gebhart/patrepeval huggingface dataset:
CXCR4 chemokine receptor antagonists: nickel(ii) complexes of configurationally restricted macrocycles (2012)

Tetraazamacrocyclic complexes of transition metals provide useful units for incorporating multiple coordination interactions into a single protein binding molecule. They can be designed with available sites for protein interactions via donor atom-containing amino acid side chains or labile ligands, such as H(2)O, allowing facile exchange. Three configurationally restricted nickel(II) cyclam complexes with either one or two macrocyclic rings were synthesised and their ability to abrogate the CXCR4 chemokine receptor signalling process was assessed (IC(50) = 8320, 194 and 14 nM). Analogues were characterised crystallographically to determine the geometric parameters of the acetate binding as a model for aspartate. The most active nickel(II) compound was tested in several anti-HIV assays against representative viral strains showing highly potent EC(50) values down to 13 nM against CXCR4 using viruses, with no observed cytotoxicity (CC(50) > 125 μM).
Direct Monitoring of γ‐Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized 13C‐Labeled Molecular Probe (2016)

The γ-glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ-Glu-[1-(13) C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) (13) C magnetic resonance (MR). The properties of γ-Glu-[1-(13) C]Gly are suitable for in vivo HP (13) C metabolic analysis since the chemical shift between γ-Glu-[1-(13) C]Gly and its metabolic product, [1-(13) C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2 O at 9.4 T). We also demonstrate that γ-Glu-[1-(13) C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin.
AB04. Novel approaches for testosterone replacement therapy (2014)

Surging interest in addressing male hypogonadism in recent years has resulted in the identification and development of novel pharmacotherapeutic approaches that may yield increased serum testosterone levels. Testosterone replacement therapy is controversial with concerns surrounding its proper indications and potential side effects. However, interest remains strong to explore treatment options that may address the signs and symptoms of male hypogonadism. Several testosterone preparations are commercially available at this time, and these encompass assorted routes of delivery with specific generic names and dosage recommendations. Routes of delivery include oral, intramuscular, subcutaneous, transdermal and buccal preparations. The routes of administration confer various advantages and disadvantages with respect to efficacy, physiologic levels, duration of effect, ease of administration, and cost. Besides testosterone formulations, alternative options are in development or are used in an off-label mode such as selective androgen receptor modulators (SARMS), selective estrogen receptor modulators (SERMS; clomiphene citrate, enclomiphene), aromatase inhibitors, dihydrotestosterone and human chorionic gonadotropin. These alternatives are hoped to reduce side effects believed to be associated with exogenous testosterone therapy and may be particularly advantageous in the young male with primary hypogonadism whose interest is to preserve normal spermatogenesis (which may be impaired by feedback control mechanisms resulting from exogenous testosterone therapy). Ongoing investigation may reveal select roles for these therapies in the management of male hypogonadism.
Synthesis of 5‐Bromoisoquinoline and 5‐Bromo‐8‐nitroisoquinoline (2004)

Abstract Isoquinoline N‐ Bromosuccinimide 5‐Bromoisoquinoline 5‐Bromo‐8‐nitroisoquinoline
Comprehensive laboratory and field testing of cavity ring-down spectroscopy analyzers measuring H 2 O, CO 2 , CH 4 and CO (2015)

Abstract. To develop an accurate measurement network of greenhouse gases, instruments in the field need to be stable and precise and thus require infrequent calibrations and a low consumption of consumables. For about ten years, cavity ring-down spectroscopy (CRDS) analyzers have been available that meet these stringent requirements for precision and stability. Here, we present the results of tests of CRDS instruments in the laboratory (47 instruments) and in the field (15 instruments). The precision and stability of the measurements are studied. We demonstrate that, thanks to rigorous testing, newer models generally perform better than older models, especially in terms of reproducibility between instruments. In the field, we see the importance of individual diagnostics during the installation phase, and we show the value of calibration and target gases that assess the quality of the data. Finally, we formulate recommendations for use of these analyzers in the field.
Diode pumped LiLa/sub 1-x/Nd/sub x/(MoO/sub 4/)/sub 2/ and Nd:Bi/sub 4/Ge/sub 3/O/sub 12/ lasers (2002)

