gebhart/patrepeval huggingface dataset:
Improved haplotyping of rare variants using next-generation sequence data (2012)

Accurate identification of haplotypes in sequenced human genomes can provide invaluable information about population demography and fine-scale correlations along the genome, thus empowering both population genomic and medical association studies. Yet phasing unrelated individuals remains a challenging problem. Incorporating available data from high throughput sequencing into traditional statistical phasing approaches is a promising avenue to alleviate these issues. We present a novel statistical method that expands on an existing graphical haplotype reconstruction method (shapeIT) to incorporate phasing information from paired-end read data. The algorithm harnesses the haplotype graph information estimated by shapeIT from genotypes across the population and refines haplotype likelihoods for a given individual to be compatible with the sequencing data. Applying the method to HapMap individuals genotyped on the Affymetrix Axiom chip at 7,745,081 SNPs and on a trio sequenced by Complete Genomics, we found that the inclusion of paired end read data significantly improved phasing, with reductions in switch error on the order of 4-15% against shapeIT across all panels. As expected, the improvements were found to be most significant at sites harboring rare variants; furthermore, we found that longer read sizes and higher throughput translated to greater decreases in switching error, as did higher variance in the size of the insert separating the two reads--suggesting that multi-platform next generation sequencing may be exploited to yield particularly accurate haplotypes. Overall, the phasing improvements afforded by this new method highlight the power of integrating sequencing read information and population genotype data for reconstructing haplotypes in unrelated individuals.
A 1-Year, Open Label, Randomized Phase II Dose Finding Study of Degarelix for the Treatment of Prostate Cancer in North America (2008)

Degarelix treatment for 1 year resulted in a fast, profound and sustained suppression of testosterone and prostate specific antigen with no evidence of testosterone surge. Degarelix was well tolerated.
Two-Dimensional Separation of Ionic Species by Hyphenation of Capillary Ion Chromatography × Capillary Electrophoresis-Mass Spectrometry (2015)

The separation of complex mixtures such as biological or environmental samples requires high peak capacities, which cannot be established with a single separation technique. Therefore, multidimensional systems are in demand. In this work, we present the hyphenation of the two most important (orthogonal) techniques in ion analysis, namely, ion chromatography (IC) and capillary electrophoresis (CE), in combination with mass spectrometry. A modulator was developed ensuring a well-controlled coupling of IC and CE separations. Proof-of-concept measurements were performed using a model system consisting of nucleotides and cyclic nucleotides. The data are presented in a multidimensional contour plot. Analyte stacking in the CE separation could be exploited on the basis of the fact that the suppressed IC effluent is pure water.
ECG Signals for Biometric Applications - Are we there yet? (2014)

The potential of the electrocardiographic (ECG) signal as a biometric trait has been ascertained in the literature over the past decade. The inherent characteristics of the ECG make it an interesting biometric modality, given its universality, intrinsic aliveness detection, continuous availability, and inbuilt hidden nature. These properties enable the development of novel applications, where non-intrusive and continuous authentication are critical factors. Examples include, among others, electronic trading platforms, the gaming industry, and the auto industry, in particular for car sharing programs and fleet management solutions. However, there are still some challenges to overcome in order to make the ECG a widely accepted biometric. In particular, the questions of uniqueness (inter-subject variability) and permanence over time (intra-subject variability) are still largely unanswered. In this paper we focus on the uniqueness question, presenting a preliminary study of our biometric recognition system, testing it on a database encompassing 618 subjects. We also performed tests with subsets of this population. The results reinforce that the ECG is a viable trait for biometrics, having obtained an Equal Error Rate of 9.01% and an Error of Identification of 15.64% for the entire test population.
Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the <i>ADRB1</i> Arg389Arg Genotype (2021)

[Figure: see text].
The Use of Flashing Drums and Microchannel Heat Exchangers to Generate Steam in Large Integral Light Water Reactors (2015)

