gebhart/patrepeval huggingface dataset:
The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells (2020)

The in-clinic phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib (CAL-101) and duvelisib (IPI-145) have demonstrated high rates of response and progression-free survival in clinical trials of B-cell malignancies, such as chronic lymphocytic leukemia (CLL). However, a high incidence of adverse events has led to frequent discontinuations, limiting the clinical development of these inhibitors. By contrast, the dual PI3Kδ/casein kinase-1-ε (CK1ε) inhibitor umbralisib (TGR-1202) also shows high rates of response in clinical trials but has an improved safety profile with fewer severe adverse events. Toxicities typical of this class of PI3K inhibitors are largely thought to be immune mediated, but they are poorly characterized. Here, we report the effects of idelalisib, duvelisib, and umbralisib on regulatory T cells (Tregs) on normal human T cells, T cells from CLL patients, and T cells in an Eμ-TCL1 adoptive transfer mouse CLL model. Ex vivo studies revealed differential effects of these PI3K inhibitors; only umbralisib treatment sustained normal and CLL-associated FoxP3+ human Tregs. Further, although all 3 inhibitors exhibit antitumor efficacy in the Eμ-TCL1 CLL model, idelalisib- or duvelisib-treated mice displayed increased immune-mediated toxicities, impaired function, and reduced numbers of Tregs, whereas Treg number and function were preserved in umbralisib-treated CLL-bearing mice. Finally, our studies demonstrate that inhibition of CK1ε can improve CLL Treg number and function. Interestingly, CK1ε inhibition mitigated impairment of CLL Tregs by PI3K inhibitors in combination treatment. These results suggest that the improved safety profile of umbralisib is due to its role as a dual PI3Kδ/CK1ε inhibitor that preserves Treg number and function.
Simple magnetic charge model for representation of emi responses from a buried UXO (2004)

Low frequency electromagnetic induction (EMI) sensing, operating from ten's of Hertz up to several hundred's of kHz, has been identified as one of most promising technologies for detection and discrimination of subsurface metallic objects, particularly unexploded ordnance (UXO's). In EMI sensing, which is a pure EM diffusion rather than wave phenomena, displacement currents within an object and its surrounding medium are negligible. Therefore the scattered field outside the object can be represented as a sum of quasi-static magnetic fields radiated by magnetic charges placed on a fictitious surface. This paper presents a simple surface magnetic charge model for fast and accurate representation of EMI signal for any metallic scatterer of interest. The magnetic charges and Green's function associated with them are much simpler than magnetic dipoles and their dyadic Green's functions. The simplicity and computational accuracy of the magnetic charge model makes it an alternative candidate to the simple dipole model for buried metallic object discrimination in EMI frequency range. In addition, for a given object the amplitudes of the magnetic charges are unique and they can be used to discriminate an object of interest from innocuous items. The amplitudes of the responding magnetic charges are determined from measured data. Several numerical results are presented to demonstrate the accuracy and superior computational speed of the proposed method. I. Introduction
Limitations of ROC on Imbalanced Data: Evaluation of LVAD Mortality Risk Scores (2020)

Objective: This study illustrates the ambiguity of ROC in evaluating two classifiers of 90-day LVAD mortality. This paper also introduces the precision recall curve (PRC) as a supplemental metric that is more representative of LVAD classifiers performance in predicting the minority class. Background: In the LVAD domain, the receiver operating characteristic (ROC) is a commonly applied metric of performance of classifiers. However, ROC can provide a distorted view of classifiers ability to predict short-term mortality due to the overwhelmingly greater proportion of patients who survive, i.e. imbalanced data. Methods: This study compared the ROC and PRC for the outcome of two classifiers for 90-day LVAD mortality for 800 patients (test group) recorded in INTERMACS who received a continuous-flow LVAD between 2006 and 2016 (mean age of 59 years; 146 females vs. 654 males) in which mortality rate is only %8 at 90-day (imbalanced data). The two classifiers were HeartMate Risk Score (HMRS) and a Random Forest (RF). Results: The ROC indicates fairly good performance of RF and HRMS classifiers with Area Under Curves (AUC) of 0.77 vs. 0.63, respectively. This is in contrast with their PRC with AUC of 0.43 vs. 0.16 for RF and HRMS, respectively. The PRC for HRMS showed the precision rapidly dropped to only 10% with slightly increasing sensitivity. Conclusion: The ROC can portray an overly-optimistic performance of a classifier or risk score when applied to imbalanced data. The PRC provides better insight about the performance of a classifier by focusing on the minority class.
Low leakage normally-off tri-gate GaN MISFET (2012)

