gebhart/patrepeval huggingface dataset:
SAFETY AND CLINICAL ACTIVITY OF TEMSIROLIMUS IN COMBINATION WITH RITUXIMAB AND DHAP IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA–REPORT OF THE PROSPECTIVE, MULTICENTER PHASE II STORM TRIAL (2017)

Purpose: To evaluate the safety, tolerability and efficacy of the combination of the mTOR inhibitor Temsirolimus and a standard salvage regimen (R-DHAP) in patients with relapsed or refractory diffuse large cell B-cell lymphoma (DLBCL). Methods: This is a prospective, multicenter, phase II, open-label study. Patients with relapsed or refractory DLBCL with a maximum of two prior treatment lines were eligible. The STORM regimen consisted of Rituximab 375 mg/m2 (day 2) and DHAP (Dexamethasone 40 mg days 3-6, Cisplatine 100 mg/m2 day 3, Cytarabine 2 × 2 g/m2 day 4) with Temsirolimus added on day 1 and 8 of a 21-day cycle, with 2-4 cycles planned. In part I, dose levels of 25, 50, 75 and 100 mg for Temsirolimus were predefined. Based on the observed toxicity profile, the independent data safety committee recommended a Temsirolimus dose of 25 mg given on day 1 and 8 for the part II extension cohort of the trial. Results: We here report on 55 patients (pts), 15 from part I and 40 from part II. Five pts were not evaluable for response. Of the evaluable 50 patients, median age was 63 years, and median number of prior regimen was 1. Temsirolimus dose was 50 mg on day 1 and 8 in 7 pts from the part I of the trial and 25 mg in the remaining 48 pts. The overall response rate was 78% (39/50pts) with 28 partial and 11 complete responses. In addition, two patients with SD hat a negative PET-CT; however, because no baseline PET-CT was available, these patients were not assessed as responses. After a median follow-up of 10 months for the total study population, median PFS and OS have not been reached. Early safety analysis includes preliminary data of 22 pts. The most frequent non-hematologic side effects were nausea (14 pts, 64%), epistaxis (11 pts, 50%), fatigue (12 pts, 55%), fever (11 pts, 50%) and diarrhea (11 pts, 50%). Frequent grade 3/4 events (n > 2) included leukopenia (21 pts, 95%), thrombocytopenia (20 pts, 91%), lymphopenia (11pts, 50%), anemia (8 pts, 36%), neutropenia (10 pts, 45%), renal failure (3 pts, 20%) and infections (7 pts, 32%, bladder infection, esophagus infection, central venous access infection, soft tissue infection, mucositis). Two therapy-related deaths occurred (one patient died from sepsis during neutropenia, another from cerebral bleeding, both events occurring after cycle 3). Conclusion: Temsirolimus can be safely added to DHAP and Rituximab with promising activity. Keywords: diffuse large B-cell lymphoma (DLBCL); mTor inhibitors; salvage treatment
Editorial Comment (2016)

No AccessJournal of UrologyNew Technology and Techniques1 Jul 2016Editorial Comment Ralph V. Clayman Ralph V. ClaymanRalph V. Clayman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.01.128AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, 196(1), p. 233 References 1 : Developments in the technique of endoscopic combined intrarenal surgery in the prone split-leg position. Urology2014; 84: 565. Google Scholar © 2016 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 196Issue 1July 2016Page: 233 Advertisement Copyright & Permissions© 2016 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ralph V. Clayman More articles by this author Expand All Advertisement PDF downloadLoading ...
Plasma Protein Adsorption and Biological Identity of Systemically Administered Nanoparticles (2017)

Although a variety of nanoparticles (NPs) have been used for drug delivery applications, their surfaces are immediately covered by plasma protein corona upon systemic administration. As a result, the adsorbed proteins create a unique biological identity of the NPs that lead to unpredictable performance. The protein corona on NPs could also impede active targeting, induce off-target effects, trigger particle clearance and even provoke toxicity. This article reviews the fundamentals of NP-plasma protein interaction, the consequences of the interactions, and provides insights into the correlations of protein corona with biodistribution and cellular delivery. We hope that this review will trigger additional questions and possible solutions that lead to more favorable developments in NP-based targeted delivery systems.
Antimicrobial activity of nisin incorporated in pectin and polylactic acid composite films against Listeria monocytogenes (2008)

