gebhart/patrepeval huggingface dataset:
Enhanced therapeutic efficacy against an ovarian tumor xenograft of immunotoxins used in conjunction with recombinant alpha-interferon. (1990)

The antitumor effects of two immunotoxins were evaluated in vitro and in vivo against the human ovarian carcinoma cell line, OVCAR-3. The immunotoxins used were composed of recombinant ricin A chain (rRTA) covalently attached to a monoclonal antibody directed toward the human transferrin receptor (45412/rRTA, also called 454A12 MAB-rRTA by Cetus Corporation) or Pseudomonas exotoxin coupled to an anticarcinoma monoclonal antibody (NR-LU-10/PE). Preliminary characterization of the NR-LU-10 antigen by immunoprecipitation and cellular fluorescence demonstrated two dominant cell surface polypeptide moieties with molecular weights of 40,000 and 45,000 and a minor component with a molecular weight of 33,000. The immunotoxins were used alone or in combination with recombinant human alpha-interferon (rhIFN-alpha). Protein synthesis was inhibited in a dose-dependent manner in OVCA-3 cells incubated in vitro with either NR-LU-10/PE or 454A12/rRTA (50% inhibitory concentrations, 1 and 75 ng/ml, respectively). Unconjugated NR-LU-10 or 454A12 abrogated the activity of the relevant immunotoxins. Concomitant incubation in vitro of OVCAR-3 cells with NR-LU-10/PE or 454A12/rRTA and a noncytotoxic concentration of rhIFN-alpha potentiated the inhibitory activity of the immunotoxins via a mechanism independent of antigenic upregulation. This potentially synergistic combination was then tested in vivo. The median survival time (MST) of mice given injections i.p. of 4 x 10(6) OVCAR-3 cells was 46 days. Cohorts of mice that received intracavitary treatment beginning 5 days posttumor cell inoculation with either 0.25 or 0.5 microgram of NR-LU-10/PE every other day for a total of 10 treatments exhibited a significantly increased MST of 63 and 104 days, respectively (P less than 0.0001). Likewise, the i.p. injection of either 2.5 or 10 micrograms of 454A12/rRTA given in an identical schedule resulted in a MST of 89 and greater than 120 days, respectively (P less than 0.0001). When rhIFN-alpha was administered i.p. in conjunction with those doses of either immunotoxin, a significant increase in the MST was observed in comparison with mice given immunotoxin alone. The combination of 5 x 10(4) units of rhIFN-alpha and 0.25 microgram of NR-LU-10/PE resulted in 67% long-term survivors (greater than 120 days) compared with only 13% survival of mice given the immunotoxin alone. Similarly, 2.5 micrograms of 454A12/rRTA plus rhIFN-alpha resulted in an enhanced therapeutic response (89% long-term survivors) when compared with 454A12/rRTA alone (29%).(ABSTRACT TRUNCATED AT 400 WORDS)
Breakthroughs in Andrology Real-Time Fine Morphology of Motile Human Sperm Cells is Associated With IVF-ICSI Outcome (2002)

The aim of the present prospective study was to de- termine whether subtle sperm morphological characteristics affect the outcome of intracytoplasmic sperm injection (ICSI), and if so, to identify those that are relevant. For this purpose, we developed a new method, the motile sperm organelle morphology examination (MSOME). The examination is performed in real time using an in- verted light microscope equipped with high-power Nomarski optics enhanced by digital imaging to achieve a magnification up to 6300. MSOME was applied to the leftover sperm fraction selected for mi- croinjection in 100 random couples referred for ICSI treatment at 3 major in vitro fertilization centers. We found that the morphological normalcy of the entire sperm cell, according to MSOME criteria, was positively associated with ICSI fertilization rate (area under the re- ceiver operating characteristics (ROC) curve, 88%) but not with preg- nancy outcome. The morphological normalcy of the sperm nucleus, defined by MSOME, was significantly and positively associated with both fertilization rate and pregnancy outcome (areas under the ROC curve, 72% and 74%, respectively). These findings indicate that ICSI-associated pregnancy rate may be affected by subtle morpho- logical malformations of the sperm nucleus, which may remain un- detected by the embryologist during the routine selection procedure.
Analysis and Adaptation of Integration Time in PMD Camera for Visual Servoing (2010)

