gebhart/patrepeval huggingface dataset:
Study on Fracture of Glass: Control of Crack Generation and Growth in Glass (2009)

ガラスの実用強度はガラス表面のキズに大きく影 響される。例えば、キズのないシリカガラスファイ バの強度は液体窒素温度で約10~15GPa、室温で5 ~6GPaであるが、実測される通常のシリカガラス の強度はその2桁程度小さい値となる。これはガラ ス表面のキズによるものであり、従ってガラス表面 のキズを制御すればガラスの実用強度も上昇する。 ガラスの物性はガラス組成に大きく依存するが、 強度も例外ではない。ガラスの強度はクラックの発 生挙動と密接な関係があるが、その挙動もガラス組 成に依存する。当社ではこれまでクラックが発生し にくいガラスとしてLess Brittle Glass(LBガラス) を報告してきたが、このガラスはTable 1に示すよう に通常の窓ガラス(ソーダライムガラス)と類似し た組成であるにもかかわらず、ビッカースインデン テーションを行ったときのクラック発生荷重は極め て大きい。Figure 1にソーダライムガラスとLBガラ Res. Reports Asahi Glass Co., Ltd., 59(2009)
Differentiation of Muramidase and -Lysin (1966)

Although β-lysin and muramidase are similar in their bacterial spectrum, heat stability, and adsorption by bentonite on an asbestos-cellulose filter pad of the Seitz type, they differ in other respects. β-lysin is relatively more effective as a bactericidal agent for Bacillus subtilis than for Micrococ-cus lysodeikticus. This quantitative relationship is reversed with muramidase. Unlike muramidase, purified β-lysin did not reduce the optical density of killed suspensions of bacteria, Anti-β-lysin serum did not neutralize the bactericidal activity of muramidase. Serum β-lysin and muramidase were separated by gel filtration with a Sephadex G-75 column.
Deployment and exploitation of deceptive honeybots in social networks (2013)

As social networking sites such as Facebook and Twitter are becoming increasingly popular, a growing number of malicious attacks, such as phishing and malware, are exploiting them. Among these attacks, social botnets have sophisticated infrastructure that leverages compromised user accounts, known as bots, to automate the creation of new social networking accounts for spamming and malware propagation. Traditional defense mechanisms are often passive and reactive to non-zero-day attacks. In this paper, we adopt a proactive approach for enhancing security in social networks by infiltrating botnets with honeybots. We propose an integrated system named SODEXO which can be interfaced with social networking sites for creating deceptive honeybots and leveraging them for gaining information from botnets. We establish a Stackelberg game framework to capture strategic interactions between honeybots and botnets, and use quantitative methods to understand the tradeoffs of honeybots for their deployment and exploitation in social networks. We design a protection and alert system that integrates both microscopic and macroscopic models of honeybots and optimally determines the security strategies for honeybots. We corroborate the proposed mechanism with extensive simulations and comparisons with passive defenses.
Testing Code Security (2007)

The huge proliferation of security vulnerability exploits, worms, and viruses place an incredible drain on both cost and confidence for manufacturers and consumers. The release of trustworthy code requires a specific set of skills and techniques, but this information is often dispersed and decentralized, encrypted in its own jargon and terminology,
Insulin and cyclic AMP act at different levels on transcription of the L‐type pyruvate kinase gene (1997)

We previously demonstrated that, in hepatocytes in primary culture, the role of insulin on induction of L-type pyruvate kinase (L-PK) gene expression was mainly to induce glucokinase synthesis, needed for glucose phosphorylation to glucose 6-phosphate. However, we show here that when hepatocytes have been isolated from rats starved for 72 h, glucose and constitutive glucokinase expression was not sufficient to fully stimulate the L-PK promoter, low insulin concentrations being still required. In addition, activation remains sensitive to cAMP inhibition, but cannot be reproduced in the absence of insulin by a competitive cAMP antagonist. We propose that both insulin and cAMP act on expression of the L-PK gene at, at least, two levels: positive and negative regulation of glucokinase gene expression, and more downstream levels.
Determination of the Conformational Flexibility of Methyl α-Cellobioside in Solution by NMR Spectroscopy and Molecular Simulations (2004)

