gebhart/patrepeval huggingface dataset:
Alzheimer’s Disease: Development of Disease-Modifying Treatments Is the Challenge for Our Generation (2012)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTAlzheimer's Disease: Development of Disease-Modifying Treatments Is the Challenge for Our GenerationCraig W. LindsleyCite this: ACS Chem. Neurosci. 2012, 3, 11, 804–805Publication Date (Web):November 21, 2012Publication History Published online21 November 2012Published inissue 21 November 2012https://pubs.acs.org/doi/10.1021/cn300190fhttps://doi.org/10.1021/cn300190feditorialACS PublicationsCopyright © 2012 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1492Altmetric-Citations14LEARN 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 (133 KB) Get e-AlertscloseSUBJECTS:Cancer therapy,Medicinal chemistry,Peptides and proteins,Pharmaceuticals,Targeting Get e-Alerts
Perturbation theory for anisotropic dielectric interfaces, and application to subpixel smoothing of discretized numerical methods (2008)

We derive a correct first-order perturbation theory in electromagnetism for cases where an interface between two anisotropic dielectric materials is slightly shifted. Most previous perturbative methods give incorrect results for this case, even to lowest order, because of the complicated discontinuous boundary conditions on the electric field at such an interface. Our final expression is simply a surface integral, over the material interface, of the continuous field components from the unperturbed structure. The derivation is based on a "localized" coordinate-transformation technique, which avoids both the problem of field discontinuities and the challenge of constructing an explicit coordinate transformation by taking the limit in which the coordinate perturbation is infinitesimally localized around the boundary. Not only is our result potentially useful in evaluating boundary perturbations, e.g., from fabrication imperfections, in highly anisotropic media such as many metamaterials, but it also has a direct application in numerical electromagnetism. In particular, we show how it leads to a subpixel smoothing scheme to ameliorate staircasing effects in discretized simulations of anisotropic media, in such a way as to greatly reduce the numerical errors compared to other proposed smoothing schemes.
High-mechanical-strength single-pulse draw tower gratings (2004)

The inscription of fiber Bragg gratings during the drawing process is shown to be a very useful method to realize sensor arrays with high numbers of gratings and excellent mechanical strength and also type two gratings with high temperature stability. Results of single pulse grating arrays with numbers between ten and >100 and definite wavelengths and positions for sensor applications were achieved at 1550nm and 830nm using new photosensitive fibers developed in IPHT. Single pulse type-1 gratings at 1550 nm with more than 30% Reflectivity were shown first time to our knowledge. The mechanical strength of this fiber with an Ormocer coating with those single pulse gratings is the same like standard telecomm fibers. Weibull plots of fiber tests will be shown. At 830 nm we reach more than 10% reflectivity with single pulse writing during the fiber drawing in photosensitive fibers with less than 16 dB transmission loss. These gratings are useful for stress and vibration sensing applications. Type two gratings with reflectivity near 100% and smooth spectral shape and spectral width of about 1 nm reach temperature stability above 1200 K. They are also realized in the fiber drawing process. These Gratings are useful for temperature sensor applications.
Polymorphisms Identified through Genome-Wide Association Studies and Their Associations with Type 2 Diabetes in Chinese, Malays, and Asian-Indians in Singapore (2009)

Context: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized. Objective: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. Design: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians. Results: In Chinese, SNPs in CDKAL1 [odds ratio (OR) 1.19; P 2 10 4 ], HHEX (OR 1.15; P 0.013), and KCNQ1 (OR 1.21; P 3 10 4 ) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR 1.22; P 3.7 10 4 ), HHEX (OR 1.12; P 0.044), SLC30A8 (OR 1.12; P 0.037), and KCNQ1 (OR 1.19 -1.25; P 0.003-2.5 10 4 ) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR 1.13; P 3 10 4 ), CDKN2A/B (OR 1.16; P 9 10 5 ), HHEX (OR 1.14; P 6 10 4 ), and KCNQ1 (OR 1.16 -1.20; P 3 10 4 to 3 10 6 ) with T2DM. SLC30A8 (OR 1.06; P 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry. Conclusions: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.
Comblike Liquid-Crystalline Polymers from Ionic Complexation of Dendronized Polymers and Lipids (2007)