Summary form only given. The number of attractive laser properties of the uniaxial LiLa/sub 1-x/Nd/sub x/(MoO/sub 4/)/sub 2/ (Nd:LLM) and cubic structure Nd:Bi/sub 4/Ge/sub 3/O/sub 12/ (Nd:BGO) crystals were demonstrated previously by flash lamp pumping. The main purposes of our investigations were the growth of these optically perfect highly concentrated Nd/sup 3+/ doped crystals and study of their lasing characteristics under CW diode pumping.
Performance of Stereo Multiplexing in Single Channel and DWDM Systems Using Direct Detection with Optimum Dispersion Maps (2012)

We present Stereo Multiplexing, a novel technique that permits simultaneous direct detection of two modulated optical carriers. This is accomplished by modulating the optical carriers with the difference and the sum of two signals. The linear performance of Stereo-multiplexed DQPSK signals is compared to single-carrier DQPSK and dualcarrier DQPSK. Subsequently, by means of simulations, the robustness of each format is compared for single channel and DWDM transmission of 55.5 Gb/s through 1040 km of SMF. This is done by searching the optimum dispersion map and input powers for each format and looking at the stability of the performance around the optimum. We show that the best performance and robustness is obtained by sharing the information between two carriers, and that Stereo is only 1dB below dual-carrier NRZ-DQPSK. We discuss the penalty associated with designing a DWDM system based only on the optimization of transmission of single channel.
Simple procedure for the fabrication of flexible NMR shim coils (2013)

Photolithography allows simple fabrication of flexible NMR shim coils. Here we demonstrate this procedure by fabricating optimized first-order shim coils for a transverse field orientation “Halbach” permanent magnet cylinder.
Regulation of pancreatic acinar cell insulin receptors by insulin (1984)

In vivo pancreatic acini from normal mice are exposed to very high concentrations of insulin. To determine whether insulin receptors in these acini are downregulated by this endogenous insulin, insulin receptors on acini from both normal and diabetic mice were studied. Isolated acini from normal mice, which have accompanying islets of Langerhans, were studied under conditions where endogenous insulin was minimized. These acini bound 50% less 125I-insulin than acini from mice made diabetic with streptozotocin. Computer analysis of competition-inhibition curves showed a decrease in the number of insulin receptors in acini from normal mice when compared with acini from diabetic mice; however, the IC50 (a measure of receptor affinity) remained unchanged at approximately 1 nM. To study further the regulation of acinar cell insulin receptors, acini from diabetic mice were placed in suspension culture for 24 h. Addition of 1 microM insulin during the culture period led to a 30% decrease in subsequent 125I-insulin binding; the presence or absence of either epidermal growth factor or carbachol was without effect on insulin binding. The decrease in binding induced by insulin resulted from a change in receptor number without an alteration of the IC50. Measurement of total acinar cell insulin receptors by solubilization of these acini in 1% Triton X-100 showed that this insulin-induced decrease was due to a change in the total number of cellular insulin receptors. The present study suggests, therefore, that insulin can regulate its own receptor on pancreatic acini and that in vivo insulin receptors in normal pancreatic cells are downregulated, presumably due to high ambient insulin concentrations.
Identifying a panel of genes/proteins/miRNAs modulated by arsenicals in bladder, prostate, kidney cancers (2018)

Arsenic and arsenic-derivative compounds, named as arsenicals, represent a worldwide problem for their effect on the human health and, in particular, for their capability to increase the risk of developing cancer such as kidney, bladder and prostate cancer. The main source of arsenical exposure is drinking water. Nowadays, it is well known that the chronic exposure to arsenicals leads to a series of epigenetic alterations that have a role in arsenic-induced effects on human health including cancer. Based on these observations, the aim of our study was to select by network analysis the genes/proteins/miRNAs implicated in kidney, bladder and prostate cancer development upon arsenical exposure. From this analysis we identified: (i) the nodes linking the three molecular networks specific for kidney, bladder and prostate cancer; (ii) the relative HUB nodes (RXRA, MAP3K7, NR3C1, PABPC1, NDRG1, RELA and CTNNB1) that link the three cancer networks; (iii) the miRNAs able to target these HUB nodes. In conclusion, we highlighted a panel of potential molecules related to the molecular mechanisms of arsenical-induced cancerogenesis and suggest their utility as biomarkers or therapeutic targets.
Diversity of reaction of azoalkenes in cycloadditions (1991)

