gebhart/patrepeval huggingface dataset:
Complex promoter and coding region β <sub>2</sub> -adrenergic receptor haplotypes alter receptor expression and predict <i>in vivo</i> responsiveness (2000)

The human beta(2)-adrenergic receptor gene has multiple single-nucleotide polymorphisms (SNPs), but the relevance of chromosomally phased SNPs (haplotypes) is not known. The phylogeny and the in vitro and in vivo consequences of variations in the 5' upstream and ORF were delineated in a multiethnic reference population and an asthmatic cohort. Thirteen SNPs were found organized into 12 haplotypes out of the theoretically possible 8,192 combinations. Deep divergence in the distribution of some haplotypes was noted in Caucasian, African-American, Asian, and Hispanic-Latino ethnic groups with >20-fold differences among the frequencies of the four major haplotypes. The relevance of the five most common beta(2)-adrenergic receptor haplotype pairs was determined in vivo by assessing the bronchodilator response to beta agonist in asthmatics. Mean responses by haplotype pair varied by >2-fold, and response was significantly related to the haplotype pair (P = 0.007) but not to individual SNPs. Expression vectors representing two of the haplotypes differing at eight of the SNP loci and associated with divergent in vivo responsiveness to agonist were used to transfect HEK293 cells. beta(2)-adrenergic receptor mRNA levels and receptor density in cells transfected with the haplotype associated with the greater physiologic response were approximately 50% greater than those transfected with the lower response haplotype. The results indicate that the unique interactions of multiple SNPs within a haplotype ultimately can affect biologic and therapeutic phenotype and that individual SNPs may have poor predictive power as pharmacogenetic loci.
<title>Regularization technique for restoration of x-ray fluoroscopic images</title> (1995)

X-ray fluoroscopic images are degraded by x-ray scattering within the subject and veiling glare in the image intensifer. Densitometric accuracy is further degraded by beam hardening. Scattering, veiling glare, or both are modeled as a blurred representation of the primary image plus an offset. If the image can be represented by convolution of the primary with a known response function, then an estimate of the primary component of the image can be computed by deconvolution. We describe a technique for estimating a parameterized response function so that a good estimate of the subject density profile can be recovered even if the response function parameters are not known in advance. This is important for x-ray imaging (particularly fluoroscopy) since the acquisition parameters are variable. A reference object designed to be uncorrelated with the subject is imaged in superposition with the subject. The unknown parameters are then adjusted to minimize a cost function subject to the constraint that the correlation between the known reference density and the estimated subject density be zero. The method can be extended to include a correction for beam hardening.
Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing (2010)

Half of prostate cancers harbor gene fusions between TMPRSS2 and members of the ETS transcription factor family. To date, little is known about the presence of non-ETS fusion events in prostate cancer. We used next-generation transcriptome sequencing (RNA-seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes ETV1 and ERG, and four involving non-ETS genes such as CDKN1A (p21), CD9, and IKBKB (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene RSRC2. The novel gene fusions are found to be of low frequency, but, interestingly, the non-ETS fusions were all present in prostate cancer harboring the TMPRSS2-ERG gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement-prone phenotype.
Induction of antigen-specific parasiticidal cytotoxic T cell splenocytes by a major membrane protein (P30) of <i>Toxoplasma gondii</i>. (1988)