A new tri-gate normally-off GaN metal-insulator-semiconductor field effect transistor (MISFET) is presented in this paper. By using a three-dimensional gate structure with combination of a sub-micron gate recess, the new device achieves a very low off-state drain leakage current of 0.6 μA/mm at a breakdown voltage of 565 V while maintains a low on-resistance of 2.1 mΩ·cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The new device has an on/off current ratio of more than 8 orders of magnitude and a sub-threshold slope of 86±9 mV/decade. The threshold voltage of the new device is 0.80±0.06 V with a maximum drain current of 530 mA/mm. These results confirm the great potential of the tri-gate normally-off GaN-on-Si MISFETs for the next generation of power electronics.
Complexation thermodynamics of free and graft oligomers with complementary polymers (1991)

Abstract The dilute solution complexation equilibrium between linear macromolecules and smaller complementary oligomers is considered when: (1) the oligomers are free in solution; and (2) the oligomers are covalently attached at one end to the polymer. A general statistical mechanical framework is developed and is illustrated using a simple random walk model for polymer conformation. The statistical mechanical partition functions are formulated using a generating function technique, allowing thermodynamic averages in the complexed state to be calculated. Loops, trains, and tails of all possible length are allowed in the conformation of a complexed oligomer. Simulation results for the free oligomer case are compared with those obtained for oligomers covalently attached to the polymeric molecular. The model provides a theoretical explanation for the experimentally observed enhancement of complexation of oligomers grafted to the complementary polymers.
HMGB1–C1q complexes regulate macrophage function by switching between leukotriene and specialized proresolving mediator biosynthesis (2019)

Macrophage polarization is critical to inflammation and resolution of inflammation. We previously showed that high-mobility group box 1 (HMGB1) can engage receptor for advanced glycation end product (RAGE) to direct monocytes to a proinflammatory phenotype characterized by production of type 1 IFN and proinflammatory cytokines. In contrast, HMGB1 plus C1q form a tetramolecular complex cross-linking RAGE and LAIR-1 and directing monocytes to an antiinflammatory phenotype. Lipid mediators, as well as cytokines, help establish a milieu favoring either inflammation or resolution of inflammation. This study focuses on the induction of lipid mediators by HMGB1 and HMGB1 plus C1q and their regulation of IRF5, a transcription factor critical for the induction and maintenance of proinflammatory macrophages. Here, we show that HMGB1 induces leukotriene production through a RAGE-dependent pathway, while HMGB1 plus C1q induces specialized proresolving lipid mediators lipoxin A4, resolvin D1, and resolvin D2 through a RAGE- and LAIR-1-dependent pathway. Leukotriene exposure contributes to induction of IRF5 in a positive-feedback loop. In contrast, resolvins (at 20 nM) block IRF5 induction and prevent the differentiation of inflammatory macrophages. Finally, we have generated a molecular mimic of HMGB1 plus C1q, which cross-links RAGE and LAIR-1 and polarizes monocytes to an antiinflammatory phenotype. These findings may provide a mechanism to control nonresolving inflammation in many pathologic conditions.
Disruption of POGZ Is Associated with Intellectual Disability and Autism Spectrum Disorders (2016)

