gebhart/patrepeval huggingface dataset:
Genomic expression profiling of TNF-α-treated BDC2.5 diabetogenic CD4+T cells (2008)

TNF-alpha plays an important role in immune regulation, inflammation, and autoimmunity. Chronic TNF exposure has been shown to down-modulate T cell responses. In a mouse T cell hybridoma model, TNF attenuated T cell receptor (TCR) signaling. We have confirmed that chronic TNF and anti-TNF exposure suppressed and increased T cell responses, respectively. In adult TCR (BDC2.5) transgenic nonobese diabetic mice, DNA microarray analysis of global gene expression in BDC2.5 CD4(+) T cells in response to chronic TNF or anti-TNF exposure showed that genes involved in functional categories including T cell signaling, cell cycle, proliferation, ubiquitination, cytokine synthesis, calcium signaling, and apoptosis were modulated. Genes such as ubiquitin family genes, cytokine inducible Src homology 2-containing genes, cyclin-dependent kinase inhibitors p21, p57, calmodulin family genes (calmodulin-1, -2, and -3) and calcium channel voltage-dependent, N type alpha1B subunit (CaV2.2) were induced by TNF, whereas Vav2, Rho GTPase-activating protein, calcium channel voltage-dependent, L type alpha1C subunit (CaV1.2), IL-1 receptor-associated kinase-1 and -2, and IL enhancer binding factor 3 were reduced by TNF. Genes such as CaV1.2 and proliferating cell nuclear antigen, repressed by TNF, were induced by anti-TNF treatment. Further, we showed that chronic TNF exposure impaired NF-kappaB and adaptor protein 1 transactivation activity, leading to T cell unresponsiveness. Thus, our results present a detailed picture of transcriptional programs affected by chronic TNF exposure and provide candidate target genes that may function to mediate TNF-induced T cell unresponsiveness.
High-Throughput Low-Energy Self-Timed CAM Based on Reordered Overlapped Search Mechanism (2013)

This paper introduces a reordered overlapped search mechanism for high-throughput low-energy content-addressable memories (CAMs). Most mismatches can be found by searching a few bits of a search word. To lower power dissipation, a word circuit is often divided into two sections that are sequentially searched or even pipelined. Because of this process, most of match lines in the second section are unused. Since searching the last few bits is very fast compared to searching the rest of the bits, we propose to increase throughput by asynchronously initiating second-stage searches on the unused match lines as soon as a first-stage search is complete. In our circuit implementation, each word circuit is independently controlled by a locally generated timing signal rather than a global signal. This allows the circuits to be in the required phase for their own local operation: evaluate or precharge, instead of having to synchronize their phase to the rest of the word circuits, which greatly reduces the cycle time. As a design example, a 128 × 64-bit CAM is implemented and evaluated by HSPICE simulation under a 90 nm CMOS technology. The proposed asynchronous CAM operates 5.98 times faster than a synchronous CAM with 14.2% smaller energy dissipation. The post-layout proposed CAM achieves 385-ps cycle delay time and 0.773 fJ/bit/search and is also evaluated under different corner conditions and PVT variations to guarantee it operates properly.
Abstract IA004: Metabolic mechanisms of prostate cancer progression that feed nuclear receptors (2023)

