gebhart/patrepeval huggingface dataset:
The efficiency of the cytoarchitecture of the organ of Corti for active cochlear amplification (2016)

A “Y”-shaped structure of cells formed by the basally tilted force generating outer hair cells (OHC) and apically tilted passive phalangeal process (PhP) connected to a Deiter cell (DC) has been hypothesized to be an essential organ of Corti (OoC) building block for cochlear amplification (Yoon et al., 2011). We developed a COMSOL finite-element model of the mouse cochlea, taking into account the spatial arrangement of Y-shaped elements and the 3-D fluid-structure interaction. The model was validated by comparison with previously reported basilar membranę (BM) displacement for both passive and active cases (Lee et al., 2015). The baseline model can reproduce an increase of 40 dB gain of the BM (re stapes velocity) for low level sounds. However, the absence of the PhP results in an unstable response of the BM for active cases. The model with the roles of the PhP and OHC switched, could not reproduce the active gain. Finally, the model with reversed titling orientation of OHC and PhP cells generated significantly lower gains (specially for lower frequencies), but also results in broader resonance peaks. These results demonstrate the efficiency of the natural cytoarchitecture of the OoC. [Work supported by NIH grant R01 DC 07910.]
Successful autologous cord blood transplantation in a child with acquired severe aplastic anemia (2013)

Over 400 cases of pediatric SAA occur annually in the United States. A growing number of children with SAA may have had their stem cells harvested through cord blood collection. We describe a nine-yr-old male with SAA treated successfully with an autologous cord blood transplant following immunoablative chemotherapy. With the increasing number of people cryopreserving autologous cord blood, the use of autologous cord blood in the treatment of SAA might be considered as initial therapy. This case serves to discuss approaches to preparative therapy as well as the potential complications in this growing cohort of patients.
Regulatory strategies for early device development and approval (2022)

The development of new technology to treat unmet clinical needs is an important component of modern cardiovascular disease. The need for this has been emphasized in the past several years beginning with the Food and Drug Administration (FDA) guidance document on Early Feasibility Studies in 2012 and then the 21st Century Cures legislation. A number of steps need to be considered in this process by the stakeholders involved including physician innovators and scientists, professional societies such as Society for Cardiovascular Angiography & Interventions, regulatory agencies, and medical device companies. This article focuses on the early iterative steps required to optimize the process and achieve the goal of timely efficient innovation and device development in cardiovascular disease.
Expression and characterization of EF-hand I loop mutants of aequorin replaced with other loop sequences of Ca2+-binding proteins: an approach to studying the EF-hand motif of proteins (2016)

The binding properties of Ca(2+) to EF-hand I of aequorin (AQ) were characterized by replacing the loop sequence of EF-hand I (AQ[I]) with other known loop sequences of Ca(2+)-binding proteins, including photoproteins (aequorin, clytin-I, clytin-II and mitrocomin), Renilla luciferin-binding protein (RLBP) and calmodulin (CaM). For evaluation of the binding affinity of Ca(2+) to AQ[I] mutants, the half-decay time of the maximum intensity in the luminescence reaction triggered by Ca(2+) was used as an indicator and 22 kinds of AQ[I] mutants were expressed in Escherichia coli cells. AQ[I] mutants replaced with the EF-hand I and EF-hand III from photoproteins showed sufficient luminescence activity, but it was not shown by other EF-hands from RLBP and CaM. An AQ[I] mutant with a lysine or arginine residue at the second position of the non-conserved amino acid residue showed a slow-decay pattern of luminescence, indicating that the Ca(2+)-binding affinity to aequorin was reduced by a positive charge at the second position of the loop sequence. The specific loop sequence of the EF-hand I motif in aequorin caused the specific Ca(2+)-triggered luminescence pattern.
CRAWDAD dataset ucsd/sigcomm2001 (v. 2002-04-23) (2002)

This dataset includes SNMP and tcpdump records from 4 access points at a three-day computer-science conference.
Quantitative analysis of treatments using real‐time image gated spot‐scanning with synchrotron‐based proton beam therapy system log data (2020)

