gebhart/patrepeval huggingface dataset:
Gene Therapy of Skin Adhesion Disorders (Mini Review) (2012)

Gene therapy is a potential treatment for severe inherited disorders for which there is little hope of finding a conventional cure. These include lethal diseases like immunodeficiencies and metabolic disorders, and non lethal conditions associated to poor quality of life and life-long symptomatic treatments, like muscular dystrophy, cystic fibrosis or thalassemia. Skin adhesion defects belong to both groups. For the non-lethal forms, gene therapy, or transplantation of cultured skin derived from genetically corrected epidermal stem cells, represents a very attractive therapeutic option, and potentially a definitive treatment. Recent advances in gene transfer and stem cell culture technology are making this option closer than ever. This paper critically reviews the progress and prospects of gene therapy for skin adhesion defects, and the factors currently limiting its development.
Remote collection and measurement of photogenerated carriers swept by surface acoustic waves in GaN (2004)

The interaction of surface acoustic waves and photogenerated carriers in GaN has been used for the fabrication of a remote ultraviolet detector where the carrier collector electrode is far away from the illuminated region. In this device, the recombination of the photogenerated carriers at the region where they are created is prevented by the potential fields associated with the acoustic wave, and the carriers are swept by the acoustic wave to the collector electrode. This effect is strongly dependent on the frequency and power of the acoustic waves and therefore of the input radio frequency signal. New optoelectronic devices based on the combination of the acoustic and electronic properties of the semiconductors can be envisaged.
Genetic encoding of non‐natural amino acids in Drosophila melanogaster Schneider 2 cells (2010)

Insect cells are useful for the high-yield production of recombinant proteins including chemokines and membrane proteins. In this study, we developed an insect cell-based system for incorporating non-natural amino acids into proteins at specific sites. Three types of promoter systems were constructed, and their efficiencies were compared for the expression of the prokaryotic amber suppressor tRNA(Tyr) in Drosophila melanogaster Schneider 2 cells. When paired with a variant of Escherichia coli tyrosyl-tRNA synthetase specific for 3-iodo-L-tyrosine, the suppressor tRNA transcribed from the U6 promoter most efficiently incorporated the amino acid into proteins in the cells. The transient and stable introductions of these prokaryotic molecules into the insect cells were then compared in terms of the yield of proteins containing non-natural amino acids, and the "transient" method generated a sevenfold higher yield. By this method, 4-azido-L-phenylalanine was incorporated into human interleukin-8 at a specific site. The yield of the azido-containing IL-8 was 1 microg/1 mL cell culture, and the recombinant protein was successfully labeled with a fluorescent probe by the Staudinger-Bertozzi reaction.
Antisense oligonucleotide treatment ameliorates IFN-γ–induced proteinuria in APOL1-transgenic mice (2019)

African Americans develop end-stage renal disease at a higher rate compared with European Americans due to 2 polymorphisms (G1 and G2 risk variants) in the apolipoprotein L1 (APOL1) gene common in people of African ancestry. Although this compelling genetic evidence provides an exciting opportunity for personalized medicine in chronic kidney disease, drug discovery efforts have been greatly hindered by the fact that APOL1 expression is lacking in rodents. Here, we describe a potentially novel physiologically relevant genomic mouse model of APOL1-associated renal disease that expresses human APOL1 from the endogenous human promoter, resulting in expression in similar tissues and at similar relative levels as humans. While naive APOL1-transgenic mice did not exhibit a renal disease phenotype, administration of IFN-γ was sufficient to robustly induce proteinuria only in APOL1 G1 mice, despite inducing kidney APOL1 expression in both G0 and G1 mice, serving as a clinically relevant "second hit." Treatment of APOL1 G1 mice with IONIS-APOL1Rx, an antisense oligonucleotide (ASO) targeting APOL1 mRNA, prior to IFN-γ challenge robustly and dose-dependently inhibited kidney and liver APOL1 expression and protected against IFN-γ-induced proteinuria, indicating that the disease-relevant cell types are sensitive to ASO treatment. Therefore, IONIS-APOL1Rx may be an effective therapeutic for APOL1 nephropathies and warrants further development.
Sigma Receptors and Cocaine Abuse (2011)

