gebhart/patrepeval huggingface dataset:
261-OR: Dorzagliatin, a Dual-Acting Glucokinase Activator. Improves Insulin Secretion and Glucose Sensitivity in Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY) (2022)

Glucokinase maturity onset diabetes of the young (GCK-MODY) is caused by heterozygous inactivating mutations in GCK that is not responsive to conventional glucose lowering drugs. We investigated the effects of dorzagliatin, a novel allosteric activator of hepatic and beta-cell GCK on insulin secretion rates (ISR) and glucose sensitivity (GS) in GCK-MODY and recent onset type 2 diabetes (T2D) . In a double-blind, randomized cross-over study, 8 GCK-MODY (mean±SD age 36.1­±6.4years) and T2D subjects (mean age 50.2±6.9 years, median T2D duration 0.90 [0.60-1.42] years) underwent 2-hour 12 mmol/L hyperglycemic clamps following a single oral dose of dorzagliatin 75mg or matched placebo. Insulin and C-peptide were measured. GCK-MODY group showed significantly higher absolute (mean±SD 432±85 versus 272±91 pmol/min/m2, p=0.002) and incremental (342­±91 vs. 241±74 pmol/min/m2, p=0.004) second-phase ISR following dorzagliatin versus placebo. Dorzagliatin significantly improved GS in GCK-MODY (51±21 vs. 33­±13 pmol/min/m2 per mmol/L p=0.028) with an upward and leftward shift in ISR-glucose response. In T2D, basal ISR was significantly improved following dorzagliatin (102±57 vs. 60±42, p=0.018) with smaller increases in second phase ISR and GS. Dorzagliatin improves second phase ISR and GS, with larger effects in GCK-MODY than T2D. Disclosure E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. L.Chen: Employee; Hua Medicine. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp &amp; Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. K.Wang: None. C.K.P.Lim: None. S.Tsoi: None. B.Fan: None. A.Luk: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. E.Ferrannini: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Oramed Pharmaceuticals, Consultant; Elgia Therapeutics, Research Support; Janssen Research &amp; Development, LLC, Oramed Pharmaceuticals, Sanofi-Aventis U.S., Speaker's Bureau; Boehringer Ingelheim International GmbH. A.Mari: Consultant; Lilly, Research Support; Lilly. Funding Hua Medicine Investigator Initiated Clinical Research
Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice (2000)

Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium. Hyperplasia was evident in these mice by 2-3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6-7 months of age. Well differentiated adenocarcinomas appeared in mice 6 months or older. Less differentiated tumors, diagnosed as small cell carcinomas, were also observed in two of the older mice. Both lobes of the mouse prostate gland (dorsolateral and ventral) presented preneoplastic and neoplastic changes. The incidence of tumors in mice >/=6 months of age (38 mice total) was 50%. The development of neoplasia in these transgenic mice appeared to follow a stepwise progression through early preneoplastic changes that ultimately culminated in frank neoplasia. These mice offer an animal model for prostate cancer that will allow study of the stepwise development of this disease and the mechanism(s) whereby IGF-1 mediates this process.
Interplay of RUNX1/MTG8 and DNA Methyltransferase 1 in Acute Myeloid Leukemia (2005)

The translocation t(8;21)(q22;q22) in acute myeloid leukemia (AML) results in the expression of the fusion protein RUNX1/MTG8, which in turn recruits histone deacetylases (HDAC) to silence RUNX1 target genes [e.g., interleukin-3 (IL-3)]. We previously reported that expression of the RUNX1/MTG8 target gene IL-3 is synergistically restored by the combination of inhibitors of HDACs (i.e., depsipeptide) and DNA methyltransferases (DNMT; i.e., decitabine) in RUNX1/MTG8-positive Kasumi-1 cells. Thus, we hypothesized that DNMT1 is also part of the transcriptional repressor complex recruited by RUNX1/MTG8. By a chromatin immunoprecipitation assay, we identified a RUNX1/MTG8-DNMT1 complex on the IL-3 promoter in Kasumi-1 cells and in primary RUNX1/MTG8-positive AML blasts. The physical association of RUNX1/MTG8 with DNMT1 was shown by coimmunoprecipitation experiments. Furthermore, RUNX1/MTG8 and DNMT1 were concurrently released from the IL-3 promoter by exposure to depsipeptide or stabilized on the promoter by decitabine treatment. Finally, we proved that RUNX1/MTG8 and DNMT1 were functionally interrelated by showing an enhanced repression of IL-3 after coexpression in 293T cells. These results suggest a novel mechanism for gene silencing mediated by RUNX1/MTG8 and support the combination of HDAC and DNMT inhibitors as a novel therapeutic approach for t(8;21) AML.
The Search for Selective, Neutral Anion Receptors (1994)

