gebhart/patrepeval huggingface dataset:
Selective degradation-inducing probes for studying cereblon (CRBN) biology (2021)

Targeted protein degradation represents a rapidly growing area in drug discovery and development. Moreover, small molecules that induce the targeted degradation of a given protein also represent an important addition to the chemical probes toolbox as these compounds can achieve selective protein knockdown, thus providing an approach that is orthogonal to genetic knockdowns. In order to develop degradation-inducing chemical probes for studying cereblon (CRBN) biology, we generated six CRBN-CRBN (homo-PROTAC) degraders and six CRBN-VHL (hetero-PROTAC) degraders. From these compounds we identified two potent and selective CRBN degraders (<b>ZXH-4-130</b> and <b>ZXH-4-137</b>), both of which are CRBN-VHL compounds. We characterized these lead degraders by quantitative proteomics in five cell lines (MM1.S, Kelly, SK-N-DZ, HEK293T, and MOLT-4) and observed high selectivity for CRBN in all cell lines. Furthermore, we directly compared our compounds to current lead CRBN degraders and demonstrated how these probes can be used as chemical knockdown reagents for studying CRBN-dependent processes. Overall, our work provides a roadmap for thorough degrader characterization by combination western and proteomic analysis, as illustrated by the identification of <b>ZXH-4-130</b> and <b>ZXH-4-137</b> as CRBN-knockdown tool compounds suitable for cell-based studies.
Optimal replication for min-cut partitioning (1992)

Heuristics for replicating logic have been shown to reduce pin count and wiring density in partitioned logic networks. We present an efficient algorithm for determining an optimal min-cuf replication set for a k-partitioned graph in O(knmlog(n2/m)) time. For the NP-hard case with limited size partition components, we propose a new replication heuristic which reduces the worst-case running time by a factor of O( k2) over previous methods. Ezperimental results are presented.
Effect of Formulation Adjuvants on Gastrointestinal Absorption of Leuprolide Acetate (1993)

Leuprolide acetate, [D-Leu6-desGly10]LH-RH ethylamide, a highly potent superagonist of luteinizing hormone-releasing hormone (LH-RH), was administered by intraduodenal (ID) injection to male castrate rats in a saline solution. Absorption was low, approximately 0.01% and 0.08% by oral (PO) and ID administration respectively, compared with intravenous (i.v.) controls. An aqueous formulation and a water in oil emulsion of a lipophilic salt, a decane sulfonic acid derivative of [D-Leu6-desGly10]LH-RH ethylamide gave ID bioavailabilities of approximately 0.2% and 1%, respectively. Evaluation of formulation effects on the oral absorption of leuprolide showed that lipophilicity, surfactant and vehicle properties significantly affected ID absorption of leuprolide. Absolute bioavailability of the drug in typical emulsion systems ranged from approximately 3 to 10% and represent an improvement of about 100 fold in gastrointestinal bioavailability of this peptide. The implications of these findings relative to the effect of formula adjuvants on oral absorption of leuprolide and other peptides following ID administration are discussed.
Strategies for the development of monoclonal antibodies for in vivo imaging: their use in the imaging of ovarian carcinoma. (1987)

There are a number of strategies that have been used for the development of monoclonal antibodies which recognise tumour associated antigens. These include the use of whole tumour cells or membrane components as the immunogen, and the use of differentiation antigens, for example the human milk fat globule. The monoclonal antibody HMFG-2 was developed using the latter strategy and has been shown to react with a large molecular weight mucin-like molecule which appears to be highly immunogenic in the mouse. The HMFG-2 antibody is proving to be extremely useful in the localisation of ovarian tumours and is being used in a number of clinics. This antibody and its antigen have a number of characteristics which have contributed to its success in imaging ovarian carcinomas, including the repetitive nature of the antigenic epitope and the antibody's affinity.
A language space representation for speech recognition (2015)