Sigma receptors have been well documented as a protein target for cocaine and have been shown to be involved in the toxic and stimulant actions of cocaine. Strategies to reduce the access of cocaine to sigma receptors have included antisense oligonucleotides to the sigma-1 receptor protein as well as small molecule ligand with affinity for sigma receptor sites. These results have been encouraging as novel protein targets that can attenuate the actions of cocaine are desperately needed as there are currently no medications approved for treatment of cocaine toxicity or addiction. Many years of research in this area have yet to produce an effective treatment and much focus was on dopamine systems. A flurry of research has been carried out to elucidate the role of sigma receptors in the blockade of cocaine effects but this research has yet to yield a clinical agent. This review summarizes the work to date on the linkage of sigma receptors and the actions of cocaine and the progress that has been made with regard to small molecules. Although there is still a lack of an agent in clinical trials with a sigma receptor mechanism of action, work is progressing and the ligands are becoming more selective for sigma systems and the potential remains high.
Alpes: a low profile electronically steered antenna for MobileSat(R) applications (2002)

An electronically steered phased array antenna for L-band mobile satellite communications applications using the Optus MobileSat(R) system is described. The antenna uses circularly polarised microstrip radiating elements in a conical arrangement with a profile only 120 mm in height including the radome. A closed loop tracking system based on the received RF signal strength and an open loop tracking system based on a gyroscope for beam steering during shadow conditions are incorporated within the antenna. The antenna has been designed and tested to operate in tough environmental conditions as encountered when mounted on road and track vehicles.
The use of five-alpha reductase inhibitors and their association with reclassification and pathologic outcomes in the Canary Prostate Active Surveillance Study (PASS). (2017)

22 Background: The outcomes of patients who enroll in active surveillance (AS) programs for prostate cancer (PCa) while currently taking five-alpha reductase inhibitors (5-ARIs) have not been well defined. Previous studies suggest that the initiation of 5-ARIs after enrolling in AS decreases the rate of reclassification and/or treatment for PCa, but there is still an FDA black box warning about the risk of grade risk prostate cancer while on 5-ARI. The objective of this study was to evaluate the safety of remaining on a 5-ARI after initiating AS for PCa. Methods: All men were enrolled in PASS. Inclusion criteria were current or never 5-ARI user, Gleason 3+3 or 3+4 PCa at diagnosis, ≤ 34% core ratio at diagnosis and ≥ 1 surveillance biopsy. Reclassification was defined as an increase in Gleason score and/or ratio of biopsy cores positive for cancer to ≥ 34%. Results: 1045 men were included in this study, 938 who had never used a 5-ARI and 107 5-ARI users. 5-ARI users had larger prostate volume (51 cc vs 40 cc, p &lt; 0.01), a higher rate of BPH (77% vs 29%, p &lt; 0.01) and older age (65 vs 62 years, p &lt; 0.01). All other clinical parameters, including serum PSA, were statistically similar. Kaplan Meier analysis of any reclassification is shown in the figure. There was no significant difference in any reclassification (p = 0.12). The use of 5-ARI at diagnosis was significantly protective for reclassification in a proportional hazards model (HR 0.68, p = 0.03); this difference was not significant after accounting for serum PSA, BMI, prostate size and positive cores ratio at diagnosis (HR 0.78, p = 0.18). There was no significant effect on adjusted analysis when evaluating for disease upgrading. 171 patients underwent radical prostatectomy (RP), 158 never 5-ARI users and 13 5-ARI users. There were no statistically significant differences when evaluating for Gleason grade or adverse pathology. 5-ARI users had a longer median time to RP (3.6 vs 2.1 years, p = 0.045). Conclusions: There is no association between 5-ARI use at diagnosis and reclassification on AS for men in the Canary PASS cohort. 5-ARI users have a longer median time to RP and do not have more severe PCa at RP.
Decreased T‐regulatory cells are associated with blood pressure elevation and sympathoexcitaton in hypertensive rats (875.10) (2014)

