gebhart/patrepeval huggingface dataset:
Strong bias in the location of functional promoter polymorphisms (2005)

A considerable proportion of heritable human phenotypic variation is thought to result from altered gene expression. Unfortunately, it is currently impossible to use bioinformatic analysis to discriminate between DNA sequence variants that are likely to influence gene expression and those that are not. In an attempt to define some of the characteristics of promoter polymorphisms with functional effects on gene expression, we examined 674 haplotypes representing 247 unique gene promoters using a standardized reporter gene assay system. Sequence variants that altered gene expression by 1.5-fold or more were strongly biased toward a location in the core and proximal promoter regions, 50% being within the first 100 bases 5' to the transcription start site. No bias was seen in the allele frequencies of functional and nonfunctional sequence variants. Only 33% of the functional variants were found in known consensus transcription factor binding sequences or motifs, which suggests that either there are many unknown transcription factor binding motifs or other, unknown mechanisms are involved. The genes with functional polymorphisms that are reported here for the first time include AGTRL2, CAT, CHRNA5, CTSG, CYP2D6, DLD, ERCC1, GABRA1, GABRP, HNRPH3, HIP1, IGKV1-9, KCNJ15, KCNK6, KLK1, MSMB, MYOC, NPY2R, NOTCH4, ORM2, PEDF, PTPRCAP, ST16 (IL24), SULT1A1, and TSHR.
Chemo-enzymic backbone engineering of proteins. Site-specific incorporation of synthetic peptides that mimic the 64-74 disulfide loop of granulocyte colony-stimulating factor. (1994)

We present the concept of chemo-enzymic backbone engineering of proteins. Recombinant DNA techniques are used to produce appropriate proteins that are enzymically fragmented to give the starting materials. These fragments are modified specifically at their chain termini either enzymically (coupling of a hydrazide to the C terminus) or chemically (periodate oxidation of N-terminal serine to a glyoxylyl function). The modified fragments, which need no side protection whatever, are mixed together and religate themselves spontaneously under mild conditions. The hydrazone bond thus formed can be reduced if desired, which stabilizes the linkage and enhances the flexibility of the local conformation. In this way biologically or chemically derived structures can be incorporated into the protein, and the choice of the chemical ones is free of all of the constraints of the genetic code. We believe that this combined approach gives access to constructions that could not be derived by either recombinant or chemical methods alone. We illustrate the particularity of this concept by the engineered modifications of the 64-74 disulfide loop region of human granulocyte colony-stimulating factor. Analogs constructed include one which, in spite of having a nonpeptide link in its backbone, has full biological activity.
Towards programmable enterprise WLANS with Odin (2012)

We present Odin, an SDN framework to introduce programmability in enterprise wireless local area networks (WLANs). Enterprise WLANs need to support a wide range of services and functionalities. This includes authentication, authorization and accounting, policy, mobility and interference management, and load balancing. WLANs also exhibit unique challenges. In particular, access point (AP) association decisions are not made by the infrastructure, but by clients. In addition, the association state machine combined with the broadcast nature of the wireless medium requires keeping track of a large amount of state changes. To this end, Odin builds on a light virtual AP abstraction that greatly simplifies client management. Odin does not require any client side modifications and its design supports WPA2 Enterprise. With Odin, a network operator can implement enterprise WLAN services as network applications. A prototype implementation demonstrates Odin's feasibility.
U-3′-BCIP: a chromogenic substrate for the detection of RNase A in recombinant DNA expression systems (1991)

The synthesis of the bovine pancreatic ribonuclease A (RNase A, EC 3.1.27.5) chromogenic substrate uridine-3'-(5-bromo-4-chloroindol-3-yl)-phosphate (U-3'-BCIP) is described. RNase A catalyzes the hydrolysis of U-3'-BCIP to release a halogenated indol-3-ol that undergoes rapid aerobic oxidation to the dark blue 5,5'-dibromo-4,4'-dichloroindigo. Preliminary kinetic studies indicate that this compound may have practical use for assaying RNase A activity both in vitro and in vivo, e.g. in screening bacterial colonies for RNase A produced by recombinant DNA methods.
Formation, nature, and stability of the arsenic-silicon-oxygen alloy for plasma doping of non-planar silicon structures (2014)