Abstract The androgen axis is central to prostate cancer physiology and therapy. Androgens are gonadal and extragonadal in origin, both of which stimulate the androgen receptor (AR). The use of medical castration (ADT), adrenal androgen ablation (i.e., abiraterone) and potent AR antagonists (i.e., enzalutamide, apalutamide, darolutamide), has yielded complex clinical states of prostate cancer, including disease states that are resistant to multiple forms of hormonal therapy. One of the major questions that arises is whether men can be identified who will benefit from earlier intensive hormonal therapy. Another question is whether alternative hormonal treatment strategies can be used to address resistance to the current generation of hormonal therapies. We propose that identification of steroid metabolic dependencies is part of the answer to both of these questions. Approximately half of men with prostate cancer inherit an activating missense in the first and rate-limiting enzyme that converts extragonadal precursor steroids to dihydrotestosterone (DHT). The “adrenal-permissive” HSD3B1(1245C) allele encodes for a 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) enzyme that increases tumor DHT synthesis from adrenal DHEA. Heterozygous or homozygous HSD3B1(1245C) inheritance confers poor outcomes after ADT. Furthermore, men with HSD3B1(1245C) inheritance and castration-resistant prostate cancer (CRPC) treated with abiraterone or enzalutamide still have poorer outcomes. Together, these data suggest that directly targeting this metabolic lesion is necessary for optimal therapy in these men. We recently discovered that phosphorylation of the 3βHSD1 tyrosine 344 by the BMX kinase is necessary for androgen biosynthesis and CRPC in xenograft models. These findings have led to the launch of the Maverick clinical trial in the Prostate Cancer Clinical Trials Consortium (PCCTC) that combines abiraterone plus BMX inhibition with abivertinib in men with CRPC. In sum, this accumulating body of evidence suggests that steroid metabolic dependencies should be considered as an essential part of cancer metabolism, particularly in the context of developmental therapeutics for prostate cancer. Citation Format: Nima Sharifi. Metabolic mechanisms of prostate cancer progression that feed nuclear receptors [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA004.
Tissue Selective Androgen Receptor Modulators (SARMs) Increase Pelvic Floor Muscle Mass in Ovariectomized Mice (2016)

Stress urinary incontinence (SUI), a prevalent condition, is represented by an involuntary leakage of urine that results, at least in part, from weakened or damaged pelvic floor muscles and is triggered by physical stress. Current treatment options are limited with no oral therapies available. The pelvic floor is rich in androgen receptor and molecules with anabolic activity including selective androgen receptor modulators (SARMs) may serve as therapeutic options for individuals with SUI. In this study, two SARMs (GTx-024 and GTx-027) were evaluated in a post-menopausal animal model in order to determine their effect on pelvic floor muscles. Female C57BL/6 mice were ovariectomized and their pelvic muscles allowed to regress. The animals were then treated with vehicle or doses of GTx-024 or GTx-027. Animal total body weight, lean body mass, and pelvic floor muscle weights were measured along with the expression of genes associated with muscle catabolism. Treatment with the SARMs resulted in a restoration of the pelvic muscles to the sham-operated weight. Coordinately, the induction of genes associated with muscle catabolism was inhibited. Although a trend was observed towards an increase in total lean body mass in the SARM-treated groups, no significant differences were detected. Treatment of an ovariectomized mouse model with SARMs resulted in an increase in pelvic floor muscles, which may translate to an improvement of symptoms associated with SUI and serves as the basis for evaluating their clinical use. J. Cell. Biochem. 118: 640-646, 2017. © 2016 Wiley Periodicals, Inc.
Correlation between miRNA and gene expression profiles and response to neoadjuvant chemotherapy in patients with locally advanced and inflammatory breast cancer. (2011)

548 Background: Gene expression profiling may predict for pathologic complete response (pCR) after neoadjuvant therapy (NT). Identification of both miRNA and gene expression may yield novel targets and improved NT. Methods: Patients (pts) with HER2− locally advanced/inflammatory breast cancer (BC) were randomized to receive docetaxel, doxorubicin, cyclophosphamide (TAC, arm A), or A and C given every 2 weeks × 4, followed by carboplatin and nab-paclitaxel (arm B). Pts with HER2+ BC received NT similar to arm B, with trastuzumab (arm C). Core biopsies were snap-frozen prior to NT, and RNA was extracted for gene array analysis (MammaPrint, BluePrint: basal, luminal, and HER2 profiling, and Agilent 44K microarray), and for deep sequence miRNA analysis with the Solexa/Illumina platform. Pathological assessment included grade, ER, HER2 expression, and evidence of residual BC vs.pCR. Unsupervised hierarchical clustering analysis and Fisher’s exact tests were utilized to assess for correlation between miRNA and gene expression, and pathologic assessment. Significant analysis of microarrays (SAM) was used to identify miRNAs differentially expressed and predictive for response (pCR vs. other) to NT. Results: miRNA expression was measured in 72 of 119 enrolled pts; 487 of the 882 miRNAs sequenced, were expressed with raw counts of > 10 in at least 3 pts. miRNA expression patterns revealed three distinct pt clusters, which were significantly associated with the 3 BluePrint subtypes and ER status (Fisher’s exact test, P-values < 1e-5), and moderately associated with HER2 status and MammaPrint classes at borderline significance (P-value: 0.08 and 0.05). SAM identified 6 up and 9 down-regulated miRNAs associated with pCR in HER2− patients (N=43, 4 pCRs) with ≥2 fold changes at false discovery rate (FDR) < 10%. No significant signals of miRNA expression associated with pCR were found in HER2+ pts (N=28; 13 pCRs) at the same FDR level. Conclusions: Combined assessment of miRNA and gene expression patterns is feasible, and pending validation, may yield information leading to individualized and improved NT.
Studies of cholecystokinin-stimulated biliary secretions reveal a high molecular weight copper-binding substance in normal subjects that is absent in patients with Wilson's disease. (1988)

