gebhart/patrepeval huggingface dataset:
O2‐12‐02: TOR AND NO AS REGULATORS OF BRAIN VASCULAR FUNCTION IN A MOUSE MODEL OF AD (2014)

Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease and reduces amyloid-beta accumulation in (h)APP transgenic mice modeling AD. To investigate the effects of reduction of mTOR activity by rapamycin on hemodynamic, vascular and metabolic functions in brains of hAPP mice we used multi-metric imaging systems (MRI and PET). Our results demonstrate that hAPP mice have significantly reduced cerebral blood flow (CBF) and vascular density that is not related to metabolic changes, especially in areas that have a prominent role in learning and memory. Chronic rapamycin restored vascular density and CBF, reduced vascular amyloidosis and microhemorrhages, decreased amyloid burden, and relieved AD-like cognitive deficits in hAPP mice. Reduction of mTOR activity also restored CBF in aged rats and in a model of atherosclerosis, suggesting that the mechanisms by which attenuation of mTOR activity restores CBF are common to different models of vascular disease, and to brain aging. In vivo multiphoton imaging of brain vessels revealed that rapamycin induced an increase in nitric oxide (NO) in vascular endothelium that was followed by vasodilation. Administration of an inhibitor of NO synthases reversed the protective effects of rapamycin on brain blood flow and vascular density, indicating that rapamycin preserves vascular integrity and CBF in AD mouse brains through NO signaling. Our data suggest that the preservation of vascular density and brain blood flow may be key to the maintenance of cognitive function in the hAPP mouse model of AD. Rapamycin, an FDA-approved drug that is already used in the clinic, may have promise as a therapy for AD and possibly for age-associated brain diseases beyond AD alone.
Coarse-Grained Nonlinear System Identification (2020)

We introduce Coarse-Grained Nonlinear Dynamics, an efficient and universal parameterization of nonlinear system dynamics based on the Volterra series expansion. These models require a number of parameters only quasilinear in the system's memory regardless of the order at which the Volterra expansion is truncated; this is a superpolynomial reduction in the number of parameters as the order becomes large. This efficient parameterization is achieved by coarse-graining parts of the system dynamics that depend on the product of temporally distant input samples; this is conceptually similar to the coarse-graining that the fast multipole method uses to achieve $\mathcal{O}(n)$ simulation of n-body dynamics. Our efficient parameterization of nonlinear dynamics can be used for regularization, leading to Coarse-Grained Nonlinear System Identification, a technique which requires very little experimental data to identify accurate nonlinear dynamic models. We demonstrate the properties of this approach on a simple synthetic problem. We also demonstrate this approach experimentally, showing that it identifies an accurate model of the nonlinear voltage to luminosity dynamics of a tungsten filament with less than a second of experimental data.
Adaptive Decentralized MAC for Event-Triggered Networked Control Systems (2016)

Control over shared communication networks is a key challenge in design and analysis of cyber-physical systems. The quality of control in such systems might be degraded due to the congestion while accessing the scarce communication resources. In this paper, we consider a multiple-loop networked control system (NCS), where all control loops share a communication network. Medium Access Control (MAC) is performed in contention-based fashion using a multi-channel slotted ALOHA protocol, where each control loop decides locally whether to attempt a transmission based on some error thresholds. We further introduce a local event-based resource-aware scheduling design with an adaptive choice of the error thresholds for a transmission. This leads to a hybrid channel access mechanism where the control loops are deterministically categorized into two sets of eligible and ineligible sub-systems for transmission in an event-based fashion, before a random process to select the available channels. In addition, employing the introduced policy, we show the stability of the resulting NCS in terms of Lyapunov stability in probability. We illustrate numerically the efficiency of our proposed approach in terms of reducing the average networked-induced error variance, and show the superiority of the adaptive event-based scheduler compared to the scheduling design with non-adaptive thresholds.
Quality control of apheresis platelets: a multicentre study to evaluate factors that can influence pH measurement (2017)

The strong intradonor correlation of pH measurements and the association between donor characteristics and pH results suggest that donor factors play a role in the quality of platelets.
Machine Learning Models Identify Inhibitors of SARS-CoV-2 (2020)

