gebhart/patrepeval huggingface dataset:
Identification of PTCH1 requirement for influenza virus using random homozygous gene perturbation. (2009)

Influenza infection remains a leading cause of infectious disease-mediated morbidity and mortality. Accumulating evidence indicates that most variants of seasonal and pandemic influenza have developed resistance to conventional therapies. Such information has spawned new interest in identifying novel approaches to target influenza. Our laboratories have been developing a new strategy of Host-Oriented Therapeutics, which seeks to target host molecules in a safe and effective manner that prevents the virus from causing disease. Using an improved discovery technology, Random Homozygous Gene Perturbation (RHGP), we identified the PTCH1 protein as an essential host target that critically controls influenza virus infection. We further demonstrated that targeted intervention against PTCH1 using antibodies or siRNA decreases influenza infection. Finally, we demonstrated the involvement of PTCH1 in influenza infection outside of the laboratory by showing that genetic variations of PTCH1 relate to decreased disease morbidity in the field. Altogether, these findings have important implications for the development of novel, host-directed therapeutics to improve influenza disease management.
A finite-set model-based predictive battery thermal management in connected and automated hybrid electric vehicles (2018)

The connected and automated hybrid electric vehicles (CAHEVs) have the potential to improve safety by mitigating traffic accidents. A crucial problem of the CAHEVs is that the Lithium-ion batteries are highly temperature-sensitive and may be premature aging at high working temperatures. Consequently, an effective and efficient battery thermal management (BTM) system is required with the minimum possible cooling energy consumption. To achieve the multiple objectives, a finite-set model-based (FSMB) predictive control strategy for the BTM in a CAHEV is presented, in which an improved cost function is proposed for better performances. Based on the predictive model of battery temperatures, the optimum cooling approach is determined with consideration of the future road information and battery charge/discharge power. The hardware-in-the-loop (HIL) test based on a Toyota Prius HEV model and the UDDS road cycle is conducted, and the results demonstrate the effectiveness of the proposed BTM strategy in both temperature control and energy saving.
Scalable MOSFET Short-channel Charge Model for All Regions (2006)

A scalable short-channel MOSFET charge model valid for all bias regions is presented. As the device length is reduced, long-channel intrinsic charge model cannot predict the short-channel dynamic behavior correctly. The extrinsic capacitances, such as overlap capacitance and bias-dependent fringing capacitance, must be included in the charge model as they are comparable to the intrinsic capacitance at short-channel dimensions. In order to ensure model scalability over geometry, short-channel effects must be included in the core charge model. This paper extends the short-channel models, such as bulk-charge sharing and potential-barrier lowering, for charge modeling that is valid for all regions. The model is verified by comparison with numerical simulations for three short-channel devices, 0.5, 0.25 and 0.09 µm. It is shown that the model accurately scales with the short-channel capacitances.
Initial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC). (2023)

