gebhart/patrepeval huggingface dataset:
A FFAR1 full agonist restores islet function in models of impaired glucose-stimulated insulin secretion and diabetic non-human primates (2022)

The free fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-induced insulin secretion from pancreatic β-cells. At least 3 distinct binding sites exist on the FFAR1 receptor and numerous synthetic ligands have been investigated for their anti-diabetic actions. Fasiglifam, binds to site-1 and stimulates intra-cellular calcium release and improves glycemic control in diabetic patients. Recently, small molecule FFAR1 agonists were discovered which bind to site-3, stimulating both intra-cellular calcium and cAMP, resulting in insulin and glucagon-like peptide-1 (GLP-1) secretion. The ability of our site-3 FFAR1 agonist (compound A) to control blood glucose was evaluated in spontaneously diabetic cynomolgus monkeys during an oral glucose tolerance test. In type-2 diabetic (T2D) animals, significant reductions in blood glucose and insulin were noted. To better understand the mechanism of these <i>in vivo</i> findings, we evaluated the effect of compound A in islets under several conditions of dysfunction. First, healthy human and non-human primate islets were treated with compound A and showed potentiation of insulin and glucagon secretion from both species. Next, we determined glucose-responsive insulin secretion under gluco-lipotoxic conditions and from islets isolated from type-2 diabetic humans. Despite a dysfunctional phenotype that failed to secrete insulin in response to glucose, site-3 FFAR1 agonism not only enhanced insulin secretion, but restored glucose responsiveness across a range of glucose concentrations. Lastly, we treated <i>ex vivo</i> human islets chronically with a sulfonylurea to induce secondary beta-cell failure. Again, this model showed reduced glucose-responsive insulin secretion that was restored and potentiated by site-3 FFAR1 agonism. Together these data suggest a mechanism for FFAR1 where agonists have direct effects on islet hormone secretion that can overcome a dysfunctional T2D phenotype. These unique characteristics of FFAR1 site-3 agonists make them an appealing potential therapy to treat type-2 diabetes.
Human autosomal recessive osteopetrosis maps to 11q13, a position predicted by comparative mapping of the murine osteosclerosis (oc) mutation (1998)

Autosomal recessive osteopetrosis is a rare congenital disorder characterized by the development of abnormally dense bones, acrocephaly, severe anemia, hepatosplenomegaly and progressive deafness and blindness. The clinical course is rapidly progressive and is lethal at a very young age in the absence of a bone marrow transplant. The failure to remodel developing bone that is the basis of the disease process is most likely due to a dysfunction of the bone resorptive cell, the osteoclast. This phenotype is similar to that of the murine mutation osteosclerosis (oc), which is localized to proximal mouse chromosome 19. Given the similarity between the human and murine phenotypes, we tested whether human osteopetrosis maps to a region of conserved synteny. Microsatellite markers in the region of 11q12-13 were found to be linked to osteopetrosis in two consanguineous Bedouin kindreds. Recombination events were used to define the disease interval to an approximately 14 cM region between D11S1983 and D11S2371. A maximum LOD score of 7. 94 was obtained with D11S449 at straight theta = 0.
Non-equilibrium signal integration in hydrogels (2020)

Materials that perform complex chemical signal processing are ubiquitous in living systems. Their synthetic analogs would transform developments in biomedicine, catalysis, and many other areas. By drawing inspiration from biological signaling dynamics, we show how simple hydrogels have a previously untapped capacity for non-equilibrium chemical signal processing and integration. Using a common polyacrylic acid hydrogel, with divalent cations and acid as representative stimuli, we demonstrate the emergence of non-monotonic osmosis-driven spikes and waves of expansion/contraction, as well as traveling color waves. These distinct responses emerge from different combinations of rates and sequences of arriving stimuli. A non-equilibrium continuum theory we developed quantitatively captures the non-monotonic osmosis-driven deformation waves and determines the onset of their emergence in terms of the input parameters. These results suggest that simple hydrogels, already built into numerous systems, have a much larger sensing space than currently employed.
Photonic-crystal fiber amplifier generating 1.1-MW peak-power, spectrally narrow, diffraction-limited pulses at 1064 nm (2006)