We demonstrate stable arsenic-silicon-oxide film formation during plasma doping of arsenic into non-planar silicon surfaces through investigation of the nature and stability of the ternary oxide using first principles calculations with experimental validations. It is found that arsenic can be co-mingled with silicon and oxygen, while the ternary oxide exhibits the minimum energy phase at x ≈ 0.3 in AsxSi1−xO2−0.5x. Our calculations also predict that the arsenic-silicon-oxide alloy may undergo separation into As-O, Si-rich As-Si-O, and Si-O phases depending on the composition ratio, consistent with experimental observations. This work highlights the importance of the solid-state chemistry for controlled plasma doping.
4-Alkyl- and 4-Cinnamylglutamic Acid Analogues Are Potent GluR5 Kainate Receptor Agonists (2000)

Enantiomerically pure (2S,4R)-4-substituted glutamic acids were prepared and tested for homomeric GluR5 and GluR6 kainate subtype receptor affinity. Some of the 4-cinnamyl analogues showed high selectivity and potency (K(i) < 25 nM) for the GluR5 receptors. The greatest selectivity and potency were achieved with the 3-(2-naphthyl)prop-2-enyl compound. This compound, LY339434, has negligible activity at the AMPA and kainate receptors GluR1, -2, -4 and -6. Although, LY339434 shows agonist activity at NMDA receptors in cultural hippocampal neurons (approximate EC(50) of 2.5 microM), we consider that LY339434 should be a useful pharmacological tool for the investigation of the functional role of GluR5 kainate receptors.
Multi-Scale Multi-Task FCN for Semantic Page Segmentation and Table Detection (2017)

Page segmentation and table detection play an important role in understanding the structure of documents. We present a page segmentation algorithm that incorporates state-of-the-art deep learning methods for segmenting three types of document elements: text blocks, tables, and figures. We propose a multi-scale, multi-task fully convolutional neural network (FCN) for the tasks of semantic page segmentation and element contour detection. The semantic segmentation network accurately predicts the probability at each pixel of the three element classes. The contour detection network accurately predicts instance level "edges" around each element occurrence. We propose a conditional random field (CRF) that uses features output from the semantic segmentation and contour networks to improve upon the semantic segmentation network output. Given the semantic segmentation output, we also extract individual table instances from the page using some heuristic rules and a verification network to remove false positives. We show that although we only consider a page image as input, we produce comparable results with other methods that relies on PDF file information and heuristics and hand crafted features tailored to specific types of documents. Our approach learns the representative features for page segmentation from real and synthetic training data. %, and produces good results on real documents. The learning-based property makes it a more general method than existing methods in terms of document types and element appearances. For example, our method reliably detects sparsely lined tables which are hard for rule-based or heuristic methods.
Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary to reduced co‐factor pyridoxal‐5′‐phosphate availability (2010)

We describe two neonates presenting with perinatal hypophosphatasia and severe epileptic encephalopathy resulting in death. Both had increased levels of urinary vanillactate, indicating functional deficiency of aromatic amino acid decarboxylase, a pyridoxal-5-phosphate (PLP)-dependent enzyme required for dopamine and serotonin biosynthesis. Clinical findings and results of subsequent metabolic investigations were consistent with secondary pyridoxine-deficient encephalopathy. These patients highlight the importance of tissue non-specific alkaline phosphatase in the neuronal PLP-dependent metabolism of neurotransmitters. In addition, the disturbance of PLP metabolism appears to underlie the predominant neurological presentation in our patients. We recommend the measurement of serum alkaline phosphatase (ALP) during the assessment of perinatal seizures.
Structure-Activity Relationships of 1,3-Benzoxazole-4-carbonitriles as Novel Antifungal Agents with Potent in Vivo Efficacy (2011)

