gebhart/patrepeval huggingface dataset:
Feasibility and safety of targeting mitochondria for cancer therapy – preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor (2022)

Mitochondria are key tumor drivers, but their suitability as a therapeutic target is unknown. Here, we report on the preclinical characterization of Gamitrinib (<i>GA mit</i>ochondrial ma<i>tri</i>x <i>in</i>h<i>ib</i>itor), a first-in-class anticancer agent that couples the Heat Shock Protein-90 (Hsp90) inhibitor 17-allylamino-geldanamycin (17-AAG) to the mitochondrial-targeting moiety, triphenylphosphonium. Formulated as a stable (≥24 weeks at -20°C) injectable suspension produced by microfluidization (<200 nm particle size), Gamitrinib (>99.5% purity) is heavily bound to plasma proteins (>99%), has intrinsic clearance from liver microsomes of 3.30 mL/min/g and minimally penetrates a Caco-2 intestinal monolayer. Compared to 17-AAG, Gamitrinib has slower clearance (85.6 ± 5.8 mL/min/kg), longer t<sub>1/2</sub> (12.2 ± 1.55 h), mean AUC<sub>0-t</sub> of 783.1 ± 71.3 h∙ng/mL, and unique metabolism without generation of 17-AG. Concentrations of Gamitrinib that trigger tumor cell killing (IC<sub>50</sub> ~1-4 µM) do not affect cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2B6, CYP2C8 or ion channel conductance (Nav1.5, Kv4.3/KChIP2, Cav1.2, Kv1.5, KCNQ1/mink, HCN4, Kir2). Twice weekly IV administration of Gamitrinib to Sprague-Dawley rats or beagle dogs for up to 36 d is feasible. At dose levels of up to 5 (rats)- and 12 (dogs)-fold higher than therapeutically effective doses in mice (10 mg/kg), Gamitrinib treatment is unremarkable in dogs with no alterations in clinical-chemistry parameters, heart function, or tissue histology, and causes occasional inflammation at the infusion site and mild elevation of serum urea nitrogen in rats (≥10 mg/kg/dose). Therefore, targeting mitochondria for cancer therapy is feasible and well tolerated. A publicly funded, first-in-human phase I clinical trial of Gamitrinib in patients with advanced cancer is ongoing (ClinicalTrials.gov NCT04827810).
Central neuronal loss and behavioral impairment in mice lacking neurotrophin receptor p75 (1999)

The neurotrophin receptor p75 is a low-affinity receptor that binds neurotrophins. To investigate the role of p75 in the survival and function of central neurons, p75 null-mutant and wild type litter mate mice were tested on behavioral tasks. Null mutants showed significant performance deficits on water maze, inhibitory avoidance, motor activity, and habituation tasks that may be attributed to cognitive dysfunction or may represent a global sensorimotor impairment. The p75 null-mutant and wild type litter mate mice were assessed for central cholinergic deficit by using quantitative stereology to estimate the total neuronal number in basal forebrain and striatum and for subpopulations expressing the high-affinity tyrosine receptor kinase A (trkA) neurotrophin receptor and choline acetyltransferase (ChAT). In the adult brain, cholinergic neurons of the basal forebrain receive target-derived trophic support, whereas cholinergic striatal neurons do not. Adult p75 null-mutant mice had significant reduction of basal forebrain volume by 25% and had a corresponding significant loss of 37% of total basal forebrain neurons. The basal forebrain population of ChAT-positive neurons in p75-deficient mice declined significantly by 27%, whereas the trkA-positive population did not change significantly. There was no significant change in striatal volume or in striatal neuronal number either in total or by cholinergic subpopulation. These results demonstrate vulnerability to the lack of p75 in adult central neurons that are neurotrophin dependent. In addition, the loss of noncholinergic central neurons in mice lacking p75 suggests a role for p75 in cell survival by an as yet undetermined mechanism. Possible direct and indirect effects of p75 loss on neuronal survival are discussed.
Automatic Acquisition of Time-Slice Image Sequences (2010)

Acquisition of consistent multi-camera image data such as for time-slice sequences (widely known by their use as cinematic effects, e.g. in “The Matrix”) is a challenging task, especially when using low-cost image sensors. Many different steps such as camera calibration and color conformation are involved, each of which poses individual problems. We have developed a complete and extendable setup for recording a time-slice image sequence displaying a rotation around the subject utilizing a circular camera array. Integrating all the aforementioned steps into a single environment, this setup includes geometrical and color calibration of the camera hardware utilizing a novel, multi-functional calibration target as well as a software color adaption to refine the calibration results. To obtain a steadily rotating animation, we have implemented an image rectification which compensates for inevitable mounting inaccuracies and creates a smooth viewpoint trajectory based on the geometrical calibration of the cameras.
A Mouse Carrying Genetic Defect in the Choice Between T and B Lymphocytes (1998)

Transgenic mice with human CD3epsilon gene have been shown to exhibit early arrest of T cell development in the thymus. The present study shows that, instead of T cells, B cells are generated in the thymus of a line, tg epsilon26, of the human CD3epsilon transgenic mice. The accumulation of mature B cells in the thymus was found only in tg epsilon26 mice, not in other human CD3epsilon transgenic mouse lines or other T cell-deficient mice, including CD3-epsilon knockout mice and TCR-beta/TCR-delta double knockout mice. Hanging drop-mediated transfer into 2-deoxyguanosine-treated thymus lobes showed that lymphoid progenitor cells rather than thymus stromal cells were responsible for abnormal B cell development in tg epsilon26 thymus, and that tg epsilon26 fetal liver cells were destined to become B cells in normal thymus even in the presence of normal progenitor cells undergoing T cell development. These results indicate that lymphoid progenitor cells in tg epsilon26 mice are genetically defective in thymic choice between T cells and B cells, generating B cells even in normal thymus environment. Interestingly, tg epsilon26 thymocytes expressed GATA-3 and TCF-1, but not LEF-1 and PEBP-2alpha, among T cell-specific transcription factors that are involved in early T cell development, indicating that GATA-3 and TCF-1 expressed during thymocyte development do not necessarily determine the cell fate into T cell lineage. Thus, tg epsilon26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective.
KrF excimer laser-based patterning system for dual applications in both lithography and ablation (2020)

A proof-of-concept Krypton Fluoride excimer laser-based patterning system was designed and constructed with dual applications in lithography and laser-ablation patterning. For the lithographic patterning application, utilizing a typical positive-tone chemical amplification resist material, potential for sub-&mu;m patterning was realized with ultimate resolution obtained at 0.8&mu;m 1:1 lines-and-spaces (L/S). Moreover, extremely large depth-of-focus was confirmed, e.g. 50&mu;m at 5&mu;m 1:1 L/S. For the laser-ablation patterning application, ultimate resolutions of up to 1.2&mu;m 1:1 L/S were obtained using a novolac-based material. It was also understood that higher exposure energy per shot can aid in pattern profile enhancement. Results obtained here show the potential of the patterning system for &mu;m and sub-&mu;m level patterning of thick resist films.
Synthesis of Dinucleotide Non‐Symmetrical Triester Phosphate Phosphoramidites and Their Incorporation Within Oligonucleotides (2023)

In this protocol article, the synthesis of dinucleotide non-symmetrical triester phosphate phosphoramidites will be highlighted. Specifically, we use a selective transesterification starting with tris(2,2,2-trifluoroethyl) phosphate to afford a dinucleotide derivative phosphate ester. Substitution of the final trifluoroethyl group with various alcohols affords a dinucleotide triester phosphate with a hydrophobic group, which can then be deprotected and converted to a phosphoramidite for incorporation within oligonucleotides. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of a DMT- and TBS-protected unsymmetrical dinucleotide Basic Protocol 2: Synthesis of a DMT-protected unsymmetrical dinucleotide phosphotriester monoalcohols Basic Protocol 3: Synthesis of DMT-protected phenylethyl phosphotriester dinucleotide phosphoramidites Basic Protocol 4: Synthesis, purification, and characterization of RNAs containing triester phosphate modifications.
Selective conversion of polyethylene wastes to methylated aromatics through cascade catalysis (2023)

Polyethylene was selective converted into methylated aromatics over the catalysts of aluminosilicate MFI zeolite nanosheets (s-ZSM-5) and mesoporous MFI zeolite modified with zinc species (Zn/meso-ZSM-5).
Minimal Residual Disease-Based Risk Stratification in Chinese Childhood Acute Lymphoblastic Leukemia by Flow Cytometry and Plasma DNA Quantitative Polymerase Chain Reaction (2013)

Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1-10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4) were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4). We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.
ChemInform Abstract: Syntheses, Crystal Structures, and Physical Properties of La5Cu6O4S7 and La5Cu6.33O4S7. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
FLEW (2022)

WiFi is the de facto standard for providing wireless access to the Internet using the 2.4GHz ISM band. Tens of billions of WiFi devices were shipped worldwide and WiFi Access Points (APs) are ubiquitous in public, enterprise and personal environments. We have also witnessed the fast growth of IoT (Internet of Things) devices. With more stringent board-space and power requirements, many IoT devices use more power-efficient, lower-cost and smaller wireless chips, such as Bluetooth or proprietary wireless chips. Due to the mismatch of different wireless technologies, these devices access the Internet indirectly via far less ubiquitous IoT gateways. Bluetooth and most proprietary wireless chips are based on FSK (Frequency-Shift Keying) modulation since FSK can be implemented with extremely simple and low-power FM (Frequency Modulation) circuits.
Effect of Coating Thickness on the Friction Coefficients and Torque-Tension Relationship in Threaded Fasteners (2009)

This paper experimentally investigates the effect of coating thickness on the thread, bearing friction coefficients, and torque-tension relationship in threaded fasteners, as well as an investigation into the effect of coating thickness on surface roughness properties. The torque-tension relationship is highly sensitive to frictional changes. Two different coating thicknesses are investigated using two bolt thread pitch; test data are collected for a preselected level of bolt tension. The experimental setup collects real-time data on the tightening torque, bolt tension, and the corresponding reaction torque. Test data are used for calculating the thread and bearing friction coefficients, as well as the overall torque-tension relationship for two different coating thicknesses. The study would provide an insight into the variation in the torque-tension relationship, which is a key factor that significantly affect the reliability and safety of bolted assemblies in many mechanical and structural applications.
Combination of Thiazide Diuretics and Angiotensin Receptor Blockers Attenuates Osteoporosis in Hypertensive Rats (2010)

A series of clinical studies have shown that thiazide diuretics (TD) might reduce the risk of bone fractures. We also recently demonstrated that angiotensin receptor blockers (ARB) ameliorated ovariectomy (OVX)-induced osteoporosis in a hypertensive rat model. In this study, we examined whether a combination of TD and ARB might have additional effects on osteoporosis in a hypertensive rat model. In spontaneous hypertensive rats, estrogen deficiency induced by OVX resulted in a significant increase in osteoclast activation as assessed by tartrate-resistant acid phosphatase (TRAP) activity in the tibia, accompanied by a significant decrease in bone mineral density (BMD) evaluated by dual-energy X-ray absorptiometry and an increase in urinary deoxypyridinoline. Treatment with high-dose ARB, valsartan (3 mg Kg-1day-1), attenuated the OVX-induced decrease in BMD and increased TRAP activity and urinary deoxypyridinoline, whereas low-dose ARB, valsartan (1 mg Kg-1day-1), or low-dose TD, hydrochlorothiazide (0.2 mg Kg-1day-1), did not. Of importance, administration of low-dose valsaltan in combination with hydrochlorothiazide significantly decreased the magnitude of bone mineral loss compared with the effect of administration of high-dose valsartan alone. These results demonstrated that treatment with TD in combination with ARB attenuated osteoporosis additionally in a hypertensive rat model. Keywords: Bone, thiazide diuretics, angiotensin type 1 receptor blocker, osteoporosis, tartrate-resistant acid phosphatase, dual-energy X-ray absorptiometry, Hypertension, angiotensin converting enzyme, ACE, RANKL, Rat Ovariectomy Osteoporosis Model, TRAP, RIA, Radioimmunoassay, DEXA, β-blockers, anti-hypertensive drugs, osteoclasts
Distributed chance-constrained task allocation for autonomous multi-agent teams (2012)

This research presents a distributed chance-constrained task allocation framework that can be used to plan for multi-agent networked teams operating in stochastic and dynamic environments. The algorithm employs an approximation strategy to convert centralized problem formulations into distributable sub-problems that can be solved by individual agents. A key component of the distributed approximation is a risk adjustment method that allocates individual agent risks based on a global risk threshold. The results show large improvements in distributed stochastic environments by explicitly accounting for uncertainty propagation during the task allocation process.
Polarimetric Multi-View Inverse Rendering (2020)

A polarization camera has great potential for 3D reconstruction since the angle of polarization (AoP) of reflected light is related to an object's surface normal. In this paper, we propose a novel 3D reconstruction method called Polarimetric Multi-View Inverse Rendering (Polarimetric MVIR) that effectively exploits geometric, photometric, and polarimetric cues extracted from input multi-view color polarization images. We first estimate camera poses and an initial 3D model by geometric reconstruction with a standard structure-from-motion and multi-view stereo pipeline. We then refine the initial model by optimizing photometric and polarimetric rendering errors using multi-view RGB and AoP images, where we propose a novel polarimetric rendering cost function that enables us to effectively constrain each estimated surface vertex's normal while considering four possible ambiguous azimuth angles revealed from the AoP measurement. Experimental results using both synthetic and real data demonstrate that our Polarimetric MVIR can reconstruct a detailed 3D shape without assuming a specific polarized reflection depending on the material.
Nonvolatile Memory Elements Based on Organic Materials (2007)

Abstract Many organic electronic devices exhibit switching behavior, and have therefore been proposed as the basis for a nonvolatile memory (NVM) technology. This Review summarizes the materials that have been used in switching devices, and describes the variety of device behavior observed in their charge–voltage (capacitive) or current–voltage (resistive) response. A critical summary of the proposed charge‐transport mechanisms for resistive switching is given, focusing particularly on the role of filamentary conduction and of deliberately introduced or accidental nanoparticles. The reported device parameters (on–off ratio, on‐state current, switching time, retention time, cycling endurance, and rectification) are compared with those that would be necessary for a viable memory technology.
Synthesis, Structure–Activity Relationship, and Mechanistic Studies of Aminoquinazolinones Displaying Antimycobacterial Activity (2020)

Phenotypic whole-cell screening against <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) in glycerol-alanine-salts supplemented with Tween 80 and iron (GASTE-Fe) media led to the identification of a 2-aminoquinazolinone hit compound, sulfone <b>1</b> which was optimized for solubility by replacing the sulfone moiety with a sulfoxide <b>2</b>. The synthesis and structure-activity relationship (SAR) studies identified several compounds with potent antimycobacterial activity, which were metabolically stable and noncytotoxic. Compound <b>2</b> displayed favorable <i>in vitro</i> properties and was therefore selected for <i>in vivo</i> pharmacokinetic (PK) studies where it was found to be extensively metabolized to the sulfone <b>1</b>. Both derivatives exhibited promising PK parameters; however, when <b>2</b> was evaluated for <i>in vivo</i> efficacy in an acute TB infection mouse model, it was found to be inactive. In order to understand the <i>in vitro</i> and <i>in vivo</i> discrepancy, compound <b>2</b> was subsequently retested <i>in vitro</i> using different <i>Mtb</i> strains cultured in different media. This revealed that activity was only observed in media containing glycerol and led to the hypothesis that glycerol was not used as a primary carbon source by <i>Mtb</i> in the mouse lungs, as has previously been observed. Support for this hypothesis was provided by spontaneous-resistant mutant generation and whole genome sequencing studies, which revealed mutations mapping to glycerol metabolizing genes indicating that the 2-aminoquinazolinones kill <i>Mtb in vitro</i> via a glycerol-dependent mechanism of action.
Synthesis and Biological Evaluation of Novel Taxoids Designed for Targeted Delivery to Tumors. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Identification of optimal topologies for crashworthiness with the evolutionary level set method (2017)

Structural topology optimisation (TO) methods are well established in many engineering disciplines. However, for highly non-linear problems, including crashworthiness, methods are less developed and still subject to active research. In particular, due to the simplifications made in the state-of-the-art methods as well as heuristic character of most of them, the optimality of the obtained structures is arguable. In this paper, a TO approach based on the level set method and evolutionary algorithms is presented. The method is free from the heuristic assumptions and therefore, allows for a direct optimisation of the underlying crash problem. As a result, a reliable information about the optima of crash problems can be obtained. In order to assure the consistency of the results, a comprehensive study of optimisation settings is performed and discussed. Optimisation results for 2D crash test cases are presented and general conclusions concerning the behaviour of the optimal crash structures are derived.
ChemInform Abstract: Saturated Heterocycles. Part 203. A Solid‐State NMR Study of Ring‐ Chain Tautomerism in 1,3‐O,N‐Heterocycles (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Photo‐alignment material with azobenzene‐functionalized polymer linked in film (2002)

Abstract Application of a new azo‐polymer as a photo‐alignment material for liquid crystals (LCs) was demonstrated. 4‐(Vinyloxyethyloxy)azobenzene (VAZO), which has thermally reactive vinyl ether groups, reacted with the OH groups of poly(4‐hydroxystyrene) (PHS) during the baking process. The azo‐attached polymer (PHS‐VAZO) film showed anisotropic spectra after exposure to 365‐nm linear polarized light (LPL) unlike the VAZO‐doped poly(methylmethacrylate) (PMMA) film. The anisotropy of the film was small at high concentration of the azo‐chromophore because of thermal randomization of the polarized state. In the evaluation of photo‐alignment of the LC, the LC hybrid cell using the PHS‐VAZO film achieved high LC alignment. The azo‐attached polymer using the thermal reaction of vinyl ethers is useful for a photo‐alignment material. Copyright © 2002 John Wiley &amp; Sons, Ltd.
Effect of N incorporation on boron penetration from p+ polycrystalline-Si through HfSixOy films (2003)

We demonstrate that incorporating N in Hf-silicate films reduces B penetration through the dielectric film. By modeling the B depth profiles, we calculated the B diffusivities through Hf-silicate (HfSixOy) to be ∼2× higher than the corresponding diffusivities for Hf-silicon oxynitride (HfSixOyNz). B diffusion through grain boundaries after HfSixOy crystallization is believed to be responsible for the enhanced B diffusivity observed. Suppression of crystallization observed in HfSixOyNz films is attributed to the lower Hf content in the films and the incorporation of N. The decreased B penetration observed in HfSixOyNz is a combination of absence of grain boundaries and the fact that N blocks B diffusion by occluding diffusion pathways. The minimum temperatures for B penetration are estimated to be approximately 950 and 1050 °C for HfSixOy and HfSixOyNz, respectively.
Vienna Cancer Stem Cell Club (VCSCC): 20 year jubilee and future perspectives (2023)

The VCSCC will continue to advance the field and to develop LSC-detecting and LSC-eradicating concepts through which diagnosis, prognostication, and therapy of blood cancer patients should improve.