Integral pressurized water reactors are innovative reactors in which all of the components typically associated with the nuclear steam supply system of a nuclear power station are located within the reactor pressure vessel. In order to facilitate this modification in large [~1000-MW(electric)] light water reactors (LWRs), compact heat exchangers such as microchannel heat exchangers must be used. Previous attempts at using microchannel heat exchangers were unsuccessful since they are prone to vapor locking and crud blockage when the primary coolant boils. Therefore, the authors propose the use of a flashing drum to facilitate boiling in conjunction with a primary microchannel heat exchanger for a large integral LWR. The integral inherently safe light water reactor (I2S-LWR) is used as a basis for the implementation of this novel concept. The high-temperature, high-pressure secondary water generated in the secondary loop through heating in the microchannel primary heat exchanger of the I2S-LWR is sent to a flashing drum where 99.9% pure vapor is extracted and sent to the turbines. This prevents boiling in the primary heat exchanger that in turn reduces crud deposition, flow instabilities, and the potential for channel blockage or vapor locking in the small channel sizes of microchannel heat exchangers. The benefits and disadvantages of this approach are presented in this paper. Unfortunately, this innovative approach to nuclear steam generation for integral LWRs is challenged by a potential decrease in thermodynamic efficiency. Therefore, a sensitivity study is presented that explores the impact of several design variables on the thermodynamic efficiency of the plant. As part of this study, a simple and a complex Rankine cycle were modeled in order to determine the impact that system design modifications can play in recovering thermodynamic efficiency lost by the steam drum. Both cycles utilize turbines, condensers, and condensate/recirculation pumps, while the complex Rankine cycle utilizes a four-stage turbine with subsequent separation and open feedwater heaters. The optimized efficiencies for the simple and complex Rankine cycles are 31% and 33%, respectively, indicating that additional system enhancements to the power conversion system could compensate for the inclusion of a flashing drum.
Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. (1992)

Serotonin is a neuromodulator that mediates a wide range of effects by interacting with multiple receptors. Using a strategy based on nucleotide sequence homology between genes encoding receptors that interact with guanine nucleotide-binding proteins, we have isolated a mouse gene encoding an additional serotonin receptor. When expressed in cultured cells, it displayed the pharmacological profile and coupling with adenylate cyclase characteristic of the 5HT1B receptor subtype. In NIH 3T3 cells expressing this receptor, serotonin induced a decrease in forskolin-stimulated cAMP levels. This effect was blocked by pertussis toxin, indicating that the 5HT1B receptor interacts with a pertussis toxin-sensitive guanine nucleotide-binding protein. To obtain clues as to the possible function of the 5HT1B receptor, we have analyzed its pattern of expression in the adult mouse brain by in situ hybridization. Our results, together with previous autoradiographic studies, suggest that the 5HT1B receptors are localized presynaptically on the terminals of striatal neurons and Purkinje cells and that they might modulate the release of neurotransmitters such as gamma-aminobutyric acid. The predominant expression of the 5HT1B receptor in the striatum and cerebellum points to an involvement of this receptor in motor control.
Design Features and Performance Details of Brush Seals for Turbine Applications (2006)

Adaptive and contacting seals such as brush seals have been successfully applied to turbomachinery for several years. In large steam turbine applications, however, various challenges still persist. Special focus is directed at the long-term performance and longevity of brushes on conventional spring-backed seal segments in steam turbines. This issue is particularly related to wear during startup conditions. This paper discusses the results of wear tests, derived from simulated transient turbine behavior, where the resultant seal leakage under steady state conditions is monitored. It is shown that the brush seal is significantly capable of adapting to varying operating conditions, but exhibits a degree of performance degradation during the initial startups. Together with previously reported mid-term wear data and an experience based long-term phenomenological approach a general model for brush seal performance degradation is developed. This model can be used for performance prediction and exerts influence on brush seal design.
A phase I trial of intratumoral (i.t.) administration of reovirus in patients with histologically confirmed recurrent malignant gliomas (MGs) (2006)

