gebhart/patrepeval huggingface dataset:
A theoretical approach to select effective antisense oligodeoxyribonucleotides at high statistical probability (1999)

Up to now, out of approximately 20 antisense oligodeoxyribonucleotides (as ODN) selected and tested against a given target gene, only one species shows substantial suppression of target gene expression. In part, this seems to be related to the general assumption that the structures of local target sequences or antisense nucleic acids are unfavorable for efficient annealing. Experimental approaches to find effective as ODN are extremely expensive when including a large number of antisense species and when considering their moderate success. Here, we make use of a systematic alignment of computer-predicted secondary structures of local sequence stretches of the target RNA and of semi-empirical rules to identify favorable local target sequences and, hence, to design more effective as ODN. The intercellular adhesion molecule 1 (ICAM-1) gene was chosen as a target because it had been shown earlier to be sensitive to antisense-mediated gene suppression. By applying the protocol described here, 10 ICAM-1-directed as ODN species were found that showed substantially improved inhibition of target gene expression in the endothelial cell line ECV304 when compared with the most effective published as ODN. Further, 17 out of 34 antisense species (50%) selected on the theoretical basis described here showed significant (>50%) inhibition of ICAM-1 expression in mammalian cells.
2.4 Gbps, 7 mW All-Digital PVT-Variation Tolerant True Random Number Generator for 45 nm CMOS High-Performance Microprocessors (2012)

This paper describes an all-digital PVT-variation tolerant true-random number generator (TRNG), fabricated in 45 nm high-k/metal-gate CMOS, targeted for on-die entropy generation in high-performance microprocessors. The TRNG harvests differential thermal-noise at the diffusion nodes of a pre-charged cross-coupled inverter pair to resolve out of metastability, generating one random bit/cycle. A self-calibrating 2-step tuning mechanism using coarse-grained configurable inverters and fine-grained programmable clock delay generators, along with an entropy-tracking feedback loop provide tolerance to 20% PVT variation-induced device mismatches, enabling lowest-reported energy-consumption of 2.9 pJ/bit with a dense layout occupying 4004 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , while achieving: (i) 2.4 Gbps random bit throughput, 7 mW total power consumption with 0.7 mW leakage power component, measured at 1.1 V, 50°C, (ii) random bitstreams that passes all NIST RNG tests with raw entropy/bit measured up to 0.9999999993, (iii) good distribution of 1's with 4-bit entropy of 3.97996 and high-entropy pattern probability of 0.066 (iv) wide operating supply voltage range with robust sub-threshold voltage performance of 14 Mbps, 5.6 μW, measured at 280 mV, 50°C, (v) 12 fine-grained high-entropy settings for the TRNG to dither in during steady-state operation, (vi) <;3% error while using an analytical ergodic Markov chain model for predicting pattern probabilities and (vii) 200x higher throughput and 9x higher energy-efficiency than previously reported implementations. Design modifications for robust operation in 22 nm high-volume manufacturing in the presence of 3σ process variations demonstrate scalability of the all-digital design to future technologies.
Fabrication of microfluidic devices using polydimethylsiloxane (2010)

Polydimethylsiloxane (PDMS) is nearly ubiquitous in microfluidic devices, being easy to work with, economical, and transparent. A detailed protocol is provided here for using PDMS in the fabrication of microfluidic devices to aid those interested in using the material in their work, with information on the many potential ways the material may be used for novel devices.
Identification of the Escherichia coli K-12 ybhE Gene as pgl , Encoding 6-Phosphogluconolactonase (2004)

