gebhart/patrepeval huggingface dataset:
Exploring the Determinants of Trace Amine-Associated Receptor 1’s Functional Selectivity for the Stereoisomers of Amphetamine and Methamphetamine (2013)

Amphetamines are widely abused drugs that interfere with dopamine transport and storage. Recently, however, another mechanism of action was identified: stereoselective activation of the GαS protein-coupled trace amine-associated receptor 1 (TAAR1). To identify structural determinants of this stereoselectivity, we functionally evaluated six mutant receptors in vitro and then used homology modeling and dynamic simulation to predict drug affinities. Converting Asp102 to Ala rendered mouse and rat TAAR1 (mTAAR1 and rTAAR1, respectively) insensitive to β-phenylethylamine, amphetamine (AMPH), and methamphetamine (METH). Mutating Met268 in rTAAR1 to Thr shifted the concentration-response profiles for AMPH and METH isomers rightward an order of magnitude, whereas replacing Thr268 with Met in mTAAR1 resulted in profiles leftward shifted 10-30-fold. Replacing Asn287 with Tyr in rTAAR1 produced a mouselike receptor, while the reciprocal mTAAR1 mutant was rTAAR1-like. These results confirm TAAR1 is an AMPH/METH receptor in vitro and establish residues 102 (3.32) and 268 (6.55) as major contributors to AMPH/METH binding with residue 287 (7.39) determining species stereoselectivity.
Achieving the ergodic capacity with lattice codes (2015)

The performance of lattice codes in the additive white Gaussian noise (AWGN) channel has attracted much attention lately, however, their performance under ergodic fading channels has been relatively unexplored. We show that lattice coding and decoding achieve the capacity of the ergodic point-to-point and multiple-access channels (MAC). Additionally, a low-complexity scheme is proposed for the ergodic MAC. At moderate and high signal-to-noise ratio (SNR), the sum rate achieved by the low-complexity scheme is within a constant gap to the ergodic MAC sum capacity, whereas at low SNR the gap to capacity diminishes quadratically with linear SNR decrease.
A synthesis of a 1,1′-desymmetrised ferrocene backbone and its facile one-pot double-“click” functionalisation (2013)

A one-pot, four-component, copper-catalysed double-“click” functionalisation of a novel 1,1′-desymmetrised ferrocene backbone is reported. Using an array of alkynes and azides, a library of ferrocene compounds was developed, demonstrating the scope of this methodology for its potential application in the assembly of novel materials, ligands or biological sensors.
In vivo imaging of the human rod photoreceptor mosaic (2010)

Although single cone receptors have been imaged <i>in vivo</i>, to our knowledge there has been no observation of rods in the living normal eye. Using an adaptive optics ophthalmoscope and post processing, evidence of a rod mosaic was observed at 5° and 10° eccentricities in the horizontal temporal retina. For four normal human subjects, small structures were observed between the larger cones and were observed repeatedly at the same locations on different days, and with varying wavelengths. Image analysis gave spacings that agree well with rod measurements from histological data.
Does Therapeutic Drug Monitoring of Ribavirin in HCV Genotype 3 Treatment With Sofosbuvir and Ribavirin Still Have a Role? (2014)

Brochot, Etienne PharmD, PhD; Bodeau, Sandra PharmD, PhD; Duverlie, Gilles PharmD, PhD Author Information
Alchemical Absolute Protein-Ligand Binding Free Energies for Drug Design (2021)

Recent advances in relative protein-ligand binding free energy calculations have shown the value of alchemical methods in drug discovery. Accurately assessing absolute binding free energies remains a challenging endeavour, mostly limited to small model cases. We demonstrate accurate absolute binding free energy estimates for 128 pharmaceutically relevant ligands across 7 proteins using a highly parallelizable non-equilibrium method. These calculations also provide detailed physical insight into the structural determinants of binding, identifying subtle rotamer rearrangements between protein apo and holo states that are crucial for binding. The challenge behind absolute binding free energy calculations stems in large part from the need to explicitly account for the protein’s apo state. In this work we present several approaches to obtain apo state ensembles, including a novel rigorous method to generate protein-ligand ensembles for the ligand in its decoupled state. Altogether, we present an effective open-source protocol for prospective application in drug discovery.
Another look at HMAC. (2012)