The number of languages for which speech recognition systems have become available is growing each year. This paper proposes to view languages as points in some rich space, termed language space, where bases are eigen-languages and a particular selection of the projection determines points. Such an approach could not only reduce development costs for each new language but also provide automatic means for language analysis. For the initial proof of the concept, this paper adopts cluster adaptive training (CAT) known for inducing similar spaces for speaker adaptation needs. The CAT approach used in this paper builds on the previous work for language adaptation in speech synthesis and extends it to Gaussian mixture modelling more appropriate for speech recognition. Experiments conducted on IARPA Babel program languages show that such language space representations can outperform language independent models and discover closely related languages in an automatic way.
In vitro analysis of peri‐articular soft tissues passive constraining effect on hip kinematics and joint stability (2012)

This study showed that femoral head anatomical centre displacement within the acetabulum occurs and increases with increasing removal of peri-articular soft tissues, confirming their influence on hip stability. Hip kinematics was also influenced by peri-articular soft tissues; specifically range of motion increases with increasing removal of those tissues. From clinicians' point of view, they have therefore to consider the influence of their surgeries on peri-articular soft tissues, since excessive translations may promote hip arthritis.
Templated nanoporous spin-on glass for high density interconnect applications (2003)

This work focused on the development, characterization, and optimization of the properties of silsesquioxane-based, low dielectric constant porous materials for use in high density interconnect applications. The goal was to modify a commercially available spin-on-glass (methylsilsesquioxane), and introduce porosity into the films to lower the effective dielectric constant of the silsesquioxane resin. The pores were created by adding a sacrificial polymer (substituted norbornene polymer) to the silsesquioxane matrix, and then thermally decomposing the sacrificial polymer within the films to form nano-size voids (/spl sim/5 nm). Studies of the pore size and distribution, pore interconnectivity, chemical bonding of the sacrificial polymer to the spin-on-glass, and the mechanical, electrical and optical properties of the films have been performed. Transmission electron microscopy experiments were conducted to investigate the pore size distribution as a function of molecular weight, concentration and type of functional groups within the sacrificial polymer, and polymer loading level. The mechanical properties were investigated using nanoindentation techniques, and, in general, it was shown that the porous films had superior fracture toughness (resistance to cracking) compared to those without pores.
Laser Radar Receiver Performance Improvement by Inter Symbol Interference (2012)

The power of laser radar received echoes varies over a large range due to many factors such as target distance, size, reflection ratio, etc, which leads to the difficulty of decoding codes from the received noise buried signals for spectrum code modulated laser radar. Firstly, a pseudo-random noise (PN) code modulated laser radar model is given, and the problem to be addressed is discussed. Then, a novel method based on Inter Symbol Interference (ISI) is proposed for resolving the problem, providing that only Additive White Gaussian Noise (AWGN) exists. The ISI effect is introduced by using a high pass filter (HPF). The results show that ISI improves laser radar receiver decoding ratio, thus the peak of the correlation function of decoded codes and modulation codes. Finally, the effect of proposed method is verified by a simple experiment.
Synthesis and Self-Organization of α,ω-Substituted Oligothiophenes with Long, Branched Alkyl Substituents (2007)

A series of long oligothiophenes without β-substituents, up to an undecamer, as highly attractive electronic materials is presented. The new synthetic strategy for these compounds is based on the combination of ring-closure and metal-catalyzed coupling reactions. The use of a soluble diketo precursor preserves good solubility of the intermediate products in the course of the multistep synthesis until the very last reaction and gives rise to good yields and high purity of the final oligomers. The characterization of the oligothiophenes by UV−vis spectroscopy reveals the formation of aggregates in solution. Additionally, DSC measurements and polarization microscopy show the presence of thermotropic liquid crystalline phases of some of the oligomers.
Controlled Radical Polymerization of (Meth)acrylates by ATRP with NiBr2(PPh3)2 as Catalyst (1998)

