gebhart/patrepeval huggingface dataset:
Synthesis and pharmacological examination of 1-(3-methoxy-4-methylphenyl)-2-aminopropane and 5-methoxy-6-methyl-2-aminoindan: similarities to 3,4-(methylenedioxy)methamphetamine (MDMA) (1991)

The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5-methoxy-6-methyl-2-aminoindan (11) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Both 6 and 11 were found to substitute with high potency in 3,4-(methylenedioxy)methamphetamine (1) and (S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (2) trained rats. In the latter assay, both enantiomers of 6 had identical potencies, but their dose-response curves were not parallel. Racemic 6, but not 11, partially substituted for LSD. Racemic 6 and 11 did not substitute in (S)-amphetamine-trained rats. All of the test compounds were potent inhibitors of [3H]-5-HT uptake into synaptosomes in vitro, with the S enantiomer of 6 being most active. Rat brain monoamine levels were unaltered 1 week following a single high dose (10 or 20 mg/kg, sc) of 6 or 11, or two weeks following a subacute dosing regimen (20 mg/kg, sc, twice a day for 4 days). In addition, radioligand-binding parameters in rat brain homogenate with the 5-HT uptake inhibitor [3H]paroxetine were unchanged after subacute dosing with either racemic 6 or 11. The results indicate that compounds 6 and 11 have animal behavioral pharmacology similar to the methylenedioxy compounds 1 and 2, but that they do not induce the serotonin neurotoxicity that has been observed for the latter two drugs.
Words or Characters? Fine-grained Gating for Reading Comprehension (2016)

Previous work combines word-level and character-level representations using concatenation or scalar weighting, which is suboptimal for high-level tasks like reading comprehension. We present a fine-grained gating mechanism to dynamically combine word-level and character-level representations based on properties of the words. We also extend the idea of fine-grained gating to modeling the interaction between questions and paragraphs for reading comprehension. Experiments show that our approach can improve the performance on reading comprehension tasks, achieving new state-of-the-art results on the Children's Book Test dataset. To demonstrate the generality of our gating mechanism, we also show improved results on a social media tag prediction task.
Receptor for Thyrotropin-releasing Hormone in Plasma Membranes of Bovine Anterior Pituitary Gland (1973)

Abstract The receptor for thyrotropin-releasing hormone has been located in the plasma membranes of bovine anterior pituitary gland. Treatment of membranes with phospholipase A, phospholipase C, or digitonin or addition of lysophosphatidylcholine diminishes or completely destroys the ability of membranes to bind 3H-labeled thyrotropin-releasing hormone. Phospholipase D was without effect. These reductions in thyrotropin-releasing hormone binding capacity stem from a decrease in the affinity for thyrotropin-releasing hormone of the membrane-located receptor. The effects of phospholipase A were completely Ca2+-dependent. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine are the four major phospholipids of adenohypophyseal cell plasma membranes. When added in excess of 1 mg per ml to intact plasma membranes, sonicated suspensions of these four phospholipids present either singly or in combination result in an inhibition of thyrotropin-releasing hormone binding. If plasma membranes are used with a concentration of phospholipase A or C to give a reduction in thyrotropin-releasing hormone binding of at least 50%, partial recovery of binding activity is achieved on phospholipid addition. Inhibition of thyrotropin-releasing hormone binding by phospholipid addition to intact membranes is mediated by a decrease in the Vmax of the reaction. These data show membrane phospholipids to be intimately involved in the receptor for thyrotropin-releasing hormone.
The Archaeoglobus fulgidus d -Lactate Dehydrogenase Is a Zn 2+ Flavoprotein (1999)

Archaeoglobus fulgidus, a hyperthermophilic, archaeal sulfate reducer, is one of the few organisms that can utilize D-lactate as a sole source for both carbon and electrons. The A. fulgidus open reading frame, AF0394, which is predicted to encode a D-(-)-lactate dehydrogenase (Dld), was cloned, and its product was expressed in Escherichia coli as a fusion with the maltose binding protein (MBP). The 90-kDa MBP-Dld fusion protein was more efficiently expressed in E. coli when coexpressed with the E. coli dnaY gene, encoding the arginyl tRNA for the codons AGA and AGG. When cleaved from the fusion protein by treatment with factor Xa, the recombinant Dld (rDld) has an apparent molecular mass of 50 kDa, similar to that of the native A. fulgidus Dld enzyme. Both the purified MBP-Dld fusion protein and its rDld cleavage fragment have lactate dehydrogenase activities specific for D-lactate, are stable at 80 degrees C, and retain activity after exposure to oxygen. The flavin cofactor FAD, which binds rDld apoprotein with a 1:1 stoichiometry, is essential for activity.
Generalized Hypermobility, Knee Hyperextension, and Outcomes After Anterior Cruciate Ligament Reconstruction: Prospective, Case‐Control Study With Mean 6 Years Follow‐up (2017)

Level III, case control study.
P3‐371: Stimulation of innate immunity via Toll‐like receptor 9 mitigates Alzheimer pathology (2010)

Immunotherapy has a significant impact on Alzheimer's disease (AD) related pathology. One limitation with immunotherapeutic approaches is clearance of vascular amyloid and associated hemorrhages. This is an important issue since cerebral amyloid angiopathy (CAA) is present in virtually all AD cases and in about 1/3 of cognitively normal elderly individuals. Our research group postulated stimulation of innate immunity as an alternative approach to overcome these side effects. In addition, the effectiveness of this novel approach for tau related pathology has not been addressed. Recently, stimulation of innate immune responses via the Toll-like receptors (TLRs) has emerged as an effective method both for activating macrophages/microglia, and for inducing specific humoral immune responses. Various CpG DNA drugs that are Toll-like receptor 9 (TLR9) agonists are safe in humans and rodents. We utilized type B CpG oligodeoxynucleotides (ODNs) to stimulate innate immunity in Tg2576 AD mice. In addition, we tested the effect of the TLR9 agonist CpG ODN on microglial uptake and degradation of Aβ42 in culture. Bone marrow-derived perivascular macrophages stimulated with CpG ODN may play an important role in the regulation of CAA. We conducted studies to examine the effect of CpG ODN on perivascular macrophages using rhodamine-conjugated dextran amine Mini-Ruby injected into the cisterna magna and confocal microscopy. We found that stimulation of TLR9 signaling led to a remarkable reduction of total amyloid burden, along with Aβ oligomers, which correlated with significant behavioral improvements. CpG ODN treatment reduced the CAA burden without any evidence of increased cerebral microhemorrhages. In vitro results indicate that TLR9 activation enhances microglial uptake and degradation of aggregated Aβ42. Confocal microscopy images of dextran-positive perivascular macrophages revealed an increase in cortical perivascular macrophages in CpG ODN injected animals compared to control animals, suggesting that these cells are involved in the reduction of CAA. To better evaluate the efficacy of our approach, studies using mouse model of congophilic angiopathy and triple-transgenic AD model which develops plaques and tangles, are underway. Stimulation of innate immunity through TLR9 signaling represents a novel immunotherapeutic approach for AD. Present results provide essential information prior to any clinical use of CpG ODN.
VisBiz: A Simplified Visualization of Business Operation (2005)

In this poster, we present a new technique, VisBiz, for interactively visualizing business operations. The basic idea of this technique is to visually mining relationships between important operation parameters (attributes) and to map the parameters into visualizations. VisBiz simplifies the complexity by partitioning the operation into multiple attribute circular graphs. VisBiz allows the analysis of business data as follows:
Diagnosis of Erdheim—Chester disease by using computerized tomography—guided stereotactic biopsy of a caudate lesion (2004)

