gebhart/patrepeval huggingface dataset:
A Review of Stapled Peptides and Small Molecules to Inhibit Protein–Protein Interactions in Cancer (2016)

Disruption of binding of two or more molecules to a protein surface is a common basis of inhibition of many biological activities. Smallmolecule inhibitors, antibodies, proteins, and peptidomimetics have been examined as ways to antagonize receptor activity. The peptide α-helix plays a crucial role in the function of many proteins. Hence, much effort has been invested in mimicking α-helices at the binding interface of two proteins to competitively inhibit their interactions. Peptide stapling involves choosing two amino acids on the same face of a native peptide sequence for substitution with non-native amino acids whose side chains can be "stapled" together. The focus of this review is to survey the prevalence in literature of stapled peptides and small-molecule antagonists of interactions of selected mammalian cancer targets, such as β-catenin, BH3-only members of the Bcl-2 family of proteins, eIF4E/G, estrogen receptor complexes, EZH2, Mdm2, Notch, p110α, and survivin. The increasing interest in protein targets currently considered to be "undruggable" with greater selectivity for existing targets, with the goal of overcoming the omnipresent problem of resistance, could be served well by utilizing information about protein-protein interactions to develop both small-molecule and stapled peptide inhibitors.
High Current Density and Nonlinearity Combination of Selection Device Based on TaO<sub><i>x</i></sub>/TiO<sub>2</sub>/TaO<sub><i>x</i></sub> Structure for One Selector–One Resistor Arrays (2012)

We demonstrate a high-performance selection device by utilizing the concept of crested oxide barrier to suppress the sneak current in bipolar resistive memory arrays. Using a TaO(x)/TiO(2)/TaO(x) structure, high current density over 10(7) A cm(-2) and excellent nonlinear characteristics up to 10(4) were successfully demonstrated. On the basis of the defect chemistry and SIMS depth profile result, we found that some Ta atoms gradually diffused into TiO(2) film, and consequently, the energy band of the TiO(2) film was symmetrically bent at the top and bottom TaO(x)/TiO(2) interfaces and modified as a crested oxide barrier. Furthermore, the one selector-one resistor device exhibited significant suppression of the leakage current, indicating excellent selector characteristics.
S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors (2005)

The defining characteristic of a tumor cell is its ability to escape the constraints imposed by neighboring cells, invade the surrounding tissue and metastasize to distant sites. This invasive property of tumor cells is dependent on activation of proteinases at the cell surface. The serine proteinase plasmin is one of the key proteinases that participate in the pericellular proteolysis associated with the invasive program of tumor cells. The assembly of plasminogen and tissue plasminogen activator at the endothelial cell surface or on the fibrin clot provides a focal point for plasmin generation and therefore plays an important role in maintaining blood fluidity and promoting fibrinolysis. S100A10, a member of the S100 family of Ca2+-binding proteins, is a dimeric protein composed of two 11 kDa subunits. Typically, S100A10 is found in most cells bound to its annexin A2 ligand as the heterotetrameric (S100A10)2(annexin A2)2 complex, AIIt. In addition to an intracellular distribution, S100A10 is present on the extracellular surface of many cells. The carboxyl-terminal lysines of S100A10 bind tPA and plasminogen resulting in the stimulation of tPA-dependent plasmin production. Carboxypeptidases cleave the carboxyl-terminal lysines of S100A10, resulting in a loss of binding and activity. Plasmin binds to S100A10 at a distinct site and the formation of the S100A10-plasmin complex stimulates plasmin autoproteolysis thereby providing a highly localized transient pulse of plasmin activity at the cell surface. The binding of tPA and plasmin to S100A10 also protects against inhibition by physiological inhibitors, PAI-1 and alpha2-antiplasmin, respectively. S100A10 also colocalizes plasminogen with the uPA-uPAR complex thereby localizing and stimulating uPA-dependent plasmin formation to the surface of cancer cells. The loss of S100A10 from the extracellular surface of cancer cells results in a significant loss in plasmin generation. In addition, S100A10 knock-down cells demonstrate a dramatic loss in extracellular matrix degradation and invasiveness as well as reduced metastasis. Annexin A2 plays an important role in plasminogen regulation by controlling the levels of extracellular S100A10 and by acting as a plasmin reductase. The mechanism by which annexin A2 regulates the extracellular levels of S100A10 is unknown. This review highlights the important part that S100A10 plays in plasmin regulation and the role this protein plays in cancer cell invasiveness and metastasis.
Comparative analysis of marketed factor VIII products: recombinant products are not alike vis‐a‐vis soluble protein aggregates and subvisible particles (2018)