The depth perception in the objects of a scene can be useful for tracking or applying visual servoing in mobile systems. 3D time-of-flight (ToF) cameras provide range images which give measurements in real time to improve these types of tasks. However, the distance computed from these range images is very changing with the integration time parameter. This paper presents an analysis for the online adaptation of integration time of ToF cameras. This online adaptation is necessary in order to capture the images in the best condition irrespective of the changes of distance (between camera and objects) caused by its movement when the camera is mounted on a robotic arm.
An Inhibitor Binding Pocket Distinct from the Catalytic Active Site on Human β-APP Cleaving Enzyme (2005)

Beta-APP cleaving enzyme (BACE) is responsible for the first of two proteolytic cleavages of the APP protein that together lead to the generation of the Alzheimer's disease-associated Abeta peptide. It is widely believed that halting the production of Abeta peptide, by inhibition of BACE, is an attractive therapeutic modality for the treatment of Alzheimer's disease. BACE is an aspartyl protease, and there is significant effort in the pharmaceutical community to apply traditional design methods to the development of active site-directed inhibitors of this enzyme. We report here the discovery of a ligand binding pocket within the catalytic domain of BACE that is distinct from the enzymatic active site (i.e., an exosite). Peptides, initially identified from combinatorial phage peptide libraries, contain the sequence YPYF(I/L)P(L/I) and bind specifically to this exosite, even in the presence of saturating concentrations of active site-directed inhibitors. Binding of peptides to the BACE exosite leads to a concentration-dependent inhibition of proteolysis for APP-related, protein-based substrates of BACE. The discovery of this exosite opens new opportunities for the identification and development of novel and potentially selective small molecule inhibitors of BACE that act through exosite, rather than active site, binding interactions.
Inhibitory effect of PYY on vagally stimulated acid secretion is mediated predominantly by Y1 receptors (1996)

Two molecular forms of peptide YY (PYY), PYY-(1--36) and PYY-(3--36), are abundant in rabbit intestine and blood. We have previously shown that PYY-(1--36) (PYYI) activates equipotently Y1 and Y2 receptors and PYY-(3--36) (PYY II) is a highly selective agonist for Y2 receptors. In the present study, we examined the effect of exogenous infusion of PYY on vagally stimulated gastric acid secretion in awake rabbits with chronic gastric fistula. To determine the specific PYY receptor(s) that mediates this effect, we used a highly selective Y1 agonist, Pro34-PYY, a synthetic PYY, and a Y2-selective agonist, PYY II. Vagal stimulation of acid secretion was elicited by an intravenous bolus injection of insulin (0.125 U/kg) 30 min after beginning a 180-min intravenous infusion of either PYY I, PYY II, or [Pro34]-PYY after a 50 micrograms/kg i.v. bolus of atropine followed immediately by a 500 micrograms/kg sc injection. During infusion of 200 pmol.kg 1.h-1 PYY I, acid output was significantly inhibited to 45 +/- 13% of maximum acid output 60 min after injection of insulin. Similarly, acid output during infusion of 200 pmol.kg-1.h-1 [Pro34]-PYY was significantly inhibited to 52 +/- 12% of maximum. In contrast, acid output during infusion of 200 pmol.kg-1.h-1 of PYY II was not significantly inhibited (101 +/- 18% of maximum). Infusion of double the dose (400 pmol.kg-1.h-1) of PYY II resulted in acid inhibition (51 = 15% of maximum), whereas infusion of the same dose did not significantly enhance acid inhibition by infusion of either PYY I or [Pro34]-PYY (28 +/- 11 and 42 +/- 15% of maximum). These results indicate that PYY, acting predominantly at Y1 receptors, is a potent inhibitor of vagally stimulated acid secretion in adult rabbits.
ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy (2017)

Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children and infants. SMA is caused by deletions or mutations of <i>Survival Motor Neuron 1</i> (<i>SMN1</i>) gene. <i>SMN2</i>, a nearly identical copy of <i>SMN1</i>, cannot compensate for the loss of <i>SMN1</i> due to predominant skipping of exon 7. While various regulatory elements that modulate <i>SMN2</i> exon 7 splicing have been proposed, intronic splicing silencer N1 (ISS-N1) has emerged as the most promising target thus far for antisense oligonucleotide-mediated splicing correction in SMA. Upon procuring exclusive license from the University of Massachussets Medical School in 2010, Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical development of Spinraza<sup>™</sup> (synonyms: Nusinersen, IONIS-SMN<sub>RX</sub>, ISIS-SMN<sub>RX</sub>), an antisense drug based on ISS-N1 target. Spinraza<sup>™</sup> showed very promising results at all steps of the clinical development and was approved by US Food and Drug Administration (FDA) on December 23, 2016. Spinraza<sup>™</sup> is the first FDA-approved treatment for SMA and the first antisense drug to restore expression of a fully functional protein via splicing correction. The success of Spinraza<sup>™</sup> underscores the potential of intronic sequences as promising therapeutic targets and sets the stage for further improvement of antisense drugs based on advanced oligonucleotide chemistries and delivery protocols.
Molecular defects in the mannose binding lectin pathway in dermatological disease: Case report and literature review (2010)

Mannose-binding lectin (MBL) and the Mannose-binding lectin-associated serine proteases (MASPs) are an essential aspect of innate immune responses that probably play an important but understudied role in cutaneous function. The MBL-MASP pathway appears to exert its primary role by assisting in the clearance of apoptotic skin cells (thus preventing accumulation and a subsequent autoimmune response) and promoting opsonophagocytosis of invading pathogens, limiting their dissemination. Deficiencies of the pathway have been described and are associated with infectious, autoimmune and vascular complications. However, the role of this pathway in dermatological disease is essentially unexplored. We describe 6 patients presenting with recurrent inflammatory and/or infectious skin conditions who also demonstrated severely low MBL levels. One patient also had a defect in the MASP2 gene. Genotype analysis revealed specific point mutations in the MBL2 promoter in all 6 patients and a variant MASP-2 gene in one patient. Five patients presented recurrent pustular skin infections (cellulitis, folliculitis and cutaneous abscess). A case of Grover's disease and one forme fruste of Behcet's syndrome (orogenital ulcers) were also observed. The patients responded to antimicrobial therapy, although in some, recurrence of infection was the rule. It appears that MBL deficiency may contribute to recurrent skin infections and to certain forms of inflammatory skin disease. The mechanisms may relate to the role of this pathway in innate immunity, removal of apoptotic cells and in immune complexes. Further study of MBL pathway defects in dermatological disease is required.
In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. (1997)

The present study demonstrated in vivo and in vitro antimetastatic activities of a major intestinal bacterial metabolite M1 formed from protopanaxadiol saponins of ginseng (the root of Panax ginseng C. A. Meyer) in comparison with its whole standardized extract and ginsenosides Rb1, Rb2, and Rc. Although Ginseng extract (1 mg/mouse) and ginsenosides (0.5 mg/mouse) significantly inhibited lung metastasis produced by i.v. injection of B16-BL6 melanoma cells in syngeneic mice (27-61% of untreated control), they hardly inhibited the invasion and migration of B16-BL6 melanoma and HT1080 fibrosarcoma cells in vitro. However, the intestinal bacterial metabolite M1 inhibited lung metastasis of melanoma cells and in vitro tumor cell invasion and migration at nontoxic or marginally toxic concentrations. Additionally, pharmacokinetic studies of ginsenoside Rb1 and M1 after oral administration (2 mg/mouse) revealed that intact Rb1 was not detectable in serum for 24 h by HPLC analysis, whereas the level of M1 in the serum reached maximum at 8 h (8.5 +/- 0.4 micrograms/ml) after Rb1 administration and at 2 h (10.3 +/- 1.0 micrograms/ml) after M1 administration. These findings suggest that the in vivo antimetastatic effect by oral administration of ginsenosides is mediated by their metabolic component M1.
How Many Species Are There on Earth and in the Ocean? (2011)

The diversity of life is one of the most striking aspects of our planet; hence knowing how many species inhabit Earth is among the most fundamental questions in science. Yet the answer to this question remains enigmatic, as efforts to sample the world's biodiversity to date have been limited and thus have precluded direct quantification of global species richness, and because indirect estimates rely on assumptions that have proven highly controversial. Here we show that the higher taxonomic classification of species (i.e., the assignment of species to phylum, class, order, family, and genus) follows a consistent and predictable pattern from which the total number of species in a taxonomic group can be estimated. This approach was validated against well-known taxa, and when applied to all domains of life, it predicts ,8.7 million (61.3 million SE) eukaryotic species globally, of which ,2.2 million (60.18 million SE) are marine. In spite of 250 years of taxonomic classification and over 1.2 million species already catalogued in a central database, our results suggest that some 86% of existing species on Earth and 91% of species in the ocean still await description. Renewed interest in further exploration and taxonomy is required if this significant gap in our knowledge of life on Earth is to be closed.
Immunological properties of hepatitis B core antigen fusion proteins. (1990)