Reactions of the azoalkenes (E,E)-4-methyl-N-phenyl-2,3-diazapenta-2,4-diene-5-carboxamide 2 and methyl (E,Z)-3-methyl-4-phenylcarbamoyl-1,2-diazabuta-1,3-diene-1-carboxylate 3, having respectively an electron-rich and an electron-poor group on nitrogen, are described. Compound 2, is a stable compound and its stereochemistry was established as E,Eby X-ray crystallography; compound 3 is much less stable and was assigned the E,Z stereochemistry on the basis of its 1H NMR spectrum and the crystal structure of a derivative 17.Of a wide variety of substrates, only azo esters react with 2, which behaves as a heterodiene. The 1,2,3,6-tetra hydro-1,2,3,4-tetrazine 7 obtained from 2 by reaction with dimethyl azodicarboxylate is unstable and on work up yields a 4,5-dihydro-1H-1,2,3-triazole 9a(whose structure was established by X-ray crystallography). This isomerisation is probably acid catalysed since, by inclusion of acid, 7 tautomerises to a 1,2,3,4-tetrahydro-1,2,3,4-tetrazine 8 which then ring contracts to 9a, followed by a decarboxylative elimination of methyl carbamate to yield the 1,2,3-triazole 10.The azoalkene 3 is unreactive to electron-poor substrates, but reacts with cyclopentadiene both as a heterodiene and as a dienophile (at CC) to give as Diels–Alder adducts the tetrahydro-1H-cyclopenta[c]pyridazine 16 and the bicyclo[2.2.1]hept-2-ene 17 respectively. With ethyl vinyl ether 3 gave the ethoxytetrahydropyridazine 18 which eliminated EtOH in acid to the dihydro tautomers 19 and 20 which on basic hydrolysis and oxidation give the pyridazine 21.
New and Efficient Synthesis of Racemic Cyclopent-3-en-1-yl Nucleoside Analogues and Their Derivatives (2006)

A new, efficient synthesis of racemic cyclopent-3-en-1-yl nucleoside analogues has been developed starting from cyclopentadiene. The key step is the regioselective hydroboration of an intermediately formed mixture of two alkylated cyclopentadienes to give one cyclopentenol. The remaining double bond was further functionalized by hydroboration, epoxidation, cis -hydroxylation and cyclopropanation.
Hybrid green LEDs with n-type ZnO substituted for n-type GaN in an inverted p-n junction (2009)

Recently, the GaN and ZnO materials systems have attracted considerable attention because of their use in a broad range of emerging applications including light-emitting diodes (LEDs) and solar cells. GaN and ZnO are similar materials with direct wide bandgaps, wurtzite crystal structure, high thermal stability and comparable thermal expansion coefficients, which makes them well suited for heterojunction fabrication. Two important advantages of GaN over ZnO are the reliable p-type doping and the mature know-how for bandgap engineering. Thus GaN-based LEDs can be made to emit from the deep UV right into the green through alloying with Al and In, respectively. The performance is not identical at all wavelengths, however, and the performance of InGaN-based green LEDs is still relatively poor [1,2]. This is largelt due to the relatively high In content in the active layers, which makes them unstable at the elevated substrate temperatures (Ts) typically used for the growth of the p-type GaN top layer and thus causes In to leak out of the active layers in the InGaN/GaN Multi-Quantum Wells (MQW) [2,3]. This significantly reduces the performance & lifetime of the LEDs. In this work, an n-type ZnO was substituted for the n-type GaN layer in an (In)GaN-based green LED with an inverted p-n structure (see inset of Figure 1). The top layer was thus the n-type ZnO rather than p-type GaN. Through use of Pulsed Laser Deposition (PLD) for this ZnO growth, the ultimate growth step could thus be performed at significantly lower Ts than is typically required for GaN growth in Metal-Organic Chemical Vapor Deposition (MOCVD). High crystallographic quality of the final hybrid LED structure & the integrity of the MQWs were confirmed by X-Ray Diffraction. The devices showed rectifying I/V characteristics with a turn-on voltage of 2.5 V (Figure 1) & a discrete green Electroluminescence (EL) emission peaked at around 510 nm, which was readily visible to the naked eye (Figure 2). These results indicate that PLD-grown ZnO could be a good alternative to MOCVD-grown GaN for the n-type layer & that such inverted hybrid structures could hold the prospect for the development of green LEDs with superior performance.
Pairing in the Presence of a Pseudogap (2015)

