gebhart/patrepeval huggingface dataset:
Rational design, synthesis and evaluation of “smart”, uncharged bis‐oxime antidotes of OP inhibited human acetylcholinesterase (2020)

Organophosphate (OP) intoxications from nerve agent and OP pesticide exposure are treated by outdated, questionably efficient pyridinium aldoxime‐based therapies. Pyridinium cations hamper central nervous system (CNS) uptake, while structural diversity of OPs prevents efficient reactivation of OP inhibited acetylcholinesterase (AChE). Improvements must include much better reactivation of AChE in the CNS. We present here seven novel uncharged bis‐oximes created from our X‐ray structures of an uncharged monoxime, RS194B, reversibly bound to human AChE (hAChE). Bis‐oxime protonation results in equilibration between up to sixteen distinct ionization forms, including uncharged forms capable of diffusing into CNS and multiple zwitterionic forms optimal for reactivation reactions. Conformationally diverse zwitterions acting as structural variants of the compound significantly improved in vitro reactivation of diverse OP‐hAChEs. The enhanced reactivation orientation for one of the bis‐oximes was confirmed by X‐ray structure. Our novel, CNS directed bis‐oximes represent a promising class of “smart”, accelerated antidotes against OP intoxication. Support or Funding Information This research was supported by the CounterACT Program, National Institutes of Health Office of the Director (NIH OD), and the National Institute of Neurological Disorders and Stroke (NINDS), [Grant Numbers U01 NS083451 and R21 NS098998] and by the UCSD Academic Senate grant BG084144.
ChemInform Abstract: Nonclassical 2,4‐Diamino‐6‐(aminomethyl)‐5,6,7,8‐tetrahydroquinazoline Antifolates: Synthesis and Biological Activities. (1995)

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.
&lt;title&gt;New positive-tone deep-UV photoresist based on poly(4-hydroxystyrene) and an acid labile protecting group&lt;/title&gt; (1995)

Conventional acid catalyzed, chemically amplified DUV photoresists are susceptible to environmental contamination and post exposure delay effects resulting in `T-topping' and linewidth variation. These phenomena are directly relatable to uncontrolled diffusion of the photoactive acid generator within the photoresist or from the diffusion of basic contaminants into the resist. The diffusion process can be controlled by a combination of materials and processing optimization. This paper describes a new positive tone DUV photoresist based on poly(4-hydroxystyrene) protected with the isopropyloxycarbonyl (i-POC) functionality. This protecting group is considerably less acid labile than the tert-butyloxycarbonyl (t-BOC) group and the resulting polymer is considerably more thermally stable than a t-BOC protected poly(4-hydroxystyrene). As such, the i-POC based polymer is more amenable to processing at higher temperatures.
Innovative Dual-Chamfer Edge Technology Leads to Performance Gains in PDC Bits (2015)

Abstract The dual-chamfer diamond cutter is a new technology combining a primary chamfer with a secondary edge, enabling greater footage to be drilled without compromising rate of penetration (ROP). The average distance drilled in the Mississippi Lime formation was increased by 40% while maintaining comparable ROP to offsets and with significantly improved dull bit conditions, resulting in greater reliability. Since 2013, more than 1, 500 runs with bits utilizing dual-chamfer technology were performed in Oklahoma. The dull state was significantly improved, resulting in reduced incidence of ring outs, core outs and other deleterious bit damage. The data presented in this paper are based on over 130 laboratory drilling tests. Chip flow analysis was conducted using a unique visual pressurized single-cutter test machine. Full-bit testing was carried out in a pressurized drilling simulator to compare drilling performance. Cutter wear life testing was conducted using an aggressive granite wear test protocol where a 100 to 200% increase in cutter life was documented by edge geometry changes. Chamfering polycrystalline diamond compact (PDC) cutters has a significant positive effect on edge durability and overall longevity. This concept has not changed over several decades since the introduction of chamfered PDC cutters. Many investigations were conducted with either a singular change to the chamfer height or chamfer angle or with combined edge geometries. These investigations, however, showed only limited success. The new geometry is based on a thorough understanding of historic investigations and failures observed on how diamond cutter wear flats are formed and degrade. Developments in the drilling sector with greater use of high-power directional motors results in more intermittent off-center drilling with high cutter edge loading. In addition, cutter developments now use leaching methods to reduce cutter wear and better control thermal cyclic loading. A leached diamond layer makes diamond cutters more susceptible to impact damage, resulting in greater premature and catastrophic failures. For the customer, the improved cutter technology resulted in significant cost savings and more confidence in tool life, enabling greater endurance and durability. Ultimately, the new cutter technology enables lower drilling costs and opens more drilling frontiers that were previously unprofitable.
Photonic quantum walks in a fiber based recursion loop (2011)