Summary An extruded composite food packaging film containing pectin, polylactic acids (PLAs) and nisin was developed to inhibit Listeria monocytogenes . The mechanical properties and surface structure of the film were also examined. Cells of L. monocytogenes were reduced by 2.1, 4.5 and 3.7 log units mL −1 by the pectin plus PLA (pectin/PLA) film containing nisin (1000 IU mL −1 of tested liquid) in Brain Heart Infusion (BHI) broth, liquid egg white and orange juice, respectively, after 48 h at 24 °C. Pectin played an important roll in embedding nisin into the film. The pectin/PLA film had a similar stiffness but lower tensile strength, elongation and fracture energy than the pure PLA film. These data suggested that nisin incorporated into the pectin/PLA film was an effective approach to reducing L. monocytogenes in a typical growth medium (e.g. BHI broth) as well as in foods (e.g. orange juice and liquid egg).
Tuning of Natural Killer Cell Reactivity by NKp46 and Helios Calibrates T Cell Responses (2012)

Natural killer (NK) cells are lymphocytes involved in antimicrobial and antitumoral immune responses. Using N-ethyl-N-nitrosourea mutagenesis in mice, we identified a mutant with increased resistance to viral infections because of the presence of hyperresponsive NK cells. Whole-genome sequencing and functional analysis revealed a loss-of-function mutation in the Ncr1 gene encoding the activating receptor NKp46. The down-regulation of NK cell activity by NKp46 was associated with the silencing of the Helios transcription factor in NK cells. NKp46 was critical for the subsequent development of antiviral and antibacterial T cell responses, which suggests that the regulation of NK cell function by NKp46 allows for the optimal development of adaptive immune responses. NKp46 blockade enhanced NK cell reactivity in vivo, which could enable the design of immunostimulation strategies in humans.
The influence of SiOx and SiNx passivation on the negative bias stability of Hf–In–Zn–O thin film transistors under illumination (2010)

The stability of hafnium indium zinc oxide thin film transistors under negative bias stress with simultaneous exposure to white light was evaluated. Two different inverted staggered bottom gate devices, each with a silicon oxide and a silicon nitride passivation, were compared. The latter exhibits higher field effect mobility but inferior subthreshold swing, and undergoes more severe shifts in threshold voltage (VT) during negative bias illumination stress. The time evolution of VT fits the stretched exponential equation, which implies that hydrogen incorporation during the nitride growth has generated bulk defects within the semiconductor and/or at the semiconductor/gate dielectric interface.
Enantiopure Chiral Derivatives of the Fragrance Materials Majantol and Sila-majantol:  A Bioisosteric Carbon/Silicon Switch with Drastic Effects on the Sensory Characteristics (2003)

The C/Si analogues 2-methyl-2-(3-methylbenzyl)but-3-en-1-ol (2a) and (hydroxymethyl)methyl(3-methylbenzyl)vinylsilane (2b) are chiral derivatives of the achiral fragrance materials majantol (1a) and sila-majantol (1b). Compounds 2a and 2b were synthesized as racemates, and the respective (+)- and (−)-enantiomers were obtained by chromatographic resolution (HPLC) of rac-2a and rac-2b using a chiral stationary phase. The enantiomerically pure compounds (+)-2a, (−)-2a, (+)-2b, and (−)-2b (optical rotations determined in methanol) were studied for their sensory properties. Both the odor character and the odor intensity of the silicon compounds (+)-2b and (−)-2b differ totally from those of the respective carbon analogues (+)-2a and (−)-2a.
2.5D Deep Learning for CT Image Reconstruction using a Multi-GPU implementation (2018)

