gebhart/patrepeval huggingface dataset:
Enhanced Electron Flux and Reduced Calmodulin Dissociation May Explain “Calcium-independent” eNOS Activation by Phosphorylation (2000)

Bovine endothelial nitric oxide synthase (eNOS) is phosphorylated directly by the protein kinase Akt at serine 1179. Mutation of this residue to the negatively charged aspartate (S1179D eNOS) increases nitric oxide (NO) production constitutively, in the absence of agonist challenge. Here, we examine the potential mechanism of how aspartate at 1179 increases eNOS activity using purified proteins. Examination of NO production and cytochrome c reduction resulted in no substantial changes in the K(m)/EC(50) for L-arginine, calmodulin, and calcium, whereas there was a 2-fold increase in the rate of NO production for S1179D and a 2-4-fold increase in reductase activity (based on cytochrome c reduction). The observed increase in activity for both assays of NOS function indicates that a faster rate of electron flux through the reductase domain is likely the rate-limiting step in NO formation from eNOS. In addition, S1179D eNOS did show an increased resistance to inactivation by EGTA compared with wild type eNOS. These results suggest that a negative charge imposed at serine 1179, either by phosphorylation or by replacement with aspartate, increases eNOS catalytic activity by increasing electron flux at the reductase domain and by reducing calmodulin dissociation from activated eNOS when calcium levels are low.
A Theoretical Study of Epidural Electrical Stimulation of the Spinal Cord Part I: Finite Element Analysis of Stimulus Fields (1985)

This first paper, of two, describes a three-dimensional finite element computer model representing nonhomogeneous electrical conductivity of the human thorax. The spinal canal is treated in detail, taking account of various tissue types and other biological materials. Solutions are presented for the electrical fields generated within the spinal cord from bipolar epidural electrodes. Included in an Appendix is a validation study which compares experimental data in the literature, for subdural electrode arrays in a monkey, to theoretical solutions following the same method as the main work.
A new cohesive short-stretch bandage and its application (2001)

The undisputed optimum treatment for venous leg ulcers is compression therapy, where an external appliance (multilayer, short-stretch bandaging and compression hosiery) promotes venous return through graduated compression of the tissues and capillaries. However, this is not always acceptable to the patient, particularly when the patient's social life is affected with malodour and pain associated with venous leg ulcers, thereby reducing quality of life. There is a psychosocial consideration when the bandaging system is bulky, hot and difficulty is found with the fitting of shoes. An alternative and clinically effective solution is essential if the wound is to heal. In this case study, the patient was provided with a cohesive and short-stretch compression bandage (Actico), which allowed her to continue her social life while effectively treating her ulcer.
Carbon in silicon: Modeling of diffusion and clustering mechanisms (2002)

Carbon often appears in Si in concentrations above its solubility. In this article, we propose a comprehensive model that, taking diffusion and clustering into account, is able to reproduce a variety of experimental results. Simulations have been performed by implementing this model in a Monte-Carlo atomistic simulator. The initial path for clustering included in the model is consistent with experimental observations regarding the formation and dissolution of substitutional C–interstitial C pairs (Cs–Ci). In addition, carbon diffusion profiles at 850 and 900 °C in carbon-doping superlattice structures are well reproduced. Finally, under conditions of thermal generation of intrinsic point defects, the weak temperature dependence of the Si interstitial undersaturation and the vacancy supersaturation in carbon-rich regions also agree with experimental measurements.
Advanced Glycation and Lipoxidation End Products (2000)

The uremic syndrome is usually attributed to the retention of a variety of compounds as a result of a deficient renal clearance. These retention solutes are taken to induce biochemical disorders characteristic of uremic complications. However, as recently noted by Vanholder and De Smet ([1][1]),
Lack of functional and expression homology between human and mouse aldo-keto reductase 1C enzymes: implications for modelling human cancers (2009)