A synchrotron-based real-time image gated spot-scanning proton beam therapy (RGPT) system with inserted fiducial markers can irradiate a moving tumor with high accuracy. As gated treatments increase the beam delivery time, this study aimed to investigate the frequency of intra-field adjustments corresponding to the baseline shift or drift and the beam delivery efficiency of a synchrotron-based RGPT system. Data from 118 patients corresponding to 127 treatment plans and 2810 sessions between October 2016 and March 2019 were collected. We quantitatively analyzed the proton beam delivery time, the difference between the ideal beam delivery time based on a simulated synchrotron magnetic excitation pattern and the actual treatment beam delivery time, frequency corresponding to the baseline shift or drift, and the gating efficiency of the synchrotron-based RGPT system according to the proton beam delivery machine log data. The mean actual beam delivery time was 7.1 min, and the simulated beam delivery time in an ideal environment with the same treatment plan was 2.9 min. The average difference between the actual and simulated beam delivery time per session was 4.3 min. The average frequency of intra-field adjustments corresponding to baseline shift or drift and beam delivery efficiency were 21.7% and 61.8%, respectively. Based on our clinical experience with a synchrotron-based RGPT system, we determined the frequency corresponding to baseline shift or drift and the beam delivery efficiency using the beam delivery machine log data. To maintain treatment accuracy within ± 2.0 mm, intra-field adjustments corresponding to baseline shift or drift were required in approximately 20% of cases. Further improvements in beam delivery efficiency may be realized by shortening the beam delivery time.
Chirality Solely Due to the Presence of an Excited State (1988)

meso-Diketones in which only one carbonyl group is electronically excited must be chiral. A strategy for the synthesis of the first molecule of this kind is based on this concept. Starting from the optically active dioxetane 1 (ee ca. 69%) the excited adamantanedione 2 was obtained, whose optical activity, however, could not be ascertained experimentally since the close spatial proximity of the carbonyl groups enables rapid racemization in the excited state.
Inhibition of nitric oxide production. Mechanisms of vascular albumin leakage. (1993)

The mechanisms by which nitric oxide modulates microvascular albumin exchange were investigated by monitoring leukocyte-endothelial cell adhesion and fluorescein isothiocyanate-albumin leakage in rat mesenteric venules exposed to NG-nitro-L-arginine methyl ester (L-NAME). L-NAME elicited an initial rapid increase followed by a slower rate of albumin accumulation in the interstitial space. The initial phase of albumin leakage preceded the L-NAME-induced leukocyte adherence and emigration, whereas the magnitude of the albumin leakage observed in the later phase of L-NAME exposure was highly correlated with the number of adherent and emigrated leukocytes in the same segment of venule. Monoclonal antibodies (MAbs) directed against adhesion molecules CD11/CD18, ICAM-1, or P-selectin, but not a nonbinding MAb, attenuated the albumin leakage induced by L-NAME. WEB2086, a platelet activating factor antagonist, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) reduced the leukocyte adherence and emigration as well as the increased albumin leakage. Only 8-br-cGMP and the P-selectin MAb attenuated the platelet-leukocyte aggregation elicited by L-NAME. Phalloidin, which promotes endothelial junctional integrity, inhibited both the early and late phases of albumin leakage. Overall, these findings suggest that the increased albumin leakage observed in postcapillary venules after inhibition of nitric oxide production involves a mechanism that includes a role for cGMP, platelet activating factor, leukocyte-endothelial cell adhesion, and the endothelial cell cytoskeleton.
Ultimate-Gradient SRF Test Cavity and Low Loss Tangent Measurements in Ultra Pure Sapphire (2011)

A test cavity has been designed to test wafer samples of superconducting materials at 1.3 GHz. Operating in TE01 mode, this mushroom shaped cavity creates a unique distribution of surface fields. The surface magnetic field on the sample wafer is 3.75 times greater than elsewhere on the Niobium (Nb) cavity surface. This made possible by loading the cavity with an ultra-pure sapphire just above the sample wafer. The maximum field seen by the Nb wall is only 25% of the value deposited on the sample surface. Therefore, it should be possible to push the sample wafer well beyond the BCS limit for Nb while still obtaining a respectable Q. The sapphires loss tangent and dielectric constant must be measured to finalize the design for the Wafer Test Cavity. A sapphire loaded CEBAF cavity has been constructed and tested; these results on the dielectric constant and loss tangent will be presented.
Association of epigenetic inactivation of the WRN gene with anticancer drug sensitivity in cervical cancer cells (2012)