The authors present the case of a 27-year-old woman with Erdheim-Chester disease (ECD) and extensive intracranial involvement, in whom the initial diagnosis of ECD was established based on computerized tomography (CT)-guided stereotactic biopsy of a caudate lesion. Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis of unknown origin that is clinically characterized by bone pain, diabetes insipidus, and exophthalmos. The radiological hallmarks of the disease include symmetrical sclerosis of the long bones with epiphysial sparing and increased tracer uptake in lesions seen on scintigraphic imaging. Erdheim-Chester disease is characterized histologically by the presence of infiltrating lipid-laden histiocytes that commonly involve the retroperitoneum, orbits, skin, pericardium, lungs, and long bones. Although the occurrence of diabetes insipidus often precedes the diagnosis of ECD by more than a decade in most patients, magnetic resonance imaging- and CT-documented central nervous system involvement is exceedingly rare. In the setting of neurological involvement, neurosurgical biopsy has been reported seven times in the literature, with only one of these biopsies being the basis for the initial diagnosis of the disease. The authors' case represents only the second time the disease has been diagnosed by means of neurosurgical biopsy, highlighting the diagnostic difficulties that patients with EDC present. Skeletal radiographs were confirmatory in this case and this modality should be emphasized as the simplest and most direct route to the diagnosis. The degree of neurological involvement further distinguishes the case presented from prior reports in the literature. The multiple bilateral intraaxial lesions were intensely enhancing on contrast CT scans, distributed infra- and supratentorially, involving both white and gray matter, and associated with diffuse cerebral edema. The case presented is also remarkable by virtue of the symmetrical involvement of the caudate nuclei, representing the first such example documented in the literature. The diagnosis, treatment, and outcome in this patient are discussed, and a review of the literature is presented.
Measuring Dielectric Properties of Ceramic Powders at Microwave Frequencies for Material Processing Applications (2020)

Abstract Ceramic powders are commonly used as precursors for several ceramic part manufacturing processes. Their dielectric characterization is necessary for all the cases where electromagnetic radiation is used to induce heating. In support of such activities at the U.S. Naval Research Laboratory, the present work introduces a technique for measuring the complex dielectric constants of ceramic powders at microwave frequencies. The data produced by this technique is critical for the proper modeling of ceramic powder microwave absorption and will assist in ongoing research into volumetric microwave sintering. This technique involves a transmission line measurement using a network analyzer and waveguide setup. Dielectric parameters are then extracted from these measurements using two established methods. Complex relative permittivity measurements are presented for ceramic powders ofyttria stabilized zirconia (YSZ), barium titanate (BaTiO3), zinc oxide (ZnO), and titanium dioxide (TiO2) as well as a method for containing the sample shape during measurement. Experiments were carried out between 25 and 40GHz; in the Ka microwave band. Experimental results suggest that the dielectric constant (ε′) of these powders are similar to those of bulk. Results are compared to lower frequency reference data showing reasonable agreement.
Data from CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; T cells engineered with chimeric antigen receptors (CAR) recognizing CD19 can induce complete remission of B-cell malignancies in clinical trials; however, in some disease settings, CAR therapy confers only modest clinical benefit due to attenuated persistence of CAR T cells. The purpose of this study was to enhance persistence and augment the antitumor activity of adoptively transferred CD19CAR T cells by restimulating CAR&lt;sup&gt;+&lt;/sup&gt; T cells through an endogenous cytomegalovirus (CMV)-specific T-cell receptor.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; CMV-specific T cells from CMV seropositive healthy donors were selected after stimulation with pp65 protein and transduced with clinical-grade lentivirus expressing the CD19R:CD28:ζ/EGFRt CAR. The resultant bispecific T cells, targeting CMV and CD19, were expanded via CD19 CAR-mediated signals using CD19-expressing cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The bispecific T cells proliferated vigorously after engagement with either endogenous CMVpp65 T-cell receptors or engineered CD19 CARs, exhibiting specific cytolytic activity and IFNγ secretion. Upon adoptive transfer into immunodeficient mice bearing human lymphomas, the bispecific T cells exhibited proliferative response and enhanced antitumor activity following CMVpp65 peptide vaccine administration.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; We have redirected CMV-specific T cells to recognize and lyse tumor cells via CD19CARs, while maintaining their ability to proliferate in response to CMV antigen stimulation. These results illustrate the clinical applications of CMV vaccine to augment the antitumor activity of adoptively transferred CD19CAR T cells in patients with B-cell malignancies. &lt;i&gt;Clin Cancer Res; 21(13); 2993–3002. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Abstract 2421: An adenoviral vaccine encoding full-length inactivated human HER2 exhibits potent immunogenicity and enhanced therapeutic efficacy without oncogenicity (2010)

