gebhart/patrepeval huggingface dataset:
Antisense-Oligonucleotide Mediated Exon Skipping in Activin-Receptor-Like Kinase 2: Inhibiting the Receptor That Is Overactive in Fibrodysplasia Ossificans Progressiva (2013)

Fibrodysplasia ossificans progressiva (FOP) is a rare heritable disease characterized by progressive heterotopic ossification of connective tissues, for which there is presently no definite treatment. A recurrent activating mutation (c.617G→A; R206H) of activin receptor-like kinase 2 (ACVR1/ALK2), a BMP type I receptor, has been shown as the main cause of FOP. This mutation constitutively activates the BMP signaling pathway and initiates the formation of heterotopic bone. In this study, we have designed antisense oligonucleotides (AONs) to knockdown mouse ALK2 expression by means of exon skipping. The ALK2 AON could induce exon skipping in cells, which was accompanied by decreased ALK2 mRNA levels and impaired BMP signaling. In addition, the ALK2 AON potentiated muscle differentiation and repressed BMP6-induced osteoblast differentiation. Our results therefore provide a potential therapeutic approach for the treatment of FOP disease by reducing the excessive ALK2 activity in FOP patients.
Live video analytics at scale with approximation and delay-tolerance (2017)

Video cameras are pervasively deployed for security and smart city scenarios, with millions of them in large cities worldwide. Achieving the potential of these cameras requires efficiently analyzing the live videos in real-time. We describe VideoStorm, a video analytics system that processes thousands of video analytics queries on live video streams over large clusters. Given the high costs of vision processing, resource management is crucial. We consider two key characteristics of video analytics: resource-quality tradeoff with multi-dimensional configurations, and variety in quality and lag goals. VideoStorm's offline profiler generates query resource-quality profile, while its online scheduler allocates resources to queries to maximize performance on quality and lag, in contrast to the commonly used fair sharing of resources in clusters. Deployment on an Azure cluster of 101 machines shows improvement by as much as 80% in quality of real-world queries and 7× better lag, processing video from operational traffic cameras.
A role for nerve growth factor in sympathetic sprouting in rat dorsal root ganglia (1999)

The role of nerve growth factor (NGF) and glial-derived neurotrophic factor (GDNF) in sympathetic sprouting within the dorsal root ganglion was investigated. In nerve-intact rats, intrathecal NGF (1 mg/ml, 14 days) but not GDNF (1 mg/ml, 14 days) induced extensive sprouting of tyrosine hydroxylase immunoreactive (TH-IR) fibres and formation of pericellular TH-IR baskets within lumbar DRGs. TH-IR baskets were distributed equally to trkA-expressing and trkA-negative neuronal profiles. Sciatic nerve transection (14-21 days) induced TH-IR baskets within lumbar DRG's around neuronal profiles with both intact and lesioned axons. The percentage of neuronal profiles surrounded by TH-IR baskets following sciatic transection was unaffected following peripheral application of the NGF sequestering antibody, trkA-IgG (1 mg/ml, 14 days). Intracellular responses were recorded from sensory neurons in an in vitro DRG/peripheral nerve preparation following bath application of noradrenaline. In preparations from animals treated 14 days previously with intrathecal NGF, 69% of neurons responded with depolarizing responses whilst 18% of neurons responded to bath applied noradrenaline in tissue prepared from naive animals. Our data indicate that sympathetic neurons sprout into the DRG in response to sciatic nerve injury and intrathecal NGF but not GDNF. Distribution of sympathetic sprouts within the DRG is independent of whether target neurons are injured or express trkA. Sequestration of NGF at the peripheral injury site does not influence basket formation within the DRG. It is likely that functional noradrenergic connections exist between sympathetic sprouts and sensory neuron cell bodies following exogenous NGF.
Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing (2012)

Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through Darwinian selection. (Funded by the Medical Research Council and others.).
A placebo‐controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis (1996)

Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.
SMAA: Enhanced Subpixel Morphological Antialiasing (2012)

Abstract We present a new image‐based, post‐processing antialiasing technique, which offers practical solutions to the common, open problems of existing filter‐based real‐time antialiasing algorithms. Some of the new features include local contrast analysis for more reliable edge detection, and a simple and effective way to handle sharp geometric features and diagonal lines. This, along with our accelerated and accurate pattern classification allows for a better reconstruction of silhouettes. Our method shows for the first time how to combine morphological antialiasing (MLAA) with additional multi/supersampling strategies (MSAA, SSAA) for accurate subpixel features, and how to couple it with temporal reprojection; always preserving the sharpness of the image. All these solutions combine synergies making for a very robust technique, yielding results of better overall quality than previous approaches while more closely converging to MSAA/SSAA references but maintaining extremely fast execution times. Additionally, we propose different presets to better fit the available resources or particular needs of each scenario.
Purification of Cryptosporidium Oocysts and Sporozoites by Cesium Chloride and Percoll Gradients (1987)

