gebhart/patrepeval huggingface dataset:
Reverse transcriptase inhibition potentiates target therapy in BRAF-mutant melanomas: effects on cell proliferation, apoptosis, DNA-damage, ROS induction and mitochondrial membrane depolarization (2020)

Target therapies based on BRAF and MEK inhibitors (MAPKi) have changed the therapeutic landscape for metastatic melanoma patients bearing mutations in the BRAF kinase. However, the emergence of drug resistance imposes the necessity to conceive novel therapeutic strategies capable to achieve a more durable disease control. In the last years, retrotransposons laying in human genome have been shown to undergo activation during tumorigenesis, where they contribute to genomic instability. Their activation can be efficiently controlled with reverse transcriptase inhibitors (RTIs) frequently used in the treatment of AIDS. These drugs have demonstrated anti-proliferative effects in several cancer models, including also metastatic melanoma. However, to our knowledge no previous study investigated the capability of RTIs to mitigate drug resistance to target therapy in BRAF-mutant melanomas. In this short report we show that the non-nucleoside RTI, SPV122 in combination with MAPKi strongly inhibits BRAF-mutant melanoma cell growth, induces apoptosis, and delays the emergence of resistance to target therapy in vitro. Mechanistically, this combination strongly induces DNA double-strand breaks, mitochondrial membrane depolarization and increased ROS levels. Our results shed further light on the molecular activity of RTI in melanoma and pave the way to their use as a novel therapeutic option to improve the efficacy of target therapy. Video Abstract.
Inhibition of neutrophil activation by <i>p</i>‐bromophenacyl bromide and its effects on phospholipase A<sub>2</sub> (1986)

In an effort to elucidate the nature of the inhibitory effects of p ‐bromophenacyl bromide (pBPB) on neutrophil stimulation, we have examined its effects on several stages of stimulus‐response coupling. Pretreatment of rat neutrophils with pBPB resulted in a dose‐ and time‐dependent irreversible inhibition of both N‐formylmethionyl‐leucylphenylalanine (fMet‐Leu‐Phe)‐induced lysosomal enzyme release and change in transmembrane potential. Inhibition of the biological responses to the chemotactic peptide f Met‐Leu‐Phe was not due to receptor inactivation since f Met‐Leu‐[ 3 H]‐Phe binding to the formyl peptide receptor was not significantly altered by pBPB pretreatment. Inhibition by pBPB of phorbol myristate acetate (PMA)‐induced changes in transmembrane potential and the generation of superoxide (0– 2 ) was also observed. pBPB treatment appeared to inhibit activation of the NADPH oxidase without a direct effect on the oxidase itself. This inhibitory effect was not accompanied by cell death or decrease in cellular titratable sulphydryl groups (at least at doses &lt; 20 μM). There was, however, significant inhibition of a membranous fraction of f Met‐Leu‐Phe‐induced phospholipase A 2 activity by pretreatment with 10 μM pBPB, although total cellular phospholipase A 2 was only minimally (&lt; 20% inhibition) affected. These data would indicate that pBPB inhibits an early event associated with stimulus‐response coupling in rat polymorphonuclear leukocytes (i.e. change in transmembrane potential). The inhibitory effects of pBPB may be secondary to the inhibition of a critical membranous fraction of cell bound phospholipase A 2 activity or its activation, necessary for the initiation of cell activation.
Electrospun PLGA and β-TCP (Rebossis-85) in a Lapine Posterolateral Fusion Model. (2019)

ReBOSSIS-85 can be used as an extender negating the need for large amounts of local or iliac crest bone in posterolateral fusions.
Analysis of Desiccation and Vitrification Characteristics of Carbohydrate Films by Shear-Wave Resonators (2005)

Desiccated state preservation of mammalian cells and tissues in the presence of carbohydrates has started to show promise in the last two decades. Certain carbohydrates play a major role in preservation by reducing molecular mobility in the desiccated state. In this communication, the feasibility of utilizing shear-wave resonators to collect real-time molecular mobility information during desiccation and vitrification of carbohydrate based thin films was demonstrated. Simultaneous quartz crystal microbalance experimentation and optical imaging were utilized to determine the conditions for thin film formation and the vitrification kinetics of certain carbohydrate solutions of biological importance. Using the technique presented here, it was possible to gain insight into the vitrification characteristics of carbohydrate solutions establishing the basics for future research with quantitative analysis of film properties and experimentation with live mammalian cells.
Modeling and control of a CLC Resonant Dual Active Bridge (2014)

