gebhart/patrepeval huggingface dataset:
Abstract 5077: A novel small molecule menin-MLL inhibitor for potential treatment of MLL-rearranged leukemias (2017)

Abstract Patients with MLL-rearranged leukemia typically have a poor prognosis. With chemotherapy and stem cell transplantation as current standard of care, the 5-year survival rate is estimated to be only about 35%. As the leukemogenic activity of MLL fusion proteins has been shown to be dependent on their direct interaction with menin, development of small molecules that block the menin-MLL interaction is a promising therapeutic strategy for the treatment of this disease. Although small molecule menin-MLL inhibitors have been reported, previously published compounds exhibited modest cellular potency and/or poor pharmacokinetic properties. We now describe a novel, potent, and selective small molecule menin-MLL inhibitor that effectively treats MLL leukemias in in vivo models and demonstrate its potential clinical utility. The compound selectively inhibits the growth of a panel of MLL-rearranged cell lines relative to non MLL-rearranged cell lines, displays favorable pharmacokinetic properties, and induces tumor regression in an MV4;11 subcutaneous xenograft mouse model, with durable tumor suppression even after dosing is discontinued. In both the MV4;11 and MOLM13 disseminated leukemia models, the compound confers a prolonged survival benefit compared to an untreated group when dosed orally once daily at doses that are well-tolerated in the animals. We have used this potent and selective menin inhibitor to investigate the functional cellular response of MLL-rearranged cell lines to menin inhibition, assessing cell growth, cell cycle and gene expression responses over time, and compared that response to other epigenetic inhibitors and demonstrate significantly increased apoptosis which correlates with tumor regression measured both in early and long term readouts in xenograft and systemic leukemia models. We describe a menin-MLL inhibitor with optimized drug-like properties that demonstrates potential clinical utility in preclinical models of MLL leukemias. The compound is currently under further preclinical evaluation. Citation Format: Tao Wu, Linda Kessler, Shuangwei Li, Trupta Purohit, Shisheng Li, Hongzhi Miao, Brian Linhares, Rasmus Hansen, Jeff Kucharski, Yi Wang, Ke Yu, Katarzyna Kempinska, Tess Ely, Szymon Klossowski, Ata Zarieh, Ulf Peters, Jun Feng, Yvonne Yao, Yuan Liu, Bo Wen, Francis Burrows, Duxin Sun, Jingchuan Zhang, Levan Darjania, Dana Hu-Lowe, Patrick Zarrinkar, Liansheng Li, Tomasz Cierpicki, Jolanta Grembecka, Pingda Ren, Yi Liu. A novel small molecule menin-MLL inhibitor for potential treatment of MLL-rearranged leukemias [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5077. doi:10.1158/1538-7445.AM2017-5077
Sphingosine kinase inhibitors: a review of patent literature (2006-2015) (2016)

Sphingosine kinase (SphK1 & SphK2) is the sole source of the pleiotropic lipid mediator, sphingosine-1-phosphate (S1P). S1P has been implicated in a variety of diseases such as cancer, Alzheimer's disease, sickle cell disease and fibrosis and thus the biosynthetic route to S1P is a logical target for drug discovery. Areas covered: In this review, the authors consider the SphK inhibitor patent literature from 2006-2016 Q1 with the emphasis on composition of matter utility patents. The Espacenet database was queried with the search term 'sphingosine AND kinase' to identify relevant literature. Expert opinion: Early inhibitor discovery focused on SphK1 with a bias towards oncology indications. Structurally, the reported inhibitors occupy the sphingosine 'J-shaped' binding pocket. The lack of cytotoxicity with improved SphK1 inhibitors raises doubt about the enzyme as an oncology target. SphK2 inhibitors are featured in more recent patent applications. Interestingly, both SphK1 and SphK2 inhibition and gene 'knockout' share opposing effects on circulating S1P levels: SphK1 inhibition/gene ablation decreases, while SphK2 inhibition/gene ablation increases, blood S1P. As understanding of S1P's physiological roles increases and more drug-like SphK inhibitors emerge, inhibiting one or both SphK isotypes could provide unique strategies for treating disease.
New telechelic polymers and sequential copolymers by polyfunctional <i>ini</i>tiator‐transfer agents (inifers). XXX. Synthesis and quantitative terminal functionalization of α,ω‐diarylpolyisobutylenes (1983)