5515 Background: LGSOC is a RAS/MAPK pathway driven cancer that constitutes ≤10% of ovarian cancer. There are no FDA approved treatments specifically for LGSOC. Avutometinib is a novel small molecule RAF/MEK clamp. Focal adhesion kinase (FAK) activation is a resistance mechanism to RAF/MEK inhibition, and defactinib, a small molecule inhibitor of FAK, has shown synergistic antitumor activity with avutometinib in preclinical models. The combination of avutometinib and defactinib has demonstrated a high rate of confirmed and durable responses (overall response rate [ORR] = 46%) in recurrent LGSOC (Banerjee S, ESMO 2021). Methods: A registration-directed phase 2, adaptive, multicenter, randomized study was initiated to evaluate avutometinib ± defactinib in patients with KRAS mutant (mt) and KRAS wild-type (wt) recurrent LGSOC to identify the optimal regimen based on confirmed ORR by blinded independent central review (Part A) and determine the efficacy of the optimal regimen (Part B) (NCT04625270). Pts were randomized to avutometinib 4 mg orally (PO), twice weekly, 3 weeks on, 1 week off (mono) or avutometinib 3.2 mg PO twice weekly + defactinib 200 mg PO BID 3 weeks on, 1 week off (combo). Key inclusion criteria include histologically confirmed recurrent LGSOC, known KRAS status and prior systemic therapy with platinum chemotherapy. Unlimited additional prior lines, including prior MEK inhibitor, were permitted. Here we present efficacy results from Part A (evaluable patients, N=59) and safety data from all pts enrolled (N=121). Results: In Part A, the median number of prior systemic regimens was 3 for mono, and 4 for combo. In evaluable patients, a confirmed ORR of 7% (2/30) was observed for mono (13% KRAS mt, 0% KRAS wt), and an ORR of 28% (8/29) was observed for combo (27% KRAS mt, 29% KRAS wt). Two of 4 patients previously treated with a MEK inhibitor showed a confirmed partial response (PR) on the combination arm. A high disease control rate (PR or SD ≥ 8 weeks) was observed for both mono (90%) and combo (93%). The majority of treatment related adverse events (AEs, any grade) for combo (N=57) were mild to moderate. The most common Grade ≥3 AEs for combo were blood CPK increase (15.8%), fatigue (5.3%), diarrhea (3.5%), dermatitis acneiform (1.8%), and rash (1.8%). A similar AE profile was observed for mono (N=64). Most AEs were manageable/reversible. On the combo arm, 90.6% (±20%) of planned doses were given and 9% (n=5) of pts discontinued due to AEs [asymptomatic elevated blood CPK (n=3) and fatigue (n=2)]. Conclusions: The interim data support avutometinib + defactinib as an active go-forward regimen in heavily-pretreated recurrent LGSOC, regardless of KRAS status. No new safety signals were observed, and most AEs were mild to moderate. Enrollment continues in Part B for the combination of avutometinib and defactinib. Clinical trial information: NCT04625270 .
The Efficiency of the Metal Catalysts in the Nucleophilic Substitution of Alcohols is Dependent on the Nucleophile and Not on the Electrophile (2013)

In this study, we investigate the effect of the electrophiles and the nucleophiles for eight catalysts in the catalytic SN 1 type substitution of alcohols with different degree of activation by sulfur-, carbon-, oxygen-, and nitrogen-centered nucleophiles. The catalysts do not show any general variance in efficiency or selectivity with respect to the alcohols and follow the trend of alcohol reactivity. However, when it comes to the nucleophile, the eight catalysts show general and specific variances in the efficiency and selectivity to perform the desired substitution. Interestingly, the selectivity of the alcohols to produce the desired substitution products was found to be independent of the electrophilicity of the generated carbocations but highly dependent on the ease of formation of the cation. Catalysts based on iron(III), bismuth(III), and gold(III) show higher conversions for S-, C-, and N-centered nucleophiles, and Bi(III) was the most efficient catalyst in all combinations. Catalysts based on rhenium(I) or rhenium(VII), palladium(II), and lanthanum(III) were the most efficient in performing the nucleophilic substitution on the various alcohols with the O-centered nucleophiles. These catalysts generate the symmetrical ether as a by-product from the reactions of S-, C-, and N-centered nucleophiles as well, resulting in lower chemoselectivity.
Preliminary Intelligibility Tests of a Monaural Speech Segregation System (2008)

Human listeners are able to understand speech in the presence of a noisy background. How to simulate this perceptual ability remains a great challenge. This paper describes a preliminary evaluation of intelligibility of the output of a monaural speech segregation system. The system performs speech segregation in two stages. The first stage segregates voiced speech using supervised learning of harmonic features, and the second stage segregates unvoiced speech by subtracting noise energy that is estimated from voiced intervals and onset/offset based segmentation. Objective evaluation in terms of the match to ideal binary time-frequency masks shows substantial improvements. Tests with human subjects indicate that the system improves intelligibility for young listeners when the input SNR is very low, but does not aid elderly listeners. This preliminary evaluation identifies aspects of the system that should be improved in order to produce consistent improvement in intelligibility in noisy environments. Index Terms: speech segregation, computational auditory scene analysis, ideal binary mask, supervised learning, onset/offset
Evaluation of a new injury model to study medial collateral ligament healing: Primary repair versus nonoperative treatment (1991)

