gebhart/patrepeval huggingface dataset:
Cryptococcus neoformans Capsular GXM Conformation and Epitope Presentation: A Molecular Modelling Study (2020)

The pathogenic encapsulated <i>Cryptococcus neoformans</i> fungus causes serious disease in immunosuppressed hosts. The capsule, a key virulence factor, consists primarily of the glucuronoxylomannan polysaccharide (GXM) that varies in composition according to serotype. While GXM is a potential vaccine target, vaccine development has been confounded by the existence of epitopes that elicit non-protective antibodies. Although there is evidence for protective antibodies binding conformational epitopes, the secondary structure of GXM remains an unsolved problem. Here an array of molecular dynamics simulations reveal that the GXM mannan backbone is consistently extended and relatively inflexible in both <i>C. neoformans</i> serotypes A and D. Backbone substitution does not alter the secondary structure, but rather adds structural motifs: β DGlcA and β DXyl side chains decorate the mannan backbone in two hydrophillic fringes, with mannose-6-O-acetylation forming a hydrophobic ridge between them. This work provides mechanistic rationales for clinical observations-the importance of O-acetylation for antibody binding; the lack of binding of protective antibodies to short GXM fragments; the existence of epitopes that elicit non-protective antibodies; and the self-aggregation of GXM chains-indicating that molecular modelling can play a role in the rational design of conjugate vaccines.
Challenges of and Opportunities for a Large Diverse Software Team (2022)

A large software team consisting of members with different expertise, skillsets, personalities, ethnicities, and involving collaboration on a large and complex software product presents many technical and cultural challenges, but also provides unique opportunities. In this article, we discuss the essential issues we faced when successfully transforming a collection of various independently developed software libraries into one large integrated product: the eXtreme-scale scientific Software Development Kit (xSDK). We argue it is just as important to pay attention to cultural challenges, such as establishment of reliable communication channels that considers, among others, differences in personalities and backgrounds as well as overcoming geographical separation and time-zone distribution when collaborating, as technical challenges. Finally, we discuss opportunities stemming from participating in a large diverse software team, such as increased internal expertise, variety of skillsets, broadened connections to external experts, and access to a larger pool of ideas or solutions.
Anodal and cathodal thresholds during transthoracic stimulation (1988)

A physiological mechanism is proposed for a phenomenon observed in experimental studies: the ventricular threshold during transthoracic stimulation is slightly lower if the electrode closer to the heart is a cathode rather than an anode. This result can be attributed to the discrete structure of the myocardium. In such a structure, the end of each cardiac bundle proximal to the cathode is depolarized, while the distal end is hyperpolarized. Since the transmembrane potential depends upon the gradient, which decreases between proximal and distal ends, the magnitude of the transmembrane potential is somewhat smaller at the distal end. Thus a larger stimulus is required to raise the distal end above the threshold.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Flexible exception handling in the OPERA process support system (2002)

Exceptions are one of the most pervasive problems in process support systems. In installations expected to handle a large number of processes, having exceptions is bound to be a normal occurrence. Any programming tool intended for large, complex applications has to face this problem. However, current process support systems, despite their orientation towards complex, distributed, and heterogeneous applications, provide almost no support for exception handling. This paper shows how flexible mechanisms for failure handling are incorporated into the OPERA process support system using a combination of programming language concepts and transaction processing techniques. The resulting mechanisms allow the construction of fault-tolerant workflow processes in a transparent and flexible way while ensuring reusability of workflow components.
Highly ordered tailored three-dimensional hierarchical nano/microporous gold–carbon architectures (2012)

The preparation and characterization of three-dimensional hierarchical architectures, consisting of monolithic nanoporous gold or silver films formed on highly ordered 3D microporous carbon supports, are described. The formation of these nano/microporous structures involves the electrodeposition or sputtering of metal alloys onto the lithographically patterned multi-layered microporous carbon, followed by preferential chemical dealloying of the less noble component. The resulting hierarchical structure displays a highly developed 3D interconnected network of micropores with a nanoporous metal coating. Tailoring the nanoporosity of the metal films and the diameter of the large micropores has been accomplished by systematically changing the alloy compositions via control of the deposition potential, plating solution and coarsening time. SEM imaging illustrates the formation of unique biomimetic nanocoral- or nanocauliflower-like self-supporting structures, depending on the specific preparation conditions. The new 3D hierarchical nano/microporous architectures allow for enhanced mass transport and catalytic activity compared to common nanoporous films prepared on planar substrates. The functionality of this new carbon–gold hierarchical structure is illustrated for the greatly enhanced performance of enzymatic biofuel cells where a substantially higher power output is observed compared to the bare microporous carbon substrate.
Activation-Induced Resetting of Cerebral Oxygen and Glucose Uptake in the Rat (1998)