We report identification of the Escherichia coli ybhE gene as the pgl gene that encodes 6-phosphogluconolactonase. A tentative identification was first made based on the known approximate location of the pgl gene and the similarity of the presumptive ybhE-encoded protein sequence to a known Pgl enzyme. To test this notion, the ybhE gene was deleted and replaced with a drug marker. Like previously characterized pgl mutants, the ybhE deletion mutant had a Blu- phenotype (dark-blue staining with iodine due to accumulation of starch after growth on minimal maltose) and demonstrated impaired growth on minimal glucose medium when combined with a pgi mutation. Biochemical assay of crude extracts for 6-phosphogluconolactonase enzymatic activity showed that ybhE encodes this activity. The ybhE gene was transferred from the E. coli chromosome to an expression vector. This ybhE clone complemented both the precise deletion of the ybhE gene and a larger deletion, pglDelta8, for the Blu- phenotype and for phosphogluconolactonase activity, confirming that ybhE is the pgl gene. A newly observed phenotype of pgl strains is a lowered frequency of appearance of Bgl+ mutants that can utilize the beta-glucoside salicin. This is likely due to poor growth of Bgl+ pgl strains on salicin due to the accumulation of 6-phosphogluconolactone.
Indicators for optical oxygen sensors (2012)

Continuous monitoring of oxygen concentration is of great importance in many different areas of research which range from medical applications to food packaging. In the last three decades, significant progress has been made in the field of optical sensing technology and this review will highlight the one inherent to the development of oxygen indicators. The first section outlines the bioanalytical fields in which optical oxygen sensors have been applied. The second section gives the reader a comprehensive summary of the existing oxygen indicators with a critical highlight on their photophysical and sensing properties. Altogether, this review is meant to give the potential user a guide to select the most suitable oxygen indicator for the particular application of interest.
Movers and shakers (2013)

The human intestinal microbiota is one of the most densely populated ecosystems on Earth, containing up to 10 ( 13) bacteria/g and in some respects can be considered an organ itself given its role in human health. Bacteriophages (phages) are the most abundant replicating entities on the planet and thrive wherever their bacterial hosts exist. They undoubtedly influence the dominant microbial populations in many ecosystems including the human intestine. Within this setting, lysogeny appears to be the preferred life cycle, presumably due to nutrient limitations and lack of suitable hosts protected in biofilms, hence the predator/prey dynamic observed in many ecosystems is absent. On the other hand, free virulent phages in the gut are more common among sufferers of intestinal diseases and have been shown to increase with antibiotic usage. Many of these phages evolve from prophages of intestinal bacteria and emerge under conditions where their bacterial hosts encounter stress suggesting that prophages can significantly alter the microbial community composition. Based on these observations, we propose the "community shuffling" model which hypothesizes that prophage induction contributes to intestinal dysbiosis by altering the ratio of symbionts to pathobionts, enabling pathobiont niche reoccupation. The consequences of the increased phage load on the mammalian immune system are also addressed. While this is an area of intestinal biology which has received little attention, this review assembles evidence from the literature which supports the role of phages as one of the biological drivers behind the composition of the gut microbiota.
Treatment of Fabry’s Disease with the Pharmacologic Chaperone Migalastat (2016)

Among all randomly assigned patients (with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy), the percentage of patients who had a response at 6 months did not differ significantly between the migalastat group and the placebo group. (Funded by Amicus Therapeutics; ClinicalTrials.gov numbers, NCT00925301 [study AT1001-011] and NCT01458119 [study AT1001-041].).
Molecular genetic alterations in superficial and locally advanced human bladder cancer. (1991)