1563 Background: Reovirus is an oncolytic virus which replicates preferentially in transformed cells possessing activated Ras signaling pathways. Promising activity was found in in vivo models of MGs and in a phase I trial in patients (pts.) with cutaneous metastases from systemic cancer. We performed this dose-escalation trial of i.t. administration of reovirus to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) in pts. with recurrent MG. Response, survival and time to progression (TTP) were secondary aims. Methods: Pts. were ≥ 18 yrs old, had a KPS ≥ 60, received prior radiotherapy ± chemotherapy, a histologically proven recurrence of MG and recurred ≤ 3 times. Reovirus was administered i.t. stereotactically at one of three dose levels (1 × 10 7 , 1 × 10 8 or 1 × 10 9 TCID50) in a volume of 0.9 mls. Results: Twelve pts. were treated at 3 dose levels; seven were men, the median (mdn) KPS was 80, mdn age was 53.5 yrs, 10 had glioblastoma multiforme, one anaplastic astrocytoma and another anaplastic oligoastrocytoma. There were the 1 st , 2 nd or 3 rd recurrences in 6, 5 and 1 pts., respectively. During i.t. viral administration all pts. were treated with prophylactic anticonvulsants and 6 (50%) were receiving corticosteroids. The 1 st , 2 nd and 3 rd cohorts contained 3, 6 and 3 pts., respectively. There were no grade 3 or 4 adverse events definitely or probably related to the administration of reovirus. A transient increase in GGT was possibly related to reovirus administration and a patient experienced grade 3 motor weakness that could be related to post-injection edema. Viral shedding and systemic immune responses were examined but results are pending. There were no CR, or PR; a pt. had SD, 10 PD and one was not evaluable. The mdn survival was 20 weeks (range, 6–171), 6 pts. survived > 6 months and 3 are alive 6, 7 and 40 months from the reovirus injection. The mdn TTP was 4.3 weeks (range: 3.4–39). Conclusions: A MTD was not reached. The intratumoral administration or reovirus was well tolerated in patients with recurrent MGs. Phase 2 studies in MGs are planned. [Table: see text]
Trac-It: A Smart User Interface for a Real-Time Location-Aware Multimodal Survey Tool (2008)

Transportation professionals strive to gain a deeper understanding of household travel behavior patterns for the purposes of modeling, planning, and maintaining transportation systems. Decision-makers also strive to utilize these patterns for educating, promoting and encouraging the use of alternatives to driving in general and to driving alone in particular. This paper focuses on using innovative technology in travel data collection. The ubiquity of portable devices, such as mobile phones and personal digital assistants (PDAs) in today’s world, provides opportunities to revolutionize travel surveys. In the past, data have been obtained through labor intensive paper and/or telephone interviews then input into computers for analyses. While mobile devices can be utilized as modern survey replacements, the requirement of constant user interaction presents many challenges. This paper discusses the design and field tests of TRAC-IT, a smart application for mobile devices that interrelates real-time user input with global positioning system (GPS) data, while adapting to user behavior to create a comprehensive tool that improves the quality and quantity of collected data. Initial limited field tests show a mean of 6.2 reported daily trips per individual. More comprehensive travel behavior data are anticipated when TRAC-IT is used by a larger number of households for longer durations.
User Models Sharing and Reusability: A Component-based Approach (2012)

Abstract. The current state of affairs in user modeling is that user models are developed ad-hoc, as part of a specific application. The proprietary user models are evidence of the lack of standard user-modeling processes and the amount of unnecessary rework done. Nowadays, when people tend to share information, open source is available, and Component-based software development is a common practice, it is time to adopt it for user modeling as well. The Component-based user-modeling approach suggests a practical alternative to the ad-hoc development of user models: user-modeling components that can evolve and be developed collaboratively and incrementally by the user modeling community, enabling reuse and flexibility, leading towards new and advanced user models built from existing components.
In-Memory Data Rearrangement for Irregular, Data-Intensive Computing (2015)