This paper proposes a linear large signal state-space model for a phase controlled CLC (Capacitor Inductor Capacitor) Resonant Dual Active Bridge (RDAB). The proposed model is useful for fast simulation and for the estimation of state variables under large signal variation. The model is also useful for control design because the slow changing dynamics of the dq variables are relatively easy to control. Simulation results of the proposed model are presented and compared to the simulated circuit model to demonstrate the proposed model's accuracy. This proposed model was used for the design of a Proportional-Integral (PI) controller and it has been implemented in the circuit simulation to show the proposed models usefulness in control design.
Impact of β-glycerophosphate on the bioenergetic profile of vascular smooth muscle cells (2020)

In chronic kidney disease, hyperphosphatemia is a key pathological factor promoting medial vascular calcification, a common complication associated with cardiovascular events and mortality. This active pathophysiological process involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs) via complex intracellular mechanisms that are still incompletely understood. Little is known about the effects of phosphate on the bioenergetic profile of VSMCs during the onset of this process. Therefore, the present study explored the effects of the phosphate donor β-glycerophosphate on cellular bioenergetics of VSMCs. Mitochondrial and glycolytic functions were determined utilizing extracellular flux analysis in primary human aortic VSMCs following exposure to β-glycerophosphate. In VSMCs, β-glycerophosphate increased basal respiration, mitochondrial ATP production as well as proton leak and decreased spare respiratory capacity and coupling efficiency, but did not modify non-mitochondrial or maximal respiration. β-Glycerophosphate-treated VSMCs had higher ability to increase mitochondrial glutamine and long-chain fatty acid usage as oxidation substrates to meet their energy demand. β-Glycerophosphate did not modify glycolytic function or basal and glycolytic proton efflux rate. In contrast, β-glycerophosphate increased non-glycolytic acidification. β-Glycerophosphate-treated VSMCs had a more oxidative and less glycolytic phenotype, but a reduced ability to respond to stressed conditions via mitochondrial respiration. Moreover, compounds targeting components of mitochondrial respiration modulated β-glycerophosphate-induced oxidative stress, osteo-/chondrogenic signalling and mineralization of VSMCs. In conclusion, β-glycerophosphate modifies key parameters of mitochondrial function and cellular bioenergetics in VSMCs that may contribute to the onset of phenotypical transdifferentiation and calcification. These observations advance the understanding of the role of energy metabolism in VSMC physiology and pathophysiology of vascular calcification during hyperphosphatemia. KEY MESSAGES: β-Glycerophosphate modifies key parameters of mitochondrial respiration in VSMCs. β-Glycerophosphate induces changes in mitochondrial fuel choice in VSMCs. β-Glycerophosphate promotes a more oxidative and less glycolytic phenotype of VSMCs. β-Glycerophosphate triggers mitochondrial-dependent oxidative stress in VSMCs. Bioenergetics impact β-glycerophosphate-induced VSMC calcification.
Conversational In-Vehicle Dialog Systems: The past, present, and future (2016)

Automotive technology rapidly advances with increasing connectivity and automation. These advancements aim to assist safe driving and improve user travel experience. Before the realization of a full automation, in-vehicle dialog systems may reduce the driver distraction from many services available through connectivity. Even when a full automation is realized, in-vehicle dialog systems still play a special role in assisting vehicle occupants to perform various tasks. On the other hand, in-vehicle use cases need to address very different user conditions, environments, and industry requirements than other uses. This makes the development of effective and efficient in-vehicle dialog systems challenging; it requires multidisciplinary expertise in automatic speech recognition, spoken language understanding, dialog management (DM), natural language generation, and application management, as well as field system and safety testing. In this article, we review research and development (R&D) activities for in-vehicle dialog systems from both academic and industrial perspectives, examine findings, discuss key challenges, and share our visions for voice-enabled interaction and intelligent assistance for smart vehicles over the next decade.
Orally active 1-(cyclohexyloxycarbonyloxy)alkyl ester prodrugs of cefotiam. (1987)