Intellectual disability (ID) and autism spectrum disorders (ASD) are genetically heterogeneous, and a significant number of genes have been associated with both conditions. A few mutations in POGZ have been reported in recent exome studies; however, these studies do not provide detailed clinical information. We collected the clinical and molecular data of 25 individuals with disruptive mutations in POGZ by diagnostic whole-exome, whole-genome, or targeted sequencing of 5,223 individuals with neurodevelopmental disorders (ID primarily) or by targeted resequencing of this locus in 12,041 individuals with ASD and/or ID. The rarity of disruptive mutations among unaffected individuals (2/49,401) highlights the significance (p = 4.19 × 10(-13); odds ratio = 35.8) and penetrance (65.9%) of this genetic subtype with respect to ASD and ID. By studying the entire cohort, we defined common phenotypic features of POGZ individuals, including variable levels of developmental delay (DD) and more severe speech and language delay in comparison to the severity of motor delay and coordination issues. We also identified significant associations with vision problems, microcephaly, hyperactivity, a tendency to obesity, and feeding difficulties. Some features might be explained by the high expression of POGZ, particularly in the cerebellum and pituitary, early in fetal brain development. We conducted parallel studies in Drosophila by inducing conditional knockdown of the POGZ ortholog row, further confirming that dosage of POGZ, specifically in neurons, is essential for normal learning in a habituation paradigm. Combined, the data underscore the pathogenicity of loss-of-function mutations in POGZ and define a POGZ-related phenotype enriched in specific features.
Chain Dynamics in Antiplasticized and Annealed Poly(ethylene terephthalate) Determined by Solid-State NMR and Correlated with Enhanced Barrier Properties (2012)

Using solid-state NMR, site-specific chain dynamics from the hertz to mid-kilohertz regime were examined in compression-molded films of poly(ethylene terephthalate) (PET), PET filled with 2 wt % acetanilide or phenacetin, and PET annealed below and above the glass transition temperature (Tg). More specifically, 13C relaxation time in the rotating frame, 1H–13C cross-polarization times, and 13C chemical-shift anisotropy exchange were measured at natural abundance. 13C CP/MAS spectra revealed that PET annealed above Tg was 28% crystalline, and all other PET samples were completely amorphous. Relaxation times in these polymers were analyzed using stretched exponentials which yielded characteristic time constants. The filled PET and PET annealed above Tg exhibited suppressed chain dynamics across the entire hertz to mid-kilohertz regime that were correlated with reduced CO2 and O2 permeabilities. Using the centerband-only detection of exchange (CODEX) sequence, the fraction of flipping phenylene rings was observed to decrease in these polymers, with the decrease in the semicrystalline sample consistent with the crystalline fraction.
Synthesis and structural features of complexes [(P∩P)2Rh][hfacac] containing hexafluoroacetyl- acetonate as a noncoordinating anion (2001)

The synthesis and characterization of complexes [(P ∩ P) 2 Rh][hfacac] (P ∩ P = chelating bidentate phosphine ligand R 2 P(CH 2 ) n PR 2 (2a-g), hfacac = hexafluoroacetylacetonate anion) (4) is reported. The molecular structures of 4a (R = Ph, n = 1) and 4f (R = Cy, n = 2) in the solid state were determined by single-crystal X-ray diffraction. The complexes crystallize in the monoclinic space groups C2/c (No. 15) and P2 1 /n (No. 14), respectively. No coordinative interaction between the rhodium center of the cation [(P ∩ P) 2 Rh] + (4a + , 4f + ) and the hfacac anion is evident in either cases. In the crystal structure of 4a, hydrogen bonds between the oxygen atoms of the hfacac anion and methylene protons of the CH 2 bridges of the phosphine ligand lead to highly symmetric chains of regularly alternating cations and anions. The coordination geometry around the rhodium center in 4a + is ideally square-planar, whereas 4f + is significantly distorted towards a tetrahedron with an angle between the two P 2 Rh moieties of 18.6°. The cation 4b + (R = Cy, n = 1) was investigated in form of the tetrafluoroborate salt for comparison. The compound [{Cy 2 P(CH 2 )PCy 2 } 2 Rh][BF 4 ] crystallizes as a THF solvate (4b′) in the triclinic space group P[Formula: see text] (No. 2) containing ideally square-planar [(P ∩ P) 2 Rh] + cations. Key words: rhodium, chelating ligands, coordination modes, 1,3-diketonates, phosphorus ligands.
AUTOMATED ACQUISITION AND PROCESSING OF MULTICHANNEL COMPLEX RESISTIVITY DATA (2006)

