gebhart/patrepeval huggingface dataset:
Discovery of Tricyclic Triazolo- and Imidazopyridine Lactams as M1 Positive Allosteric Modulators (2018)

This Letter describes the chemical optimization of a new series of muscarinic acetylcholine receptor subtype 1 (M<sub>1</sub>) positive allosteric modulators (PAMs) based on novel tricyclic triazolo- and imidazopyridine lactam cores, devoid of M<sub>1</sub> agonism, e.g., no M<sub>1</sub> ago-PAM activity, in high expressing recombinant cell lines. While all the new tricyclic congeners afforded excellent rat pharmacokinetic (PK) properties (CL<sub>p</sub> < 8 mL/min/kg and t<sub>1/2</sub> > 5 h), regioisomeric triazolopyridine analogues were uniformly not CNS penetrant ( K<sub>p</sub> < 0.05), despite a lack of hydrogen bond donors. However, removal of a single nitrogen atom to afford imidazopyridine derivatives proved to retain the excellent rat PK and provide high CNS penetration ( K<sub>p</sub> > 2), despite inclusion of a basic nitrogen. Moreover, 24c was devoid of M<sub>1</sub> agonism in high expressing recombinant cell lines and did not induce cholinergic seizures in vivo in mice. Interestingly, all of the new M<sub>1</sub> PAMs across the diverse tricyclic heterocyclic cores possessed equivalent CNS MPO scores (>4.5), highlighting the value of both "medicinal chemist's eye" and experimental data, e.g., not sole reliance (or decision bias) on in silico calculated properties, for parameters as complex as CNS penetration.
A framework for assessing amorphous oxide semiconductor thin‐film transistor passivation (2012)

Abstract Amorphous oxide semiconductor thin‐film transistors (TFTs) are moving towards commercialization for a variety of display applications. Invariably, display applications require a bottom‐gate TFT configuration in which passivation of the top channel layer surface is required. The objective of this work is to propose a conceptual model framework for assessing TFT passivation schemes, within the context of amorphous oxide semiconductor electronics. This model involves first estimating the energy of the charge neutrality levels (CNLs) for the channel and passivation layers. Then, an energy band diagram is drawn to establish the relative position of these CNLs prior to their establishment of intimate contact. A situation in which the passivation layer CNL is below that of the channel layer CNL is considered undesirable because interface state electronic transfer from the channel to the passivation layer leads to formation of an accumulation layer at this interface. Although the opposite case in which the passivation layer CNL is above that of the channel layer CNL is more desirable, the ideal situation would be when both CNLs align because no interface state electronic transfer would occur. This framework is then employed in a discussion of the passivation of indium gallium zinc oxide and zinc tin oxide bottom‐gate TFTs.
Challenging endings: How telomeres prevent fragility (2021)

It has become apparent that difficulties to replicate telomeres concern not only the very ends of eukaryotic chromosomes. The challenges already start when the replication fork enters the telomeric repeats. The obstacles encountered consist mainly of noncanonical nucleic acid structures that interfere with replication if not resolved. Replication stress at telomeres promotes the formation of so-called fragile telomeres displaying an abnormal appearance in metaphase chromosomes though their exact molecular nature remains to be elucidated. A substantial number of factors is required to counteract fragility. In this review we promote the hypothesis that telomere fragility is not caused directly by an initial insult during replication but it results as a secondary consequence of DNA repair of damaged replication forks by the homologous DNA recombination machinery. Incomplete DNA synthesis at repair sites or partial chromatin condensation may become apparent as telomere fragility. Fragility and DNA repair during telomere replication emerges as a common phenomenon which exacerbates in multiple disease conditions.
Perspective—The Feasibility of Continuous Protein Monitoring in Interstitial Fluid (2023)

