gebhart/patrepeval huggingface dataset:
Effect of Janus kinase (JAK) signaling inhibition on lineage plasticity and drug sensitivity in castrate resistant prostate cancer. (2023)

227 Background: Despite the remarkable successes of targeted cancer therapies, certain cancers, including lung, breast, and prostate cancer and melanoma, invariably become resistant to therapy. One mechanism of secondary resistance—lineage plasticity—arises when cells alter their identity and transition into aggressive states. In the case of prostate cancer, cells can acquire a neuroendocrine histology. This is often associated with a loss of tumor suppressor genes, such as TP53, RB1, and PTEN. However, while these genomic events initiate plasticity, tumor progression is not always associated with successive genomic alterations. This, in essence, not only poses a clinical challenge, but also confronts us with a wide-open biological question—what are the molecular underpinnings of lineage plasticity, and importantly, can the process be reversed? Methods: To study the temporal evolution of lineage plasticity and its relationship to androgen receptor signaling inhibitor (ARSI) resistance, we utilized genetically engineered mouse models (GEMMs) and murine organoids that were deleted for Tp53, Rb1, and/or Pten. Single cell RNA analyses were utilized to dissect which genes and pathways were up-regulated and most associated with the progression of plasticity. Plasticity-associated genes and pathways were perturbed using FDA-approved inhibitors or genetic editing tools. The presence of these pathways was confirmed in a subset of metastatic index lesions obtained by radiologically guided biopsies and as visualized by metabolic imaging. Furthermore, relevant findings were functionally validated in human tumor derived organoids (“tumoroids”). Results: Using GEMMs and organoid models, we found the lineage plasticity depended on increased Janus Kinase (JAK) and fibroblast growth factor receptor (FGFR) activity. Pharmacologic inhibition using FDA–approved inhibitors of JAK/STAT (ruxolitinib) and FGFR (erdafinitib), or through genetic knockdown, demonstrated increased androgen receptor (AR) signaling and restored ARSI sensitivity. These findings were further validated in a subset of ARSI-insensitive human tumoroids. By performing single cell RNA sequencing on mCRPC tumors biopsies, the presence of highly plastic JAK/STAT- and FGFR-high cells were confirmed, with implications for stratifying patients for clinical trials. Conclusions: JAK/STAT and FGFR signaling pathways promote lineage plasticity and result in complete insensitivity to androgen receptor signaling inhibitors (ARSIs). FDA-approved inhibitors of JAK/STAT (ruxolitinib) and FGFR (erdafitinib) synergize to reverse lineage plasticity and restore ARSI sensitivity.
Pentoxifylline modulates activation of human neutrophils by amphotericin B in vitro (1992)

The antifungal agent amphotericin B (AmB) alters neutrophil (polymorphonuclear leukocyte [PMN]) function, and this may be the mechanism for some of the adverse effects caused by AmB. AmB is a potent inhibitor of PMN migration, increases PMN adherence and aggregation, and primes PMN for increased oxidative activity in response to a second stimulus. AmB also stimulates mononuclear leukocytes (MNLs) to release inflammatory mediators which augment the effects of AmB on PMN function. In the present study, we observed that the methylxanthine derivative pentoxifylline decreased the effects of AmB on PMN function. AmB (2 micrograms/ml) priming doubled PMN chemiluminescence stimulated by fMet-Leu-Phe. In the presence of MNLs, AmB priming increased fMet-Leu-Phe-stimulated PMN chemiluminescence to 622% of unprimed PMN activity. Pentoxifylline (100 microM) blunted the rise in AmB-augmented PMN chemiluminescence in the presence of MNLs to 282% of unprimed PMN activity, and pentoxifylline metabolites were active at 10 microM. Pentoxifylline (100 microM) also blocked AmB-augmented PMN oxidative activity in whole blood, as measured by nitroblue tetrazolium reduction. In the presence of MNL, AmB (2 micrograms/ml) doubled the expression of the important PMN adherence factor Mac-1. Pentoxifylline (1 mM) decreased AmB-stimulated PMN Mac-1 expression back to unstimulated amounts. In the presence of MNLs, AmB (2 micrograms/ml) decreased PMN nondirected and directed migration to fMet-Leu-Phe to 40 and 38% of control PMN migration, respectively. Pentoxifylline (300 microM) counteracted AmB inhibition of nondirected and directed migration to fMet-Leu-Phe, resulting in migration that was 71 and 87% of control PMN migration, respectively. In contrast, the methylxanthine caffeine (100 muM) increased AmB-enhanced chemiluminescence but did not affect AmB-inhibited PMN migration. Pentoxifylline should be evaluated as adjunctive therapy to lessen the inflammatory damage caused by AmB.
Supplementary Table 2 from CD16<sup>+</sup>NKG2A<sup>high</sup> Natural Killer Cells Infiltrate Breast Cancer–Draining Lymph Nodes (2023)