Abstract With the ongoing SARS-CoV-2 pandemic there is an urgent need for the discovery of a treatment for the coronavirus disease (COVID-19). Drug repurposing is one of the most rapid strategies for addressing this need and numerous compounds have been selected for in vitro testing by several groups already. These have led to a growing database of molecules with in vitro activity against the virus. Machine learning models can assist drug discovery through prediction of the best compounds based on previously published data. Herein we have implemented several machine learning methods to develop predictive models from recent SARS-CoV-2 in vitro inhibition data and used them to prioritize additional FDA approved compounds for in vitro testing selected from our in-house compound library. From the compounds predicted with a Bayesian machine learning model, CPI1062 and CPI1155 showed antiviral activity in HeLa-ACE2 cell-based assays and represent potential repurposing opportunities for COVID-19. This approach can be greatly expanded to exhaustively virtually screen available molecules with predicted activity against this virus as well as a prioritization tool for SARS-CoV-2 antiviral drug discovery programs. The very latest model for SARS-CoV-2 is available at www.assaycentral.org .
Assessing Technical and Economic Feasibility of Complete Bioremediation for Soils Chronically Polluted with Petroleum Hydrocarbons (2017)

Petroleum hydrocarbons are highly persistent in the environment and represent a significant risk for humans, biodiversity, and the ecosystems. Frequently, hydrocarbon-contaminated sites remain polluted for decades due to a lack of proper decontamination treatments. Although bioremediation techniques have gained attention for being environmentally friendly, cost-effective and applicable in situ, their application is still limited. Each polluted soil has particularities, therefore, the bioremediation approach for a contaminated site is unique. Bioremediation cost studies are usually based on hypothetical assumptions rather than technical or experimental data. The research aims of this study were to clean-up chronically hydrocarbon-polluted soils using aerobic and anaerobic bioremediation techniques and to carry out an economic evaluation of the most promising bioremediation treatments. The results showed that aerobic biostimulation with vermicompost and aerobic bioaugmentation plus air venting were the most effective treatments, degrading 78% and 73% of total petroleum hydrocarbons (TPH) in chronically hydrocarbonpolluted soils after six weeks, respectively. In contrast, no significant degradation of hydrocarbon was observed by anaerobic biostimulation treatments with lactate and acetate. An economic evaluation of the aerobic treatments were carried out. This analysis revealed that the cost of treating one cubic meter of soil by biostimulation is US$ 59, while bioaugmentation costs US$77. This study provides a clear structure of costs for both aerobic bioremediation approaches based on projections made from these lab-scale incubations. These values represent the first step towards a better understanding of the feasibility of such treatments at larger scales, which is crucial to move on industrial bioremediation of soils chronically polluted with petroleum hydrocarbons.
Shiga Toxin 2–Specific but Not Shiga Toxin 1–Specific Human Monoclonal Antibody Protects Piglets Challenged with EnterohemorrhagicEscherichia coliProducing Shiga Toxin 1 and Shiga Toxin 2 (2010)

Escherichia coli strains that produce Shiga toxin 2 (Stx2) are isolated from hemolytic-uremic syndrome (HUS) cases more frequently than are strains that produce both Shiga toxin 1 (Stx1) and Stx2, whereas strains that produce only Stx1 are rarely isolated from HUS cases. Studies have implicated Stx2 as the sole contributor to acute kidney failure and other systemic complications in humans. The aim of the present study was to determine whether Stx2-specific antibody would be as effective against Shiga toxin-producing Escherichia coli (STEC) strains that produce both Stx1 and Stx2 as it is against strains that produce only Stx2, compared with Stx1-specific antibody. We found that Stx2-specific and Stx1-specific antibodies protected 100% and 0% of piglets, respectively, against oral challenge with a Stx1- and Stx2-producing STEC strain. We conclude that Stx2-specific antibody is sufficient to protect piglets, and possibly humans, against STEC strains that produce both toxins.
PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity (2010)

The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.
Treatment of Corneal Diseases or Refractive Errors with Laser Processing (2004)

