gebhart/patrepeval huggingface dataset:
NMR screening and crystal quality of bacterially expressed prokaryotic and eukaryotic proteins in a structural genomics pipeline (2005)

In the Joint Center for Structural Genomics, one-dimensional (1D) 1H NMR spectroscopy is routinely used to characterize the folded state of protein targets and, thus, serves to guide subsequent crystallization efforts and to identify proteins for NMR structure determination. Here, we describe 1D 1H NMR screening of a group of 79 mouse homologue proteins, which correlates the NMR data with the outcome of subsequent crystallization experiments and crystallographic structure determination. Based on the 1D 1H NMR spectra, the proteins are classified into four groups, "A" to "D." A-type proteins are candidates for structure determination by NMR or crystallography; "B"-type are earmarked for crystallography; "C" indicates folded globular proteins with broadened line shapes; and "D" are nonglobular, "unfolded" polypeptides. The results obtained from coarse- and fine-screen crystallization trials imply that only A- and B-type proteins should be used for extensive crystallization trials in the future, with C and D proteins subjected only to coarse-screen crystallization trials. Of the presently studied 79 soluble protein targets, 63% yielded A- or B-quality 1D 1H NMR spectra. Although similar yields of crystallization hits were obtained for all four groups, A to D, crystals from A- and B-type proteins diffracted on average to significantly higher resolution than crystals produced from C- or D-type proteins. Furthermore, the output of refined crystal structures from this test set of proteins was 4-fold higher for A- and B-type than for C- and D-type proteins.
Developing an antibiotic effective against multi-drug resistant bacteria. (2014)

The emergence of multi-drug resistant pathogenic bacteria is one of the great challenges to modern medicine. The gram positive cocci Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus faecalis (VRE) are two particularly virulent examples. In vivo studies have shown that the eukaryotic like 'mevalonate' isoprenoid pathway used by these pathogenic cocci is essential to their growth and virulence [1]. Our structures of HMG-CoA reductase (HMGR) from P. mevalonii demonstrated that the bacterial enzymes are structurally distinct from the human enzymes allowing for specific antibacterial activity [2]. High throughput in vitro screening against bacterial HMGR at the Southern Research Center, Birmingham, AL uncovered a lead compound with an IC50 of 80 µM with a competitive mode of action. Our x-ray crystal structures of HMGR from E. faecalis complexed with the lead compound and its variations have informed the synthesis of new inhibitors that have improved the IC50 to 5 µM [3]. Studies of this compound show it to be active against both MRSA and VRE in culture, effective against these bacteria in biofilms, and efficacious in a model system of eukaryotic infection. Structures and kinetics of these compounds will be presented and future directions discussed.
The effect of temporal frequency variation on threshold contrast sensitivity deficits in optic neuritis. (1983)

The effect of increasing temporal frequency on contrast sensitivity anomalies in unilateral optic neuritis has been investigated. For 4 c/deg gratings no change in the deficit was observed at any temporal frequency whereas there was a tendency for the deficit to decrease with increase in temporal frequency for 0-5 c/deg gratings. The latter effect was not observed in a case of optic neuritis with severe deficit and not in two cases of other optic nerve pathology. An explanation based on the assumption that "threshold scotomata" might be present in cases of demyelinating optic nerve disease is proposed.
Electron Transport and Nanomorphology in Solution‐Processed Polymeric Semiconductor n‐Doped with an Air‐Stable Organometallic Dimer (2017)

This study investigates electron transport and distribution of an organometallic dimer‐based dopant (RuCp*Mes)2 in benchmarked P(NDI2OD‐T2) films, in which electron transport is not affected by deep traps originating from atmospheric contaminants. The electron mobility of P(NDI2OD‐T2) can be enhanced by &gt;10‚ in diodes with reduced thermal activation energy using (RuCp*Mes)2 dopants, which is rationalized by the filling up of tail electronic states by doping induced carriers. n‐doping with (RuCp*Mes)2 can also improve electron injection at Schottky contacts in nanoscale transport measurements confirmed by conducting atomic force microscopy. The results suggest that the (RuCp*Mes)2 dopants are homogenously distributed throughout the P(NDI2OD‐T2) film, at least laterally, at moderate doping concentrations. Thus, these results demonstrate an opportunity of using air‐stable molecular n‐doping to modulate charge transport properties for solution‐processed organic optoelectronic devices.
Doubly Robust Inference for Targeted Minimum Loss Based Estimation in Randomized Trials with Missing Outcome Data (2017)

