gebhart/patrepeval huggingface dataset:
Increased expression of CYP17A1 indicates an effective targeting of the androgen receptor axis in castration resistant prostate cancer (CRPC) (2014)

Recent breakthrough therapies targeting androgen receptor signalling in castration resistant prostate cancer (CRPC) involve multifunctional androgen receptor (AR) blockade and exhaustive androgen deprivation. Nevertheless, limitations to an enduring effectiveness of new drugs are anticipated in resistance mechanisms occurring under such treatments. In this study we used CRPC cell models VCaP and LNCaP as well as AR-negative PC-3- and non-neoplastic epithelial BPH-1-cells treated with 5, 10 or 25 μmol/L abiraterone hydrolyzed from abiraterone acetate (AA). The origin of CYP17A1 up-regulation under AA treatment was investigated in CRPC cell models by qRT-PCR and western-blot procedures. AA treatments of AR positive CRPC cell models led to decreased expression of androgen regulated genes such as PSA. In these cells diminished expression of androgen regulated genes was accompanied by an up-regulation of CYP17A1 expression within short-term treatments. No such effects became evident in AR-negative PC-3 cells. AR directed siRNA (siAR) used in VCaP cells significantly reduced mRNA expression and AR protein abundance. Such interference with AR signalling in the absence of abiraterone acetate also caused a marked up-regulation of CYP17A1 expression. Down-regulation of androgen regulated genes occurs in spite of an elevated expression of CYP17A1, the very target enzyme for this drug. CYP17A1 up-regulation already takes place within such short treatments with AA and does not require adaptation events over several cell cycles. CYP17A1 is also up-regulated in the absence of AA when AR signalling is physically eliminated by siAR. These results reveal an immediate counter-regulation of CYP17A1 expression whenever AR-signalling is inhibited adequately but not a persisting adaptation yielding drug resistance.
In vivo antitumour effect of combretastatin A-4 phosphate added to fractionated irradiation. (2006)

The present data indicate a size-dependent increase in tumour growth delay from combining fractionated irradiation with CA-4-P.
Out and about guerrilla style (2006)

Pakuma has recently brought out a range of ‘multi purpose urban bags’, one of which is the Choroka K2. It can hold laptops of up to 15.4 inches and pretty much anything else you may need during a day out and about.
Temperature Dependency on Thermal Reliability Test Result by Sintered Silver Interconnection (2020)

(1) . (TST) . . 150 . 100 (2) . TST . (TST)
<i>Sinorhizobium meliloti</i> Requires a Cobalamin-Dependent Ribonucleotide Reductase for Symbiosis With Its Plant Host (2010)

Vitamin B 12 (cobalamin) is a critical cofactor for animals and protists, yet its biosynthesis is limited to prokaryotes. We previously showed that the symbiotic nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti requires cobalamin to establish a symbiotic relationship with its plant host, Medicago sativa (alfalfa). Here, the specific requirement for cobalamin in the S. meliloti–alfalfa symbiosis was investigated. Of the three known cobalamin-dependent enzymes in S. meliloti, the methylmalonyl CoA mutase (BhbA) does not affect symbiosis, whereas disruption of the metH gene encoding the cobalamin-dependent methionine synthase causes a significant defect in symbiosis. Expression of the cobalamin-independent methionine synthase MetE alleviates this symbiotic defect, indicating that the requirement for methionine synthesis does not reflect a need for the cobalamin-dependent enzyme. To investigate the function of the cobalamin-dependent ribonucleotide reductase (RNR) encoded by nrdJ, S. meliloti was engineered to express an Escherichia coli cobalamin-independent (class Ia) RNR instead of nrdJ. This strain is severely defective in symbiosis. Electron micrographs show that these cells can penetrate alfalfa nodules but are unable to differentiate into nitrogen-fixing bacteroids and, instead, are lysed in the plant cytoplasm. Flow cytometry analysis indicates that these bacteria are largely unable to undergo endoreduplication. These phenotypes may be due either to the inactivation of the class Ia RNR by reactive oxygen species, inadequate oxygen availability in the nodule, or both. These results show that the critical role of the cobalamin-dependent RNR for survival of S. meliloti in its plant host can account for the considerable resources that S. meliloti dedicates to cobalamin biosynthesis.
Evaluating Clinical Accuracy of Continuous Glucose Monitoring Systems:Continuous Glucose – Error Grid Analysis (CG-EGA) (2008)

