gebhart/patrepeval huggingface dataset:
High Affinity Dopamine D3Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice (2015)

The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially in models of relapse. Nevertheless, poor bioavailability, metabolic instability, and/or predicted toxicity have impeded success in translating these drug candidates to clinical use. Herein, we report a series of D3R-selective 4-phenylpiperazines with improved metabolic stability. A subset of these compounds was evaluated for D3R functional efficacy and off-target binding at selected 5-HT receptor subtypes, where significant overlap in SAR with D3R has been observed. Several high affinity D3R antagonists, including compounds 16 (Ki = 0.12 nM) and 32 (Ki = 0.35 nM), showed improved metabolic stability compared to the parent compound, PG648 (6). Notably, 16 and the classic D3R antagonist SB277011A (2) were effective in reducing self-administration of heroin in wild-type but not D3R knockout mice.
Cascade Storage and Delivery System for a Multi Mission Space Exploration Vehicle (MMSEV) (2012)

NASA is developing a Multi Mission Space Exploration Vehicle (MMSEV) for missions beyond Low Earth Orbit (LEO). The MMSEV is a pressurized vehicle used to extend the human exploration envelope for Lunar, Near Earth Object (NEO), and Deep Space missions. The Johnson Space Center is developing the Environmental Control and Life Support System (ECLSS) for the MMSEV. The MMSEV s intended use is to support longer sortie lengths with multiple Extra Vehicular Activities (EVAs) on a higher magnitude than any previous vehicle. This paper presents an analysis of a high pressure oxygen cascade storage and delivery system that will accommodate the crew during long duration Intra Vehicular Activity (IVA) and capable of multiple high pressure oxygen fills to the Portable Life Support System (PLSS) worn by the crew during EVAs. A cascade is a high pressure gas cylinder system used for the refilling of smaller compressed gas cylinders. Each of the large cylinders are filled by a compressor, but the cascade system allows small cylinders to be filled without the need of a compressor. In addition, the cascade system is useful as a reservoir to accommodate low pressure needs. A regression model was developed to provide the mechanism to size the cascade systems subject to constraints such as number of crew, extravehicular activity duration and frequency, and ullage gas requirements under contingency scenarios. The sizing routine employed a numerical integration scheme to determine gas compressibility changes during depressurization and compressibility effects were captured using the Soave-Redlich-Kwong (SRK) equation of state. A multi-dimensional nonlinear optimization routine was used to find the minimum cascade tank system mass that meets the mission requirements. The sizing algorithms developed in this analysis provide a powerful framework to assess cascade filling, compressor, and hybrid systems to design long duration vehicle ECLSS architecture. 1
Aromatic PMOs: tolyl, xylyl and dimethoxyphenyl groups integrated within the channel walls of hexagonal mesoporous silicas (2001)

There exists a need to synthesize PMOs with bridging organic groups beyond the few that are accessible from commercially available bis(triethoxysilyl)organic precursors. To fulfill this need, three new periodic mesoporous arylsilicas, aromatic PMOs, having bridging aromatic organic groups as an integral part of the framework have been synthesized and structurally characterized. The surfactant-templated synthesis employed new precursors consisting of two triethoxysilyl groups connected via toluene, p-xylene or 1,4-dimethoxybenzene. Diffraction and microscopy together with 13C CP-MAS NMR, 29Si MAS NMR and FT-Raman/IR measurements proved that the aryl–silica bonds in the new precursors and aromatic PMOs are stable under hydrolytic polycondensation self-assembly and surfactant acid extraction conditions. These PMOs have an ordered hexagonal channel mesostructure, some degree of ordering of aromatic groups likely through π–π stacking in the channel walls, a large pore volume and surface area, and relatively thick arylsilica walls whose dimensions seem to scale with the spatial demands of the aryl group.
Self-assembling peptides cross-linked with genipin: resilient hydrogels and self-standing electrospun scaffolds for tissue engineering applications (2018)