Background: Previous reports have suggested that T‐regulatory cells (Tregs) prevent angiotensin II (AngII)‐induced hypertension and organ damage. Abnormal sympathoexcitation is a major factor in the pathogenesis of hypertension. The aim of the present study was to determine whether Tregs are involved in the development of hypertension, and whether blockade of brain AngII type 1 receptors (AT1R)‐induced sympathoinhibition affects Tregs or not. Methods and Results: We examined Tregs in stroke‐prone spontaneously hypertensive rats (SHRSP) at 3 week (early pre‐hypertensive stage), 5 week (late pre‐hypertensive stage), or 15 week (established hypertensive stage) old, and in age‐matched normotensive Wistar‐Kyoto rats (WKY). CD4+CD25+Foxp3+ cells in the spleen and blood did not differ between WKY and early pre‐hypertensive SHRSP, whereas significantly decreased both in late pre‐hypertensive and established hypertensive SHRSP (p&lt;0.05). In established hypertensive SHRSP, intracerebroventricular infusion of losartan (AT1R blocker) for 2 weeks was done to cause depressor response with central sympathoinhibition, and Foxp3 mRNA expression in the spleen was significantly higher than in vehicle‐treated SHRSP. Conclusion: Decreases in T‐Regulatory cells precede blood pressure elevation in SHRSP, thereby Tregs play a key role in the development of hypertension associated with sympathoexcitation.
Tea polyphenol (−)‐epigallocatechin‐3‐gallate inhibits nicotine‐ and estrogen‐induced α9‐nicotinic acetylcholine receptor upregulation in human breast cancer cells (2010)

We found that the EGCG could be used as an agent for blocking smoking (Nic)- or hormone (E2)-induced breast cancer cell proliferation by inhibiting of α9-nAChR signaling pathway. This study reveals the novel antitumor mechanisms of EGCG, and these results may have significant applications for chemopreventive purposes in human breast cancer.
The value of internal carotid systolic velocity ratio for assessing carotid artery stenosis with Doppler sonography. (1999)

Using the ICSV/DICSV ratio for the Doppler detection of carotid artery stenosis is advantageous when the ICSV is 100 cm/sec or greater.
Nanometer Scale Actuation Of Magnetic Head Elements in Hard Disk Drives with Built-In Microheater (2006)

Today's head/disk interface design has a wide flying height distribution due to manufacturing tolerances, environmental variations, and write-induced thermal protrusion. To reduce the magnetic spacing loss caused by these effects, we developed an active head slider with a nano-thermal actuator. The magnetic spacing of these sliders can be controlled in-situ during drive operations. After simulating the heat transfer in the slider to obtain the thermal deformation of the air-bearing surface, we fabricated a thermal actuator using thin-film processing. An evaluation done using a read/write tester showed a linear reduction in the magnetic height as electric power was applied to the actuator. The actuator's stroke was 2.5 nm per 50 mW with a time constant of 1 msec.
Genome-Wide Polysome Profiling Reveals an Inflammation-Responsive Posttranscriptional Operon in Gamma Interferon-Activated Monocytes (2008)

We previously showed that ribosomal protein L13a is required for translational silencing of gamma interferon (IFN-gamma)-induced ceruloplasmin (Cp) synthesis in monocytes. This silencing also requires the presence of the GAIT (IFN-gamma activated inhibitor of translation) element in the 3' untranslated region (UTR) of Cp mRNA. Considering that Cp is an inflammatory protein, we hypothesized that this mechanism may have evolved to silence a family of proinflammatory proteins, of which Cp is just one member. To identify the other mRNAs that are targets for this silencing, we performed a genome-wide analysis of the polysome-profiled mRNAs by using an Affymetrix GeneChip and an inflammation-responsive gene array. A cluster of mRNAs encoding different chemokines and their receptors was identified as common hits in the two approaches and validated by real-time PCR. In silico predicted GAIT hairpins in the 3' UTRs of the target mRNAs were confirmed as functional cis-acting elements for translational silencing by luciferase reporter assays. Consistent with Cp, the newly identified target mRNAs also required L13a for silencing. Our studies have identified a new inflammation-responsive posttranscriptional operon that can be regulated directly at the level of translation in IFN-gamma-activated monocytes. This regulation of a cohort of mRNAs encoding inflammatory proteins may be important to resolve inflammation.
Wafer-scale high-density edge coupling for high throughput testing of silicon photonics (2018)