The conformational flexibility of methyl α-cellobioside in water and dimethyl sulfoxide solutions was investigated by 1D 1H,1H T-ROESY experiments. In combination with molecular dynamics simulations, effective proton−proton distances could be derived using experimentally determined cross-relaxation rates. An anti-ψ-conformational state was present in both solvents confirming a previous flexibility hypothesis at this torsion angle. In water solution, an anti-φ-conformational state was also detected and quantified. These results show that already at the disaccharide level a large flexibility is present at the glycosidic linkage. In addition to the syn-conformation which is present to ∼93% for the title compound in water solution, the minor anti-φ- and anti-ψ-conformational states are populated to ∼2% and ∼5%, respectively.
Immunostimulatory DNA-Based Vaccines Elicit Multifaceted Immune Responses Against HIV at Systemic and Mucosal Sites (2001)

Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathogen-associated molecular patterns that are potent stimulators of innate immunity. We tested the ability of ISS to act as an immunostimulatory pathogen-associated molecular pattern in a model HIV vaccine using gp120 envelope protein as the Ag. Mice immunized with gp120 and ISS, or a gp120:ISS conjugate, developed gp120-specific immune responses which included: 1) Ab production; 2) a Th1-biased cytokine response; 3) the secretion of beta-chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV; 4) CTL activity; 5) mucosal immune responses; and 6) CD8 T cell responses that were independent of CD4 T cell help. Based on these results, ISS-based immunization holds promise for the development of an effective preventive and therapeutic HIV vaccine.
Incidence of Atrial Fibrillation following Alcohol Septal Ablation for Hypertrophic Cardiomyopathy (2016)

Despite relieving LVOT obstruction and improving mitral regurgitation severity via ASA, new-onset AF remained a common complication of hypertrophic cardiomyopathy.
Spiruchostatin A is a class I specific histone deacetylase (HDAC) inhibitor with distinct pharmacodynamic properties compared to non-specific hydroxamate inhibitors. (2006)

5047 Histone acetylation is one mechanism by which chromatin structure and its transcription is regulated. Histone acetylation and histone deacetylation, controlled by histone acetyltransferases and histone deacetylases (HDACs) respectively, play key roles in gene regulation. The inhibition of HDACs may result in chromatin remodeling, upregulation of key tumor suppressor genes and loss of fidelity during mitosis. Therefore, HDAC inhibitors are being evaluated in the clinic as anti-cancer therapeutics. CRA-026440 is a novel HDAC inhibitor. It displayed potent inhibition against human HDAC enzymes (Ki: 4-20 nM) and exhibited sub-μΜ growth inhibition against a panel of human cancer cell lines. CRA-026440 exhibited significant anti-tumor activity in vivo, both as a single agent and in combination with Avastin or 5FU. Here, we present data on CRA-026440: 1) The mechanism(s) of action:. A) Anti-angiogenesis: Examination of CRA-026440 in vitro in the rat aortic ring angiogenesis assay suggested possible anti-angiogenic activity. This activity was further corroborated by finding that the treatment of CRA-026440 in vivo had lead to the down-regulation of tumor angiogenesis-related genes such as VEGF and KDR. B) Tumor cell signaling. The effects of CRA-026440 on tumor cell proliferation and survival signals were examined in HCT 116. A panel of targets including caspase 3, B-catenin, CREB, HSP27, JNK, Jun, c-kit, Lck, Ikb, ERK, AKT, p38, p70, STAT3, IRS1, and EGFR were examined. Time-dependent induction of Erk and p70 (S6) phosphorylation, STAT3 protein level, and caspase 3 activation following the treatment of CRA-026440 was observed. 2) CRA-026440 was further examined in vivo in a panel of tumor xenograft models. Statistically significant efficacy was achieved in a U937 histiocytic lymphoma xenograft model and in an HCT 116 xenograft model. The CWR-22RV1 prostate tumor xenograft showed resistance to CRA-026440. The availability of xenograft models displaying a spectrum of sensitivities to CRA-026440 renders it possible to use such models for the identification and validation of efficacy bio-markers. In addition, the pharmacokinetic profile of CRA-026440 in xenograft model will be presented. In summary, CRA-026440, a potent broad-spectrum HDAC inhibitor, exhibited anti-proliferative and anti-angiogenic activities. Exploratory efforts on CRA-026440-related cellular signal transduction events may help shed light on the molecular response involved in CRA-026440’s anti-proliferative activities. Further examination may identify rational combination strategy that results in therapeutic synergy. With the continued examination of its mechanism of action, we hope to deliver targeted therapy by selecting rational dose regimen, combinatorial strategy and patient selection.
Testosterone functions as a tumor suppressor in glioblastoma (2022)