A series of 1,3-benzoxazole-4-carbonitriles was synthesized and evaluated for its antifungal activity, solubility, and metabolic stability. Among those compounds, 4-cyano-N,N,5-trimethyl-7-[(3S)-3-methyl-3-(methylamino)pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-2-carboxamide (16b) exhibited potent in vitro activity against Candida species, higher water solubility, and improved metabolic stability compared to lead compound 1. Compound 16b showed potent in vivo efficacy against mice Candida infection models and good bioavailability in rats.
A combined open and percutaneous technique for repair of tendo Achillis. Comparison with open repair (1995)

A combined open and percutaneous operative technique has been devised for repair of tendo Achillis. This minimises postoperative scarring. We compared the long-term results of 12 patients treated by this method with the results of 10 who had undergone an open repair. The combined open and percutaneous repair gave significantly better relief of symptoms during everyday activities (p < 0.05), better single-limb hopping (p < 0.02) and a greater chance of returning to sport (p < 0.01). There were no significant differences between the two treatments as regards to active range of ankle motion, calf circumference or the ability to stand on tiptoe. The new technique gave better cosmetic results.
Speed and Accuracy in Digital Network Simulation Based on Structural Modeling (1982)

Speed and accuracy are fundamental simulation requirements. Simulation is not worthwhile without adequate accuracy, and massive simulations and fault simulations are impossible without adequate speed. Accuracy requirements for simulation are a sufficient repertoire of nodal states, quantitative timing, and, most importantly, adequate structural detail. A variety of techniques have provided speed for simulation, but additional speed is needed.
Boosted Voltage Scheme with Active Body-Biasing Control on PD-SOI for Ultra Low Voltage Operation (2007)

In this paper, we propose an Active Body-biasing Controlled (ABC)-Bootstrap PTL (Pass-Transistor Logic) on PD-SOI for ultra low power design. Although simply lowering the supply voltage (V DD ) causes a lack of driving power, our boosted voltage scheme employing a strong capacitive coupling with ABC-SOI improves a driving power and allows lower voltage operation. We also present an SOI-SRAM design boosting the word line (WL) voltage higher than V DD in short transition time without dual power supply rails. Simulation results have shown improvement in both the delay time and power consumption.
A predistortion linearizer using envelope-feedback technique with simplified carrier cancellation scheme for class-A and class-AB power amplifiers (2000)

A predistortion linearization method using an envelope-feedback technique is proposed and implemented in this paper. This linearizer compensates the gain and phase nonlinearity of power amplifier (PA) simultaneously by controlling both variable attenuator and phase shifter with the feedback of only the difference signal between input and output envelopes. A new carrier cancellation scheme composed of a minimization circuit, log detector, and vector modulator is also presented. This circuit achieves adaptive control of the linearizer by enabling direct measurement of out-of-band power. It is well suited to a multichannel system where the allocated channels are time variant. The principle of the proposed linearizer is described and simple AM-AM distortion analysis is presented analytically and graphically based on the conceptual schematic diagram. A two-tone test for a class-A PA at 1.855 GHz with frequency spacing of 1 MHz showed intermodulation-distortion reduction of maximum 16 dB and stable operation over 5-dB output power variation up to 4-dB backoff from the saturation power level. The proposed linearizer is also applicable to class-AB PA's without further special adjustments. The adaptation circuit is fully implemented with analog integrated circuits, which can further extend its applicability with the integration technology.
Trienoic Fatty Acids and Plant Tolerance of High Temperature (2000)

The chloroplast membrane of higher plants contains an unusually high concentration of trienoic fatty acids. Plants grown in colder temperatures have a higher content of trienoic fatty acids. Transgenic tobacco plants in which the gene encoding chloroplast omega-3 fatty acid desaturase, which synthesizes trienoic fatty acids, was silenced contained a lower level of trienoic fatty acids than wild-type plants and were better able to acclimate to higher temperatures.
Guidance of oligodendrocytes and their progenitors by substratum topography (1995)

