gebhart/patrepeval huggingface dataset:
Inhibition of NOX1/4 with GKT137831: a potential novel treatment to attenuate neuroglial cell inflammation in the retina (2015)

NOX1/4 enzyme inhibition with GKT137831 has potent anti-inflammatory effects in the retina, indicating its potential as a treatment for a variety of vision-threatening retinopathies.
In vitro cytotoxicity of paclitaxel-transferrin conjugate on H69 cells. (1998)

Transferrin is a serum glycoprotein involved in iron transport. Transferrin acts also in cell growth regulation through membrane receptors. The number of transferrin receptors is increased in tumor and other rapidly dividing cells. This renders transferrin suitable for use in cytotoxic drugs targetting tumor cells. Paclitaxel was derivatized on 2' carbon and coupled with trasferrin using glutaraldehyde. The cytotoxicity of the conjugate was evaluated on small cell carcinoma of the lung cell line (H69). As compared to paclitaxel, the conjugate exhibited a slight decrease in cytotoxicity.
Clinical Relevance and Management of Drug‐Related QT Interval Prolongation (2003)

Much attention recently has focused on drugs that prolong the QT interval, potentially leading to fatal cardiac dysrhythmias (e.g., torsade de pointes). We provide a detailed review of the published evidence that supports or does not support an association between drugs and their risk of QT prolongation. The mechanism of drug-induced QT prolongation is reviewed briefly, followed by an extensive evaluation of drugs associated with QT prolongation, torsade de pointes, or both. Drugs associated with QT prolongation are identified as having definite, probable, or proposed associations. The role of the clinician in the prevention and management of QT prolongation, drug-drug interactions that may occur with agents known to affect the QT interval, and the impact of this adverse effect on the regulatory process are addressed.
Retinoic acid receptors in myeloid leukemia: characterization of receptors in retinoic acid-resistant K-562 cells (1991)

Although mRNA for the retinoic acid receptor alpha (RAR-alpha) is expressed in many different myeloid leukemias, most of these leukemia cells exhibit little if any phenotypic response when exposed to retinoic acid (RA). To determine whether such RA resistance is related to altered RA receptor structure or function, we performed a detailed analysis of nuclear RA receptors in RA-resistant K-562 cells. These cells exhibit RA receptors of the same approximate molecular weight and similar kd as those exhibited by the RA-sensitive HL-60 leukemia cell line, but the number of RA receptors in the RA-resistant K-562 cells (80 per cell) is significantly lower than that exhibited by RA- sensitive HL-60 cells (550 per cell). Retroviral-mediated transduction of RAR-alpha cDNA into K-562 significantly increased the number of RA receptors to 2,000 per cell. These RAR-alpha-transduced K-562 cells, when incubated with RA, exhibit diminished cell proliferation associated with decreased c-myc expression and an accumulation of cells in G0/G1. In addition, these RA-treated cells exhibit downregulation of the CD15 surface antigen and a slight increase in hemoglobin production but manifest no other evidence of significant erythroid, megakaryocytic, or myeloid differentiation. These results indicate that an elevated number of nuclear RA receptors can be involved in altering proliferation but not necessarily the differentiation of certain RA- treated myeloid leukemia cells.
Discriminant analysis of vegetable oils by near‐infrared reflectance spectroscopy (1994)

Abstract Discriminant analysis of four vegetable oil types (cotton‐seed, peanut, soybean and canola) was performed by near‐infrared reflectance spectroscopy. The objective of this study was to provide an alternate method to differentiate vegetable oil types and to classify unknown oil samples. Second derivative spectra of the vegetable oils were subjected to discriminate analysis with Mahalanobis distances principles. A four‐wavelength (1704, 1802, 1816 and 2110 nm) equation was derived, which produced a sum of inverse squared distance of 0.0548. Although all four groups were successfully separated with a chi square of 18.9, the soybean oil group is more dispersed in space than the other three groups. Iodine values of the soybean oil samples suggest that this group may have a wide range of hydrogenation states. Discriminant analysis can be successfully used to differentiate vegetable oil types and possibly could also be used to differentiate degree of hydrogenation and oxidative states of oils.
Growth and Development of Gastrointestinal Cells (1985)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Nanodiscs in Membrane Biochemistry and Biophysics (2017)