This work describes the self-assembly behavior, the structure, the state, and phase diagrams of comblike liquid-crystalline polymers obtained by supramolecular ionic complexation of cationic dendronized polymers (PG1−PG3) and anionic sulfonated lipid surfactants. In order to characterize the influence of both the polymer and the surfactant on the microphase separation of these complexes, dendronized polymers with generation 1 ≤ n ≤ 3, carrying 2n positive charges per monomer, were complexed with a stoichiometric amount of anionic sodium alkyl monosulfate surfactants with hydrocarbon chain of C8, C12, C14, and C18 lengths. Supramolecular complexes were obtained in water, and the complexation process was monitored by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance. After drying and thermal annealing under high vacuum, the complexes showed thermotropic liquid-crystalline behavior as demonstrated by both cross-polarized optical microscopy and differential scanning calorimetry. Small-angle X-ray scattering allowed determining the respective lattice parameters and type of structures for all the complexes considered. Depending on both generation and lipid chain length, amorphous isotropic fluid, columnar rectangular, columnar hexagonal, columnar tetragonal, and lamellar phases were observed, each characterized by a specific order−disorder transition temperature (TODT).
Supplementary Table 1 from Homozygous Deletions and Chromosome Amplifications in Human Lung Carcinomas Revealed by Single Nucleotide Polymorphism Array Analysis (2023)

Supplementary Table 1 from Homozygous Deletions and Chromosome Amplifications in Human Lung Carcinomas Revealed by Single Nucleotide Polymorphism Array Analysis
Sensing the local magnetic environment through optically active defects in a layered magnetic semiconductor (2022)

Atomic-level defects in van der Waals (vdW) materials are essential building blocks for quantum technologies and quantum sensing applications. The layered magnetic semiconductor CrSBr is an outstanding candidate for exploring optically active defects owing to a direct gap in addition to a rich magnetic phase diagram including a recently hypothesized defect-induced magnetic order at low temperature. Here, we show optically active defects in CrSBr that are probes of the local magnetic environment. We observe spectrally narrow (1 meV) defect emission in CrSBr that is correlated with both the bulk magnetic order and an additional low temperature defect-induced magnetic order. We elucidate the origin of this magnetic order in the context of local and non-local exchange coupling effects. Our work establishes vdW magnets like CrSBr as an exceptional platform to optically study defects that are correlated with the magnetic lattice. We anticipate that controlled defect creation allows for tailor-made complex magnetic textures and phases with the unique ingredient of direct optical access.
Microbial Biosensor for the Detection of Protease-Virulent Factors from Pathogens (2017)

Abstract : The PI has been successful in the detection of protease-virulent factors from pathogens through whole cell and protein-based biosensor designs. Other means of detecting pathogens are reported through the detection of microbial signaling molecules and environmental cue sensing. The PI designed a protease sensing whole-cell biosensor, and they compiled a library of tools used to engineer the microbial cell to respond at different threshold concentrations and response time. This confers the advantage of flexibility in detecting the protease-toxin which can pave the road for engineering microbes to facilitate bioremediation of contaminated water sources. The protein-based biosensor created functions as a quick method of detection that offers rapid response time. Used in tandem, both of these biosensors would function to detect the presence and clear the toxin. These biosensors demonstrated could be added on to the toolkit for detection of other contaminants that would be present in the water supply. As a whole, the design of these biosensors can provide rapid identification of various types of contaminants in a water supply and ultimately serve to reduce the possibility of water-related infections for deployed individuals.
Enantioselective Hydrogenation of N−H Imines (2009)

N-H ketoimines 3a-3v are readily prepared in high yield via organometallic addition to nitriles and isolated as corresponding bench-stable hydrochloride salts. Homogeneous asymmetric hydrogenation of unprotected N-H ketoimines 3a-3v using Ir-(S,S)-f-binaphane as catalyst provides chiral amines 4a-4v in 90-95% yield with enantioselectivities up to 95% ee.
Mechanism of how carbamylation reduces albumin binding to FcRn contributing to increased vascular clearance (2020)