Real-time continuous monitoring of proteins in-vivo holds great potential for personalized medical applications. Unfortunately, a prominent knowledge gap exists in the fundamental biology regarding protein transfer and correlation between interstitial fluid and blood. Additionally, technological sensing will require affinity-based platforms that cannot be robustly protected in-vivo and will therefore be challenged in sensitivity, longevity, and fouling over multi-day to week timelines. Here we use electrochemical aptamer sensors as a model system to discuss further research necessary to achieve continuous protein sensing.
Clinical pharmacology of single‐ and multiple‐ascending doses ofACT‐178882, a new direct renin inhibitor, and its pharmacokinetic interaction with food and midazolam (2012)

This study investigated the tolerability, safety, pharmacokinetics, and pharmacodynamics of ACT-178882, a new direct renin inhibitor, as well as its interaction with food and midazolam. Healthy male subjects received either single (10-1000 mg) or multiple doses (30-600 mg) administered once daily for 14 days of ACT-178882, placebo, or 20 mg enalapril in the fasted state. Following a 2-week washout, the single dose of 30 mg ACT-178882 was also administered in the fed state. In the multiple-ascending-dose part, subjects were dosed with midazolam on days -2, 2, and 12 to investigate interactions with CYP3A4. Dizziness and headache were the most frequently reported adverse events. No clinically relevant changes occurred for body weight, vital signs, clinical laboratory variables, and ECG although both enalapril and ACT-178882 tended to decrease systolic blood pressure. Following single doses of ACT-178882, t1/2 and tmax varied from 18.7 to 24.7 h and from 3 to 5 h, respectively, and food had no significant effect. Steady-state conditions were achieved after 4-6 days of dosing and accumulation was minimal. ACT-178882 pharmacokinetics were dose proportional. ACT-178882 but not enalapril dose-dependently increased Cmax and area under the concentration-time curve of midazolam. Single and multiple doses of ACT-178882 dose-dependently increased active renin and decreased plasma renin activity, whereas enalapril increased both variables. No effects on urinary excretion of creatinine, potassium, and the 6β-hydroxycortisol/cortisol ratio were observed, whereas sodium and aldosterone excretion was decreased by both ACT-178882 and enalapril. The current results with ACT-178882 warrant further clinical investigation of this renin inhibitor in hypertensive patients.
Magnetoresistivity of micron size (10·0) epitaxial Co wires (1999)

Magnetoresistivity effects in association with the magnetic domain structure were studied by using 1 /spl mu/m wide epitaxial (10/spl middot/0) Co wires oriented parallel and perpendicular to the magnetic easy [001] axis. The parallel wire exhibited a large anisotropic magnetoresistivity ratio of /spl sim/11 % at 5 K, which turned to be negative above 214 K due to the temperature variable anisotropic magnetoresistivity effect. A negative domain wall contribution to the resistivity was observed only in the temperature range from 200 K to 220 K. On the contrary, the perpendicular wire exhibited a small positive wall contribution ranging from 3/spl times/10/sup -4/ /spl mu//spl Omega/cm at 5 K to 6.9/spl times/10/sup -4/ /spl mu//spl Omega/cm at 300 K.
18F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis (2018)