We present a flexible and robust system for implementing one‐dimensional coined quantum walks. A recursion loop in the optical network together with a translation of the spatial into the time domain ensures the possible increment of the step number without need of additional optical elements. An intrinsic phase stability assures a high degree of coherence and hence guarantees a good scalability of the system. We performed a quantum walk over 27 steps and analyzed the 54 output modes. Furthermore, we estimated that up to 100 steps can be realized with only minor changes in the used components.
A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2 (2015)

An understanding of the effects of hypergravity on energy homeostasis is necessary in managing proper physiological countermeasures for aerospace missions. This study investigated whether a single or multiple load(s) of mice to hypergravity has an effect on molecules associated with energy metabolism. In the liver, AMPKα level and its signaling were repressed 6 h after a load to +9 Gz hypergravity for 1 h, and then gradually returned toward normal. AMPKα level was restored after 3 loads to +9 Gz, suggestive of preconditioning adaptation. In cDNA microarray analyses, 221 genes were differentially expressed by +9 Gz, and the down-regulated genes included Nrf2 targets. Nrf2 gene knockout abrogated the recovery of AMPKα elicited by 3 loads to +9 Gz, indicating that Nrf2 plays a role in the adaptive increase of AMPKα. In addition, +9 Gz stress decreased STAT3, FOXO1/3 and CREB levels, which was attenuated during the resting time. Similarly, apoptotic markers were enhanced in the liver, indicating that the liver may be vulnerable to hypergravity stress. Preconditioning loads prevented hepatocyte apoptosis. Overall, a load of mice to +9 Gz hypergravity causes AMPKα repression with liver injury, which may be overcome by multiple loads to hypergravity as mediated by Nrf2.
Unikernels Everywhere (2017)

Video streaming dominates the Internet's overall traffic mix, with reports stating that it will constitute 90% of all consumer traffic by 2019. Most of this video is delivered by Content Delivery Networks (CDNs), and, while they optimize QoE metrics such as buffering ratio and start-up time, no single CDN provides optimal performance. In this paper we make the case for elastic CDNs, the ability to build virtual CDNs on-the-fly on top of shared, third-party infrastructure at a scale. To bring this idea closer to reality we begin by large-scale simulations to quantify the effects that elastic CDNs would have if deployed, and build and evaluate MiniCache, a specialized, minimalistic virtualized content cache that runs on the Xen hypervisor. MiniCache is able to serve content at rates of up to 32 Gb/s and handle up to 600K reqs/sec on a single CPU core, as well as boot in about 90 milliseconds on x86 and around 370 milliseconds on ARM32.
SMRT; Not So Smart in Multiple Myeloma. (2007)