Abstract A sex difference in the incidence and outcome of patients with glioblastoma (GBM), the most common primary malignant brain tumor, has been well established, as male patients experience a worse prognosis. However, the contribution of sex hormones to anti-tumor immunity has not been fully explored. To test this, we orthotopically implanted syngeneic mouse GBM cells into male mice after castration or sham surgery to assess survival differences. Castrated immune-competent mice succumbed to tumors significantly faster than the sham surgery group, and this was rescued by exogenous testosterone administration. In contrast, immune-deficient NSG castrated mice survived longer than sham animals, suggesting a role for immune cells in the survival difference. Flow cytometry analysis of tumor-infiltrating immune cells further showed decreased cytokine production in T cells from castrated mice, while no difference was found in immune cell infiltration. Flank tumor experiments suggested brain-specific regulation of T cell recruitment, as tumor growth was delayed in castrated mice, with higher infiltration of CD8+ T cells but decreased cytokine production. Surprisingly, mass spectrometry of serum revealed upregulated levels of circulating corticosterone in castrated mice regardless of tumor presence, suggesting that castration may induce systemic immunosuppression via upregulation of glucocorticoids. Taken together, our data demonstrate that testosterone regulates T cell immunity, possibly via glucocorticoids, and ultimately affects GBM tumor growth. Given the decreased level of testosterone in aged males with higher risk of GBM, these findings further suggest the potential therapeutic intervention of testosterone in GBM. Supported by grants from NIH (P01 CA245705)
KinderMiner Web: a simple web tool for ranking pairwise associations in biomedical applications (2020)

<ns3:p> Many important scientific discoveries require lengthy experimental processes of trial and error and could benefit from intelligent prioritization based on deep domain understanding. While exponential growth in the scientific literature makes it difficult to keep current in even a single domain, that same rapid growth in literature also presents an opportunity for automated extraction of knowledge via text mining. We have developed a web application implementation of the KinderMiner algorithm for proposing ranked associations between a list of target terms and a key phrase. Any key phrase and target term list can be used for biomedical inquiry. We built the web application around a text index derived from PubMed. It is the first publicly available implementation of the algorithm, is fast and easy to use, and includes an interactive analysis tool. The KinderMiner web application is a public resource offering scientists a cohesive summary of what is currently known about a particular topic within the literature, and helping them to prioritize experiments around that topic. It performs comparably or better to similar state-of-the-art text mining tools, is more flexible, and can be applied to any biomedical topic of interest. It is also continually improving with quarterly updates to the underlying text index and through response to suggestions from the community. The web application is available at <ns3:ext-link xmlns:ns4="http://www.w3.org/1999/xlink" ext-link-type="uri" ns4:href="https://www.kinderminer.org">https://www.kinderminer.org</ns3:ext-link> . </ns3:p>
Sulfonylurea-Grafted Polymers for Langerhans Islet Stimulation (1996)

The preliminary results of the in vitro bioactivities of sulfonylurea (a glyburide analogue) grafted copolymers, evaluated by adding the copolymers into normal rat islet cultures and measuring insulin concentration in the supernatant, was presented. A hydrophobic polymerizable sulfonylurea monomer showed the stimulatory effect on rat islets at glucose concentrations of 50 mg/dL and 100 mg/dL with equivalent stimulation indices to glyburide, a potent sulfonylurea drug, while less effect was observed at a glucose concentration of 200 mg/dL. The water solubilities and bioactivities of sulfonylurea polymers may be influenced by the polymer backbone structure. Since it is suggested that the sulfonylurea receptors are located in the lipid phase on the ATP-sensitive K+ channels, solubilization of sulfonylurea into and its diffusion through the lipid phase in the cell membrane may affect the interactions of sulfonylurea with its receptors. With sulfonylurea polymer, sulfonylurea unit in the polymer can interact with its receptor, but this interaction would be affected to some extent by the polymer structure.
Cover Picture: Nano‐characterization of Cast Structures by FIB‐Tomography (Adv. Eng. Mater. 01‐02/2008) (2008)

Abstract The cover shows the 3D‐FIB reconstruction of an AlSi8Mg5 alloy with: AlFeSiMg aluminides (red), Mg 2 Si Chinese script (yellow∥, and Si lamellae (cyan/Al‐transparent). The “tomograph” was obtained using SE‐images for drawing the particle contours and low resolution EDS maps for phase identification (analyzed volume [xyz] = 14.0 × 7.9 × 7.0 μm 3 ). More details can be found in the article by F. Lasagni et al. on page 62.
Defined MSC exosome with high yield and purity to improve regenerative activity (2021)