Abstract. HMAC is the most widely-deployed cryptographic-hash-function-based message authentication code. First, we describe a security issue that arises because of inconsistencies in the standards and the published literature regarding keylength. We prove a separation result between two versions of HMAC, which we denote HMACstd and HMACBel, the former being the real-world version standardized by Bellare et al. in 1997 and the latter being the version described in Bellare’s proof of security in his Crypto 2006 paper. Second, we describe how HMACNIST (the FIPS version standardized by NIST), while provably secure (in the single-user setting), succumbs to a practical attack in the multi-user setting. Third, we describe a fundamental defect from a practice-oriented standpoint in Bellare’s 2006 security result for HMAC, and show that because of this defect his proof gives a security guarantee that is of little value in practice. We give a new proof of NMAC security that gives a stronger result for NMAC and HMAC and we discuss why even this stronger result by itself fails to give convincing assurance of HMAC security. 1.
Stratix 10 NX Architecture (2022)

The advent of AI has driven the exploration of high-density low-precision arithmetic on FPGAs. This has resulted in new methods in mapping both arithmetic functions as well as dataflows onto the fabric, as well as some changes to the embedded DSP Blocks. Technologies outside of the FPGA realm have also evolved, such as the addition of tensor structures for GPUs, as well as the introduction of numerous AI ASSPs, all of which have a higher claimed performance and efficiency than current FPGAs. In this article, we will introduce the Stratix 10 NX device, which is a variant of FPGA specifically optimized for the AI application space. In addition to the computational capabilities of the standard programmable soft-logic fabric, a new type of DSP Block provides the dense arrays of low-precision multipliers typically used in AI implementations. The architecture of the block is tuned for the common matrix-matrix or vector-matrix multiplications in AI, with capabilities designed to work efficiently for both small and large matrix sizes. The base precisions are INT8 and INT4, along with shared exponent support to support block FP16 and block FP12 numerics. All additions/accumulations can be done in INT32 or IEEE-754 single precision floating point (FP32), and multiple blocks can be cascaded together to support larger matrices. We will also describe methods by which the smaller precision multipliers can be aggregated to create larger multipliers that are more applicable to standard signal processing requirements. In the AI market, the FPGA must compete directly with other types of devices, rather than occupy a unique niche. Deterministic system performance is as important as the performance of individual FPGA elements, such as logic, memory, and DSP. We will show that the feed forward datapath structures that are needed to support the typical AI matrix-vector and matrix-matrix multiplication operations can consistently close timing at over 500 MHz on a mid-speed grade device, even if all of the Tensor Blocks on the device are used. We will also show a full-chip NPU processor implementation that out performs GPUs at the same process node for a variety of AI inferencing workloads, even though it has a lower operating frequency of 365 MHz. In terms of overall compute throughput, Stratix 10 NX is specified at 143 INT8/FP16 TOPs/FLOPs or 286 INT4/FP12 TOPS/FLOPs. Depending on the configuration, power efficiency is in the range of 1–4 TOPs or TFLOPs/W.
Investigation on interference rejection combining receiver in heterogeneous networks for LTE-Advanced downlink (2013)

In Long-Term Evolution (LTE)-Advanced, heterogeneous networks where low power nodes such as picocells are overlaid onto macrocells were extensively investigated to improve further the system throughput per unit area. In heterogeneous networks, to achieve an offloading gain from macrocells to picocells, cell range expansion (CRE) is applied. Additionally, inter-cell interference coordination (ICIC) is applied to reduce the severe inter-cell interference transmitted from the macrocells to the sets of user equipment (UEs) connected to the picocells. In such cases, since the interference statistics are completely different from traditional well-planned macrocell deployments according to the parameters specified for CRE and ICIC, it is important to investigate using the interference rejection combining (IRC) receiver because it effectively improves the cell-edge user throughput by suppressing interference from the surrounding cells. To clarify the improvement in user throughput due to the IRC receiver, this paper investigates the interference statistics and evaluates the user throughput performance of the IRC receiver in heterogeneous networks employing CRE and ICIC. Simulation results show that the throughput gain from the IRC receiver becomes small due to a reduction in the severe inter-cell interference from ICIC. However, we clarify that a cell-edge user throughput gain from the IRC receiver exceeding 10% is achieved compared to the conventional minimum mean square error (MMSE) receiver in a heterogeneous network with four picocells within each macrocell. Furthermore, we show that the same parameters specified for CRE and ICIC can be set regardless of the IRC or conventional MMSE receiver.
Percutaneous repair of punctured subclavian artery under fluoroscopy (2002)