&lt;p&gt;Supplementary Table 2&lt;/p&gt;
Max-Margin Infinite Hidden Markov Models (2014)

Infinite hidden Markov models (iHMMs) are nonparametric Bayesian extensions of hidden Markov models (HMMs) with an infinite number of states. Though flexible in describing sequen-tial data, the generative formulation of iHMMs could limit their discriminative ability in sequen-tial prediction tasks. Our paper introduces max-margin infinite HMMs (M2iHMMs), new infinite HMMs that explore the max-margin principle for discriminative learning. By using the theory of Gibbs classifiers and data augmentation, we de-velop efficient beam sampling algorithms with-out making restricting mean-field assumptions or truncated approximation. For single variate clas-sification, M2iHMMs reduce to a new formula-tion of DP mixtures of max-margin machines. Empirical results on synthetic and real data sets show that our methods obtain superior perfor-mance than other competitors in both single vari-ate classification and sequential prediction tasks.
Significant radiation reduction in interventional fluoroscopy using a novel eye controlled movable region of interest (2016)

The first in vivo evaluation of ECR demonstrated that this technology has objectively reduced KAP and operator irradiation by approximately 75% without interfering with the performance of fluoroscopically guided interventional procedures. In addition, reduced scatter production subjectively improved device visualization. These findings indicate the practicability of achieving better radiation optimization.
System-on-Package (SOP) Technology, Characterization and Applications (2006)

A silicon-based system-on-package (SOP) is described. Novel capabilities of SOP are expected to enable lower cost, more efficient and higher performance electronic systems. Newly developed technology elements include: electrical silicon through-vias, fine-pitch, high bandwidth wiring, fine pitch solder interconnection, fine pitch known-good-die, and advanced microchannel cooling. Applications may range from miniaturized consumer products such as integrated function cell phones to high performance computers. SOP technology and related chip stacking challenges have been investigated and robust technology options are reported. Silicon through-vias can be fabricated using copper, tungsten, composite or alternate conductors. Via design and structure are discussed for vias in thin silicon packages mounted on a supporting substrate as well as thick silicon package that can be handled without a supporting substrate. Fine-pitch, high bandwidth wiring has been fabricated, characterized and shows greatest bandwidth for shorter interconnection distances. Fine pitch area array solder interconnections have been fabricated and characterized electrically, mechanically and with accelerated reliability testing. These fine pitch interconnections can enable the high bandwidth wiring for chip-to-chip interconnection. Integrated decoupling capacitors have been fabricated using parallel plate and trench technology. The integrated decoupling capacitors can provide under-chip, low inductance bypassing to minimize noise from simultaneous switching noise. New fine pitch, area array test technology provides a path to wafer level test for known-good-die, functional test, and burn-in for the fine pitch chip I/O. Advanced microchannel cooling can be leveraged to support high power, close proximity chips and chip stacks for cooling > 300 W/cm/sup 2/. This IBM research paper describes the design, technical challenges and progress for next generation SOP technology, chip stacking, characterization, and potential new applications.
Efficient multi-objective optimization of wireless network problems on wireless testbeds (2014)