This study exposes significant lack of phylogenetic and functional homology between human and murine AKR1C enzymes. Therefore, we conclude that mice are not suitable to model the role of AKR1C in human cancers and leukemia.
Photoreceptor Regulation of CONSTANS Protein in Photoperiodic Flowering (2004)

Many plants flower in response to seasonal fluctuations in day length. The CONSTANS (CO) gene of Arabidopsis promotes flowering in long days. Flowering is induced when CO messenger RNA expression coincides with the exposure of plants to light. However, how this promotes CO activity is unknown. We show that light stabilizes nuclear CO protein in the evening, whereas in the morning or in darkness the protein is degraded by the proteasome. Photoreceptors regulate CO stability and act antagonistically to generate daily rhythms in CO abundance. This layer of regulation refines the circadian rhythm in CO messenger RNA and is central to the mechanism by which day length controls flowering.
Low power consumption and high resolution 1280X960 Gate Assisted Photonic Demodulator pixel for indirect Time of flight (2020)

A 1280×960 floating diffusion storage global shutter image sensor is implemented in a 3D stacked back illuminated indirect time of flight sensor (iToF). The sensor, achieves 18,000e- full well capacity and 32% quantum efficiency (QE) with a pyramid surface for diffraction (PSD) structure [1], utilizing a 3.5µm pixel. Low power consumption is also achieved, due to low leakage current for the iToF pixel and low resistance Cu-Cu connection metal wiring. These device architectures enable high resolution and wide dynamic range 3D depth sensing for both near and far objects.
Antineoplastic agents 393. Synthesis of the trans-isomer of combretastatin A-4 prodrug. (1998)

The (E)-stilbene isomer (2a) of the (Z)-combretastatin A-4 prodrug (1b) was efficiently prepared from (E)-combretastatin A-4 by a reaction sequence employing phosphorylation (dibenzyl chlorophosphite), cleavage (trimethyliodosilane) of the benzyl ester and reaction of the resulting phosphoric acid with sodium methoxide. The sodium phosphate product (2c) was also found to be an important side-product, presumably from iodine-catalyzed isomerization, when the analogous synthetic route was used to obtain the combretastatin A-4 prodrug (1b). The phosphoric acid precursor of prodrug 1b derived from (Z)-combretastatin A-4 (1a) was converted into a series of metal cation and ammonium cation salts to evaluate effects on human cancer cell growth, antimicrobial activities and solubility behavior.
A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice (2009)

Massive liver resection and small-for-size liver transplantation pose a therapeutic challenge, due to increased susceptibility of the remnant/graft to ischemia reperfusion injury (IRI) and impaired regeneration. We investigated the dual role of complement in IRI versus regeneration in mice. Complement component 3 (C3) deficiency and complement inhibition with complement receptor 2-complement receptor 1-related protein y (CR2-Crry, an inhibitor of C3 activation) provided protection from hepatic IRI, and while C3 deficiency also impaired liver regeneration following partial hepatectomy (PHx), the effect of CR2-Crry in this context was dose dependent. In a combined model of IRI and PHx, either C3 deficiency or high-dose CR2-Crry resulted in steatosis, severe hepatic injury, and high mortality, whereas low-dose CR2-Crry was protective and actually increased hepatic proliferative responses relative to control mice. Reconstitution experiments revealed an important role for the C3a degradation product acylation-stimulating protein (ASP) in the balance between inflammation/injury versus regeneration. Furthermore, liver regeneration was dependent on the putative ASP receptor, C5L2. Several potential mechanisms of hepatoprotection and recovery were identified in mice treated with low-dose CR2-Crry, including enhanced IL-6 expression and STAT3 activation, reduced hepatic ATP depletion, and attenuated oxidative stress. These data indicate that a threshold of complement activation, involving ASP and C5L2, promotes liver regeneration and suggest a balance between complement-dependent injury and regeneration.
An FPGA architecture for DRAM-based systolic computations (2002)

