gebhart/patrepeval huggingface dataset:
319. Rationally Designed AAV Inverted Terminal Repeats Enhance Gene Targeting (2016)

Basic and clinical applications of mammalian genetic engineering rely on selective pressure and/or, ironically, DNA damage at or near the modification site to obtain relevant efficiencies. In regards to the later situation, continuously evolving endonuclease technologies remain focused on the generation of a site-specific DNA double strand break to stimulate homology directed repair (HDR). The stimulation of HDR is thus dictated by the ability of the endonuclease platform to specifically recognize its cognate site, with safety concerns dictated by its promiscuity influenced by its persistence. To eliminate the serious safety concerns associated with designer endonucleases while maintaining efficient HDR, it was hypothesized that rational modification of a viral DNA repair substrate would enhance gene editing without the requirement for induced chromosomal damage. Specifically, modifications of the adeno-associated virus (AAV) inverted terminal repeat sequence (ITR), in a viral vector context, were evaluated for stimulation of HDR in human cells. The results demonstrate an approximate 30-fold enhancement of AAV gene targeting using a particular rationally designed ITR sequence. Characterization of this event suggests that differences in the inherent ITR-initiated transcriptional activity and altered interactions with host DNA repair proteins contribute to the enhancement in HDR. The collective results demonstrate for the first time that alterations in the ITR sequence can enhance AAV gene targeting. Importantly, the refinement of such vectors may offer a safer alternative to site-specific endonuclease technologies as on- and off-target DNA cleavage concerns are eliminated.
Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions (2010)

We have developed several multifunctional thiourea catalysts bearing a tertiary amine or an 1,2-amino alcohol in expectation of their synchronous activation of a nucleophile and an electrophile through both acid-base and hydrogen-bonding interactions. From these studies, it was revealed that the weak acidity of thioureas compared with metallic Lewis acids could be overcome by this modification. The bifunctional aminothiourea could be used efficiently for a wide range of diastereoselective and enantioselective nucleophilic reactions such as Michael addition of 1,3-dicarbonyl compounds to nitroolefines, aza-Henry reaction of nitroalkanes to N-Boc imines, and hydrazination of cyclic beta-keto esters. We also discovered that multifunctional thiourea catalyst, bearing an 1,2-amino alcohol moiety, significantly accelerated the Petasis-type reaction of alkenylboronic acids to N-phenoxycarbonyl quinolinium salts, prepared from quinolines and phenyl chloroformate, to afford 1,2-addition products with high enantioselectivity (up to 97% ee). Furthermore, to expand the synthetic applicability of the thiourea-catalyzed asymmetric reactions, tandem organocatalyzed reactions were explored to establish the concise one-pot synthesis of chiral densely functionalized three-, five-, and six-membered compounds.
Exploring the use of crowdsourcing to support empirical studies in software engineering (2010)

The power and the generality of the findings obtained through empirical studies are bounded by the number and type of participating subjects. In software engineering, obtaining a large number of adequate subjects to evaluate a technique or tool is often a major challenge. In this work we explore the use of crowdsourcing as a mechanism to address that challenge by assisting in subject recruitment. More specifically, through this work we show how we adapted a study to be performed under an infrastructure that not only makes it possible to reach a large base of users but it also provides capabilities to manage those users as the study is being conducted. We discuss the lessons we learned through this experience, which illustrate the potential and tradeoffs of crowdsourcing software engineering studies.
Latest Advances in Modified/Functionalized Carbon Nanotube- Based Gas Sensors (2013)