We report a master-oscillator fiber-amplifier system featuring a large-core Yb-doped photonic crystal fiber and generating diffraction-limited, sub-ns pulses with peak power in excess of 1.1MW and negligible optical nonlinearities.
Development of a prophylactic vaccine for lung squamous cell carcinoma (2020)

Abstract High-grade bronchial dysplasia is a marker for high risk of lung squamous cell carcinoma (SCC). Cancer vaccines targeting dysplasia could prevent the progression to SCC and decrease lung cancer incidence in population at risk. In order to develop a vaccine to prevent lung SCC we need to identify antigens and epitopes within them able to elicit a potent Type I anti-tumor immune response. One caveat to develop a prophylactic vaccine targeting dysplasia is that driver mutations (neo-antigens) are not known. Many mutations appear late in lung cancer and are not shared between patients. However, upregulated non-mutated proteins are needed from the early stages of cancer to support the new proliferation requirements of the cells, are common between patients and are good candidates for a preventive vaccine. Type I CD4+ T cells (Th1) secreting interferon-gamma (IFN-g) are necessary for enhanced function of antigen presenting cells, epitope spreading and activation of cytotoxic CD8+ T cells. However, non-mutated tumor self-antigens frequently induce Type II CD4+ T cells (Th2), which secrete cytokines that inhibit the function of Th1 and CD8+ T cells. To develop a prophylactic lung cancer vaccine we have: (1) searched in public datasets genes that are upregulated in bronchial dysplasia and maintain upregulation in SCC; (2) used web based algorithms for class II epitope prediction followed by functional ELISPOT screening to identified epitopes eliciting IFN-g (Th1) and/or IL-10 (Th2) responses; (3) selected only the Th1 epitopes (excluding the Th2 epitopes) to evaluated efficacy of the vaccines in a chemically induced rodent model of SCC. Preliminary data shows that we can reduce dysplasia frequency in vaccinated mice treated with the carcinogen.
Circuit planning tool over heterogeneous networks (2011)

currently, there is no existing solution or tool to efficiently route a high-speed circuit over heterogeneous DWDM networks under multi-vendor environment, although each vendor may provide a planning tool to route a circuit within its own sub-network domain. This is mainly due to the lack of common technology for optical reachability calculation across vendor sub-networks. Each sub-network has its own proprietary parameters or formulas to calculate whether an optical path is reachable or not. To route a circuit across heterogeneous networks, we rely on the common function provided by each vendor tool to determine all reachable paths within each sub-network, i.e, the reachability matrix for each sub-network. Here reachability matrix is defined as a list of all reachable paths within the sub-network. Then we build a weighted cost graph based on the reachability matrices and apply the shortest path algorithm to find a cost efficient route. Finally we address the DWDM (Dense Wavelength Division Multiplex) sub-network selection, regenerator placement, and wavelength assignment on the selected route. The systematical methodology has been implemented in a circuit planning tool for high-speed circuits (up to 100Gbps) and used in a real heterogeneous DWDM network since 2009.
C^C* cyclometalated platinum(ii) N-heterocyclic carbene complexes with a sterically demanding β-diketonato ligand – synthesis, characterization and photophysical properties (2015)

Neutral cyclometalated platinum(ii) N-heterocyclic carbene complexes [Pt(C^C*)(O^O)] with C^C* ligands based on 1-phenyl-1,2,4-triazol-5-ylidene and 4-phenyl-1,2,4-triazol-5-ylidene, as well as acetylacetonato (O^O = acac) and 1,3-bis(2,4,6-trimethylphenyl)propan-1,3-dionato (O^O = mesacac) ancillary ligands were synthesized and characterized. All complexes are emissive at room temperature in a poly(methyl methacrylate) (PMMA) matrix with emission maxima in the blue region of the spectrum. High quantum efficiencies and short decay times were observed for all complexes with mesacac ancillary ligands. The sterically demanding mesityl groups of the mesacac ligand effectively prevent molecular stacking. The emission behavior of these emitters is in general independent of the position of the nitrogen in the backbone of the N-heterocyclic carbene (NHC) unit and a variety of substituents in 4-position of the phenyl unit, meta to the cyclometalating bond.
A Multi-Stage Hybrid Scheduler for Codebook-Based MU-MIMO System (2009)