Abstract Multiple myeloma (MM), a clonal B-cell malignancy, characterized by accumulation of plasma cells in bone marrow is the second most hematological malignancy in United States. In the BM, the myeloma and stromal cells secrete cytokines, which support the growth and survival of the myeloma cells. We previously showed that JAG2, one of the NOTCH ligand, is over-expressed in MM cells (Blood. 2004 Dec 1;104(12)). We hypothesized that over-expression of JAG2 in myeloma cells induce secretion of IL-6 from the stromal cells and subsequently enhances the proliferation of myeloma cells. JAG2 has been shown to be over-expressed in all cell lines and patient samples studied To identify the mechanism for JAG2 overexpression in MM cells, we assessed the potential modifications of the JAG2 promoter in MM cell lines as well as patient samples (an JAG2 negative controls) by studying both methylation and histone acetylation level of the JAG2 promoter. We show that difference in H4 acetylation level might play a crucial role in JAG2 expression. Acetylation state of histones can be regulated by the recruitment of histone deacetylases (HDACs). HDACs are typically recruited to promoter regions through interaction with nuclear co-repressors such as SMRT. The cell lines and patient samples studied presented significantly reduced levels of SMRT. Therefore, based on these observations we propose a model in which partial down-regulation of SMRT recruits less active HDAC3 (as confirmed by immunoprecipitation). As a result the deactylation process of histones in the JAG2 promoter region has been impaired and the cells lost their regulatory mechanism on transcriptional regulation of JAG2. This provides a mechanistic explanation for JAG2 over-expression in MM and on the direct involvement of the SMRT co-repressor in MM pathogenesis.
Molecular Pathogenesis of Rickettsioses and Development of Novel Anti-Rickettsia Treatment by Comginatorial Peptide-Based Libraries (2005)

Abstract : The purpose of this study is to utilize adaptein libraries coded within pantropic retroviral vectors that confer protection against rickettsial pathogens and to study the molecular pathogenesis of rickettsioses. The following specific aims were proposed: 1) To establish heterogeneous cell populations, with each cell expressing a unique member of a complex combinatorial peptide-based (e.g., adaptein) library and challenge with R. prowazekii, R. rickettsii, and O. tsutsugamushi; 2) To determine the role of NF-kB, cytokines, ROS and NO in intracellular killing of rickettsia-infected monolayers containing adapteins and 3) To characterize signal transduction pathways modulating the cytoskeletal events responsible for the increased vascular permeability. During the fourth year of the project, rickettsial challenges performed with SV-HCEC cells were continued and expansion of the resistant colonies was not possible. We are currently conducting experiments with a murine and a human monocytic cell line that grow in suspension. Both cell lines have been infected with pantropic retroviruses and challenging experiments are underway. Experiments with SVHCEC cells have elucidated the role of rickettsiae and cytokines in modulating permeability across infected monolayers. Confocal microscopy studies also syggest that these changes might in part be due to changes in p120 distribution in adherens junctions. The role of nitric oxide and its derivative peroxinitrite in increased permeability across infected monolayers has also been elucidated.
Stratocumulus Cloud Clearings and Notable Thermodynamic and Aerosol Contrasts across the Clear–Cloudy Interface (2015)

Abstract Data from three research flights, conducted over water near the California coast, are used to investigate the boundary between stratocumulus cloud decks and clearings of different sizes. Large clearings exhibit a diurnal cycle with growth during the day and contraction overnight and a multiday life cycle that can include oscillations between growth and decay, whereas a small coastal clearing was observed to be locally confined with a subdiurnal lifetime. Subcloud aerosol characteristics are similar on both sides of the clear–cloudy boundary in the three cases, while meteorological properties exhibit subtle, yet important, gradients, implying that dynamics, and not microphysics, is the primary driver for the clearing characteristics. Transects, made at multiple levels across the cloud boundary during one flight, highlight the importance of microscale (~1 km) structure in thermodynamic properties near the cloud edge, suggesting that dynamic forcing at length scales comparable to the convective eddy scale may be influential to the larger-scale characteristics of the clearing. These results have implications for modeling and observational studies of marine boundary layer clouds, especially in relation to aerosol–cloud interactions and scales of variability responsible for the evolution of stratocumulus clearings.
Photosensitive protein patterning with electrophoretic deposition (2010)

