gebhart/patrepeval huggingface dataset:
Key Features Determining the Specificity of Aspartic Proteinase Inhibition by the Helix-forming IA3 Polypeptide (2006)

The 68-residue IA(3) polypeptide from Saccharomyces cerevisiae is essentially unstructured. It inhibits its target aspartic proteinase through an unprecedented mechanism whereby residues 2-32 of the polypeptide adopt an amphipathic alpha-helical conformation upon contact with the active site of the enzyme. This potent inhibitor (K(i) < 0.1 nm) appears to be specific for a single target proteinase, saccharopepsin. Mutagenesis of IA(3) from S. cerevisiae and its ortholog from Saccharomyces castellii was coupled with quantitation of the interaction for each mutant polypeptide with saccharopepsin and closely related aspartic proteinases from Pichia pastoris and Aspergillus fumigatus. This identified the charged K18/D22 residues on the otherwise hydrophobic face of the amphipathic helix as key selectivity-determining residues within the inhibitor and implicated certain residues within saccharopepsin as being potentially crucial. Mutation of these amino acids established Ala-213 as the dominant specificity-governing feature in the proteinase. The side chain of Ala-213 in conjunction with valine 26 of the inhibitor marshals Tyr-189 of the enzyme precisely into a position in which its side-chain hydroxyl is interconnected via a series of water-mediated contacts to the key K18/D22 residues of the inhibitor. This extensive hydrogen bond network also connects K18/D22 directly to the catalytic Asp-32 and Tyr-75 residues of the enzyme, thus deadlocking the inhibitor in position. In most other aspartic proteinases, the amino acid at position 213 is a larger hydrophobic residue that prohibits this precise juxtaposition of residues and eliminates these enzymes as targets of IA(3). The exquisite specificity exhibited by this inhibitor in its interaction with its cognate folding partner proteinase can thus be readily explained.
High-speed CMOS switch designs for free-space optoelectronic MIN's (1998)

We present the theory, experimental results, and analytical modeling of high-speed complementary metal-oxide-semiconductor (CMOS) switches, with a two-dimensional (2-D) layout, suitable for the implementation of packet-switched free-space optoelectronic multistage interconnection networks (MIN's). These switches are fully connected, bidirectional, and scaleable. The design is based on the implementation of a half-switch, which is a two-to-one multiplexer, using a 2-D layout. It introduces a novel self-routing concept, with contention detection and packet drop-and-resend capabilities. It uses three-valued logic, with 2.5 V being the third value for a 5 V power supply. Simulations show that for a 0.8-/spl mu/m CMOS technology the switches can operate at speeds up to 250 Mb/s. Scaled-down versions of the switches have been successfully implemented in 2.0 /spl mu/m CMOS. The analytical modeling of these switches show that large scale free-space optoelectronic MIN's using this concept could offer close to Terabit/sec throughput capabilities for very reasonable power and area figures. For example, a 4096 channel system could offer 256 Gb/s aggregate throughput for a total silicon area of about 18 cm/sup 2/ and a total power consumption (optics plus electronics) of about 90 W.
A novel image sensor for video compression (2002)

A novel image sensor on which video signals can be compressed is proposed. Since the video signal is compressed on an imager plane by using fast analog processing, the amount of image data read out from the imager can be significantly reduced with very small latency. The proposed system can be potentially applied to high pixel rate cameras such as those for high speed imaging and high resolution imaging. Conditional replenishment is employed for the video compression algorithm. Analog circuits are designed both for processing in each pixel and for controlling the entire data rate. The behavior of the circuit is investigated on the basis of both an analog circuit simulator and a scale-up-circuit. A VLSI chip is designed and is under fabrication.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Calixarenes as Platforms for the Construction of Multimetallic Complexes (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Which Do Endohedral Ti2C80 Metallofullerenes Prefer Energetically:  Ti2@C80 or Ti2C2@C78? A Theoretical Study (2005)

Four possible isomers of the Ti2C80 metallofullerene are discussed in detail at the B3LYP DFT level of theory: two isomers in Ti2@C80 formula with two Ti atoms encapsulated inside a C80 cage and the other two in Ti2C2@C78 formula with a Ti2C2 cluster involved inside a C78 cage. In the encaged Ti2C2 cluster, there are end-on and side-on C2 bridging modes into the two Ti atoms. The optimized end-on cluster has a linear Ti-C-C-Ti array, whereas the side-on cluster has a butterfly-like structure where the two Ti atoms and the C2 unit do not lie in a plane. DFT calculations show that the Ti2C2@C78 molecule with the end-on Ti2C2 cluster is energetically most favorable in the four isomers. Stabilities of the Ti2C80 molecules are essentially dominated by Ti binding sites inside fullerene cages. The Ti atoms bind over the hexagon rings in preference to a junction between hexagon and pentagon rings. In the Ti2C2@C78 molecules, orbital interactions between the Ti2C2 cluster and the outer cage play a significant role in determining the C2 bridging modes into the dititanium center and their relative stabilities.
Synthesis and Structure Activity Relationship of Tetrahydroisoquinoline-Based Potentiators of GluN2C and GluN2D ContainingN-Methyl-d-aspartate Receptors (2013)