High-throughput functional testing of silicon photonics is a key challenge for scalable manufacturing. We present a technique for wafer-scale testing using high-density edge couplers that add excess loss of <2.2dB without requiring additional footprint.
Artificial Intelligence in the Open World (2008)

Opening Session of the Annual Meeting, Association for the Advancement of Artificial Intelligence. Presidential Lecture.
A cell-based screening system for influenza A viral RNA transcription/replication inhibitors (2013)

Although two classes of antivirals, NA inhibitors and M2 ion channel blockers, are licensed for influenza treatment, dual resistant mutants, including highly pathogenic H5N1 viruses, have appeared. Alternative treatment options are, therefore, needed. Influenza A viral RNA (vRNA) transcription/replication is a promising target for antiviral development, since it is essential for virus replication. Accordingly, an efficient and reliable method to identify vRNA transcription/replication inhibitors is desirable. Here, we developed a cell-based screening system by establishing a cell line that stably expresses influenza viral ribonucleoprotein complex (vRNP). Compound library screening using this cell line allowed us to identify a compound that inhibits vRNA transcription/replication by using reporter protein expression from virus-like RNA as a readout and virus replication in vitro. vRNP-expressing cells have potential as a simple and convenient high-throughput screening (HTS) system, and, thus, are promising to identify vRNA transcription/replication inhibitors for various RNA viruses, especially for primary screens.
Human Primary T Cells: A Practical Guide v2 (2018)

Human primary T cells are invaluable and feasible model systems to study the characteristics of the human immune cells in various contexts, including but not limited to cancer immunotherapy. Following isolation of T cells from fresh human blood samples, it is possible to culture, expand, and manipulate these cells, which allows extensive investigation for research purposes. Techniques for isolation and handling of T cells are well-established but parts of the protocols can highly vary across different labs. These differences in the protocols are, often, there due to historical reasons and are only supported by anecdotal evidence. We systematically modified basic components of the T cell culturing protocols and collected data on how they altered the final yield. Here, based on these data, we provide practical hints and tips on basic cellular and molecular techniques for handling primary human T cells. We hope that this guide will serve as a reference point to allow evaluate, discuss, and improve current practices in T cell culturing and manipulation.
A Multi-Physics Finite Element Model of a 35A Automotive Connector Including Multiscale Rough Surface Contact (2010)

Electrical contacts influence the reliability and performance of relays, electrical connectors, high power connectors, and similar systems, and are therefore a key region which needs to be considered. In the current study, a new inclusive multi-physics (involving mechanical, thermal and electrical fields) finite element model (FEM) of a 35A automotive connector has been developed. The contact resistance is predicted using a multiscale rough surface contact method and is embedded in the multi-physics FEM. The coupled connector model is solved to obtain stresses, contact pressures, electrical and thermal contact resistances, voltage, current density and temperature distributions. The results for the present connector show that the current conducts through a small volume of the connector and more optimal designs are possible that better use the connector material. The model is a powerful tool that can be used for the basic connector characterization, prototype evaluation and design through various material properties and surface finishes.
Chlorella vulgaris protects against lead‐induced hepatic toxicity in rats (2008)

This study was accomplished to investigate the effect of Chlorella vulgaris against lead‐induced oxidative stress especially associated with the liver fibrosis. Six weeks old Sprague‐Dawley male rats (n=10/group) were randomly divided into control group (Control; treated with drinking water) and lead‐chlorella groups (Pb+C0, Pb+C2, Pb+C5 and Pb+C10; treated with drinking water containing 200 ppm lead acetate + different concentrations of chlorella 0, 2, 5 and 10% by diet for 4 weeks). Superoxide dismutase activity was decreased in Pb+C0 compared to Control but increased in Pb+C2, Pb+C5 and Pb+C10 (128.9, 165.8 and 167.4% respectively) compared to Pb+C0 (P&lt;0.05). And also glutathione peroxidase and glutathione reductase activity were increased in lead‐chlorella groups compared to Pb+C0 (P&lt;0.05). The glutathione contents were decreased in Pb+C0 compared with other groups (P&lt;0.05). But contents of thiobarbituric acid reactive substances were increased in Pb+C0 (P&lt;0.05). The protein expression of transforming growth factor β1 and matrix metalloproteinase‐2 was significantly increased in Pb+C0 compared to Control but decreased in lead‐chlorella groups. These results indicate that chlorella may have protective effect against lead‐induced hepatic toxicity in rats. [This study was supported by Daesang Co. Ltd. WelLife Health Business.]
Visualization of Molecular Transport by the DSMC Method (1996)

