gebhart/patrepeval huggingface dataset:
Predicting distributions with Linearizing Belief Networks (2015)

Conditional belief networks introduce stochastic binary variables in neural networks. Contrary to a classical neural network, a belief network can predict more than the expected value of the output $Y$ given the input $X$. It can predict a distribution of outputs $Y$ which is useful when an input can admit multiple outputs whose average is not necessarily a valid answer. Such networks are particularly relevant to inverse problems such as image prediction for denoising, or text to speech. However, traditional sigmoid belief networks are hard to train and are not suited to continuous problems. This work introduces a new family of networks called linearizing belief nets or LBNs. A LBN decomposes into a deep linear network where each linear unit can be turned on or off by non-deterministic binary latent units. It is a universal approximator of real-valued conditional distributions and can be trained using gradient descent. Moreover, the linear pathways efficiently propagate continuous information and they act as multiplicative skip-connections that help optimization by removing gradient diffusion. This yields a model which trains efficiently and improves the state-of-the-art on image denoising and facial expression generation with the Toronto faces dataset.
Inside Windows NT infrastructures (1998)

From the Publisher:
With Windows NT becoming the dominant operating system in corporations today, IT professionals have a real need for hard answers to nuts-and-bolts questions about how to work with NT. This kind of information can really only be provided by Microsoft's NT Performance Group, where author David Iseminger works. As a result, this book contains real-world information that just hasn't been available before.
Enantioselective Heck Arylations of Acyclic Alkenyl Alcohols Using a Redox-Relay Strategy (2012)

Progress in the development of asymmetric Heck couplings of arenes and acyclic olefins has been limited by a tenuous understanding of the factors that dictate selectivity in migratory insertion and β-hydride elimination. On the basis of key mechanistic insight recently garnered in the exploration of selective Heck reactions, we report here an enantioselective variant that delivers β-, γ-, or δ-aryl carbonyl products from acyclic alkenol substrates. The catalyst system imparts notable regioselectivity during migratory insertion and promotes the migration of the alkene's unsaturation toward the alcohol to ultimately form the ketone product. The reaction uses aryldiazonium salts as the arene source, yields enantiomeric products from opposite starting alkene configurations, and uses a readily accessible ligand. The racemic nature of the alkenol substrate does not bias the enantioselection.
The uppers and downers of drug development : why do some drug projects succeed in development while others fail? : an exploration into the conditions associated with the success and failure of UK rare cancer drug projects (2016)

The organisation of drug development has radically changed in the last 40 years due to changes in the scientific knowledge base and the availability of new forms of finance. Stimulated by breakthroughs in biotechnology, new investment has facilitated changes to the strategies and structure of the industry. Furthermore, scientific advances have provided greater understanding of disease, drug targets and disease-drug interactions, particularly in oncology. Yet new ways of organising innovation bring new challenges. This thesis provides evidence to inform new policies and business models by assessing the non-technical conditions associated with the success and failure of drug development projects. The thesis presents an integrative theoretical framework that supports a multi-dimensional analysis of the network, organisation and individuals involved in drug projects. This approach is applied to case studies of 11 development projects for rare cancer drugs involving UK organisations. These cases are then compared and contrasted through a descriptive multi-case analysis and a Qualitative Comparative Analysis.
 
The findings contribute towards an understanding of the environmental conditions for the successful development of drugs. Firstly, the concept of project drag is introduced, to draw attention to the accumulation of issues during development that can cause projects lose momentum and lead to termination. The organisational environment around firms is found to be key; common disruptions are identified, particularly within small firms which are more vulnerable to industrial dynamics than larger organisations. This thesis also highlights mechanisms that can mediate adverse conditions; key individuals, their networks, power and consistent enthusiasm for projects can mediate project drag. The thesis also makes a methodological contribution in the formation and operationalisation of an integrative framework for project evaluation which provides a foundation for further research in this area. The thesis is concluded with policy recommendations of pathways that contribute towards the successful development of drug projects.
TSUNAMI: a path oriented scheme for algebraic test generation (2002)