Background Recombinant protein technologies have facilitated the development of novel factor VIII (FVIII) therapeutics with improved production efficiency, potency and half-live, and a low risk of viral transmission. The increasing number of recombinant FVIII (rFVIII) products and information on their efficacy, safety and cost allow patients and healthcare professionals to adjust treatment to individual needs. Nonetheless, 20-32% of previously untreated patients with severe hemophilia A develop inhibitory antibodies to rFVIII following treatment. The root cause of the immunogenicity of rFVIII products is not well understood. Data for human interferon and human insulin products suggest that critical quality parameters such as soluble protein aggregates (SPAs) and subvisible particles (SVPs) influence the immunogenicity of protein therapeutics. Therefore, we analyzed SPA and SVP concentrations in commercially available rFVIII products and determined how these parameters change upon exposure of rFVIII products to relevant stress conditions. Objectives Compare critical quality parameters such as SPA and SVP concentrations in rFVIII products under intended use and use-relevant stress conditions. Methods Nine rFVIII products (≥ 3 lots each) were analyzed by high-performance liquid chromatography-size exclusion chromatography (HPLC-SEC) and flow cytometry-based particle analysis. Results/conclusions SPAs and SVPs were present at different concentrations in all freshly reconstituted rFVIII products: SPA concentrations ranged from 0.2% to 11.6%; SVPs were 0.7 × 10<sup>6</sup> to 114.0 × 10<sup>6</sup> / 1000 IU. Under use-relevant stress conditions (agitation and shear stress) the products formed additional SPAs and SVPs to different degrees. The collected data indicate that product quality determines its propensity to form SVPs and SPAs, and highlights differences between marketed rFVIII products.
Effect of surface‐modifying macromolecules and solvent evaporation time on the performance of polyethersulfone membranes for the separation of chloroform/water mixtures by pervaporation (1994)

Abstract Polyethersulfone (PES) membranes using different evaporation periods were fabricated by the phase‐inversion method. Pervaporation experiments were conducted for chloroform/water mixtures to determine the selectivity of the PES membranes. It was found that chloroform could be concentrated in the permeate from chloroform/water binary feed mixtures by PES membranes prepared using longer evaporation periods, and that the selectivity of PES membranes in pervaporation could be reversed by shorter evaporation periods. This study also showed that by adding surface‐modifying macromolecules (SMM) up to 1 wt % into the casting solution, chloroform enrichment in the permeate could be increased by 50%. Chloroform enrichment increased with increasing SMM concentration until an optimal value, after which the enrichment decreased. © 1994 John Wiley & Sons, Inc.
A Distributed Assignment Method for Dynamic Traffic Assignment Using Heterogeneous-Adviser Based Multi-Agent Reinforcement Learning (2020)

The Dynamic Traffic Assignment (DTA) is one of the important measures to alleviate urban network traffic congestion. The congestions are usually caused by stochastic traffic demands, which are generally unassignable from time dimension in the real-world but are assumed to be assignable in existing DTA methods (i.e. real-time travel demands). In this paper, a distributed DTA method for preventing urban network traffic congestion caused by stochastic real-time travel demands by improving Multi-Agent Reinforcement Learning (MARL). A team structure, which consists of decision-makers and advisers, is designed to learn parallelly in realistic DTA tasks. To reduce the size of the solution space adaptively, the dynamic critical values advised by adviser agents are adopted as constraints for the strategy space of decision-makers (i.e. main agents). A collaborative heterogeneous-adviser mechanism is designed to avoid deviation of guidance. To enhance the adaptability of DTA to the changeable external environment, the mixed strategy concept is introduced to improve the decision-making process of main agents. The respective mapping mechanisms are designed to define adaptive learning rates to improve the sensitivity of MARL. The Sioux Falls (SF) network is established as a test platform via a Dynamic Network Loading (DNL). The effectiveness of the suggested DTA method is assessed through numerical simulations SF network. Under the influence of the scenario with stochastic real-time travel demands, the results show that the proposed method outperforms in terms of the throughput of the network and the individual average travel time among the overall network. Additionally, the ability of the proposed method in response to the external environment rapidly has also been demonstrated. Adopting the suggested method can improve the state of the art to assign stochastic real-time travel demands dynamically and to avoid potential traffic congestion fundamentally.
Acid Ionic Liquids as a New Hardener in Urea-Glyoxal Adhesive Resins (2016)

