proper use of JTLs and PTLs. The placement problem is divided into subproblems in order to reduce the computational cost. The placement method is composed of three steps, i.e., (i) Cell clustering, (ii) Cell placement and JTL routing in each cluster, and (iii) Cluster placement. Routing among clusters are performed using PTLs. We applied the proposed design flow to sample circuits with several hundreds of gates. Though the circuit area is not fully optimized, the latency of the circuits designed with the proposed methods are smaller than those of the circuits designed manually.
Asprosin Neutralizing Antibodies as a Treatment for Metabolic Syndrome (2020)

Abstract Recently, we discovered a new glucogenic and centrally-acting orexigenic hormone – asprosin. Asprosin is elevated in metabolic syndrome (MS) patients, and importantly, its genetic loss results in reduced appetite, leanness and robust insulin sensitivity, leading to protection from MS. Here we demonstrate that anti-asprosin monoclonal antibodies (mAbs) are a dual-effect pharmacologic therapy that targets the two key pillars of MS – over-nutrition and the blood glucose burden. Anti-asprosin mAbs from three distinct species lowered appetite and body weight, and improved blood glucose in a dose-dependent and epitope-agnostic fashion in three independent MS mouse models, with an IC 50 of ∼1.5 mg/kg. In addition, mAb treatment ameliorated MS associated dyslipidemia and hepatic dysfunction. The mAbs displayed half-life of over 3 days in vivo, with equilibrium dissociation-constants in picomolar to low nanomolar range. This evidence paves the way for further development towards an investigational new drug application and subsequent human trials for treatment of MS, a defining physical ailment of our time.
A Photoactive Polymer with Azobenzene Chromophore in the Side Chains (2007)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTA Photoactive Polymer with Azobenzene Chromophore in the Side ChainsLiming Ding and Thomas P. RussellView Author Information Department of Polymer Science & Engineering, University of Massachusetts, Amherst, Massachusetts 01003 Cite this: Macromolecules 2007, 40, 6, 2267–2270Publication Date (Web):February 13, 2007Publication History Received17 November 2006Revised13 December 2006Published online13 February 2007Published inissue 1 March 2007https://pubs.acs.org/doi/10.1021/ma062653rhttps://doi.org/10.1021/ma062653rbrief-reportACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views1245Altmetric-Citations43LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Azobenzene,Irradiation,Monomers,Photoisomerization,Quantum mechanics Get e-Alerts
Accounting for Solvent in Structure-Based Drug Design (2011)

Water plays a crucial role in the mediation of protein-ligand interactions, as underscored by the fact that most X-ray crystal structures (of sufficient resolution) of protein-ligand complexes possess water molecules at the protein-ligand interface. In this chapter, the accuracy and reliability of ordered waters observed in crystal structures is discussed. Additionally, the thermodynamic aspects of the inclusion of water in ligand binding to proteins is described, with the goal of providing practical guidelines for dealing with ordered water molecules during structure-guided lead optimization.
Somatosensory tinnitus: Current evidence and future perspectives (2017)

In some individuals, tinnitus can be modulated by specific maneuvers of the temporomandibular joint, head and neck, eyes, and limbs. Neuroplasticity seems to play a central role in this capacity for modulation, suggesting that abnormal interactions between the sensory modalities, sensorimotor systems, and neurocognitive and neuroemotional networks may contribute to the development of somatosensory tinnitus. Current evidence supports a link between somatic disorders and higher modulation of tinnitus, especially in patients with a normal hearing threshold. Patients with tinnitus who have somatic disorders seems to have a higher chance of modulating their tinnitus with somatic maneuvers; consistent improvements in tinnitus symptoms have been observed in patients with temporomandibular joint disease following targeted therapy for temporomandibular disorders. Somatosensory tinnitus is often overlooked by otolaryngologists and not fully investigated during the diagnostic process. Somatic disorders, when identified and treated, can be a valid therapeutic target for tinnitus; however, somatic screening of subjects for somatosensory tinnitus is imperative for correct selection of patients who would benefit from a multidisciplinary somatic approach.
Nematicidal Activity of Cyclotides: Toxicity Against Caenorhabditis elegans (2023)