Oligodendrocyte progenitors arise in subventricular zones and migrate extensively during development before differentiating into mature oligodendrocytes, which myelinate nerve tracts in the central nervous system. We have used microfabricated substrata, containing periodic patterns of contours similar to those of central nervous system axons to assess the influence in vitro of substratum topography on oligodendrocytes isolated from 7 day rat optic nerve. Antiganglioside antibody A2B5 positive oligodendrocyte-type 2 astrocyte progenitors, and galactocerebroside positive and myelin basic protein positive oligodendrocytes, were highly aligned by surface contours as small as 100 nm depth and 260 nm repeat spacing. Rat optic nerve astrocytes also aligned on surface contours, but rat hippocampal and cerebellar neurons were unresponsive. Oligodendrocytes demonstrated enhanced parallel extension of their processes on narrow repeating topography in an arrangement similar to that found in the intact optic nerve. This is in marked contrast to the phenotype displayed by this cell type on planar substrata. Neither oligodendrocytes nor oligodendrocyte-type 2 astrocyte progenitors showed high-order F-actin cytoskeletal networks; thus their alignment on gratings is unlikely to result from deformation of actin cables and focal contacts. In contrast, aligned astrocytes showed striking arrangements of actin stress fibres. These results establish glial cells as potentially the most topographically sensitive cell types within the central nervous system. Furthermore, the topographical pattern inducing maximal alignment of oligodendrocyte lineage cells corresponds to the diameters of single axons within the 7 day optic nerve. Thus the migration of oligodendrocyte-type 2 astrocyte progenitors and axonal ensheathment by oligodendrocytes may be guided by axonal topography within the developing nerve.
Targeting Androgen Receptor Activation Function-1 with EPI to Overcome Resistance Mechanisms in Castration-Resistant Prostate Cancer (2016)

These findings support EPI as a promising therapeutic agent to treat CRPC, particularly against tumors driven by constitutively active AR splice variants that are resistant to LBD-targeting drugs. Clin Cancer Res; 22(17); 4466-77. ©2016 AACRSee related commentary by Sharp et al., p. 4280.
Amantadine Treatment of Fatigue Associated With Multiple Sclerosis (1989)

Fatigue is a common symptom of multiple sclerosis (MS) that is without an effective treatment. A double-blind, controlled study of fatigue treatment was conducted to evaluate the efficacy of amantadine hydrochloride in treating MS-associated fatigue. Since fatigue cannot be characterized by a single symptom or behavior, a variety of neuropsychological, behavioral, and self-report measures were used to monitor changes across different systems. According to patients' daily diary ratings, amantadine produced small but statistically significant improvements in fatigue across four of seven dimensions (overall energy level, concentration, problem solving, and sense of well-being). In addition, patients with MS who were taking amantadine performed slightly better on the Stroop Interference Test, an attentional measure of freedom from distracting information. Although retrospective reports by patients with MS did not confirm the degree of improvement recorded on a daily basis, the study's results suggested that amantadine may offer modest benefits in alleviating the day-to-day subjective experience of fatigue.
Sprite: a simple, cheat-proof, credit-based system for mobile ad-hoc networks (2004)

Mobile ad hoc networking has been an active research area for several years. How to stimulate cooperation among selfish mobile nodes, however, is not well addressed yet. In this paper, we propose Sprite, a simple, cheat-proof, credit-based system for stimulating cooperation among selfish nodes in mobile ad hoc networks. Our system provides incentive for mobile nodes to cooperate and report actions honestly. Compared with previous approaches, our system does not require any tamper-proof hardware at any node. Furthermore, we present a formal model of our system and prove its properties. Evaluations of a prototype implementation show that the overhead of our system is small. Simulations and analysis show that mobile nodes can cooperate and forward each other's messages, unless the resource of each node is extremely low.
Lebrikizumab in the personalized management of asthma (2012)