Membrane proteins play a most important part in metabolism, signaling, cell motility, transport, development, and many other biochemical and biophysical processes which constitute fundamentals of life on the molecular level. Detailed understanding of these processes is necessary for the progress of life sciences and biomedical applications. Nanodiscs provide a new and powerful tool for a broad spectrum of biochemical and biophysical studies of membrane proteins and are commonly acknowledged as an optimal membrane mimetic system that provides control over size, composition, and specific functional modifications on the nanometer scale. In this review we attempted to combine a comprehensive list of various applications of nanodisc technology with systematic analysis of the most attractive features of this system and advantages provided by nanodiscs for structural and mechanistic studies of membrane proteins.
Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. (1999)

The mammalian target of rapamycin (mTOR) has been shown to link growth factor signaling and posttranscriptional control of translation of proteins that are frequently involved in cell cycle progression. However, the role of this pathway in cell survival has not been demonstrated. Here, we report that rapamycin, a specific inhibitor of mTOR kinase, induces G1 cell cycle arrest and apoptosis in two rhabdomyosarcoma cell lines (Rh1 and Rh30) under conditions of autocrine cell growth. To examine the kinetics of rapamycin action, we next determined the rapamycin sensitivity of rhabdomyosarcoma cells exposed briefly (1 h) or continuously (6 days). Results demonstrate that Rh1 and Rh30 cells were equally sensitive to rapamycin-induced growth arrest and apoptosis under either condition. Apoptosis was detected between 24 and 144 h of exposure to rapamycin. Both cell lines have mutant p53; hence, rapamycin-induced apoptosis appears to be a p53-independent process. To determine whether induction of apoptosis by rapamycin was specifically due to inhibition of mTOR signaling, we engineered Rh1 and Rh30 clones to stably express a mutant form of mTOR that was resistant to rapamycin (Ser2035-->Ile; designated mTOR-rr). Rh1 and Rh30 mTOR-rr clones were highly resistant (>3000-fold) to both growth inhibition and apoptosis induced by rapamycin. These results are the first to indicate that rapamycin-induced apoptosis is mediated by inhibition of mTOR. Exogenous insulin-like growth factor (IGF)-I protected both Rh1 and Rh30 from apoptosis, without reactivating ribosomal p70 S6 kinase (p70S6K) downstream of mTOR. However, in rapamycin-treated cultures, the response to IGF-I differed between the cell lines: Rh1 cells proliferated normally, whereas Rh30 cells remained arrested in G1 phase but viable. Rapamycin is known to inhibit synthesis of specific proteins but did not inhibit synthesis or alter the levels of mTOR. To examine the rate at which the mTOR pathway recovered, the ability of IGF-I to stimulate p70S6K activity was followed in cells treated for 1 h with rapamycin and then allowed to recover in medium containing > or =100-fold excess of FK506 (to prevent rapamycin from rebinding to its cytosolic receptor FKBP-12). Our results indicate that, in Rh1 cells, rapamycin dissociates relatively slowly from FKBP-12, with a t1/2 of approximately 17.5 h. in the presence of FK506, whereas there was no recovery of p70S6K activity in the absence of this competitor. This was of interest because rapamycin was relatively unstable under conditions of cell culture having a biological t1/2 of approximately 9.9 h. These results help to explain why cells are sensitive following short exposures to rapamycin and may be useful in guiding the use of rapamycin analogues that are entering clinical trials as novel antitumor agents.
Differentiation of Prostate Cancer From Normal Prostate Tissue: Role of Hotspots in Pharmacokinetic MRI and Histologic Evaluation (2010)