The data rearrangement engine (DRE) performs in-memory data restructuring to accelerate irregular, data-intensive applications. An emulation on a field-programmable gate array shows how the DRE could improve speedup, memory bandwidth, and energy consumption on three representative benchmarks.
Holographic wavefront sensor (2005)

In this talk we will present a new zonal wavefront sensor. The device consists of a multiplexed hologram which can reconstruct multiple diffracted beams to an image plane with the input of a single object beam. In operation, a wavefront incident on the hologram is divided up into various output beams according to the presence and strength of particular aberrations present in the input. The Zernike terms are then simply read out according to the location of the foci on the image plane CCD. The wavefront information is thus derived without the need for any computations; in effect representing an all-optical, massively parallel processing method with virtually limitless bandwidth. Furthermore, because of the minimal computing electronics required this type of sensor is compact and permits active wavefront sensing for very small imaging devices.
Cheap Paxos (2004)

Asynchronous algorithms for implementing a fault-tolerant distributed system, which can make progress despite the failure of any F processors, require 2F + 1 processors. Cheap Paxos, a variant of the Paxos algorithm, guarantees liveness under the additional assumption that the set of nonfaulty processors does not "jump around" too fast, but uses only F + 1 main processors that actually execute the system and F auxiliary processors that are used only to handle the failure of a main processor. The auxiliary processors take part in reconfiguring the system to remove the failed processor, after which they can remain idle until another main processor fails.
A semi-persistent clustering technique for VLSI circuit placement (2005)

Placement is a critical component of today's physical synthesis flow with tremendous impact on the final performance of VLSI designs. However, it accounts for a significant portion of the over-all physical synthesis runtime. With complexity and netlist size of today's VLSI design growing rapidly, clustering for placement can provide an attractive solution to manage affordable placement runtime. Such clustering, however, has to be carefully devised to avoid any adverse impact on the final placement solution quality. In this paper we present a new bottom-up clustering technique, called best-choice, targeted for large-scale placement problems. Our best-choice clustering technique operates directly on a circuit hypergraph and repeatedly clusters the globally best pair of objects. Clustering score manipulation using a priority-queue data structure enables us to identify the best pair of objects whenever clustering is performed. To improve the runtime of priority-queue-based best-choice clustering, we propose a lazy-update technique for faster updates of clustering score with almost no loss of solution quality. We also discuss a number of effective methods for clustering score calculation, balancing cluster sizes, and handling of fixed blocks. The effectiveness of our best-choice clustering methodology is demonstrated by extensive comparisons against other standard clustering techniques such as Edge-Coarsening [12] and First-Choice [13]. All clustering methods are implemented within an industrial placer CPLACE [1] and tested on several industrial benchmarks in a semi-persistent clustering context.
<i>CYP3A5</i>genotype predicts renal CYP3A activity and blood pressure in healthy adults (2003)

A single-nucleotide polymorphism (A6986G) in the cytochrome p-450 3A5 (CYP3A5) gene distinguishes an expressor (*1) and a reduced-expressor (*3) allele and largely predicts CYP3A5 content in liver and intestine. CYP3A5 is the prevailing CYP3A isoform in kidney. We report that, among renal microsomes from 21 organ donors, those from *1/*3 individuals had at least eightfold higher mean kidney microsomal CYP3A5 content and 18-fold higher mean CYP3A catalytic activity than did those from *3/*3 individuals (P = 0.0001 and P = 0.0137, respectively). We also report significant associations between the A6986G polymorphism and systolic blood pressure (P = 0.0007), mean arterial pressure (P = 0.0075), and creatinine clearance (P = 0.0035) among 25 healthy African-American adults. These associations remained significant when sex, age, and body mass index were taken into account. The mean systolic blood pressure of homozygous CYP3A5 expressors (*1/*1) exceeded that of homozygous nonexpressors (*3/*3) by 19.3 mmHg. We speculate whether a high CYP3A5 expressor allele frequency among African-Americans may contribute to a high prevalence of sodium-sensitive hypertension in this population.
On the Application of Vector Quantization and Hidden Markov Models to Speaker-Independent, Isolated Word Recognition (1983)