Copper is unique among cations in that its balance is regulated by the liver. The liver regulates copper balance by excretion of copper (we call it regulatory copper) in the bile destined for loss in the stool. However, most copper secreted into the gastrointestinal tract, for example, that in saliva and gastric juice, is reabsorbed. The biochemical mechanism by which the normal liver "packages" regulatory copper to prevent its reabsorption is not understood. Whatever the mechanism, it appears to have failed in Wilson's disease, because patients with Wilson's disease do not excrete adequate amounts of regulatory copper in their bile to prevent copper accumulation. In the present work, we have studied cholecystokinin-stimulated biliary secretions obtained by intestinal intubation of five normal subjects and five patients with Wilson's disease. Studies of these secretions reveal: (1) that normal but not Wilson's disease biliary samples had a copper-containing peak in the void volume from Sephadex G-75 columns; (2) that the amount of copper in this peak extrapolated to 24 hours of secretion was appropriate to maintain normal copper balance; (3) that the amount of copper in this peak increased with dietary copper supplementation of normal subjects; (4) that normal but not Wilson's disease biliary samples cross-reacted with each of two ceruloplasmin antibodies; and (5) that the high molecular weight Sephadex G-75 fraction from normal but not from Wilson's disease biliary samples cross-reacted with ceruloplasmin antibody. We postulate that the high molecular weight copper-containing substance observed with Sephadex chromatography in normal biliary samples but absent in Wilson's disease samples is the copper-packaging mechanism for copper balance regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Outcomes of multimodality therapy for gallbladder cancer in the United States (US): Analysis of the National Cancer Data Base (NCDB). (2016)

313 Background: Management of gallbladder cancer (GBCA) is largely based on small observational studies, and it is unknown how various treatment modalities are applied in the community. The objective of this study was to describe the utilization of surgery (S), chemotherapy (Ct) and chemoradiation (CRT), and associated overall survival (OS) in the US. Methods: We selected adult patients (pts) with GBCA diagnosed in 2004-2012 from the NCDB—a population-wide registry capturing &gt; 70% of incident cancers in the US. We identified pts undergoing S, Ct and concurrent CRT. We assumed adjuvant (Adj) therapy if it was started within 4 months (mo) of S. Stage was grouped as: T1-T3N0, node-positive (N+), T4 (N0 or N+) or metastatic (M1). OS was calculated from diagnosis, with 95% confidence intervals (CI). Results: We identified 22,574 GBCA pts. Median age was 71 years. There were 69% women, 71% white non-Hispanic, 10% white Hispanic, 14% black and 4% Asian pts. Distribution of stage groups was: in situ, 4%; T1N0, 8%; T2N0, 16%; T3N0, 13%; N+, 14%; T4, 3%; M1, 38%; unknown, 4%. Most non-metastatic pts underwent S, but only a minority received Adj Ct or CRT (Table). Among M1 and T4 pts, 44% received Ct, but 29% got no cancer-directed therapy. Median OS for M+ or T4 pts was 4 and 7 mo, respectively. It was 8 and 11 mo, respectively, if Ct was given. Conclusions: These OS estimates provide realistic prognosis for GBCA pts treated with various modalities in the US. Adj therapy is rarely delivered in locally advanced (T3N0 or T1-3N+) GBCA. Survival in T4 and M1 GBCA remains poor even with palliative Ct. Novel therapeutic approaches for GBCA of all stages are needed. [Table: see text]
A university teaching simulation facility (1987)