In this paper, we propose a multi-stage hybrid scheduling scheme for codebook-based precoding systems, which provides a framework to apply different scheduling criterions at different scheduling stages for selecting user equipment (UEs). Numerical simulation results show that the proposed scheme effectively fills the performance gap between maximum carrier-to-interference (Max C/I) power ratio and Proportional Fairness (PF) methods, and provides an important means at the media access control (MAC) layer to lever between aggregate cellular throughput and geometry-specific per-user fairness, in order to meet the requirements of more precise quality of service (QoS) provision for future mobile communication systems.
Ultrasmall channel add/drop devices based on in-plane proportional hetero photonic crystals (2003)

We propose a new concept of in-plane proportional hetero photonic crystals (PCs) to obtain optimum performance of PC-based devices at multiple wavelengths. Ultrasmall channel add/drop device is successfully demonstrated based on the concept.
Pregabalin as a Pain Therapeutic: Beyond Calcium Channels (2020)

Initially developed to generate new treatments for epilepsy, gabapentin, and pregabalin ("gabapentinoids") were engineered to mimic the action of GABA and to modulate GABA metabolism. Rather than their intended pharmacological action on GABA neurotransmission, instead, they exhibit a high affinity for the α2δ-1 and α2δ-2 subunits of voltage-activated calcium channels, wherein binding of gabapentinoids inhibits cellular calcium influx and attenuates neurotransmission. Despite a lack of activity on GABA levels, gabapentin and pregabalin are effective at suppressing seizures and subsequently approved as a new class of antiepileptic therapy for partial-onset epilepsy. Through the same hypothesized molecular mechanism and by controlling neuronal hyperexcitability, gabapentinoids demonstrate clear efficacy in pain management, which has arguably been their most extensively prescribed application to date. In this review, we focus on pregabalin as a second-generation gabapentinoid widely employed in the treatment of a variety of pain conditions. We also discuss the wider functional roles of α2δ subunits and the contributions that pregabalin might play in affecting physiological and pathophysiological processes.
Video vs. text for lab instruction and concept learning (2012)

Given the popularity of YouTube and other video dissemination websites, it is reasonable to assume that the digital natives of today might prefer video-based instruction, especially for a computer lab activity in an Information Systems course. Consider the specificity of a video that shows students exactly what to click versus the potential ambiguity of text instructions. At first look, video appears to offer a significantly superior instruction format compared to text, especially for the digital native generation. However, after two years of experimenting with video instructions, we no longer make this assumption. We present an experiment that examines the differences between online video and online text instructions with respect to concept learning, task completion time, retention, and student impression. Our results indicate that video and text perform similarly, which is surprising since we are investigating a type of task and an audience that appear, on the surface, to be well-suited for video instructions. Our experiments are supported by an innovative web-based lab delivery system that provides a framework for evaluating different forms of instruction and user interface designs by collecting students' responses, impressions of the experience, and timing data.
Length of Mucin-Like Domains Enhance Cell-Ebola Virus Adhesion by Increasing Binding Probability (2020)

Abstract The Ebola virus (EBOV) hijacks normal physiological processes by apoptotic mimicry in order to be taken up by the cell it infects. The initial adhesion of the virus to the cell is based on the interaction between T-cell immunoglobulin and mucin domain protein, TIM, on the cell-surface and phosphatidylserine (PS) on the viral outer surface. Therefore, it is important to understand the interaction between EBOV/PS and TIM, with selective blocking of the interaction as a potential therapy. Recent experimental studies have shown that for TIM-dependent EBOV entry, a Mucin-like Domain (MLD) with a length of at least 120 amino acids is required, possibly due to the increase of area of the PS-coated surface sampled. We examine this hypothesis by modeling the process of TIM-PS adhesion using a coarse-grained molecular model. We find that the strength of bound PS−TIM pairs is essentially independent of TIM length. TIMs with longer MLDs have higher average binding strengths because of an increase in the probability of binding between EBOV and TIM proteins. Similarly, we find that for larger persistence length (less flexible) the average binding force decreases, again because of a reduction in the probability of binding. Statement of Significance This work studies the mechanism of TIM-dependent adhesion of the Ebola virus to a cell. Through coarse grained modeling we show that longer TIM stalks adhere more easily as they can sample a larger area, thus offering a mechanistic interpretation of an experimental finding. Better mechanistic understanding can lead to therapeutic ideas for blocking adhesion.
An automatic battery equalizer based on forward and flyback conversion for series-connected battery strings (2017)

