gebhart/patrepeval huggingface dataset:
Vasoprotection by nitric oxide: mechanisms and therapeutic potential (2002)

Endothelial production of nitric oxide (nitrogen monoxide, NO) has become a major research area in vascular biology. Some of the most important effects that NO exerts in the vascular wall are potentially vasoprotective, because these effects maintain important physiological functions such as vasodilation, anticoagulation, leucocyte adhesion, smooth muscle proliferation, and the antioxidative capacity. During the last 2 decades it has become apparent that a variety of diseases are associated with an impairment of endothelium-dependent NO activity. One of the major causes is believed to be an increased production of reactive oxygen species, in particular superoxide, which have been shown to interfere with many steps of the NO--cyclic guanosine monophosphate (cGMP) pathway. This phenomenon has been found in diverse conditions such as atherosclerosis, hypertension, diabetes, hypercholesterolemia, heart failure, and cigarette smoking. The aim of this review is to examine the cellular and molecular mechanisms whereby NO exerts potentially vasoprotective effects and to discuss pharmacologic approaches targeting the NO pathway in view of their potential to improve endothelial function and to reduce the progression of atherosclerotic vascular disease. We conclude that there is compelling evidence for vasoprotective actions of NO which are mediated by cGMP-dependent and cGMP-independent mechanisms. These effects may contribute to the beneficial effects of established drugs such as ACE inhibitors or statins. Unfortunately, clinical data on the effect of long-term treatment with nitrates on the progression of coronary artery disease are lacking. Finally, L-arginine or new activators of the NO pathway may become therapeutic options in the future.
Subtalar Joint Axis Location and Rotational Equilibrium Theory of Foot Function (2001)

A new theory of foot function based on the spatial location of the subtalar joint axis in relation to the weightbearing structures of the plantar foot is proposed. The theory relies on the concept of subtalar joint rotational equilibrium to explain how externally generated forces, such as ground reaction force, and internally generated forces, such as ligamentous and tendon tensile forces and joint compression forces, affect the mechanical behavior of the foot and lower extremity. The biomechanical effect of variations among individuals in the spatial location of the subtalar joint axis are explored, along with their clinical consequences, to offer an additional theory of foot function, which may improve on existing podiatric biomechanics theory.
Hyperkalemic cardioplegia for adult and pediatric surgery: end of an era? (2013)

Despite surgical proficiency and innovation driving low mortality rates in cardiac surgery, the disease severity, comorbidity rate, and operative procedural difficulty have increased. Today's cardiac surgery patient is older, has a "sicker" heart and often presents with multiple comorbidities; a scenario that was relatively rare 20 years ago. The global challenge has been to find new ways to make surgery safer for the patient and more predictable for the surgeon. A confounding factor that may influence clinical outcome is high K(+) cardioplegia. For over 40 years, potassium depolarization has been linked to transmembrane ionic imbalances, arrhythmias and conduction disturbances, vasoconstriction, coronary spasm, contractile stunning, and low output syndrome. Other than inducing rapid electrochemical arrest, high K(+) cardioplegia offers little or no inherent protection to adult or pediatric patients. This review provides a brief history of high K(+) cardioplegia, five areas of increasing concern with prolonged membrane K(+) depolarization, and the basic science and clinical data underpinning a new normokalemic, "polarizing" cardioplegia comprising adenosine and lidocaine (AL) with magnesium (Mg(2+)) (ALM™). We argue that improved cardioprotection, better outcomes, faster recoveries and lower healthcare costs are achievable and, despite the early predictions from the stent industry and cardiology, the "cath lab" may not be the place where the new wave of high-risk morbid patients are best served.
An Inductively Powered Scalable 32-Channel Wireless Neural Recording System-on-a-Chip for Neuroscience Applications (2010)