The immunogenicity of a 19 amino acid peptide from foot-and-mouth disease virus has previously been shown to approach that of the inactivated virus from which it was derived after multimeric particulate presentation as an N-terminal fusion with hepatitis B core antigen. In this report we demonstrate that rhinovirus peptide-hepatitis B core antigen fusion proteins are 10-fold more immunogenic than peptide coupled to keyhole limpet hemocyanin and 100-fold more immunogenic than uncoupled peptide with an added helper T-cell epitope. The fusion proteins can be readily administered without adjuvant or with adjuvants acceptable for human and veterinary application and can elicit a response after nasal or oral dosing. The fusion proteins can also act as T-cell-independent antigens. These properties provide further support for their suitability as presentation systems for "foreign" epitopes in the development of vaccines.
From patterns to pathways: gene expression data analysis comes of age: gene expression data analysis comes of age (2002)

The major differences in diagnostic assignment rates provide arguments for the utility of diagnostic interviews in inpatient clinical settings but need further research, especially on factors that affect clinical diagnostic assignment in "real world" settings.
A nonlinear loop filter for quantization noise removal in hybrid video compression (2005)

We propose a high-performance, nonlinear, loop filter that reduces quantization noise over video frames composed of locally uniform regions (smooth, high frequency, texture, etc.) separated by singularities. Unlike earlier work, the designed filter is not limited to block based transform coders and provides a robust solution for intra as well as differentially encoded frames. Our formulation based on sparse decompositions allows us to take advantage of the spatial dependencies inherent in video frames while incorporating temporal dependencies through the information provided by previously decoded frames. The proposed filter results in 10% improvements in rate (at typical distortions) in combination with significant visual quality improvements, especially around singularities.
Cell-penetrating Peptides (2002)

Cellular uptake of a family of cationic cell-penetrating peptides (examples include Tat peptides and penetratin) have been ascribed in the literature to a mechanism that does not involve endocytosis. In this work we reevaluate the mechanisms of cellular uptake of Tat 48-60 and (Arg)(9). We demonstrate here that cell fixation, even in mild conditions, leads to the artifactual uptake of these peptides. Moreover, we show that flow cytometry analysis cannot be used validly to evaluate cellular uptake unless a step of trypsin digestion of the cell membrane-adsorbed peptide is included in the protocol. Fluorescence microscopy on live unfixed cells shows characteristic endosomal distribution of peptides. Flow cytometry analysis indicates that the kinetics of uptake are similar to the kinetics of endocytosis. Peptide uptake is inhibited by incubation at low temperature and cellular ATP pool depletion. Similar data were obtained for Tat-conjugated peptide nucleic acids. These data are consistent with the involvement of endocytosis in the cellular internalization of cell-penetrating peptides and their conjugates to peptide nucleic acids.
Perturbations in Gastric Physiology inHelicobacter pyloriDuodenal Ulcer: Are They All Epiphenomena? (1997)

These data and speculations offer one possible explanation for why duodenal ulcer occurs in only some people--those with high acid secretion--and suggest that the combination of high duodenal acid load and H. pylori infection is sufficient to result in duodenal ulcer disease.
Heat-Treated Fe/N/C Catalysts for O2 Electroreduction:  Are Active Sites Hosted in Micropores? (2006)

Limited availability of platinum is a potential threat to fuel cell commercialization. Since the 1970s, alternative catalysts to the electrochemical reduction of oxygen have been obtained from heat treatment at T > 600 degrees C of carbon with a non-noble metal and a source of nitrogen atoms. However, the process by which the heat treatment activates these materials remains an open question. Here, we report that the activation process of carbon black and iron acetate heat-treated in NH(3) comprises three consecutive steps: (i) incorporation of nitrogen atoms in the carbon, (ii) micropore formation through reaction between carbon and ammonia, and (iii) completion of active sites in the micropores by reaction of iron with ammonia. Step (ii) is the slowest. Moreover, the microporous surface per mass of catalyst controls the macroscopic activity when enough nitrogen atoms are incorporated in the structure of the carbon support. These facts should help in determining the structure of the active sites and in identifying methods to increase the site density of such catalysts.
Episomal maintenance of a bovine papilloma virus vector in transgenic mice. (1987)