The effect of acidic ionic liquid (IL) as a new catalyst on the properties of wood-based panels bonded with urea-glyoxal (UG) resins was investigated. Different levels of <i>N</i>-methyl-2-pyrrolidone hydrogen sulfate ([HNMP] HSO₄ (0, 1, 2, 3 wt %)) were added to prepared UG resin. The resin was then used for preparing laboratory particleboard panels. Then, the properties of the prepared panels were evaluated. The structure of the prepared UG resin was studied by <sup>13</sup>C NMR, and thermal curing behavior of the resin before and after the addition of IL was measured by DSC. Additionally, the main oligomers formed in the UG reaction were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectroscopy. The results indicated that IL can be used as an efficient catalyst for UG resin. The physicochemical tests indicated that the addition of [HNMP] HSO₄ from 0 to 3 wt % decreased the pH value of the glue-mix, and the pH decreased on curing to the same level as urea-formaldehyde resins. The gel accelerated with increasing catalyst content and with the decreasing of the pH in the UG resin. The panels prepared with IL had higher mechanical strength and dimensional stability compared to those made from UG resins containing NH₄Cl. Scanning electron microscope (SEM) micrographs showed that the panels prepared with ionic liquid presented low porous. DSC analysis showed that the addition of IL to the UG resin decrease the energy of activation of the curing reaction to render possible cross-linking. The MALDI TOF results indicated a preponderant linearity of the oligomers formed, implying a high energy of activation of curing for UG resins.
Screening for Biotinidase Deficiency in Newborns: Worldwide Experience (1990)

Between January 24, 1984, and December 31, 1988, 29 screening programs for biotinidase deficiency in newborns were established in 12 countries, and 4,396,834 newborns were screened. The worldwide incidence is based on screening programs in Australia, Austria, Canada, Italy, Japan, Mexico, New Zealand, Scotland, Spain, Switzerland, The United States, and West Germany. Biotinidase deficiency was detected in 72 newborns; 32 had profound biotinidase deficiency (less than 10% of mean normal activity level) and 40 had partial deficiency (10% to 30% of mean normal activity level). The combined incidence of profound and partial deficiency was 1 case per 61,067 live births (1:49 500 to 1:79 544; 95% confidence interval), the estimated frequency of the recessive allele was 0.0040, and the frequency of heterozygosity was estimated to be 1:123. Profound deficiency occurred in 1 per 137,401 live births (1:109,300 to 1:211,200), and partial deficiency in 1 per 109,921 live births (1:86,600 to 1:159,700). Most available parents of children with profound and partial deficiency had biotinidase activity levels intermediate between zero and mean normal activity levels. Six children with profound deficiency were symptomatic at, or soon after, the time of diagnosis; no infant with partial deficiency has become symptomatic, but little is known about the natural history of infants with partial deficiency. Most children whose biotinidase deficiency was detected by newborn screening were white, one was black, and one Hispanic; biotinidase deficiency has not been detected in Oriental children. Although 8 pilot programs have terminated, 21 will continue either indefinitely or until predetermined targets are reached, and 3 new programs were scheduled to begin in January 1989.(ABSTRACT TRUNCATED AT 250 WORDS)
Optical PSK modulation using injection-locked DFB semiconductor lasers (1990)

Injection-locked distributed feedback (DFB) semiconductor lasers, with strong single longitudinal mode selection provided by the distributed grating are found to be appropriate for optical phase shift keying (PSK) modulation. Both small-signal analysis and large-signal numerical simulations are performed on the optical PSK modulation properties. The main limitations are found to arise from the anomalous bandwidth reduction near the edge of the locking range and the time needed to damp the relaxation oscillation. By the tradeoff of the two effects, parameter optimization is obtained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
ChemInform Abstract: Synthesis and Biological Evaluation of 3‐Arylisoquinolines as Antitumor Agents. (1998)