There is a need for improved therapies for severe asthma. Lebrikizumab, a humanized monoclonal antibody that binds to interleukin (IL)-13, is under development for the treatment of poorly controlled asthma. This article reviews the potential role of IL-13 in the pathogenesis of asthma, the efficacy and safety of lebrikizumab in humans, and progress in patient selection for lebrikizumab therapy. IL-13 is a T-helper (Th2) cell-derived cytokine implicated in inflammatory responses in asthma, including serum immunoglobulin-E synthesis, mucus hypersecretion, and subepithelial fibrosis. Blocking the pro-inflammatory effects of IL-13 with lebrikizumab has the potential to improve asthma control. Published data on the efficacy and safety of lebrikizumab in the treatment of asthma are relatively limited. The late asthmatic response after inhaled allergen challenge is reduced by almost 50%, following treatment with lebrikizumab. In a Phase II study performed in 219 adults with poorly controlled asthma despite inhaled corticosteroids (MILLY trial), lebrikizumab produced an improvement in prebronchodilator forced expiratory volume in 1 second of 5.5% compared with placebo at 12 weeks, but had no effects on other efficacy end points. Adverse effects were similar to placebo, except that musculoskeletal side effects occurred slightly more often with lebrikizumab. Stratifying patients into a high Th2 phenotype using serum periostin, which is upregulated in lung epithelial cells by IL-13, may identify individuals responsive to blockade of IL-13. In the MILLY trial, lebrikizumab treatment was associated with greater improvement in lung function in patients with elevated serum periostin levels compared with those with low periostin levels. Two large Phase III randomized controlled trials in patients with uncontrolled asthma are underway to establish the safety and efficacy of lebrikizumab when administered over a 52-week period. These studies will also help to determine whether identifying patients with a Th2 high inflammatory phenotype using serum periostin allows a personalized approach to the treatment of asthma.
The polyadenylation signal of influenza virus RNA involves a stretch of uridines followed by the RNA duplex of the panhandle structure (1991)

Appropriate RNAs are transcribed and amplified and proteins are expressed after transfection into cells of in vitro-reconstituted RNA-protein complexes and infection with influenza virus as the helper. This system permits us to study the signals involved in transcription of influenza virus RNAs. For the analysis we used a plasmid-derived RNA containing the reporter gene for chloramphenicol acetyltransferase (CAT) flanked by the noncoding sequences of the NS RNA segment of influenza A/WSN/33 virus. Mutations were then introduced into both the 5' and 3' ends, and the resulting RNAs were studied to determine their transcription in vitro and their CAT expression activity in the RNA-protein transfection system. The results reveal that a stretch of uninterrupted uridines at the 5' end of the negative-strand RNA is essential for mRNA synthesis. Also, a double-stranded RNA "panhandle" structure generated by the 5'- and 3'-terminal nucleotides appears to be required for polyadenylation, since opening up of these base pairs diminished mRNA synthesis and eliminated expression of CAT activity by the mutant RNAs. Finally, it was shown that this double-stranded RNA structural requirement is not sequence specific, since a synthetic GC clamp can replace the virus-coded RNA duplex. The data suggest that the viral RNA polymerase adds poly(A) by a slippage (stuttering) mechanism which occurs when it hits the double-stranded RNA barrier next to the stretch of uridines.
Vibrational spectroscopy for milk fat quantification: line shape analysis of the Raman and infrared spectra (2016)

This paper presents a systematic analysis of the infrared absorption spectra and Raman scattering of the triacylglycerol molecule predominant in raw bovine milk. Gas chromatography measurements were also performed and revealed the palmitic, stearic, and oleic acids as the most predominant fatty acids in the composition of milk. Based on the gas chromatography results, infrared, and Raman spectra of the triacylglycerol with this combination of fatty acids were simulated. The theoretical spectra were compared with the experimental ones of milk fat and fluid raw milk. Assignment of bands of milk fat was proposed, which can be used for a quality monitoring of the product. We also performed a multivariate model of partial least squares from samples of fluid milk with different concentrations of fat. As a result, the most important variables in the projection were selected as vibrational markers for quality monitoring and quantifying of this important constituent of milk. Copyright © 2016 John Wiley &amp; Sons, Ltd.
Procedural Constraints in the Extended RBAC and the Coloured Petri Net Modeling (2005)

This paper presents the Coloured Petri Net modeling for security analysis of the Extended Role Based Access Control systems.