While Model Based Iterative Reconstruction (MBIR) of CT scans has been shown to have better image quality than Filtered Back Projection (FBP), its use has been limited by its high computational cost. More recently, deep convolutional neural networks (CNN) have shown great promise in both denoising and reconstruction applications. In this research, we propose a fast reconstruction algorithm, which we call Deep Learning MBIR (DL-MBIR), for approximating MBIR using a deep residual neural network. The DL-MBIR method is trained to produce reconstructions that approximate true MBIR images using a 16 layer residual convolutional neural network implemented on multiple GPUs using Google Tensorflow. In addition, we propose 2D, 2.5D and 3D variations on the DL-MBIR method and show that the 2.5D method achieves similar quality to the fully 3D method, but with reduced computational cost.
Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells (2019)

FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts. Silencing of FUT2, but not FUT1, significantly changed the cuboidal morphology to dense clusters of small and round cells with reduced adhesion to polystyrene and extracellular matrix, including laminin, fibronectin and collagen. Silencing of FUT1 or FUT2 suppressed cell migration in wound healing assay, whereas FUT1 and FUT2 overexpression increased cell migration and invasion in vitro and metastasis of breast cancer in vivo. A decrease in mesenchymal like markers such as fibronectin, vimentin, and twist, along with increased epithelial like marker, E-cadherin, was observed upon FUT1/2 knockdown, while the opposite was noted by overexpression of FUT1 or FUT2. As expected, FUT1 or FUT2 knockdown reduced Globo H, whereas FUT1 or FUT2 overexpression showed contrary effects. Exogenous addition of Globo H-ceramide reversed the suppression of cell migration by FUT1 knockdown but not the inhibition of cell adhesion by FUT2 silencing, suggesting that at least part of the effects of FUT1/2 knockdown were mediated by Globo H. Our results imply that FUT1 and FUT2 play important roles in regulating growth, adhesion, migration and CSC properties of breast cancer, and may serve as therapeutic targets for breast cancer.
Experimental Layer-Wound Mock-Up Coil for HTS MRI Magnet Using BSCCO Tape (2009)

Typical coils with BSCCO tape are wound in a pancake or double-pancake style to minimize the strain in the tape by reducing or eliminating the edge-wise bending. Stainless steel reinforced tapes are frequently used in the winding process to increase the strength and reduce the strain due to winding tension and handling. However, an MRI magnet requires high current density in the winding pack. This high current density in the winding pack gives a higher field in the imaging volume and also allows for a reduction in the overall magnet size. Layer winding was preferred for a better tolerance control and for a reduction in the number of joints, which are known sources of resistance and therefore locations of instability in the coil. A mock-up coil was wound using a high-current-density type of BSCCO tape without the typical stainless steel reinforcement. The coil was layer-wound which involved a few inline lap joints embedded in the winding pack. The test of the coil reveals a few issues that need to be addressed. Investigations and analysis lead to a better understanding of the issues. This paper discusses the lessons learned and solutions for using non-reinforced tape in a layer-wound coil, while controlling insulation dimensions within the build.
Supplementary Figure 2 from GDC-0941, a Novel Class I Selective PI3K Inhibitor, Enhances the Efficacy of Docetaxel in Human Breast Cancer Models by Increasing Cell Death <i>In Vitro</i> and <i>In Vivo</i> (2023)

&lt;p&gt;PDF file, 137KB, Time-Lapse Photomicrographs of HCC-1954 Breast Cancer Cells Treated with GDC-0941, Docetaxel (DTX) or the Combination of Both Drugs.&lt;/p&gt;
Deep Learning for Confidence Information in Stereo and ToF Data Fusion (2017)

This paper proposes a novel framework for the fusion of depth data produced by a Time-of-Flight (ToF) camera and a stereo vision system. The key problem of balancing between the two sources of information is solved by extracting confidence maps for both sources using deep learning. We introduce a novel synthetic dataset accurately representing the data acquired by the proposed setup and use it to train a Convolutional Neural Network architecture. The machine learning framework estimates the reliability of both data sources at each pixel location. The two depth fields are finally fused enforcing the local consistency of depth data taking into account the confidence information. Experimental results show that the proposed approach increases the accuracy of the depth estimation.
Home accidents in elderly people. (1992)