We attempted to define the role of tumor suppressor genes in the pathogenesis of human bladder cancer through a combined molecular genetic and immunohistochemical approach. Thirty-four bladder tumors (1 Pis, 6 Pa, 5 P1, 3 P3a, 18 P3b, 1 P4; 8 low grade and 26 high grade tumors) have been analyzed. Restriction fragment length polymorphism analysis directed at 5 suspected or established tumor suppressor gene regions (3p21-25, 11p15, 13q14, 17p11-13, and 18q21) was combined with immunohistochemical using Rb-PMG3-245 monoclonal antibody directed at the retinoblastoma (Rb) gene product. Tumor grade correlated with deletions of 3p (P = 0.004) and 17p (P = 0.063). Tumor stage correlated with deletions of 3p (P = 0.010), 17p (P = 0.015) and altered Rb expression (P = 0.054). Vascular invasion correlated only with deletions of 17p (P = 0.038). No marker correlated with positive lymph nodes. Our results suggest that altered Rb expression occurs in all grades and stages of bladder cancer but is more commonly associated with invasive tumors. Genetic alterations of 3p, 11p, 17p, and 18q are rare events in low grade, superficial tumors, whereas they are more common in high grade and invasive bladder cancer. The role of these genetic alterations in the prognosis of bladder cancer will require additional follow-up and further studies.
Combining data mining and machine learning for effective user profiling (1996)

This paper describes the automatic design of methods for detecting fraudulent behavior. Much of the design is accomplished using a series of machine learning methods. In particular, we combine data mining and constructive induction with more standard machine learning techniques to design methods for detecting fraudulent usage of cellular telephones based on profiling customer behavior. Specifically, we use a rulelearning program to uncover indicators of fraudulent behavior from a large database of cellular calls. These indicators are used to create profilers, which then serve as features to a system that combines evidence from multiple profilers to generate high-confidence alarms. Experiments indicate that this automatic approach performs nearly as well as the best hand-tuned methods for detecting fraud. Introduction In the United States, cellular fraud costs the telecommunications industry hundreds of millions of dollars per year (Walters &amp;amp; Wilkinson 1994). A specific kind of cellul...
Genetic mapping of Vibrio cholerae enterotoxin structural genes (1984)

The structural genes which constitute the cholera toxin operon, ctxAB, were genetically mapped in the Vibrio cholerae El Tor strain RV79. This strain of V. cholerae contains two copies of the ctx operon located on a 7-kilobase-pair tandemly duplicated region. We began by isolating a vibriophage VcA1 insertion mutation in one of the two ctxA genes located in this region. The mutant carrying this ctxA::VcA1 insertion, DC24, was converted to a VcA1-facilitated donor by introduction of the conjugal plasmid pSJ15, which carries an inserted copy of a defective VcA1-like prophage. The donor characteristics of DC24(pSJ15) indicated that the ctxA::VcA1 insertion mutation was near the trp region of the V. cholerae chromosome. Subsequent RV79 three-factor crosses were performed between VcA1-facilitated donors and recipient strains carrying one of two structural gene mutations in ctx, either delta ctxA23P Kmr or delta ctx-7922. The former was constructed by an in vivo marker exchange procedure and could be scored either by its kanamycin resistance phenotype or by its lack of DNA sequences homologous to the ctxA region. The delta ctx-7922 mutation is a total deletion of both ctx copies of strain RV79. The three-factor cross data strongly suggest that the two ctx loci of RV79 map between the nal and his genes of V. cholerae in the trp nal his linkage group. Physical analysis and heterologous crosses between an RV79 El Tor donor and a 569B classical recipient indicates that one of the two 569B ctx operon copies maps in the same region as the RV79 ctx loci (i.e., linked to nal). Together with previously published observations, these data show that the ctx structural genes are not closely linked to other genes known to affect toxin production in V. cholerae.
Neonatal Hearing Loss in the Indigent (2002)