A large amount of research focuses on experimentally optimizing performance of wireless solutions. Finding the optimal performance settings typically requires investigating all possible combinations of design parameters, while the number of required experiments increases exponentially for each considered design parameter. The aim of this paper is to analyze the applicability of global optimization techniques to reduce the optimization time of wireless experimentation. In particular, the paper applies the Efficient Global Optimization (EGO) algorithm implemented in the SUrrogate MOdeling (SUMO) toolbox inside a wireless testbed. The proposed techniques are implemented and evaluated in a wireless testbed using a realistic wireless conference network problem. The performance accuracy and experimentation time of an exhaustively searched experiment is compared against a SUMO optimized experiment. In our proof of concept, the proposed SUMO optimizer reaches 99.51% of the global optimum performance while requiring 10 times less experiments compared to the exhaustive search experiment.
Design and Implementation of Safety Functions on a Novel CPLD-Based Fail-Safe System Architecture (2010)

In the case of a fault fail-safe systems achieve and maintain a safe state for people, environment and property. These systems are usually realized using microcontroller-based architectures. With respect to cost per unit and development effort for fail-safe systems, industry has to consider new approaches. An option is to realize simple safety functions using architectures that include CPLDs. A novel hardware architecture for embedded fail-safe systems is the outcome of recent research efforts at SIEMENS. This architecture is homogeneously redundant and contains, in contrast to similar systems, exclusively two CPLDs instead of microcontrollers. This paper is presenting design and implementation of the very first fail-safe system based on this architecture. This system targets the market of industrial automation. The fail-safe system enhances a power converter with safety functions. To achieve the required safety integrity, adequate measures able to detect random and permanent faults, are implemented. The novel fail-safe system adheres to the draft of the second edition of the IEC 61508, which includes requirements for the realization of safety functions using CPLDs, the IEC 61800-5-2 and the EN ISO 13849.
Prediction of Flame Burning Velocity at Early Flame Development Time With High Exhaust Gas Recirculation and Spark Advance (2017)

Diluting spark-ignited (SI) stoichiometric combustion engines with excess residual gas improves thermal efficiency and allows the spark to be advanced toward maximum brake torque (MBT) timing. However, flame propagation rates decrease and misfires can occur at high exhaust gas recirculation (EGR) conditions and advanced spark, limiting the maximum level of charge dilution and its benefits. The misfire limits are often determined for a specific engine from extensive experiments covering a large range of speed, torque, and actuator settings. To extend the benefits of dilute combustion while at the misfire limit, it is essential to define a parameterizable, physics-based model capable of predicting the misfire limits, with cycle to cycle varied flame burning velocity as operating conditions change based on the driver demand. A cycle-averaged model is the first step in this process. The current work describes a model of cycle-averaged laminar flame burning velocity within the early flame development period of 0–3% mass fraction burned. A flame curvature correction method is used to account for both the effect of flame stretch and ignition characteristics, in a variable volume engine system. Comparison of the predicted and the measured flame velocity was performed using a spark plug with fiber optical access. The comparison at a small set of spark and EGR settings at fixed load and speed, shows an agreement within 30% of uncertainty, while 20% uncertainty equals ± one standard deviation over 2000 cycles.
Protocatechuic Acid from Alpinia oxyphylla Induces Schwann Cell Migration via ERK1/2, JNK and p38 Activation (2015)