The Werner (WRN) gene codes for a DNA helicase that contributes to genomic stability and has been identified as the gene responsible for progeria. Recent studies have shown reduced WRN expression due to aberrant DNA hypermethylation in cancer cells. Furthermore, WRN expression is thought to affect sensitivity to DNA topoisomerase I inhibitors in cancer therapy. In this study, we examined the relationship between aberrant DNA hypermethylation of WRN and the sensitivity of cervical cancer cells to anticancer drugs. DNA was extracted from samples from 22 patients with primary cervical cancer and 6 human cervical cancer-derived cell lines. Aberrant DNA hypermethylation was analyzed by methylation-specific PCR. WRN expression in cultured cells before and after addition of 5-aza-2-deoxycytidine, a demethylating agent, was examined using RT-PCR. The sensitivity of cells to anticancer drugs was determined using a collagen gel droplet embedded culture drug sensitivity test (CD-DST). siRNA against WRN was transfected into a cervical cancer-derived cell line with high WRN expression. Changes in drug sensitivity after silencing WRN were determined by CD-DST. Aberrant DNA hypermethylation and decreased expression of WRN were detected in 7/21 cases of primary cervical cancer and in two cervical cancer-derived cell lines. These two cell lines showed high sensitivity to CPT-11, a topoisomerase I inhibitor, but became resistant to CPT-11 after treatment with 5-aza-2-deoxycytidine. Transfection of siRNA against WRN increased the sensitivity of the cells to CPT-11. Aberrant DNA hypermethylation of WRN also increased the sensitivity of cervical cancer cells to CPT-11. Therefore, epigenetic inactivation of this gene may be a biomarker for selection of drugs for the treatment of cervical cancer. This is the first report to show a relationship between the methylation of the WRN gene and sensitivity to CPT-11 in gynecological cancers.
Inflammatory pseudotumor of the urinary bladder: a report of five cases and review of the literature. (2001)

We describe five patients who recently presented with gross hematuria secondary to inflammatory pseudotumors of the bladder along with a review of the literature. At presentation, four of the five patients were clinically misdiagnosed as malignancies of which two were further believed to be leiomyosarcomas on initial histological examination because of their spindle-cell appearance. Conservative excision either by transurethral resection or partial cystectomy was curative in all cases. The main importance of these rare, benign lesions is to differentiate them from malignant tumors for which they may be mistaken, thus avoiding radical surgery and its attendant complications.
Preparative biotransformations (2001)

Covering: 1999. Previous review: J. Chem. Soc., Perkin Trans. 1, 2000, 611.
Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs (2013)

Chronic hyperglycemia in type-1 diabetes mellitus is associated with oxidative stress (OS) and sudden death. Mechanistic links remain unclear. We investigated changes in electrophysiological (EP) properties in a model of chronic hyperglycemia before and after challenge with OS by GSH oxidation and tested reversibility of EP remodeling by insulin. Guinea pigs survived for 1 mo following streptozotocin (STZ) or saline (sham) injection. A treatment group received daily insulin for 2 wk to reverse STZ-induced hyperglycemia (STZ + Ins). EP properties were measured using high-resolution optical action potential mapping before and after challenge of hearts with diamide. Despite elevation of glucose levels in STZ compared with sham-operated (P = 0.004) and STZ + Ins (P = 0.002) animals, average action potential duration (APD) and arrhythmia propensity were not altered at baseline. Diamide promoted early (<10 min) formation of arrhythmic triggers reflected by a higher arrhythmia scoring index in STZ (P = 0.045) and STZ + Ins (P = 0.033) hearts compared with sham-operated hearts. APD heterogeneity underwent a more pronounced increase in response to diamide in STZ and STZ + Ins hearts compared with sham-operated hearts. Within 30 min, diamide resulted in spontaneous incidence of ventricular tachycardia and ventricular fibrillation (VT/VF) in 3/6, 2/5, 1/5, and 0/4 STZ, STZ + Ins, sham-operated, and normal hearts, respectively. Hearts prone to VT/VF exhibited greater APD heterogeneity (P = 0.010) compared with their VT/VF-free counterparts. Finally, altered EP properties in STZ were not rescued by insulin. In conclusion, GSH oxidation enhances APD heterogeneity and increases arrhythmia scoring index in a guinea pig model of chronic hyperglycemia. Despite normalization of glycemic levels by insulin, these proarrhythmic properties are not reversed, suggesting the importance of targeting antioxidant defenses for arrhythmia suppression.
The HosA Histone Deacetylase Regulates Aflatoxin Biosynthesis Through Direct Regulation of Aflatoxin Cluster Genes (2019)