This paper proposes an equalizer using multi-winding transformers based on forward and flyback conversion. The voltage equalization can be achieved based on forward conversion in one group and flyback conversion among different groups. Contrary to the conventional equalizers using multi-winding transformers, the proposed equalizer only requires one MOSFET for each cell and does not need additional demagnetizing circuits to reset the magnetic energy stored in the multi-winding transformers, resulting in a smaller size and lower cost. Moreover, only one pair of complementary control signals are employed for all MOSFETs, and energy can be automatically and directly delivered from any cells with high voltages to any cells with low voltages. The validity of the proposed automatic equalizer is verified through experimental results, and the balancing efficiency among cells can reach up to 89.4% over a wide range of balancing conditions.
Assessment of the scatterometry capability to detect an etch process deviation (2013)

The aim of this paper is to present a new method of in-line determination of etching tool parameters deviation during the transistor fabrication. For that, we study the possibility to use an optical metrology technique, the scatterometry, and its capability to determine quickly and accurately the temporal evolution of geometric dimensions of a periodic pattern. In this case, this optical tool can be considered as an external monitoring probe. The experiments developed in this article are based on a DOE where 20 different experiments are made, followed both by scatterometric measurements and internal etching tool probes. Comparing the two outputs, we determine the correlations between the evolution of the geometrical parameters of the pattern and the fluctuation of the internal tool parameters. We conclude that the use of a scatterometer following the evolution of the geometrical parameters of a pattern during an etching process is also a good tool to in-line anticipate the drift of the etching parameters.
A Delay Locked Loop Synchronization Scheme for High Frequency Multiphase Hysteretic DC-DC Converters (2007)

This paper reports a delay locked loop (DLL) based hysteretic controller for high-frequency multiphase buck DC-DC converters. The DLL control loop employs the switching frequency from a hysteretic comparator to automatically synchronize the remaining phases. A dedicated duty cycle control loop is used to enable current sharing and ripple cancellation. We demonstrate a 25-70MHz 4-phase converter with fast hysteretic control and output conversion range of 17%-80% while achieving a peak efficiency of 83% and peak-to-peak ripple within 10% in standard 0.6μm 5V CMOS process.
Modeling and Simulation of a Surface Micromachined Knudsen Pump (2006)

This paper presents a simulation model for a silicon micromachined Knudsen pump that combines analytical and numerical methods. It involves numerical modeling of the thermal response, followed by an analytical estimate of the pumping using Kennard's model. The loss of performance resulting from gas diffusion though walls of the pump is specifically addressed. The results are subsequently validated against the previously reported experimental measurements of a single-stage Knudsen pump. This device, which has a total footprint of less than 1500 × 2000 μm2, has multiple narrow channels connecting two cavities, one of which is heated. This cavity is further connected through a wide channel to a third cavity, which remains at ambient. The simulation model for this device predicts a vacuum pressure of 0.47 atm. at an input power of 97.6 mW, which deviates less than 20% from the experimentally observed data. Finally, the paper extends the concept of single stage pumping to a multi-stage pump. While Kennard's model is used for modeling the first stage, the simulation for subsequent stages, which are characterized by a relatively high Knudsen number, uses an empirically corrected
Workshop on Numerical Analysis of Human and Surrogate Response to Accelerative Loading (2014)