We present an inductively powered 32-channel wireless integrated neural recording (WINeR) system-on-a-chip (SoC) to be ultimately used for one or more small freely behaving animals. The inductive powering is intended to relieve the animals from carrying bulky batteries used in other wireless systems, and enables long recording sessions. The WINeR system uses time-division multiplexing along with a novel power scheduling method that reduces the current in unused low-noise amplifiers (LNAs) to cut the total SoC power consumption. In addition, an on-chip high-efficiency active rectifier with optimized coils help improve the overall system power efficiency, which is controlled in a closed loop to supply stable power to the WINeR regardless of the coil displacements. The WINeR SoC has been implemented in a 0.5-μ m standard complementary metal-oxide semiconductor process, measuring 4.9×3.3 mm(2) and consuming 5.85 mW at ±1.5 V when 12 out of 32 LNAs are active at any time by power scheduling. Measured input-referred noise for the entire system, including the receiver located at 1.2 m, is 4.95 μVrms in the 1 Hz~10 kHz range when the system is inductively powered with 7-cm separation between aligned coils.
Current status of integrated HFE V and V system of APR1400 (2006)

The first Advanced Light Water Reactor called Advanced Power Reactor (APR1400) has many specific features such as passive safety features, digital I and C, and digitalized main control room design. This digital-based neo-concept main control room design needs comprehensive verification and validation process to get the license for construction. An integrated system for APR1400 MMIS design validation is under development by KEPRI with the participating of KHNP. The facility which is based on the NUREG/CR-6393 and ANS3.5 can simulate all of the dynamic functions and responses of APR1400, and measure the human factors by using conventional subject methods and measuring the operator's biological signals. This system will be used in human factors V and V process of the PRM (NUREG0711) of APR1400 MMIS design. (authors)
Deeply-Recursive Convolutional Network for Image Super-Resolution (2016)

We propose an image super-resolution method (SR) using a deeply-recursive convolutional network (DRCN). Our network has a very deep recursive layer (up to 16 recursions). Increasing recursion depth can improve performance without introducing new parameters for additional convolutions. Albeit advantages, learning a DRCN is very hard with a standard gradient descent method due to exploding/ vanishing gradients. To ease the difficulty of training, we propose two extensions: recursive-supervision and skip-connection. Our method outperforms previous methods by a large margin.
Recent developments in superconducting cyclotrons (2002)

Superconducting cyclotrons have come of age: three machines have been operating on a regular basis since several years. These first generation machines have benefited from improvement programs and new equipment, while proposals for further expansion of their capabilities have been elaborated. The most significant events of 1994 have been the first beams in two new machines: the AGOR cyclotron in Orsay (France) and the K800 cyclotron in Catania (Italy). The first beam of the machine in Catania, Ni ions at 30 MeV/A, crowned a long construction effort, requiring transport of the magnet from Milan and assembly of the accelerator at its final location on the island of Sicily. AGOR, the first machine of a new generation, accelerated and extracted /spl alpha/-particles with an energy of 50 MeV/A, proving the validity of a number of novel design features. The vitality of the concept of using superconducting coils in a cyclotron is demonstrated by new proposals for such machines, to be used in cancer therapy.
Schistosome Calcium Channel β Subunits (2001)

Schistosomes are parasitic flatworms that cause schistosomiasis, a major tropical disease. The current drug of choice against schistosomiasis is praziquantel (PZQ), which has minimal side effects and is potent against all schistosome species. The mode of action of PZQ is unknown, though the drug clearly affects Ca(2+) homeostasis in worms, and there is indirect evidence for interaction of PZQ with schistosome voltage-gated Ca(2+) channels. We have cloned and expressed two Ca(2+) channel beta subunits, one from Schistosoma mansoni and one from Schistosoma japonicum. These two subunits (SmCa(v)beta A and SjCa(v)beta) have structural motifs that differ from those found in other known beta subunits. Surprisingly, coexpression of either SmCa(v)beta A or SjCa(v)beta with a cnidarian (CyCa(v)1) or mammalian (Ca(v)2.3) Ca(2+) channel alpha(1) subunit results in a striking reduction in current amplitude. In the case of Ca(v)2.3, this current reduction can be partially reversed by addition of 100 nm PZQ, which results in a significant increase in current amplitude. Thus, these unusual schistosome beta subunits can confer PZQ sensitivity to an otherwise PZQ-insensitive mammalian Ca(2+) channel, indicating that a possible target for PZQ action is the interaction between beta subunits and pore-forming alpha(1) subunits in schistosomes.
Discovery of Selective Irreversible Inhibitors for Bruton’s Tyrosine Kinase (2006)