In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize interference. During baseline conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1). During activation cerebral glucose uptake increased disproportionately to cerebral oxygen uptake, and the cerebral oxygen to glucose uptake ratio was 4.2. The accumulated excess glucose uptake during 6 minutes of activation amounted to 2.4 micromol/g. Activation was terminated by closure of the sheltering box. In the postactivation period, the cerebral oxygen to glucose uptake ratio rose to a maximum of 6.4. This response is exactly opposite to the excess cerebral glucose uptake observed during activation.
Robust perpendicular magnetic anisotropy of Co3Sn2S2 phase in sulfur deficient sputtered thin films (2021)

Perpendicular magnetic anisotropy (PMA) in magnetic thin films is a fundamental key feature in the design of spintronic devices. As one of magnetic Weyl semimetals, ${\mathrm{Co}}_{3}{\mathrm{Sn}}_{2}{\mathrm{S}}_{2}$ has been studied for its large anomalous Hall effect (AHE), uniaxial crystalline magnetic anisotropy, and half metallicity. In this study, we investigated the effect of off-stoichiometric composition on the PMA and AHE of ${\mathrm{Co}}_{3}{\mathrm{Sn}}_{2}{\mathrm{S}}_{x}$ thin films fabricated by the sputtering technique. The prepared thin films have off-stoichiometric S compositions $x$ of 1.54 (S poor) and 3.27 (S rich) as well as the nearly stoichiometric one of 2.02. In addition to the ${\mathrm{Co}}_{3}{\mathrm{Sn}}_{2}{\mathrm{S}}_{2}$ phase, the segregated Co metal is found to contribute to the measured magnetization in the S-poor and S-rich films. The coercive field of perpendicular magnetization in all the films is much larger than that in the ${\mathrm{Co}}_{3}{\mathrm{Sn}}_{2}{\mathrm{S}}_{2}$ bulk crystals despite the fact that effective perpendicular magnetic anisotropy constants (${K}_{\mathrm{u}}^{\mathrm{eff}}$) between the prepared films are significantly different. In addition, the ${K}_{\mathrm{u}}^{\mathrm{eff}}$ values of two samples with $x=2.02$ and 2.22 are comparable to those of the bulk crystals. In contrast to the isotropic magnetization behavior in the S-rich film, the S-poor film holds the PMA feature. This result means that the PMA is more robust in the S-poor film than in the S-rich film. For the electrical transport properties, a large tangent of Hall angle of about 0.2 is observed for both the nearly stoichiometric and the S-poor films. This large tangent of Hall angle demonstrates that the Weyl feature of ${\mathrm{Co}}_{3}{\mathrm{Sn}}_{2}{\mathrm{S}}_{2}$ phase is well maintained even in the S-poor thin films as well as the nearly stoichiometric films although the amount of Co segregation in both S-poor and S-rich films is similar. Our findings on the influence of off-stoichiometry on the PMA and AHE are beneficial to design magnetic devices incorporated with the Weyl features of ${\mathrm{Co}}_{3}{\mathrm{Sn}}_{2}{\mathrm{S}}_{2}$.
Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes (2015)

Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign.
Minimizing Long-Chain Polysulfide Formation in Li-S Batteries by Using Localized Low Concentration Highly Fluorinated Electrolytes (2021)

Electrolytes that suppress the formation of long-chain polysulfides and limit the sulfur (S) cathode dissolution and polysulfide shuttle effect, while maintaining high active material utilization and long cycle life, have long been sought for advancing Li-S battery applications. Here we demonstrate that localized electrolytes based on fluorinated ethers with the total salt concentration of only 0.1 M show remarkable performance characteristics. By systematically reducing the fraction of sulfolane (SL) as a cosolvent with 1,1,2,2-tetrafluoroethyl 2,2,3,3-tetrafluoropropylether (HFE), we reveal a dramatic change in the cell discharge behavior. The higher voltage ∼2.4 V plateau corresponding to the formation of long-chain polysulfide shrank, while the medium voltage ∼2.1 V plateau corresponding to the transformation to short-chain polysulfides almost disappeared. Additionally, a third low voltage plateau (∼1.9 V) emerges as S transform directly to a short chain polysulfides and Li 2 S, which have significantly lower solubilities. This plateau extended with increasing HFE and became a dominant process. When compared with the traditional dimethoxyethane/1,3-dioxolane (DME/DIOX) electrolyte solvent mixture, the reported electrolytes offer substantially higher capacity and coulombic efficiency due to decreased solubility for Li + in the HFE, causing a shift to favoring short chain length polysulfides in the discharge reaction.
Metal-on-Metal: All Things Bright and Beautiful!-In the Affirmative (2002)