NiBr2(PPh3)2 has been found to be an efficient catalyst for the ATRP of methyl methacrylate (MMA) and n-butyl acrylate (n-BuA) initiated by an alkyl halide in the absence of any activator (e.g., Lewis acid) at 85 °C. The molecular weight distribution of the poly(meth)acrylates is narrow (Mw/Mn = 1.1−1.4). However, some side reactions (more likely coupling reactions) are observed at high monomer conversions in the case of n-BuA. An excess of PPh3 has proved to increase the polymerization rate of MMA while preserving the control of the molecular parameters. When the catalyst/initiator molar ratio is too small (e.g., 0.05), the polymerization rate decreases, the polydispersity increases, and the initiation is less efficient. α-Acid and α-hydroxyl end groups have been successfully attached to the chains by using functional initiators, such as 2-bromo-2-methylpropionic acid and 2,2‘,2‘ ‘-tribromoethanol. Reactivity ratios for the MMA/n-BuA comonomer pair have been measured and found to be close to the values observed for a conventional free-radical polymerization. Diethyl meso-2,5-dibromoadipate has been used as a difunctional initiator for the n-BuA polymerization, leading to α,ω-bromo-poly(n-BuA) of narrow molecular weight distribution. Finally, the thermal stability of PMMA is consistent with the lack of termination reactions, while Tg is as high as 125 °C.
Optical bandgap modelling from the structural arrangement of carbon nanotubes (2018)

The optical bandgap properties of vertically-aligned carbon nanotube (VACNT) arrays were probed through their interaction with white light, with the light reflected from the rotating arrays measured with a spectrometer. The precise deterministic control over the structure of vertically-aligned carbon nanotube arrays through electron beam lithography and well-controlled growth conditions brings with it the ability to produce exotic photonic crystals over a relatively large area. The characterisation of the behaviour of these materials in the presence of light is a necessary first step toward application. Relatively large area array structures of high-quality VACNTs were fabricated in square, hexagonal, circular and pseudorandom patterned arrays with length scales on the order of those of visible light for the purpose of investigating how they may be used to manipulate an impinging light beam. In order to investigate the optical properties of these arrays a set of measurement apparatus was designed which allowed the accurate measurement of their optical bandgap characteristics. The patterned samples were rotated under the illuminating white light beam, revealing interesting optical bandgap results caused by the changing patterns and relative positions of the scattering elements (VACNTs).
Abstract 4707: Genetically engineered NY-ESO-1-specific T cells in HLA-A2+ patients with synovial sarcoma (2015)

Abstract NY-ESO-1 is expressed in ∼70% of synovial sarcomas and not expressed in vital tissues. We report interim results of NCT01343043 evaluating safety and activity of autologous T cells engineered to express an HLA-A2+ restricted, affinity-enhanced T cell receptor (TCR) targeting NY-ESO-1. HLA-A2+ patients with unresectable, metastatic, or recurrent synovial sarcoma were eligible if tumors expressed NY-ESO-1 by IHC. Lymphocytes were activated using anti-CD3/28 microbeads, genetically modified with a lentivector, then cryopreserved. Subjects received fludarabine 30mg/m2/d (D-6 to -2) and cyclophosphamide 1800mg/m2/d (D-3,-2), and infusion of engineered T cells. Systemic IL-2 was not administered. Nine subjects have received NY-ESO-1 cell infusions. Median transduced T cell dose was 3.4 × 109 cells (range 0.4-14.4), 60×106 cells/kg (range 5.7-165.5), and median transduction efficiency was 45.8%. Toxicity likely attributable to the T cells included fever, and grade 1-2 cytokine release syndrome. No autoimmune toxicity has been observed. Circulating engineered NY-ESO-1 cells were detected in all patients, peaking 3-21 days post-infusion. Persistence has been evaluated beyond 3 months in 4 subjects, all of whom had detectable NY-ESO-1 cells at 4 mos, 6 mos+, 12 mos+ and 12 mos+. We identified persisting NY-ESO-1 T cells using dextamer and/or anti-vβ13.1 mAbs, and observed that a high fraction of CD4+ and CD8+ NY-ESO-1 TCR expressing T cells were CD45RA+CCR7+CD95+, consistent with a stem cell memory phenotype. Persisting cells also demonstrate a polyfunctional (IFN-γ and TNF-α) and cytotoxic (CD107a and granzyme B) signature without overexpression of exhaustion markers (PD-1, LAG-3, and TIM-3). Of 8 patients whose follow-up is sufficient to assess response, 4 experienced objective responses (1CR x 9 mos, 1PR x 9 mos, 2PR x 6 mos). Tumor shrinkage could not be attributed to chemotherapy alone as progressive decreases in tumor size were observed over several months following completion of the lymphodepleting regimen. All PR patients (2 upon signs of progression and 1 still responding to therapy) ultimately underwent resection for residual disease and two remain without evidence of disease. Adoptive immunotherapy with NY-ESO-1 engineered T cells shows promising results in synovial sarcoma with acceptable toxicity. High dose IL-2 is not required for therapeutic benefit with this regimen. Citation Format: Melinda S. Merchant, Sandra P. D'Angelo, Hua Zhang, Donna Bernstein, Gwen Binder-Scholl, Tom Holdich, Luca Melchiori, Dan Williams, Marylene Fortin, Yoav Peretz, Jason Howe, Michael Mehler, Bruce A. Hug, Matthew Wright, Stephen Grupp, Paul A. Meyers, William Tap, Bent Jakobsen, Crystal L. Mackall. Genetically engineered NY-ESO-1-specific T cells in HLA-A2+ patients with synovial sarcoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4707. doi:10.1158/1538-7445.AM2015-4707
Efficient Identification of a Multi-Objective Pareto Front on a Wireless Experimentation Facility (2016)