Infection with Toxoplasma gondii has become a major cause of morbidity in patients with AIDS. To investigate the mechanisms responsible for immune responses to toxoplasma Ag we used a highly purified membrane protein (P30) of T. gondii to stimulate an in vitro Ag-specific cytotoxic T cell response. P30 immune mouse splenocytes reduced extracellular T. gondii plaque-forming units by more than 50% when incubated at an E/T ratio of 10:1 or greater. By using a [3H]uracil radioisotope release assay, the effect of the immune splenocytes was determined to be a direct parasite lytic mechanism. The immune splenocytes were P30 Ag specific and of the Thy 1.2, Lyt2,3+ (CD4-, CD8+) phenotype, specific for mouse cytotoxic T cells. Opsonization of the parasites with monoclonal P30-reactive mAb did not enhance parasiticidal activity. Culture supernatants obtained during the 2-h cytotoxic assay were not parasiticidal, and anti-asialo-GM1 antibody plus C did not destroy the parasiticidal activity of the P30 responder cells. Accordingly, we have identified an Ag-specific subset of CD4-, CD8+, P30 responder T cells that are directly parasiticidal to extracellular T. gondii, and that exhibit cytotoxicity independent of antibody opsonization, lymphokine secretion, NK cell activity, and, apparently, MHC involvement as well.
A new power sensitivity method of ranking branch outage contingencies for voltage collapse (2002)

The objective of this paper is to present a powerful procedure for identifying severe single branch outage contingencies with respect to saddle-mode bifurcation induced voltage collapse, given a power system operating point, a load demand forecast, and a generation dispatch. The new power sensitivity ranking algorithm for voltage collapse, called /spl lambda//MVA sensitivity, provides more accurate "distance to collapse" estimates than linear admittance sensitivity, yet requires only slightly more computation time. The distinguishing features are the ability (1) to rank all branches in a large-scale power system quickly, and (2) to estimate the outage contingency bifurcation values accurately. As an illustration, the new /spl lambda//MVA sensitivity ranking algorithm can estimate all 6689 single branch outage contingency bifurcation points (/spl lambda/*/sub ctgc/) of a 3493 bus power system within 3% relative error, except for two branches within 7%, in less than 4 min on a 180 MHz PentiumPro PC.
Towards a Workload for Evolutionary Analytics (2013)

Emerging data analysis involves the ingestion and exploration of new data sets, application of complex functions, and frequent query revisions based on observing prior query answers. We call this new type of analysis evolutionary analytics and identify its properties. This type of analysis is not well represented by current benchmark workloads. In this paper, we present a workload and identify several metrics to test system support for evolutionary analytics. Along with our metrics, we present methodologies for running the workload that capture this analytical scenario.
Role of probiotics in reducing the risk of gestational diabetes (2015)

Overweight and obesity currently constitute a major threat to human well-being. Almost half of the female population are currently overweight. Pregnant overweight women are at risk of gestational diabetes affecting the health of the mother and the child, in both the short and long term. Notwithstanding the extensive scientific interest centred on the problem, research efforts have thus far been unable to devise preventive strategies. Recent scientific advances point to a gut microbiota dysbiosis, with ensuing low-grade inflammation as a contributing element, in obesity and its comorbidities. Such findings would suggest a role for specific probiotics in the search for preventive and therapeutic adjunct applications in gestational diabetes. The aim of the present paper was to critically review recent demonstrations of the role of intestinal microbes in immune and metabolic regulation, which could be exploited in nutritional management of pregnant women by probiotic bacteria. By modulating specific target functions, probiotic dietary intervention may exert clinical effects beyond the nutritional impact of food. As this approach in pregnancy is new, an overview of the role of gut microbiota in shaping host metabolism, together with the definition of probiotics are presented, and finally, specific targets and potential mechanisms for probiotics in pregnancy are discussed. Pregnancy appears to be the most critical stage for interventions aiming to reduce the risk of non-communicable disease in future generations, beyond the immediate dangers attributable to the health of the mother, labour and the neonate. Specific probiotic interventions during pregnancy provide an opportunity, therefore, to promote the health not only of the mother but also of the child.
scAAVengr, a transcriptome-based pipeline for quantitative ranking of engineered AAVs with single-cell resolution (2021)

This work was supported by funding from the Ford Foundation, NEI/NIH, Research to Prevent Blindness, Foundation Fighting Blindness, UPMC Immune Transplant and Therapy Center, and the Van Sloun fund for canine genetic research.
Optimal Factoring of FIR Filters (2014)