An experimental telerobotics (TR) simulation is described suitable for studying human operator (HO) performance. Simple manipulator pick-and-place and tracking tasks allowed quantitative comparison of a number of calligraphic display viewing conditions. A number of control modes could be compared in this TR simulation, including displacement, rate, and acceleratory control using position and force joysticks. A homeomorphic controller turned out to be no better than joysticks; the adaptive properties of the HO can apparently permit quite good control over a variety of controller configurations and control modes. Training by optimal control example seemed helpful in preliminary experiments.
Hardware Architecture for List SC Decoding of Polar Codes (2013)

We present a hardware architecture and algorithmic improvements for list SC decoding of polar codes. More specifically, we show how to completely avoid copying of the likelihoods, which is algorithmically the most cumbersome part of list SC decoding. The hardware architecture was synthesized for a blocklength of N = 1024 bits and list sizes L = 2, 4 using a UMC 90nm VLSI technology. The resulting decoder can achieve a coded throughput of 181 Mbps at a frequency of 459 MHz.
Building an on-chip spectrum sensor for cognitive radios (2014)

Next generation cognitive radio networks require an RF and mixed signal hardware architecture that can achieve low-energy, very wideband spectrum sensing. We survey state-of-the-art low-power CMOS building blocks as potential candidates for realizing such an architecture. For the critical analog-to-digital converter, we compare time-interleaved and frequency- interleaved architectures, including system- level simulations, and frequency-interleaving is shown to provide significant advantages. Measurement results from a 3.8 mW 5 GHz bandwidth analog domain frequency interleaver are presented to confirm the possibility of a very low-energy frequency domain digitizer. Coupled with DSP for calibration and signal feature extraction, this architecture has significant promise for cognitive spectrum sensing.
Advantages of CMOS photonics for future transceiver applications (2010)

The advantages of CMOS photonics for next generation transceiver applications are outlined in terms of raw bandwidth, channel capacity, reach, power, cost, link performance and reliability. The advantages for future integration with host chips area also discussed.
Efficacy and toxicity of surufatinib in neuroendocrine tumors: A systematic review and meta‐analysis (2022)

The incidence and prevalence of neuroendocrine neoplasms (NENs) has increased in the US in recent decades. These are well-vascularized tumors, but no antiangiogenic drug has been approved for treatment of extra-pancreatic NENs. The aim is to assess efficacy and safety of surufatinib in pancreatic and extra-pancreatic NETs. We searched PubMed, Embase, Cochrane Library, Web of Science and Clinicaltrials.gov. Clinical trials and observational studies that provided safety and efficacy data in clinical terms were included. Characteristics of the study, baseline characteristics of participants, treatment drugs, measures of efficacy, and toxicity (≥grade 3 adverse effects) were extracted. The meta-analysis was performed using the "R" programming language. Risk ratio (RR) of objective response (OR)/partial response (PR) was 8.55 (95% CI: 1.68-43.66, I<sup>2</sup> = 0) in favor of surufatinib. The hazard ratio (HR) of progression-free survival (PFS) was 0.48 (95% CI: 0.25-0.92, I<sup>2</sup> = 77%) in favor of surufatinib. The risk of ≥grade 3 adverse effects: diarrhea, hypertension, hypertriglyceridemia, proteinuria, and vomiting were high with the use of surufatinib. Quality of life (QoL) was similar in surufatinib and placebo groups except for the diarrhea that was high with surufatinib. Lack of randomized clinical trials in non-Chinese population. Surufatinib is well tolerated and is more effective than placebo in both pancreatic and extra-pancreatic NETs. More multicenter randomized, double-blinded clinical trials are needed to confirm these results.
A system scenario for wireless broadband access with multimedia support (2002)