Tsang, John MD, FRCPC; Martin, Michael MD, FRCPC; Machan, Lindsay MD, FRCPC Author Information
Prio: Private, Robust, and Scalable Computation of Aggregate Statistics (2017)

This paper presents Prio, a privacy-preserving system for the collection of aggregate statistics. Each Prio client holds a private data value (e.g., its current location), and a small set of servers compute statistical functions over the values of all clients (e.g., the most popular location). As long as at least one server is honest, the Prio servers learn nearly nothing about the clients' private data, except what they can infer from the aggregate statistics that the system computes. To protect functionality in the face of faulty or malicious clients, Prio uses secret-shared non-interactive proofs (SNIPs), a new cryptographic technique that yields a hundred-fold performance improvement over conventional zero-knowledge approaches. Prio extends classic private aggregation techniques to enable the collection of a large class of useful statistics. For example, Prio can perform a least-squares regression on high-dimensional client-provided data without ever seeing the data in the clear.
Assessment of complete basis set methods for calculation of enthalpies of formation (1998)

Three complete basis set models of Petersson et al. [J. Chem. Phys. 104, 2598 (1996)], CBS-Q, CBS-q, and CBS-4, have been assessed on the G2 neutral test set of 148 molecules [J. Chem. Phys. 106, 1063 (1997)]. The average absolute deviations with experiment of the calculated enthalpies of formation from the three CBS methods are 1.57 kcal/mol (CBS-Q), 2.13 kcal/mol (CBS-q), and 3.06 kcal/mol (CBS-4). The maximum deviations of the methods are 11.2, 10.3, and 14.4 kcal/mol. respectively. The most accurate method, CBS-Q, has an average absolute deviation similar to that of G2 theory. The three CBS methods have also been assessed on a 40 molecule set using isodesmic bond separation reactions to calculate enthalpies of formation. There is a significant improvement in the accuracy of the enthalpies compared to those calculated using atomization energies, although not as much as for G2 theory. In a test on naphthalene, enthalpies calculated using the CBS methods have large deviations. The CBS-Q method has a deviation of 28.7 kcal/mol and, surprisingly, the deviation increases to 34.3 kcal/mol when isodesmic bond separation reaction energies are used.
Stabilizing Supported Ni Catalysts for Dry Reforming of Methane by Combined La Doping and Al Overcoating Using Atomic Layer Deposition (2022)

Deposition of La2O3 and Al2O3 on Al2O3-supported Ni catalysts was performed to study their effects on heterogeneous catalysts for the dry reforming of methane (DRM) reaction. An alumina-supported Ni catalyst (Ni/Al2O3, 2 wt % of Ni), synthesized via incipient wetness impregnation, loses ∼87% of its initial activity within 45 h under DRM conditions. While overcoating of Al2O3 on this catalyst via atomic layer deposition (ALD) helps stabilize the catalytic activity in long time-on-stream (TOS) tests, this overcoated catalyst is ca. 40 times less active than the uncoated catalyst at peak activity. This Al2O3-overcoated Ni/Al2O3 catalyst also exhibits a long induction period (∼20 h) due to the slow reduction of Ni2+ within the catalytically inactive nickel aluminate (NiAl2O4) phase, formed by the interaction of metallic Ni with the Al2O3 overcoat during pre-DRM treatment at the 700 °C reaction temperature. Here, we report that, while doping small amounts of La (∼0.03 wt %) into the Ni/Al2O3 catalyst does not significantly affect the catalytic activity or stability by itself, the addition of ALD-Al2O3 on top of the La2O3-promoted Ni catalysts significantly suppresses the long TOS deactivation, helps recover the peak activity of uncoated Ni/Al2O3, and eliminates the DRM induction period. This strategy obtains the stabilization benefits of Al2O3 overcoating on Ni/Al2O3 while, at the same time, avoiding the formation of undesirable NiAl2O4 species.
Cognitive Rehabilitation Interventions for Neglect and Related Disorders: Moving from Bench to Bedside in Stroke Patients (2006)