Cyclotides are a unique family of stable and cyclic mini-proteins found in plants that have nematicidal and anthelmintic activities. They are distributed across the Rubiaceae, Violaceae, Fabaceae, Cucurbitaceae, and Solanaceae plant families, where they are posited to act as protective agents against pests. In this study, we tested the nematicidal properties of extracts from four major cyclotide-producing plants, <i>Oldenlandia affinis</i>, <i>Clitoria ternatea</i>, <i>Viola odorata</i>, and <i>Hybanthus enneaspermus</i>, against the free-living model nematode <i>Caenorhabditis elegans</i>. We evaluated the nematicidal activity of the cyclotides kalata B1, cycloviolacin O2, and hyen D present in these extracts and found them to be active against the larvae of <i>C. elegans</i>. Both the plant extracts and isolated cyclotides exerted dose-dependent toxicity on the first-stage larvae of <i>C. elegans</i>. Isolated cyclotides caused death or damage upon interacting with the worms' mouth, pharynx, and midgut or membrane. Cycloviolacin O2 and hyen D produced bubble-like structures around the <i>C. elegans</i> membrane, termed blebs, implicating membrane disruption causing toxicity and death. All tested cyclotides lost their toxicity when the hydrophobic patches present on them were disrupted via a single-point mutation. The present results provide a facile assay design to measure and explore the nematicidal activities of plant extracts and purified cyclotides on <i>C. elegans</i>.
RNA LEVER Mediates Long-Range Regulation of ε-globin by Keeping PRC2 in Check (2020)

Summary Polycomb Repressive Complex 2 (PRC2) is an epigenetic regulator required for gene silencing during embryonic development. Previous studies have reported that PRC2 interacts with RNA in a promiscuous manner, but the biological functions of such interaction are unknown. Here we present a seesaw mechanism for the regu l ation of ε-globin through inacti v ating E ZH2 by an upstream non-coding R NA (LEVER). We show that LEVER, a non-coding RNA identified by RNA immunoprecipitation sequencing (RIP-seq) of the PRC2 core subunit EZH2 and Nanopore sequencing, binds PRC2 and thereby prevents the accumulation of H3K27 methylation along the genomic region where LEVER RNA is transcribed. The open chromatin within the LEVER locus in turn competes for the chromatin interaction between the ε-globin promoter and the Locus Control Region (LCR), working as a negative regulatory element of ε-globin expression. Hence, LEVER RNA negatively regulates ε-globin by sequestering PRC2 from repressing the LEVER locus, which is a competitor of the ε-globin-LCR interaction.
Synthesis and Reactivity of N‐tert‐Butanesulfinyl Glycosylamines (2015)

Abstract A study of the preparation and of the reactivity of N ‐ tert ‐butanesulfinyl glycosylamines is reported for the first time. As they react readily as latent imine equivalents with a variety of carbon nucleophiles, these new carbohydrate derivatives constitute very useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar‐ C ‐glycosides.
The role of sugar, vitrification and membrane phase transition in seed desiccation tolerance (1994)

In a search for the mechanism of desiccation tolerance, a comparison was made between orthodox (desiccation‐tolerant) soybean ( Glycine max [L.] Merrill) and recalcitrant (desiccation‐intolerant) red oak ( Quercus rubra L.) seeds. During the maturation of soybean seeds, desiccation tolerance of seed axes is correlated with increases in sucrose, raffinose and stachyose. In cotyledons of mature oak seeds, sucrose levels are equal to those in mature soybeans, but oligosaccharides are absent. By using the thermally stimulated current method, we observed the glassy state in dry soybean seeds during maturation. Oak cotyledons showed the same phase diagram for the glass transition as did mature soybeans. By using X‐ray diffraction, we found the maturation of soybeans to be associated with an increased ability of membranes to retain the liquid crystalline phase upon drying, whereas the mature oak cotyledonary tissue existed in the gel phase under similar dry conditions. These findings lead to the conclusion that the glassy state is not sufficient for desiccation tolerance, whereas the ability of membranes to retain the liquid crystalline phase does correlate with desiccation tolerance. An important role for soluble sugars in desiccation tolerance is confirmed, as well as their relevance to membrane phase changes. However, the presence of soluble sugars does not adequately explain the nature of desiccation tolerance in these seeds.
Unusual base-induced transformations of 2′,6′-dihydroxyacetophenone oxime (1973)

P. Crabbé, A. Villarino and J. M. Muchowski, J. Chem. Soc., Perkin Trans. 1, 1973, 2220 DOI: 10.1039/P19730002220