A gas sensor is a device that when exposed to gaseous species, is able to alter one or more of its physical properties, so that can be measured and quantified, directly or indirectly. These devices are used for applications in homeland security, medical diagnosis, environmental pollution, food processing, industrial emission, public security, agriculture, aerospace and aeronautics, among others. Desirable characteristics of a gas sensor are selectivity for differ‐ ent gases, sensitivity at low concentrations, fast response, room temperature operation (some applications may require high temperature), low power consumption, low-cost, low maintenance and portability. Traditional techniques like gas chromatography (GC), GC cou‐ pled to mass spectrometry (GC-MS), Fourier transmission infrared spectroscopy (FTIR) and atomic emission detection (AED) provide high sensitivity, reliability and precision, but they are also bulky, time consuming, power consuming, operate at high temperature, and the high maintenance and requirement of trained technicians translate in high costs. In an effort to overcome those disadvantages, research in the area has been focused on the search for functional sensing materials.
Binding of the glycan of the major outer membrane protein of Chlamydia trachomatis to HeLa cells (1994)

Recent studies have shown that the major outer membrane protein (MOMP) of Chlamydia trachomatis is glycosylated. The glycan of the MOMP of C. trachomatis serovar L2 was separated from the glycoprotein with N-glycanase, reduced with tritiated NaBH4, and tested for its ability to interact with HeLa cells. The [3H]glycan was shown to attach readily to HeLa cells at 25 or 37 degrees C. This process was slower at 4 degrees C. Competition for possibly similar receptor sites on HeLa cells between the glycan and a sugar, an aminosaccharide, or elementary bodies (EBs) was then studied. D-Galactose, D-mannose, or N-acetylglucosamine was shown to reduce the attachment of the glycan to HeLa cells at concentrations of 0.1 to 0.5 M. Sedoheptulose, D-fructose, or sialic acid did not inhibit the binding of glycan to HeLa cells. The presence of at least 100 native or UV-inactivated EBs per HeLa cell interfered with the glycan's ability to bind to HeLa cells. Heat-inactivated EBs did not compete with the glycan for binding. In the reverse situation, nonradiolabeled glycan prevented the EBs from infecting and forming inclusions in HeLa cells. Incubation of [3H]glycan with rabbit immune serum prepared against antigens of whole EB and the MOMP inhibited attachment. In contrast, incubation of glycan with mouse monoclonal antibodies against the protein portion of the MOMP or the chlamydial lipopolysaccharide did not inhibit attachment. These results suggest that the glycan portion of the MOMP is involved in the attachment process of C. trachomatis organisms to HeLa cells.
Passive Noise Analysis Studies on Tampering Indication (2018)

Idaho National Laboratory (INL) is part of a multi-laboratory research project tasked with investigating methods for detection of tampering on unattended/remotely monitored systems (UMS) in International Atomic Energy Agency (IAEA) installations. Ensuring that the detector signals received at the IAEA cabinet are authentic is central to the independence of IAEA’s safeguards conclusions. INL is investigating a passive noise analysis technique in the frequency domain to detect tampering. Prior work performed by INL showed a proof-of-principle method in which changes in ambient conditions could be observed in the frequency spectrum. In this paper several new findings, as well as further investigation into prior findings used for tamper indication, will be presented. Information from various parts of the spectrum and the whole spectrum can be used to determine temperature changes, modifications made to a pre-amplifier/amplifier or the replacement, changes to the neutron detector, replacement of the transmission cable, tapping into the cable and teeing off the signal from the cable. Future work will investigate the viability of these indicators to detect tampering for normal operation, noisy environments and real world applications.
Parsimonious Tomography (2018)

Network tomography using end-to-end probes provides a powerful tool for monitoring the performance of internal network elements. However, active probing can generate tremendous traffic, which degrades the overall network performance. Meanwhile, not all the probing paths contain useful information for identifying the link metrics of interest. This observation motivates us to study the optimal selection of monitoring paths to balance identifiability and probing cost. Assuming additive link metrics (e.g., delays), we consider four closely-related optimization problems: 1) Max-ILCost that maximizes the number of identifiable links under a probing budget, 2) Max-Rank-Cost that maximizes the rank of selected paths under a probing budget, 3) Min-Cost-IL that minimizes the probing cost while preserving identifiability, and 4) Min-Cost-Rank that minimizes the probing cost while preserving rank. While (1) and (3) are hard to solve, (2) and (4) are easy to solve, and the solutions give a good approximation for (1) and (3). Specifically, we provide an optimal algorithm for (4) and a (1?1/e)-approximation algorithm for (2). We prove that the solution for (4) provides tight upper/lower bounds on the minimum cost of (3), and the solution for (2) provides upper/lower bounds on the maximum identifiability of (1). Our evaluations on real topologies show that solutions to the rank-based optimization (2, 4) have superior performance in terms of the objectives of the identifiability-based optimization (1, 3), and our solutions can reduce the total probing cost by an order of magnitude while achieving the same monitoring performance.
ICAM-1 as a molecular target for triple negative breast cancer (2014)