The medial collateral ligament (MCL) of the rabbit left hindlimb was ruptured by a rod placed beneath it, resulting in a "mop-end" tear of the ligament substance with simultaneous injury to the insertion sites. Using this model, we compared primary ligament repair and nonoperative treatment using biomechanical and histologic techniques at time zero, 10 days, and 6 and 12 weeks postoperatively. Biomechanical evaluation included measurement of varus-valgus (V-V) knee rotation, in situ load on the MCL, and tensile testing of the femur-MCL-tibia complex (FMTC). The V-V rotation of all experimental knees decreased over time. At 12 weeks, V-V rotation of experimental knees was still 1.3 times larger than that of controls. Primary repair initially decreased V-V rotation, but at 6 and 12 weeks there was no statistical difference between operated and nonoperated knees. The in situ load on the MCL followed the same trends. There was no significant effect of MCL repair on any of the tensile properties. However, postoperative healing time significantly improved the FMTC structural properties in both experimental groups. Failure modes of the FMTCs and histologic sections of the ligament insertion sites indicated that after injury the ligament insertion to bone recovered more slowly than the ligament substance. Tensile testing of the FMTC showed that even at 12 weeks postoperatively the mechanical properties of the healed ligament material remained significantly different from those of the controls.
A State-Based Sensitivity Analysis for Distinguishing the Global Importance of Predictor Variables in Artificial Neural Networks (2016)

Artificial neural networks (ANNs) are powerful empirical approaches used to model databases with a high degree of accuracy. Despite their recognition as universal approximators, many practitioners are skeptical about adopting their routine usage due to lack of model transparency. To improve the clarity of model prediction and correct the apparent lack of comprehension, researchers have utilized a variety of methodologies to extract the underlying variable relationships within ANNs, such as sensitivity analysis (SA). The theoretical basis of local SA (that predictors are independent and inputs other than variable of interest remain “fixed” at predefined values) is challenged in global SA, where, in addition to altering the attribute of interest, the remaining predictors are varied concurrently across their respective ranges. Here, a regression-based global methodology, state-based sensitivity analysis (SBSA), is proposed for measuring the importance of predictor variables upon a modeled response within ANNs. SBSA was applied to network models of a synthetic database having a defined structure and exhibiting multicollinearity. SBSA achieved the most accurate portrayal of predictor-response relationships (compared to local SA and Connected Weights Analysis), closely approximating the actual variability of the modeled system. From this, it is anticipated that skepticisms concerning the delineation of predictor influences and their uncertainty domains upon a modeled output within ANNs will be curtailed.
Novel approaches, including systems biology, to HIV vaccine research and development: Report from a Global HIV Vaccine Enterprise Working Group (2010)

Abstract The Global HIV Vaccine Enterprise convened a two-day workshop on August 10-11 2009, at the Fred Hutchison Cancer Research Center offices in Seattle, WA, to discuss the application of novel approaches,including systems biology, to HIV vaccine research and development. The goals of this Working Group were to identify key scientific issues and opportunities that have emerged since the Enterprise Scientific Strategic Plan1 was published in 2005, and to make recommendations to Enterprise stakeholders.
A 19Gb/s RX for VSR-C2C Links with Clock-Less DFE and High-BW CDR Based on Master-Slave ILOs in 14nm CMOS (2018)

A receiver with a reference-less clocking architecture for high-density VSR-C2C links is described. It features clockless DFE and a high-bandwidth CDR based on master-slave ILOs for phase generation/rotation. The receiver is implemented in 14nm CMOS and characterized at 19Gb/s. It achieves a power-efficiency of 2.9pJ/b while recovering error-free data (BER<; 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> ) across a 15dB loss channel. The jitter tolerance BW of the receiver is 250MHz and the INL of the ILO-based phase-rotator (32Step/ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">UI</sub> ) is <;1-LSB.
ChemInform Abstract: Synthesis of 7‐Deaza‐8‐bromo Cyclic Adenosine 5′‐Diphosphate Ribose ( VI): The First Hydrolysis Resistant Antagonist at the cADPR Receptor. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A 1.5 V 2.4/2.9 mW 79/50 dB DR ΣΔ modulator for GSM/WCDMA in a 0.13 μm digital process (2003)