Using the ArF excimer laser to alter corneal tissue is now applicable to the field of ophthalmology. For the treatment of corneal scarring or corneal dystrophy, phototherapeutic keratectomy (PTK) may be performed, and photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK) is useful to treat refractive errors such as myopia, hyperopia, or astigmatism. A videokeratoscope and wavefront sensor are useful for the evaluation of corneal topography and the quality of vision following refractive surgery.
Continuity equation and the Fokker–Planck approach (2014)

In the previous chapter, the notion of a homogeneous population of neurons was introduced. Neurons within the population can be independent, fully connected, or randomly connected, but they should all have identical, or at least similar, parameters and all neurons should receive similar input. For such a homogeneous population of neurons, it is possible to predict the population activity in the stationary state of asynchronous firing (Section 12.4). While the arguments we made in the previous chapter are general and do not rely on any specific neuron model, they are unfortunately restricted to the stationary state.
Pangenomic analysis reveals plant NAD + manipulation as an important virulence activity of bacterial pathogen effectors (2023)

Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) has emerged as a key component in prokaryotic and eukaryotic immune systems. The recent discovery that Toll/interleukin-1 receptor (TIR) proteins function as NAD<sup>+</sup> hydrolases (NADase) links NAD<sup>+</sup>-derived small molecules with immune signaling. We investigated pathogen manipulation of host NAD<sup>+</sup> metabolism as a virulence strategy. Using the pangenome of the model bacterial pathogen <i>Pseudomonas syringae</i>, we conducted a structure-based similarity search from 35,000 orthogroups for type III effectors (T3Es) with potential NADase activity. Thirteen T3Es, including five newly identified candidates, were identified that possess domain(s) characteristic of seven NAD<sup>+</sup>-hydrolyzing enzyme families. Most <i>Pseudomonas syringae</i> strains that depend on the type III secretion system to cause disease, encode at least one NAD<sup>+</sup>-manipulating T3E, and many have several. We experimentally confirmed the type III-dependent secretion of a novel T3E, named HopBY, which shows structural similarity to both TIR and adenosine diphosphate ribose (ADPR) cyclase. Homologs of HopBY were predicted to be type VI effectors in diverse bacterial species, indicating potential recruitment of this activity by microbial proteins secreted during various interspecies interactions. HopBY efficiently hydrolyzes NAD<sup>+</sup> and specifically produces 2'cADPR, which can also be produced by TIR immune receptors of plants and by other bacteria. Intriguingly, this effector promoted bacterial virulence, indicating that 2'cADPR may not be the signaling molecule that directly initiates immunity. This study highlights a host-pathogen battleground centered around NAD<sup>+</sup> metabolism and provides insight into the NAD<sup>+</sup>-derived molecules involved in plant immunity.
Effects of Aged Black Garlic Extracts on the Tight Junction Permeability and Cell Invasion in Human Gastric Cancer Cells (2010)

본 연구에서는 흑마늘 열수 추출물(ABG)의 암세포 전이억제 효능을 검정하였다. AGS AGS 인체위암세포의 이동성과 침윤성을 억제하였으며, 이는 TER의 증가와 연관성이 있었다. 또한 ABG에 의한 AGS 위암세포의 침윤성 억제는 TIMPs 발현 증가에 의한 MMPs의 발현 및 활성 저하에 의한 것임을 알 수 있었다. 아울러 AGS 위암세포에서 과발현을 나타내는 TJ 단백질인 claudins의 발현 저하 등이 ABG의 항전이 효과에 연관되어 있음을 알 수 있었다. 이상의 결과는 흑마늘 열수 추출물이 단순한 암세포의 증식억제를 통한 암예방 및 항암활성 뿐만 아니라 암세포의 전이 또한 효과적으로 억제할 수 있음을 보여주며, 이와 연관된 보다 구체적인 분자세포생물학적 접근 및 in vivo 연구의 필요성이 요구됨을 의미한다. Garlic (Allium sativum) has been well-known as a folk remedy for a variety of ailments since ancient times, and it is well documented that enhanced garlic consumption leads to a decrease in incidences of cancer. Tight junctions (TJs) are critical structures for the maintenance of cellular polarity, acting as paracellular permeability barriers and playing an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. Matrix metalloproteinases (MMPs) have been implicated as possible mediators of invasiveness and metastasis in some cancers. In this study, we investigated the potential effects of water extract of aged black garlic (ABG) on the correlation between tightening of TJs and anti-invasive activity in human gastric carcinoma AGS cells. The inhibitory effects of ABG on cell motility and invasiveness were found to be associated with increased tightness of TJs, which was demonstrated by an increase in transepithelial electrical resistance. Additionally, the activities of MMP-2 and -9 in AGS cells were inhibited by treatment with ABG, and this was also correlated with a decrease in the expression of their mRNA and proteins. Furthermore, RT-PCR and immunoblotting results indicated that ABG repressed the levels of the claudin proteins, major components of TJs that play a key role in the control and selectivity of paracellular transport. In conclusion, these results suggest that ABG treatment may inhibit tumor metastasis and invasion, and therefore may act as a dietary source to decrease the risk of developing cancer.
A high power density DC-DC converter for distributed PV architectures (2013)

