gebhart/patrepeval huggingface dataset:
Chaperone-mediated autophagy is involved in the execution of ferroptosis (2019)

Necroptosis and ferroptosis are two distinct necrotic cell death modalities with no known common molecular mechanisms. Necroptosis is activated by ligands of death receptors such as tumor necrosis factor-α (TNF-α) under caspase-deficient conditions, whereas ferroptosis is mediated by the accumulation of lipid peroxides upon the depletion/or inhibition of glutathione peroxidase 4 (GPX4). The molecular mechanism that mediates the execution of ferroptosis remains unclear. In this study, we identified 2-amino-5-chloro-N,3-dimethylbenzamide (CDDO), a compound known to inhibit heat shock protein 90 (HSP90), as an inhibitor of necroptosis that could also inhibit ferroptosis. We found that HSP90 defined a common regulatory nodal between necroptosis and ferroptosis. We showed that inhibition of HSP90 by CDDO blocked necroptosis by inhibiting the activation of RIPK1 kinase. Furthermore, we showed that the activation of ferroptosis by erastin increased the levels of lysosome-associated membrane protein 2a to promote chaperone-mediated autophagy (CMA), which, in turn, promoted the degradation of GPX4. Importantly, inhibition of CMA stabilized GPX4 and reduced ferroptosis. Our results suggest that activation of CMA is involved in the execution of ferroptosis.
50 tesla superconducting solenoid for fast muon cooling ring (2007)

A conceptual design is presented for the 50 Tesla superconducting solenoids that are required for an optimized fast cooling ring in current designs for multi-TeV muon colliders. The solenoid utilizes high-performance multifilament Bi-2212/Ag round strand. The conductor is a cable-in-conduit consisting of six such strands cabled around a thin-wall spring tube then drawn within an outer sheath. The spring tube and the sheath are made from high-strength superalloy Inconel. The solenoid coil comprises 5 concentric shells supported independently in the conventional manner. Each shell consists of a winding of the structured cable, impregnated in the voids between cables but empty inside so that the spring tubes decouple stress so that it cannot strain- degrade the fragile strands, and a high-E stress shell. An expansion bladder is located between the winding and the stress shell. It is pressurized and then frozen to provide hydraulic compressive preload to each shell. These provisions makes it possible to accommodate ~10 T field contribution from each shell without degradation, and to distribute refrigeration so that heat is removed throughout the volume of the windings.
Influence of Seed Pre-treatments with Plant Growth Regulators on Metabolic Alterations of Germinating Maize Embryos Under Stressing Temperature Regimes (1989)

The germination performance of maize seeds (Zea mays L. cv. Partap-1) pre-treated individually with the substituted phthalimide AC 94,377 (1-(3-chlorophthalimido)-cyclohexanecarboxamide), GA4+7 and ABA was markedly improved under sub- and supra-optimal temperature regimes. ABA was especially stimulatory at the sub-optimal temperature. Metabolic alterations in the germinating embryos of treated seeds revealed an increased accumulation of soluble sugars and proteins compared with the controls under stressing temperatures. The activities of acid phosphatase, invertase, catalase and peroxidase were seemingly related to the alleviation metabolism. It is suggested that gibberellins and abscisic acid may have positive regulatory effects in triggering the system for stress alleviation.
Optimal algorithms for hierarchical web caches (2013)

Hierarchical topologies have been applied in many existing systems that provide public IPTV or massive content delivery services. The efficient operation of these services requires massive bandwidth resources. Data caching has emerged as an effective way in reducing bandwidth consumption and accelerating content access. In hierarchical caching systems requests for content are routed upwards until they reach a cache that stores a copy of the requested file. When the requested file is found, it is sent on the reverse path to the client. In this work, we focus on the problem of caching redundant copies of content in intermediate caches on the reverse path in order to minimize the bandwidth consumption within a given time horizon. The above problem is known to be NP-hard. However, we show that replacing the cache capacity constraints by a cost term paid each time we store a file in a cache, results to the tractable problem of minimizing the overall bandwidth and caching expenses. We use its optimal solution to establish a novel algorithm for the efficient solution of the original problem. We furthermore study the case that segments of encoded versions of the files instead of only complete files are allowed to be stored at the caches. We show that this problem is of polynomial complexity. Numerical experiments for typical popularity distributions reveal the performance distance between the proposed algorithms and heuristic algorithms that are commonly applied nowadays.
Endothelins and pulmonary diseases (1994)