Orally active 1-(alkyl substituted cyclohexyloxycarbonyloxy)alkyl ester prodrugs (9b-h) of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]-3- [[[1-(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thio]-methyl]ceph+ ++-3- em-4-carboxylic acid (cefotiam, CTM) have been studied as well as the thia (9i) and aza (9j) analogs. These represent derivatives of the 1-(cyclohexylacetoxy)ethyl ester (2) of CTM. The syntheses and oral bioavailability (BA) in mice are described. Among them, the 1-(cyclohexyloxycarbonyloxy)butyl ester (9h) gave the highest BA, 93.5%; the esters having a cyclohexyloxy group in the ester moiety gave BAs of more than 75%, although the BA of the 1-(ethoxycarbonyloxy)ethyl ester (9a) was only 23.9%. The thia analog showed a moderate BA, 46%, but the aza analog, 9j, did not show a BA of CTM. These results indicate that the 1-(substituted cyclohexyloxycarbonyloxy)alkyl group was the suitable promoiety to improve the oral BA of CTM. Chiral 1-(alkoxycarbonyloxy)alkyl groups used as the ester moiety, gave an almost 1: 1 mixture of diastereoisomeric esters. These were tested as such. However, an experiment in which the separated isomers of the 1-(cyclohexyloxycarbonyloxy)ethyl ester (9d) were administered orally confirmed that both diastereoisomers gave identical BAs.
Occult Ovarian Failure: A Syndrome of Infertility, Regular Menses, and Elevated Follicle-Stimulating Hormone Concentrations (1988)

Ten women with infertility, regular menses, and elevated plasma FSH concentrations after a failed in vitro fertilization attempt were studied throughout a spontaneous menstrual cycle. Plasma estradiol, progesterone, inhibin, LH, and FSH concentrations were measured by RIA on days 1, 8, 15, and 22 and compared with the ovarian steroid and gonadotropin profiles obtained from seven endocrine-normal women. The elevated FSH concentrations in the hypergonadotropic group were not associated with significant changes in E2 and P4, but an increase in LH concentrations was found on days 1, 8, and 22 (medians of 18 and 4, 17 and 6, and 7 and less than 3 U/L for the hypergonadotropic and normal groups, respectively; P less than 0.01). Their plasma inhibin concentrations [213, 242, 747, and 561 U/L (median values on days 1-7, 8-14, 15-21, and 22-28)] were normal. Autoantibodies to adrenal, thyroid, or ovary were present in five (50%) women, and antiovarian antibodies were present in 4. Two women gave a family history of thyroid disease, and one woman was hypothyroid. Repeat assessment 3-6 months revealed persistently elevated FSH concentrations in five (63%) of eight women; the other three had normal ovarian steroid and gonadotropin concentrations. The triad of infertility, regular menses, and elevated plasma FSH concentrations describes a group of women with occult ovarian failure, a condition of compensated granulosa cell function, which may be an early stage of premature ovarian failure. These women with occult ovarian failure had an impaired response to ovarian hyperstimulation and may be at increased risk of developing polyglandular autoimmunity.
Porous aligned ZnSr-doped β-TCP/silk fibroin scaffolds using ice-templating method for bone tissue engineering applications (2021)

The bone is a complex and dynamic structure subjected to constant stress and remodeling. Due to the worldwide incidence of bone disorders, tissue scaffolds and engineered bone tissues have emerged as solutions for bone grafting, which require sophisticated scaffolding architectures while keeping high mechanical performance. However, the conjugation of a bone-like scaffold architecture with efficient mechanical properties is still a critical challenge for biomedical applications. In this sense, the present study focused on the modulating the architecture of silk fibroin (SF) scaffolds crosslinked with horseradish peroxidase and mixed with zinc (Zn) and strontium (Sr)-doped β-tricalcium phosphate (ZnSr.TCP) to mimic bone structures. The ZnSr.TCP-SF hydrogels were tuned by programmable ice-templating parameters, and further freeze-dried, in order to obtain 3D scaffolds with controlled pore orientation. The results showed interconnected channels in the ZnSr.TCP-SF scaffolds that mimic the porous network of the native subchondral bone matrix. The architecture of the scaffolds was characterized by microCT, showing tunable pore size according to freezing temperatures (-196 °C: ∼80.2 ± 20.5 µm; -80 °C: ∼73.1 ± 20.5 µm; -20 °C: ∼104.7 ± 33.7 µm). The swelling ratio, weight loss, and rheological properties were also assessed, revealing efficient scaffold integrity and morphology after aqueous immersion. Thus, the ZnSr.TCP-SF scaffolds made of aligned porous structure were developed as affordable candidates for future applications in clinical osteoregeneration and <i>in vitro</i> bone tissue modelling.
Molecular Basis for Barbed End Uncapping by CARMIL Homology Domain 3 of Mouse CARMIL-1 (2010)