In differentiation of cancerous and normal prostate tissue, use of perfusion in the entire region is superior to use of perfusion and blood volume in MRI hotspots.
Biochemical and enzymatic characterization of blood group ABH and related histo-blood group glycosphingolipids in the epithelial cells of porcine small intestine (1997)

Non-acid glycosphingolipids were isolated from small intestinal epithelial cells of a single blood group A pig. One very predominant blood group compound was obtained chemically pure upon HPLC fractionation. It was characterized by mass spectrometry and 1H NMR spectroscopy to be the type 1 chain blood group A hexaglycosylceramide. Support for the presence of minute amounts of additional A glycolipids was obtained by mass spectrometry and immunostaining of TLC plates with anti-A antibodies specific for A type 2 chain, A type 3 and 4 chain, and the ALe(b) determinant. Among precursor chains, globoside (type 4) and lactotetraosylceramide (type 1) were immunologically identified, whereas no neolactotetraosylceramide (type 2) and gangliotetraosylceramide reactivities were detected. We addressed the question whether the predominant expression of type 1 chain based A glycolipids reflects a restricted glycolipid precursor chain specificity of the alpha 1-2 fucosyl- and/or the alpha 1-3 N-acetylgalactosaminyltransferases, or if the biosynthesis of the precursor chains themselves is regulated. All precursor core saccharides, lacto- (type 1), neolacto-(type 2), and gangliotetraosylceramide as well as globopentaosylceramide (type 4), could serve as acceptors for fucose in vitro when a crude microsomal fraction obtained from mechanically released, porcine intestinal epithelial cells was used as an enzyme source. Under the same conditions an N-acetylgalactosamine residue could be transferred to the blood group H structures based on these core saccharide chains. Lactotriaosylceramide, but not gangliotriaosylceramide, could serve as an acceptor for UDP-galactose. When the product was digested with beta-galactosidase (EC 3.2.1.23) from S.pneumoniae, under conditions where it specifically cleaves Gal beta 1-4 residues, approximately 40% of the radioactivity was cleaved off, indicating that a substantial amount of neolactotetraosylceramide was made in vitro, as opposed to the predominance of lactotetraosylceramide-based structures found in vivo.
Octreotide Treatment Results in the Inhibition of GH Gene Expression in the Adenoma of the Patients with Acromegaly. (1994)

Seven patients with growth hormone (GH)-secreting pituitary adenoma were treated preoperatively with octreotide (Sandostatin or SMS 201-995; a somatostatin analogue), and were compared with 18 non-treated patients in their clinical courses and adenoma analyses. Octreotide treatment improved the endocrinological data in all 7 cases. The octreotide-treated adenomas were soft and easily removed by suction and curettage. The postoperative normalization of endocrinological data was encountered more often in the octreotide-treated cases than in the non-treated, although the statistical significance was not observed by the limited number of cases. The adenoma tissues were examined with conventional histology and immunohistochemistry, and the amount of GH messenger ribonucleic acid (mRNA) was quantitatively assessed. The studies demonstrated: 1) No fibrosis nor necrosis was observed in the adenomas from the octreotide-treated patients. 2) Immunohistochemistry for human GH revealed no remarkable differences between the octreotide-treated and the non-treated adenomas. 3) The amounts of GH mRNA in the adenoma from the octreotide-treated patients were 4.2 +/- 1.8 (mean +/- SEM; expressed in an arbitrary unit) and were significantly less than those from the non-treated (33.6 +/- 9.1). These data suggest that octreotide inhibits not only GH release from the adenoma but also its biosynthesis.
Informational Lesions: Optical Perturbation of Spike Timing and Neural Synchrony Via Microbial Opsin Gene Fusions (2009)