Difficult, but not impossible! Though anions are large and coordinatively saturated—and therefore slow to form adducts—they do form complexes selectively and efficiently with the novel coronands and cryptands specially tailored to be large enough and to contain ionic, Lewis acidic, or dipolar groups. These host molecules can be, for instance, modified carboranes and crown ethers or tricyclic borane–amine adducts (as in the formation of 1).
Imaging nanosized gold colloids by atomic force microscopy: a direct comparison with transmission electron microscopy (1996)

Gold colloids have been prepared on carbon-coated copper grids using poly(lysine) as a chemical adhesive. The particles have been imaged using contact mode atomic force microscopy (AFM). The same individual particles have then been imaged by high-resolution transmission electron microscopy (HRTEM). Comparison of the images shows that the particle height determined by AFM agrees remarkably well with that determined by TEM, but that the width of the images is consistently higher than the height. Doublets and triplets can be resolved well but subtle shape differences are poorly reproduced by AFM.
Wideband flexible transmitter and receiver pair for implantable wireless neural recording applications (2007)

This paper presents a complete wideband 900 MHz wireless link with 75 MHz bandwidth consisting of an integrated flexible transmitter and a custom-designed receiver for wireless multichannel neural recording and biotelemetry applications. The transmitter is basically an LC-tank voltage controlled oscillator (VCO) with multiple tunable parameters. The hybrid tank consists of binary weighed PMOS varactors and a surface-mount (SMD) off-chip inductor, which also acts as an antenna to minimize the transmitter size. Taking advantage of two sets of PMOS varactors operating as three terminal devices, we were able to shift the VCO frequency-voltage (F-V) curve along the vertical axis by 16 MHz around its 920 MHz center frequency. We could also shift the VCO high gain region along the horizontal axis by 1.3 V, and finally change the VCO gain from 1.24 MHz/V to 23.8 MHz/V. The VCO was fabricated in the AMI-0.5 pm standard CMOS process and occupies 230 × 220 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . It draws 2.2 mA from ±1.5 V supplies. The receiver band can be tuned from 50 MHz to 1 GHz and its gain is adjustable from −14 to 21 dB. Using the SMD transmitter antenna, we received −53 dBm signal power in −100 dBm noise floor at the distance of 1 m with an 8.33 cm 1/4 λ monopole receiver antenna. Measurement results showed that when transmitting a 1 MHz square wave with 15 ns rising and falling edges across this wireless link, the received down converted signal has 10 ns delay and 20 ns frequency shifts.
Studium der Wirkung der Gammastrahlung auf die L‐Ascorbinsäure (1963)

Abstract Die Wirkung ionisierender Strahlung auf die L‐Ascorbinsäureoxydation in Modellösungen und Obst wurde verfolgt. Es wurde ermittelt, daß der Oxydationsverlauf der L‐Ascorbinsäure im Bereich der untersuchten Dosen und Konzentrationen der L‐Ascorbinsäure linear ist. Die Oxydationsgeschwindigkeit ist der L‐Ascorbinsäurekonzentration und der Strahlungsintensität indirekt proportional. Eine ähnliche Beziehung gilt auch für die weitere, jedoch langsamer verlaufen‐den Destruktion der Dehydroascorbinsäure. Die Reaktionsgeschwindigkeit der L‐Ascorbinsäure wird weiterhin durch niedrige pH‐Werte und bei Gegenwart von Sauerstoff und Schwermetall‐ionen erhöht. Nicotinsäure und Katalase weisen eine Schutzwirkung bezüglich der Ascorbinsäure auf. Die L‐Ascorbinsäureretention bei durch ionisierende Strahlen behandeltem frischem Obst ist auch bei längerer Lagerungsfrist günstig.
Flexural Behavior and Design of High-Strength Concrete Members (2005)