Endothelins (ETs) are expressed in several types of cell in human lung, including airway epithelial cells, pulmonary vascular endothelial cells, submucosal glands, and type II pneumocytes. There is evidence for increased expression of ET-1 in several pulmonary diseases, including asthma, fibrosing alveolitis, and pulmonary hypertension, suggesting that ET-1 may play a pathophysiological role. ET binding sites are widely distributed and are localized to airway and pulmonary vascular smooth muscle, fibroblasts, submucosal glands, and airway nerves, indicating that ETs may have widespread effects. ET-1 and ET-3 are potent constrictors of human airway smooth muscle via a direct effect on ET receptors in airway smooth muscle; these receptors are probably ETB receptors. ETs may have other effects on airway function, including constriction of bronchial vessels, increased plasma exudation, increased mucus secretion, airway smooth muscle hyperplasia, and possibly increased fibrogenesis; these effects may be mediated via ETA receptors. ET-1 is a potent constrictor of human pulmonary vessels, whereas ET-3 is less effective, suggesting a predominance of ETA receptors. Similarly, chemotaxis and mitogenesis of pulmonary vascular fibroblasts and smooth muscle are mediated via ETA receptors. These findings implicate ETs in various pulmonary diseases and suggest that ET antagonists may be useful in their treatment.
Genome‐wide analysis reveals conserved transcriptional responses downstream of resting potential change in <i>Xenopus</i> embryos, axolotl regeneration, and human mesenchymal cell differentiation (2015)

Endogenous bioelectric signaling via changes in cellular resting potential (V mem) is a key regulator of patterning during regeneration and embryogenesis in numerous model systems. Depolarization of V mem has been functionally implicated in dedifferentiation, tumorigenesis, anatomical re-specification, and appendage regeneration. However, no unbiased analyses have been performed to understand genome-wide transcriptional responses to V mem change in vivo. Moreover, it is unknown which genes or gene networks represent conserved targets of bioelectrical signaling across different patterning contexts and species. Here, we use microarray analysis to comparatively analyze transcriptional responses to V mem depolarization. We compare the response of the transcriptome during embryogenesis (Xenopus development), regeneration (axolotl regeneration), and stem cell differentiation (human mesenchymal stem cells in culture) to identify common networks across model species that are associated with depolarization. Both subnetwork enrichment and PANTHER analyses identified a number of key genetic modules as targets of V mem change, and also revealed important (well-conserved) commonalities in bioelectric signal transduction, despite highly diverse experimental contexts and species. Depolarization regulates specific transcriptional networks across all three germ layers (ectoderm, mesoderm, and endoderm) such as cell differentiation and apoptosis, and this information will be used for developing mechanistic models of bioelectric regulation of patterning. Moreover, our analysis reveals that V mem change regulates transcripts related to important disease pathways such as cancer and neurodegeneration, which may represent novel targets for emerging electroceutical therapies.
Optical Proximity Correction (2009)

In low k 1 imaging, high-spatial-frequency components of the mask spectrum carry a sizable fraction of the transmitted light energy. These components are not captured by the low-pass pupil. For example, only the first orders are used in the imaging of dense patterns with periods p Ì â¤1 under off-axis illumination. As a result, images are distorted from the original patterns because of the loss of these high-frequency components. There are primarily four types of image shape distortion. They are illustrated in Fig. 4.1. Proximity effect refers to features with the same nominal critical dimension (CD) printing differently because of environmental variations. The most typical scenario is shown in Fig. 4.1 (a), which plots the printed dimension of a nominally d Ì =0.4 line as a function of pitch. As the pitch increases separation between adjacent lines widens; the imaged linewidth varies by as much as 15% as spacing changes. This type of distortion results in increased across-chip linewidth variation (ACLV). Image distortion also manifests itself as nonlinearity. As opposed to proximity effect, which describes variation of the same nominal CD with environment, nonlinearity refers to changes of the nominal CD not reflected linearly in the printed image. Figure 4.1(b) shows the simulated linewidth as a function of the effective mask size. For large dimensions, a unit change in nominal dimension results in a unit change in the printed dimension, but nonlinearity becomes an increasing concern as the CD decreases. In addition to increased linewidth variation, nonlinearity can also lead to nonprinting of critical features.
Adversarial Generative Nets: Neural Network Attacks on State-of-the-Art Face Recognition. (2018)