Rarefied gas flows through the circular tubes with a finite length were numerically simulated by the Direct Simulation of Monte Carlo method. The effects of boundary conditions, such as accommodation coefficients and surface temperatures at the solid surfaces of the tubes are discussed. The rarefied gas flows covered are the range from rough vacuum to extremely high vacuum conditions. According to the results of free molecular flow, the transmission probabilities increase with decreasing momentum accommodation coefficients. On the other hand, the probabilities increase with decreasing the surface temperatures.
Far-infrared perturbation of reaction rates in myoglobin at low temperatures (1989)

We present evidence that far-infrared radiation of 50.5 ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}1}$ enhances the recombination rates of photodissociated sperm whale myoglobin at temperatures below 180 K. The enhancement disappears above the glass transition of the glycerol solvent at 180 K. Control experiments show that the enhancement in recombination kinetics cannot be attributed to simple solvent heating but instead is involved with protein absorption of far-infrared radiation.
Online story scheduling in web advertising (2009)

We study an online job scheduling problem motivated by storyboarding in web advertising, where an advertiser derives value from uninterrupted sequential access to a user surfing the web. The user ceases to browse with probability 1 – β at each step, independently. Stories (jobs) arrive online; job s has length ℓs and per-unit value vs. A value vs is obtained for every unit of the job that is scheduled consecutively without interruption, discounted for the time at which it is scheduled. Jobs can be preempted, but no further value can be derived from the residual unscheduled units of the job. We seek an online algorithm whose total reward is competitive against that of the offline scheduler that knows all jobs in advance. We consider two models based on the maximum delay that can be allowed between the arrival and scheduling of a job. In the first, a job can be scheduled anytime after its arrival; in the second a job is lost unless scheduled immediately upon arrival, preempting a currently running job if needed. The two settings correspond to two natural models of how long an advertiser retains interest in a relevant user. We show that there is, in fact, a sharp separation between what an online scheduler can achieve in these two settings. In the first setting with no deadlines, we give a natural deterministic algorithm with a constant competitive ratio against the offline scheduler. In contrast, we show that in the sharp deadline setting, no (deterministic or randomized) online algorithm can achieve better than a polylogarithmic ratio.
New radiosensitizing regimens, drugs, prodrugs, and candidates. (2004)

There have been significant advances over the last decade in the understanding of cellular, biochemical, and molecular effects of ionizing radiation combined with certain types of cytotoxic drugs and prodrugs, as well as new "targeted" biological agents in human tumor and normal cells. At the same time, new information has evolved regarding specific genetic and epigenetic changes found in certain human cancers, which result in alterations in ionizing radiation damage recognition and damage repair processes. As a result, novel targeting approaches for human tumor radiosensitization is an active area for translational and clinical research in radiation oncology. In this article, we review the current status of existing and new radiosensitizing regimens.
Visual tracking with sensing dynamics compensation using the Expectation-Maximization algorithm (2013)

Advances in vision-based technologies allow robots to perform sophisticated and intelligent tasks. Even with these advances, there still remain inherent problems with using vision-based technologies. Slow sampling rate and large latency is a problem associated with most vision hardware used in industry. We refer to these characteristics as the sensing dynamics associated with the vision sensor. This paper presents a compensation method that alleviates sensing dynamics issues in visual feedback tracking problems. We view the sensing dynamics compensation problem as two separate mathematical problems. Namely, we first deal with identifying the target model and then we deal with estimating the target position using the identified model and delayed measurements. The Expectation-Maximization algorithm and Kalman filtering are utilized to solve each problem respectively. The visual servo scheme associated with the proposed approach is also studied. Simulations and experiments are designed to test the performance capability of the proposed method.