Continuous Glucose Sensors (CGS) generate rich and informative continuous data streams which have the potential to improve the glycemic condition of the patient with diabetes. Such data are critical to the development of closed loop systems for automated glycemic control. Thus the numerical and clinical accuracy of such must be assured. Although numerical point accuracy of these systems has been described using traditional statistics, there are no requirements, as of yet, for determining and reporting the rate (trend) accuracy of the data generated. In addition, little attention has been paid to the clinical accuracy. of these systems. Continuous Glucose-Error Grid Analysis (CG-EGA) is the only method currently available for assessing the clinical accuracy of such data and reporting this accuracy for each of the relevant glycemic ranges, - hypoglycemia, euglycemia, hyperglycemia. This manuscript reviews the development of the original Error Grid Analysis (EGA) and describes its inadequacies when used to determine point accuracy of CGS systems. The development of CG-EGA as a logical extension of EGA for use with CGS is described in detail and examples of how it can be used to describe the clinical accuracy of several CGS are shown. Information is presented on how to obtain assistance with the use of CG-EGA.
Niemann–Pick disease type C2 protein induces triglyceride accumulation in silkworm and mammalian cell lines (2014)

Silkworm haemolymph induced both the cessation of growth and an increase in triglyceride (triacylglycerol) storage in BmN4 cells. We purified the growth inhibitory factor from the silkworm haemolymph and identified this protein as the Bombyx mori PP (promoting protein), an orthologue of NPC2 (Niemann-Pick disease type C2) protein. Recombinant silkworm NPC2 inhibited cellular proliferation and increased triglyceride accumulation in BmN4 cells. Injection of either the recombinant protein or antiserum of NPC2 into living silkworms increased or decreased respectively triglyceride levels in the fat body. A mutation that depletes the cholesterol-binding capacity did not abolish the activity of NPC2. We further revealed that NPC2 induced the phosphorylation of AMPK (AMP-activated protein kinase) and that an AMPK inhibitor suppressed NPC2-dependent triglyceride accumulation. These findings suggest that NPC2 induces triglyceride accumulation via the activation of AMPK independently of its cholesterol-binding capacity in the silkworm.
Utility of a Clinical Decision Support System in Weight Loss Prediction After Head and Neck Cancer Radiotherapy (2019)

Our preliminary results demonstrate that physicians' decisions may be improved by a weight loss CDSS model, especially among less-experienced physicians. Additional study with a larger cohort of patients and more participating physicians is thus warranted for understanding the usefulness of CDSSs.
Current blockage experiments: force time histories on obstacle arrays in combined steady and oscillatory motion (2013)

Abstract This paper revisits the problem of forces on obstacle arrays in combined waves and an in-line steady current. The intended application is the design and reassessment of offshore platforms. A series of experiments are performed on planar grids moved in both steady and oscillatory motion through otherwise stationary water. Detailed comparisons are made to a wave-current–structure interaction model recently presented by Taylor, Santo &amp; Choo ( Ocean Engng , vol. 57, 2013, pp. 11–24). We present new features of the model and test these against the experimental data. For relatively small current speed ( ${u}_{c} $ ) compared with oscillatory velocity amplitude ( ${u}_{w} $ ) with phase angle ( $\omega t$ ), the drag force time history on grids with solid area ( $A$ ) and projected frontal area ( ${A}_{f} $ ) is well approximated by a summation of the wave drag and the current drag components independently, so there is no ${u}_{w} \times {u}_{c} $ cross-term. The wave drag component is proportional to $\cos \omega t\vert \cos \omega t\vert $ , while the current drag component to $\vert \cos \omega t\vert $ , i.e. it is phase-locked to the oscillatory wave crests. The form of the predicted time history is new, so much of this paper is occupied in testing the adequacy of this theoretical form both in terms of an improved Morison-type formulation and also in the precise variation of the experimental drag force in time. We show that the measured crest and trough peak values of the drag force are consistent with the force peaks and troughs of the model prediction. The odd frequency harmonics of the measured drag force scale as the square of the oscillatory velocity amplitude $({ u}_{w}^{2} )$ and on the total hydrodynamic area ( ${C}_{d} A$ ). The shape of the odd harmonics is very similar to that for a pure oscillatory motion without steady current, but there are also even frequency harmonics associated with the current component. The even harmonics of the force scale as the square of the current speed $({ u}_{c}^{2} )$ and on the ${A}_{f} $ , not on the ${C}_{d} A$ . All of the above features are identified within the experimental data, and provide considerable support for the new current blockage model. The new model is also shown to fit the entire force time history well for a wide range of individual cases, with different blockage ratio ( $A/ {A}_{f} $ ) and number of grids, requiring only calibration of the Morison-type drag and inertia coefficients. In contrast, the industry-standard form of the Morison equation can only be matched at a single instant of the oscillation cycle, so present practice should be regarded as seriously inadequate for combined steady current and oscillatory flow acting on obstacle arrays.
Ultra-wideband communications : An overview (2009)