Radio access networks are evolving towards the support for mobile multimedia services with quality of service (QoS) guarantees. While this trend is clearly seen, a relation to the fixed network evolution and the legacy wireless systems has to be kept in mind. This paper discusses a general reference scenario for broadband radio access networks with QoS support. In this context the required entities, distribution of functionalities and interfaces are studied in detail using ATM core network and wireless ATM radio access network as example technologies. Finally, an ATM based system demonstrator is discussed.
Optimization of iron oxide nanoparticle detection using ultrashort echo time pulse sequences: Comparison of T1, T2*, and synergistic T1 − T2* contrast mechanisms (2011)

Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T(1) shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T(2)*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T(1) and T(2)* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T(1) contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T(2)* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T(1) and T(2)* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor-targeted IONPs in vivo.
Proceedings of the 14th International Conference on Information Processing in Sensor Networks (2015)

Welcome to the 14th IEEE/ACM International Conference on Information Processing in Sensor Networks (IPSN 2015) in Seattle, USA. IPSN is one of the flagship research conferences of the networked sensing and control community, and continues to serve as a major forum for cuttingedge research results.
Investigation of metal contamination induced by a through silicon via reveal process using direct Si/Cu grinding and residual metal removal (2016)

Abstract We investigated metal contamination induced by a through silicon via (TSV) reveal process using direct Si/Cu grinding and residual metal removal. A complementary metal oxide semiconductor (CMOS) wafer including TSVs was bonded to a glass support substrate, and a TSV reveal process was performed by direct Si/Cu grinding and residual metal removal. Then, metal contamination near the SiO 2 /Si interface on the front side of the wafer was investigated by using a pulsed-MOS capacitor technique and measuring the effective generation lifetime and effective surface generation velocity before and after this TSV reveal process. The results of Zerbst analysis showed that the changes in average effective generation lifetime and average effective surface generation velocity were −5.4 and +4.2%, respectively. These results demonstrate that the effect of metal contamination induced by our TSV reveal process on circuit components is small.
Metabolomics—A Promising Approach to Pituitary Adenomas (2019)

<b>Background:</b> Metabolomics-the novel science that evaluates the multitude of low-molecular-weight metabolites in a biological system, provides new data on pathogenic mechanisms of diseases, including endocrine tumors. Although development of metabolomic profiling in pituitary disorders is at an early stage, it seems to be a promising approach in the near future in identifying specific disease biomarkers and understanding cellular signaling networks. <b>Objectives:</b> To review the metabolomic profile and the contributions of metabolomics in pituitary adenomas (PA). <b>Methods:</b> A systematic review was conducted via PubMed, Web of Science Core Collection and Scopus databases, summarizing studies that have described metabolomic aspects of PA. <b>Results:</b> Liquid chromatography tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) spectrometry, which are traditional techniques employed in metabolomics, suggest amino acids metabolism appears to be primarily altered in PA. N-acetyl aspartate, choline-containing compounds and creatine appear as highly effective in differentiating PA from healthy tissue. Deoxycholic and 4-pyridoxic acids, 3-methyladipate, short chain fatty acids and glucose-6-phosphate unveil metabolite biomarkers in patients with Cushing's disease. Phosphoethanolamine, N-acetyl aspartate and myo-inositol are down regulated in prolactinoma, whereas aspartate, glutamate and glutamine are up regulated. Phosphoethanolamine, taurine, alanine, choline-containing compounds, homocysteine, and methionine were up regulated in unclassified PA across studies. Intraoperative use of ultra high mass resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which allows localization and delineation between functional PA and healthy pituitary tissue, may contribute to achievement of complete tumor resection in addition to preservation of pituitary cell lines and vasopressin secretory cells, thus avoiding postoperative diabetes insipidus. <b>Conclusion:</b> Implementation of ultra high performance metabolomics analysis techniques in the study of PA will significantly improve diagnosis and, potentially, the therapeutic approach, by identifying highly specific disease biomarkers in addition to novel molecular pathogenic mechanisms. Ultra high mass resolution MALDI-MSI emerges as a helpful clinical tool in the neurosurgical treatment of pituitary tumors. Therefore, metabolomics appears to be a science with a promising prospect in the sphere of PA, and a starting point in pituitary care.