In this paper we show that misclassification attacks against face-recognition systems based on deep neural networks (DNNs) are more dangerous than previously demonstrated, even in contexts where the adversary can manipulate only her physical appearance (versus directly manipulating the image input to the DNN). Specifically, we show how to create eyeglasses that, when worn, can succeed in targeted (impersonation) or untargeted (dodging) attacks while improving on previous work in one or more of three facets: (i) inconspicuousness to onlooking observers, which we test through a user study; (ii) robustness of the attack against proposed defenses; and (iii) scalability in the sense of decoupling eyeglass creation from the subject who will wear them, i.e., by creating universal sets of eyeglasses that facilitate misclassification. Central to these improvements are adversarial generative nets, a method we propose to generate physically realizable attack artifacts (here, eyeglasses) automatically.
Synthesis of bicyclic 1,4-thiazepines as novel anti-<i>Trypanosoma brucei brucei</i> agents (2019)

1,4-Thiazepines derivatives are pharmacologically important heterocycles with different applications in medicinal chemistry. In the present work, we describe the preparation of new bicyclic thiazolidinyl-1,4-thiazepines <b>3</b> by reaction between azadithiane compounds and Michael acceptors. The reaction scope was explored and the yields were optimized. The activity of the new compounds was evaluated against <i>Nippostrongylus brasiliensis</i> and <i>Caenorhabditis elegans</i> as anthelmintic models and <i>Trypanosoma brucei brucei.</i> The most active compound was <b>3l</b>, showing an EC<sub>50</sub> = 2.8 ± 0.7 μM against <i>T. b. brucei</i> and a selectivity index >71.
The Antioxidant Vitamins and Cardiovascular Disease: A Critical Review of Epidemiologic and Clinical Trial Data (1995)

The epidemiologic data suggest that antioxidant vitamins reduce cardiovascular disease, with the clearest effect for vitamin E; however, completed randomized trials do not support this finding. Much of this controversy should be resolved by the ongoing large-scale and long-term randomized trials designed specifically to evaluate effects on cardiovascular disease.
The Development of Orange Pigment Overlying Choroidal Metastasis (2015)

The development of orange pigment is not pathognomonic for choroidal melanoma but may be seen in other lesions such as carcinoma metastasis.
Collaborative Radio Resource Management for femto-cell networks (2010)

This paper investigates Collaborative Radio Resource Management (CRRM) for femto-cell network deployments. The aim of the approach is to exploit the advantages of rapid and un-planned deployment of femto-cells, supporting more than one Radio Access Technology (RAT). The proposed approach overcomes deficiencies in existing methods that rely either on accurate determination geographic location, proximity or simultaneous support for multiple RATs. The aim of the proposed approach is to exploit the opportunities for femto-cells to use different RAT and RAT modes (such as frequency bands or bandwidths) and determine how best to share radio resources. The first problem in achieving this goal is RAT selection, followed by determining when to trigger handover of RAT and finally when to reconfigure RAT mode (such as change frequency band or bandwidth of the RAT). In this paper we address these problems and assess the advantages of a novel lightweight method of supporting CRRM functions.
An Open Label, Dose Escalation Study of AVE9633 Administered as a Single Agent by Intravenous (IV) Infusion Weekly for 2 Weeks in 4-Week Cycle to Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia (AML). (2007)