We describe the design and construction of a multichannel, broad band full waveform complex resistivity system developed at INL. This system is primarily used for laboratory monitoring&lt;br&gt;experiments focused on permeable reactive barriers. These experiments can run from days to months. As such experiments can create significant amounts of data (both in direct cr data as well as in auxiliary data) acquisition and experimental control have been completely automated. Full waveform data is collected continuously by a dedicated computer, with each dataset taking about 2 hours to collect. As soon as a dataset is completed, data gets transferred to a webserver throug webservice calls. At the server, data is parsed into a MySQL relational database, and processed to extract phase and amplitude information from each data. Users can access raw and processed data, compare temporal evolution of specific data channels and match the data to different models using a webinterface. This type of automation allows users to focus on data interpretation rather than on data handling, and provides for tools for remote collaboration and research.
Double-stage gate drive circuit for parallel connected IGBT modules (2009)

Solid state modulators are increasingly being used in pulsed power applications. In these applications IGBT modules must often be connected in parallel due to their limited power capacity. In a previous paper, we introduced a control method for balancing the currents in the IGBTs. In this paper, we investigate techniques to minimize the modules' rise and fall times, which can positively impact the modulator's output pulse parameters, which in turn must meet the application's specifications. Further, a reduction in rise and fall times lowers switching losses and thus increases the modulator's efficiency. To reduce the voltage rise time of the pulse without increasing the maximal over-voltage of the parallel IGBTs we have investigated a double-stage gate driver with protection circuits to avoid over-voltages and over-currents. Additionally voltage edge detection has been implemented to improve current balancing. Our measurement results reveal the dependency of the rise-time and turnoff losses on the design parameters of the gate drive. We show that our design achieves a 62% reduction in the turn-off rise time, and a 32% reduction in the turn-off losses.
The “β-Fluorine Effect” in the Non-Metal Hydride Radical Deoxygenation of Fluorine-Containing Nucleoside Xanthates (2000)

An alternative method to conduct a Barton-McCombie deoxygenation in nucleosides is described. The utility of the procedure is limited to structures with an electronegative substituent, particularly fluorine, in the beta-position relative to the radical center. The process is radical in nature and triggered by peroxides. The abstraction of hydrogen from the solvent is favorably influenced by the presence of a beta-fluorine.
A Hybrid System for Preventing Postsurgical Adhesions (2008)

Purdue University, West Lafayette, Indiana (Yeo) Children's Hospital, Harvard Medical School, Boston, Massachusetts, [email protected] (Kohane)
Pinning Modes and Interlayer Correlation in High-Magnetic-Field Bilayer Wigner Solids (2007)

We report studies of pinning mode resonances in the low total Landau filling (nu) Wigner solid of a series of bilayer hole samples with negligible interlayer tunneling and with varying interlayer separation d. Comparison of states with equal layer densities (p,p) to single layer states (p,0) produced in situ by biasing, indicates that there is interlayer quantum correlation in the solid at small d. Also, the resonance frequency at small d is decreased just near nu = 1/2 and 2/3, indicating the importance in the solid of correlations related to those in the fractional quantum Hall effects.
Biased T-Cell Antigen Receptor Repertoire in Lyme Arthritis (1998)

A common concern with many autoimmune diseases of unknown etiology is the extent to which tissue T-lymphocyte infiltrates, versus a nonspecific infiltrate, reflect a response to the causative agent. Lyme arthritis can histologically resemble rheumatoid synovitis, particularly the prominent infiltration by T lymphocytes. This has raised speculation about whether Lyme synovitis represents an ongoing response to the causative spirochete, Borrelia burgdorferi, or rather a self-perpetuating autoimmune reaction. In an effort to answer this question, the present study examined the repertoire of infiltrating T cells in synovial fluid from nine Lyme arthritis patients, before and after stimulation with B. burgdorferi. Using a highly sensitive and consistent quantitative PCR technique, a comparison of the T-cell antigen receptor (TCR) beta-chain variable (Vbeta) repertoires of the peripheral blood and synovial fluid showed a statistically significant increase in expression of Vbeta2 and Vbeta6 in the latter. This is remarkably similar to our previous findings in studies of rheumatoid arthritis and to other reports on psoriatic skin lesions. However, stimulation of synovial fluid T cells with B. burgdorferi provoked active proliferation but not a statistically significant increase in expression of any TCR Vbeta, including Vbeta2 and Vbeta6. Collectively, the findings suggest that the skewing of the TCR repertoire of fresh synovial fluid in Lyme arthritis may represent more a synovium-tropic or nonspecific inflammatory response, similar to that occurring in rheumatoid arthritis or psoriasis, rather than a specific Borrelia reaction.
Supplementary Figure 3 from microRNA-205 Regulates HER3 in Human Breast Cancer (2023)