Outcome of excision of natal cleft sinus and primary closure compared with that of excision and secondary healing.Figures are medians (ranges) Primary closure Secondary Success Failure healing (n= 17) (n=6) (n=23) Days in hospital I (0)* 1 (1-2)* 3 (2-3) (day case) Days to healing 14 (0)* 37 5(26-48)t 41(29-51) (removal of sutures) Days off work 17 (15-21)* 38-5 (28-49)t 42 (28-56) Outpatient visits 2 (0)* 5-5 (4-6)t 6 (4-7) Visits by district nurse 0* 3 (2-5)t 4 (4-6)
O1‐01‐02: A NOVEL MURINE KNOCK‐IN MODEL FOR PROGRANULIN‐DEFICIENT FRONTOTEMPORAL DEMENTIA WITH NONSENSE‐MEDIATED MRNA DECAY (2018)

Frontotemporal dementia (FTD) is the most common neurodegenerative disorder in individuals under age 60 and has no treatment or cure. Since many cases of FTD result from GRN nonsense mutations, an animal model for this type of mutation is highly desirable for understanding pathogenesis and testing therapies. We generated and characterized GrnR493X knock-in mice, which model the most common human GRN mutation, a premature stop codon at arginine 493 (R493X). Homozygous GrnR493X mice have markedly reduced Grn mRNA levels, lack detectable progranulin protein, and phenocopy Grn knockout mice, with CNS microgliosis, reduced synaptic density, lipofuscinosis, hyper-inflammatory macrophages, excessive grooming behavior, and reduced survival. Inhibition of nonsense-mediated mRNA decay (NMD) by genetic, pharmacological, or antisense oligonucleotide-based approaches showed that NMD contributes to the reduced mRNA levels in GrnR493X mice and cell lines and in fibroblasts from patients containing the GRNR493X mutation. The expressed truncated R493X mutant protein was functional in several assays in progranulin-deficient cells, suggesting that NMD inhibition could be an effective as a therapeutic approach for treating progranulin deficiency caused by the R493X mutation. The GrnR493X mice and associated cell lines provide novel model systems to identify therapies for treating FTD resulting from GRN nonsense mutations.
Thermal analysis and non-isothermal crystallization kinetic of PET/UiO-66 nanocomposite (2022)

The thermal and crystallization properties of poly (ethylene terephthalate) (PET) in the presence of metal–organic frameworks (MOFs) such as UiO-66(Zr) have been systematically studied. Under the best conditions, UiO-66(Zr) functions as a key nucleating agent in the PET scheme. In this work, a merge between UiO-66 and PET was used to increase compatibility, however, the tetra oxidation of Zr4+ revealed by defects in UiO-66 was used to enhance the reaction between PET and UiO-66 as well. Additionally, PET containing varying amounts of UiO-66 were made-up. UiO-66 has high nucleation effectiveness in the matrix of PET due to its large specific surface area and coordination of Zr4+. When compared between the formation PET and PET/UiO-66 matrix, the rate of crystallization for PET/UiO-66 nanocomposite was considerably accelerated, and the temperature of crystallization for PET-UiO-66 was remarkably increased or decreased with increasing UiO-66 content, indicating that adding UiO-66 to PET accelerates crystallization. The thermal stability of PET/UiO-66 nanocomposites in terms of characteristic temperature and kinetic parameters, as well as the dispersion of UiO-66, were examined using both (DSC) and (TGA) under non-isothermal circumstances. The degrading response rate (dx/dt)p and the kinetic exponent n of PET/UiO-66 nanocomposites are estimated and analyzed.
Novel hybrid organic-inorganic sol-gel materials based on highly efficient heterocyclic push-pull chromophores (1999)

We report the synthesis of sol-gel materials based on highly efficient heterocycle-based push-pull chromophores showing second- and third-order nonlinear optical activity. We show the proper functionalization of the best performing chromophores and their incorporation into a hybrid organic- inorganic sol-gel matrix. Different types of functionalization of the active molecule have been considered, including hydroxyl and alkoxysilyl end-groups. The functionalization strategy responded to different criteria such as stability and synthetic availability of the final molecular precursors, their solubility, and the used synthetic approach to the sol-gel material. The synthesis of the sol-gel materials has been tuned in order to preserve molecular properties and control important factors such as final concentration of the active dye in the matrix. Both acid- and base-catalyzed sol-gel synthesis has been taken into account. 3-Glycidoxypropyltrimethoxysilane and 3- aminopropyltriethoxysilane have been used as the organically modified alkoxides to prepare the hybrid organic-inorganic matrix. Characterization of the spectroscopic properties of the sol-gel materials is presented.
Epicardial substrate ablation for Brugada syndrome (2016)