Abstract While HER2 oncogene directed therapies such as lapatinib and trastuzumab confer clinical benefits, a majority of metastatic HER2+ patients eventually experience progressive disease; however, their tumors remain strongly HER2+. Thus, current therapeutic limitations combined with continued HER2 expression in patients makes immunotherapeutic vaccination against HER2 an attractive strategy. But as HER2 is an oncogene, it is imperative to develop HER2 vaccines with maximal immunologic potential, but minimal oncologic potential. To address these issues, we created recombinant adenoviral vectors expressing the extracellular domain of HER2 (Ad-HER2-ECD), ECD plus the transmembrane domain (Ad-HER2-ECD-TM) and full length HER2 inactivated for kinase function (Ad-HER2-ki) and determined their relative immunogenicity, anti-tumor effectiveness, as well as their oncogenic potential. As an immunotherapeutic vaccine, we found that that both Ad-HER2-ki and Ad-HER2-ECD-TM were highly effective in eliciting significant T-cell and antibody responses to HER2 in naïve mouse models compared to plasmid vaccination with HER2-ki constructs, thus validating the immunologic efficacy of the adenoviral platform. In contrast, we did not observe any induction of HER2 specific T-cell or antibody responses in HER2-ECD vaccinated animals. While the strong immune responses from both Ad-HER2-ki and Ad-HER2-ECD-TM vectors translated into significantly retarded tumor growth in naïve animals, our studies revealed that Ad-HER2ki vaccinated animals had the most significant HER2-specific T-cell responses as well as the most significant anti-tumor response. When a HER2+ tolerant mouse model was used, we observed that direct Ad-HER2-ki vaccination elicited only slightly diminished T-cell and antibody responses compared to HER2 naïve mice. Most significantly, we were able to demonstrate that Ad-HER2-ki vaccination of HER2+ tolerant mice elicits significant anti-HER2+ tumor responses. Subsequent investigation into the oncogenicity associated with strong overexpression of HER2-ki revealed no evidence for its oncogenic functionality in terms of phosphorylation or transcriptional signature in primary human cells. We also found no evidence for its oncogenicity in enabling enhanced cellular proliferation, anchorage-independent growth, or transformation in vivo. In sum, we found that vaccination with mutationally inactivated, non-oncogenic Ad-HER2-ki results in robust polyclonal immune responses to HER2 in tolerant models, which translate into strong and effective anti-tumor responses in vivo. Ad-HER2-ki is thus a safe and promising vaccine for evaluation in clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2421.
Synthesis of a homologous series of ketomethylene arginyl pseudodipeptides and application to low molecular weight hirudin-like thrombin inhibitors (1992)