Alpinia oxyphylla MIQ (Alpinate Oxyphyllae Fructus, AOF) is an important traditional Chinese medicinal herb whose fruits is widely used to prepare tonics and is used as an aphrodisiac, anti salivary, anti diuretic and nerve-protective agent. Protocatechuic acid (PCA), a simple phenolic compound was isolated from the kernels of AOF. This study investigated the role of PCA in promoting neural regeneration and the underlying molecular mechanisms. Nerve regeneration is a complex physiological response that takes place after injury. Schwann cells play a crucial role in the endogenous repair of peripheral nerves due to their ability to proliferate and migrate. The role of PCA in Schwann cell migration was determined by assessing the induced migration potential of RSC96 Schwann cells. PCA induced changes in the expression of proteins of three MAPK pathways, as determined using Western blot analysis. In order to determine the roles of MAPK (ERK1/2, JNK, and p38) pathways in PCA-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production, the expression of several MAPK-associated proteins was analyzed after siRNA-mediated inhibition assays. Treatment with PCA-induced ERK1/2, JNK, and p38 phosphorylation that activated the downstream expression of PAs and MMPs. PCA-stimulated ERK1/2, JNK and p38 phosphorylation was attenuated by individual pretreatment with siRNAs or MAPK inhibitors (U0126, SP600125, and SB203580), resulting in the inhibition of migration and the uPA-related signal pathway. Taken together, our data suggest that PCA extract regulate the MAPK (ERK1/2, JNK, and p38)/PA (uPA, tPA)/MMP (MMP2, MMP9) mediated regeneration and migration signaling pathways in Schwann cells. Therefore, PCA plays a major role in Schwann cell migration and the regeneration of damaged peripheral nerve.
A high-frequency single-side PWM multiple bus distributed power system (2002)

The design consideration and implementation of a high frequency (HF) PWM-wave bus distributed power system (DPS) is presented. The system utilizes a 100 kHz, 48 V peak PWM bus for AC voltage distribution. The load converter consists of different level output magamps post-regulators. Bus regulation is accomplished through a simplified front-end design consisting of a boost PFC converter cascaded with a two-switch forward converter. Experimental results are presented for operation at 5 V DC and 3.3 V DC with 200 W output.
ChemInform Abstract: Tandem Diels‐Alder Cycloadditions in Organic Synthesis (1996)

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.
Phrase boundary assignment from text in multiple domains (2012)

Detecting and modeling proper phrasing from an input text string is an important aspect when producing synthesis that sounds intelligible and natural. Knowledge of proper phrase structure influences, e.g., the placement and length of pauses, and the realization of phrase-final boundary contours, both of which can have an effect in a listener’s percepts ranging from naturalness to semantic interpretation. In this work, we look at modeling the occurrence, and types, of phrase breaks from purely textual features, paying close attention to how the performance of the systems generalizes inand out-of-domain for corpora of various types (such as broadcast news, spontaneous speech, and synthesis databases), and as a function of various subsets of syntactical and lexical features investigated.
New developments of high-power single emitters and laser bars at JENOPTIK (2011)

High-power single emitters and laser bars find several growing industrial applications such as materials processing. A steady increase in efficiency and output power is needed to conquer new markets. The development of high-end diode lasers usually starts with the development of the epitaxial structure. Therefore, simulations have been performed before the optimized layer structures have been tested using broad area (BA) lasers. Single emitter laser diodes are needed for fiber coupling with a minimal loss of light. We developed such emitters with high output powers at a small far field angle showing output powers of more than 20 W around 940 nm. The high-quality laser bars available at JENOPTIK have been improved and extended to new wavelength ranges. At the lower end, laser bars have been developed around and below 800 nm. At the higher end, design parameters have been optimized for 1060 nm emission wavelength.
Detecting internal defects of a steel plate by using low-frequency magnetic flux leakage method (2017)

Steel is an important material in modern society. It is widely used in our lives, such as in buildings, bridges, and airplanes. We previously reported an analysis method for examining the internal defects of metal structures with eddy current testing (ECT) over a wide range of frequencies. However, internal defects in steel plates are difficult to detect using ECT. In this paper, we present a low-frequency magnetic flux leakage (MFL) method for the nondestructive evaluation of internal defects in steel structures, and an analysis and imaging method that uses the phase of a magnetic field to examine internal defects. By analyzing the phase change in the detected signal, the internal defects can be detected with no magnetic fluctuation. The phase map of the measured magnetic field exhibits good correlation with the simulation results. The two-dimensional magnetic phase map can be used to visualize the internal defects. This new method has been validated through both experiment and simulation.
Exploring the vulnerability of CMPs to soft errors with 3D stacked nonvolatile memory (2013)