Abstract Objective To compare the risk factor profile for neonatal hearing loss (HL), and the follow‐up rate of those identified with HL in an indigent population with those in an insured population. Study Design Retrospective review. Methods We studied 4526 neonates from the high‐risk nursery or neonatal intensive care unit from two adjacent hospitals in Houston, Texas. Ben Taub General Hospital (BTGH) is a county public hospital that serves mainly the indigent. Texas Children's Hospital (TCH) is a private tertiary care center that serves patients with private insurance and Medicaid. Results Overall, 133 infants failed the screening test. Follow‐up diagnostic testing identified 48 patients with definite HL. Although nearly twice as many patients at BTGH failed screening compared with TCH (88 vs. 45), four times as many patients at BTGH did not return for diagnostic testing (43 vs. 10). When a hearing aid was needed, there was a delay in getting one at BTGH ( P &lt;.05). There was a higher prevalence of dysmorphic facial features and central nervous system disease and a lower prevalence of long‐term ventilatory support at BTGH ( P &lt;.05). There were no differences between BTGH and TCH in the prevalence of low birth weight, neonatal asphyxia, syndromic stigmata, neonatal infection, family history of HL, or neonatal transfusion ( P &gt;.1). Conclusions Significant differences in the risk factor profile for neonatal HL exist between the indigent and the general population. A worrisome problem exists with the timely intervention in hearing‐impaired indigent neonates.
DNA-dependent adenosinetriphosphatase C1 from mouse FM3A cells has DNA helicase activity. (1992)

In our previous study, we identified four chromatographically distinct DNA-dependent ATPases, B, C1, C2, and C3, in mouse FM3A cells (Tawaragi, Y., Enomoto, T., Watanabe, Y., Hanaoka, F., and Yamada, M. (1984) Biochemistry 23, 529-533). The DNA-dependent ATPase C1 has been purified and characterized in detail. A divalent cation and a polynucleotide cofactor were required for the ATPase activity. Poly(dT), single-stranded circular DNA, and heat-denatured DNA were very effective. Almost no ATPase activity was observed with S1 nuclease-treated native DNA. ATPase C1 hydrolyzed ATP only among the ribo- and deoxyribonucleoside triphosphates tested, and this fact distinguished ATPase C1 from ATPases B, C2, and C3, because the latter enzymes are capable of hydrolyzing both ATP and dATP. The purified DNA-dependent ATPase C1 fraction was shown to have a DNA helicase activity that was dependent on hydrolysis of ATP. The helicase activity and DNA-dependent ATPase activity cosedimented at 5.2 S on glycerol gradient centrifugation. Both activities showed similar preferences for nucleoside 5'-triphosphates and similar requirements for divalent cations. The DNA helicase activity was inhibited by the addition of single-stranded DNAs that served as cofactor for the ATPase activity. The efficiency of a single-stranded DNA to inhibit DNA helicase activity correlated well with the capacity of the DNA to serve as cofactor for DNA-dependent ATPase activity. The helicase was shown to migrate along the DNA strand in the 5' to 3' direction, which is the same direction of migration of the mouse DNA helicase B (Seki, M., Enomoto, T., Yanagisawa, J., Hanaoka, F., and Ui, M. (1988) Biochemistry 27, 1766-1771).
Total-body irradiation and autologous bone marrow transplant in the treatment of high-risk Ewing's sarcoma and rhabdomyosarcoma. (1993)

Consolidation of patients with metastatic or high-risk localized pediatric sarcomas with 8 Gy TBI plus ABMT has failed to improve the outcome of this group of patients. Metastatic disease at diagnosis continues to confer the poorest prognosis. New therapeutic strategies are needed to consolidate more effectively the remissions that can be achieved in the majority of these patients.
Influence of steel factor on hemoglobin synthesis in sickle cell disease (1992)