Alternative Bearing Surfaces
The Potency and Specificity of the Interaction between the IA3 Inhibitor and Its Target Aspartic Proteinase fromSaccharomyces cerevisiae (2001)

The yeast IA3 polypeptide consists of only 68 residues, and the free inhibitor has little intrinsic secondary structure. IA3 showed subnanomolar potency toward its target, proteinase A from Saccharomyces cerevisiae, and did not inhibit any of a large number of aspartic proteinases with similar sequences/structures from a wide variety of other species. Systematic truncation and mutagenesis of the IA3 polypeptide revealed that the inhibitory activity is located in the N-terminal half of the sequence. Crystal structures of different forms of IA3 complexed with proteinase A showed that residues in the N-terminal half of the IA3 sequence became ordered and formed an almost perfect alpha-helix in the active site of the enzyme. This potent, specific interaction was directed primarily by hydrophobic interactions made by three key features in the inhibitory sequence. Whereas IA3 was cut as a substrate by the nontarget aspartic proteinases, it was not cleaved by proteinase A. The random coil IA3 polypeptide escapes cleavage by being stabilized in a helical conformation upon interaction with the active site of proteinase A. This results, paradoxically, in potent selective inhibition of the target enzyme.
Achieving energy efficiency in LTE with joint D2D communications and green networking techniques (2013)

In this paper, the joint operation of cooperative device-to-device (D2D) communications and green cellular communications is investigated. An efficient approach for grouping mobile terminals (MTs) into cooperative clusters is described. In each cluster, MTs cooperate via D2D communications to share content of common interest. Furthermore, an energy-efficient technique for putting BSs in sleep mode in an LTE cellular network is presented. Finally, both methods are combined in order to ensure green communications for both the users' MTs and the operator's BSs. The studied methods are investigated in the framework of OFDMA-based state-of-the-art LTE cellular networks, while taking into account intercell interference and resource allocation.
大范围连续调谐的InAs／InP（100）外腔量子点激光器 (2016)

实现了一种工作在连续波（CW）模式下InAs/InP（100）外腔量子点激 光器（EC-QDL）。激光器采用小型化的Littrow 外腔结构,中心波长为1.6μm且输出光方向固定。在室温条件下, 对InAs/InP（100）量子点外腔激光器进行了一系列性能测试。实验结果表明,器件的单模大范围波长调谐达56.5nm,覆盖波长从1566.9623.4 nm,获得30 GHz的无跳模连续调谐范围,在中心波长1.6μm附近单模输出功率达8mW,并在无跳模连续调谐范围内获得了30dB以上的边模抑制比（SMSR）。
New Alternative to Selectively Fracture Stimulate Extended-Reach, Horizontal Wells (2009)

Abstract The requirements of oil and gas producers to maximize hydrocarbon recovery in low-permeability environments have often been satisfied by drilling longer cased or openhole horizontal sections, or by maximizing reservoir contact by perforating multiple laterals or branches to the main bore. As production declines, these complex well completions have brought many challenges to well interventions and stimulations. The number of such complex wells and the number of selective packerless fracture stimulations in long horizontal sections has increased significantly in the last few years, especially in Saudi Arabia in oil/gas producing wells, and eventually, for improving injectivity of water-injector wells. The selective and packerless fracture stimulation technology in wells completed with long, horizontal openholes or cased holes has not been possible until now, especially when coiled tubing is used. This is because the coiled tubing, when equipped with the selective fracturing tool, will not be able to reach the entire horizontal section without the use of mechanical tractors or agitators and because of the incompatibility of the tool assembly and tractor/agitator systems. This paper presents, for the first time, the new tool designed to make tractor/agitator systems compatible with the selective fracturing tool. It presents a detailed job design and considerations used to perform the first field application of the tool in Saudi Arabia.
A critical review on latest innovations and future challenges of electrochemical technology for the abatement of organics in water (2023)