New insights suggest that the most efficient FIR digital filters can be created by using a scaled sequence of stages, each representing a factor of the filter's transfer function. A crucial capability for building such filters concerns finding the best FIR filter factors, then carefully scaling and sequencing them. The efficiency of the resulting structure depends heavily upon obtaining such optimal factors. We offer an algorithm to find, scale and sequence optimally factored FIR filters.
Synthesis and Biological Studies of a New Class of Antitumor Platinum Complexes (1983)

A series of platinum complexes having the general formula LPtCl3, where L is a ligand bearing a formal positive charge, have been prepared and have been demonstrated to exhibit significant antitumor activity. Complexes with this formulation satisfy the generally accepted criteria for structural features required in an antitumor-active platinum complex, but are expected to possess kinetic advantages when compared to the prototype antitumor platinum complex, cis-dichlorodiamineplatinum (II). Complexes have been prepared where L is a monoprotonated diamine and also where L is a protonated amino-olefin. All complexes have been examined for cytotoxicity against L1210 leukemia in cell culture, and selected compounds have been tested for antitumor activity in vivo (L1210 leukemia in BDF1 mice). One compound, where L is protonated 3-aminoquinuclidine, has significant in vivo activity, with T/C approaching 150%.
Design and fabrication of an integrated programmable floating-gate microphone (2003)

An integrated, programmable floating-gate capacitive microphone has been designed and fabricated. The conducting floating-gate is electrically insulated and is "programmed" by injecting electrons into it using Fowler-Nordheim tunneling through a thin silicon dioxide film, thus capable of simulating an electret and generating a permanent electric field. A current-driving buffer based on metal-oxide-semiconductor field-effect transistors is integrated to reduce the capacitive loading of the microphone. The fabrication process is MOS compatible and promises the potential of integrating a variety of signal processing electronic circuits.
An optical 4-fiber bi-directional line-switched ring (2003)

An optical four-fiber bidirectional line-switched ring is presented. Results from optical protection switching experiments show that restoration in <50 ms is possible. A self-healing, bandwidth efficient, and scalable optical transport network evolving from this architecture is possible.
A support vector machine approach for detection of microcalcifications (2002)

In this paper, we investigate an approach based on support vector machines (SVMs) for detection of microcalcification (MC) clusters in digital mammograms, and propose a successive enhancement learning scheme for improved performance. SVM is a machine-learning method, based on the principle of structural risk minimization, which performs well when applied to data outside the training set. We formulate MC detection as a supervised-learning problem and apply SVM to develop the detection algorithm. We use the SVM to detect at each location in the image whether an MC is present or not. We tested the proposed method using a database of 76 clinical mammograms containing 1120 MCs. We use free-response receiver operating characteristic curves to evaluate detection performance, and compare the proposed algorithm with several existing methods. In our experiments, the proposed SVM framework outperformed all the other methods tested. In particular, a sensitivity as high as 94% was achieved by the SVM method at an error rate of one false-positive cluster per image. The ability of SVM to out perform several well-known methods developed for the widely studied problem of MC detection suggests that SVM is a promising technique for object detection in a medical imaging application.
Mobile traffic forecasting for maximizing 5G network slicing resource utilization (2017)

The emerging network slicing paradigm for 5G provides new business opportunities by enabling multi-tenancy support. At the same time, new technical challenges are introduced, as novel resource allocation algorithms are required to accommodate different business models. In particular, infrastructure providers need to implement radically new admission control policies to decide on network slices requests depending on their Service Level Agreements (SLA). When implementing such admission control policies, infrastructure providers may apply forecasting techniques in order to adjust the allocated slice resources so as to optimize the network utilization while meeting network slices' SLAs. This paper focuses on the design of three key network slicing building blocks responsible for (i) traffic analysis and prediction per network slice, (ii) admission control decisions for network slice requests, and (iii) adaptive correction of the forecasted load based on measured deviations. Our results show very substantial potential gains in terms of system utilization as well as a trade-off between conservative forecasting configurations versus more aggressive ones (higher gains, SLA risk).
Self-delivering RNAi compounds as therapeutic agents in the central nervous system to enhance axonal regeneration after injury (2022)