We have used a bovine papillomavirus-based vector to generate transgenic mice. Transgenic mice result from either pronuclear or cytoplasmic injections of the vector into fertilized eggs. Of 30 mice generated by microinjection, 27 (90%) contained the vector in its episomal form, at less than one copy per cell. This represents a highly efficient means of gene transfer in which the transgene is in a controlled genetic environment.
Protocols for oligonucleotide conjugates : synthesis and analytical techniques (1994)

Protecting Groups in Oligonucleotide Synthesis Incorporation of Modified Bases into Oligonucleotides Functionalization of Oligonucleotides with Amino Groups and Attachment of Amino Specific Reporter Groups Functionalization of Oligonucleotides by the Incorporation of Thio-Specific Reporter Groups Postsynthesis Functionalization of Oligonucleotides Oligonucleotide-Enzyme Conjugates Oligonucleotides Containing Degenerate Bases: Synthesis and Uses Synthesis of [15N]-Labeled DNA Fragments Analysis and Purification of Synthetic Oligonucleotides by High Performance Liquid Chromatography Sequence Analysis of Oligodeoxyribonucleotides Gel-Capillary Electrophoresis Analysis of Oligonucleotides Nuclear Magnetic Resonance Studies of Oligonucleotides Mass Spectrometry of Nucleotides and Oligonucleotides Extracting Thermodynamic Data from Equilibrium Melting Curves for Oligonucleotide Order-Disclosure Transitions Index
Detection of MYCN gene amplification and deletions of chromosome 1p in neuroblastoma by in situ hybridization using routine histologic sections. (1993)

Application of this methodology to formalin-fixed samples of neuroblastoma will permit comprehensive retrospective studies of these two genetic markers using archived tumors. In situ hybridization surveys will have widespread applications for studying known genetic aberrations in individual cells of a variety of solid tumors and for determining interrelationships and clinical significance in relation to tumor progression and patient outcome.
Small peptides radiolabeled with 99mTc. (1996)

99mTc labeled small peptides are characterized by rapid pharmacokinetics and tissue penetration. Furthermore, small peptides are readily synthesized and the desired pharmacokinetic behavior may be engineered into the molecule. They are well suited for development as radiopharmaceuticals.
Homologous recombination is required for AAV-mediated gene targeting (2006)

High frequencies of gene targeting can be achieved by infection of mammalian cells with recombinant adeno-associated virus (rAAV) vectors [D. W. Russell and R. K. Hirata (1998) Nature Genet., 18, 325-330; D. W. Russell and R. K. Hirata (2000) J. Virol., 74, 4612-4620; R. Hirata et al. (2002) Nat. Biotechnol., 20, 735-738], but the mechanism of targeting is unclear and random integration often occurs in parallel. We assessed the role of specific DNA repair and recombination pathways in rAAV gene targeting by measuring correction of a mutated enhanced green fluorescent protein (EGFP) gene in cells where homologous recombination (HR) or non-homologous end-joining (NHEJ) had been suppressed by RNAi. EGFP-negative cells were transduced with rAAV vectors carrying a different inactivating deletion in the EGFP, and in parallel with rAAV vectors carrying red fluorescent protein (RFP). Expression of RFP accounted for viral transduction efficiency and long-term random integration. Approximately 0.02% of the infected GFP-negative cells were stably converted to GFP positive cells. Silencing of the essential NHEJ component DNA-PK had no significant effect on the frequency of targeting at any time point examined. Silencing of the SNF2/SWI2 family members RAD54L or RAD54B, which are important for HR, reduced the rate of stable rAAV gene targeting approximately 5-fold. Further, partial silencing of the Rad51 paralogue XRCC3 completely abolished stable long-term EGFP expression. These results show that rAAV gene targeting requires the Rad51/Rad54 pathway of HR.
Inhibition of integrin function by a cyclic RGD-containing peptide prevents neointima formation. (1994)

Inhibition of integrin function by an RGD-containing peptide results in reduction of the development of a neointima. This effect is due both to an early event, which could be due to inhibition of secretion of PDGF by the platelets with blocked alpha IIb beta 3, and to a late event, possibly by interference with smooth muscle cell alpha v beta 3.