An algorithm is presented for generating tests for single stuck line faults using a combination of algebraic processing and conventional path oriented search. Unlike conventional test generation algorithms, this algorithm uses algebraic methods to determine the complete set of input assignments that will propagate an error signal through a gate in a path to a primary output. The algorithm uses ordered binary decision diagrams (BDDs) for algebraic processing. For a large number of circuits that are amenable to analysis using BDDs, the algorithm is faster than previous algebraic methods. The algorithm has been implemented as the program TSUNAMI. Experimental results demonstrate that for most circuits TSUNAMI can generate test sets for all faults in fairly small amounts of time and is very efficient for hard-to-detect and redundant faults. Moreover, since a large set of tests is generated for each fault, these sets can be compacted to a very high degree. Using benchmark circuits as a reference, TSUNAMI obtains test sets up to 70% smaller than test sets generated by conventional algorithms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Self-aligned current confinement structure using AlAs/InP tunnel junction in GaInAsP/InP semiconductor lasers (1999)

We propose a current confinement structure which can be self-formed by thermal annealing of a electrode metal with a self-aligning process. The migrated metal selectively destroys an AlAs/InP tunnel junction to form a high resistance isolation layer. The hole current can be injected through a preserved tunnel junction window. We confirmed its lateral confinement effect from the near-field pattern of fabricated GaInAsP/InP stripe lasers. The proposed current confinement structure is very simple and useful for the lateral injection in semiconductor optical devices including long-wavelength vertical-cavity surface-emitting lasers.
Specificity of photolabeling of beta-cell membrane proteins with an 125I-labeled glyburide analog. (1992)

The interaction between sulfonylureas and membrane proteins from a hamster insulin-secreting tumor (HIT) cell line has been examined. Four HIT cell membrane proteins were covalently linked to an 125I-labeled glyburide analog by photolabeling. Three photolabeled polypeptides of M(r) 65,000, 55,000, and 30,000 were identified as low affinity "glyburide receptors." These proteins appear to be of similar abundance, when quantitated by photolabeling, with half-maximal displacements (Ki values) by glyburide, glipizide, and tolbutamide in the low micromolar range. The glyburide analog is more tightly bound to a M(r) 140,000 protein with dissociation constants, determined by filtration binding assays and by photolabeling, of 7 and 9.0 nM, respectively. The labeled analog was displaced from the M(r) 140,000 protein by glyburide, glipizide and tolbutamide with Ki values of 3.3 nM, 103 nM, and 25 microM, respectively, as estimated by photolabeling. Optimal conditions established for visualizing the M(r) 140,000 band on autoradiograms prepared after UV cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis include irradiating the radioligand-receptor complex at 1.5 J/cm2 at 312 nm, followed by heating samples in pH 9.0 sodium dodecyl sulfate-gel sample buffer. With receptor sites partially occupied (5 nM radioligand), approximately 0.75% of the protein is photocoupled to the radioligand and visualized by autoradiography. Our results confirm that the M(r) 140,000 polypeptide contains the beta-cell high affinity glyburide binding site and show that the second generation sulfonylurea antidiabetic drugs have a selective increase in affinity for this receptor.
Human insulin prepared by recombinant DNA techniques and native human insulin interact identically with insulin receptors. (1981)

Human insulin synthesized from A and B chains separately produced in Escherichia coli from cloned synthetic genes (prepared by the Eli Lilly Research Laboratories, Indianapolis, IN) was characterized by examining its interaction with human cultured lymphocytes, human circulating erythrocytes in vitro, and isolated rat fat cells. The binding behavior of the biosynthetic insulin with human cells was indistinguishable from that of native human or porcine insulins, with respect to affinity, association and dissociation kinetics, negative cooperativity, and the down-regulation of lymphocyte receptors. Similarly, the biosynthetic insulin was as potent as the native insulins in stimulating lipogenesis in isolated rat fat cells. We also examined the receptor binding characteristics of 125I-labeled human and porcine insulins monoiodinated solely at Tyr-A14, which were obtained by means of high-performance liquid chromatography of the iodination reaction mixture (this material was prepared by B. Frank, Eli Lilly Research Laboratories). In all aspects studied, the pure [TyrA14-125I]iodoinsulins were superior as tracers to the monoiodoinsulin purified by the more conventional method of gel filtration.
Palaeoecology of Triassic stem turtles sheds new light on turtle origins (2004)

Competing hypotheses of early turtle evolution contrast sharply in implying very different ecological settings-aquatic versus terrestrial-for the origin of turtles. We investigate the palaeoecology of extinct turtles by first demonstrating that the forelimbs of extant turtles faithfully reflect habitat preferences, with short-handed turtles being terrestrial and long-handed turtles being aquatic. We apply this metric to the two successive outgroups to all living turtles with forelimbs preserved, Proganochelys quenstedti and Palaeochersis talampayensis, to discover that these earliest turtle outgroups were decidedly terrestrial. We then plot the observed distribution of aquatic versus terrestrial habits among living turtles onto their hypothesized phylogenies. Both lines of evidence indicate that although the common ancestor of all living turtles was aquatic, the earliest turtles clearly lived in a terrestrial environment. Additional anatomical and sedimentological evidence favours these conclusions. The freshwater aquatic habitat preference so characteristic of living turtles cannot, consequently, be taken as positive evidence for an aquatic origin of turtles, but must rather be considered a convergence relative to other aquatic amniotes, including the marine sauropterygians to which turtles have sometimes been allied.
Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: participation of nitric oxide and TNF‐alpha (2007)