This letter reports on the micro-patterning of the photosensitive protein of bacterioRhodopsin (bR) geared toward bioelectronics-based image sensors. bR proteins are denatured by existing micro-fabrication processes, including destructive high-temperature (>100°C) heating and organic solvent cleansing. In our process, the desired area of the electrode for immobilizing bR is defined by a hydrophobic polymer that repels bR. After micro-fabrication, bR is selectively formed on the defined areas using electrophoretic deposition. A 5-µ m patterning resolution was achieved. An 8 × 8 photosensor array was fabricated, and its output electric charge was detected.
Peptide sequences that target proteins to lysosomes for enhanced degradation during serum withdrawal (1987)

Ribonuclease A (RNase A) microinjected into human diploid fibroblasts is degraded with a half-life of 80-100 h in the presence of serum, but its half-life declines to 40 h when cells are deprived of serum. This increased degradation in response to serum withdrawal results from an increased rate of uptake of microinjected RNase A from the cytosol into lysosomes. The cells' ability to recognize RNase A for this enhanced degradation is based on some feature of amino acids 1-20. Covalent linkage of S-peptide to other proteins results in enhanced lysosomal degradation of the conjugate in response to serum withdrawal. The authors have further defined the essential region of RNase S-peptide to be within residues 7-11, KFERQ. Coinjection of radiolabeled RNase A and excess unlabeled pentapeptide specifically blocks the enhanced degradation of RNase A. Affinity-purified polyclonal IgGs raised against KFERQ immunoprecipitate 25-30% of radiolabeled cytosolic proteins from human fibroblasts. Pulse-chase experiments indicate that these proteins are preferentially degraded upon serum withdrawal while degradation of nonimmuno-precipitated proteins is unaffected. These results suggest that peptide sequences similar to KFERQ are contained within cellular proteins and that such sequences target proteins to lysosomes for enhanced degradation during serum withdrawal.
ChemInform Abstract: Electrosynthesis of α‐Arylated β‐Substituted Cyclopropylphosphonates. Synthesis of a Phosphonic Analogue of Minalcipran. (2000)

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.
Unified high-level synthesis and module placement for defect-tolerant microfluidic biochips (2005)

Microfluidic biochips promise to revolutionize biosensing and clinical diagnostics. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. This problem is also identified by the 2003 ITRS document as a major system-level design challenge beyond 2009. We focus here on the automated design of droplet-based microfluidic biochips. We present a synthesis methodology that unifies operation scheduling, resource binding, and module placement for such "digital" biochips. The proposed technique, which is based on parallel recombinative simulated annealing, can also be used after fabrication to bypass defective cells in the microfluidic array. A real-life protein assay is used to evaluate the synthesis methodology.
Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor (2006)

Tissue factor (TF) plays an important role in hemostasis, inflammation, angiogenesis, and the pathophysiology of atherosclerosis and cancer. In this article we uncover a mechanism in which protein S, which is well known as the cofactor of activated protein C, specifically inhibits TF activity by promoting the interaction between full-length TF pathway inhibitor (TFPI) and factor Xa (FXa). The stimulatory effect of protein S on FXa inhibition by TFPI is caused by a 10-fold reduction of the K(i) of the FXa/TFPI complex, which decreased from 4.4 nM in the absence of protein S to 0.5 nM in the presence of protein S. This decrease in K(i) not only results in an acceleration of the feedback inhibition of the TF-mediated coagulation pathway, but it also brings the TFPI concentration necessary for effective FXa inhibition well within range of the concentration of TFPI in plasma. This mechanism changes the concept of regulation of TF-induced thrombin formation in plasma and demonstrates that protein S and TFPI act in concert in the inhibition of TF activity. Our data suggest that protein S deficiency not only increases the risk of thrombosis by impairing the protein C system but also by reducing the ability of TFPI to down-regulate the extrinsic coagulation pathway.
Teenage pregnancy as a risk factor for placental abruption: Findings from the prospective Japan environment and children’s study (2021)

In the Japanese general population, besides advanced maternal age, teenage pregnancy was associated with placental abruption. Recently, the mean maternal age has been changing in Japan. Therefore, it is important for obstetric care providers to provide proper counseling to young women based on up-to-date evidence.
A Clinical Perspective on the Relevance of Research Domain Criteria in Electronic Health Records (2015)