Missing outcome data is one of the principal threats to the validity of treatment effect estimates from randomized trials. The outcome distributions of participants with missing and observed data are often different, which increases the risk of bias. Causal inference methods may aid in reducing the bias and improving efficiency by incorporating baseline variables into the analysis. In particular, doubly robust estimators incorporate estimates of two nuisance parameters: the outcome regression and the missingness mechanism, to adjust for differences in the observed and unobserved groups that can be explained by observed covariates. Such nuisance parameters are traditionally estimated using parametric models, which generally preclude consistent estimation, particularly in moderate to high dimensions. Recent research on missing data has focused on data-adaptive estimation of the nuisance parameters in order to achieve consistency, but the large sample properties of such estimators are poorly understood. In this article we discuss a doubly robust estimator that is consistent and asymptotically normal (CAN) under data-adaptive consistent estimation of the outcome regression or the missingness mechanism. We provide a formula for an asymptotically valid confidence interval under minimal assumptions. We show that our proposed estimator has smaller finite-sample bias compared to standard doubly robust estimators. We present a simulation study demonstrating the enhanced performance of our estimators in terms of bias, efficiency, and coverage of the confidence intervals. We present the results of an illustrative example: a randomized, double-blind phase II/III trial of antiretroviral therapy in HIV-infected persons, and provide R code implementing our proposed estimators.
Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside-binding lectin, galectin-3. (1996)

Animal lectins play important roles in a variety of biological processes via their recognition of glycoconjugates. Galectin-3 is a beta-galactoside-binding lectin previously designated as epsilon BP (IgE-binding protein), CBP35, Mac-2, L-29, and L-34, and its expression has been associated with various physiological and pathological processes, including cell growth, tumor transformation, and metastasis. Galectin-3 is widely distributed in various tissues and cell types and is expressed in many leukocytes, with the notable exception of B and T lymphocytes. We now report that galectin-3 is abundantly expressed in a number of human T lymphotropic virus (HTLV)-I-infected human T cell lines, including F6T, HUT 102, K3T, MT-2, and SLB-I, but is not expressed in non-HTLV-I-infected T cell lines such as Jurkat, CEM, and MOLT-4. In addition, the galectin-3 level was markedly increased in human thymocytes after infection with HTLV-I as compared with uninfected thymocytes. The up-regulation of galectin-3 expression appeared to correlate well with HTLV-I gene expression, as undetectable or very low levels of galectin-3 were found in the S1T and ATL-1K cell lines, which are nonproductively infected with HTLV-I. In co-transfection experiments, the galectin-3 promoter was significantly up-regulated by expression vectors encoding the 40-kd Tax protein, a potent transactivator in HTLV-I. Analysis of various Tax mutants suggested that galectin-3 promoter induction is dependent on activation of the cyclic-AMP-responsive element binding protein/activation transcription factor family of transcription factors and, to a lesser extent, nuclear factor-kappa B/Rel induction. Transfection of human promonocytic U-937 cells with an HTLV-I Tax expression vector induced galectin-3 expression in this cell line. Functionally, galectin-3 was shown to activate interleukin-2 production in Jurkat T cells. Together, these findings raise the possibility that HTLV-I Tax production induces the transcription and subsequent synthesis and secretion of galectin-3, which in turn may further activate these T cells and contribute to the altered properties of cell growth found in adult T cell leukemia induced by HTLV-I.
First shear horizontal mode plate wave in LiNbO<inf>3</inf> showing 20 km/s phase velocity (2015)