Abstract AVE9633/huMy9-6-DM4 is an immunoconjugate composed of a humanized monoclonal IgG1 antibody, huMy9-6, which specifically targets the CD33 antigen, conjugated through a disulfide link to the maytansine derivative DM4, a potent tubulin inhibitor. The CD33 antigen is expressed on the surface of myeloid cells. After the conjugate is bound to the CD33 antigen it is internalized and the cytotoxic is released within the target cell. We report preliminary results of the ongoing phase I dose escalation study of AVE9633 in patients with refractory/relapsed CD33+ AML. The study regimen consists of AVE9633 IV infusion on Day 1 and Day 8 of a 28-day cycle. To date, dose levels of 30 (n=1), 50 (n=3), 75 (n=3), 105 (n=3) and 130 (n=3) mg/m2 on Day 1 and Day 8 have been investigated. Patients received 1 (n=2), 2 (n=5), 3 (n=2) and 4 (n=4) cycles of AVE9633. No dose-limiting toxicity was noted so far. Nine patients experienced mild to moderate infusion reactions, mostly on Day1 of Cycle1. One patient at 130 mg/m2 presented grade 3 ALT elevation of 3 days duration. Free DM4, measured by LC/MS/MS was detectable at 105 and 130 mg/m2 in the range of 5 to 10 ng/mL. AVE9633/huMy9-6-DM4 exposure (measuring, by ELISA method, all antibodies containing at least one molecule of DM4) increased proportionally with the administered dose. Using Flow Cytometry Assay, saturation and down regulation of CD33 on peripheral and marrow blasts were observed from the dose of 50 mg/m2. There was one CRp in a 68-year old woman with refractory AML, achieved after 4 cycles of AVE9633 given at 105 mg/m2 × 2, with a 4-month continuing CRp as of 7/07 (she is receiving AVE9633 105 mg/m2 once monthly). One PR occurred in a 81-year old woman with refractory AML after one cycle at 130 mg/m2 × 2, persistent after the second cycle (third cycle is ongoing). Two patients had &gt;50% decrease in bone marrow blasts, at 105 mg/m2 × 2 (from 25% to 8% after two cycles) and at 130 mg/m2 × 2 (from 35% to 9% after one cycle). One additional patient at 75 mg/m2 × 2 presented clearance of peripheral blasts by Day 10 of Cycle1. Mean DM4/IgG on the surface of peripheral blasts (available for one patient at 130 mg/m2) progressively decreased after the infusion, from 3.09 on day 1 to 0.28 on Day 8, and then increased to 2.64 after the second infusion of AVE9633 on Day 8. These preliminary results show that AVE9633 is well tolerated, with manageable safety profile, allowing outpatient treatment. Evidence of anti-leukemia activity was observed in 5 patients. The study is continuing with the evaluation of 150 mg/m2 × 2. Evaluation of closer drug administrations which might enhance efficacy appears warranted.
Fiber Bragg grating inscription by high-intensity femtosecond UV laser light: comparison with other existing methods of fabrication (2005)

By use of high-intensity (approximately 200 GW/cm2) femtosecond 264-nm laser light and a phase mask technique, Bragg grating inscription in a range of different photosensitive and standard telecom fibers (both H2-free and H2-loaded) was studied. The dependences of the induced refractive index modulation versus the incident fluence as well as the thermal decay curves were compared with similar dependences for gratings fabricated by other existing methods. It was shown that with high-intensity UV laser irradiation, two-quantum photoreactions occur in the irradiated fiber core, that result in a significant photosensitivity enhancement of the investigated fibers in comparison with conventional low-intensity 248-nm exposure (by 6-128 times, depending on fiber type and irradiation intensity).
Abstract 3487: A novel role of transient receptor potential vanilloid type 2 (TRPV2) for augmentation of chemotherapeutic drug efficacy in triple-negative breast cancer (2015)