Capping protein (CP) is a ubiquitously expressed, 62-kDa heterodimer that binds the barbed end of the actin filament with approximately 0.1 nm affinity to prevent further monomer addition. CARMIL is a multidomain protein, present from protozoa to mammals, that binds CP and is important for normal actin dynamics in vivo. The CARMIL CP binding site resides in its CAH3 domain (CARMIL homology domain 3) located at or near the protein's C terminus. CAH3 binds CP with approximately 1 nm affinity, resulting in a complex with weak capping activity (30-200 nm). Solution assays and single-molecule imaging show that CAH3 binds CP already present on the barbed end, causing a 300-fold increase in the dissociation rate of CP from the end (i.e. uncapping). Here we used nuclear magnetic resonance (NMR) to define the molecular interaction between the minimal CAH3 domain (CAH3a/b) of mouse CARMIL-1 and CP. Specifically, we show that the highly basic CAH3a subdomain is required for the high affinity interaction of CAH3 with a complementary "acidic groove" on CP opposite its actin-binding surface. This CAH3a-CP interaction orients the CAH3b subdomain, which we show is also required for potent anti-CP activity, directly adjacent to the basic patch of CP, shown previously to be required for CP association to and high affinity interaction with the barbed end. The importance of specific residue interactions between CP and CAH3a/b was confirmed by site-directed mutagenesis of both proteins. Together, these results offer a mechanistic explanation for the barbed end uncapping activity of CARMIL, and they identify the basic patch on CP as a crucial regulatory site.
Minimizing the Risk of Casing Failures Across Plastic Salts with Tailored Cements and Software Analysis: Case Histories from the Williston Basin, North Dakota (2018)

Abstract A significant challenge associated with cementing across salt zones in the Williston basin is mitigating risks of casing collapse or deformation. An operator (Operator A) in this area reported that six of their old wells experienced casing failures/deformation caused by salt creep. Post-job analysis showed that these older wells used conventional cement designs. Based on the lessons learned from successful cement jobs for other operators in the same region and knowledge about salt creep loads, tailored fluid systems were proposed with optimized job design and placement procedures for Operator A's upcoming wells. This study demonstrates the benefits of the proposed modifications by comparing the logs and outcomes of old and new wells. Through post-job analysis, this study highlights the importance of using cementing simulation and modeling software to design a dependable barrier. The casing inspection logs and cement bond logs across salts from old wells indicated that deformation occurred within a few weeks of cementing. The use of a tailored cement system with enhanced mechanical properties, along with specialized spacer systems and effective centralization, showed improvement in bond logs, no casing deformation, and better casing-cement bonding in the new wells for Operator A. Pre-job simulations were performed using in-house cementing software to verify the cement job and to help ensure that the cement was effectively placed in the annulus. Cement sheath integrity modeling software was used to simulate the actual exerted loads from plastic salt formations and subsequent drilling, completion, and production operations. This software uses a semi-empirical creep law that describes the creep process of a wide variety of salts. The cement system with enhanced mechanical properties showed sufficient endurance to provide a dependable barrier to the salt creep loads experienced in Williston basin wells. Although the use of salt vs. salt-free slurries is debated for salt zone cementing, this study shows that salt-free cements with enhanced mechanical properties can be used successfully when there is no risk of cement gelation during placement. North Dakota salts principally contain halite (NaCl), which does not pose a risk of gelation. The case histories and field studies discussed establish cement systems and practices that can help to minimize the risk of casing deformation and improve the cement bond across salt zones in the Williston basin in North Dakota. This tailoring tool, with its unique ability to exert salt creep loads, helps to minimize the risk of cement sheath failure through tailored barrier designs. This information should help the petroleum industry to address long-term well integrity problems associated with cementing across plastic salts.
Soft robotic tentacle arm element actuated by rolled dielectric elastomer artificial muscles (2022)