We describe here the synthesis and evaluation of a series of tetrahydroisoquinolines that show subunit-selective potentiation of NMDA receptors containing the GluN2C or GluN2D subunits. Bischler-Napieralski conditions were employed in the key step for the conversion of acyclic amides to the corresponding tetrahydroisoquinoline-containing analogs. Compounds were evaluated using both two-electrode voltage clamp recordings from Xenopus laevis oocytes and imaging of mammalian BHK cells loaded with Ca(2+)-sensitive dyes. The most potent analogues had EC50 values of 300 nM and showed over 2-fold potentiation of the response to maximally effective concentrations of glutamate and glycine but had no effect on responses from NMDA receptors containing the GluN2A or GluN2B subunits AMPA, kainate, and GABA or glycine receptors or a variety of other potential targets. These compounds represent a potent class of small molecule subunit-selective potentiators of NMDA receptors.
ChemInform Abstract: Enantioselective α‐Chlorination of Aldehydes with Recyclable Fluorous (S)‐Pyrrolidine—Thiourea Bifunctional Organocatalyst. (2010)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
One-to-One and Three-to-One Internal Resonances in MEMS Shallow Arches (2017)

The nonlinear modal coupling between the vibration modes of an arch-shaped microstructure is an interesting phenomenon, which may have desirable features for numerous applications, such as vibration-based energy harvesters. This work presents an investigation into the potential nonlinear internal resonances of a microelectromechanical systems (MEMS) arch when excited by static (DC) and dynamic (AC) electric forces. The influences of initial rise and midplane stretching are considered. The cases of one-to-one and three-to-one internal resonances are studied using the method of multiple scales and the direct attack of the partial differential equation of motion. It is shown that for certain initial rises, it is possible to activate a three-to-one internal resonance between the first and third symmetric modes. Also, using an antisymmetric half-electrode actuation, a one-to-one internal resonance between the first symmetric and the second antisymmetric modes is demonstrated. These results can shed light on such interactions that are commonly found on micro and nanostructures, such as carbon nanotubes.
Effects of Random Mutagenesis in a Putative Substrate-Binding Domain of Geranylgeranyl Diphosphate Synthase upon Intermediate Formation and Substrate Specificity (1997)

Archaeal geranylgeranyl diphosphate (GGPP) synthase catalyzes the consecutive condensation of isopentenyl diphosphate (IPP) with allylic diphosphates to produce GGPP with significant amounts of intermediates. To obtain information about the amino acids involved in the condensation and the release of intermediates, we randomly mutagenized two proximal regions, I and II, of the Sulfolobus acidocaldarius GGPP synthase gene and created two degenerate libraries, I and II, respectively. Regions I and II correspond to amino acid residues 170-173 and 166-168, respectively. The prenyltransferase activities of about 200 clones were analyzed using the in vivo red-white system and the conventional in vitro assay. Although, in library I, no mutated enzymes that failed to catalyze the formation of GGPP were found, as assayed with the red-white system, almost all the mutated enzymes exhibited weak GGPP synthesis activity, and many produced large amounts of intermediates. The formation of intermediates increased as the concentration of IPP was decreased or as the concentration of the allylic substrate was increased. These phenomena can be regarded as a reflection of the increased K(m) for IPP and the decreased affinity for products including intermediates. On the other hand, no mutants from library II showed such changes. These results suggest that the region from 170 to 173 is concerned in the recognition of both IPP and allylic diphosphates, and that the change in responsiveness to prenyl diphosphates causes a change in intermediate formation.
Cloning, Expression, Purification and Characterization of an Isotype of Clytin, a Calcium-Binding Photoprotein from the Luminous Hydromedusa Clytia gregarium (2008)