Currently, cognitive radio using a white space of digital TV (DTV) channels is receiving a lot of attention. One of the key devices of a cognitive radio handset is a tunable filter capable of adjusting frequency and bandwidth (BW) throughout DTV band. The authors developed ultra-wideband resonators in a DTV band and ultra-wideband filters fully covering all DTV channels using 0th shear horizontal mode plate wave (SH <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</inf> ) in a (0°, 120°, 0°) LiNbO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> plate. However, they are fabricated on a self-suspended ultra-thin LiNbO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> plate of only 0.5–0.6 µm in thickness, which is mechanically fragile and difficult to fabricate at high yield. A much higher phase velocity than that of SH <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</inf> is required to make the plate practically thicker. The objective of this study is to explore a different mode of plate wave showing much higher phase velocity and wide BW. By FEM simulation, it is clarified that a first SH mode (SH <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> ) plate wave propagating in two kinds of new proposed structures, which are different from suitable SH <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</inf> mode structures for wide BW, has higher velocity than 20,000 m/s and wide BW of 24%.
PO-300 CIP2A-mediated regulation of senescence in basal-like breast cancer (2018)

Introduction Basal-like breast cancer (BLBC) is an aggressive breast cancer molecular subtype, and it lacks efficient therapy options. Expression levels of oncoprotein CIP2A are increased in BLBC as compared to other breast cancer subtypes. Our results demonstrate that high CIP2A expression significantly predicts poor patient survival in triple negative breast cancer, that constitutes a major subset of BLBC. CIP2A inhibition also significantly impairs tumour growth of human BLBC xenografts. Previously, we have shown that CIP2A promotes breast cancer by inhibiting senescent growth arrest (Laine et al. Cancer Discov 2013). Induction of senescence and senescence associated secretome (SASP) has been shown to alter function of tumour infiltrating immune cells. Based on this we hypothesise that in addition to effects of CIP2A-mediated senescence inhibition to tumour cell-intrinsic mechanisms, it may impact infiltrating immune cells and thus therapy response. Material and methods To investigate the role of CIP2A in BLBC a carcinogen DMBA-induced tumour formation approach in Cip2a-/- mouse model was applied. In order to test our hypothesis about the effect of CIP2A-targeted senescence in immune cells we have set up mouse mammary tumour cell and organoid cultures from a spontaneous BLBC genetically engineered mouse model K14Cre;Brca1fl/fl;Tp53fl/fl. These cultures are genetically manipulated by CRISPR/Cas9 system to knock out CIP2A both prior to transplantation into recipient mice and in established tumours. To validate the in vivo findings we are using several different human breast cancer patient cohorts. Results and discussions Our results demonstrate that CIP2A-deficient mice are severely impaired in a formation of DMBA-induced basal-like mammary tumours. Together with the clinical data, these results suggest that CIP2A is a novel driver oncoprotein, and a potential therapeutic target, in human BLBC. In addition, we have validated the tumour cell-intrinsic role of CIP2A in K14Cre;Brca1fl/fl;Tp53fl/fl BLBC mouse model as loss of CIP2A induces senescent growth arrest in mammary gland tumour cells in vitro. Currently, we are studying the interplay between the immune system and CIP2A-inhibited tumours in vitro and in vivo. Conclusion Overall, this study will address feasibility of CIP2A targeting as a novel approach to combat basal-like breast cancer. Results of this project will also enhance our general understanding of cross-talk between senescent cancer cells and the tumour environment in this clinically challenging human cancer type.
AAV9-MCT8 Delivery at Juvenile Stage Ameliorates Neurological and Behavioral Deficits in a Mouse Model of MCT8-Deficiency (2022)