Triple negative breast cancers (TNBCs) have a high mortality rate owing to aggressive proliferation and metastasis and a lack of effective therapeutic options. Herein, we describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human TNBC cell lines and tissues, and demonstrate that ICAM-1 is a potential molecular target and biomarker for TNBC therapy and diagnosis. We synthesized ICAM-1 antibody-conjugated iron oxide nanoparticles (ICAM-IONPs) as a magnetic resonance imaging (MRI) probe to evaluate tumor targeting. Quantitative analysis of ICAM-1 surface expression predicted the targeting capability of ICAM-IONPs to TNBC cells. MRI of the TNBC xenograft tumor after systemic administration of ICAM-IONPs, coupled with iron quantification and histology, demonstrated a significant and sustained MRI contrast enhancement and probe accumulation in tumors with ICAM-1 overexpression relative to control. Identification of ICAM-1 as a TNBC target and biomarker may lead to the development of a new strategy and platform for addressing a critical gap in TNBC patient care.
Blockade of CC chemokine receptor 5 (CCR5)-tropic human immunodeficiency virus-1 replication in human lymphoid tissue by CC chemokines. (1998)

The CC chemokines MIP-1alpha, MIP-1beta, and RANTES suppress replication of certain HIV-1 strains in cultured PBMC and T cell lines by blocking interaction of gp120 with CC chemokine receptor 5 (CCR5). However, the same chemokines can enhance HIV-1 replication in cultured macrophages. The net effect of chemokines on HIV-1 infection in intact lymphoid tissue, the major reservoir of HIV-1 in vivo, is unknown and unpredictable since the tissue contains both T lymphocytes and macrophages. Here we show that exogenous MIP-1alpha, MIP-1beta, and RANTES markedly suppressed replication of CCR5-tropic HIV-1 strains in blocks of human lymphoid tissue infected ex vivo. Moreover, endogenous MIP-1alpha, MIP-1beta, and RANTES were upregulated in tissues infected ex vivo with CXC chemokine receptor 4-tropic but not CCR5-tropic HIV-1. Such an upregulation may contribute to the virus phenotype shift in the course of HIV disease in vivo.
Relationships between EEG Coherence and Neuropsychological Tests in Dementia (1995)

Previous research has demonstrated differences in resting state EEG coherence among groups of subjects with dementia of the Alzheimer type (DAT), multi-infarct dementia (MID), and normal elderly controls. Since reduced coherence between brain sites has been thought to reflect functional disconnection between brain areas, we hypothesized that decreased coherence would be associated with cognitive dysfunction as assessed by neuropsychological tests. We correlated several neuropsychological tests with four coherence variables and found that reduced coherence was associated with impairment on specific neuropsychological tests in ways that conform to and supplement current knowledge about the localization of brain functions. The results are consistent with the hypothesis that coherence reflects a functional breakdown in communication between brain areas, and that coherence may be a more precise way to localize brain function than other EEG variables.
Processing Parameters Optimization on Control of Residual Stresses and Distortion during High-Speed Milling of Thin-Walled Workpiece (2012)