The therapeutic use of RNAi has grown but often faces several hurdles related to delivery systems, compound stability, immune activation, and on-target/off-tissue effects. Self-delivering RNAi (sdRNA) molecules do not require delivery agents or excipients. Here we demonstrate the ability of sdRNA to reduce the expression of PTEN (phosphatase and tensin homolog) to stimulate regenerative axon regrowth in the injured adult CNS. PTEN-targeting sdRNA compounds were tested for efficacy <i>in vivo</i> by intravitreal injection after adult rat optic nerve injury. We describe critical steps in lead compound generation through the optimization of nucleotide modifications, enhancements for stability in biological matrices, and screening for off-target immunostimulatory activity. The data show that PTEN expression <i>in vivo</i> can be reduced using sdRNA and this enhances regeneration in adult CNS neurons after injury, raising the possibility that this method could be utilized for other clinically relevant nervous system indications.
<title>ISee: perceptual features for image library navigation</title> (2002)

To develop more satisfying image navigation systems, we need tools to construct a semantic bridge between the user and the database. In this paper we present an image indexing scheme and a query language, which allow the user to introduce a cognitive dimension to the search. At an abstract level, this approach consists of: 1) learning the natural language that humans speak to communicate their semantic experience of images, 2) understand the relationships between this language and objective measurable image attributes, and then 3) develop the corresponding feature extraction schemes. In our previous work we have conducted a number of subjective experiments in which we asked human subjects to group images, and then explain verbally why they did so. The results of this study indicated that part of the abstraction involved in image interpretation is often driven by semantic categories, which can be broken into more tangible semantic entities, i.e. objective semantic indicators. By analyzing our experimental data, we identified some candidate semantic categories (i.e. portraits, people, crowds, cityscapes, landscapes, etc.), discovered their underlying semantic indicators (i.e. skin, sky, water, object, etc.), and derived important low-level image descriptors accounting for our perception of these indicators. In our recent work we have used these findings to develop a set of image features that match the way humans communicate image meaning, and a semantic-friendly query language for browsing and searching diverse collections of images. We have implemented our approach into an Internet search engine, ISee, and tested it on a large number of images. The results we obtained are very promising.
Tl2O3 vapor process of making Tl-Ba-Ca-Cu-O superconductors (1988)

A new process for making Tl-Ba-Ca-Cu-O superconductors which is based on reactions between solid precursor Ba-Ca-Cu-oxides and vapor Tl2O3 has been developed. The Tl2O3 vapor process allows Tl-Ba-Ca-Cu-O superconductors to be easily made in the forms of complex bulk components, wires and fibers, and thick and thin films, and minimizes problems caused by toxicity and volatility of Tl starting compounds.
A microphone array for hearing aids (2001)

A directional acoustic receiving system is a form of a necklace including an array of two or more microphones mounted on a housing supported on the chest of a user by a conducting loop encircling the user's neck. Signal processing electronics contained in the same housing receive and combine the microphone signals in such a manner as to provide an amplified output signal which emphasizes sounds of interest arriving in a direction forward of the user. The amplified output signal drives the supporting conducting loop to produce a representative magnetic field. An electroacoustic transducer including a magnetic field pick up coil for receiving the magnetic field is mounted in or on the user's ear and generates an acoustic signal representative of the sounds of interest. The microphone output signals are weighted (scaled) and combined to achieve desired spatial directivity responses. The weighting coefficients are determined by an optimization process. By bandpass filtering the weighted microphone signals, with a set of filters covering the audio frequency range, and summing the filtered signals, a receiving microphone array with a small aperture size is caused to have a directivity pattern that is essentially uniform over frequency in two or three dimensions. This method enables the design of highly-directive-hearing instruments which are comfortable, inconspicuous, and convenient to use. The array provides the user with a dramatic improvement in speech perception over existing hearing aid designs, particularly in the presence of background noise, reverberation, and feedback.
Purification and characterization of the receptor for pituitary adenylate cyclase-activating polypeptide. (1993)