We propose an FPGA chip architecture based on a conventional FPGA logic array core, in which I/O pins are clocked at a much higher rate than that of the logic array that they serve. Wide data paths within the chip are time multiplexed at the edge of the chip into much faster and narrower data paths that run off-chip. This kind of arrangement makes it possible to interface a relatively slow FPGA core with high speed memories and data streams, and is useful for many pin-limited FPGA applications. For efficient use of the highest bandwidth DRAMs, our proposed chip includes a RAMBUS DRAM interface, a burst-transfer controller, and burst buffers. This proposal is motivated by our work with virtual processor cellular automata (CA) machines-a kind of SIMD computer. Our next generation of CA machines requires reconfigurable FPGA-like processors coupled to the highest speed DRAMs and SRAMs available. Unfortunately, no current FPGA chips have appropriate DRAM I/O support or the speed needed to easily interface with pipelined SRAMs. The chips proposed would make a wide range of large-scale CA simulations of 3D physical systems practical and economical-simulations that are currently well beyond the reach of any existing computer. These chips would also be well suited to a broad range of other simulation, graphics and DSP-like applications.
Quantitative Proteomic Analysis of Dystrophic Dog Muscle (2011)

Duchenne muscular dystrophy (DMD) is caused by null mutations in the dystrophin gene, leading to progressive and unrelenting muscle loss. Although the genetic basis of DMD is well resolved, the cellular mechanisms associated with the physiopathology remain largely unknown. Increasing evidence suggests that secondary mechanisms, as the alteration of key signaling pathways, may play an important role. In order to identify reliable biomarkers and potential therapeutic targets, and taking advantage of the clinically relevant Golden Retriever Muscular Dystrophy (GRMD) dog model, a proteomic study was performed. Isotope-coded affinity tag (ICAT) profiling was used to compile quantitative changes in protein expression profiles of the vastus lateralis muscles of 4-month old GRMD vs healthy dogs. Interestingly, the set of under-expressed proteins detected appeared primarily composed of metabolic proteins, many of which have been shown to be regulated by the transcriptional peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α). Subsequently, we were able to showed that PGC1-α expression is dramatically reduced in GRMD compared to healthy muscle. Collectively, these results provide novel insights into the molecular pathology of the clinically relevant animal model of DMD, and indicate that defective energy metabolism is a central hallmark of the disease in the canine model.
A new class of photochromic 1,2-diarylethenes; synthesis and switching properties of bis(3-thienyl)cyclopentenes (1998)

A novel synthetic route to diarylethenes fixed in a cyclopentene based on titanium-mediated carbonyl coupling leads to bis(3-thienyl)cyclopentenes that show photochromic behaviour similar to that of known diarylethenes.
Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks (2016)

State-of-the-art object detection networks depend on region proposal algorithms to hypothesize object locations. Advances like SPPnet [1] and Fast R-CNN [2] have reduced the running time of these detection networks, exposing region proposal computation as a bottleneck. In this work, we introduce a Region Proposal Network (RPN) that shares full-image convolutional features with the detection network, thus enabling nearly cost-free region proposals. An RPN is a fully convolutional network that simultaneously predicts object bounds and objectness scores at each position. The RPN is trained end-to-end to generate high-quality region proposals, which are used by Fast R-CNN for detection. We further merge RPN and Fast R-CNN into a single network by sharing their convolutional features-using the recently popular terminology of neural networks with 'attention' mechanisms, the RPN component tells the unified network where to look. For the very deep VGG-16 model [3] , our detection system has a frame rate of 5 fps (including all steps) on a GPU, while achieving state-of-the-art object detection accuracy on PASCAL VOC 2007, 2012, and MS COCO datasets with only 300 proposals per image. In ILSVRC and COCO 2015 competitions, Faster R-CNN and RPN are the foundations of the 1st-place winning entries in several tracks. Code has been made publicly available.
Serial analysis of gene expression in non-small cell lung cancer. (1998)