Evidence that the pseudogap (PG) in a near-optimally doped Bi$_2$Sr$_2$CaCu$_2$O$_{8+δ}$ sample destroys the BCS logarithmic pairing instability [1] raises again the question of the role of the PG in the high-temperature superconducting cuprates [2]. The elimination of the BCS instability is consistent with the view that the PG competes with superconductivity. However, as noted in [1], the onset of superconductivity with a $T_c \sim 90$ K suggests an alternative scenario in which the PG reflects the formation of short range pairing correlations. Here, we report results obtained from a dynamic cluster quantum Monte Carlo approximation (DCA) for a 2D Hubbard model and conclude that (1) the PG, like the superconductivity, arises due to short-range antiferromagnetic correlations and (2) contrary to the usual case in which the pairing instability arises from the Cooper instability, here, the strength of the spin-fluctuations increases as the temperature decreases leading to the pairing instability.
Data anonymity in multi-party service model (2011)

Existing approaches for protecting privacy in public database consider a service model where a service provider publishes public datasets that consist of data gathered from clients. We extend the service model to the multi-service providers setting. In the new model, a service provider obtains anonymized datasets from other service providers who gather data from clients and then publishes or uses the anonymized datasets generated from the obtained anonymized datasets. We considered a new service model that involves more than two data holders and a data user, and proposed a new privacy requirement. Furthermore, we discussed feasible approaches searching a table that satisfies the privacy requirement and showed a concrete algorithm to find the table.
Adapting to intermittent faults in multicore systems (2008)

Future multicore processors will be more susceptible to a variety of hardware failures. In particular, intermittent faults, caused in part by manufacturing, thermal, and voltage variations, can cause bursts of frequent faults that last from several cycles to several seconds or more. Due to practical limitations of circuit techniques, cost-effective reliability will likely require the ability to temporarily suspend execution on a core during periods of intermittent faults.
Additional file 1: Figure S1. of Regulated internalization of NMDA receptors drives PKD1-mediated suppression of the activity of residual cell-surface NMDA receptors (2015)

The endocytosis of NMDARs (the GluN1 subunit). (PDF 62 kb)
3-D-TCAD-Based Parasitic Capacitance Extraction for Emerging Multigate Devices and Circuits (2013)

In recent years, the multigate field-effect transistor (FET) has emerged as the most viable contender for technology scaling down to the sub-10-nm nodes. The nonplanar nature of multigate devices, along with rapidly shrinking front-end-of-line (FEOL) and back-end-of-line (BEOL) features, has compounded the problem of parasitics extraction in future technology nodes. In this paper, for the first time, we address the above problem through a holistic 3-D-technology CAD (3-D-TCAD) flow for the extraction of FEOL/(FEOL+BEOL) capacitances in generic multigate circuit layouts, using a transport analysis-based approach. We investigate device-level parasitic capacitances in 3-D-process-simulated bulk and silicon-on-insulator FinFETs, and uncover capacitance scaling trends for candidate single/multifin multigate FETs along the 22-nm/14-nm/10-nm technology nodes. Leveraging automated structure synthesis algorithms, we synthesize 3-D multigate 6T SRAM structures using the process-simulated devices, and examine the effects of fin pitch, gate pitch, and fin count on circuit-level parasitics. Thereafter, we show that traditional segregated FEOL/BEOL modeling approaches fail to provide accurate estimates, by back-annotating 3-D-TCAD-extracted capacitances into mixed-mode write simulations of a 6T FinFET SRAM bitcell. Finally, using FinFET NAND2 logic gate delay simulations, we establish the fact that capturing parasitics accurately is as important as modeling device transport accurately, and that performance/dynamic behavior in multigate circuits is highly sensitive to both factors.
Reward, motivation, and emotion of pain and its relief (2017)