Chronic kidney disease results in high serum urea concentrations leading to excessive protein carbamylation, primarily albumin. This is associated with increased cardiovascular disease and mortality. Multiple methods were used to address whether carbamylation alters albumin metabolism. Intravital two-photon imaging of the Munich Wistar Frömter (MWF) rat kidney and liver allowed us to characterize filtration and proximal tubule uptake and liver uptake. Microscale thermophoresis enabled quantification of cubilin (CUB7,8 domain) and FcRn binding. Finally, multiple biophysical methods including dynamic light scattering, small-angle X-ray scattering, LC-MS/MS and in silico analyses were used to identify the critical structural alterations and amino acid modifications of rat albumin. Carbamylation of albumin reduced binding to CUB7,8 and FcRn in a dose-dependent fashion. Carbamylation markedly increased vascular clearance of carbamylated rat serum albumin (cRSA) and altered distribution of cRSA in both the kidney and liver at 16 h post intravenous injection. By evaluating the time course of carbamylation and associated charge, size, shape, and binding parameters in combination with in silico analysis and mass spectrometry, the critical binding interaction impacting carbamylated albumin's reduced FcRn binding was identified as K524. Carbamylation of RSA had no effect on glomerular filtration or proximal tubule uptake. These data indicate urea-mediated time-dependent carbamylation of albumin lysine K524 resulted in reduced binding to CUB7,8 and FcRn that contribute to altered albumin transport, leading to increased vascular clearance and increased liver and endothelial tissue accumulation.
Genomics and pathotypes of the many faces ofEscherichia coli (2022)

Escherichia coli is the most researched microbial organism in the world. Its varied impact on human health, consisting of commensalism, gastrointestinal disease, or extraintestinal pathologies, has generated a separation of the species into at least eleven pathotypes (also known as pathovars). These are broadly split into two groups, intestinal pathogenic E. coli (InPEC) and extraintestinal pathogenic E. coli (ExPEC). However, components of E. coli's infinite open accessory genome are horizontally transferred with substantial frequency, creating pathogenic hybrid strains that defy a clear pathotype designation. Here, we take a birds-eye view of the E. coli species, characterizing it from historical, clinical, and genetic perspectives. We examine the wide spectrum of human disease caused by E. coli, the genome content of the bacterium, and its propensity to acquire, exchange, and maintain antibiotic resistance genes and virulence traits. Our portrayal of the species also discusses elements that have shaped its overall population structure and summarizes the current state of vaccine development targeted at the most frequent E. coli pathovars. In our conclusions, we advocate streamlining efforts for clinical reporting of ExPEC, and emphasize the pathogenic potential that exists throughout the entire species.
Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist. (1990)

8319, ((+-)-2-Amino-N-ethyl-alpha-(3-methyl-2-thienyl)benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced [3H] TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia.
Submicron full‐color LED pixels for microdisplays and micro‐LED main displays (2020)

Abstract We demonstrate a bottom‐up approach to the construction of micro‐LEDs as small as 150 nm in lateral dimension. Molecular beam epitaxy (MBE) is used to fabricate such nanostructured LEDs from InGaN, from the blue to red regions of the spectrum, providing a single material set useful for an entire RGB display.
Generation of 100+++ Gbit/s signals using multilevel modulation formats (2007)

Multilevel modulation formats are used as the enabling technology to obtain 120 Gbit/s per channel bit rates, and 240 Gbit/s when polarisation multiplexing is added. Using OTDM, this can be extended even further.
Application of Precast Concrete Barrier Adjacent to Steep Roadside Slope (2010)

When concrete barriers are installed adjacent to drop-offs or steep roadside slopes such as 1.5H:1V, a cast-in-place concrete moment slab is usually attached to the base of the barrier to resist lateral and overturning forces during vehicle impact. Cast-in-place construction can require more time on-site to build forms, pour the concrete, and allow for curing. This time constraint results in an increase in disruption to traffic and more exposure for construction workers. Furthermore, the installation of a moment slab is very costly and requires an additional construction phase to build the slab. Because the slab is normally under the shoulder and possibly the lanes, the disruption of traffic flow is increased. A new application of a precast 42-in.-tall single-slope concrete barrier for use in front of steep slopes was developed that does not require a moment slab. The lateral movement of the barrier is restricted by embedding it in soil. This design also reduces the embankment behind the barrier to 2 ft. The embedded barrier application was successfully evaluated under Manual for Assessing Safety Hardware Test Level 3 criteria. The permanent deflection of the barrier was 5.5 in. The use of the embedded concrete barrier in lieu of the typically installed barrier with a moment slab is expected to result in cost savings of approximately $300 per linear foot and reduced time to construct.
Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production (2005)