Self-assembling peptides (SAPs) are synthetic bioinspired biomaterials that can be feasibly multi-functionalized for applications in surgery, drug delivery, optics and tissue engineering (TE). Despite their promising biocompatibility and biomimetic properties, they have never been considered real competitors of polymers and/or cross-linked extracellular matrix (ECM) natural proteins. Indeed, synthetic SAP-made hydrogels usually feature modest mechanical properties, limiting their potential applications, due to the transient non-covalent interactions involved in the self-assembling phenomenon. Cross-linked SAP-hydrogels have been recently introduced to bridge this gap, but several questions remain open. New strategies leading to stiffer gels of SAPs may allow for a full exploitation of the SAP technology in TE and beyond. We have developed and characterized a genipin cross-linking strategy significantly increasing the stiffness and resiliency of FAQ(LDLK)3, a functionalized SAP already used for nervous cell cultures. We characterized different protocols of cross-linking, analyzing their dose and time-dependent efficiency, influencing stiffness, bioabsorption time and molecular arrangements. We choose the best developed protocol to electrospin into nanofibers, for the first time, self-standing, water-stable and flexible fibrous mats and micro-channels entirely made of SAPs. This work may open the door to the development and tailoring of bioprostheses entirely made of SAPs for different TE applications.
Situations and policies (2012)

In this paper, we first describe a system we have implemented that takes expressions of policies, expressed in a fragment of English called SBVR SE (Semantics of Business Vocabulary and Rules Structured English), an OMG standard, and automatically translates them into an executable semantic web formalism (OWL 2 and semantic web rules). Specifically, we describe how these policies can be used to automatically enforce compliance with policies and to reconcile multiple policies specified by independent parties. The scenarios implemented concern information sharing via XMPP (“instant messaging”). We then outline how situations can be characterized as policy-compliant or policy-violating. In some cases, situations are policy compliant or violating because of events and actions that they contain. We show that our formalism supports this analysis.
Predicting Learning Difficulty Based on Gaze and Pupil Response (2018)

E-Learning is transforming the way education is imparted. Today, millions of students take self-paced online courses. However, the content and language complexity often hinders comprehension and this together with lack of immediate help from the course instructor leads to weak learning outcomes. Ability to predict difficult content in real time enables eLearning systems to adapt content as per students' level of learning. The recent introduction of low-cost eye trackers has opened the new class of applications based on eye response. Eye tracking devices can record eye response to the visual element or concept causing a learning difficulty. The response and the variations in eye response to the same concept over time may be indicative of the level of learning. In this paper, we use eye movement measures to predict the levels of learning associated with a term/concept. The main contribution of this study is the spatio-temporal analysis of eye response to a term/concept. Proposed system analyses slide images, extracts words (terms), maps the eye response to words, and prepares a term-response map. A majority voting classifier trained with terms of known learning levels uses this term response map to classify a term as novel or familiar. The proposed system achieves 61% accuracy when predicting learning difficulty.
Picosecond carrier dynamics in highly excited InGaAs/InP/InGaAsP/InP structures (1992)

The carrier dynamics in highly excited In1-xGaxAs/InP/In1-xGaxAsyP1-y/InP structures, with x=0.47 and y=0.9, have been investigated by the picosecond dynamic grating technique. The carrier recombination time tau R and the ambipolar diffusion coefficient Da at a non-equilibrium carrier density of about 1019 cm-3 have been determined for layers of InGaAs, InP and InGaAsP on InP substrates. The influence of many-body effects and reabsorption of emitted photons on the carrier diffusion at high excitation levels are discussed.
EXTH-32. TARGETED STAT3 INHIBITION IMPAIRS MDSC MOBILIZATION AND RECRUITMENT IN GLIOBLASTOMA (2020)