Abstract Novel aromatic‐telechelic polyisobutylenes were prepared and characterized: α,ω‐diphenylpolyisobutylene, α‐phenyl‐ω‐tolylpolyisobutylene, and α,ωditolylpolyisobutylene. The syntheses involved the preparation of asymmetric telechelic prepolymers (α‐phenyl‐ω‐tert‐chloropolyisobutylene and α‐tolyl‐ω‐tert‐chloropolyisobutylene) by the minifer method and quantitative alkylation of benzene and toluene by the prepolymer. The terminal aromatic rings of these telechelic polyisobutylenes were quantitatively nitrated, acetylated, and chlorosulfonated and a series of further novel telechelic products was obtained. Characterization of these derivatives provided additional proof for the telechelic structure of the starting prepolymers. The quantitative reduction of nitroaryl‐telechelic polyisobutylene by SnCl 2 /HCl led to aminoaryl‐telechelic polyisobutylene which was used to cure bisphenol‐A diglycidyl ether. These new flexible epoxy networks exhibited outstanding heat and hydrolytic stability combined with satisfactory mechanical properties.
A system-on-chip EPC Gen-2 passive UHF RFID tag with embedded temperature sensor (2010)

An RFID tag features a temperature sensor with gain-error compensation, a dual-path clock generator for both accurate link frequency and low power applications, and a zero-mask CMOS OTP memory array for low cost. The tag executes EPC-compliant SENSE-WRITEREAD commands with -6 dBm sensitivity and +0.4/-1.1°C error with one-point calibration.
Proactive management of software aging (2001)

Software failures are now known to be a dominant source of system outages. Several studies and much anecdotal evidence point to “software aging” as a common phenomenon, in which the state of a software system degrades with time. Exhaustion of system resources, data corruption, and numerical error accumulation are the primary symptoms of this degradation, which may eventually lead to performance degradation of the software, crash/hang failure, or other undesirable effects. “Software rejuvenation” is a proactive technique intended to reduce the probability of future unplanned outages due to aging. The basic idea is to pause or halt the running software, refresh its internal state, and resume or restart it. Software rejuvenation can be performed by relying on a variety of indicators of aging, or on the time elapsed since the last rejuvenation. In response to the strong desire of customers to be provided with advance notice of unplanned outages, our group has developed techniques that dete ct the occurrence of software aging due to resource exhaustion, estimate the time remaining until the exhaustion reaches a critical level, and automatically perform proactive software rejuvenation of an application, process group, or entire operating system, depending on the pervasiveness of the resource exhaustion and our ability to pinpoint the source. This technology has been incorporated into the IBM Director for xSeries servers. To quantitatively evaluate the impact of different rejuvenation policies on the availability of cluster systems, we have developed analytical models based on stochastic reward nets (SRNs). For time-based rejuvenation policies, we determined the optimal rejuvenation interval based on system availability and cost. We also analyzed a rejuvenation policy based on prediction, and showed that it can further increase system availability and reduce downtime cost. These models are very general and can capture a multitude of cluster system characteristics, failure behavior, and performabil ity measures, which we are just beginning to explore.
Optical Reflectance Spectroscopy to Differentiate Renal Tumor From Normal Parenchyma (2008)

Optical reflectance spectroscopy can help distinguish tumor from normal renal tissue in specimens immediately removed at surgery. Optical reflectance spectroscopy may allow real-time assessment of positive margins during partial nephrectomy.
Validation of a fast method for quantification of intra‐abdominal and subcutaneous adipose tissue for large‐scale human studies (2015)