In order to maximize the solar energy harvesting capabilities, power converters for photovoltaic (PV) systems have to be designed for high efficiency, accurate maximum power point tracking (MPPT) and voltage/current performance. When many converters are used in distributed PV systems, power density also becomes an important factor since it allows for simpler system integration. In this paper, a high power density string level MPPT DC-DC converter suitable for distributed medium to large scale PV installations is presented. A simple partial power processing topology implemented exclusively with silicon carbide devices provides high efficiency and high power density. A 3.5kW, 100 kHz converter is designed and tested to verify the proposed methods.
<title>Fiber optic system for spatially averaged temperature measurements</title> (1992)

Using an optical fiber whose transmission loss depends in a linear way on temperature, a thermometric system can be designed that will allow direct measurement of the temperature averaged along the length of the fiber. This paper describes such a system used to test the feasibility of using rare earth-doped fibers in practical distributed measurements of average temperature.
Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2) (2022)

Myovant Sciences.
Application-Specific Processing on a General-Purpose Core via Transparent Instruction Set Customization (2005)

Application-specific instruction set extensions are an effective way of improving the performance of processors. Critical computation subgraphs can be accelerated by collapsing them into new instructions that are executed on specialized function units. Collapsing the subgraphs simultaneously reduces the length of computation as well as the number of intermediate results stored in the register file. The main problem with this approach is that a new processor must be generated for each application domain. While new instructions can be designed automatically, there is a substantial amount of engineering cost incurred to verify and to implement the final custom processor. In this work, we propose a strategy to transparent customization of the core computation capabilities of the processor without changing its instruction set. A congurable array of function units is added to the baseline processor that enables the acceleration of a wide range of data flow subgraphs. To exploit the array, the microarchitecture performs subgraph identification at run-time, replacing them with new microcode instructions to configure and utilize the array. We compare the effectiveness of replacing subgraphs in the fill unit of a trace cache versus using a translation table during decode, and evaluate the tradeoffs between static and dynamic identification of subgraphs for instruction set customization.
Relationship between the activity of mitochondrial respiratory chain complexes and feed efficiency in fat-tailed Ghezel lambs1 (2011)