Immune cell-mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (<sup>18</sup>F-FDG and <sup>18</sup>F-1-(2'-deoxy-2'-fluoro-arabinofuranosyl)cytosine [<sup>18</sup>F-FAC]) and hepatocyte biology (<sup>18</sup>F-2-deoxy-2-fluoroarabinose [<sup>18</sup>F-DFA]) can visualize and quantify liver-infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. <b>Methods:</b> Mice treated with concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with <sup>18</sup>F-FDG, <sup>18</sup>F-FAC, and <sup>18</sup>F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis were imaged with <sup>18</sup>F-FDG, <sup>18</sup>F-FAC, and <sup>18</sup>F-DFA PET. <sup>18</sup>F-FAC PET was performed on mice treated with ConA and vehicle or with ConA and dexamethasone. Biopsy samples of patients with autoimmune hepatitis were immunostained for deoxycytidine kinase. <b>Results:</b> Hepatic accumulation of <sup>18</sup>F-FDG and <sup>18</sup>F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of <sup>18</sup>F-DFA was 41% lower, in a mouse model of autoimmune hepatitis than in control mice. Increased hepatic <sup>18</sup>F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic <sup>18</sup>F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic <sup>18</sup>F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic <sup>18</sup>F-FDG accumulation by 109% and decreased hepatic <sup>18</sup>F-DFA accumulation by 20% but had no effect on hepatic <sup>18</sup>F-FAC accumulation (nonsignificant 2% decrease). <sup>18</sup>F-FAC PET provided a noninvasive biomarker of the efficacy of dexamethasone for treating the autoimmune hepatitis model. Infiltrating leukocytes in liver biopsy samples from patients with autoimmune hepatitis express high levels of deoxycytidine kinase, a rate-limiting enzyme in the accumulation of <sup>18</sup>F-FAC. <b>Conclusion:</b> Our data suggest that PET can be used to noninvasively visualize activated leukocytes and inflamed hepatocytes in a mouse model of autoimmune hepatitis.
Making the Difference in Semantic Web Service Composition (2007)

Automation of Web service composition is one of the most interesting challenges facing the Semantic Web today. In this paper we propose a mean of performing automated Web service composition by exploiting semantic matchmaking between Web service parameters (i.e., outputs and inputs) to enable their connection and interaction. The key idea is that the matchmaking enables, at run time, finding semantic compatibilities among independently defined Web service descriptions. To this end, our approach extends existing methods in order to explain misconnections between Web services. From this we generate Web service compositions that realize the goal, satisfying and optimizing the semantic connections between Web services. Moreover a process of relaxing the hard constraints is introduced in case the composition process failed. Our system is implemented and interacting with Web services dedicated on a Telecom scenario. The preliminary evaluation results showed high efficiency and effectiveness of the proposed approach. Copyright © 2007, Association for the Advancement of Artificial Intelligence (www.aaai.org). All rights reserved.
Oncoplastic parenchymal resection (2020)

Oncoplastic techniques continue to advance the limits of breast-conservation surgery by permitting larger volumes of tissue to be excised while yielding an acceptable cosmetic result. The diagnosis of ductal carcinoma in situ (DCIS) has risen in the era of modern mammography, necessitating a coordinated approach between the oncologic resection and possible subsequent oncoplastic reconstruction. Oncoplastic planning will be influenced by a variety of factors including the type of oncologic surgical resection performed, the utilization or elimination of radiotherapy from the treatment algorithm, and methods for assessing DCIS margin status. The oncologic surgical approach to DCIS has traditionally been determined by factors such as tumor size and pathologic classification, age, and patient or provider choice or concern for risk of recurrence and desire to avoid repeat intervention. The optimum choice will be determined by breast size and percentage breast excision together with tumor location, need for re-excision, degree of ptosis, and timing of radiotherapy.
High drain current and low on-resistance in AlGaN/GaN HEMTs with Au-plated ohmic electrodes (2015)

This paper describes the effect of thickening Au-plated ohmic electrodes in AlGaN/GaN HEMTs on the drain current and on-resistance. By increasing the thickness of Au-plated ohmic electrodes up to 5 μm, the fabricated AlGaN/GaN HEMT with a total gate width from 2 to 10 mm exhibited an increase in the maximum drain current by about 50 % and a reduction in the on-resistance by more than 40 %.
An integrated technology CAD system for process and device designers (1993)

A workstation-based integrated system with a highly interactive X/Motif user interface is discussed. At present, TSUPREM3, TSUPREM4 and TPISCES have been integrated into this system. The components of the integrated TCAD system include a generic process recipe editor, a mask editor, a 2-D wafer structure builder (using 1-D/2-D process simulation profiles), a mesh generator for 2-D device simulation, a device simulation recipe editor, and graphical postprocessors for both process and device analysis. The user of this system inputs the specification of a process recipe and the layout of the device structure to be fabricated. The system then runs process and device simulation using incremental and shared simulation strategies to generate wafer structure and electrical device characteristics. An interactive user interface guides the user through the process and device simulation flow. thereby aiding what-if analysis of process and device tradeoffs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Supplementary Figures 1-8 from Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins (2023)