Central obesity is the hallmark of a number of non-inheritable disorders. The advent of imaging techniques such as MRI has allowed for a fast and accurate assessment of body fat content and distribution. However, image analysis continues to be one of the major obstacles to the use of MRI in large-scale studies. In this study we assess the validity of the recently proposed fat-muscle quantitation system (AMRA(TM) Profiler) for the quantification of intra-abdominal adipose tissue (IAAT) and abdominal subcutaneous adipose tissue (ASAT) from abdominal MR images. Abdominal MR images were acquired from 23 volunteers with a broad range of BMIs and analysed using sliceOmatic, the current gold-standard, and the AMRA(TM) Profiler based on a non-rigid image registration of a library of segmented atlases. The results show that there was a highly significant correlation between the fat volumes generated by the two analysis methods, (Pearson correlation r = 0.97, p < 0.001), with the AMRA(TM) Profiler analysis being significantly faster (~3 min) than the conventional sliceOmatic approach (~40 min). There was also excellent agreement between the methods for the quantification of IAAT (AMRA 4.73 ± 1.99 versus sliceOmatic 4.73 ± 1.75 l, p = 0.97). For the AMRA(TM) Profiler analysis, the intra-observer coefficient of variation was 1.6% for IAAT and 1.1% for ASAT, the inter-observer coefficient of variation was 1.4% for IAAT and 1.2% for ASAT, the intra-observer correlation was 0.998 for IAAT and 0.999 for ASAT, and the inter-observer correlation was 0.999 for both IAAT and ASAT. These results indicate that precise and accurate measures of body fat content and distribution can be obtained in a fast and reliable form by the AMRA(TM) Profiler, opening up the possibility of large-scale human phenotypic studies.
A Diruthenium-Substituted Polyoxometalate as an Electrocatalyst for Oxygen Generation (2004)

Transition metal heteropolyanions have been used to catalyze a variety of organic oxidations but have not previously been used for O2 generation, despite sharing some structural similarities with dioxoruthenium water-oxidation catalysts. In this study, we report that the di-Ru-substituted polyoxometalate (POM) [Ru2Zn2(H2O)2(ZnW9O34)2]14- can be used to catalyze the electrochemical generation of O2. By comparing the behavior of this compound to that observed using a mono-Ru-substituted POM catalyst, we show that adjacent Ru sites are necessary to observe O2 generation. These observations suggest a reaction pathway involving two Ru-bound oxygen species combining to form O2 and are consistent with the accepted mechanism of electrochemical oxygen evolution. Finally, analysis of the observed electrode kinetics yields a Tafel slope of roughly 120 mV, which is similar to values reported previously for perovskite anodes.
Expanding the Genetic Repertoire of the Methylotrophic Yeast <i>Pichia pastoris</i> (2009)

To increase the utility of protein mutagenesis with unnatural amino acids, a recombinant expression system in the methylotrophic yeast Pichia pastoris was developed. Aminoacyl-tRNA synthetase/suppressor tRNA (aaRS/tRNA(CUA)) pairs previously evolved in Saccharomyces cerevisiae to be specific for unnatural amino acids were inserted between eukaryotic transcriptional control elements and stably incorporated into the P. pastoris genome. Both the Escherichia coli tyrosyl- and leucyl-RS/tRNA(CUA) pairs were shown to be orthogonal in P. pastoris and used to incorporate eight unnatural amino acids in response to an amber codon with high yields and fidelities. In one example, we show that a recombinant human serum albumin mutant containing a keto amino acid (p-acetylphenylalanine) can be efficiently expressed in this system and selectively conjugated via oxime ligation to a therapeutic peptide mimetic containing an permittivity-(2-(aminooxy)acetyl)-L-lysine residue. Moreover, unnatural amino acid expression in the methylotrophic host was systematically optimized by modulation of aaRS levels to express mutant human serum albumin in excess of 150 mg/L in shake flasks, more than an order of magnitude better than that reported in S. cerevisiae. This methodology should allow the production of high yields of complex proteins containing unnatural amino acids whose expression is not practical in existing systems.
Tracking system for moving subjects (1976)

Electronic system automatically focuses camera or spotlight on moving object. Subject is equipped with miniature ultrasonic or radio transmitter; its signal is picked up by two or more detectors, is phase detected and fed into computer which determines position of subject and sends command signals to servo for camera or spotlight.
Adaptive repair of pulse-compressed radar waveforms: Seeing the forest despite the trees (2004)