The lack of an adequate system for the in vitro cultivation of Cryptosporidium spp. has forced researchers to work on infected feces or tissues. Molecular and immunological analyses of Cryptosporidium stages must be preceded by complex preparatory steps involving the concentration, storage, purification, excystation of oocysts, and purification of sporozoites. This paper describes two new procedures for the purification of Cryptosporidium. The first, consisting of pretreatment of oocysts with sodium hypochlorite followed by concentration using a Percoll gradient, is suitable for nucleic acid analyses. The second, a concentration of untreated oocysts using a Cesium chloride gradient, is suitable for biochemical and immunological studies, but requires "fresh" oocysts.
Hyperbranched PbS and PbSe Nanowires and the Effect of Hydrogen Gas on Their Synthesis (2007)

We report a chemical vapor deposition (CVD) synthesis of hyperbranched single-crystal nanowires of both PbS and PbSe using PbCl2 and S/Se as precursors under hydrogen flow. Multiple generations of nanowires grow perpendicularly from the previous generation of nanowires in an epitaxial fashion to produce dense clusters of a complex nanowire network structure. The flow rate and duration of the hydrogen co-flow in the argon carrier gas during the CVD reactions are found to have a significant effect on the morphology of the PbS/PbSe grown, from hyperbranched nanowires to micrometer-sized cubes. No intentional catalyst was employed for the nanowire synthesis, but it is suggested that elemental lead that has been reduced from the vapor by the hydrogen might serve as a vapor-liquid-solid (VLS) catalyst for the anisotropic growth of PbS/PbSe. The nanowires were also investigated with Raman spectroscopy. These PbS and PbSe nanostructures can have applications in photovoltaics because multiple exciton generation has been demonstrated in nanocrystals of both materials.
Activity of Gentamicin, Tobramycin, Polymyxin B, and Colistimethate in Mouse Protection Tests with Pseudomonas aeruginosa (1975)

Mouse protection tests were carried out with four antibiotics and six strains of Pseudomonas aeruginosa. All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of Pseudomonas was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of Pseudomonas that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic.
Ig V region gene expression in small lymphocytic lymphoma with little or no somatic hypermutation. (1989)

Using the polymerase chain reaction we examined for specific Ig kappa-L chain V region gene (V kappa gene) rearrangement in small lymphocytic non-Hodgkin's lymphomas that express Ig bearing a major kappa-L chain associated cross-reactive Id, designated 17.109. Previously, we identified the 17.109-cross-reactive Id in chronic lymphocytic leukemia as a serologic marker for expression of a highly conserved V kappa gene, designated Humkv325. Using sense-strand oligonucleotides specific for the 5'-end of this V kappa gene and antisense oligonucleotide specific for a J kappa region consensus sequence, we could amplify specifically Humkv325 when juxtaposed with J kappa through Ig gene rearrangement. This allowed us to amplify rearranged V kappa genes from DNA isolated from minute amounts of lymphoma biopsy material for molecular analyses. Our studies demonstrate that 17.109-reactive SL NHL, with or without associated CLL, rearrange, and presumably express, Humkv325 without substantial somatic diversification. Our data suggest that malignant B cells in SL NHL, in contrast to NHL of follicular center cell origin, may express immunoglobulin variable region genes with little or no somatic hypermutation.
Effect of annexin-1 on experimental autoimmune encephalomyelitis (EAE) in the rat (1998)

Annexin-1, a calcium-dependent phospholipid binding protein, has been shown to act as an endogenous central neuroprotectant, notably against cerebral ischaemic damage. In the present study we extend these findings to an animal model of multiple sclerosis, EAE, and report that endogenous annexin-1 is expressed in ED1+ macrophages and resident astrocytes localized within the lesions in the central nervous system (CNS). Intracerebroventricular (i.c.v.) administration of an NH2-terminal fragment spanning amino acids 1-188 of annexin-1 after the onset of the clinical symptoms significantly reduced both the neurological severity as well as weight loss of mild EAE. Immunoneutralization of endogenous brain annexin-1 failed to exacerbate the clinical features of EAE. Thus, although the role of endogenous annexin-1 in the pathogenesis of EAE remains to be determined, our findings suggest that annexin-1 may be of therapeutic benefit to the treatment of multiple sclerosis.
Direct Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors (2007)