We used the serial analysis of gene expression (SAGE) method to systematically analyze transcripts present in non-small cell lung cancer. Over 226,000 SAGE tags were sequence analyzed from two independent primary lung cancers and two normal human bronchial/tracheal epithelial cell cultures. A total of 226,000 SAGE tags were sequence identified, representing 43,254 unique transcripts. Comparison of the tags present in the tumor with those identified in the normal tissue revealed 175 transcript tags that were overrepresented in the normal tissue and 142 tags that were overexpressed in the tumor by 10-fold or more. Northern hybridization was performed on 15 of the most abundantly expressed tags identified in the tumors. These tags were derived from either a known gene or a matched expressed sequence tag clone. The transcripts for 3 of the 15 genes, PGP 9.5, B-myb, and human mutT, were abundantly expressed in primary lung cancers (10 of 18, 15 of 18, and 6 of 12 tumors, respectively). In contrast, the presence of PGP9.5 and B-myb was much less frequent in primary tumors derived from other tissue origins. These results suggest that at least a portion of the transcripts identified by SAGE are frequently associated with lung cancer, and that their overexpression may contribute to lung tumorigenesis. The identification and further characterization of genes generated by SAGE should provide potential new targets for the diagnosis, prognosis, and therapy of lung cancer.
Promiscuity as a functional trait: intrinsically disordered regions as central players of interactomes (2013)

Because of their pervasiveness in eukaryotic genomes and their unique properties, understanding the role that ID (intrinsically disordered) regions in proteins play in the interactome is essential for gaining a better understanding of the network. Especially critical in determining this role is their ability to bind more than one partner using the same region. Studies have revealed that proteins containing ID regions tend to take a central role in protein interaction networks; specifically, they act as hubs, interacting with multiple different partners across time and space, allowing for the co-ordination of many cellular activities. There appear to be three different modules within ID regions responsible for their functionally promiscuous behaviour: MoRFs (molecular recognition features), SLiMs (small linear motifs) and LCRs (low complexity regions). These regions allow for functionality such as engaging in the formation of dynamic heteromeric structures which can serve to increase local activity of an enzyme or store a collection of functionally related molecules for later use. However, the use of promiscuity does not come without a cost: a number of diseases that have been associated with ID-containing proteins seem to be caused by undesirable interactions occurring upon altered expression of the ID-containing protein.
How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension (2011)

Excess dietary salt is a major cause of hypertension. Nevertheless, the specific mechanisms by which salt increases arterial constriction and peripheral vascular resistance, and thereby raises blood pressure (BP), are poorly understood. Here we summarize recent evidence that defines specific molecular links between Na(+) and the elevated vascular resistance that directly produces high BP. In this new paradigm, high dietary salt raises cerebrospinal fluid [Na(+)]. This leads, via the Na(+)-sensing circumventricular organs of the brain, to increased sympathetic nerve activity (SNA), a major trigger of vasoconstriction. Plasma levels of endogenous ouabain (EO), the Na(+) pump ligand, also become elevated. Remarkably, high cerebrospinal fluid [Na(+)]-evoked, locally secreted (hypothalamic) EO participates in a pathway that mediates the sustained increase in SNA. This hypothalamic signaling chain includes aldosterone, epithelial Na(+) channels, EO, ouabain-sensitive α(2) Na(+) pumps, and angiotensin II (ANG II). The EO increases (e.g.) hypothalamic ANG-II type-1 receptor and NADPH oxidase and decreases neuronal nitric oxide synthase protein expression. The aldosterone-epithelial Na(+) channel-EO-α(2) Na(+) pump-ANG-II pathway modulates the activity of brain cardiovascular control centers that regulate the BP set point and induce sustained changes in SNA. In the periphery, the EO secreted by the adrenal cortex directly enhances vasoconstriction via an EO-α(2) Na(+) pump-Na(+)/Ca(2+) exchanger-Ca(2+) signaling pathway. Circulating EO also activates an EO-α(2) Na(+) pump-Src kinase signaling cascade. This increases the expression of the Na(+)/Ca(2+) exchanger-transient receptor potential cation channel Ca(2+) signaling pathway in arterial smooth muscle but decreases the expression of endothelial vasodilator mechanisms. Additionally, EO is a growth factor and may directly participate in the arterial structural remodeling and lumen narrowing that is frequently observed in established hypertension. These several central and peripheral mechanisms are coordinated, in part by EO, to effect and maintain the salt-induced elevation of BP.
Results of an Initial Experience With Custom-fit Positioning Total Knee Arthroplasty in a Series of 48 Patients (2008)