The standard matched filter used in radar pulse compression is known to generate range sidelobes in the vicinity of large targets which can result in the masking of smaller nearby targets. Significant research has been done to obtain waveform/filter pairs that possess low sidelobes with minimal mismatch loss. However, there exists no single waveform/filter pair that can completely eliminate masking for all possible scenarios as demonstrated by the well-known ambiguity function. This paper presents an adaptive approach to radar pulse compression in which the received signal is employed to adaptively determine the appropriate receive filter to apply for each individual range cell. Furthermore, in contrast to previous work on adaptive pulse compression, the work herein addresses the repair (i.e. unmasking) of range cells masked by sidelobes from a large target after standard pulse compression has occurred. Therefore, the proposed approach, denoted as Pulse Compression Repair (PCR), is applicable to legacy radar systems in which replacing the current pulse compression system is not feasible.
Swarm Intelligence for Electrical Design Space Exploration (2007)

Today's high speed electrical systems exhibit ever increasing complexity generation after generation. This increased complexity results in additional design parameters which the system designer must choose carefully to obtain the optimum design. Often, the number of these design variables is large enough that a brute-force search of the design space is not feasible. Statistical techniques like design of experiments (DoE) cannot accurately find the best and worst case corners. This paper introduces the concept of swarm intelligence for the first time for electrical design space exploration. Specifically, the discrete particle swarm optimization (PSO) is used to arrive at an optimum combination of design parameters for various electrical interfaces. The PSO algorithm is shown to have great potential as a robust and efficient alternative to statistical techniques currently used in high speed electrical design optimization.
Aluminum Alloy Bearings Containing Hard Particles Fitted for Use with Nodular Cast Iron Shaft (1983)

<div class="htmlview paragraph">High tin and aluminum alloy bearings can seize easily when used with nodular cast iron shafts. The authors have investigated the process of seizure between such nodular cast iron shafts and high tin and aluminum alloy bearings, and found that the seizures are normally caused by a combination of burrs around the graphite at the surface of the nodular cast iron shafts and abrasive aluminum debris adhering to the shaft. In an attempt to remove the burrs and abrasive aluminum debris, the authors dispersed hard particles in the alloy bearings. The new alloy used has a chemical composition of Al Si 3, Sn 10 and Pb 1.5 and, as a result bearings formed from it do not require a lead-based overlay. This arrangement provides much higher seizure resistance than overlayed copper and lead alloy bearings when used with nodular cast iron shafts. The bearings made with this alloy can be used in all engines with nodular cast iron shafts without any problems whatsoever.</div>
Tapered Fabry-Perot waveguide optical demultiplexer (1993)

We describe a novel waveguide spectrometer for use in wavelength division multiplexing (WDM) systems. A high refractive index resonator is coupled to a waveguide and extracts light from the waveguide at its resonance frequency. A taper in the thickness of the resonator allows light of different wavelengths to be extracted at different positions. A structure is fabricated for use at 750 nm with a measured dispersion of 29 nm/cm and a wavelength resolution of 1 nm. The device operation is in good agreement with first-order coupled-mode calculations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
88. Structural Studies Into the Stability of Novel In Silico Reconstructed Ancestral AAV Vectors (2015)

Adeno-associated virus (AAV) vectors have emerged as therapy preferred clinical in vivo gene transfer system. Yet, their sensitivity to pre-existing immunity (PEI) and low carrying capacity remain major drawbacks that limit broad applications. We previously hypothesized and have shown that ancestral species of AAV, which we inferred using statistical and bio-informatic approaches, and generated synthetically, have reduced susceptibility to PEI. Here, our ambition was to study from a biophysical and structural perspective the evolutionary process of AAV using these novel reagents, and to develop correlates of those measures with virus and vector phenotypes. By the means of polyacrylamide gel electrophoresis, intrinsic fluorescence spectroscopy and differential scanning fluorescence, we derive the thermostability profiles of 6 contemporary AAV serotypes (AAV1, AAV2, AAV5, AAV8, AAV9, rh32.33) and 3 ancestral AAV serotypes, called Anc80, Anc81 and Anc82 and differing from AAV8 in VP1 protein sequence by 9.3%, 7.8% and 5.3%, respectively. A theoretical structure of Anc80L0065 VP3 monomer was derived by homology modeling and compared to the crystal structures of AAV2, AAV8 and rh32.33. Structural modeling indicates significant sequence and structure differences between ancestral and contemporary VP3 protein subunits in loops I, IV, VII and VIII, regions that were shown to be involved in antibody and cell receptor binding. Surprisingly, Anc80, Anc81 and Anc82 showed an increase in capsomer melting temperature of approximately 20°C in comparison to AAV8, while vector genome is accessible at lower temperatures. Evolutionary intermediates between Anc80 and AAV8 demonstrate unique melting properties that permit the identification of a limited set of capsid determinants to the thermodynamic stability of AAVs. Our reconstructed phylogeny of AAVs emerges as a relevant tool for sequence-function analysis of AAV vectors.
Stacked switched capacitor energy buffer architecture (2012)