This paper presents an overview of ultra-wideband (UWB) communications systems, i.e., systems with very large relative and/or absolute bandwidth. The large bandwidth and low power spectral density mandated for UWB systems allows their use as overlays over existing (legacy) systems, i.e., they can be used in the same frequency range as existing systems without causing undue interference. We also describe the most common types of UWB systems, including time-hopping impulse radio, frequency hopping, and multi-band OFDM. We furthermore discuss interference aspects and the peculiarities of UWB propagation channels.
The nom Profit-Maximizing Operating System (2016)

In the near future, cloud providers will sell their users virtual machines with CPU, memory, network, and storage resources whose prices constantly change according to market-driven supply and demand conditions. Running traditional operating systems in these virtual machines is a poor fit: traditional operating systems are not aware of changing resource prices and their sole aim is to maximize performance with no consideration of costs. Consequently, they yield low profits.
ChemInform Abstract: Optical Properties of GaAs Confined in the Pores of MCM‐41. (1998)

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.
An Embryo-Defective Mutant of Arabidopsis Disrupted in the Final Step of Biotin Synthesis (1998)

Auxotrophic mutants have played an important role in the genetic dissection of biosynthetic pathways in microorganisms. Equivalent mutants have been more difficult to identify in plants. The bio1 auxotroph of Arabidopsis thaliana was shown previously to be defective in the synthesis of the biotin precursor 7, 8-diaminopelargonic acid. A second biotin auxotroph of A. thaliana has now been identified. Arrested embryos from this bio2 mutant are defective in the final step of biotin synthesis, the conversion of dethiobiotin to biotin. This enzymatic reaction, catalyzed by the bioB product (biotin synthase) in Escherichia coli, has been studied extensively in plants and bacteria because it involves the unusual addition of sulfur to form a thiophene ring. Three lines of evidence indicate that bio2 is defective in biotin synthase production: mutant embryos are rescued by biotin but not dethiobiotin, the mutant allele maps to the same chromosomal location as the cloned biotin synthase gene, and gel-blot hybridizations and polymerase chain reaction amplifications revealed that homozygous mutant plants contain a deletion spanning the entire BIO2-coding region. Here we describe how the isolation and characterization of this null allele have provided valuable insights into biotin synthesis, auxotrophy, and gene redundancy in plants.
Biologic variations of plasma cells in the bone marrow of smoldering multiple myeloma (SMM) and multiple myeloma (MM) patients: Multiple biopsies in the same patient. (2013)

e19506 Background: The European Myeloma Network has reported that plasma cell (PC) enumeration by flow cytometry (FC) varies depending on quality of aspirate pull and field biopsied. We conducted a prospective study to evaluate PC site variation content in the core biopsy (CB), PC viability (V) and proportion of monoclonal PCs based on immunophenotypic characteristics, anticoagulant use, and aspirate (A) pull sequence in SMM and MM treatment-naïve patients. Methods: Untreated SMM (n=5) and MM (n=5) patients underwent bilateral bone marrow (BM) A and CB. Bilateral first-pull A were anticoagulated with ethylenediaminetetraacetic acid (EDTA). The second-pull A were anticoagulated with heparin. CB were performed after obtaining all A. The first pull A was sent for morphology and FC evaluation, and the second-pull for FC. CB infiltration by PC was assessed by CD138 immunohistochemistry (IHC). Analysis of PC by FC used CD markers: 19, 45, 20, 38, 138, 27, 28, 19, 81, 126, 200 and 117. V was measured by FC using 7-amino-actinomycin D exclusion. We used the two-tailed Wilcoxon signed rank test to determine the significance of the difference between paired values. Results: The mean difference in estimated percentage of PC infiltration between the right and left CB was 0.033 +/- 0.017 (p=0.25). Phenotypic analysis of PCs by FC showed similar expression of CD markers. PC V was significantly lower in samples anticoagulated with EDTA when compared to heparin (p&lt;0.005), suggesting that the latter is superior for PC analysis. Of importance, the fraction of abnormal PCs determined by FC did not differ significantly between the two sides, use of EDTA/heparin or order of A pull (p&gt;0.05). Conclusions: Based on IHC and FC, our results suggest that in untreated patients with SMM or MM there are no major differences in the estimated number or immunophenotypic characteristics and distribution of PC in marrow samples obtained from two distant bone sites. These observations have implications for current diagnostic and treatment of MM and its precursor disease. More advanced molecular profiling may find biological variation in bone marrow tumor PC extracted from different locations.
Closed-Form Minkowski Sum Approximations for Efficient Optimization-Based Collision Avoidance (2022)