The American Concrete Institute (ACI) is a leading authority and resource worldwide for the development and distribution of consensus-based standards, technical resources, educational programs, certification programs, and proven expertise for individuals and organizations involved in concrete design, construction, and materials, who share a commitment to pursuing the best use of concrete.
Comparison of the effects of hyaluronidase and hyaluronic acid on probiotics growth (2013)

Observations might suggest a possible protective role of both hyaluronidase and low doses of hyaluronic acid towards some strains, supporting their in vivo proliferation and engraftment after oral administration. Hyaluronidase introduction into growth medium greatly enhanced the bacterial growth up to 72 hours.
A Dynamic Model of the Deformation of a Diamond Mesh Cod-End of a Trawl Net (2008)

A dynamic model of a diamond mesh cod-end subject to harmonic forcing is developed. The partial differential equations governing the displacements of the cod-end and the tension in the twine are first derived and then analyzed using the harmonic balance method by substituting a harmonic series for the dependent variables and the forcing term. A closed-form solution is derived for the case of rigid-body motion, where there is no deformation of the cod-end geometry, along with the conditions for the forcing under which this motion occurs. A pressure loading, which varies linearly over a portion of the cod-end and varies harmonically with time, is then introduced as a first representation of the loading on the cod-end that results from the pressure and acceleration forces on the catch due to surge motion of the towing vessel. The resulting sets of equations for the static and the first and second harmonic terms are solved numerically in a sequential manner, and the results presented for a number of cases. These results show that, due to the nonlinearity of the system, the oscillatory motion of the cod-end is asymmetric, and that the deformation of the net and the amplitude of oscillation increases as the region over which the forcing is applied increases. The model is the basis for a more complete coupled catch/cod-end model.
Reactions of Active Nitrogen with Organic Substrates. I. The Monomeric Products of the Reaction with 1,3-Butadiene (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactions of Active Nitrogen with Organic Substrates. I. The Monomeric Products of the Reaction with 1,3-ButadieneAkira. Tsukamoto and Norman N. LichtinCite this: J. Am. Chem. Soc. 1962, 84, 9, 1601–1605Publication Date (Print):May 1, 1962Publication History Published online1 May 2002Published inissue 1 May 1962https://pubs.acs.org/doi/10.1021/ja00868a018https://doi.org/10.1021/ja00868a018research-articleACS PublicationsRequest reuse permissionsArticle Views68Altmetric-Citations15LEARN 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-Alertsclose Get e-Alerts
Design of Remote Monitoring System Based on Embedded System (2013)

The embedded technology has widely applied in the remote monitoring system. This paper is mainly for remote monitoring system project design based on embedded Web technology. And on the basis of the overall system design, it has separately carried on the detailed design and analysis to the software and hardware structure.
Two sequential layers of antibody‐mediated control of Legionella pneumophila infection (2019)

Protective immunity against intracellular pathogens, including bacteria, usually relies on cellular immunity. However, antibodies are also implicated in mediating protection against intracellular bacteria. In case of airway infection with Legionella pneumophila (Lpn), the causative agent of Legionnaires' disease, pre-existing Lpn-specific antibodies were shown to afford protection within two days of infection. Here we dissected the early kinetics of Ab-mediated protection against airway Lpn infection and observed two kinetically and mechanistically distinct phases of protection by passively administered antibodies. Within the first hour of infection, Lpn-opsonizing antibodies provided almost 10-fold protection in an antibody Fc-dependent, but FcR-independent manner. Later on, by two days post infection, Lpn-specific Ab-mediated protection strictly involved FcγR, Syk kinase activity in alveolar macrophages and induction of reactive oxygen species (ROS). The findings presented here contribute to the understanding of the mechanisms of Ab-mediated control of Lpn infection in actively or passively immunized individuals.
Performance of Bituminous and Hydraulic Materials in Pavements (2017)