<b><i>Background:</i></b> Allan-Herndon-Dudley syndrome (AHDS) is a severe psychomotor disability disorder that also manifests characteristic abnormal thyroid hormone (TH) levels. AHDS is caused by inactivating mutations in monocarboxylate transporter 8 (MCT8), a specific TH plasma membrane transporter widely expressed in the central nervous system (CNS). <i>MCT8</i> mutations cause impaired transport of TH across brain barriers, leading to insufficient neural TH supply. There is currently no successful therapy for the neurological symptoms. Earlier work has shown that intravenous (IV), but not intracerebroventricular adeno-associated virus serotype 9 (AAV9) -based gene therapy given to newborn <i>Mct8</i> knockout (<i>Mct8<sup>-/y</sup></i>) male mice increased triiodothyronine (T<sub>3</sub>) brain content and partially rescued TH-dependent gene expression, suggesting a promising approach to treat this neurological disorder. <b><i>Methods:</i></b> The potential of IV delivery of AAV9 carrying human MCT8 was tested in the well-established Mct8<sup>-/y</sup>/Organic anion-transporting polypeptide 1c1 <i>(Oatp1c1)<sup>-/ -</sup></i> double knockout (dKO) mouse model of AHDS, which, unlike <i>Mct8</i><sup><i>-/y</i></sup> mice, displays both neurological and TH phenotype. Further, as the condition is usually diagnosed during childhood, treatment was given intravenously to P30 mice and psychomotor tests were carried out blindly at P120-P140 after which tissues were collected and analyzed. <b><i>Results:</i></b> Systemic IV delivery of AAV9-MCT8 at a juvenile stage led to improved locomotor and cognitive functions at P120-P140, which was accompanied by a near normalization of T<sub>3</sub> content and an increased response of positively regulated TH-dependent gene expression in different brain regions examined (thalamus, hippocampus, and parietal cortex). The effects on serum TH concentrations and peripheral tissues were less pronounced, showing only improvement in the serum T<sub>3</sub>/reverse T<sub>3</sub> (rT<sub>3</sub>) ratio and in liver <i>deiodinase 1</i> expression. <b><i>Conclusion:</i></b> IV administration of AAV9, carrying the human MCT8, to juvenile dKO mice manifesting AHDS has long-term beneficial effects, predominantly on the CNS. This preclinical study indicates that this gene therapy has the potential to ameliorate the devastating neurological symptoms in patients with AHDS.
Polyelectrolyte Microcapsules as Antigen Delivery Vehicles To Dendritic Cells: Uptake, Processing, and Cross‐Presentation of Encapsulated Antigens (2009)

Eingeschleuste Wirkung: Abbaubare Polyelektrolytmikrokapseln (PMs; siehe Bild) als Antigentransporter werden von dendritischen Zellen (DCs) durch Makropinocytose aufgenommen. Nach der Aufnahme bricht die Schale der Mikrokapseln auf, worauf der Cytoplasmainhalt in die hohlen PM-Kerne eindringt, sodass die DCs das eingekapselte Antigen effizient prozessieren können.
Semantic Channel Equalizer: Modelling Language Mismatch in Multi-User Semantic Communications (2023)

We consider a multi-user semantic communications system in which agents (transmitters and receivers) interact through the exchange of semantic messages to convey meanings. In this context, languages are instrumental in structuring the construction and consolidation of knowledge, influencing conceptual representation and semantic extraction and interpretation. Yet, the crucial role of languages in semantic communications is often overlooked. When this is not the case, agent languages are assumed compatible and unambiguously interoperable, ignoring practical limitations that may arise due to language mismatching. This is the focus of this work. When agents use distinct languages, message interpretation is prone to semantic noise resulting from critical distortion introduced by semantic channels. To address this problem, this paper proposes a new semantic channel equalizer to counteract and limit the critical ambiguity in message interpretation. Our proposed solution models the mismatch of languages with measurable transformations over semantic representation spaces. We achieve this using optimal transport theory, where we model such transformations as transportation maps. Then, to recover at the receiver the meaning intended by the teacher we operate semantic equalization to compensate for the transformation introduced by the semantic channel, either before transmission and/or after the reception of semantic messages. We implement the proposed approach as an operation over a codebook of transformations specifically designed for successful communication. Numerical results show that the proposed semantic channel equalizer outperforms traditional approaches in terms of operational complexity and transmission accuracy.
Host materials for blue phosphorescent OLEDs (2012)