Improving the vulnerability to soft errors is one of the important design goals for future architecture design of Chip-MultiProcessors (CMPs). In this study, we explore the soft error characteristics of CMPs with 3D stacked NonVolatile Memory (NVM), in particular, the Spin-Transfer Torque Random Access Memory (STT-RAM), whose cells are immune to radiation-induced soft errors and do not have endurance problems. We use 3D stacking as an enabler for modular integration of STT-RAM memories with minimum disruption in the baseline processor design flow, while providing further interconnection and capacity advantages. We take an in-depth look at alternative replacement schemes to explore the soft error resilience benefits and design trade-offs of 3D stacked STT-RAM and capture the multivariable optimization challenges microprocessor architectures face. We propose a vulnerability metric, with respect to the instruction and data in the core pipeline and through the cache hierarchy, to present a comprehensive system evaluation with respect to reliability, performance, and power consumption for our CMP architectures. Our experimental results show that, for the average workload, replacing memories with an STT-RAM alternative significantly mitigates soft errors on-chip, improves the performance by 14.15%, and reduces power consumption by 13.44%.
Insulin stimulates serine and tyrosine phosphorylation in the juxtamembrane region of the insulin receptor (1993)

Insulin-stimulated autophosphorylation of the cytoplasmic juxtamembrane region of the human insulin receptor was examined by Tricine/SDS-PAGE. Various mutant receptor molecules were used to identify two tryptic phosphopeptides associated with the juxtamembrane region which accounts for 15% of the autophosphorylation of partially purified insulin receptor. These phosphopeptides were immunoprecipitated with an antipeptide antibody against the juxtamembrane sequence and were phosphorylated exclusively on tyrosine. Substitution of both Tyr960 and Tyr953 with alanine eliminated insulin-stimulated phosphorylation of the juxtamembrane region without affecting tyrosine autophosphorylation in the C terminus or regulatory regions. Monosubstitution of Tyr960 with phenylalanine or alanine reduced phosphorylation in the juxtamembrane region by more than 50%, and manual Edman degradation indicated that Tyr960 was phosphorylated in wild-type receptor. In vivo, phosphorylation of the juxtamembrane region accounts for one-third of the insulin receptor phosphorylation and contains both phosphoserine and phosphotyrosine. Deletion of Tyr960 and 11 adjacent amino acids eliminated insulin-stimulated phosphorylation of the juxtamembrane region. Substitution of Tyr960 reduced this phosphorylation by more than 50%. The insulin receptor also undergoes serine phosphorylation outside of the juxtamembrane region which depends on the presence of Tyr1151. Together with our previous studies, this report suggests that phosphorylation of Tyr960 may play an important role in signal transduction by the insulin receptor.
Black-Blood Multicontrast Imaging of Carotid Arteries with DANTE-prepared 2D and 3D MR Imaging (2014)

The DANTE delay alternating with nutation for tailored excitation -prepared multicontrast 2D two-dimensional BB black blood technique is a promising new tool for MR imaging of carotid artery walls. Additionally, the 3D three-dimensional DASH DANTE-prepared FLASH sequence enables 3D three-dimensional high-spatial-resolution fast T1-weighted imaging of carotid artery walls. ©RSNA, 2014 Online supplemental material is available for this article .
ChemInform Abstract: STUDIES OF HETEROCYCLIC COMPOUNDS PART 16, MECHANISM OF ELECTROPHILIC SUBSTITUTION OF 6A‐THIATHIOPHTHENS AND RELATED COMPOUNDS, NITROSATION WITH REARRANGEMENT (1974)

Abstract Die Thiathiophthene (I) reagieren mit salpetriger Säure unter Umlagerung zu den Oxadithiaazapentalenen (II).
Characterization of ferroelectric gate Mos capacitors formed by mod technique for nonvolatile memory applications (1998)

Abstract Metal/ferroelectric/insulator/semiconductor (MFIS) -structured ferroelectric gate MOS capacitors were fabricated and characterized. The metalorganic decomposition (MOD) technique was employed for the deposition of not only the ferroelectric but also the insulator, which has been usually deposited by e-beam evaporation. the experimental results indicate the usefulness of this technique for the fabrication of this heterostructure, which will accelerate the material research in this field.