Wireless systems often need to optimize multiple conflicting objectives (low delay, high reliability, and low cost), which are difficult to fulfill simultaneously. In such cases, the wireless system exhibits multiple optimal operation points, referred to as the optimal Pareto front (OPF). However, due to the large number of parameter settings to be evaluated and the time-consuming nature of performing wireless experiments, it is typically not possible to identify the OPF by exhaustively evaluating all possible settings. Instead, for many use cases, an approximation is good enough. To this end, this paper applies a multi-objective surrogate-based optimization (MOSBO) toolbox to efficiently optimize wireless systems and approximate the OPF using a limited number of iterations. Moreover, a real Wi-Fi conferencing scenario is optimized that has two conflicting objectives (exposure and audio quality) and four configurable parameters (Tx-Power, Tx-Rate, Codec Bit-Rate, and Codec Frame-Length). The benefits of using the MOSBO approach for such a network problem is demonstrated by approximating the OPF using 94 iterations instead of requiring the exploration of 6528 different parameter combinations, while still dominating 96.58% of the complete design space.
Lewis Acid Mediated Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Amines. Scope and Mechanistic Investigation (2007)

The first asymmetric [2,3]-sigmatropic rearrangement of achiral allylic amines has been realized by quaternization of the amines with an enantiomerically pure diazaborolidine and subsequent treatment with Et3N. The resultant homoallylic amines were obtained in good yields and excellent ee's. The observed diastereo- and enantioselectivities were rationalized by invoking a kinetically controlled process, and support for this model was obtained from an NMR spectroscopic investigation of the chiral Lewis acid-substrate complex. The structure of the Lewis acid-product complex was established by X-ray crystallographic analysis and supported the proposed mechanism.
Improved Magnetron Stability and Reduced Noise in Efficient Transmitters for Superconducting Accelerators (2018)

State of the art high-current superconducting accelerators require efficient RF sources with a fast dynamic phase and power control. This allows for compensation of the phase and amplitude deviations of the accelerating volt-age in the Superconducting RF (SRF) cavities caused by microphonics, etc. Efficient magnetron transmitters with fast phase and power control are attractive RF sources for this application. They are more cost effective than traditional RF sources such as klystrons, IOTs and solid-state amplifiers used with large scale accelerator projects. However, unlike traditional RF sources, controlled magnetrons operate as forced oscillators. Study of the impact of the controlling signal on magnetron stability, noise and efficiency is therefore important. This paper discusses experiments with 2.45 GHz, 1 kW tubes and verifies our analytical model which is based on the charge drift approximation.
Bromotyrosine Alkaloids from the Sponge Pseudoceratina verrucosa (1996)