A series of highly selective irreversible inhibitors for Bruton's tyrosine kinase (Btk) was developed using a structural bioinformatics approach. Their capabilities to modulate Btk's activity were characterized both in vitro and in vivo. Oral treatment with once-a-day dosing of compound 4 greatly inhibited disease development in a rodent rheumatoid arthritis (RA) model. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2452/2007/z600221_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Ordered and Coordinated Rearrangement of the TCR α Locus: Role of Secondary Rearrangement in Thymic Selection (2001)

The Ag receptor of the T lymphocyte is composed of an alphabeta heterodimer. Both alpha- and beta-chains are products of the somatic rearrangement of V(D)J segments encoded on the respective loci. During T cell development, beta-chain rearrangement precedes alpha-chain rearrangement. The mechanism of allelic exclusion ensures the expression of a single beta-chain in each T cell, whereas a large number of T cells express two functional alpha-chains. Here we demonstrate evidence that TCR alpha rearrangement is initiated by rearranging a 3' Valpha segment and a 5' Jalpha segment on both chromosomes. Rearrangement then proceeds by using upstream Valpha and downstream Jalpha segments until it is terminated by successful positive selection. This ordered and coordinated rearrangement allows a single thymocyte to sequentially express multiple TCRs with different specificities to optimize the efficiency of positive selection. Thus, the lack of allelic exclusion and TCR alpha secondary rearrangement play a key role in the formation of a functional T cell repertoire.
Phosphorylation of Moesin by Rho-associated Kinase (Rho-kinase) Plays a Crucial Role in the Formation of Microvilli-like Structures (1998)

Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, phosphorylates moesin at Thr558 in vitro. Here, using a site- and phosphorylation state-specific antibody, we found that the expression of dominant active RhoA in COS7 cells induced moesin phosphorylation and the formation of microvilli-like structures at apical membranes where the Thr558-phosphorylated moesin accumulated, whereas the expression of dominant negative Rho-kinase inhibited both of these processes. The expression of dominant active Rho-kinase also induced moesin phosphorylation. When COS7 cells expressing moesin or moesinT558A (substitution of Thr by Ala) were cultured under serum-depleted conditions, there were few microvilli-like structures, whereas microvilli-like structures remained in the cells expressing moesinT558D (substitution of Thr by Asp). The expression of moesinT558A inhibited the dominant active RhoA-induced formation of microvilli-like structures. These results indicate that Rho-kinase regulates moesin phosphorylation downstream of Rho in vivo and that the phosphorylation of moesin by Rho-kinase plays a crucial role in the formation of microvilli-like structures.
Multiple myeloma exhibits novel dependence on GLUT4, GLUT8, and GLUT11: implications for glucose transporter-directed therapy (2012)

Multiple myeloma is one of numerous malignancies characterized by increased glucose consumption, a phenomenon with significant prognostic implications in this disease. Few studies have focused on elucidating the molecular underpinnings of glucose transporter (GLUT) activation in cancer, knowledge that could facilitate identification of promising therapeutic targets. To address this issue, we performed gene expression profiling studies involving myeloma cell lines and primary cells as well as normal lymphocytes to uncover deregulated GLUT family members in myeloma. Our data demonstrate that myeloma cells exhibit reliance on constitutively cell surface-localized GLUT4 for basal glucose consumption, maintenance of Mcl-1 expression, growth, and survival. We also establish that the activities of the enigmatic transporters GLUT8 and GLUT11 are required for proliferation and viability in myeloma, albeit because of functionalities probably distinct from whole-cell glucose supply. As proof of principle regarding the therapeutic potential of GLUT-targeted compounds, we include evidence of the antimyeloma effects elicited against both cell lines and primary cells by the FDA-approved HIV protease inhibitor ritonavir, which exerts a selective off-target inhibitory effect on GLUT4. Our work reveals critical roles for novel GLUT family members and highlights a therapeutic strategy entailing selective GLUT inhibition to specifically target aberrant glucose metabolism in cancer.
A Sequential Niche Technique for Multimodal Function Optimization (1993)