The spatial neglect syndrome, defined by asymmetric attention and action not attributed to primary motor or sensory dysfunction and accompanied by functional disability, is a major cause of post-stroke morbidity. In this review, we consider the challenges and obstacles facing scientific researches wishing to evaluate the mechanisms and effectiveness of rehabilitation interventions. Spatial neglect is a heterogeneous disorder, for which consensus research definitions are not currently available, and it is unclear which of the deficits associated with the syndrome causes subsequent disability. We review current opinion about methods of assessment, suggest a rational approach to selecting therapies which requires further study, and make systems-level and theoretical recommendations for building theory. We lastly review some creative questions for consideration in future research.
Analysis of Anxious Word Usage on Online Health Forums (2016)

Nicolas Rey-Villamizar, Prasha Shrestha, Farig Sadeque, Steven Bethard, Ted Pedersen, Arjun Mukherjee, Thamar Solorio. Proceedings of the Seventh International Workshop on Health Text Mining and Information Analysis. 2016.
A fine-grained protection mechanism in object-based operating systems (2002)

The paper describes the design and implementation of a flexible, fine-grained protection mechanism for operating systems based on an object/thread model. The mechanism has the following features: (1) it provides fine-grained protection: each thread has a list of keys (capabilities) and inherits object's keys when it invokes an abject. (2) The mechanism is very flexible: a combination of multiple keys are used to represent various conditions for accessing objects. (3) It allows a group of keys to be defined as key group, which realizes hierarchical, integrated key processing and management. (4) Users can specify an SCL (subject control list), which defines a list of objects that a subject can invoke. This is used to restrict subjects; suspected subjects are only allowed to access the objects specified in the SCL. The proposed mechanism is being implemented in an object-based operating system which the authors are developing. Implementation techniques to improve efficiency are also described.
Microflow size exclusion chromatography to preserve micromolar affinity complexes and achieve subunit separations for native state mass spectrometry (2022)

For high throughput native mass spectrometry (MS) protein characterization, it is advantageous to desalt and separate proteins by size exclusion chromatography (SEC). Sensitivity, resolution, and speed in these methods remain limited by standard SEC columns. Moreover, the efficient packing of small bore columns is notoriously difficult. SEC sensitivity is inherently limited because solutes are not focused into concentrated bands and low affinity native complexes may dissociate on column. Recent work evaluated the suitability of crosslinked gel media in small bore formats for online desalting. Here, small bore format online SEC for native MS studies is again investigated but with alternative materials. We systematically studied the utility of diol and hydroxy terminated polyethylene oxide (PEO) bonded 1.7 µm organosilica particles as packed into 1 mm ID stainless steel (SS) hardware and hardware treated with hydrophilic hybrid surface technology (h-HST). For the equivalent diol-bonded particle and hardware, UV limits of detection (LODs) were reduced 32 to 89% with a microflow separation (15 µL/min) on a 1 × 50 mm column as compared to a 4.6 × 150 mm high-flow separation (300 µL/min) at the same linear velocity. Run times were also shortened by 45%. A switch from SS to h-HST hardware led to a significant reduction in secondary interactions and a corresponding improvement in detection limits for trastuzumab, myoglobin, IgG and albumin for both UV and MS. Coupling of the small bore columns to multichannel microflow emitters resulted in 10 to 100-fold gains in MS sensitivity, depending on the analyte. MS LOD values were significantly reduced into the low attomole ranges. Columns were then evaluated for their effects on the preservation of complexes, including concanavalin A, in its apo and ligand-bound states, and three therapeutically relevant noncovalent systems previously undetected on large column formats. The results suggest that the detection of large complexes by SEC is not just a function of sensitivity but is directly affected by chemical secondary interactions. The ability to detect 0.1 to 1 MDa complexes, with between 1 and 40 micromolar dissociation constants, represents a critical advancement for high-throughput native MS workflows as applied to the analysis of therapeutics.
Quantitative Determination of Phenytoin and Phenobarbital in Capillary Blood by Ames Seralyzer (1987)