The custom-fit approach to total knee arthroplasty in conjunction with removal of osteophytes and preservation of ligaments rapidly returned function; restored motion, stability, and postoperative mechanical axis alignment; effected high patient satisfaction; and had an acceptable clinical outcome.
Intravenous golimumab in rheumatoid arthritis (2014)

Intravenous golimumab in a dosage of 2 mg/kg, initially given every 4 weeks but then every 8 weeks, in addition to methotrexate, is effective in the treatment of patients with rheumatoid arthritis. This weight-based infusion is administered over thirty minutes with an acceptable safety profile. Since it is a relatively new formulation, more time will be required to assess its specific role in the rheumatologists' armamentarium and to appreciate more fully its long-term safety.
Leakage-Abuse Attacks against Order-Revealing Encryption. (2016)

Order-preserving encryption and its generalization order-revealing encryption (OPE/ORE) allow sorting, performing range queries, and filtering data — all while only having access to ciphertexts. But OPE and ORE ciphertexts necessarily leak information about plaintexts, and what level of security they provide in practice has been unclear. In this work, we introduce new leakage-abuse attacks that recover plaintexts from OPE/ORE-encrypted databases. Underlying our new attacks is a framework in which we cast the adversary's challenge as a non-crossing bipartite matching problem. This allows easy tailoring of attacks to a specific scheme's leakage profile. In a case study of customer records, we show attacks that recover 99% of first names, 97% of last names, and 90% of birthdates held in a database, despite all values being encrypted with the OPE scheme most widely used in practice. We also show the first attack against the recent frequency-hiding Kerschbaum scheme, to which no prior attacks have been demonstrated. Our attack recovers frequently occurring plaintexts most of the time.
Interconnection Protocols for Interorganization Networks (1987)

This paper analyzes the technical implications of interconnecting networks across organization boundaries. Such Interorganizational Networks (ION's) are used increasingly to support exchange of CAD/CAM data between manufacturers and subcontractors, software distribution from vendors to users, customer input to suppliers' orderentry systems, and the shared use of expensive computational resources by research laboratories, as examples. We begin by demonstrating that interorganization connections are not satisfied by traditional network design criteria of connectivity and transparency. A primary high-level requirement is access control, and therefore, participating organizations must be able to limit connectivity and make network boundaries visible. We summarize an approach to access control in ION's, based on nondiscretionary control, that allows interconnecting organizations to combine gateway, network, and system-level mechanisms to enforce cross-boundary control over invocation and information flow while minimizing interference with internal operations [6], [4]. The focus of this paper is on the underlying interconnection protocols that are needed to support these access control mechanisms. We describe in detail a particular protocol, called a visa scheme [7]. The visa scheme uses access control servers to authorize a session request and visas to authenticate that successive packets belong to the authorized connection. Control is distributed among the ION participants and each may make its own design tradeoffs between performance and trust. In order to support interorganization communication two (or more) organizations must be able to communicate with one another's access control servers and their respective packet-level gateways and nodes (source/destination) must implement the visa scheme. The security of the proposed mechanism varies according to the security of an organization's components (access control server, gateway, and select hosts) and the encryption function used. The visa scheme's purpose is to allow an organization to modify and trust only those internal systems that require ION access; all other internal systems are inaccessible from and to the ION gateway. We conclude by comparing and contrasting the visa approach to the use of higher level gateways.