Due to their suitability for human-robot interactions the importance of soft robots is increasing in the last years. In this paper, a Soft Robotic tentacle arm element actuated by rolled dielectric elastomer actuators (RDEAs) is presented. A 2D-bending-element has been developed which consists of a central vertical flexible beam and two rigid horizontal platforms onto which two antagonistic RDEA are connected. By exploiting the buckling instability of the beam, high angular deflections can be achieved. We consider this combination of a buckling beam and antagonistic RDEAs an important step towards realizing the full potential of DEAs as artificial muscles.
An Improved Authentication Protocol Dependent on Registration Center for Multiserver Environment (2017)

In many protocols, registration center (RC) is just responsible for users' and servers' registration, so a malicious server may cheat users to serve as another legal server. It's necessary to verify the legality of both users and servers with the help of a third trusted party such as RC. In 2012, Li et al. proposed a dynamic identity based authentication protocol for multiserver environment. But their protocol is susceptible to insider attack, eavesdropping attack, masquerade attack and password guessing attack. Besides, their protocol can't provide user's anonymity. In this paper, we propose an improved authentication protocol dependent on RC for multiserver environment to remedy the aforementioned security flaws. Compared with previous protocols independent on RC, in our protocol RC is one of parties in authentication phase to verify the legality of users and servers, which can effectively avoid server spoofing attack. Our protocol only uses nonce, one-way hash function and exclusive-OR operation in its implementation, and it is much more secure and practical.
Emission properties of apokamp discharge at atmospheric pressure in air, argon, and helium (2017)

Emission spectra of the plasma jet of apokamp discharge in air, helium, and argon are studied. Apokamp at atmospheric pressure is formed in the areas of strengthening of the electric field near the bends in the channel of the pulse-periodic discharge and is directed perpendicularly to the discharge channel. Apokamp consists of a bright narrow “appendage” connected with the discharge channel and with the diffuse jet emerging from the channel. It is shown that, in helium, the emission of the diffuse part of apokamp is dominated by N2 and N2 +, while emission of the “appendage” display lines and bands of He, N2, N2 +, O, and OH. In argon, emission spectra of the diffuse part of the plasma jets contain not only N2 and N2 +, but also Ar lines. It is assumed that the surrounding air plays an important role in the formation of the diffuse part of apokamp in helium and argon.
Thermo-optical behavior of rare-earth-doped low-NA fibers in high power operation (2006)

The influence of the internal temperature gradient in rare-earth-doped low-numerical-aperture fibers on modal properties is analyzed. We provide guidelines when a single-mode fiber turns into a multimode fiber and how the mode-field-diameter is affected.
ChemInform Abstract: Cation Control of Diastereoselectivity in Iridium‐Catalyzed Allylic Substitutions. Formation of Enantioenriched Tertiary Alcohols and Thioethers by Allylation of 5H‐Oxazol‐4‐ones and 5H‐Thiazol‐4‐ones. (2014)

Abstract Enantioselective Ir‐catalyzed allylation of substituted oxazolones occurs with high diastereoselectivity by employing the corresponding zinc enolates.
Current Issues of the Charcot-Marie-Tooth Disease (2007)

Hereditary motor and sensory neuropathy (HMSN), or Charcot-Marie-Tooth (CMT) disease, was described by Charcot and Marie in France and, independently, by Tooth in England in 1886. CMT is the most common form of inherited motor and sensory neuropathy, and is a genetically heterogeneous group of disorders in the peripheral nervous system. Traditionally, CMT has been subclassified into autosomal dominant inherited demyelinating (CMT1) and axonal (CMT2) neuropathies, X-linked neuropathy (CMTX), and autosomal recessive inherited neuropathy (CMT4). There are several related peripheral neuropathies, such as Déjérine-Sottas neuropathy (DSN), congenital hypomyelination neuropathy (CHN), hereditary neuropathy with liability to pressure palsies (HNPP), and giant axonal neuropathy (GAN). A large amount of new information on the genetic causes of CMT has become available, and mutations causing the disease have been associated with more than 20 different genes and 40 chromosomal loci. Advances in our understanding of the molecular basis of CMT have revealed an enormous diversity in genetic mechanisms, despite the clinical entity that is relatively uniform at presentation. Recent studies have shown therapeutic effects of certain chemicals in animal models of CMT1A, which suggests potential therapies for the most common form of CMT, CMT1A. This review focuses on the subgroups of inherited motor and sensory neuropathy on which there has been an explosion of new molecular genetic information over the past decade.