A technique is described that allows unimodal function optimization methods to be extended to locate all optima of multimodal problems efficiently. We describe an algorithm based on a traditional genetic algorithm (GA). This technique involves iterating the GA but uses knowledge gained during one iteration to avoid re-searching, on subsequent iterations, regions of problem space where solutions have already been found. This gain is achieved by applying a fitness derating function to the raw fitness function, so that fitness values are depressed in the regions of the problem space where solutions have already been found. Consequently, the likelihood of discovering a new solution on each iteration is dramatically increased. The technique may be used with various styles of GAs or with other optimization methods, such as simulated annealing. The effectiveness of the algorithm is demonstrated on a number of multimodal test functions. The technique is at least as fast as fitness sharing methods. It provides an acceleration of between 1 and l0p on a problem with p optima, depending on the value of p and the convergence time complexity.
Understanding cytochrome c function: engineering protein structure by semisynthesis (1993)

Semisynthesis is a method of protein engineering that relies primarily on chemical manipulations of peptide fragments derived from natural proteins to produce intermediates for reassembly into defined analogs. In this respect it differs fundamentally from total chemical synthesis, but like it, it has unique capabilities for introducing noncoded amino acids or site-specific labels into the protein product. A favorite subject for semisynthesis is the redox protein cytochrome c: a vital link in the respiratory chain. The tactics that have evolved in the half dozen laboratories so engaged are briefly described. More than 100 semisynthetic analogs of this protein have resulted from this effort and have contributed to our understanding of the way in which the function of cytochrome c is determined by its three-dimensional structure. Questions concerning the folding and stability of the protein, the setting of heme redox potential, control and specificity of interaction with potential redox partners, and the mechanism of electron transfer are considered. A growing synergy between this approach and genetic methods will ensure that protein engineering by semisynthesis continues to increase our knowledge of this and other proteins.
The Nude mouse in experimental and clinical research (1978)

The nude mouse in experimental and clinical research , The nude mouse in experimental and clinical research , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Fast and sensitive liquid chromatography/electrospray mass spectrometry method to study ocular penetration of EDL‐155, a novel antitumor agent for retinoblastoma in rats (2009)

Our group has used the tetrahydroisoquinoline derivative EDL-155 to treat glioblastoma in animal models and it is currently being evaluated in the treatment of ocular cancers. The purpose of this study was to develop a rapid and sensitive liquid chromatography and tandem mass spectrometry (LC-MS/MS) method to study the plasma and vitreous humor disposition of EDL-155 in rats. Animals received a single periocular injection of EDL-155 (20 mg/kg). Animals were sacrificed at specified times (5, 60, 120, 240 and 360 min) and plasma and vitreous humor samples were obtained. EDL-155 was isolated by protein precipitation and the extracts were analyzed by reversed-phase high-pressure liquid chromatography (HPLC) with MS/MS detection. A structurally similar analog was used as internal standard (IS). The chromatographic run time was 3.5 min per injection. The mass spectrometer was operated in positive-ion, multiple reaction monitoring (MRM) mode. The mass transitions monitored were m/z332.2 --> 167.2 (EDL-155) and m/z391.2 --> 200.2 (IS). The lower limit of quantification (LLOQ) was 0.1 ng/ml in both vitreous humor and plasma. The method was validated for selectivity, linearity, accuracy and precision in rat vitreous humor and partially validated for accuracy and precision in rat plasma. The ion suppression, recovery and stability of the analyte in the biological matrix were also tested. The assay was rapid, sensitive and robust enough to support EDL-155 ocular penetration studies in a rodent model of intraocular cancer. Application of this method revealed that EDL-155 was rapidly passed into the vitreous humor following periocular administration. Further, vitreous humor exposure exceeded systemic exposure by approximately sevenfold. High local concentrations coupled with minimal systemic exposure supports further testing of EDL-155 as localized therapy for intraocular cancers.
Adaptive model-driven bit allocation for MPEG video coding (2000)