Abstract Transient receptor potential vanilloid type 2 (TRPV2) is a non-selective cation channel that is triggered by agonists like cannabidiol (CBD). Chemotherapeutic drugs such as doxorubicin (DOX) and paclitaxel (PAC) are routinely used for treatment of Triple negative breast cancer (TNBC) patients however, these drugs are usually resisted and show limited efficacy and more side effects at higher doses. In the present study, we analyzed the ability of TRPV2 activation in enhancing the chemotherapeutic efficacy in TNBC cells. Interestingly, we found that TRPV2 is significantly up regulated in primary and metastatic breast tumor tissues compared to normal breast tissues using tissue microarray analysis. In addition, using publically available Kaplan Miere Plotter datasets, we found that estrogen receptor (ER) negative patients with higher TRPV2 expression levels and committed to anti-tumor chemotherapy have significantly higher survival than patients committed to anti-tumor chemotherapy but have lower TRPV2 expression levels. Our in vitro studies showed that TNBC cells subjected to combination treatment of CBD and DOX show enhanced proliferation inhibition compared to cells treated with DOX only . Analysis of molecular mechanisms showed higher levels of cleaved PARP and cleaved Caspase-3 in combination treatment compared to Dox alone. Further studies revealed that CBD activates more uptake of DOX into TNBC cells. This increased uptake was abrogated upon treatment with specific TRPV2 blocker. Furthermore, TRPV2 blocker inhibited the increased levels of cleaved PARP and cleaved caspase-3 in the combination treatment. By using two orthotopic mouse model, we showed that mice treated with CBD in combination with doxorubicin have significantly less tumor weight, fewer Ki67 and CD31 positive cells, and significantly higher level of cleaved caspase 3 and cleaved PARP compared to the mice treated with CBD or DOX alone. This study suggests the use of TRPV2 agonists as an adjuvant therapy to improve the anti-tumor chemotherapeutic efficacy especially in TNBC patients. Citation Format: Mohamad M. Elbaz, Mohd W. Nasser, Helong Zhao, Ramesh K. Ganju. A novel role of transient receptor potential vanilloid type 2 (TRPV2) for augmentation of chemotherapeutic drug efficacy in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3487. doi:10.1158/1538-7445.AM2015-3487
Suppression of malignant growth of human breast cancer cells by ectopic expression of <i>integrin</i>‐<i>linked kinase</i> (2004)

Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells both in vitro and in vivo. ILK is expressed in normal breast tissue but is downregulated in metastatic breast cancer cell lines and in advanced breast cancers. Transfection of wild-type ILK into the MDA-MB-435 mammary carcinoma cells potently suppressed their growth and invasiveness in vitro and reduced the cells' ability to induce tumors and metastasize in athymic nude mice. Conversely, expression of the ankyrin repeat or catalytic domain mutants of ILK failed to suppress the growth of these cells. Growth suppression by ILK is not due to apoptosis but is mediated by its ability to block cell-cycle progression in the G1 phase and by modulating the levels of integrins. These findings directly demonstrate that ILK deficiency facilitates neoplastic growth and invasion and suggest a novel role for the ILK gene in the suppression of tumor metastasis.
Current Challenges in Translating Tissue-Engineered Heart Valves (2017)

Heart valve disease is a major health burden, treated by either valve repair or valve replacement, depending on the affected valve. Nearly 300,000 valve replacements are performed worldwide per year. Valve replacement is lifesaving, but not without complications. The in situ tissue-engineered heart valve is a promising alternative to current treatments, but the translation of this novel technology to the clinic still faces several challenges. These challenges originate from the variety encountered in the patient population, the conversion of an implant into a living tissue, the highly mechanical nature of the heart valve, the complex homeostatic tissue that has to be reached at the end stage of the regenerating heart valve, and all the biomaterial properties that can be controlled to obtain this tissue. Many of these challenges are multidimensional and multiscalar, and both the macroscopic properties of the complete heart valve and the microscopic properties of the patient's cells interacting with the materials have to be optimal. Using newly developed in vitro models, or bioreactors, where variables of interest can be controlled tightly and complex mixtures of cell populations similar to those encountered in the regenerating valve can be cultured, it is likely that the challenges can be overcome.
Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis (2010)

EudraCT No: 2005-002805-21.