The cDNA for an isotype of clytin, a calcium-binding photoprotein from the luminous jellyfish Clytia gregarium, was identified and named clytin-II. The histidine-tagged apoprotein of clytin-II expressed into the periplasmic space of Escherichia coli cells was isolated by nickel chelate affinity chromatography. Recombinant clytin-II regenerated from apoprotein by incubation with coelenterazine was purified. The yield of purified clytin-II was 13 mg from 2 l of cultured cells with purity >95%. The luminescence properties of clytin-II were characterized by comparison with clytin-I and aequorin, and semi-synthetic clytin-II was also prepared. The initial luminescence intensity of clytin-II triggered by Ca(2+) was 4.5 times higher than that of clytin-I and aequorin, but the luminescence capacity was close to clytin-I and aequorin. Thus, clytin-II is a useful protein, showing high sensitivity in the signal-to-noise ratio of luminescence intensity.
Feedback linearization and simultaneous stiffness-position control of robots with antagonistic actuated joints (2007)

In this paper, the dynamic model of a robot with antagonistic actuated joints is presented, and the problem of full linearization via static state feedback is analyzed. The use of transmission elements with nonlinear relation between the displacement and the actuated force allows to control both the position and the stiffness of each joint. The main advantage of this actuation modality is that the achieved stiffness becomes a mechanical characteristic of the system and it is not the result of an immediate control action as in the classical impedance control scheme (Davison, 2003). Different examples of implementation of this kind of devices are known in literature, even if limited to one single joint (Kjita et al., 2003; Laumond and Kineocam, 2006; Mansard and Chaumette, 2004 and 2006) and the application of antagonistic actuated kinematic chains in the field of robotic hand design is under investigation (Stasse et al., 2006). After a brief review of the dependence of the properties of antagonistic actuation on the transmission elements characteristics, a scheme for simultaneous stiffness-position control of the linearized system is presented. Finally, simulation results of a two-link antagonistic actuated arm are reported and discussed.
Steering programs via time travel (2002)

The environments that programmers traditionally use for problem-solving-with separate modes and tools for writing, compiling, testing, visualizing and debugging-derive their basic structure from historical accident, and take little advantage of human-computer interaction (HCI) research into the cognitive issues of programming. We believe that neglect of these issues impedes programmers' ability to produce reliable, maintainable software. Visual programming languages (VPLs) have begun to address this problem by creating more flexible, less modal programming environments, and we have taken a step further in this direction. In this paper, we describe a VPL in which programmers can modelessly steer as they specify, visualize, explore and alter the behavior of a program while traveling through the program's logical time. This approach supports two often-neglected cognitive principles that HCI research shows can help programmers in their problem-solving.
Endoscopic therapy for gastroesophageal reflux disease. (2005)

Endoscopic therapies aimed to reduce gastroesophageal reflux have gained an enormous enthusiasm during the last 5 years when several of them were approved by the regulatory agencies and released on the market. These novel therapies comprise 3 types of techniques: injection/bulking, plicating/suturing and radiofrequency thermal injury. Open-labelled trials performed on proton pump inhibitors-responding patients with typical gastroesophageal reflux disease (GERD) symptoms have shown an improvement in reflux symptoms during short term follow-up. Longer-term data are now available and show disappointing results with partial-thickness plications of the cardia. Randomized sham-controlled trials, which are essential to proof the efficacy of GERD endotherapy because of a known high placebo effect in the management of GERD patients, have been conducted, one with radiofrequency and one with polymer injection, and have confirmed the clinical efficacy of both techniques, although the clinical benefit was less impressive than suggested in open-labelled trials. While mechanistic studies have suggested that the compliance of the gastroesophageal junction might be altered by GERD endotherapy, objective assessment of acid reflux with ambulatory pH-metry has shown, however, minimal or no modification by the treatment. Concerns about the safety of these new techniques have raised when complications were reported as the number of treated cases increased. Currently, no definite indication is established for each technique, but numerous potential indications exist and should be addressed in the setting of carefully designed clinical trials. Physicians should be patient and wait for proof of efficacy and safety of these techniques before using them in their clinical practice. Specific and extensive warning should be obtained before starting clinical application. The present review aims to provide a comprehensive and critical view of endoscopic therapy in GERD management.
An Efficient Parallel Synthesis of Capsazepine and Capsazepine Analogs (2004)

Capsazepine (CPZ, 1) is a well-known vanilloid receptor (VR1) antagonist that has been cited widely used in the literature. However the current synthetic methods used for the total synthesis of CPZ are lengthy, involve multiple purification steps, and produce low yields. Here we describe a new and highly efficient synthesis of benzazepine 3, a synthetic precursor of CPZ, in only two steps and 59% overall yield from a commercially available tetralone 2 via a Schmidt reaction as a key step. Moreover, we apply parallel synthesis techniques to prepare CPZ and CPZ analogs. Our approach enables the possibility of preparing larger, and more diverse libraries of CPZ analogs.
Investigations of Performance and Bias in Human-AI Teamwork in Hiring (2022)