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide (PACAP38) or a truncated peptide with the same 27 amino-terminal residues (PACAP27). The PACAP receptor was solubilized from bovine brain membranes with digitonin and purified 30-fold by the combination of DEAE-Toyopearl and hydroxylapatite chromatographic analyses. The partially purified PACAP receptors were mixed with biotinylated PACAP27 to form receptor-ligand complexes and then adsorbed onto avidin-agarose. The adsorbed PACAP receptors were eluted with an acidic buffer containing 1.0 M NaCl (pH 4.0). The eluted receptors were purified further by hydroxylapatite and gel filtration chromatography. A single protein band with a M(r) = 55,000-60,000 was found in the final preparation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining. Affinity labeling of the purified receptors with 125I-PACAP27 labeled the M(r) 55,000-60,000 protein specifically. The dissociation constant and the specific activity of the purified receptors were 25.8 pM and 17.2 nmol of ligand binding per mg of protein, respectively. Inhibitory constants determined by competitive binding experiments were 30.0 pM for PACAP27, 4.6 pM for PACAP38, and 37.3 nM for vasoactive intestinal peptide. Therefore, the purified PACAP receptor retained high affinity and ligand specificity. The sequence of the amino-terminal 29 residues was derived from the purified receptor.
Role of the Amino-Terminal Region of <i>Porphyromonas gingivalis</i> Fimbriae in Adherence to Epithelial Cells (1999)

Porphyromonas gingivalis fimbriae elicit many responses in eukaryotic cells, including mitogenicity, cytokine production, epithelial cell invasion, and cellular immune response. Specific domains of the major fimbrial protein (FimA) have been shown to be important in triggering some of these functions. The goal of the present study was to identify the domain(s) of P. gingivalis FimA responsible for specific interaction with human mucosal epithelial cells. Fimbriated P. gingivalis strains have been shown to bind to buccal epithelial cells, whereas nonfimbriated strains bind at low levels or not at all. This and other studies provide evidence that FimA mediates the adherence of P. gingivalis to oral epithelial cells. To determine the specific region(s) of P. gingivalis FimA involved in epithelial cell binding, specific antipeptide antibodies were used to inhibit the binding of iodinated purified fimbriae as well as the binding of P. gingivalis cells to epithelial cells. Antibodies directed against peptides 49 to 68 (VVMANTAGAMELVGKTLAEVK) and 69 to 90 (ALTTELTAENQEAAGLIMTAEP) were found to highly inhibit both the binding of fimbriae and the binding of P. gingivalis cells to epithelial cells. The antibody against FimA peptides 69 to 90 also reacted with P. gingivalis fimbriae in immunogold labeling and immunoblot analysis, thereby indicating that this peptide domain is exposed on the surface of fimbriae. Our results suggest that the amino-terminal domain corresponding to amino acid residues 49 to 90 of the fimbrillin protein is a major epithelial cell binding domain of P. gingivalis fimbriae.
O6C-20-nor-SalA is a stable and potent KOR agonist (2017)

Salvinorin A (SalA) is a potent and selective agonist of the kappa-opioid receptor (KOR), but its instability has frustrated medicinal chemistry efforts. Treatment of SalA with weak bases like DBU leads to C8 epimerization with loss of receptor affinity and signaling potency. Here we show that replacement of C20 with H and replacement of O6 with CH2 stabilizes the SalA scaffold relative to its C8 epimer, so much so that epimerization is completely suppressed. This new compound, O6C-20-nor-SalA, retains high potency for agonism of KOR. <br>