The design of low molecular weight thrombin inhibitors IIa-d (hirutonins) that bind concurrently with the enzyme's catalytic site and auxiliary "anion-binding exosite" for fibrinogen recognition is reported. A practical synthesis of the required homologous ketomethylene arginyl dipeptide inserts [Arg psi CO(CH2)nCO] (n = 1-4) corresponding to the P1-P1' scissile position of hirutonins is described. The substitution of the scissile amide function by a ketomethylene group is compatible with the enzyme active site and conferred complete plasma proteolytic stability. This modification also enhanced enzyme affinity up to 20-fold with hirutonin-4 (IIb, n = 4) displaying highest affinity (Ki = 140 +/- 20 pM). Hirutonins 1-4 exhibited potent inhibition of plasma prothrombin time (PT) and activated partial thromboplastin time (aPTT). The inhibition was biphasic and showed good correlation with the corresponding Ki. Hirutonin-2 inhibited thrombin-mediated platelet aggregation and exhibited a strong antithrombotic effect comparable to r-hirudin in an in vivo rat arteriovenous shunt model (ED15 = 1.20 mg/kg for hirutonin-2 and 1.14 mg/kg for r-hirudin). Lower molecular weight inhibitors were obtained by substituting the six native amino acid residues (Q-S-H-N-D-G), connecting the active site and the auxiliary exosite binding elements with a variable number of interening omega-aminopentenoyl units. In addition, the exosite component was reduced to seven amino acid residues (D-F-E-P-I-P-L). Incorporation of these modifications into the bifunctional format resulted in nanomolar thrombin inhibitory peptides (IIIa-c). The resulting inhibitors were studied by molecular modeling with alpha-thrombin, and the bimolecular interactions served to explain the retention of high enzyme affinity.
Kinetic Versus Thermodynamic Orientational Preferences for a Series of Isomorphic Molecular Semiconductors (2018)

Due to the anisotropic nature of charge transport through most organic semiconductors, the orientation of the conjugated backbone is of great relevance because it may affect final device properties. Herein, we present a set of four nearly isostructural molecular organic semiconducting materials whose orientation changes drastically with a two-atom change in the conjugated framework. We investigate the X-ray diffraction patterns of these materials in the thin film, both as-deposited from solution and following melt-annealing. Following melt-annealing of the films, crystallites of all four materials orient edge-on with respect to the substrate, which indicates that this orientation is thermodynamically preferred. We can infer that the initial face-on orientation of some of the materials is due to kinetic trapping during the spin-coating process. Previous observations from the literature suggest that the edge-on orientation is the thermodynamically preferable state for many organic semiconducting materials. However, a cohesive explanation for this phenomenon remains elusive.
Compact modeling of CRS devices based on ECM cells for memory, logic and neuromorphic applications (2013)

Dynamic physics-based models of resistive switching devices are of great interest for the realization of complex circuits required for memory, logic and neuromorphic applications. Here, we apply such a model of an electrochemical metallization (ECM) cell to complementary resistive switches (CRSs), which are favorable devices to realize ultra-dense passive crossbar arrays. Since a CRS consists of two resistive switching devices, it is straightforward to apply the dynamic ECM model for CRS simulation with MATLAB and SPICE, enabling study of the device behavior in terms of sweep rate and series resistance variations. Furthermore, typical memory access operations as well as basic implication logic operations can be analyzed, revealing requirements for proper spike and level read operations. This basic understanding facilitates applications of massively parallel computing paradigms required for neuromorphic applications.
Assessment of a Personal Interactive Carbon Monoxide Breath Sensor in People Who Smoke Cigarettes: Single-Arm Cohort Study (2020)

ClinicalTrials.gov NCT04133064; https://clinicaltrials.gov/ct2/show/NCT04133064.
Integration of supercapacitor with STATCOM for electric arc furnace flicker mitigation (2008)

The STATCOM based on voltage source converter is used for voltage regulation in transmission and distribution systems. In this paper, the integration and control of energy storage systems such as supercapacitor into a distribution system STATCOM (D-STATCOM) with voltage controller is developed to enhance power quality and improve distribution system reliability. This paper develops the control concepts to charge/discharge the supercapacitor by the D-STATCOM, and validates the performance for an integrated D-STATCOM/supercapacitor system for improving distribution system performance. The potential performance improvements are verified by simulation results for rapidly varying arc-furnace loads for voltage flicker mitigation, by supplying fluctuating real power by the D-STATCOM/supercapacitor system.