Histone deacetylases (HDACs) always function as corepressors and sometimes as coactivators in the regulation of fungal development and secondary metabolite production. However, the mechanism through which HDACs play positive roles in secondary metabolite production is still unknown. Here, classical HDAC enzymes were identified and analyzed in <i>Aspergillus flavus</i>, a fungus that produces one of the most carcinogenic secondary metabolites, aflatoxin B<sub>1</sub> (AFB1). Characterization of the HDACs revealed that a class I family HDAC, HosA, played crucial roles in growth, reproduction, the oxidative stress response, AFB1 biosynthesis, and pathogenicity. To a lesser extent, a class II family HDAC, HdaA, was also involved in sclerotia formation and AFB1 biosynthesis. An in vitro analysis of HosA revealed that its HDAC activity was considerably diminished at nanomolar concentrations of trichostatin A. Notably, chromatin immunoprecipitation experiments indicated that HosA bound directly to AFB1 biosynthesis cluster genes to regulate their expression. Finally, we found that a transcriptional regulator, SinA, interacts with HosA to regulate fungal development and AFB1 biosynthesis. Overall, our results reveal a novel mechanism by which classical HDACs mediate the induction of secondary metabolite genes in fungi.
Molecular alteration of the 140-megadalton plasmid associated with loss of virulence and Congo red binding activity in Shigella flexneri (1986)

A plasmid of about 140 megadaltons has been associated with the invasiveness of Shigella flexneri. Upon subculturing in liquid media of fully virulent isolates of Shigella flexneri 2a YSH6000, which contains only a 230-kilobase-pair (kbp) plasmid in addition to 3.3- and 4.2-kbp cryptic plasmids characteristic to all S. flexneri strains, loss of invasiveness, loss of Congo red binding activity (Pcr), and complete loss of, or a deletion, or even a single-site IS insertion in the plasmid occurred simultaneously. This was ascribed to the fact that, once a noninvasive Pcr- cell has emerged, it overgrows the wild type as a consequence of its selective advantage in artificial media. A deletion map of the 230-kbp plasmid was made by analyzing SalI digests of 39 deletion derivatives plus 1 formed by insertion of an IS1-like element in independently isolated, noninvasive Pcr- mutants. Of 39 deletion derivatives, 16 belonged to a single type, and 6 belonged to another, suggesting deletion hot spots. The deletion map was confirmed and extended by analyzing 359 SalI-generated partial digests of the wild-type plasmid cloned into pBR322. Three copies of IS1-like elements were found on three different SalI fragments by Southern hybridization. Segments required for the Pcr+ phenotype seemed to occur at several different locations in the plasmid. Each of 28 representative Pcr- mutants were negative by the Sereny test. Hence, many, or possibly all, Pcr determinants were required for full virulence.
Complex vector fitting toolbox: a software package for the modelling and simulation of general linear and passive baseband systems (2021)

Abstract Complex vector fitting (CVF) is a robust method to efficiently and accurately model general linear and passive baseband systems. Such models are important for the analysis and design of modern electronic and optical communication systems. This letter introduces an efficient toolbox implementation of the CVF algorithm. The effectiveness of the code is illustrated on a suitable application example.
Indole and quinoline derivatives of 2,3‐dihydro‐l‐benzothiepin‐4(5H) one (1978)