Exosomes derived from mesenchymal stem cells (MSCs) have been studied as vital components of regenerative medicine. Typically, various isolation methods of exosomes from cell culture medium have been developed to increase the isolation yield of exosomes. Moreover, the exosome-depletion process of serum has been considered to result in clinically active and highly purified exosomes from the cell culture medium. Our aim was to compare isolation methods, ultracentrifuge (UC)-based conventional method, and tangential flow filtration (TFF) system-based method for separation with high yield, and the bioactivity of the exosome according to the purity of MSC-derived exosome was determined by the ratio of Fetal bovine serum (FBS)-derived exosome to MSC-derived exosome depending on exosome depletion processes of FBS. The TFF-based isolation yield of exosome derived from human umbilical cord MSC (UCMSC) increased two orders (92.5 times) compared to UC-based isolation method. Moreover, by optimizing the process of depleting FBS-derived exosome, the purity of UCMSC-derived exosome, evaluated using the expression level of MSC exosome surface marker (CD73), was about 15.6 times enhanced and the concentration of low-density lipoprotein-cholesterol (LDL-c), known as impurities resulting from FBS, proved to be negligibly detected. The wound healing and angiogenic effects of highly purified UCMSC-derived exosomes were improved about 23.1% and 71.4%, respectively, with human coronary artery endothelial cells (HCAEC). It suggests that the defined MSC exosome with high yield and purity could increase regenerative activity.
Differential requirements for the O-linked branching enzyme core 2 β1-6-N-glucosaminyltransferase in biosynthesis of ligands for E-selectin and P-selectin (2001)

Selectins are carbohydrate-binding adhesion molecules that play important roles in control of leukocyte traffic. Glycosyltransferases involved in selectin ligand biosynthesis include the alpha1,3-fucosyltransferases FucT-VII and FucT-IV, one or more sialyltransferases, and at least one O-linked branching enzyme. Previous studies have shown that core 2 beta1-6-N-glucosaminyltransferase (C2GlcNAcT-I; EC 2.4.1.102) is required for functional modification of PSGL-1, the leukocyte P-selectin ligand, but have been ambiguous on whether this enzyme is involved in E-selectin ligand formation. Using an attachment and rolling assay under defined shear flow in vitro, this study shows that C2GlcNAcT-I(-) lymphoid cells stably transfected with FucT-VII complementary DNA attach and roll well on E-selectin at 1.5 dynes/cm.(2) Further, attachment and rolling on P-selectin of neutrophils is sharply reduced and that of short- term polarized Th1 cells is virtually abolished, with leukocytes from C2GlcNAcT-I(-/-) mice. In contrast, both neutrophils and Th1 cells from C2GlcNAcT-I(-/-) mice attach and roll as well as wild-type cells on E-selectin. These results show that C2GlcNAcT-I is selectively required for biosynthesis of ligands for P-selectin, but is not essential for at least some E-selectin ligands. Distinct requirements for C2GlcNAcT-I in the formation of ligands for E-selectin versus P-selectin represents a novel level of regulation of expression of selectin ligands and lymphocyte traffic. (Blood. 2001;97:3806-3811)
A Probabilistic Perspective on Risk-sensitive Reinforcement Learning (2022)

Robustness is a key enabler of real-world applications of Reinforcement Learning (RL). The robustness properties of risk-sensitive controllers have long been established. We investigate risk-sensitive Reinforcement Learning (as a generalization of risk-sensitive stochastic control), by theoretically analyzing the risk-sensitive exponential (exponential of the total reward) criteria, and the benefits and improvements the introduction of risk-sensitivity brings to conventional RL. We provide a probabilistic interpretation of (I) the risk-sensitive exponential, (II) the risk-neutral expected cumulative reward, and (III) the maximum entropy Reinforcement Learning objectives, and explore their connections from a probabilistic perspective. Using Probabilistic Graphical Models (PGM), we establish that in the RL setting, maximization of the risk-sensitive exponential criteria is equivalent to maximizing the probability of taking an optimal action at all time-steps during an episode. We show that the maximization of the standard risk-neutral expected cumulative return is equivalent to maximizing a lower bound, particularly the Evidence lower Bound, on the probability of taking an optimal action at all time-steps during an episode. Furthermore, we show that the maximization of the maximum-entropy Reinforcement Learning objective is equivalent to maximizing a lower bound on the probability of taking an optimal action at all time-steps during an episode, where the lower bound corresponding to the maximum entropy objective is tighter and smoother than the lower bound corresponding to the expected cumulative return objective. These equivalences establish the benefits of risk-sensitive exponential objective and shed lights on previously postulated regularized objectives, such as maximum entropy. The utilization of a PGM model, coupled with exponential criteria, offers a number of advantages (e.g. facilitate theoretical analysis and derivation of bounds).
Secondary Efficacy Outcomes from COMPASS: A Comparison of Breath Powered™ Device Containing 22 mg Sumatriptan Powder (AVP-825) Versus Oral 100 mg Sumatriptan in Episodic Migraine (P3.059) (2015)