These findings show that a computationally derived tool based on RDoC workgroup reports identifies symptom distributions in clinician notes beyond those captured by ICD-9 codes, and these domains have significant predictive validity. More generally, they point to the possibility that clinicians already document RDoC-relevant symptoms, albeit not in a quantified form.
A Novel Approach to Targeted Oncologic Therapy - Co-culture Viability of Polymer Prodrug Conjugation to Mesenchymal Stem Cells (2020)

Background/Purpose: Conjugation of polymer prodrugs to tumor homing cells, such as Mesenchymal Stem Cells (MSCs), could provide a vehicle for actively targeted delivery of polymer prodrugs. Methods: Human Bone Marrow MSCs were conjugated to either a doxorubicin polymer prodrug or free doxorubicin and were co-cultured with T-cells. Viability was assessed through the use of a Vi-cell counter. In Vivo Migration Analysis was performed NOD SCID mice implanted with subcutaneous MDA MB-231 breast cancer xenografts. Following tumor establishment, mice were injected via lateral tail vein injection with either saline or polymer loaded MSCs. Five days following stem cell injection, mice were euthanized, tumors were harvested and sections were analyzed using fluorescent microscopy and immuno-histochemical staining for cd105. Results: T-cell viability was reduced when co-cultured with MSCs conjugated to free doxorubicin although cells co-cultured with MSCs conjugated to doxorubicin polymer did not exhibit reduced viability. Polymer loaded MSCs displayed intact tumor homing migratory ability in vivo (Figure 1). Conclusion: MSCs conjugated to doxorubicin released the drug, resulting in reduced neighboring T-cells viability. MSCs loaded with polymer maintained their migratory capacity were able to migrate to tumors in vivo. MSCs therefore represent a potential vehicle for targeted drug delivery. Future work will focus on developing methods for releasing the drug upon successful delivery to the target in vivo.
Designing the Macrocyclic Dimension in Main Group Chemistry (2017)

Outside the confines and well-established domain of organic chemistry, the systematic building of large macromolecular arrangements based on non-carbon elements represents a significant and exciting challenge. Our aim in the past two decades has been to develop robust synthetic methods to construct new types of main group architectures in a methodical way, principles of design that parallel those used in the organic arena. This Concept article addresses the fundamental thermodynamic and kinetic problems involved in the design and synthesis of main group macrocycles and looks to future developments of macromolecules in this area, as well as new applications in coordination chemistry.
Effects of mode coupling on the generation of quadrature Einstein-Podolsky-Rosen entanglement in a type-II optical parametric oscillator below threshold (2005)

We study theoretically and experimentally the quantum properties of a type-II frequency-degenerate optical parametric oscillator below threshold with a quarter-wave plate inserted inside the cavity which induces a linear coupling between the orthogonally polarized signal and idler fields. This original device provides a good insight into general properties of two-mode Gaussian states, illustrated in terms of the covariance matrix. We report on the experimental generation of a two-mode squeezed vacuum on nonorthogonal quadratures depending on the plate angle. After a simple operation, the entanglement is maximized and put into standard form, i.e., quantum correlations and anticorrelations on orthogonal quadratures. A half sum of squeezed variances as low as $0.33\ifmmode\pm\else\textpm\fi{}0.02$, well below the unit limit for inseparability, is obtained and the entanglement measured by the entropy of formation.
Chemical potentials and activities in metallurgical processes (2020)

Electrometallurgy Today, 2020, №04. SOVREMENNAYA ELEKTROMETALLURGIYA Quarterly scientific-technical and production journal. ISSN: 2415-8445, Since 1985. Text in Russian, contents and summaries in English. The journal presents the results of theoretical and experimental research carried out at the PWI in the field of electrometallurgy. Special attention is given to electroslag technology (electroslag melting, refining and casting). The journal is divided into the following main sections: electroslag technology; electron beam processes; plasma arc technology; vacuum arc remelting and vacuum induction melting; general problems of special electrometallurgy.