A 2/sup nd/ order multi-level /spl Sigma//spl Delta/ A/D converter for low-power multi-standard wireless receivers, in a single-poly 0.13 /spl mu/m digital CMOS process, has 79/50 dB dynamic range for GSM/WCDMA. The 0.2 mm/sup 2/ chip consumes 2.4/2.9 mW at 1.5 V.
Small Molecule-Guided Thermoresponsive Supramolecular Assemblies (2012)

Small organic molecules with strong intermolecular interactions have a wide range of desirable optical and electronic properties and rich phase behaviors. Incorporating them into block copolymer (BCP)-based supramolecules opens new routes to generate functional responsive materials. Using oligothiophene-containing supramolecules, we present systematic studies of critical thermodynamic parameters and kinetic pathway that govern the coassemblies of BCP and strongly interacting small molecules. A number of potentially useful morphologies for optoelectronic materials, including a nanoscopic network of oligothiophene and nanoscopic crystalline lamellae, were obtained by varying the assembly pathway. Hierarchical coassemblies of oligothiophene and BCP, rather than macrophase separation, can be obtained. Crystallization of the oligothiophene not only induces chain stretching of the BCP block the oligothiophene is hydrogen bonded to but also changes the conformation of the other BCP coil block. This leads to an over 70% change in the BCP periodicity (e.g., from 31 to 53 nm) as the oligothiophene changes from a melt to a crystalline state, which provides access to a large BCP periodicity using fairly low molecular weight BCP. The present studies have demonstrated the experimental feasibility of generating thermoresponsive materials that convert heat into mechanical energy. Incorporating strongly interacting small molecules into BCP supramolecules effectively increases the BCP periodicity and may also open new opportunities to tailor their optical properties without the need for high molecular weight BCP.
Phosphodiesterase 11A (PDE11A) Gene Defects in Patients with ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH): Functional Variants May Contribute to Genetic Susceptibility of Bilateral Adrenal Tumors (2012)

We conclude that PDE11A genetic variants may increase predisposition to AIMAH.
Modeling studies of low‐temperature aerobic NOx reduction by a sequence of LNT‐SCR catalysts (2013)

The relationship between fuel penalty and precious metal loading in coupled LNTSCR systems for NO x reduction at low temperatures is determined. Simulations of adiabatic, aerobic NO x reduction determine the impact of catalyst architecture, precious metal loading, cycle time, catalyst length and the support material. These revealed that (a) high NO x conversion can be achieved for a given precious metal loading at low temperatures (510 K) with about 0.3% fuel penalty, (b) shortened cycle time and increased pulse duty reduce the overall NO x slip from the coupled catalyst and lead to significant improvement in the NO x conversion, (c) alternate arrangement of the LNT/SCR catalysts increases the NO x conversion, (d) a monotonic decreasing PGM loading in LNT leads to higher NO x conversion compared to uniform loading, (e) for a fixed catalyst volume, there is an optimal aspect ratio that maximizes the nonisothermal effect, and (f) metal based monolith supports improve NO x conversion. © 2013 American Institute of Chemical Engineers AIChE J , 59: 3421–3431, 2013
Towards Transparent Markers (2021)

For many years, 2D fiducial markers played one of the most important roles in Augmented Reality (AR) solutions. As AR evolved, this type of marker gave place to markerless alternatives, supported by the increase in processing power of desktop and mobile platforms. Besides that, 2D fiducial markers are still used nowadays. In this work, we proposed to extend their capability by adding transparency to them. This brings different limitations on the marker construction process but on the other hand it enables new uses not possible before. Markers can now be used to manipulate virtual objects being viewed from both sides and they can also be stacked together and still be recognized. We demonstrate such new features with two different real-time samples together with an analysis regarding the main limitations of the solution, providing some application scenarios that could directly benefit from transparent markers.
Decrease in the levels of nuclear RNA precursors for alpha 2 collagen in Rous sarcoma virus transformed fibroblasts (1981)