This study was conducted to investigate relationships between mitochondrial respiratory chain complex activities, feed efficiency, and carcass traits in sheep. A group of Ghezel male lambs sired by a single ram were randomly allotted to individual pens. The lambs were fed ad libitum with a fattening diet containing 30% roughage (corn silage and alfalfa hay) and 70% concentrate for 70 d to individually phenotype each lamb for feed conversion ratio (FCR), adjusted FCR (aFCR), and residual feed intake (RFI). The lambs were then humanely killed and the liver, abdominal fat, pelvic fat, cardiac fat, warm carcass weight, and cold carcass weight, as well as the cross-sectional area of the LM and the fat depth over the 12th rib, were determined. A portion of LM was obtained to determine mitochondrial protein and respiratory chain complex activities (complexes I to V). Statistical analysis was carried out based on lambs exhibiting high and low RFI (n = 8), FCR (n = 8), or aFCR (n = 8) phenotypes. The lambs exhibiting the high-RFI phenotype consumed 110 g more feed daily (P < 0.05) than did the phenotype exhibiting low RFI, with no difference in ADG. Conversely, there was no difference in feed intake between the low- or high-FCR groups, but sheep exhibiting the low-FCR phenotype gained 70 g more (P < 0.05) per day compared with those exhibiting the high-FCR phenotype. It was determined that all 5 respiratory chain complex activities were greater (P < 0.05) in sheep exhibiting the low-RFI phenotype compared with those exhibiting the high-RFI phenotype, with significant (P < 0.001) negative correlation coefficients between RFI and respiratory chain complex activity. When efficiency was assessed using FCR, only activities of respiratory chain complexes III, IV, and V were less (P < 0.05) in the low-FCR phenotype compared with the high-FCR phenotype, and there were no differences (P > 0.1) in respiratory chain complex activities between groups when FCR was adjusted for metabolic BW (aFCR). There were no differences (P > 0.1) in carcass traits among any of the feed efficiency phenotypes. The results suggest that the inclusion of respiratory chain complex activities in breeding programs may be helpful in selecting for sheep exhibiting the low-RFI phenotype.
Ceramic synthetic substrates using solid freeform fabrication (2003)

Three-dimensional (3-D) printing techniques were used to create lost molds for advanced inhomogeneous materials made of ceramics. The utility of this process is the ability to manipulate low-loss materials, such as alumina illustrated here, into precise, fine features as periodic macroscopic inclusions in a larger host material or air. Three periodic structures were formed using solid freeform (SFF) fabrication techniques; a two-dimensional (2-D) all-dielectric electromagnetic bandgap (EBG) substrate, a 2-D metallo-dielectric substrate filter, and a 3-D woodpile EBG structure. The design of these structures is discussed and the fabricational steps are presented in detail. This process has been utilized to develop a simple two-pole filter embedded in a substrate at 10 GHz, a single resonator at 30 GHz, and a 3-D bandgap structure from 88 to 115 GHz. The wide range of features and structures that can be accurately fabricated are highlighted.
Figures S13-S19 from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERα<sup>WT</sup> and ERα<sup>MUT</sup> Breast Cancer (2023)

&lt;p&gt;H3B-5942 exhibits dose-dependent inhibition of ER target genes and shows significant efficacy ER Wt and mutant in vivo models&lt;/p&gt;
Sequential Gene Silencing Using Wavelength‐Selective Caged Morpholino Oligonucleotides (2014)

Abstract Spectrally differentiated caged morpholino oligonucleotides (cMOs) and wavelength‐selective illumination have been used to sequentially inactivate organismal gene function. The efficacy of these reverse‐genetic chemical probes has been demonstrated in zebrafish embryos, and these reagents have been employed to examine the mechanisms of mesoderm patterning.
Targeting Alpha Toxin and ClfA with a Multimechanistic Monoclonal-Antibody-Based Approach for Prophylaxis of Serious Staphylococcus aureus Disease (2016)

Alternative strategies to broad-spectrum antibiotics are required to combat the antibiotic resistance epidemic. Previous attempts at active or passive immunization against Staphylococcus aureus targeting single antigens have failed in clinical trials despite positive preclinical data. To provide broad disease and isolate coverage, an effective immunization strategy likely must target multiple virulence mechanisms of the pathogen. Herein, we tested a multimechanistic MAb combination targeting alpha toxin (AT) and clumping factor A (ClfA) that neutralizes AT-mediated cytotoxicity, blocks fibrinogen binding by ClfA, prevents bacterial agglutination, targets the bacteria for opsonophagocytic killing, and provides broad isolate coverage in a lethal-bacteremia model. Although each MAb alone was effective in bacteremia against some individual isolates, the MAb combination provided improved protection against other isolates. These results illustrate the importance of targeting multiple virulence mechanisms and highlight the potential for an MAb combination targeting AT and ClfA to effectively prevent S. aureus disease.