In AI-assisted decision-making, effective hybrid (human-AI) teamwork is not solely dependent on AI performance alone, but also on its impact on human decision-making. While prior work studies the effects of model accuracy on humans, we endeavour here to investigate the complex dynamics of how both a model's predictive performance and bias may transfer to humans in a recommendation-aided decision task. We consider the domain of ML-assisted hiring, where humans -- operating in a constrained selection setting -- can choose whether they wish to utilize a trained model's inferences to help select candidates from written biographies. We conduct a large-scale user study leveraging a re-created dataset of real bios from prior work, where humans predict the ground truth occupation of given candidates with and without the help of three different NLP classifiers (random, bag-of-words, and deep neural network). Our results demonstrate that while high-performance models significantly improve human performance in a hybrid setting, some models mitigate hybrid bias while others accentuate it. We examine these findings through the lens of decision conformity and observe that our model architecture choices have an impact on human-AI conformity and bias, motivating the explicit need to assess these complex dynamics prior to deployment.
Shock Wave Interaction with Laser-Generated Single Bubbles (2005)

The interaction of a lithotripter shock wave (LSW) with laser-generated single vapor bubbles in water is investigated using high-speed photography and pressure measurement via a fiber-optic probe hydrophone. The interaction leads to nonspherical collapse of the bubble with secondary shock wave emission and microjet formation along the LSW propagation direction. The maximum pressure amplification is produced during the collapse phase of the bubble oscillation when the compressive pulse duration of the LSW matches with the forced collapse time of the bubble.
Overview of Optical Modulators and the Properties That Affect Transmission System Performance (2012)

A large variety of optical modulators has been invented, researched, and developed over the last 40 years. is research is still very active, and at present, there are many papers published every year describing new designs and new advances in existing modulators. On the other hand, only two modulator designs are presently used in large numbers in the ber-optic communication market.
Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure (2019)

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
Subcapsular prostate cancer: Identification with mpMRI and MRI/TRUS fusion-guided biopsy. (2015)

52 Background: The subcapsular region is often under-sampled by standard 12-core transrectal ultrasound (TRUS) prostate biopsy. We retrospectively evaluated multi-parametric MRI (mpMRI) features of subcapsular prostate cancers (PCa) and their detection on MRI/TRUS fusion-guided biopsy (FgBx). Methods: All patients referred for 3T mpMRI and subsequent FgBx under an IRB-approved protocol from Jan 2010 to July 2014 were reviewed. Histologically confirmed subcapsular lesions (just inside the prostate capsule with capsular border length &gt;&gt; width) were identified. Impact of the FgBx on clinical management according to current National Comprehensive Cancer Network (NCCN) guidelines was evaluated, with prior status based on outside TRUS biopsy results. Results: Of 992 eligible patients, 33 had subcapsular prostate lesions on mpMRI. In this subpopulation, mean age, PSA, and prostate volume were 63 years (range 52-76), 8.4ng/mL (1.2-63), and 53 mL (12-125). The FgBx, consisting of targeted (TBx) and systematic (SBx) portions, confirmed PCa in 24 of 33 patients. Five cancers (21%) were only detected by TBx. The remaining 19 were diagnosed on both TBx and SBx, but in 5 of these 19 (26%), higher Gleason scores were found on TBx cores. The FgBx results more accurately classified patients’ NCCN risk scores, with 17 prior unknown or low risk PCa upgraded to higher risk scores (Table). Conclusions: Subcapsular lesions on mpMRI are rare but largely malignant. Most are found on 12-core SBx, but ~20% require TBx for diagnosis, and TBx more accurately grades &gt;25% of the lesions. The FgBx may improve clinical management of patients with subcapsular PCa, since more aggressive cancer was found in 17 of 24 patients. [Table: see text] [Table: see text] [Table: see text]
Hyperparameter Selection for Offline Reinforcement Learning. (2020)

Offline reinforcement learning (RL purely from logged data) is an important avenue for deploying RL techniques in real-world scenarios. However, existing hyperparameter selection methods for offline RL break the offline assumption by evaluating policies corresponding to each hyperparameter setting in the environment. This online execution is often infeasible and hence undermines the main aim of offline RL. Therefore, in this work, we focus on \textit{offline hyperparameter selection}, i.e. methods for choosing the best policy from a set of many policies trained using different hyperparameters, given only logged data. Through large-scale empirical evaluation we show that: 1) offline RL algorithms are not robust to hyperparameter choices, 2) factors such as the offline RL algorithm and method for estimating Q values can have a big impact on hyperparameter selection, and 3) when we control those factors carefully, we can reliably rank policies across hyperparameter choices, and therefore choose policies which are close to the best policy in the set. Overall, our results present an optimistic view that offline hyperparameter selection is within reach, even in challenging tasks with pixel observations, high dimensional action spaces, and long horizon.