Supplementary Figures 1-8 from Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins
All-solid-state electrochromic reflectance device for emittance modulation in the far-infrared spectral region (2000)

All-solid-state electrochromic reflectance devices for thermal emittance modulation were designed for operation in the spectral region from mid- to far-infrared wavelengths (2–40 μm). All device constituent layers were grown by magnetron sputtering. The electrochromic (polycrystalline WO3), ion conductor (Ta2O5), and Li+ ion-storage layer (amorphous WO3), optimized for their infrared (IR) optical thicknesses, are sandwiched between a highly IR reflecting Al mirror, and a 90% IR transmissive Al grid top electrode, thereby meeting the requirements for a reversible Li+ ion insertion electrochromic device to operate within the 300 K blackbody emission range. Multicycle optical switching and emittance modulation is demonstrated. The measured change in emissivity of the device is to 20%.
A cognitive approach to classifying perceived behaviors (2010)

This paper describes our work on integrating distributed, concurrent control in a cognitive architecture, and using it to classify perceived behaviors. We are implementing the Robot Schemas (RS) language in Soar. RS is a CSP-type programming language for robotics that controls a hierarchy of concurrently executing schemas. The behavior of every RS schema is defined using port automata. This provides precision to the semantics and also a constructive means of reasoning about the behavior and meaning of schemas. Our implementation uses Soar operators to build, instantiate and connect port automata as needed. Our approach is to use comprehension through generation (similar to NLSoar) to search for ways to construct port automata that model perceived behaviors. The generality of RS permits us to model dynamic, concurrent behaviors. A virtual world (Ogre) is used to test the accuracy of these automata. Soar's chunking mechanism is used to generalize and save these automata. In this way, the robot learns to recognize new behaviors.
Flight of the pico satellite solar cell testbed (PSSC Testbed) space experiment (2009)

The primary mission of the PSSC Testbed is to provide space flight data on two types of advanced solar cells, XTJ and ZTJ, produced by the two U.S. solar cell manufacturers, Spectrolab and Emcore, respectively. The PSSC Testbed flight data confirmed that the picosatellite can be used for measuring l-V characteristics of solar cells. Continuing monitoring of the l-V measurement will allow determining the actual degradation of the solar cells due to exposure to the space environment. Mission success for the initial low earth orbit (LEO) space flight provided proof of concept for the PSSC Testbed. Subsequent mission will fly in a geosynchronous transfer orbit (GTO), in which a 450-day radiation exposure of the solar cells will be equivalent to that of 15 years radiation exposure in geosynchronous orbit.
Rapid Disease Progression without Seroconversion following Primary Human Immunodeficiency Virus Type 1 Infection—Evidence for Highly Susceptible Human Hosts (1997)

A patient is described who rapidly progressed from primary human immunodeficiency virus (HIV) type 1 infection to death without seroconversion but with consistently high plasma viremia. His asymptomatic sex partner had been HIV-1 seropositive for >8 years prior to transmission. Analysis of viral sequences from these subjects and controls confirmed the transmission event. Although the biologic properties of the patient's virus were unremarkable, he had poor functional immune responses to HIV and an HLA haplotype associated with rapid disease progression. The disparity between immune responses and clinical course in this transmission pair, coupled with infection with an unremarkable HIV-1 isolate, underscores the crucial importance of host factors in HIV-1 pathogenesis.
Osteogenic Potential of Postnatal Skeletal Muscle–Derived Stem Cells Is Influenced by Donor Sex (2007)