Abstract BACKGROUND Glioblastoma tumors (GBM) are comprised upwards of 30 percent by glioma-associated myeloid cells (GAMs). A large fraction of GAMs are myeloid-derived suppressor cells (MDSC) thought to traffic in from peripheral circulation. MDSCs foster a hospitable environment for cancer cells by regulating immune suppression and driving resistance to immunotherapy. While signal transducer and activator of transcription 3 (STAT3) is considered to be a specific marker for MDSCs and is a known player in their phenotypic polarization in cancer, we sought to closely examine its specific role in MDSC trafficking and tumor recruitment. HYPOTHESIS Targeted inhibition of STAT3 blocks MDSC from the bone marrow, mitigating their accumulation within GBM tumors. METHODS Human and murine GBM samples were analyzed for immune-specific STAT3 phosphorylation (P-STAT3). Immune cell characterization and quantification in peripheral and GBM tissue from syngeneic murine models treated with a novel STAT3 inhibitor (LLL12B) was done. Therapeutic responses to LLL12B alone and in combination with immune checkpoint blockade were evaluated. RESULTS We found P-STAT3 to be predominantly expressed by tumor-associated immune cells in both human and murine GBM, particularly MDSCs. Circulating numbers of MDSCs dramatically increase in response to tumor burden. P-STAT3 is elevated in these cells, indicating that its activation occurs prior to tumor infiltration. LLL12B blockade of STAT3 significantly reduced the number of circulating and tumor-infiltrating MDSCs. As a single agent LLL12B reduced tumor volume and extended the survival of murine GBM models. When combined with anti-PD-1 checkpoint blockade, we observed durable survival in a significant fraction of treated mice. CONCLUSIONS These findings advocate a critically important role for STAT3 in regulating MDSC mobilization and trafficking to GBM tumors. It additionally reveals a new therapeutic mechanism of action for LLL12B that may be relevant for other direct inhibitors of STAT3, influencing their clinical applicability to treat GBM.
Consequences of BCR‐ABL Expression within the Hematopoietic Stem Cell in Chronic Myeloid Leukemia (2000)

Chronic myeloid leukemia (CML) was the first human malignancy shown to be associated with a specific cytogenetic lesion, the Philadelphia chromosomal translocation. Forty years on, many biological and biochemical properties have been ascribed to its molecular product, the BCR-ABL tyrosine kinase fusion protein. However, it has been difficult to establish their precise contribution to the deregulation of normal survival, proliferative and differentiative control in chronic phase CML and the degree to which the involvement of stem cells extends beyond their role as the aetiological target. This review will focus on our current understanding of the pathogenesis of CML from the perspective of stem cell involvement, and how the biological and biochemical properties ascribed to BCR-ABL from studies of in vitro transformation and in vivo leukemogenesis systems relate to the abnormalities manifest in the human disease.
Devalveringar och dess effekter på svensk skogsindustri (1993)

Uppsatsen beskriver devalveringar gjorda i Sverige fran 1976 och framat. Forfattarna gor en analys hur skogsbolagens rorelseresultat paverkas vid den senaste devalverigen nov- 1992.
15-15-0747-00-007a-tg7r1-cirs-channel-model-document-for-high-rate-pd-communications (2015)

The LiFi channels developed by Prof. Murat Uysal and Mr. Miramirkhani were selected as the "LiFi Reference Channel Models" by the IEEE 802.15.7r Task Group during the IEEE's latest meeting held in Bangkok, Thailand, in September. Accordingly, all companies, universities and research institutions are required to use these channel models as reference for their performance assessments and comparative analysis in the standardization proposals they will submit over the coming months. The channel models developed by them are the most realistic models available in the literature and pointed out the significance of recognition and adoption of these models by industry.
Halftoning (1999)

Abstract The sections in this article are White Noise Clustered Dot Recursive Tessellation Blue Noise Rendering Systems
Pandemic influenza viruses: time to recognize our inability to predict the unpredictable and stop dangerous gain‐of‐function experiments (2013)

> There are known knowns. There are things we know we know. We also know there are known unknowns. That is to say we know there are some things we do not know. But there are also unknown unknowns, the ones we don't know we don't know.

D.H. Rumsfeld, U.S. Secretary for Defense, February 12, 2002

For almost as long as the civil war in Syria, the scientific community has been locked in a controversy about the utility of gain‐of‐function (GOF) research to increase the transmissibility of highly pathogenic avian influenza H5N1 viruses that resulted in a year‐long moratorium (Nature, 2012a, 2012b, 2013a, 2013b). Now, for the first time since the controversy erupted in November 2011, there is a growing recognition among scientists that GOF virology – experiments with H5N1 and now H7N9 and H7N7 viruses – will not help us predict a pandemic (Morse et al, 2012; Merson et al, 2013), nor will it help us develop more effective vaccines (Butler, 2012; Malakoff, 2013), the two principal arguments for doing the research. Chinese officials have gone one step further by signalling their view that GOF research has no benefit for humanity (Malakoff, 2013; http://www.handelsblatt.com/technologie/das‐technologie‐update/healthcare/vogelgrippe‐manipulierte‐viren‐sind‐gefahr‐fuer‐menschheit/8611922.html).