In this paper we present an approach to speaker-independent, isolated word recognition in which the well-known techniques of vector quantization and hidden Markov modeling are combined with a linear predictive coding analysis front end. This is done in the framework of a standard statistical pattern recognition model. Both the vector quantizer and the hidden Markov models need to be trained for the vocabulary being recognized. Such training results in a distinct hidden Markov model for each word of the vocabulary. Classification consists of computing the probability of generating the test word with each word model and choosing the word model that gives the highest probability. There are several factors, in both the vector quantizer and the hidden Markov modeling, that affect the performance of the overall word recognition system, including the size of the vector quantizer, the structure of the hidden Markov model, the ways of handling insufficient training data, etc. The effects, on recognition accuracy, of many of these factors are discussed in this paper. The entire recognizer (training and testing) has been evaluated on a 10-word digits vocabulary. For training, a set of 100 talkers spoke each of the digits one time. For testing, an independent set of 100 tokens of each of the digits was obtained. The overall recognition accuracy was found to be 96.5 percent for the 100-talker test set. These results are comparable to those obtained in earlier work, using a dynamic time-warping recognition algorithm with multiple templates per digit. It is also shown that the computation and storage requirements of the new recognizer were an order of magnitude less than that required for a conventional pattern recognition system using linear prediction with dynamic time warping.
Optimization of the Codon Pair Usage of Human Respiratory Syncytial Virus Paradoxically Resulted in Reduced Viral Replication <i>In Vivo</i> and Reduced Immunogenicity (2019)

We subjected various open reading frames (ORFs) in the genome of respiratory syncytial virus (RSV) to codon pair optimization (CPO) by increasing the content of codon pairs that are overrepresented in the human genome without changing overall codon usage and amino acid sequences. CPO has the potential to increase the expression of the encoded protein(s). Four viruses were made: Max A (with CPO of NS1, NS2, N, P, M, and SH ORFs), Max B (with CPO of G and F), Max L (with CPO of L), and Max FLC (with CPO of all ORFs except M2-1 and M2-2). Because of the possibility of increased viral replication, each CPO virus was attenuated by the inclusion of a codon deletion mutation (Δ1313) and a missense mutation (I1314L) in the L polymerase. CPO had no effect on multicycle virus replication <i>in vitro</i>, temperature sensitivity, or specific infectivity. Max A and L, which in common had CPO of one or more ORFs of proteins of the polymerase complex, exhibited global increases in viral protein synthesis. Max B alone exhibited decreased protein synthesis, and it alone had reduced single-cycle virus replication <i>in vitro</i> All CPO RSVs exhibited marginal reductions in replication in mice and hamsters. Surprisingly, the CPO RSVs induced lower levels of serum RSV-neutralizing antibodies in hamsters. This reduced immunogenicity might reflect reduced viral replication and possibly also the decrease in CpG and UpA dinucleotides as immune stimulators. Overall, our study describes paradoxical effects of CPO of an RNA virus on viral replication and the adaptive humoral immune response.<b>IMPORTANCE</b> Using computer algorithms and large-scale DNA synthesis, one or more ORFs of a microbial pathogen can be recoded by different strategies that involve the introduction of up to thousands of nucleotide changes without affecting amino acid coding. This approach has been used mostly to generate deoptimized viruses used as vaccine candidates. However, the effects of the converse approach of generating optimized viruses are still largely unknown. Here, various ORFs in the genome of respiratory syncytial virus (RSV) were codon pair optimized (CPO) by increasing the content of codon pairs that are overrepresented in the human genome. CPO did not affect RSV replication in multicycle replication experiments <i>in vitro.</i> However, replication was marginally reduced in two rodents models. In hamsters, CPO RSVs induced lower levels of serum RSV-neutralizing antibodies. Thus, CPO of an RNA virus for a mammalian host has paradoxical effects on virus replication and the adaptive humoral immune response.