When stimulated with BMP4, both F- and M-MDSCs underwent osteogenic differentiation, although M-MDSCs had a significantly greater ALP activity and a larger increase in the expression of osteogenic genes than F-MDSCs. In the pellet culture assay, M-MDSCs showed greater mineralization than F-MDSCs. BMP4 stimulation of single cell-derived colonies from M-MDSCs showed higher levels of ALP than those from F-MDSCs. Similar results were obtained with the MDSC-BMP4 cells. In vivo, F-MDSC-BMP4 cells displayed variability in bone area and density, whereas M-MDSC-BMP4 cells showed a more consistent and denser ectopic bone formation. More bone formation was also seen in male hosts compared with female hosts, regardless of the sex of the implanted cells. These results suggest that M-MDSCs may contain more osteoprogenitor cells than F-MDSCs, which may have implications in the development of cellular therapies for bone healing.
The Impact of Heparanese and Heparin on Cancer Metastasis and Angiogenesis (2006)

Heparan sulfate (HS) proteoglycans play a key role in the self-assembly, insolubility and barrier properties of the extracellular matrix (ECM). Cleavage of HS therefore affects the integrity of tissues and hence normal and pathological phenomena involving cell migration and response to changes in the ECM. Mammalian heparanase, HS-degrading endoglycosidase,is synthesized as a latent 65 kDa precursor that undergoes proteolytic cleavage, yielding 8 kDa and 50 kDa subunits that heterodimerize to form a highly active enzyme. Heparanase is preferentially expressed in human tumors and its over-expression in tumor cells confers an invasive phenotype in experimental animals. Heparanase also releases angiogenic factors from the ECM and tumor micro environment and thereby induces an angiogenic response in vivo. Enhanced heparanase expression correlates with metastatic potential, tumor vascularity and reduced postoperative survival of cancer patients. Heparanase also promotes cell adhesion, survival and signaling events, independent of its enzymatic activity. These observations, the anti-cancerous effect of heparanase gene silencing and of heparanase inhibiting molecules as well as the unexpected identification of a predominant functional heparanase, suggest that the enzyme is a promising target for anti-cancer drug development. Here, we summarize recent progress in molecular and cellular aspects of heparanase, emphasizing its causal involvement in cancer metastasis and angiogenesis, and discuss the development of heparin-like heparanase inhibitors.
Circuit design issues affecting present and future deep sub-micron ferroelectric random-access memories (2001)

Abstract The basic architecture of ferroelectric memories (FeRAMs) is known to be very similar to that of DRAM. Consequently, many design issues for FeRAM are already known from DRAM and have been solved by applying prior DRAM solutions. However, there are also a number of issues that are unique to FeRAM. Often these issues become critical design problems that require innovative circuit-level solutions[1]. This paper discusses some of the most relevant issues affecting present and future deep sub-micron FeRAMs. In addition, new problems that have to be solved for future FeRAMs are presented.
Nonneoplastic Intramedullary Spinal Cord Lesions Mimicking Tumors (1999)

In reply: We read with interest the comments by Dr. Pittella concerning our article (3). We appreciate his mention of schistosomias as another granulomatous disease affecting the spinal cord. We acknowledge reports of spinal cord involvement of schistosomiasis (2,5,6,9,11). Dr. Pittella's comments are especially relevant given that cases of schistosomiasis mimicking an intramedullary tumor have been described (4,8,10). In our article, we summarized the New York University Medical Center experience. Although schistosomiasis, as described by Dr. Pittella, affects approximately 200 million individuals around the world, schistosomal spinal cord involvement is extremely rare in the United States (7). Two cases of spinal cord involvement of schistosomiasis were reported at our institution (1). In both cases, autopsy revealed that the findings of schistosomiasis were incidental and lacking an inflammatory granulomatous reaction. We recognize the invasion of Schistosoma as potentially leading to spinal cord involvement with clinical symptomology, but we did not experience such cases at the New York University Medical Center. Mark Lee Fred J. Epstein Ali R. Rezai David Zagzag New York, New York