Although the presence of macrophages in tumors has been correlated with poor prognosis, until now there was no direct observation of how macrophages are involved in hematogenous metastasis. In this study, we use multiphoton microscopy to show, for the first time, that tumor cell intravasation occurs in association with perivascular macrophages in mammary tumors. Furthermore, we show that perivascular macrophages of the mammary tumor are associated with tumor cell intravasation in the absence of local angiogenesis. These results show that the interaction between macrophages and tumor cells lying in close proximity defines a microenvironment that is directly involved in the intravasation of cancer cells in mammary tumors.
Design and Synthesis of a New Peptide Recognizing a Specific 16-Base-Pair Site of DNA (1995)

We designed a peptide to recognize a new 16-base-pair site (about 1.5 turns) of DNA by stitching together three peptides of the v-Jun basic region in a specified order. The binding site consists of three five-base-pair half-sites each of which is recognized by a different segment of the peptide. DNase I footprinting shows that the new peptide specifically recognizes the proposed site, and gel retardation shows that the dissociation constant is about 5 nM at 4 °C. Gel retardation shows that the new peptide does recognize the proposed trimer binding site about 10 times stronger than the dimer binding sites [having two half-sites for two arms]. These results also provide information about the relationship between specific and nonspecific binding in the recognition between protein and DNA.
Stacking fault structure in shear-induced colloidal crystallization (2006)

We report measurements of the spatial distribution of stacking faults in colloidal crystals formed by means of an oscillatory shear field at a particle volume fraction of 52% in a system where the pair potential interactions are mildly repulsive. Stacking faults are directly visualized via confocal laser scanning microscopy. Consistent with previous scattering studies, shear orders the initially amorphous colloids into close-packed planes parallel to the shearing surface. Upon increasing the strain amplitude, the close-packed direction of the (111) crystal plane shifts from an orientation parallel to the vorticity direction to parallel the flow direction. The quality of the layer ordering, as characterized by the mean stacking parameter, decreases with strain amplitude. In addition, we directly observe the three-dimensional structure of stacking faults in sheared crystals. We observe and quantify spatial heterogeneity in the stacking fault arrangement in both the flow-vorticity plane and the gradient direction, particularly at high strain amplitudes (gamma> or =3). At these conditions, layer ordering persists in the flow-vorticity plane only over scales of approximately 5-10 particle diameters. This heterogeneity is one component of the random layer ordering deduced from previous scattering studies. In addition, in the gradient direction, the stacking registry shows that crystals with intermediate global mean stacking probability are comprised of short sequences of face-centered cubic and hexagonal close-packed layers with a stacking that includes a component that is nonrandom and alternating in character.
Optimal guideRNAs for re-directing deaminase activity of hADAR1 and hADAR2 in trans (2014)

Adenosine deaminases that act on RNA (ADAR) are a class of enzymes that catalyze the conversion of adenosine to inosine in RNA. Since inosine is read as guanosine ADAR activity formally introduces A-to-G point mutations. Re-addressing ADAR activity toward new targets in an RNA-dependent manner is a highly rational, programmable approach for the manipulation of RNA and protein function. However, the strategy encounters limitations with respect to sequence and codon contexts. Selectivity is difficult to achieve in adenosine-rich sequences and some codons, like 5'-GAG, seem virtually inert. To overcome such restrictions, we systematically studied the possibilities of activating difficult codons by optimizing the guideRNA that is applied in trans. We find that all 5'-XAG codons with X = U, A, C, G are editable in vitro to a substantial amount of at least 50% once the guideRNA/mRNA duplex is optimized. Notably, some codons, including CAG and GAG, accept or even require the presence of 5'-mismatched neighboring base pairs. This was unexpected from the reported analysis of global editing preferences on large double-stranded RNA substrates. Furthermore, we report the usage of guanosine mismatching as a means to suppress unwanted off-site editing in proximity to targeted adenosine bases. Together, our findings are very important to achieve selective and efficient editing in difficult codon and sequence contexts.
A Null Mutation in Human APOC3 Confers a Favorable Plasma Lipid Profile and Apparent Cardioprotection (2008)

Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-cholesterol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.
Multi-task Sequence to Sequence Learning (2015)