OBJECTIVE: Compare efficacy of AVP-825 (22mg sumatriptan powder) and 100mg oral sumatriptan using secondary measures from the COMPASS study (NCT01667679) in adults with episodic migraines. BACKGROUND: AVP-825 is an investigational Breath Powered™ Bi-Directional™ device that delivers low-dose sumatriptan powder deep into the nasal cavity. In COMPASS, AVP-825 produced significantly greater benefit over the first 30 minutes (SPID-30) and at every timepoint between 15-90 minutes vs oral sumatriptan (primary results reported separately). DESIGN/METHODS: Multicenter, double-dummy, multi-attack crossover study with two 12-week double-blind periods. Migraineurs (2-8 attacks/month) were randomized to AVP-825 plus oral placebo or identical placebo device plus 100mg oral sumatriptan for period-1; treatments switched for period-2. Patients treated ≤5 migraines/period (<1 hour from onset, even if mild). Secondary efficacy measures included pain freedom for mild vs moderate/severe migraines, presence of migraine-associated symptoms, meaningful pain relief, pain reduction, and Clinical Disability Scale. RESULTS: 185 patients treated migraines in both periods (1531 migraines assessed). For migraines treated when pain was mild, pain freedom rate was significantly greater with AVP-825 vs oral sumatriptan at 30 (29.3[percnt] vs 17.9[percnt] P=.0004) and 45 minutes post-dose. For migraines treated when pain was moderate/severe, pain freedom rate was significantly greater with AVP-825 from 15-90 minutes (30 minutes: 12.6[percnt] vs 7.7[percnt] P=.0308). Compared with oral sumatriptan, AVP-825 showed: significantly lower nausea rates (30-90 minutes); significantly reduced photophobia (10-60 minutes) and phonophobia (15-60 minutes); and significant differences in meaningful pain relief (10-60 minutes). Pain reduction rate was significantly greater with AVP-825 (15-60 minutes); Clinical Disability Scale was significantly lower for AVP-825 (10-90 minutes). ≤2[percnt] of patients discontinued due to adverse events (AEs); no AEs were serious. CONCLUSIONS: AVP-825 (22mg sumatriptan powder) produced faster migraine pain and symptom relief than 100mg oral sumatriptan. Support: Avanir Pharmaceuticals, Inc.
Methotrexate and cytarabine inhibit progression of human lymphoma in NOD/SCID mice carrying a mutant dihydrofolate reductase and cytidine deaminase fusion gene (2004)

An SFG-based retroviral bicistronic vector containing a double-mutant dihydrofolate reductase-cytidine deaminase fusion cDNA (F/S DHFR-CD) with IRES-eGFP confers resistance to both methotrexate (MTX) and cytarabine (ara-C). Two weeks after transplantation with marrow transduced with either a fusion or a control gene (eGFP-IRES-NeoR), human lymphoma (SKI-DLCL-1) cells were injected sc into the flanks of nonobese diabetic/severe combined immune deficiency mice. In mock-transplanted mice, maximal tolerated dose (MTD) of posttransplant MTX/ara-C (15/10 mg/kg/day, x3) was unable to control tumor growth. Transfer of the fusion gene allowed doses of MTX/ara-C (25/15 mg/kg/day, x4) twofold higher than the MTD to be tolerated. The tumor burden defined the efficiency of posttransplant chemotherapy; early treatment, 48 h after tumor inoculation, provided tumor-free survival, while starting treatment after having palpable tumor growth (7 days) delayed tumor growth a median time of 28 days. In addition, the early treated group had higher gene expression in peripheral blood and marrow cells than the late treated group (P < 0.05), suggesting that early treatment allowed for enrichment of transduced marrow progenitors. These results encourage clinical studies using this retroviral fusion gene construct.