A new hematopoietic growth factor (Steel factor) has been identified which stimulates erythroid proliferation both in vitro and in vivo. We evaluated the influence of recombinant Steel factor on hemoglobin synthesis in peripheral blood (PB) BFU-E-derived cells from normal donors by radioimmunoassay (RIA) and compared it with stimulation with GM-CSF and interleukin-3 (IL-3). Only Steel factor stimulated a significant increase in BFU-E-derived colony size and a significant increase in fetal hemoglobin (HbF) in BFU-E-derived erythroblasts from 0.49% +/- 0.27% to 6.33% +/- 1.11% in serum-deprived media and from 1.88% +/- 0.24% to 11.17% +/- 0.91% in serum. To determine whether this influence on hemoglobinization also occurred in sickle cell disease, we studied 13 patients with sickle cell disease. In serum-deprived conditions, there was a significant increase in the number and size of BFU-E-derived colonies with Steel factor that was dose-dependent. In addition, the proportion of HbF in progenitor-derived cells increased by 66% from 4.1% +/- 0.6% to 6.8% +/- 1.2% with Steel factor. In serum- containing conditions studied in 12 patients, the increase in percentage of HbF was even greater, from 10.7% +/- 0.9% in control cultures to 22.5% +/- 2.6% with Steel factor. These increases in percentage of HbF were significant and dose-dependent. An increase in percentage of HbF was observed in erythroblasts harvested on day 11, 14, and 18 of culture. A decrease in mean picograms of total Hb per cell after coculture with Steel factor was noted, suggesting that growth kinetics influenced complete hemoglobinization. In serum- deprived conditions, picograms of HbF per cell was not affected by Steel factor, and in serum-containing conditions that augment in vitro HbF production it was enhanced. Thus, Steel factor stimulated a significant increase in percentage of HbF in erythroid cells from normal donors and patients with SCA in vitro.
Validation of Molecular Dynamics Simulations of Biomolecules Using NMR Spin Relaxation as Benchmarks:  Application to the AMBER99SB Force Field (2007)

Biological function of biomolecules is accompanied by a wide range of motional behavior. Accurate modeling of dynamics by molecular dynamics (MD) computer simulations is therefore a useful approach toward the understanding of biomolecular function. NMR spin relaxation measurements provide rigorous benchmarks for assessing important aspects of MD simulations, such as the amount and time scales of conformational space sampling, which are intimately related to the underlying molecular mechanics force field. Until recently, most simulations produced trajectories that exhibited too much dynamics particularly in flexible loop regions. Recent modifications made to the backbone φ and ψ torsion angle potentials of the AMBER and CHARMM force fields indicate that these changes produce more realistic molecular dynamics behavior. To assess the consequences of these changes, we performed a series of 5-20 ns molecular dynamics trajectories of human ubiquitin using the AMBER99 and AMBER99SB force fields for different conditions and water models and compare the results with NMR experimental backbone N-H S(2) order parameters. A quantitative analysis of the trajectories shows significantly improved agreement with experimental NMR data for the AMBER99SB force field as compared to AMBER99. Because NMR spin relaxation data (T1, T2, NOE) reflect the combined effects of spatial and temporal fluctuations of bond vectors, it is found that comparison of experimental and back-calculated NMR spin-relaxation data provides a more objective way of assessing the quality of the trajectory than order parameters alone. Analysis of a key mobile β-hairpin in ubiquitin demonstrates that the dynamics of mobile sites are not only reduced by the modified force field, but the extent of motional correlations between amino acids is also markedly diminished.
Mirth and laughter arising from human temporal cortex (2003)

Laughter and mirth are essential in our enjoyment of daily life and in facilitating communication. Various studies have been done relating to the emotional processing that takes place in the human cerebral cortex, but few have explored the cerebral origins of mirth. Some reports on pathological laughter have implicated the hypothalamus, brain stem, and temporal lobe.1–3

As part of the presurgical evaluation of patients with epilepsy, electric cortical stimulation is used to delineate the functional cortical areas, and sometimes this elicits various emotional responses.4 However, only two stimulation studies2,5 have been conducted with a focus on mirth and laughter. Arroyo et al suggested that the motor act of laughter and the processing of its emotional content were separately represented in, respectively, the anterior cingulate area and the basal temporal area (the fusiform gyrus or parahippocampal gyrus, or both).2 Fried et al suggested not only that laughter and mirth were represented in the presupplementary motor area, but also that there was close linkage between the motor, affective, and cognitive components of laughter.5

We report a patient in whom electric cortical stimulation applied to the inferior temporal gyrus produced mirth alone or laughter preceded by mirth, depending on the intensity of the stimulation.

A 24 year old right handed …