To test the hypothesis that intrahepatic availability of fatty acid could modify the rate of suppression of endogenous glucose production (EGP), acipimox or placebo was administered before and during a test meal. We used a modified isotopic methodology to measure EGP in 11 healthy subjects, and (1)H magnetic resonance spectroscopic measurement of hepatic triglyceride stores was also undertaken. Acipimox suppressed plasma free fatty acids markedly before the meal (0.05 +/- 0.01 mmol/l at -10 min, P = 0) and throughout the postprandial period (0.03 +/- 0.01 mmol/l at 150 min). Mean peak plasma glucose was significantly lower after the meal on acipimox days (8.9 +/- 0.4 vs. 10.1 +/- 0.5 mmol/l, P < 0.01), as was mean peak serum insulin (653.1 +/- 99.9 vs. 909 +/- 118 pmol/l, P < 0.01). Fasting EGP was similar (11.15 +/- 0.58 micromol.kg(-1).min(-1) placebo vs. 11.17 +/- 0.89 mg.kg(-1).min(-1) acipimox). The rate of suppression of EGP after the meal was almost identical on the 2 test days (4.36 +/- 1.52 vs. 3.69 +/- 1.21 micromol.kg(-1).min(-1) at 40 min). There was a significant negative correlation between the acipimox-induced decrease in peak plasma glucose and liver triglyceride content (r = -0.827, P = 0.002), suggesting that, when levels of liver fat were low, inhibition of lipolysis was able to affect glucose homeostasis. Acute pharmacological sequestration of fatty acids in triglyceride stores improves postprandial glucose homeostasis without effect on the immediate postprandial suppression of EGP.
Abstract 422: Early growth response 1 is required for radiation-induced apoptosis in normal tissues. (2013)

Abstract Although radiation therapy is a mainstay of cancer treatments, it can have deleterious effects on normal tissues, leading to poor quality of life for cancer survivors. Radiation can cause depletion of stem cells in normal tissues that can result in late sequelae, including poor learning, cognitive disorders, intestinal malabsorption, infertility, and skin injuries. Our laboratory has shown that low doses of radiation can induce apoptosis selectively in undifferentiated normal stem cells compared to adjacent differentiated cells in multiple niches including the brain and intestine. To elucidate the molecular basis underlying stem cell sensitivity to radiation, we performed discovery research to detect genomic differences between stem cells and differentiated cells. Among the candidates, the Early growth response 1 (Egr1) gene was expressed at high levels in stem cells, but not in isogenic differentiated cells. Egr1 is a zinc-finger transcription factor that is rapidly induced in response to radiation and activates the transcription of pro-apoptotic genes. Since cancer survivors can suffer from cognitive difficulties and intestinal malabsorption, we investigated the role of Egr1 in neuronal and intestinal cell death following irradiation. Knockdown of Egr1 using shRNA increased clonogenic survival in irradiated HT-22 hippocampal neuronal cells and IEC-6 intestinal epithelial cells. This increased radioprotection was largely due to reduced apoptosis in Egr1 knockdown cells. Additionally, suppression of Egr1 promoter binding by mithramycin A and chromomycin A3 also conferred radioprotection to HT-22 and IEC-6 cells. Mouse models further supported Egr1’s role in radiation-induced apoptosis. Egr1 null mice had significantly fewer apoptotic cells in the hippocampus and small intestinal crypts following irradiation, as compared to their wild-type littermates. Finally, we examined mechanisms by which Egr1 regulates radiation-induced apoptosis. Irradiation of HT-22 and IEC-6 cells led to a G2/M cell cycle arrest, which was abrogated by the knockdown of Egr1. Also, knockdown of Egr1 by shRNA and inhibition of Egr1 promoter binding both attenuated radiation induction of the pro-apoptotic factors p53, Bim, and Bax, and upregulated the anti-apoptotic protein Bcl-2. Thus, this study establishes a crucial role for Egr1 in the radiation-induced apoptosis of hippocampal and intestinal tissues. Egr1 could be a potential molecular target to minimize the normal tissue complications associated with radiation therapy. Citation Format: Yi D. Zhao, Keith M. Jacobs, Rowan M. Karvas, Dennis E. Hallahan, Dinesh Thotala. Early growth response 1 is required for radiation-induced apoptosis in normal tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 422. doi:10.1158/1538-7445.AM2013-422