We evaluated the use of serum obtained from capillary blood specimens with the Seralyzer ARIS (AMES Division Miles Laboratories) assay for phenytoin (PHT) and phenobarbital (PB). The Ames Seralyzer method is capable of measuring PHT and PB concentrations in 10 microliter of serum. Therefore, it may be used to measure concentrations of these drugs in small blood samples, such as obtained by skin puncture and capillary tube collection. In this study, simultaneous venous and capillary samples were obtained from 90 patients with epilepsy. Seralyzer results were compared with serum values from venous blood determined with a gas chromatographic (GC) method. Comparison of PHT values obtained by Seralyzer (Ys) versus GC by linear regression gave the equation: Ys = 0.36 + 0.88 X (r2 = 0.93, n = 63). The mean difference between the Seralyzer and GC was -0.96 micrograms/ml (p less than 0.001). For PB, the equation was: Ys = -0.53 + 1.07 X (r2 = 0.93, n = 31) with a mean difference of +1.28 micrograms/ml (p = 0.02).
Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity (2018)

Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer's disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid β (Aβ)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Aβ, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Aβ, without affecting metabolic function. ATZ was effective at concentrations 10 times lower than MTZ. Both MTZ and ATZ prevented mitochondrial membrane depolarization and H<sub>2</sub> O<sub>2</sub> generation, with no effects on intracellular pH or ATP production. Importantly, the drugs did not primarily affect calcium homeostasis. This work suggests a new role for carbonic anhydrases (CAs) in the Aβ-induced mitochondrial toxicity associated with AD and cerebral amyloid angiopathy (CAA), and paves the way to AD clinical trials for CAIs, FDA-approved drugs with a well-known profile of brain delivery.
Supplementary Figure S2 from NMS-E973, a Novel Synthetic Inhibitor of Hsp90 with Activity against Multiple Models of Drug Resistance to Targeted Agents, Including Intracranial Metastases (2023)

&lt;p&gt;Supplementary Figure S2 - PDF file 456K, Time-lapse imaging of A375 cells treated with NMS-E973&lt;/p&gt;
Characterization studies of two novel active pixel sensors (2007)

A United Kingdom consortium (MI3) is founded to develop advanced CMOS image sensors for scientific applications. “Vanilla,” a 520×520 array of active pixels with 25-µm pitch is fabricated in the 0.35-µm 4M2P (4 metal, 2 poly) CMOS process and uses a 3.3-V supply. It has flushed reset circuitry to attain low reset noise and random pixel access for high-speed region-of-interest (ROI) readout. “OPIC” is a 64×72 test structure array of digital pixels with 30-µm pitch, fabricated in 0.25-µm 5M1P (5 metal 1 poly) CMOS process with a 3.3/2.5-V supply. It can perform thresholding via an in-pixel comparator for sparse readout at a high frame rate. Characterization of both sensors is performed under optical illumination and x-ray exposure. For x-ray characterization, both sensors were coupled to a structured thallium-doped cesium iodide (CsI:Tl) scintillator via a fiber optic plate. Vanilla has been found to exhibit 34±3e− read noise and a spectral response of 225±5 mA/W at 500 nm and can read a 6×6 ROI at 24,395 frames/s. OPIC has 46±3e− read noise and can perform sparse readout at up to 3700 frames/s. Based on these results, Vanilla could be employed for applications where only a small portion of the image contains relevant information, while OPIC is suited to high-speed imaging applications.
An Antigenic Threshold for Maintaining Human Immunodeficiency Virus Type 1-specific Cytotoxic T Lymphocytes (2000)

Our findings suggest that a complex, rather than a monotonic, relationship exists between CTL levels and HIV-1 viremia, including what appears to be an antigenic threshold for the maintenance of CTL at a measurable level. Under conditions of "antigen excess,", CTLe levels correlate inversely with viral load. On the other hand, under conditions that are "antigen limited," the correlation appears to be direct.