Abstract : The Warrior Injury Assessment Manikin (WIAMan) Project Management Office in conjunction with the Blast Protection for Platforms and Personnel Institute hosted the Workshop on Numerical Analysis of Human and Surrogate Response to Accelerative Loading on January 7-9, 2014, at the U.S. Army Research Laboratory. This workshop addressed the numerical analysis tools available to simulate and investigate human and human surrogate response to accelerative loading induced to vehicle occupants from blast, with emphasis on underbody blast. The workshop discussion focused on evaluating the maturity of current modeling and associated experimental efforts, establishing what can be done with current tools, and what additional research is needed to advance our understanding of predicting injuries under blast loading environment. There were two keynote presentations: Dr. Scott Wagner of the Walter Reed Spine Research Laboratory gave a presentation titled A Clinical Overview of Wartime Spinal Injuries, and Mr. Michael Tegtmeyer and Dr. Warren Hardy gave a presentation titled Experimental Simulation of the Under-body Blast Environment. Dr. Wagner's presentation provided insight into current efforts to repair Soldier spine injuries from accelerative loading events in Iraq and Afghanistan. Tegtmeyer and Hardy presented the research they have led under the WIAMan program to induce accelerative loading conditions to Hybrid 3 anthropomorphic test devices as well as cadaveric specimens. The following report documents the materials presented at the workshop, summarizes the discussion and major findings, and offers some recommendations that are suitable for guiding the future of research in this area.
Single-Chip Wavelength Conversion Using a Photocurrent-Driven EAM Integrated With a Widely Tunable Sampled-Grating DBR Laser (2004)

Tunable photocurrent-driven wavelength converters using widely tunable sampled grating distributed Bragg reflector lasers, electroabsorption modulators, semiconductor optical amplifiers, and an optically preamplified receiver have been fabricated and tested. Dynamic wavelength conversion has been achieved over 40 nm with optical bandwidths up to 10 GHz.
Helios expressing regulatory T cells are correlated with decreased IL-2 producing CD8 T cells and antibody diversity in Mozambican individuals living chronically with HIV-1 (2022)

Among Mozambican people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals. Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C. Elevation in the proportion of Helios<sup>+</sup>Tregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function.
A Two-stage Segmentation Algorithm Using Robust Anisotropic Region Growing. (2003)

Region growing is a widely used image-segmentation techniques. However, oversegmentation and dependency on the starting point (seed) pose difficulties. We propose au algorithm using the robust homogeneous criteria consisting of (1) intensity and (2) no edge in-between criterion. The region is grown into pixels that satisfy both criteria. The intensity criterion ensures that no abrupt. change occurs in the image intensity inside a region. It is calculated based on the local average image intensity after rejecting outliers. The no edge in-between criterion prevents the growing across the boundaries. The segmentation algorithm consists of a (1) coarse and a (2) fine scaled segmentation. In the first stage, large regions are segmented, which include both uniform regions and regions containing a small area of intensity fluctuation. In the second stage, the remaining regions are segmented. Our experiments showed good segmentation results for both gray-scale and color images.
Overexpression of the Small RNA PA0805.1 in Pseudomonas aeruginosa Modulates the Expression of a Large Set of Genes and Proteins, Resulting in Altered Motility, Cytotoxicity, and Tobramycin Resistance (2020)

P. aeruginosa is an opportunistic pathogen of humans. With roughly 10% of its genes encoding transcriptional regulators, and hundreds of small noncoding RNAs (sRNAs) interspersed throughout the genome, P. aeruginosa is able to fine-tune its response to adapt and survive in the host and resist antimicrobial agents. Understanding mechanisms of genetic regulation is therefore crucial to combat pathogenesis. The previously uncharacterized sRNA PA0805.1 was overexpressed in P. aeruginosa strain PAO1, resulting in decreased motility, increased adherence, cytotoxicity, and tobramycin resistance. In contrast, a ΔPA0805.1 deletion mutant had increased susceptibility to tobramycin under swarming conditions. Omic approaches uncovered 1,121 transcriptomic and 258 proteomic changes in the overexpression strain compared with the empty-vector strain, which included 106 regulatory factors. Downstream of these regulators were upregulated adherence factors, multidrug efflux systems, and virulence factors in both transcriptomics and proteomics. This study provides insights into the role of the sRNA PA0805.1 in modulating bacterial adaptations.