Synchronous neural activity occurs throughout the brain in association with normal and pathological brain functions. Despite theoretical work exploring how such neural coordination might facilitate neural computation and be corrupted in disease states, it has proven difficult to test experimentally the causal role of synchrony in such phenomena. Attempts to manipulate neural synchrony often alter other features of neural activity such as firing rate. Here we evaluate a single gene which encodes for the blue-light gated cation channel channelrhodopsin-2 and the yellow-light driven chloride pump halorhodopsin from Natronobacterium pharaonis, linked by a 'self-cleaving' 2A peptide. This fusion enables proportional expression of both opsins, sensitizing neurons to being bi-directionally controlled with blue and yellow light, facilitating proportional optical spike insertion and deletion upon delivery of trains of precisely-timed blue and yellow light pulses. Such approaches may enable more detailed explorations of the causal role of specific features of the neural code.
Saccadic Reaction Times of Dyslexic and Age-Matched Normal Subjects (1990)

Saccadic reaction times (SRT) were measured in a simple task: subjects had to make saccades from a central fixation point to peripheral targets, which appeared randomly 4 deg to the left or to the right. In the first test the fixation point went off before the target appeared (gap trials); in the second test it remained on the screen (overlap trials). The distribution of SRTs for trained normal adults (N = 4), untrained normal adults (N = 11), untrained normal children (aged 9-11 years, N = 9), untrained normal teenagers (aged 15-17 years, N = 8), dyslexic children (aged 9-11 years, N = 15), and dyslexic teenagers (aged 15-17 years, N = 5) were compared, with special emphasis on the number of express saccades, ie saccades with extremely short reaction times (100-120 ms, under the present conditions). In normal adults with the gap paradigm, the distribution of reaction times typically exhibits two or three modes (express saccades, fast regular saccades, and very few slow regular saccades), whereas in the overlap paradigm only one or two modes (few fast regular saccades and many slow regular saccades) are obtained. On average, normal children produce more express saccades than naive normal adults. Dyslexic children produce more express saccades than the normal age-matched controls. Among the dyslexic children, four different types of abnormalities in their reaction times were encountered. The group of dyslexic teenagers was characterized by a larger number of express saccades at the expense of fast regular saccades in gap trials and by fewer express saccades and fewer fast regular saccades in overlap trials when compared to the age-matched control group. It is concluded that the abnormal patterns of saccadic reaction times reflect defects in the system of visual attention and/or in its control over the oculomotor system, rather than indicating a defect in the oculomotor system itself. In this context, symptoms of dyslexia appear as a combination of attentional deficits and irregular timing of saccadic eye movements.
Use of fluorogenic Scorpions for fast and sensitive detection of plant viruses* (2000)

Very recently, a novel nucleic acid detection technology based on a primer with a quenched fluorophore and a probe complementary to an internal portion of the amplicon has been developed. The primer probe, named ‘Scorpion’, fluoresces only upon hybridization with its target, i.e. if the specific extension product of the primer is synthesized during the reaction. We have used Scorpion primers in RT‐PCR assays to detect Tomato spotted wilt tospovirus and Plum pox potyvirus in naturally infected plants. Amplified products of the expected size were detected either by real‐time measurements or by visual estimation of fluorescence emission from tubes placed over an ultraviolet light source at the end of the Scorpion‐RT‐PCR. In serially diluted plant sap, the visual method allowed detection of 7.5 pg of infected plant tissue and proved at least as sensitive as visual estimation of ethidium bromide‐stained amplicons separated by gel electrophoresis.
An 8-fold βα barrel protein with redundant folding possibilities (1990)