There will be no end to the GOF saga until virologists, epidemiologists and public health officials acknowledge our fundamental inability for the moment to predict the unpredictable and until policy makers and funders move to rein in their support for GOF research.

To start its business, a virus generally has to replicate well. This process isn't invariably accompanied by pathology, but it often is. For a virus the key factor is transmission because without it the virus goes to extinction very quickly. Transmission studies, which have been the poor cousin in virology, incorporate features such as droplet size, coughing, …
Designing Electroactive Biointerface for Spatiotemporal Control of Cell Attachment and Release (2008)

In this paper, we demonstrate the use of individually addressable microelectrodes for cell sorting and cell micropatterning applications. Microelectrodes were modified with cell adhesive or non-adhesive molecules and then electrically stimulated to selectively adsorb or desorb proteins and/or mammalian cells. The switching of the surface properties was achieved by the electrochemical desorption of protein-functionalized thiols and poly(ethylene glycol) PEG silane from gold and indium tin oxide (ITO) electrodes respectively. The thiol surfaces were modified with anti-CD4 antibodies and used to capture T-cells. Upon electrical activation of the microelectrodes, both the antibodies and the T-cells were removed from the specific locations on the substrate. In addition, ITO electrodes were modified with cell- resistive PEG silane which was later electrochemically desorbed to make the surface adhesive to proteins or cells. This technique was employed to pattern two different cell types on the same substrate.
VABO: Violation-Aware Bayesian Optimization for Closed-Loop Control Performance Optimization with Unmodeled Constraints (2022)

We study the problem of performance optimization of closed-loop control systems with unmodeled dynamics. Bayesian optimization (BO) has been demonstrated effective for improving closed-loop performance by automatically tuning controller gains or reference setpoints in a model-free manner. However, BO methods have rarely been tested on dynamical systems with unmodeled constraints. In this paper, we propose a violation-aware BO algorithm (VABO) that optimizes closed-loop performance while simultaneously learning constraintfeasible solutions. Unlike classical constrained BO methods which allow an unlimited constraint violations, or ‘safe’ BO algorithms that are conservative and try to operate with near-zero violations, we allow budgeted constraint violations to improve constraint learning and accelerate optimization. We demonstrate the effectiveness of our proposed VABO method for energy minimization of industrial vapor compression systems.
High-Throughput Manufacture of 3D Fiber Scaffolds for Regenerative Medicine (2020)

Engineered scaffolds used to regenerate mammalian tissues should recapitulate the underlying fibrous architecture of native tissue to achieve comparable function. Current fibrous scaffold fabrication processes, such as electrospinning and three-dimensional (3D) printing, possess application-specific advantages, but they are limited either by achievable fiber sizes and pore resolution, processing efficiency, or architectural control in three dimensions. As such, a gap exists in efficiently producing clinically relevant, anatomically sized scaffolds comprising fibers in the 1-100 μm range that are highly organized. This study introduces a new high-throughput, additive fibrous scaffold fabrication process, designated in this study as 3D melt blowing (3DMB). The 3DMB system described in this study is modified from larger nonwovens manufacturing machinery to accommodate the lower volume, high-cost polymers used for tissue engineering and implantable biomedical devices and has a fiber collection component that uses adaptable robotics to create scaffolds with predetermined geometries. The fundamental process principles, system design, and key parameters are described, and two examples of the capabilities to create scaffolds for biomedical engineering applications are demonstrated. Impact statement Three-dimensional melt blowing (3DMB) is a new, high-throughput, additive manufacturing process to produce scaffolds composed of highly organized fibers in the anatomically relevant 1-100 μm range. Unlike conventional melt-blowing systems, the 3DMB process is configured for efficient use with the relatively expensive polymers necessary for biomedical applications, decreasing the required amounts of material for processing while achieving high throughputs compared with 3D printing or electrospinning. The 3DMB is demonstrated to make scaffolds composed of multiple fiber materials and organized into complex shapes, including those typical of human body parts.
Effect of Elevated Temperature on Adhesively Bonded Lightweight Material Single Lap Joints (2015)