The experience of pain depends on interpretation of context and past experience that guide the choice of an immediate behavioral response and influence future decisions of actions to avoid harm. The aversive qualities of pain underlie its physiological role in learning and motivation. In this review, we highlight findings from human and animal investigations that suggest that both pain, and the relief of pain, are complex emotions that are comprised of feelings and their motivational consequences. Relief of aversive states, including pain, is rewarding. How relief of pain aversiveness occurs is not well understood. Termination of aversive states can directly provide relief as well as reinforce behaviors that result in avoidance of pain. Emerging preclinical data also suggests that relief may elicit a positive hedonic value that results from activation of neural cortical and mesolimbic brain circuits that may also motivate behavior. Brain circuits mediating the reward of pain relief, as well as relief-induced motivation are significantly impacted as pain becomes chronic. In chronic pain states, the negative motivational value of nociception may be increased while the value of the reward of pain relief may decrease. As a consequence, the impact of pain on these ancient, and conserved brain limbic circuits suggest a path forward for discovery of new pain therapies.
MATHEMATICAL MODEL AND SIMULATION OF A PNEUMATIC APPARATUS FOR IN-DRILLING ALIGNMENT OF AN INERTIAL NAVIGATION UNIT DURING HORIZONTAL WELL DRILLING (2007)

Conventional methods in horizontal drilling processes incorporate magnetic surveying techniques for\ndetermining the position and orientation of the bottom-hole assembly (BHA). Such means result in an increased\nweight of the drilling assembly, higher cost due to the use of non-magnetic collars necessary for the shielding of\nthe magnetometers, and significant errors in the position of the drilling bit. A fiber-optic gyroscope (FOG) based\ninertial navigation system (INS) has been proposed as an alternative to magnetometer -based downhole\nsurveying. The utilizing of a tactical-grade FOG based surveying system in the harsh downhole environment has\nbeen shown to be theoretically feasible, yielding a significant BHA position error reduction (less than 100m over a\n2-h experiment). To limit the growing errors of the INS, an in-drilling alignment (IDA) method for the INS has been\nproposed. This article aims at describing a simple, pneumatics-based design of the IDA apparatus and its\nimplementation downhole. A mathematical model of the setup is developed and tested with Bloodshed Dev-C++.\nThe simulations demonstrate a simple, low cost and feasible IDA apparatus.
High-Rate Vector Quantization for Noisy Channels With Applications to Wideband Speech Spectrum Compression (2011)

This paper considers the high-rate performance of source coding for noisy discrete symmetric channels with random index assignment (IA). Accurate analytical models are developed to characterize the expected distortion performance of vector quantization (VQ) for a large class of distortion measures. It is shown that when the point density is continuous, the distortion can be approximated as the sum of the source quantization distortion and the channel-error induced distortion. Expressions are also derived for the continuous point density that minimizes the expected distortion. Next, for the case of mean squared error distortion, a more accurate analytical model for the distortion is derived by allowing the point density to have a singular component. The extent of the singularity is also characterized. These results provide analytical models for the expected distortion performance of both conventional VQ as well as for channel-optimized VQ. As a practical example, compression of the linear predictive coding parameters in the wideband speech spectrum is considered, with the log spectral distortion as performance metric. The theory is able to correctly predict the channel error rate that is permissible for operation at a particular level of distortion.
Maturation-Dependent HIV-1 Surface Protein Redistribution Revealed by Fluorescence Nanoscopy (2012)

Human immunodeficiency virus type 1 (HIV-1) buds from the cell as an immature particle requiring subsequent proteolysis of the main structural polyprotein Gag for morphological maturation and infectivity. Visualization of the viral envelope (Env) glycoprotein distribution on the surface of individual HIV-1 particles with stimulated emission depletion (STED) superresolution fluorescence microscopy revealed maturation-induced clustering of Env proteins that depended on the Gag-interacting Env tail. Correlation of Env surface clustering with the viral entry efficiency revealed coupling between the viral interior and exterior: Rearrangements of the inner protein lattice facilitated the alteration of the virus surface in preparation for productive entry. We propose that Gag proteolysis-dependent clustering of the sparse Env trimers on the viral surface may be an essential aspect of HIV-1 maturation.
Effect of Helicobacter pylori eradication on expression of cyclin D2 and p27 in gastric intestinal metaplasia (2001)

Over-expression of cyclin D2 and reduced expression of p27 are closely linked to H. pylori-associated intestinal metaplasia. Eradication of H. pylori infection reverses the aberrant expression of cyclin D2 and p27 in intestinal metaplasia.