Protein sequences containing redundant segments of secondary structure at both termini have the choice a priori of folding into several possible circularly permuted variants of the wild-type tertiary structure. To test this hypothesis the gene of phosphoribosyl anthranilate isomerase from yeast, which is a single-domain 8-fold beta alpha barrel protein, was modified to produce a 10-fold beta alpha homologue in Escherichia coli. It contained a duplicate of the two C-terminal beta alpha units of supersecondary structure fused to its N-terminus. Most of the protein was recovered from the insoluble fraction of disrupted cells by dissolution in guanidinium chloride solutions and refolding. Pristine protein was purified from the soluble fraction. The purified (beta alpha)10 proteins were enzymically almost fully active. Absorbance, fluorescence and circular dichroism spectra as well as the reversible unfolding behaviour of both proteins were also very similar to the properties of the original (beta alpha)8 protein. Digestion with endopeptidases converted both the pristine and the refolded (beta alpha)10 variant to the same large fragment that had the N-terminal sequence and mol. wt of the wild-type (beta alpha)8 protein. The data suggest that the folding of the (beta alpha)10 variant is controlled thermodynamically both in vivo and in vitro.
Loss of proliferative potential during terminal differentiation coincides with the decreased abundance of a subset of heterogeneous ribonuclear proteins. (1989)

The decrease in abundance of a subset of highly conserved basic nuclear proteins is established to correlate with the loss of proliferative potential in association with the process of terminal differentiation in murine mesenchymal stem cells and human keratinocytes. These proteins, designated P2Ps for proliferation potential proteins, have apparent molecular masses of 30-40 kD, are associated with the 30-40S substructures of nuclear hnRNP complexes, and are recognized by antibodies made against core proteins of hnRNP particles. They also share an epitope in common with heat shock protein-90 (hsp90) and are recognized by two mAbs against hsp90. Two-dimensional electrophoretic Western blots furthermore show that P2Ps make up a subset of hnRNP proteins. Cells that possess these proteins express the potential to proliferate whether or not they are traversing the cell cycle. These include rapidly growing cells, reversibly growth-arrested cells, and nonterminally differentiated cells. In contrast, cells that have irreversibly lost their proliferative potential, such as terminally differentiated cells, show a marked reduction in the abundance of P2Ps as determined by immunodetection on Western blots. A correlation, therefore, exists between the presence of this subset of nuclear proteins and the proliferative potential in two cell types. These results raise the possibility that as a subset of hnRNP proteins, P2Ps may mediate posttranscriptional control of the processing of specific RNAs required for cell proliferation.
Thermal stability of hepatitis E virus assessed by a molecular biological approach (2011)

Measurement of intact viral particles using the RNase-based method may provide data on the stability of RNA viruses when cell culture-based infectivity titrations are not efficient or not available. The method enables processing of large sample numbers and may be suitable to estimate stability of HEV in different types of food.
JACKSTRAWS: picking command and control connections from bot traffic (2011)

A distinguishing characteristic of bots is their ability to establish a command and control (C&amp;amp;C) channel. The typical approach to build detection models for C&amp;amp;C traf-fic and to identify C&amp;amp;C endpoints (IP addresses and do-mains of C&amp;amp;C servers) is to execute a bot in a controlled environment and monitor its outgoing network connec-tions. Using the bot traffic, one can then craft signa-tures that match C&amp;amp;C connections or blacklist the IP addresses or domains that the packets are sent to. Un-fortunately, this process is not as easy as it seems. For example, bots often open a large number of additional connections to legitimate sites (to perform click fraud or query for the current time), and bots can deliberately produce “noise ” – bogus connections that make the anal-ysis more difficult. Thus, before one can build a model for C&amp;amp;C traffic or blacklist IP addresses and domains, one first has to pick the C&amp;amp;C connections among all the network traffic that a bot produces. In this paper, we present JACKSTRAWS, a system that accurately identifies C&amp;amp;C connections. To this end, we leverage host-based information that provides insights into which data is sent over each network connection as well as the ways in which a bot processes the informa-tion that it receives. More precisely, we associate with each network connection a behavior graph that captures the system calls that lead to this connection, as well as the system calls that operate on data that is returned. By using machine learning techniques and a training set of graphs that are associated with known C&amp;amp;C con-nections, we automatically extract and generalize graph templates that capture the core of different types of C&amp;amp;C activity. Later, we use these C&amp;amp;C templates to match against behavior graphs produced by other bots. Our results show that JACKSTRAWS can accurately detect C&amp;amp;C connections, even for novel bot families that were not used for template generation. 1