This volume contains contributions from international experts, reflecting the rapid advances in the design of new improved bitumen and hydraulic bound composites, the trends in the use of waste and recycled materials and up-to-date methods of testing and evaluation.
Supraharmonics in Power Grid: Identification, Standards, and Measurement Techniques (2021)

In the electric power distribution system, power electronics technologies associated with renewable energy systems (RES) and smart grids have gained growing interest. The power electronics devices are used to convert, control, or transfer electric power from RES to the power grids. However, the continuous increase in switching frequencies resulting from these power electronics technologies has led to the emergence of new emissions in the range of 2-150 kHz, outside the classical frequency range for power quality. These emissions are known worldwide as supraharmonics (SH). These emissions negatively affect the power quality of electrical distribution systems and reduce their efficiency and lifetime. Thus, the supraharmonics emissions have been investigated in the literature, and several methods were developed focusing on identifying, measuring, and setting new standards to mitigate the impact of these emissions on the power quality. Although these individual studies have been well documented, a comparative overview of its identifications, current standards, and measurement techniques had not been described so far. Therefore, this study extensively reviews the related techniques and standards for identifying, measuring, and mitigating SH emissions. Moreover, the current research gap in this important field is highlighted, and an illustration on how this problem was tackled in the past few years is presented. Additionally, the SH characteristics alongside insights into the mitigations and measurements are highlighted and analyzed accordingly. Finally, some important recommendations to mitigate SH emissions are suggested. This review will hopefully strengthen the efforts toward the development of SH domain by providing the necessary groundwork for further mitigations, standards, and measuring techniques improvement.
Complete axillary conversion after neoadjuvant chemotherapy in locally advanced breast cancer: A step towards conserving axilla? (2004)

47% patients had complete clinical nodal response, while 19% showed complete sonographic response. Complete pathological nodal response was documented in 22% of patients. Ultrasonography was found to be more sensitive than clinical examination in assessing complete nodal response. 10% of the patients had complete pathological response of both primary tumor and axillary nodes. There was significant correlation between pathological response of primary tumor and lymph nodes (P=0.004). Patients with complete sonographic or clinical response were found to have no or minimal residual disease in axilla and hence axillary dissection may be avoided in them.
Neonatal lymphocyte subpopulations analysis and maternal preterm premature rupture of membranes: a pilot study (2021)

pPROM prompts maturation of the newborn's T-cell immune system secondary to antigenic stimulation, which correlates with pPROM latency. Maternal immunity to inflammatory conditions is associated with a decrease in non-major histocompatibility complex (MHC)-restricted cytotoxic cells.
Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions (2020)

Genetic variation can predispose to disease both through (i) monogenic risk variants that disrupt a physiologic pathway with large effect on disease and (ii) polygenic risk that involves many variants of small effect in different pathways. Few studies have explored the interplay between monogenic and polygenic risk. Here, we study 80,928 individuals to examine whether polygenic background can modify penetrance of disease in tier 1 genomic conditions - familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome. Among carriers of a monogenic risk variant, we estimate substantial gradients in disease risk based on polygenic background - the probability of disease by age 75 years ranged from 17% to 78% for coronary artery disease, 13% to 76% for breast cancer, and 11% to 80% for colon cancer. We propose that accounting for polygenic background is likely to increase accuracy of risk estimation for individuals who inherit a monogenic risk variant.
Biobehavior in Normal and Tumor-Bearing Mice of Tobacco Mosaic Virus (2013)