In the aerospace and auto industries, the residual tensile stresses will cause the structures broke and damaged. Hence, different methods were considered to optimize the machining processes. In this article, a residual stresses calculation model using AdvantEdge 2D turning was integrated with 2D milling physical model in order to analyze high-speed milling thin-walled workpiece. Through optimizing the processing parameters (improving the cutting speed and decreasing the cutting depth) during high-speed milling, not only we can get a high removal rate and receive a distribution of equably surface residual stresses, but also a slowing down trend of in-depth residual stress can be obtained. In addition, we evaluate this method using a typical part at the sensitive area, and the machining quality can be improved obviously.
Energy Flow Analysis of Excavator System Based on Typical Working Condition Load (2022)

Accurate energy flow results are the premise of excavator energy-saving control research. Only through an accurate energy flow analysis based on operating data can a practical excavator energy-saving control scheme be proposed. In order to obtain the excavator’s accurate energy flow, the excavator components’ performance and operating data requirements are obtained, and the experimental schemes are designed to collect it under typical working conditions. The typical working condition load is reconstructed based on wavelet decomposition, harmonic function, and theoretical weighting methods. This paper analyzes the excavator system’s energy flow under the typical working condition load. In operation conditions, the output energy of the engine only accounts for 50.21% of the engine’s fuel energy, and the actuation and the swing system account for 9.33% and 4%, respectively. In transportation conditions, the output energy of the engine only accounts for 49.80% of the engine’s fuel energy, and the torque converter efficiency loss and excavator driving energy account for 15.09% and 17.98%, respectively. The research results show that the energy flow analysis method based on typical working condition load can accurately obtain each excavator component’s energy margin, which provides a basis for designing energy-saving schemes and control strategies.
Generation of α-Particle Beams With a Multi-kJ, Peta-Watt Class Laser System (2020)

We present preliminary results on generation of energetic -particles driven by lasers. The experiment was performed at the Institute of Laser Engineering in Osaka using the short-pulse, high-intensity, high-energy, PW-class laser. The laser pulse was focused onto a thin plastic foil (pitcher) to generate a proton beam by the well-known TNSA mechanism which, in turn, was impinging onto a boron-nitride (BN) target (catcher) to generated alpha-particles as a result of proton-boron nuclear fusion events. Our results demonstrate generation of -particles with energies in the range 8-10 MeV and with a flux around 5 e9 sr-1.
Pegylated liposomal doxorubicin in the treatment of cancers of the breast and ovary (2006)

Peglyated liposomal doxorubicin was developed to maintain or enhance the demonstrated antineoplastic effects of doxorubicin, while improving the toxicity profile associated with this important cytotoxic agent. Accumulating clinical data have confirmed the activity of pegylated liposomal doxorubicin in cancers of the breast and ovary. Furthermore, Phase II and III trial experience has revealed that the drug produces objective responses comparable in rate and duration to doxorubicin and other single agents employed in metastatic breast cancer. In recurrent and platinum-resistant ovarian cancer, single-agent pegylated liposomal doxorubicin has assumed an important role in routine patient management.
Synchronous high‐voltage spindles in the cortex–basal ganglia network of awake and unrestrained rats (2007)

Synchronous oscillations in various frequency ranges have been recorded in several nuclei of the basal ganglia (BG) and are thought to be an information processing mechanism. High-voltage spindles (HVSs) are 5-13 Hz spike-and-wave oscillations, which are commonly recorded in rats and which have been reported in some recent studies where their occurrence in the BG has been investigated. We recorded single neurons and local field potentials (LFPs) simultaneously in the motor cortex, striatum and substantia nigra pars reticulata (SNr) of the freely moving rat. We took advantage of the high level of synchronization observed during HVSs to study signal transmission in the cortex-BG network in the awake animals. The results show that LFPs are synchronized in the motor cortex, striatum and SNr during HVS episodes and that the latter propagate from the cortex to the SNr via the striatum. Moreover, > 50% of single neurons in each of these structures are triggered by the HVS. Following the discharge of cortical cells, SNr neurons are first inhibited after approximately 19 ms and then activated after approximately 45 ms. This response is probably driven by the direct and indirect pathways, respectively, without any involvement of the hyperdirect pathway. Here, it is shown that cortex-BG connectivity can be studied using physiological signals in the freely moving animal as opposed to artificial stimulation under anaesthetized conditions. This opens the door to further studies under various experimental conditions, such as animal models of basal ganglia disorders.
Buccally Absorbed Cannabidiol Shows Significantly Superior Pain Control and Improved Satisfaction Immediately After Arthroscopic Rotator Cuff Repair: A Placebo-Controlled, Double-Blinded, Randomized Trial (2022)