Three new bromotyrosine alkaloids, pseudoceratinines A (1), B (2), and C (3), have been isolated from two specimens of the sponge Pseudoceratina verrucosa. In addition, the known alkaloids aplysamine-1 (4), aplysamine-2 (5), purealin (6), and purealidins A (7) and B (8) were found in both specimens. The structures and absolute configurations of the new products were elucidated by spectral methods.
Glial Dysfunction in Abstinent Methamphetamine Abusers (2009)

Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized (13)C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial (13)C-bicarbonate production rate from [1-(13)C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 micromol/g per min (N=5) versus controls 0.11 micromol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous (13)C MRS methods may determine 'cause and effect' between glial failure and neuronal injury.
Enantioselective synthesis of an octahydroindolizine (indolizidine) alcohol using an enzymatic resolution (2017)

A homo-chiral synthesis of (7R,8aS)-octahydro-5,5-dimethylindolizin-7-amine 8 and (7S, 8aS)-octahydro-5,5-dimethylindolizin-7-ol 9, amine building blocks which have found applications within the pharmaceutical industry, is presented. The approach uses a Novozym 435-mediated kinetic resolution of racemic octahydroindolizine (indolizidine) alcohol 13 as a key step (up to 100 g scale).
Comparative Aspects of the Endotoxin‐ and Cytokine‐Induced Endocrine Cascade Influencing Neuroendocrine Control of Growth and Reproduction in Farm Animals (2008)

Disease in animals is a well-known inhibitor of growth and reproduction. Earlier studies were initiated to determine the effects of endotoxin on pituitary hormone secretion. These studies found that in sheep, growth hormone (GH) concentration was elevated, whereas insulin-like growth factor-I (IGF-I) was inhibited, as was luteinizing hormone (LH). Examination of the site of action of endotoxin in sheep determined that somatotropes expressed the endotoxin receptor (CD14) and that both endotoxin and interleukin-I beta activated GH secretion directly from the pituitary. In the face of elevated GH, there is a reduction of IGF-I in all species examined. As GH cannot activate IGF-I release during disease, there appears to be a downregulation of GH signalling at the liver, perhaps related to altered nitration of Janus kinase (JAK). In contrast to GH downregulation, LH release is inhibited at the level of the hypothalamus. New insights have been gained in determining the mechanisms by which disease perturbs growth and reproduction, particularly with regard to nitration of critical control pathways, with this perhaps serving as a novel mechanism central to lipopolysaccharide suppression of all signalling pathways. This pathway-based analysis is critical to the developing novel strategies to reverse the detrimental effect of disease on animal production.
Compositional Generalization for Natural Language Interfaces to Web APIs (2021)

This paper presents Okapi, a new dataset for Natural Language to executable web Application Programming Interfaces (NL2API). This dataset is in English and contains 22,508 questions and 9,019 unique API calls, covering three domains. We define new compositional generalization tasks for NL2API which explore the models' ability to extrapolate from simple API calls in the training set to new and more complex API calls in the inference phase. Also, the models are required to generate API calls that execute correctly as opposed to the existing approaches which evaluate queries with placeholder values. Our dataset is different than most of the existing compositional semantic parsing datasets because it is a non-synthetic dataset studying the compositional generalization in a low-resource setting. Okapi is a step towards creating realistic datasets and benchmarks for studying compositional generalization alongside the existing datasets and tasks. We report the generalization capabilities of sequence-to-sequence baseline models trained on a variety of the SCAN and Okapi datasets tasks. The best model achieves 15\% exact match accuracy when generalizing from simple API calls to more complex API calls. This highlights some challenges for future research. Okapi dataset and tasks are publicly available at https://aka.ms/nl2api/data.