We have examined the levels of type I alpha 2 collagen RNA precursors, containing both intron and exon sequences in nuclear RNA preparations of chick embryo fibroblasts (CEF) and of CEF transformed by the Schmidt-Rupin strain of Rous sarcoma virus (RSV). We have used two different fragments of chick alpha 2 collagen genomic DNA as hybridization probes in S1 mapping experiments. Each of these DNA probes contains an entire intron. Our results indicate that the levels of the primary transcript of alpha 2 collagen RNA are much lower in RSV-CEF than in CEF. They suggest, but do not prove that the effect of the transforming protein p60src on the synthesis of alpha 2 collagen is mediated by a transcriptional control mechanism.
Dynamic Blockage Pre-Avoidance using Reconfigurable Intelligent Surfaces (2022)

Internet-of-vehicle (IoV) is a general concept referring to, e.g., autonomous drive based vehicle-to-everything (V2X) communications or moving relays. Here, high rate and reliability demands call for advanced multi-antenna techniques and millimeter-wave (mmw) based communications. However, the sensitivity of the mmw signals to blockage may limit the system performance, especially in highways/rural areas with limited building reflectors/base station deployments and high-speed devices. To avoid the blockage, various techniques have been proposed among which reconfigurable intelligent surface (RIS) is a candidate. RIS, however, has been mainly of interest in stationary/low mobility scenarios, due to the associated channel state information acquisition and beam management overhead as well as imperfect reflection. In this article, we study the potentials and challenges of RIS-assisted dynamic blockage avoidance in IoV networks. Particularly, by designing region-based RIS pre-selection as well as blockage prediction schemes, we show that RIS-assisted communication has the potential to boost the performance of IoV networks. However, there are still issues to be solved before RIS can be practically deployed in IoV networks.
The Role of Liver X Receptor-α in the Fatty Acid Regulation of Hepatic Gene Expression (2003)

Liver X receptors (LXR) alpha and beta play an important role in regulating the expression of genes involved in hepatic bile and fatty acid synthesis, glucose metabolism, as well as sterol efflux. Studies with human embryonic kidney 293 cells indicate that unsaturated fatty acids interfere with oxysterols binding to LXR and antagonize oxysterol-induced LXRalpha activity. In this report, we evaluated the effects of unsaturated fatty acids on LXR-regulated hepatic gene expression. The LXR agonist, T1317, induced mRNAs encoding sterol regulatory element-binding protein 1c (SREBP-1c) and two SREBP-1c-regulated lipogenic genes, e.g. fatty-acid synthase and the S14 protein in primary hepatocytes. Treatment of hepatocytes with eicosapentaenoic acid (20:5n-3) suppressed these mRNAs in the absence and presence of T1317. The cis-regulatory elements targeted by T1317 were not required for fatty-acid suppression of FAS or S14 promoter activity. In contrast to SREBP-1-regulated lipogenic genes, 20:5n-3 had no effect on the T1317 induction of ABCG5 or ABCG8 in the rat hepatoma cell line, FTO-2B. These two genes require LXR but not SREBP-1c for their expression. Feeding rats a diet supplemented with fish oil suppressed hepatic SREBP-1c-regulated genes and induced PPARalpha-regulated genes but had no effect on the LXR-regulated transcripts, CYP7A1, ABCG5, or ABCG8. Transfection studies, using either full-length hLXRalpha or a chimera containing only the LXRalpha ligand binding domain, indicate that a wide array of unsaturated fatty acids had little effect on LXRalpha activity in primary hepatocytes or FTO-2B. These studies suggest that LXRalpha is not a target for unsaturated fatty acid regulation in primary rat hepatocytes or in liver. Thus, oxysterol/LXR-mediated regulation of transcripts involved in bile acid synthesis or sterol efflux appear insensitive to dietary unsaturated fatty acids. The unsaturated fatty acid suppression of SREBP-1 and its targeted lipogenic genes is independent of LXRalpha