NCT04672252 (ClinicalTrials.gov identifier).
Discovery of Potent KIFC1 Inhibitors Using a Method of Integrated High-Throughput Synthesis and Screening (2014)

KIFC1 (HSET), a member of the kinesin-14 family of motor proteins, plays an essential role in centrosomal bundling in cancer cells, but its function is not required for normal diploid cell division. To explore the potential of KIFC1 as a therapeutic target for human cancers, a series of potent KIFC1 inhibitors featuring a phenylalanine scaffold was developed from hits identified through high-throughput screening (HTS). Optimization of the initial hits combined both design-synthesis-test cycles and an integrated high-throughput synthesis and biochemical screening method. An important aspect of this integrated method was the utilization of DMSO stock solutions of compounds registered in the corporate compound collection as synthetic reactants. Using this method, over 1500 compounds selected for structural diversity were quickly assembled in assay-ready 384-well plates and were directly tested after the necessary dilutions. Our efforts led to the discovery of a potent KIFC1 inhibitor, AZ82, which demonstrated the desired centrosome declustering mode of action in cell studies.
Challenges of Preoperative Diagnosis and Management of Scalene Intramuscular Angioma (2015)

Intramuscular angioma of scalene muscle is rare with only five cases reported so far. Four of them have not been suspected before surgery; one was diagnosed preoperatively by core biopsy. Preoperative diagnosis is important for management. Awareness of cytologic features could help preoperative diagnosis when need of ruling out malignancy and coagulopathy make fine needle aspiration a choice. We herein demonstrate a new case of a 27 year old male with history of hepatocellular carcinoma, who presented with a 6 cm left supraclavicular mass. The fine needle aspiration was paucicellular; however, the bland ovoid to spindle cells with a whirling and luminal arrangement in the background of blood, fatty drops and degenerate muscle are suggestive of intramuscular angioma. The magnetic resonance imagines (MRI) demonstrate a T1 isointense and T2 hyperintense ill-defined lesion splaying anterior and mid scalene muscles with subtle vascular voids at periphery. These features in combination with cytology findings indicate intramuscular angioma. The pre-operative findings are correlated to the histologic picture of mixed capillaries and varying sized venues intervening with fatty tissue and atrophic muscle. Intraoperatively, the mass is adjacent to the brachial plexus rootlets, interdigitating with the scalene muscle and pushing the carotid sheath, left subclavicular artery and vein aside. Following embolization, the mass is resected with minimal bleeding. Our case suggests that scalene intramuscular angioma can be successfully managed by surgery after embolization; preoperative diagnosis rendered by cytologic features and imaging characters would aid the planning of surgery.
Pipelined cordic architectures for fast VLSI filtering and array processing (2005)

The paper presents a revised functional description of Volder's Coordinate Rotation Digital Computer algorithm (CORDIC), as well as allied VLSI implementable processor architectures. Both pipelined and sequential structures are considered. In the general purpose or multi-function case, pipeline length (number of cycles), function evaluation time and accuracy are all independent of the various executable functions. High regularity and minimality of data-paths, simplicity of control circuits and enhancement of function evaluation speed are ensured, partly by mapping a unified set of micro-operations, and partly by invoking a natural encoding of the angle parameters. The approach benefits the execution speed in array configurations, since it will allow pipelining at the bit level, thereby providing fast VLSI implementations of certain algorithms exhibiting substantial structural pipelining or parallelism.