Brugada syndrome (BrS), characterized by the presence of coved-type ST-segment elevation followed by T-wave inversion in the right precordial electrocardiogram (ECG) leads in patients who have no structural heart disease but have a high risk of sudden cardiac death from ventricular fibrillation (VF), has captivated arrhythmia scholars and electrophysiologists for more than 2 decades. As a result, major progresses have been made toward a better understanding of the syndrome with respect to its genetic basis, underlying pathophysiology, and risk stratification.
Nonspecific Adherence and Fibril Biogenesis by Actinobacillus actinomycetemcomitans : TadA Protein Is an ATPase (2001)

Cells of Actinobacillus actinomycetemcomitans, a gram-negative pathogen responsible for an aggressive form of juvenile periodontitis, form tenaciously adherent biofilms on solid surfaces. The bacteria produce long fibrils of bundled pili, which are required for adherence. Mutations in flp-1, which encodes the major subunit of the pili, or any of seven downstream tad genes (tadABCDEFG) cause defects in fibril production, autoaggregation, and tenacious adherence. We proposed that the tad genes specify part of a novel secretion system for the assembly and transport of Flp pili. The predicted amino acid sequence of TadA (426 amino acids, 47,140 Da) contains motifs for nucleotide binding and hydrolysis common among secretion NTP hydrolase (NTPase) proteins. In addition, the tadA gene is the first representative of a distinct subfamily of potential type IV secretion NTPase genes. Here we report studies on the function of TadA. The tadA gene was altered to express a modified version of TadA that has the 11-residue epitope (T7-TAG) fused to its C terminus. The TadA-T7 protein was indistinguishable from the wild type in its ability to complement the fibril and adherence defects of A. actinomycetemcomitans tadA mutants. Although TadA is not predicted to have a transmembrane domain, the protein was localized to the inner membrane and cytoplasmic fractions of A. actinomycetemcomitans cells, indicating a possible peripheral association with the inner membrane. TadA-T7 was purified and found to hydrolyze ATP in vitro. The ATPase activity is stimulated by Triton X-100, with maximal stimulation at the critical micellar concentration. TadA-T7 forms multimers that are stable during sodium dodecyl sulfate-polyacrylamide gel electrophoresis in nonreducing conditions, and electron microscopy revealed that TadA-T7 can form structures closely resembling the hexameric rings of other type IV secretion NTPases. Site-directed mutagenesis was used to substitute Ala and Gln residues for the conserved Lys residue of the Walker A box for nucleotide binding. Both mutants were found to be defective in their ability to complement tadA mutants. We suggest that the ATPase activity of TadA is required to energize the assembly or secretion of Flp pili for tight adherence of A. actinomycetemcomitans.
Fault Management in the Time Triggered Protocol (TTP) (1994)

&lt;div class="htmlview paragraph"&gt;The Time Triggered Protocol (TTP) is an efficient real-time protocol for automotive networks. The TTP class C version of the protocol provides all services needed for the implementation of safety critical distributed fault-tolerant class C systems. The TTP class B version of the protocol provides an economical solution to class A and B applications. Both protocol versions use the same frame format on the communication network and the same application software interface. This paper describes the protocol objectives, compares the functionality of TTP/C and TTP/B, and focuses on the fault management strategy of the TTP/C protocol.&lt;/div&gt;
Synthesis, Modelling, and Anticonvulsant Studies of New Quinazolines Showing Three Highly Active Compounds with Low Toxicity and High Affinity to the GABA-A Receptor (2017)

Some novel fluorinated quinazolines (<b>5a</b>-<b>j</b>) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic resonance (NMR), <sup>13</sup>C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds <b>5b</b>, <b>5c</b>, and <b>5d</b> showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization.