gebhart/patrepeval huggingface dataset:
Polo-like kinase-1 Inhibitors and the Antiandrogen Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling (2022)

ABSTRACT Abiraterone, a standard treatment for metastatic castrate-resistant prostate cancer (mCRPC), slows disease progression by abrogating androgen synthesis and antagonizing the androgen receptor (AR). We report that inhibitors of the mitotic kinase Plk1, including the clinically active third-generation Plk1 inhibitor onvansertib, when co-administered with abiraterone, synergistically kill cancer cells from a wide variety of tumor types in an androgen-independent manner, both in vitro and in vivo . Abiraterone treatment alone results in defects in mitotic spindle orientation, failure of complete chromosome condensation, and upregulation of mitosis and mitotic-spindle related gene sets independently of its effects on AR signaling. These effects, while mild following abiraterone monotherapy, result in profound sensitization to the anti-mitotic effects of Plk1 inhibition, leading to spindle assembly checkpoint-dependent mitotic cell death and entosis. In a murine PDX model of mCRPC, combined onvansertib and abiraterone resulted in enhanced mitotic arrest and dramatic inhibition of tumor cell growth compared to either agent alone. STATEMENT OF SIGNIFICANCE A phase 2 clinical trial is underway ( NCT03414034 ) testing combined Plk1 inhibitor onvansertib and abiraterone in mCRPC patients with nascent abiraterone resistance. Our work establishes a mechanistic basis for that trial and indicates that combined abiraterone and onvansertib co-treatment may have broad utility for cancer treatment beyond mCRPC.
New Polymeric Buffer Materials with Low Driving Voltage (2012)

We present excellent polymeric buffer materials based on the poly(9,9-dioctylfluorene-co-N, N-di(phenyl)-N,N-di(3-carboethoxyphenyl)benzidine) (BFE) for highly efficient solution processed organic light emitting diodes (OLEDs). Doped BFE with 3,5-dinitrobenzonitrile (35DNBN), a strong electron acceptor results in significant improvement of current flow and driving voltage. Maximum current- and power-efficiency value of 7.2 cd/A and 5.5 lm/W are demonstrated from blue OLEDs with these doped polymeric anode buffer system. The 40 nm thick anode buffer material showed a similar current density-voltage (J-V) behavior to that of PEDOT:PSS based device. Results reveal a practical way to fabricate the highly efficient solution processed devices for low cost production of printing devices for the future.
Acid-catalyzed conversion of furfuryl alcohol to ethyl levulinate in liquid ethanol (2012)

Reaction pathways for the acid-catalyzed conversion of furfuryl alcohol (FAL) to ethyl levulinate (EL) in ethanol were investigated using liquid chromatography-mass spectrometry (LC-MS), 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and <i>ab initio</i> high-level quantum chemical (G4MP2) calculations. Our combined studies show that the production of EL at high yields from FAL is not accompanied by stoichiometric production of diethyl either (DEE), indicating that ethoxymethyl furan (EMF) is not an intermediate in the major reaction pathway. Several intermediates were observed using an LC-MS system, and three of these intermediates were isolated and subjected to reaction conditions. The structures of two intermediates were elucidated using 1D and 2D NMR techniques. One of these intermediates is EMF, which forms EL and DEE in a secondary reaction pathway. The second intermediate identified is 4,5,5-triethoxypentan-2-one, which is analogous to one of the intermediates observed in the conversion of FAL to LA in water (i.e. 4,5,5-trihydroxypentan-2-one). Furthermore, conversion of this intermediate to EL again involves the formation of DEE, indicating that it is also part of a secondary pathway. The primary pathway for production of EL involves solvent-assisted transfer of a water molecule from the partially detached protonated hydroxyl group of FAL to a ring carbon, followed by intra-molecular hydrogen shift, where the apparent reaction barrier for the hydrogen shift is relatively smaller in ethanol (21.1 kcal/mol) than that in water (26.6 kcal/mol).
Cell proliferation and differentiation in a model of human skin equivalent (2001)

Recent advances in culturing technology has permitted the production of organotypic models that may be referred to as human skin equivalents (HSE). We have studied histochemical, ultrastructural, and kinetic aspects of an HSE composed by an epidermal equivalent and a dermal equivalent separated by a basement membrane. Only keratinocytes and fibroblasts were present in the epidermal and dermal equivalents, respectively; cells of other lineages were lacking. Keratinocyte stratification and differentiation seemed similar to natural skin. Evidence is shown that such an HSE may also release growth factors such as vascular endothelial growth factor that are believed to play a role in skin grafting. The distribution of cycling cells as well as the values of the growth fraction are comparable to those observed in natural skin. Although the absence of several cells populations that reside in natural skin is a remarkable feature of this HSE, the high levels of tissue organization and cell differentiation lead us to believe that such an HSE may be considered a candidate substitute of human skin in biological, pharmacologic, and clinical applications.
Bradykinin B1 Receptor Antagonists as Novel Analgesics: A Retrospective of Selected Medicinal Chemistry Developments (2008)

Bradykinin B(1) receptor antagonists embody a potentially novel approach for the treatment of chronic pain and inflammation. The identification of non-peptide B(1) antagonists has been a notable advance in the kinin field that will allow evaluation of their therapeutic potential in the clinical realm. The current review is a high level summary of our contributions to the area that culminated in the discovery of a clinical candidate.
A 10-Gb/s CMOS clock and data recovery circuit using a secondary delay-locked loop (2004)

A 10 Gb/s clock and data recovery (CDR) circuit and a 1:4 DMUX are implemented in 0.12 /spl mu/m CMOS. The CDR employs a secondary wideband delay-locked loop (DLL) to enable independent bandwidth control for jitter transfer and jitter tolerance. The proposed clock recovery and data recovery (CRDR) system enhances the jitter tolerance at high frequencies and offers less data-pattern-dependency for CDRs that use a binary phase detector.
Gene amplifications cause high-level resistance against albicidin in Gram-negative bacteria (2022)

Abstract Antibiotic resistance is a continuously increasing concern for public health care. Understanding resistance mechanisms and their emergence is crucial for the development of new antibiotics and their effective use. Here, we report the discovery of a gene amplification-based mechanism that imparts an up to 1000-fold increase in resistance levels against the antibiotic albicidin. We show that this mechanism protects Salmonella Typhimurium and Escherichia coli by increasing the copy number of the GyrI-like transcription regulator STM3175 (YgiV) which binds albicidin. X-ray crystallography and molecular docking studies reveal a conserved binding motif that can interact with aromatic building blocks of albicidin. Phylogenetic studies suggest that this resistance mechanism is ubiquitous in Gram-negative bacteria and our experiments confirm that STM3175 homologs can convey resistance in pathogens such as Vibrio vulnificus and Pseudomonas aeruginosa .
MISSION: Ultra Large-Scale Feature Selection using Count-Sketches (2018)

Feature selection is an important challenge in machine learning. It plays a crucial role in the explainability of machine-driven decisions that are rapidly permeating throughout modern society. Unfortunately, the explosion in the size and dimensionality of real-world datasets poses a severe challenge to standard feature selection algorithms. Today, it is not uncommon for datasets to have billions of dimensions. At such scale, even storing the feature vector is impossible, causing most existing feature selection methods to fail. Workarounds like feature hashing, a standard approach to large-scale machine learning, helps with the computational feasibility, but at the cost of losing the interpretability of features. In this paper, we present MISSION, a novel framework for ultra large-scale feature selection that performs stochastic gradient descent while maintaining an efficient representation of the features in memory using a Count-Sketch data structure. MISSION retains the simplicity of feature hashing without sacrificing the interpretability of the features while using only O(log^2(p)) working memory. We demonstrate that MISSION accurately and efficiently performs feature selection on real-world, large-scale datasets with billions of dimensions.
Suppression of short-channel effects in normally-off GaN MOSFETs with deep recessed-gate structures (2020)

Abstract We have demonstrated the suppression of short-channel effects (SCEs) in normally-off GaN metal-oxide-semiconductor field-effect transistors (MOSFETs) with deep recessed-gate structures. TCAD simulation results show that the electric field concentration is effectively reduced at the recessed edge of MOSFETs with deeper recessed-gate structures. To demonstrate suppression of SCEs, MOSFET gate structures with recess depths ranging from 45 to 165 nm were fabricated and evaluated. Experimental results show that deeper recessed-gate structures are highly effective for suppressing drain-induced barrier lowering and improving subthreshold swing and threshold voltage roll-off.
Overproduction of a Dominant Mutant of the Conserved Era GTPase Inhibits Cell Division in Escherichia coli (2020)

Cell growth and division are coordinated, ensuring homeostasis under any given growth condition, with division occurring as cell mass doubles. The signals and controlling circuit(s) between growth and division are not well understood; however, it is known in <i>Escherichia coli</i> that the essential GTPase Era, which is growth rate regulated, coordinates the two functions and may be a checkpoint regulator of both. We have isolated a mutant of Era that separates its effect on growth and division. When overproduced, the mutant protein Era647 is dominant to wild-type Era and blocks division, causing cells to filament. Multicopy suppressors that prevent the filamentation phenotype of Era647 either increase the expression of FtsZ or decrease the expression of the Era647 protein. Excess Era647 induces complete delocalization of Z rings, providing an explanation for why Era647 induces filamentation, but this effect is probably not due to direct interaction between Era647 and FtsZ. The hypermorphic <i>ftsZ</i>* allele at the native locus can suppress the effects of Era647 overproduction, indicating that extra FtsZ is not required for the suppression, but another hypermorphic allele that accelerates cell division through periplasmic signaling, <i>ftsL</i>*, cannot. Together, these results suggest that Era647 blocks cell division by destabilizing the Z ring.<b>IMPORTANCE</b> All cells need to coordinate their growth and division, and small GTPases that are conserved throughout life play a key role in this regulation. One of these, Era, provides an essential function in the assembly of the 30S ribosomal subunit in <i>Escherichia coli</i>, but its role in regulating <i>E. coli</i> cell division is much less well understood. Here, we characterize a novel dominant negative mutant of Era (Era647) that uncouples these two activities when overproduced; it inhibits cell division by disrupting assembly of the Z ring, without significantly affecting ribosome production. The unique properties of this mutant should help to elucidate how Era regulates cell division and coordinates this process with ribosome biogenesis.
Synthesis and Biodegradability of Aliphatic Polyestercarbonate. (1999)

脂肪族ポリエステルにカーボネートを共重合させ, 酵素法, 土壌埋設法により生分解性を評価したところ, カーボネートの共重合比率が低い領域で融解熱の低下に伴い生分解性が向上することが確認された. また, 土壌懸濁法は生分解性試験の迅速な評価法になりうることがわかった.
Glucose Tolerance, Insulin Release, and Insulin Sensitivity in Normal-Weight Women With Previous Gestational Diabetes Mellitus (1987)

Out of 57 women with previous histories of gestational diabetes (GD), 23 were of normal weight postpartum and willing to participate in three studies characterizing oral glucose tolerance (OGTT), insulin responsiveness to intravenous glucose (glucose infusion test, GIT), and insulin sensitivity (somatostatin, insulin, and glucose infusion test, SIGIT). The experiments were performed 6-36 mo after cessation of breast-feeding. The control group comprised 10 healthy women with normal OGTT matched for age and weight. Among subjects with previous histories of GD, 9 had normal, 8 borderline, and 6 decreased OGTT. As a group, women with previous histories of GD have significantly decreased insulin response and insulin sensitivity. Furthermore, all 14 with borderline and decreased OGTT demonstrated a low early insulin response during GIT (5-min value below the upper border of the lower quartile of normals), whereas insulin sensitivity was normal in 6 and low in 8 (glucose values attained during SIGIT were lower or higher, respectively, than the lower border of the upper quartile of controls). The women with previous histories of GD and normal OGTT exhibited normal (n = 4) and low (n = 5) insulin responses. Three of the former subjects had low and the remaining 6 had normal insulin sensitivity. In conclusion, as many as 60% of normal-weight women with previous histories of GD had borderline or decreased OGTT 6-36 mo postpartum. This derangement could be due to impaired early insulin response, which in some subjects was combined with low insulin sensitivity. Follow-up of women with previous histories of GD might enlighten the pathogenesis of non-insulin-dependent diabetes mellitus.
A Structural Constitutive Model for Right Ventricular Myocardium (2011)

Although right-ventricular (RV) function is an important determinant of cardio-pulmonary performance in health and disease, RV myocardium biomechanical function has received little attention. In particular, no multiaxial data of the full-thickness RV have been reported for the passive or active myocardial states, for either normal or pathological conditions. Since an understanding of tissue-level biomechanical behavior is integral to connecting cellular behavior to organ-level performance, investigations into the RV myocardial stress-strain relationship are central in providing this link. For example, ventricular wall stress is considered to be a major driver of ventricular remodeling, and thus a better understanding of how wall stress and deformation are linked would provide unique insight into the mechanisms of RV function and ultimately failure in disease. Such knowledge would have direct applicability to improving methods to detect RV dysfunction, predicting response to disease-specific therapies and improving the timing of therapy if or when needed. Here, we present the first report on the multiaxial biomechanical behavior of viable full-thickness right-ventricular free wall (RVFW) myocardium and our initial efforts in developing a structural constitutive model for this remarkable tissue.
Hot Topic: Using a Stearoyl-CoA Desaturase Transgene to Alter Milk Fatty Acid Composition (2004)

Stearoyl-CoA desaturase enzyme converts specific medium- and long-chain saturated fatty acids to their monounsaturated form. Transgenic goats expressing a bovine beta-lactoglobulin promoter-rat stearoyl-CoA desaturase cDNA construct in mammary gland epithelial cells were produced by pronuclear microinjection. The fatty acid composition of milk from 4 female transgenic founders was analyzed on d 7, 14, and 30 of their first lactation. In 2 animals, the expression of the transgene changed the overall fatty acid composition of the resulting milk fat to a less saturated and more monounsaturated fatty acid profile at d 7 of lactation; however, this effect diminished by d 30. In addition, one animal had an increased proportion of the rumen-derived monounsaturated fatty acid C18:1 trans11 converted by stearoyl-CoA desaturase to the conjugated linoleic acid isomer C18:2 cis9 trans11. Milk that has higher proportions of monounsaturated fatty acids and conjugated linoleic acid may have benefits for human cardiovascular health.
Comment on “Walker diffusion method for calculation of transport properties of composite materials” (2000)

In a recent paper [C. DeW. Van Siclen, Phys. Rev. E 59, 2804 (1999)], a random-walk algorithm was proposed as the best method to calculate transport properties of composite materials. It was claimed that the method is applicable both to discrete and continuum systems. The limitations of the proposed algorithm are analyzed. We show that the algorithm does not capture the peculiarities of continuum systems (e.g., "necks" or "choke points") and we argue that it is the stochastic analog of the finite-difference method.
The impact of DNA methylation on the identification of recurrent prostate cancer (2007)

21086 Purpose: Biochemical (PSA) recurrence of prostate cancer following radical prostatectomy remains a major problem. Better biomarkers are needed to identify high and low-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the impact of changes in DNA methylation on biochemical recurrence in men with prostate cancer. Methods: We examined the methylation status of fifteen genes using MSP (Methylation Specific PCR) on tissue samples from 151 patients with clinically localized prostate cancer for whom at least five years of follow-up after prostatectomy was available. Results: In a multivariable logistic regression analysis, extra capsular penetration, high Gleason score, and involvement of the lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of recurrence. In addition, samples with methylation of 2 specific genes involved in cell-cell adhesion and apoptosis were associated with biochemical recurrence with an odds ratio of 5.64 (95% CI=1.47–21.7, p=0.012) compared to samples without methylation of both of these genes. The methylation status of these 2 genes had a higher sensitivity (72.3%; 95% CI=57–84.4%) for detecting recurrences than all the clinico-pathological variables (p&lt;0.02) except extra-capsular penetration (p=0.346). The methylation status of these 2 genes had a similar negative predictive value (79.0%; 95% CI=66.8–88.3%) as the individual clinico-pathological variables examined. Conclusion: DNA Methylation of specific genes is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even one considers the prognostic clinico-pathologic variables used in the clinic today. Our findings should be validated on another larger group of patients with prostate cancer who have undergone radical prosatetectomies. No significant financial relationships to disclose.
Cherenkov radiation dosimetry in water tanks – video rate imaging, tomography and IMRT & VMAT plan verification (2015)

This paper presents a survey of three types of imaging of radiation beams in water tanks for comparison to dose maps. The first was simple depth and lateral profile verification, showing excellent agreement between Cherenkov and planned dose, as predicted by the treatment planning system for a square 5cm beam. The second approach was 3D tomography of such beams, using a rotating water tank with camera attached, and using filtered backprojection for the recovery of the 3D volume. The final presentation was real time 2D imaging of IMRT or VMAT treatments in a water tank. In all cases the match to the treatment planning system was within what would be considered acceptable for clinical medical physics acceptance.
Mixed Phase Pt-Ru Catalyst for Direct Methanol Fuel Cell Anode by Flame Aerosol Synthesis (2005)

A spray-flame aerosol catalyzation technique was studied for producing Pt-Ru anode electrodes for the direct methanol fuel cell. Catalysts were produced as aerosol nanoparticles in a spray-flame reactor and deposited directly as a thin layer on the gas diffusion layer. The as-prepared catalyst was found to be a mixture of nanocrystalline, mostly unalloyed Pt and an amorphous phase mostly of Ru and to a lesser extent of Pt oxides on top of the crystalline phase. The flame-produced Pt1Ru1 demonstrated similar onset potential but 60% higher activity compared to commercially available Pt1Ru1/Vulcan carbon. The kinetics of methanol oxidation on the mixed phase catalyst was also explored by electrochemical impedance spectroscopy.
Chemogenetic ligands for translational neurotheranostics (2018)

Abstract Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for precision medicine-based clinical theranostics. DREADD ligands developed to date are not appropriate for such translational applications. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine. The second-generation DREADD agonist, Compound 21 (C21), was developed to overcome these limitations. We found that C21 has low brain penetrance, weak affinity, and low in vivo DREADD occupancy. To address these drawbacks, we developed two new DREADD agonists, JHU37152 and JHU37160, and the first dedicated positron emission tomography (PET) DREADD radiotracer, [ 18 F]JHU37107. JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [ 18 F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons and at their long-range projections, enabling for the first time, noninvasive and longitudinal neuronal projection mapping and potential for neurotheranostic applications.
Immune Responses to ESAT-6 and CFP-10 by FASCIA and Multiplex Technology for Diagnosis of M. tuberculosis Infection; IP-10 Is a Promising Marker (2012)

IP-10 seems to be an important marker for diagnosis of active and latent TB. Patients with active TB and LTBI responded with similar cytokine profiles against TB antigens but proliferative and cytokine responses were generally higher in patients with active TB.
Micromachined Tunable Dielectric Resonators (2002)

-Micromachined dielectric resonators (DR) and cavity filters are used in microwave technology. For many applications the resonance frequency of the DR must have a small degree of tunablity, to cope with drifts of different origins. Tuning can be obtained electrically or mechanically. Mechanical tuning is based on a movable metal plate placed above the resonator puck. In this work we report about the implementation of mechanical tuning in a DR by means of MEMS technology. High resistivity silicon-based, cylindrical dielectric resonators have been fabricated using micromachining techniques. Depending on the dimensions and on the excited mode, resonance frequencies are in the range of 25~50GHz. In order to obtain frequency tuning, a membrane has been fabricated and coupled to the DR as the tuning element. Membranes are made of low stress SiN and are covered with a metal layer. Preliminary measurements applied to a high resistivity silicon DR indicate that by applying a pressure of 500Pa, a tuning range of 0.6% can be achieved.
Direct absorption edge in GeSiSn alloys (2010)

The lowest direct absorption edge E 0 in ternary Ge 1-x-y Si x Sn y alloys was measured in films grown latticematched to Ge using spectroscopic ellipsometry and photoreflectance. The sample choice is dictated by possible applications of Ge 1-x-y Si x Sn y in photovoltaics as the long-sought ~ 1eV gap material to complement Ge/InGaAs/InGaP multijunctions. The compositional dependence of the E 0 transition is analyzed in detail.