Sequence to sequence learning has recently emerged as a new paradigm in supervised learning. To date, most of its applications focused on only one task and not much work explored this framework for multiple tasks. This paper examines three multi-task learning (MTL) settings for sequence to sequence models: (a) the oneto-many setting - where the encoder is shared between several tasks such as machine translation and syntactic parsing, (b) the many-to-one setting - useful when only the decoder can be shared, as in the case of translation and image caption generation, and (c) the many-to-many setting - where multiple encoders and decoders are shared, which is the case with unsupervised objectives and translation. Our results show that training on a small amount of parsing and image caption data can improve the translation quality between English and German by up to 1.5 BLEU points over strong single-task baselines on the WMT benchmarks. Furthermore, we have established a new state-of-the-art result in constituent parsing with 93.0 F1. Lastly, we reveal interesting properties of the two unsupervised learning objectives, autoencoder and skip-thought, in the MTL context: autoencoder helps less in terms of perplexities but more on BLEU scores compared to skip-thought.
IQGAP1 Plays an Important Role in the Invasiveness of Thyroid Cancer (2010)

IQGAP1, through genetic copy gain, plays an important role in the invasiveness of thyroid cancer and may represent a novel prognostic marker and therapeutic target for this cancer.
Current Developments in Gene Transfection Agents (2004)

DNA can be delivered into the cell nucleus either using physical means or specific carriers that carry the genes into the cells for gene expression). Various carriers for delivering genes have been investigated which can be divided into two main groups: viral carriers where the DNA to be delivered is inserted into a virus, and cationic molecular carriers that form electrostatic interactions with DNA). Successful gene therapy depends on the efficient delivery of genetic materials into the cells nucleus and its effective expression within these cells). Although at present the in vivo expression levels of synthetic molecular gene vectors are lower than for viral vectors and gene expression is transient, these vehicles are likely to present several advantages including safety, low-immunogenicity, capacity to deliver large genes and large-scale production at low-cost). The two leading classes of synthetic gene delivery systems that have been mostly investigated are cationic lipids and cationic polymers). This review discusses recent developments in viral vectors, physical means and molecular gene carriers). The last part focuses on our recent studies in developing a new series of biodegradable polycations for in vitro and in vivo gene transfection).
The formation of iron features in the cooling spectrum of X-ray bursts (1987)

A detailed calculation of the formation and detection of iron spectral features in X-ray bursts is presented. Observation of these features will enable the mass and radius of a neutron star to be estimated separately. Comptonization and free–free absorption and emission processes are taken into account, as well as the effects of iron in its last four states of ionization. We estimate the size of detector, with response similar to that of the EXOSAT ME, needed in order to observe the iron features. The large-area detectors on GINGA should meet this requirement. We show that the absorption feature reported at 4.1 keV from MXB 1636–536 has an equivalent width much larger than expected from Fe xxv.
Role of interleukin-2 (IL-2), IL-7, and IL-15 in natural killer cell differentiation from cord blood hematopoietic progenitor cells and from gamma c transduced severe combined immunodeficiency X1 bone marrow cells (1996)

Natural killer (NK) cells are characterized by their ability to mediate spontaneous cytotoxicity against susceptible tumor cells and infected cells. They differentiate from hematopoietic progenitor cells. Patients with X-linked severe combined immunodeficiency (SCID X1) carry mutations in the gamma c cytokine receptor gene that result in lack of both T and NK cells. To assess the role of interleukin-2 (IL-2), IL-7, and IL-15 cytokines, which share gamma c receptor subunit, in NK cell differentiation, we have studied NK cell differentiation from cord blood CD34 (+) cells in the presence of either stem cell factor (SCF), IL-2, and IL-7 or SCF and IL-15. The former cytokine combination efficiently induced CD34 (+) CD7 (+) cord blood cells to proliferate and mature into NK cells, while the latter was also able to induce NK cell differentiation from more immature CD34 (+) CD7 (-) cord blood cells. NK cells expressed CD56 and efficiently killed K562 target cells. These results show that IL-15 could play an important role in the maturation of NK cell from cord blood progenitors. Following retroviral-mediated gene transfer of gamma c into SCID X1 bone marrow progenitors, it was possible to reproduce a similar pattern of NK cell differentiation in two SCID-X1 patients with SCF + IL-2 + IL-7 and more efficiently in one of them with SCF + IL-15. These results strongly suggest that the gamma c chain transduces major signal(s) involved in NK cell differentiation from hematopoietic progenitor cells and that IL-15 interaction with gamma c is involved in this process at an earlier step than IL-2/IL-7 interactions of gamma c are. It also shows that gene transfer into hematopoietic progenitor cells could potentially restore NK cell differentiation in SCID X1 patients.