Electrolytic capacitors are often used for energy buffering applications, including buffering between single-phase ac and dc. While these capacitors have high energy density compared to film and ceramic capacitors, their life is limited and their reliability is a major concern. This paper presents a stacked switched capacitor (SSC) energy buffer architecture and some of its topological embodiments which overcome this limitation while achieving comparable effective energy density without electrolytic capacitors. The architectural approach is introduced along with design and control techniques. A prototype SSC energy buffer using film capacitors, designed for a 320 V dc bus and able to support a 135 W load has been built and tested with a power factor correction circuit. It demonstrates the effectiveness of the approach.
Design of provably correct storage arrays (2002)

In this paper we describe a hardware design method for memory and register arrays that allows the application of formal equivalence checking for comparing a high-level register transfer level (RTL) specification with a low-level transistor implementation. Equivalence checking is increasingly applied in practical design flows to verify regular logic components. However, because of their specific organization and circuit techniques, high-performance implementations of large storage arrays require particular modifications to the general flow that make them suitable for formal equivalence checking. Two techniques are outlined in this paper. First, a special hierarchical verification scheme is described that allows the application of a partitioned comparison approach of the bit-wise organized transistor-level model with the word-wise organized RTL model. Second, a modified switch-level extraction technique is presented that extends the applicability of equivalence checking from regular dynamic CMOS circuits to self-resetting CMOS (SRCMOS) circuits.
Transparent ceramic scintillators for gamma spectroscopy and radiography (2010)

Transparent ceramics combine the scintillation performance of single crystals with the ruggedness and processability of glass. We have developed a versatile, scaleable fabrication method, wherein nanoparticle feedstock is consolidated at temperatures well below melting to form inch-scale phase-pure transparent ceramics with optical scatter of α <0.1 cm<sup>-1</sup>. We have fabricated Cerium-doped Gadolinium Garnets with light yields of ~50,000 Ph/MeV and energy resolution of <5% at 662 keV. We have also developed methods to form sheets of the high-Z ceramic scintillator, Europium-doped Lutetium Oxide Bixbyite, producing ~75,000 Ph/MeV for radiographic imaging applications.
Selective loss of a subset of T helper cells in active multiple sclerosis. (1985)

Patients with active multiple sclerosis (MS) have a selective loss of a subset of T helper cells (Th), detectable by two-color fluorescence-activated cell sorter analysis of peripheral blood lymphocytes. By using pairs of monoclonal antibodies to the T-cell subset markers CD4 (Th) and CD8 [T suppressor/cytotoxic cell (Ts)] and the common leukocyte markers Lp220 and Lp95-150, five phenotypically distinct T-cell subsets have been identified in peripheral blood: two CD4+ Th cell subsets and three CD8+ Ts cell subsets. The frequencies and absolute numbers of these five populations were measured in patients with active and inactive MS and were compared with those in healthy age-matched controls and in patients with other neurologic diseases. A high frequency of patients with active MS (80%) had a selective reduction of one Th subset (CD4+ Lp220+) compared with normal controls (P less than 0.001) or patients with inactive MS (P less than 0.001). Three patients examined sequentially had a further loss of the Lp220+ Th subset as disease activity progressed. The proportion of two Ts subsets was also abnormal in patients with active MS, but this defect was not restricted to that group. Total Th and Ts cell frequencies and Th/Ts ratios were not significantly different between patient and normal control groups. Thus, two-color analysis of T-cell subsets may be a more sensitive indicator than conventional single-marker assays of abnormal immune status in MS patients.
ChemInform Abstract: Marinisporolides, Polyene‐Polyol Macrolides from a Marine Actinomycete of the New Genus Marinispora. (2009)

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