Updated water directives and ambitious targets like the United Nations’ Sustainable Development Goals (SDGs) have emerged in the last decade to tackle water scarcity and contamination. Although numerous strategies have been developed to remove water pollutants, it is still necessary to enhance their effectiveness against toxic and biorefractory organic molecules. Comprehensive reviews have highlighted the appealing features of the electrochemical technologies, but much progress has been made in recent years. In this timely review, a critical discussion on latest innovations and perspectives of the most promising electrochemical tools for wastewater treatment is presented. The work describes the performance of electrocatalytic anodes for direct electrochemical oxidation, the oxidation mediated by electrogenerated active chlorine, the electrocatalytic reduction as well as coupled approaches for synchronous anodic and cathodic processes combined with homogeneous and heterogeneous catalysis. The last section is devoted to the assessment of scale-up issues and the increase in the technology readiness level.
Direct synthesis of H2O2 from O2 and H2 over precious metal loaded TS-1 in CO2 (2007)

H2O2 was synthesized directly from O2 and H2 over precious metal loaded titanium silicalite (TS-1) in compressed CO2 and yields were measured by immediately reacting the in situ generated H2O2 with an “indicator”—pyridine. Experimental results proved that H2O2 could be effectively synthesized from O2 and H2 in compressed CO2. The effects of the following factors on H2 conversion, H2O2 selectivity and yield were examined: O2/H2 molar ratio, H2 concentration, catalyst mass, Pd content in the catalyst and the addition of Pt to the catalyst. Under the optimal reaction conditions, H2O2 yield reached 31.7% with an H2O2 selectivity of 56.1%.
The Impact of the Secondary Binding Pocket on the Pharmacology of Class A GPCRs (2022)

G-protein coupled receptors (GPCRs) are considered important therapeutic targets due to their pathophysiological significance and pharmacological relevance. Class A receptors represent the largest group of GPCRs that gives the highest number of validated drug targets. Endogenous ligands bind to the orthosteric binding pocket (OBP) embedded in the intrahelical space of the receptor. During the last 10 years, however, it has been turned out that in many receptors there is secondary binding pocket (SBP) located in the extracellular vestibule that is much less conserved. In some cases, it serves as a stable allosteric site harbouring allosteric ligands that modulate the pharmacology of orthosteric binders. In other cases it is used by bitopic compounds occupying both the OBP and SBP. In these terms, SBP binding moieties might influence the pharmacology of the bitopic ligands. Together with others, our research group showed that SBP binders contribute significantly to the affinity, selectivity, functional activity, functional selectivity and binding kinetics of bitopic ligands. Based on these observations we developed a structure-based protocol for designing bitopic compounds with desired pharmacological profile.
Melanoma and immunotherapy bridge 2015 (2016)

The PI3K/AKT/mTOR signaling pathway has been implicated in multiple cancers, and as a regulator of many key oncogenic processes. Our studies implicate a role for this pathway in resistance to both targeted and immune therapies for melanoma. Materials and methods: Melanoma cell lines and clinical specimens were utilized to study the significance and functional consequences of the PI3K/AKT/mTOR pathway. Analyses of clinical specimens were performed under institution review board-approved protocols. Results: Pilot whole genome expression profiling and synthetic lethality screens implicated oxidative phosphorylation (OxPhos) in resistance to BRAF and MEK inhibitors in BRAF-mutant human melanoma cell lines. Characterization of panels of human cell lines with de novo or acquired resistance to MAPK pathway inhibitors demonstrated that ~50 % of the cell lines exhibited a high OxPhos phenotype. The presence of high OxPhos correlated with increased expression of PGC1-alpha and with sensitivity to combined inhibition of the MAPK pathway and mTORC1/2. mTORC1/2 inhibition caused cytoplasmic sequestration of MITF and subsequent decreased expression of MITF-regulated genes, including PGC1-alpha. In vitro testing demonstrated that a direct OxPhos inhibitor similarly achieved growth inhibition and apoptosis in some human melanoma cell lines with high OxPhos. Further, the OxPhos inhibitor abrogated the growth of inhibitor-resistant BRAF mutant human melanoma cell lines in vivo. Activation of the PI3K/AKT/mTOR pathway by loss of PTEN was also shown to promote resistance to T cell mediated cell killing in vitro and in vivo. Loss of PTEN correlated with decreased CD8 cell infiltrates in clinical specimens and increased expression of immunosuppressive cytokines. While pan-PI3K inhibitors inhibited immune cell viability and function, isoform-selective inhibitors did not significantly affect immune function and they produced synergy with immunotherapy. Conclusions: The PI3K/AKT/mTOR signaling pathway is an important regulator of key cellular processes in melanoma, and should be considered as a candidate combinatorial partner for both targeted and immune therapies.