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.
正·反·合《喜马拉雅》 (2005)

正反合是黑格尔哲学里的概 念。通俗地讲,就是矛盾的否 定之否定、矛盾的对立和统一。黑格尔认 为,任何一个事物在正面发展过程中都 会自我孕育它的反面,这便是事物的 正和反。正培育出它的对立面 反,并与之发生矛盾;最终,反必 将克服正;克服正以 后的反也不是原先 的那个反了,而 是包容了正的 合。事物就是 在正反合的 不断运动中发 展的。 生活在喜 马拉雅山麓的 多波人是个古老 和原始的部落,他 们在酋长的带领下,
Application of amide hydrogen/deuterium exchange mass spectrometry for epitope mapping in human cystatin C (2016)

Human cystatin C (hCC) is a small cysteine protease inhibitor whose oligomerization by propagated domain swapping is linked to certain neurological disorders. One of the ways to prevent hCC dimerization and fibrillogenesis is to enable its interaction with a proper antibody. Herein, the sites of interaction of hCC with dimer-preventing mouse monoclonal anti-hCC antibodies Cyst28 are studied and compared with the binding sites found for mAb Cyst10 that has almost no effect on hCC dimerization. In addition, hCC epitopes in complexes with native polyclonal antibodies extracted from human serum were studied. The results obtained with hydrogen-deuterium exchange mass spectrometry (HDX MS) were compared with the previous findings made using the excision/extraction MS approach. The main results from the two complementary MS-based approaches are found to be in agreement with each other, with some differences being attributed to the specificity of each method. The findings of the current studies may be important for future design of hCC dimerization inhibitors.
IMGN853 (mirvetuximab soravtansine), a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC): Single-agent activity in platinum-resistant epithelial ovarian cancer (EOC) patients (pts). (2016)

5567 Background: IMGN853 (mirvetuximab soravtansine) is an ADC, comprising a FRα-binding antibody linked to the tubulin-disrupting maytansinoid, DM4. Here we report on the IMGN853 monotherapy expansion cohort of pts with platinum-resistant EOC as part of an ongoing phase I dose escalation trial (NCT01609556). Methods: Patients were administered IMGN853 intravenously once every 3 weeks at 6.0 mg/kg using adjusted ideal body weight. Responses were assessed according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.0. Results: A total of 48 EOC, primary peritoneal, or fallopian tube cancer pts (n = 45, 1, and 2, respectively) have been treated at 6.0 mg/kg: 2 in dose escalation; 46 in the platinum-resistant expansion cohort. Pts were heavily pretreated (median of 4 previous systemic treatments), with 100% prior platinum and taxane exposure. To date, objective tumor responses were observed in 19 pts for an overall response rate (ORR; confirmed and unconfirmed partial response [PR] or complete response [CR]) of 40%. Based on FRα expression, responses were seen in pts in each subgroup: 33% (3/9) low (25-49% of cells with ≥ moderate expression), 33% (5/15) medium (50-74% of cells with ≥ moderate expression), and 48% (11/23) high ( ≥ 75% of cells with ≥ moderate expression) expressers. The most commonly reported AEs ( > 25 % of pts) were diarrhea, blurred vision, fatigue, nausea, vomiting, peripheral neuropathy, and increased AST (aspartate aminotransferase); the majority of which were grade 1 or 2. The most frequent grade 3-4 drug related AEs were fatigue and hypotension (2 patients each - 4.2%). Four pts discontinued for AEs. Thirteen pts remain on IMGN853. The median duration of follow-up is 4.2 months. Conclusions: IMGN853 demonstrates encouraging signs of clinical activity in heavily pretreated platinum-resistant EOC pts with a manageable safety profile. Further, the ORR (48%) seen in the high FRα expression subset suggests that FRα expression may be a predictive biomarker for IMGN853 suitable for patient selection. Clinical trial information: NCT01609556.
Transition-State Enthalpy and Entropy Effects on Reactivity and Selectivity in Hydrogenolysis of<i>n</i>-Alkanes (2013)