This study investigates the effect of elevated temperature on the static load transfer capacity of adhesively bonded composite-based single lap joints. Two different types of temperature resistant adhesives as well as various joint material combinations are studied. The static load transfer capacity and corresponding failure mode are evaluated at room temperature and at elevated temperature of 285°F.
Synthesis and Characterization of Potential Impurities of Carvedilol, an Antihypertensive Drug (2010)

Carvedilol (Coreg) is a nonselective β-adrenergic blocking agent with vasodilating activity. It is used for the treatment of congestive heart failure and hypertension. During the bulk synthesis of carvedilol, we have observed six impurities: Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V, and Imp-VI. The present work describes the synthesis and characterization of these impurities.
Noninvasive Assessment of Atrial Fibrillation Complexity in Relation to Ablation Characteristics and Outcome (2018)

<b>Background:</b> The use of surface recordings to assess atrial fibrillation (AF) complexity is still limited in clinical practice. We propose a noninvasive tool to quantify AF complexity from body surface potential maps (BSPMs) that could be used to choose patients who are eligible for AF ablation and assess therapy impact. <b>Methods:</b> BSPMs (mean duration: 7 ± 4 s) were recorded with a 252-lead vest in 97 persistent AF patients (80 male, 64 ± 11 years, duration 9.6 ± 10.4 months) before undergoing catheter ablation. Baseline cycle length (CL) was measured in the left atrial appendage. The procedural endpoint was AF termination. The ablation strategy impact was defined in terms of number of regions ablated, radiofrequency delivery time to achieve AF termination, and acute outcome. The atrial fibrillatory wave signal extracted from BSPMs was divided in 0.5-s consecutive segments, each projected on a 3D subspace determined through principal component analysis (PCA) in the current frame. We introduced the nondipolar component index (NDI) that quantifies the fraction of energy retained after subtracting an equivalent PCA dipolar approximation of heart electrical activity. AF complexity was assessed by the NDI averaged over the entire recording and compared to ablation strategy. <b>Results:</b> AF terminated in 77 patients (79%), whose baseline AF CL was 177 ± 40 ms, whereas it was 157 ± 26 ms in patients with unsuccessful ablation outcome (<i>p</i> = 0.0586). Mean radiofrequency emission duration was 35 ± 21 min; 4 ± 2 regions were targeted. Long-lasting AF patients (≥12 months) exhibited higher complexity, with higher NDI values (≥12 months: 0.12 ± 0.04 vs. <12 months: 0.09 ± 0.03, <i>p</i> < 0.01) and short CLs (<160 ms: 0.12 ± 0.03 vs. between 160 and 180 ms: 0.10 ± 0.03 vs. >180 ms: 0.09 ± 0.03, <i>p</i> < 0.01). More organized AF as measured by lower NDI was associated with successful ablation outcome (termination: 0.10 ± 0.03 vs. no termination: 0.12 ± 0.04, <i>p</i> < 0.01), shorter procedures (<30 min: 0.09 ± 0.04 vs. ≥30 min: 0.11 ± 0.03, <i>p</i> < 0.001) and fewer ablation targets (<4: 0.09 ± 0.03 vs. ≥4: 0.11 ± 0.04, <i>p</i> < 0.01). <b>Conclusions:</b> AF complexity can be noninvasively quantified by PCA in BSPMs and correlates with ablation outcome and AF pathophysiology.
Complete Genome of Salmonella enterica Serovar Typhimurium Myophage Maynard (2013)

Salmonella enterica serovar Typhimurium is a pathogenic bacterium that has been a major concern for food and public safety. Phages infecting S. Typhimurium may prove to be useful therapeutics against this harmful bacterium. Here, we announce the complete genome of S. Typhimurium T4-like myophage Maynard and describe its features.