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, is recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of insulin and its combinations with resveratrol and curcumin in attenuating diabetic neuropathic pain. The study also aimed to examine the effect of these combinations on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels in streptozotocin (STZ) induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights compared with control mice. Chronic treatment with insulin (10 IU/kg/day, s.c.) and its combinations with antioxidants (resveratrol 20 mg/kg or curcumin 60 mg/kg, p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia and the hot-plate latencies. There was a significant inhibition of TNF-alpha and NO levels when these drugs were given in combination compared with their effects per se. These results indicate an antinociceptive activity of resveratrol and curcumin and point towards the beneficial effect of these combinations with insulin in attenuating diabetic neuropathic pain, possibly through the participation of NO and TNF-alpha.
Smart Antennas for Advanced Communication Systems (2012)

Blooming in data-communication applications is beyond all expectations. Smart antennas as now regarded as one of enabling technologies for next-generation wireless communication systems with its promised performance on enhancing network capacity. This paper presents a detailed analysis of the classes of smart antenna systems (SASs), including adaptive arrays, multibeam multiple-input–multiple-output (MB-MIMO) antennas, and diversity-antenna systems. This study also demonstrates practical examples of communication system with developed smart antennas, and shows that using smart antennas instead of traditional antennas highly improves the system performance.
Studies on Ovomucin (1969)

Ovomucin (B)溶液の相対粘度,極限粘度はチオグリコール酸ソーダおよび過酸化水素で処理することにより著しく低下することが認められた.これらの処理により,主として蛋白質部分に数パーセントの分解が起こり,このような化学的変化によりovomucin (B)溶液は処理前と同様に超遠心釣に単一で,電気泳動的に2成分であるが,沈降定数のより小さい,泳動図の相対面積比の異なるものに変化することが認められた.二つの処理に共通している点は処理による還元粘度または沈降定数の濃度依存性の低下で示される分子間相互作用の低下である.すなわち,チオグリコール酸ソーダおよび過酸化水素の作用部位は多少異なるとしても,その作用をうけた分子はもはや強い相互作用を示すことができず,より小さなユニットを形成するものと考えられる.これらのことから,ovomucin(B)溶液が示す高い粘性はovomucin (B)分子間の強い相互作用の寄与によるものと考えられる.
The value of animal models for drug development in multiple sclerosis (2006)

The rodent model for multiple sclerosis, experimental allergic (autoimmune) encephalomyelitis (EAE), has been used to dissect molecular mechanisms of the autoimmune inflammatory response, and hence to devise and test new therapies for multiple sclerosis. Clearly, artificial immunization against myelin may not necessarily reproduce all the pathogenetic mechanisms operating in the human disease, but most therapies tested in multiple sclerosis patients are nevertheless based on concepts derived from studies in EAE. Unfortunately, several treatments, though successful in pre-clinical EAE trials, were either less effective in patients, worsened disease or caused unexpected, severe adverse events, as we review here. These discrepancies must, at least in part, be due to genetic and environmental differences, but the precise underlying reasons are not yet clear. Our understanding of EAE pathogenesis is still incomplete and so, therefore, are any implications for drug development in these models. Here, we suggest some potential explanations based on new thinking about key pathogenic concepts and differences that may limit extrapolation from EAE to multiple sclerosis. To try to circumvent these rodent-human dissimilarities more systematically, we propose that pre-clinical trials should be started in humanized mouse models.
Alkaliphiles: Ecology, diversity and applications (1990)