Viral nanoparticles (VNPs) have shown great potential as platforms for biomedical applications. Before using VNPs for further biomedical applications, it is important to clarify their biological behavior in vivo, which is rare for rod-like VNPs. In this paper, a study of tobacco mosaic virus (TMV), a typical rod-like VNP, is performed on blood clearance kinetics, biodistributions in both normal and tumor-bearing mice, histopathology and cytotoxicity. TMV was radiolabeled with 125I using Iodogen method for in vivo quantitative analysis and imaging purpose. In the normal mice, the accumulation of TMV in the immune system led to a rapid blood clearance. The uptake of TMVs in the liver was less than that in the spleen, which is opposite to the results observed in the case of spherical VNPs. No signs of overt toxicity were observed in examined tissues according to the results of histological analysis. In addition, similar biodistribution patterns were observed in U87MG tumor-bearing mice.
Media For High-Density Optical Recording (1981)

There are many high density optical recording systems that require storage media capable of high recording and playback performance. In this paper, the general requirements which govern the selection, design, and optimization of the recording media are described. The use of a high power diode laser as the recording and playback source is also described.
Graphene Oxide-Embedded Extracellular MatrixDerived Hydrogel as a Multiresponsive Platform for 3D Bioprinting Applications (2021)

Decellularized extracellular matrices (dECMs) have shown enormous potential for the biofabrication of tissues due to their biomimetic properties that promote enhanced cellular interaction and tissue regeneration. However, biofabrication schemes requiring electrostimulation pose an additional constraint due to the insulating properties of natural materials. Here, we propose a methacryloyl-modified decellularized small intestine submucosa (SISMA) hydrogel, embedded with graphene oxide (GO) nanosheets, for extrusion-based 3D bioprinting applications that require electrostimulation. Methacryloyl biochemical modification is performed to enhance the mechanical stability of dECM constructs by mediating photo-crosslinking reactions, and a multistep fabrication scheme is proposed to harness the bioactive and hydrophilic properties of GO and electroconductive properties of reduced GO. For this, GO was initially dispersed in SISMA hydrogels by exploiting its hydrophilicity and protein adsorption capabilities, and <i>in situ</i> reduction was subsequently performed to confer electroconductive abilities. SISMA-GO composite hydrogels were successfully prepared with enhanced structural characteristics, as shown by the higher crosslinking degree and increased elastic response upon blue-light exposure. Moreover, GO was homogeneously dispersed without affecting photocrosslinking reactions and hydrogel shear-thinning properties. Human adipose-derived mesenchymal stem cells were successfully bioprinted in SISMA-GO with high cell viability after 1 week and <i>in situ</i> reduction of GO during this period enhanced the electrical conductivity of these nanostructures. This work demonstrates the potential of SISMA-GO bioinks as bioactive and electroconductive scaffolds for electrostimulation applications in tissue engineering and regenerative medicine.
Unwanted effects and interaction of intrajejunal levodopa/carbidopa administration (2014)

LCIG is a beneficial and very useful treatment option as escalation therapy for Parkinson's disease. While the side effects are not insignificant, they are justifiable in view of the severity of the disease. Attention must be paid, in particular, to malabsorption, with monitoring at baseline and in the course of treatment.
Structural basis of the methylation specificity of R.DpnI (2014)

R.DpnI consists of N-terminal catalytic and C-terminal winged helix domains that are separately specific for the Gm6ATC sequences in Dam-methylated DNA. Here we present a crystal structure of R.DpnI with oligoduplexes bound to the catalytic and winged helix domains and identify the catalytic domain residues that are involved in interactions with the substrate methyl groups. We show that these methyl groups in the Gm6ATC target sequence are positioned very close to each other. We further show that the presence of the two methyl groups requires a deviation from B-DNA conformation to avoid steric conflict. The methylation compatible DNA conformation is complementary with binding sites of both R.DpnI domains. This indirect readout of methylation adds to the specificity mediated by direct favorable interactions with the methyl groups and solvation/desolvation effects. We also present hydrogen/deuterium exchange data that support 'crosstalk' between the two domains in the identification of methylated DNA, which should further enhance R.DpnI methylation specificity.