Abstract By application of the Friedlander synthesis on 2,3‐dihydro‐l‐benzothiepin‐4(5 H ) one (4), the corresponding [4,5‐ b ]quinoline derivatives 5a and 5b were obtained. Starting from the ketone (4) and by application of the Fischer indole synthesis, 1‐benzolhiepino[4,5‐ b ]indole (6) and 1‐benzothiepino[4,5‐ b ]benzo[ g ]indole (7) were obtained. When β‐naphthylhydrazine was used in the indolisation reaction, a mixture of 1‐benzothiepino[4,5‐ b ]benzo[ e ]indole ( 8 ) and 1‐benzothiepino[4,3‐ b ]benzo[ e ] indole (9) was obtained.
A trifunctional linker suitable for conducting three orthogonal click chemistries in one pot (2016)

The feasibility of a one pot approach for conducting mutually orthogonal thiol-Michael addition, copper catalyzed azide-alkyne and inverse electron demand Diels-Alder click chemistry on a tri-functional substrate was demonstrated.
Femtosecond Stimulated Raman Spectroscopy (2006)

ADVERTISEMENT RETURN TO ISSUEPREVFEATURESNEXTFemtosecond Stimulated Raman SpectroscopyPhilipp Kukura, Sangwoon Yoon, and Richard A. MathiesCite this: Anal. Chem. 2006, 78, 17, 5952–5959Publication Date (Web):September 1, 2006Publication History Published online1 September 2006Published inissue 1 September 2006https://pubs.acs.org/doi/10.1021/ac069450lhttps://doi.org/10.1021/ac069450lnewsACS Publications. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views3549Altmetric-Citations40LEARN 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 PDF (414 KB) Get e-Alertsclose SUBJECTS:Raman spectroscopy Get e-Alerts
Crystal structure of FAF1 UBX domain in complex with p97/VCP N domain reveals a conformational change in the conserved FcisP touch‐turn motif of UBX domain (2011)

Additional Supporting Information may be found in the online version of this article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Discovery of a highly selective chemical inhibitor of matrix metalloproteinase-9 (MMP-9) that allosterically inhibits zymogen activation (2017)

Aberrant activation of matrix metalloproteinases (MMPs) is a common feature of pathological cascades observed in diverse disorders, such as cancer, fibrosis, immune dysregulation, and neurodegenerative diseases. MMP-9, in particular, is highly dynamically regulated in several pathological processes. Development of MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, a long history of failed clinical trials has demonstrated that broad-spectrum MMP inhibitors have limited clinical utility, which has spurred the development of inhibitors selective for individual MMPs. Attaining selectivity has been technically challenging because of sequence and structural conservation across the various MMPs. Here, through a biochemical and structural screening paradigm, we have identified JNJ0966, a highly selective compound that inhibited activation of MMP-9 zymogen and subsequent generation of catalytically active enzyme. JNJ0966 had no effect on MMP-1, MMP-2, MMP-3, MMP-9, or MMP-14 catalytic activity and did not inhibit activation of the highly related MMP-2 zymogen. The molecular basis for this activity was characterized as an interaction of JNJ0966 with a structural pocket in proximity to the MMP-9 zymogen cleavage site near Arg-106, which is distinct from the catalytic domain. JNJ0966 was efficacious in reducing disease severity in a mouse experimental autoimmune encephalomyelitis model, demonstrating the viability of this therapeutic approach. This discovery reveals an unprecedented pharmacological approach to MMP inhibition, providing an opportunity to improve selectivity of future clinical drug candidates. Targeting zymogen activation in this manner may also allow for pharmaceutical exploration of other enzymes previously viewed as intractable drug targets.
<title>Display bandwidth reduction via latched pixels and processing at the pixel</title> (2002)

The demand for displays with a large number of pixels is being driven by both military and commercial applications. Displays with very high information content are expected to have &gt;1Gigapixels, requiring I/O bandwidth well beyond current integrated circuit technology, if display architectures continue as they have in the past. In this paper we present a concept based on latched pixels and data processing at the pixel level that could provide a significant reduction in display bandwidth.