PCTrz, a new bipolar host material containing a phenoxy-carbazole separated from a biscarbazolyl-triazine by a non-conjugated ether bond is presented. Computational calculations demonstrated the separation of PCTrz into an oxidation and a reduction site. A phosphorescent OLED with PCTrz as host and FIrpic as blue emitter yielded high current efficiencies of up to 16.2 cd/A. Additionally two electron transporting host materials DBFTaz and DBFTazC, both containing 1,2,4-triazole moieies, were synthesized and characterized. The triazole moiety in DBFTaz was formed by a classical ring closure reaction between a N-benzoylbenzimidate and a hydrazine. For DBFTazC we used another synthetical pathway which involves subsequent coupling of a carbazole and a triazole moiety to a dibenzofuran core. Both triazoles posses high triplet energies of 2.95 eV for DBFTaz and 2.97 eV for DBFTazC, which make the compounds interesting as matrix materials for blue phosphorescent OLEDs.
Observation of Light-by-Light Scattering in Ultraperipheral Pb+Pb Collisions with the ATLAS Detector (2019)

This Letter describes the observation of the light-by-light scattering process, γγ→γγ, in Pb+Pb collisions at sqrt[s_{NN}]=5.02 TeV. The analysis is conducted using a data sample corresponding to an integrated luminosity of 1.73 nb^{-1}, collected in November 2018 by the ATLAS experiment at the LHC. Light-by-light scattering candidates are selected in events with two photons produced exclusively, each with transverse energy E_{T}^{γ}>3 GeV and pseudorapidity |η_{γ}|<2.4, diphoton invariant mass above 6 GeV, and small diphoton transverse momentum and acoplanarity. After applying all selection criteria, 59 candidate events are observed for a background expectation of 12±3 events. The observed excess of events over the expected background has a significance of 8.2 standard deviations. The measured fiducial cross section is 78±13(stat)±7(syst)±3(lumi) nb.
ChemInform Abstract: Identification of (R)‐N‐(4‐(4‐Methoxyphenyl)thiazol‐2‐yl) ‐1‐tosylpiperidine‐2‐carboxamide, ML277, as a Novel, Potent and Selective Kv7.1 (KCNQ1) Potassium Channel Activator. (2013)

Abstract Compound (I) is identified as a potent activator of KCNQ1 channels using a high‐throughput screen of the NIH Molecular Library Small Molecule Repository.
Laparoscopic repair of diaphragmatic defect by total intracorporeal suturing: clinical and technical considerations. (2001)

Laparoscopic repair of the diaphragm should be commensurate with traditional open surgical principles. In this regard, it is essential that surgeons interested in performing "advanced" laparoscopic oncologic surgery become facile in laparoscopic suturing.
Atrial Fibrillation and Catheter Ablation (2022)

In this instructional video, Drs. Jane Leopold, Elliott Antman, William Sauer, and Paul Zei provide an overview of the classification and diagnosis of atrial fibrillation, management strategies, and mitigation of stroke risk with anticoagulation therapy. The video also focuses on the new rhythm-control strategy of catheter ablation therapy, with attention to the success rate, potential complications, postprocedural monitoring for recurrence of atrial fibrillation, and consideration of ongoing anticoagulation therapy in these patients.
Interpretation of Approximate Entropy: Analysis of Intracranial Pressure Approximate Entropy During Acute Intracranial Hypertension (2005)

We studied changes in intracranial pressure (ICP) complexity, estimated by the approximate entropy (ApEn) of the ICP signal, as subjects progressed from a state of normal ICP (< 20-25 mmHg) to acutely elevated ICP (an ICP "spike" defined as ICP > 25 mmHg for < or = 5 min). We hypothesized that the measures of intracranial pressure (ICP) complexity and irregularity would decrease during acute elevations in ICP. To test this hypothesis we studied ICP spikes in pediatric subjects with severe traumatic brain injury (TBI). We conclude that decreased complexity of ICP coincides with episodes of intracranial hypertension (ICH) in TBI. This suggests that the complex regulatory mechanisms that govern intracranial pressure are disrupted during acute rises in ICP. Furthermore, we carried out a series of experiments where ApEn was used to analyze synthetic signals of different characteristics with the objective of gaining a better understanding of ApEn itself, especially its interpretation in biomedical signal analysis.