Supplementary Figure 3 from microRNA-205 Regulates HER3 in Human Breast Cancer
Magnetresonanztomografie bei ultrahohen Feldstärken - Forschungsbericht 2014 Max-Planck-Institut für biologische Kybernetik (2014)

Um die räumliche und zeitliche Auflösung der Magnetresonanztomografie zu verbessern, werden immer höhere Magnetfeldstärken verwendet: So wird das zu detektierende Signal verstärkt. Hierfür müssen technologische Herausforderungen, wie zum Beispiel die Entwicklung neuartiger Radiofrequenzspulen, bewältigt werden. Erste klinische Studien mit selbstentwickelten Spulen wurden bereits an Tumoren im menschlichen Gehirn bei einer Feldstärke von 9,4 Tesla durchgeführt. Verglichen wurden die Spektren von gesundem und tumorösem Gewebe. Die Ergebnisse zeigen großes Potenzial für medizinische Anwendungen.
Molecular cytogenetic analysis in the study of brain tumors: findings and applications (2005)

Classic cytogenetics has evolved from black and white to technicolor images of chromosomes as a result of advances in fluorescence in situ hybridization (FISH) techniques, and is now called molecular cytogenetics. Improvements in the quality and diversity of probes suitable for FISH, coupled with advances in computerized image analysis, now permit the genome or tissue of interest to be analyzed in detail on a glass slide. It is evident that the growing list of options for cytogenetic analysis has improved the understanding of chromosomal changes in disease initiation, progression, and response to treatment. The contributions of classic and molecular cytogenetics to the study of brain tumors have provided scientists and clinicians alike with new avenues for investigation. In this review the authors summarize the contributions of molecular cytogenetics to the study of brain tumors, encompassing the findings of classic cytogenetics, interphase- and metaphase-based FISH studies, spectral karyotyping, and metaphase- and array-based comparative genomic hybridization. In addition, this review also details the role of molecular cytogenetic techniques in other aspects of understanding the pathogenesis of brain tumors, including xenograft, cancer stem cell, and telomere length studies.
Write grouping for update-based cache coherence protocols (2002)

In our previous work, we demonstrated the possible performance gains from update-based cache coherence protocols for a set of fine-grain scientific applications running on a scalable shared-memory multiprocessor. In this paper, we examine in detail the hardware-based write grouping scheme presented in our earlier work. First we describe both software-based and hardware-based write grouping schemes. The software-based scheme, with its perfect knowledge of the application's write pattern, is able to achieve optimal write grouping efficiency, but not without added complexity to the application's code. Nevertheless, we use the software-based scheme to determine the optimal grouping efficiency for each application studied and then demonstrate that the hardware-based write grouping scheme is almost as efficient as the software-based scheme, but it requires little, if any, software modifications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Lymphatic draining patterns following submucosal rectal injections of methylene blue dye. (2015)

&lt;p&gt;Up to 50 μl of methylene blue was injected submucosally in the rectum prior to euthanasia. During necropsy, stained lymph nodes were identified, photographed and successively reinjected (intranodaly) to identify the next stained lymph node in the draining chain. (A) An illustration of the various pelvic lymph nodes and rectal injection sites for orientation and reference. Each colored box represents the site of each photograph in panels B-D. Panel B shows evidence of dye staining within the internal iliac lymph nodes. Panel C shows evidence of dye staining within the common iliac lymph nodes following internal iliac dye injection, interestingly an anatomic variation in the lymphatic pathway in this animal resulted in dye crossing the midline and enhancing a left common iliac node as well. Panel D shows evidence of dye staining within the para-aortic lymph node following common iliac dye injection. All images are representative of the 5 animals examined by methylene blue dye.&lt;/p&gt;