Statistical mechanics and transition state (TS) theory describe rates and selectivities of C-C bond cleavage in C2-C10 n-alkanes on metal catalysts and provide a general description for the hydrogenolysis of hydrocarbons. Mechanistic interpretation shows the dominant role of entropy, over enthalpy, in determining the location and rate of C-C bond cleavage. Ir, Rh, and Pt clusters cleave C-C bonds at rates proportional to coverages of intermediates derived by removing 3-4 H-atoms from n-alkanes. Rate constants for C-C cleavage reflect large activation enthalpies (ΔH(‡), 217-257 kJ mol(-1)) that are independent of chain length and C-C bond location in C4+ n-alkanes. C-C bonds cleave because of large, positive activation entropies (ΔS(‡), 164-259 J mol(-1) K(-1)) provided by H2 that forms with TS. Kinetic and independent spectroscopic evidence for the composition and structure of these TS give accurate estimates of ΔS(‡) for cleavage at each C-C bond. Large differences between rate constants for ethane and n-decane (~10(8)) reflect an increase in the entropy of gaseous alkanes retained at the TS. The location of C-C bond cleavage depends solely on the rotational entropies of alkyl chains attached to the cleaved C-C bond, which depend on their chain length. Such entropy considerations account for the ubiquitous, but previously unexplained, preference for cleaving nonterminal C-C bonds in n-alkanes. This mechanistic analysis and thermodynamic treatment illustrates the continued utility of such approaches even for hydrogenolysis reactions, with complexity seemingly beyond the reach of classical treatments, and applies to catalytic clusters beyond those reported here (0.6-2.7 nm; Ir, Rh, Pt).
Characterization of TiS2 as an Anode Material for Lithium Ion Batteries (2011)

Hexagonal TiS2 was synthesized as a high-capacity anode material for lithium ion batteries. X-ray diffraction (XRD) and scanning electron microscopy (SEM) indicated that this material had a layered structure with particle sizes between 10 and 20 mu m. It shows three discharge plateaus between 3.00 and 0.00 V with a reversible capacity of up to 668 mAh . g(-1). It has excellent cycling performance between 3.00 and 1.40 V. Particle pulverization and formation of Li2S lead to performance degradation because of the irreversible dissolution of Li2S into the electrolyte below 0.50 V. The addition of extra acetylene black and a decrease in particle size markedly improve the electrochemical performance of the TiS2 anode.
Osmium‐ and Ruthenium‐Based Phosphorescent Materials: Design, Photophysics, and Utilization in OLED Fabrication (2006)

Abstract Osmium(II) complexes possessing β‐diketonate, quinolinate, diimine, and C‐linked pyridyl azolate chelates reveal interesting structural and photophysical properties. Spectroscopic and dynamic measurements, in combination with theoretical analyses, have provided an important understanding of the electronically excited state properties of these complexes, such as the energy gap and nature of the lower lying states, rate for intersystem crossing, and the efficiency of corresponding radiative decay and nonradiative deactivation processes. This review also reports on the synthetic processes that lead to the neutral Os II and Ru II complexes that possess two trans ‐substituted phosphane donor ligands together with two anti ‐parallel, aligned azolate chromophores. Considerable efforts have been made to focus on utilizing these emitting materials as phosphorescent dopants for practical PLED and OLED fabrication. Consequently, the interplay between these emitting materials and device configurations is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Development of an eye-gaze controlled interface for surgical manipulators using eye-tracking glasses (2016)

Introducing robots into the operating theatre has become more popular in recent decades. Surgical manipulators have been developed to assist in surgeries like a human assistant to facilitate the surgical procedures. In this paper, we present an eye-controlled interface for the surgeon to control this kind of robot based on eye-tracking glasses. In our approach, we use the monitor for providing the endoscopic/laparoscopic feedback as the landmark for controlling the robot. The surgeon is allowed to control the robot by looking at different features of the monitor. We present the algorithm for extracting the monitor from the user's view and the method on how to differentiate the control commands with the detected monitor and the user's gaze-point. Experiments were conducted to verify the feasibility of our eye-controlled interface.