Motion planning methods for autonomous systems based on nonlinear programming offer great flexibility in incorporating various dynamics, objectives, and constraints. One limitation of such tools is the difficulty of efficiently repre-senting obstacle avoidance conditions for non-trivial shapes. For example, it is possible to define collision avoidance constraints suitable for nonlinear programming solvers in the canonical set-ting of a circular robot navigating around M convex polytopes over N time steps. However, it requires introducing (2+L)MN additional constraints and LMN additional variables, with L being the number of halfplanes per polytope, leading to larger nonlinear programs with slower and less reliable solving time. In this paper, we overcome this issue by building closed-form representations of the collision avoidance conditions by outer-approximating the Minkowski sum conditions for collision. Our solution requires only MN constraints (and no additional variables), leading to a smaller nonlinear program. On motion planning problems for an autonomous car and quadcopter in cluttered environments, we achieve speedups of 4.8x and 8.7x respectively with significantly less variance in solve times and negligible impact on performance arising from the use of outer approximations.
Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever (2016)

Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.
Testing of java web services for robustness (2004)

This paper presents a new compile-time analysis that enables a testing methodology for white-box coverage testing of error recovery code (i.e., exception handlers) in Java web services using compiler-directed fault injection. The analysis allows compiler-generated instrumentation to guide the fault injection and to record the recovery code exercised. (An injected fault is experienced as a Java exception.) The analysis (i) identifies the exception-flow 'def-uses' to be tested in this manner, (ii) determines the kind of fault to be requested at a program point, and (iii) finds appropriate locations for code instrumentation. The analysis incorporates refinements that establish sufficient context sensitivity to ensure relatively precise def-use links and to eliminate some spurious def-uses due to demonstrably infeasible control flow. A runtime test harness calculates test coverage of these links using an exception def-catch metric. Experiments with the methodology demonstrate the utility of the increased precision in obtaining good test coverage on a set of moderately-sized Java web services benchmarks.
A Novel Hypothalamic Peptide, Pituitary Adenylate Cyclase-Activating Peptide, Regulates the Function of Rat Granulosa Cells in Vitro1 (1996)

Pituitary adenylate cyclase-activating peptide (PACAP) is a novel peptide that was isolated from ovine hypothalamic tissue on the basis of its ability to stimulate cAMP accumulation in cultured rat pituitary cells. Recently we demonstrated that PACAP can stimulate cAMP accumulation and secretory function in cultured rat Sertoli cells. Since ovarian granulosa cells share many properties with Sertoli cells, we have examined the effect of PACAP (consisting of 38 or 27 amino acid residues) on cultured granulosa cell function. Granulosa cells were obtained from the ovaries of 25-day-old rats implanted with a silastic capsule containing diethylstilbestrol 5 days prior to culture. PACAP 38 (0.1 microM-0.01 pM), both alone and in the presence of the phosphodiesterase inhibitor, methylisobutylxanthine, stimulated cAMP accumulation 4-8-fold with an ED50 of approximately 100 pM. Maximal PACAP 38 or PACAP 27 stimulation of granulosa cell cAMP was significantly greater than that produced by a maximally effective concentration of FSH. Because PACAP 38 and 27 have 68% sequence homology with vasoactive intestinal peptide (VIP), and since VIP stimulates granulosa cell cAMP accumulation and estradiol and progesterone secretion, we examined the possibility that PACAP could be acting via the VIP receptor. VIP stimulated cAMP only at concentrations of 10 nM or greater, whereas the PACAP stimulation was evident at 10 pM. Moreover, only one of three potent VIP antagonists inhibited VIP stimulation of cAMP accumulation, and only at 1 microM or greater. This VIP antagonist did not inhibit PACAP 38 action at 2000-fold excess concentration. Interestingly PACAP 38 was more effective than PACAP 27 with regard to steroid secretion and the ability to induce LH responsiveness. PACAP and VIP stimulation of granulosa cell cAMP accumulation or estradiol or progesterone secretion was not additive. Thus, these data support the hypothesis that granulosa cells have specific PACAP 38 receptors and that VIP acts via these receptors. In addition, PACAPs 38 and 27 are more potent stimulators of cAMP accumulation in luteinized granulosa cells than LH. These results both pre- and postovulation, along with previous data indicating that the PACAPs are found in the ovaries, suggest a role for PACAP in the regulation of ovarian function.
Ambient Noise Interferometry from DAS Array in Underground Telecommunications Conduits (2017)

Summary Ambient noise interferometry allows us to characterize the near surface without the cost and regulatory constraints of controlled seismic sources. Geophone arrays can be expensive to install and maintain, but trenched distributed acoustic sensing (DAS) arrays have shown promise for reducing the maintenance cost of ambient noise acquisition. In this paper we test a novel, easily installed acquisition system using fibre in existing underground telecommunications conduits for ambient noise collection on the Stanford University campus. This installation only uses gravity to hold the fibre in place in the air-filled conduits, and the conduit installation method varies some throughout the site. We outline the basic theory of ambient noise interferometry for DAS measurements, present a method of using nearby earthquake response as a sensor coupling proxy, and present signal processing methods for coping with a variety of noise sources throughout the array. We show cross-correlations and dispersion calculations along a subset of the array expected to primarily yield Rayleigh waves.