Organisms with pH optima for growth in excess of prig, usually between 9 and 10, are properly defined as alkaliphiles (or sometimes alkalophiles). Most of the organisms described to date as growing under very alkaline conditions are prokaryotes, comprising a heterogeneous collection of eubaeteria (including cyanobacteria) with a few examples of archacbactesia. With the exception of the alkaliphilic archaebacteria (which are also halophilic), few of the isolates have been comprehensively classified. However, it is clear that many different taxa are represented amongst the alkaliphiles, and that some of these at least are likely to be new taxa. Alkaliphiles can be isolated from 'normal' environments such as garden soil presumably because there are transient alkaline conditions generated in such environments by biological activity, but a relatively restricted range of types results from the exploration of such environments (often Bacillus spp.). Naturally-occurring stable alkaline environments such as eutrophic soda (Na2CO3) lakes harbour a much wider range of types. A similarly wide range of types may exist in oligotrophic Ca(OH)z-dominated ground water
Synthesis, Characterization, and DFT-TDDFT Computational Study of a Ruthenium Complex Containing a Functionalized Tetradentate Ligand (2006)

A ruthenium complex trans-[Ru(L)(NCS)2], L = 4,4' ''-di-tert-butyl-4',4' '-bis(carboxylic acid)-2,2':6',2' ':6' ',2' ''-quaterpyridine (N886), was synthesized and characterized by spectroscopic and electrochemical methods. The absorption spectrum of the N886 complex shows metal-to-ligand charge-transfer transitions in the entire visible region and quasi-reversible oxidation and reduction potentials at E(1/2) = +0.38 and -1.92 V vs ferrocene, respectively. The electronic spectra of the N886 complex were calculated by density functional theory (DFT)-time-dependent DFT, which qualitatively reproduces the experimental absorption spectra for both the protonated and deprotonated species. From the analysis of the computed optical transitions of N886, we assign its absorption bands as mixed Ru/SCN-to-quaterpyridine charge-transfer transitions, which extend from the near-IR to the UV regions. The panchromatic response of the N886 complex renders it as a suitable sensitizer for solar energy conversion applications based on titanium dioxide mesoporous electrodes. The preliminary results using the N886 complex as a sensitizer in a dye-sensitized solar cell, with an electrolyte containing 0.60 M butylmethylimidazolium iodide, 0.03 M I2, and 0.50 M tert-butylpyridine in a mixture of acetonitrile and valeronitrile (volume ratio 1:1), show 40% incident photon-to-current efficiencies, yielding under standard AM 1.5 sunlight a short-circuit photocurrent density of 11.8 +/- 0.2 mA/cm(2), an open-circuit voltage of 680 +/- 30 mV, and a fill factor of 0.73 +/- 0.03, corresponding to an overall conversion efficiency of 5.85%.
Formal methods reality check: industrial usage (1995)

Based on a systematic survey and analysis of the use of formal methods in the development of a dozen industrial applications, we summarize the methods being used, characterize the styles of industrial usage, and provide recommendations for evolutionary enhancements to the technology base of formal methods. The industrial applications ranged from reverse engineering to system certification; code scale ranges from 1 KLOC to 10 KLOC's. Applications included a software infrastructure for oscilloscopes; a shutdown system for a nuclear generating station; a train protection system; an airline collision avoidance system; an engine monitoring system for shipboard engines; attitude control of satellites; security properties of both a smartcard device and a network; arithmetic units; transaction processing; a real-time database for a medical instrument; and a restructuring program for COBOL.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Rifaximin for Treatment of Hepatic Encephalopathy (2008)

Rifaximin appears to be an effective and safe treatment option for HE. Better-designed studies are needed to characterize its efficacy in the treatment of HE.
Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses (2018)

Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.
The mitochondrial inner membrane anion channel. Regulation by divalent cations and protons. (1987)

It is now well established that incubation of mitochondria at pH 8 or higher opens up an electrophoretic anion transport pathway in the inner membrane. It is not known, however, whether this transport process has any physiological relevance. In this communication we demonstrate that anion uniport can take place at physiological pH if the mitochondria are depleted of matrix divalent cations with A23187 and EDTA. Using the light-scattering technique we have quantitated the rates of uniport of a wide variety of anions. Inorganic anions such as Cl-, SO4(2-), and Fe(CN)6(4-) as well as physiologically important anions such as HCO3-, Pi-, citrate, and malate are transported. Some anions, however, such as gluconate and glucuronate do not appear to be transported. On the basis of the finding that the rate of anion uniport assayed in ammonium salts exhibits a dramatic decline associated with loss of matrix K+ via K+/H+ antiport, we suggest that anion uniport is inhibited by matrix protons. Direct inhibition of anion uniport by protons in divalent cation-depleted mitochondria is demonstrated, and the apparent pK of the binding site is shown to be about 7.8. From these properties we tentatively conclude that anion uniport induced by divalent cation depletion and that induced by elevated pH are catalyzed by the same transport pathway, which is regulated by both matrix H+ and Mg2+.