We present an adaptive model-driven bit-allocation algorithm for video sequence coding. The algorithm is based on a parametric rate-distortion model, and facilitates both picture-and macroblock-level bit allocation. A region classification scheme is incorporated into the algorithm, which exploits characteristics of human visual perception to efficiently allocate bits according to a region's visual importance. The application of this algorithm to MPEG video coding is discussed in detail. We show that the proposed algorithm is computationally efficient and has many advantages over the MPEG-2 TM5 bit-allocation algorithm.
Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779. (2002)

Recent work identifies the AKT kinase as a potential mediator of tumor expansion in multiple myeloma. The finding of PTEN mutations in several myeloma cell lines suggests that loss of PTEN function may be one mechanism by which AKT activity is increased in this disease. Because PTEN-deficient myeloma cells may have up-regulated activity of the mammalian target of rapamycin (mTOR), downstream of AKT, they may be particularly sensitive to mTOR inhibition. To test this hypothesis, we challenged myeloma cell lines with CCI-779, a newly developed analogue of rapamycin and an efficient inhibitor of mTOR. Three of four PTEN-deficient cell lines with constitutively active AKT were remarkably sensitive to cytoreduction and G(1) arrest induced by CCI-779 with ID(50) concentrations of <1 nM. In contrast, myeloma cells expressing wild-type PTEN were >1000-fold more resistant. Acute expression of a constitutively active AKT gene in CCI-779-resistant myeloma cells containing wild-type PTEN and quiescent AKT did not convert them to the CCI-779-sensitive phenotype. Conversely, expression of wild-type PTEN in CCI-779-sensitive, PTEN-deficient myeloma cells did not induce resistance. Differential sensitivity did not appear to be due to differences in the ability of CCI-779 to inhibit mTOR and induce dephosphorylation of p70S6kinase or 4E-BP1. However, CCI-779 inhibited expression of c-myc in CCI-sensitive PTEN-null myeloma cells but had no effect on expression in CCI-resistant cells. In contrast, cyclin D1 expression was not altered in either sensitive or resistant cells. These results indicate that PTEN-deficient myeloma cells are remarkably sensitive to mTOR inhibition. Although the results of transfection studies suggest that the level of PTEN and AKT function per se does not regulate sensitivity, PTEN/AKT status may be a good predictive marker of sensitivity.
Novel Surfactant-Free Stable Colloidal Nanoparticles Made of Randomly Carboxylated Polystyrene Ionomers (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTNovel Surfactant-Free Stable Colloidal Nanoparticles Made of Randomly Carboxylated Polystyrene IonomersMei Li, Ming Jiang, Lei Zhu, and Chi WuView Author Information Department of Macromolecular Science, Fudan University, Shanghai 200433, China, and Department of Chemistry, The Chinese University of Hong Kong, Hong KongCite this: Macromolecules 1997, 30, 7, 2201–2203Publication Date (Web):April 7, 1997Publication History Received4 October 1996Revised12 February 1997Published online7 April 1997Published inissue 1 April 1997https://pubs.acs.org/doi/10.1021/ma961479bhttps://doi.org/10.1021/ma961479brapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views621Altmetric-Citations55LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Aromatic compounds,Colloidal particles,Hydrocarbons,Ionomers,Nanoparticles Get e-Alerts