gebhart/patrepeval huggingface dataset:
Synthesis, Anticonvulsant and Antihypertensive Activities of 8-Substituted Quinoline Derivatives (2004)

A series of 8-substituted quinolines were synthesized and tested against seizures induced by maximal electro shock (MES), pentylenetetrazole (scMet) and antihypertensive activities. Neurologic deficit was evaluated by the rotarod test. Among the newly synthesized derivatives, several compounds with a 2-hydroxypropyloxyquinoline moiety displayed excellent anticonvulsant and antihypertensive activities. Compound 20 (8-(3'-(4''-phenylpiperazino)-2'-hydroxypropyloxy)quinoline) was potent in both series as an anticonvulsive agent. 13 (8-(3'-piperazino)-2'-hydroxypropyloxyquinoline) and 14 (8-(3'-imidazolo)-2'-hydroxypropyloxyquinoline) showed very good anticonvulsant activities in the propanol series of compound, whereas in the ethane series, 1 (8-(2'-piperazino-ethanoxy)quinoline) and 2 (8-(2'-imidazolo-ethanoxy)quinoline) were the most active as anticonvulsive agents. Compounds 20 (8-(3'-(4''-phenylpiperazino)-2'-hydroxypropyloxy)quinoline), 13 (8-(3'-piperazino)-2'-hydroxypropyloxyquinoline) and 19 (8-(3'-(4''-ethylpiperazino)-2'-hydroxypropyloxy)quinoline) have shown excellent antihypertensive activity. They have significantly antagonized the pressor response elicited by adrenaline. These pharmacological results suggest that their anticonvulsant and antihypertensive effects may be correlated to the presence of beta-blocking properties, and that those properties depend on the presence of aryloxypropanolamine.
Purification and biochemical characterization of a vacuolar serine endopeptidase induced by glucose starvation in maize roots (1996)

An endopeptidase (designated RSIP, for root-starvation-induced protease) was purified to homogeneity from glucose-starved maize roots. The molecular mass of the enzyme was 59 kDa by SDS/PAGE under reducing conditions and 62 kDa by gel filtration on a Sephacryl S-200 column. The isoelectric point of RSIP was 4.55. The purified enzyme was stable, with no auto-proteolytic activity. The enzyme activity was strongly inhibited by proteinaceous trypsin inhibitors, di-isopropylfluorophosphate, 3,4-dichloroisocoumarin and PMSF, suggesting that the enzyme is a serine protease. The maximum proteolytic activity against different protein substrates occurred at pH 6.5. With the exception of succinyl-Leu-Leu-Val-Tyr-4-methylcoumarin, no hydrolysis was detected with synthetic tryptic, chymotryptic or peptidylglutamate substrates. The determination of the cleavage sites in the oxidized B-Chain of insulin showed specificity for hydrophobic residues at the P2 and P3 positions, indicating that RSIP is distinct from other previously characterized maize endopeptidases. Both subcellular fractionation and immuno-detection in situ indicated that RSIP is localized in the vacuole of the root cells. RSIP is the first vacuolar serine endopeptidase to be identified. Glucose starvation induced RSIP: after 4 days of starvation, RSIP was estimated to constitute 80% of total endopeptidase activity in the root tip. These results suggest that RSIP is implicated in vacuolar autophagic processes triggered by carbon limitation.
Anatomy of the rat albumin promoter. (1990)

The sequences preceding the albumin mRNA start site are able to direct efficient transcription only upon introduction into cells expressing the endogenous albumin gene. In transient expression assays, the activity of a reporter gene (CAT) linked to this promoter is 100-fold higher in H4II differentiated hepatoma cells than in H5 dedifferentiated cells which no longer express their albumin gene. This tissue specificity depends on the very proximal promoter region, composed of a CCAAT box, the proximal element and a TATA box. Deletion of the CCAAT box leads to a two- to threefold decrease in activity, deletion of the proximal element (PE) results in loss of activity. The PE is a high-affinity binding site for HNF1/APF, a strictly liver specific trans-acting factor. When the affinity of this factor for PE is decreased by bacterial methylation (PE includes a dam methylase site), by mutation, or by its replacement with the homologous element from the alpha-fetoprotein gene (AFP), the activity of the short promoter (PE plus the TATA box) is abolished. This activity can be rescued in the presence of the more upstream elements: DEII, DEI and the CCAAT box (recognized, respectively, by the NF1/CTF, C/EBP and NFY/ACF factors) which are then absolutely required. Our results suggest that the upstream elements contribute to promoter activity by stabilizing the HNF1-PE complex and not by direct interaction with TFIID or the RNA polymerase. It is probable that these elements, essentially dispensable in already differentiated hepatoma cells, play a crucial role during development or differentiation to activate the promoter in cells that contain a low concentration of HNF1 and/or an HNF1 unable to open inactive chromatin alone.
Genomic characterization of type 2 polioviruses isolated from vaccine-associated cases in Brazil. (1995)

Twenty strains of P2/Sabin-related polioviruses isolated in Brazil were analyzed; ten from persistent paralytic poliomyelitis cases, three from suspected polio cases with transient paralysis, and seven from healthy contacts. The serotypes of the viral isolates were identified by the neutralization test with hyperimmune equine sera. The relationship of the isolates to the P2/Sabin strain was demonstrated by molecular hybridization and polymerase chain reaction (PCR). Partial sequencing demonstrated mutations at nucleotide 481 in the 5' noncoding region and at amino acid 143 of the capsid protein VP1 in most of these isolates from vaccine-associated cases in Brazil. These data support previous studies on the importance of mutations at these attenuated determinants in the establishment of the disease. However, the existence of isolates without mutations at these positions suggests that they are not essential. The results also strengthen the possibility of the participation of a mutation at nucleotide 398 in the establishment of the disease, and suggest that a mutation at nucleotide 491 or 500 may also be involved in this process. The isolates from healthy contacts presented the same mutations as the isolates from vaccine-associated cases with which they were in contact. This strengthens the observation that, although mutations in the genome of the P2/Sabin strain are important for the establishment of the disease, host factors are also involved.
Identification of Osteoblast/Osteocyte Factor 45 (OF45), a Bone-specific cDNA Encoding an RGD-containing Protein That Is Highly Expressed in Osteoblasts and Osteocytes (2000)

We describe the cloning and characterization of a novel bone-specific cDNA predicted to encode an extracellular matrix protein. This cDNA was identified by subtractive hybridization based upon its high expression in bone marrow-derived osteoblasts. By Northern blot analysis, we detected a single 2-kilobase mRNA transcript in bone, whereas no expression was detected in other tissues. Immunohistochemistry revealed that the protein was expressed highly in osteocytes within trabecular and cortical bone. RNA and protein expression analysis using in vivo marrow ablation as a model of bone remodeling demonstrated that this gene was expressed only in cells that were embedded within bone matrix in contrast to the earlier expression of known osteoblast markers. The cDNA was predicted to encode a serine/glycine-rich secreted peptide containing numerous potential phosphorylation sites and one RGD sequence motif. The interaction of RGD domain-containing peptides with integrins has been shown previously to regulate bone remodeling by promoting recruitment, attachment, and differentiation of osteoblasts and osteoclasts. Secretion of this RGD-containing protein from osteocytes has the potential to regulate cellular activities within the bone environment and thereby may impact bone homeostasis. We propose the name OF45 (osteoblast/osteocyte factor of 45 kDa) for this novel cDNA.
Protein-Protein Interactions in Colicin E9 DNase-Immunity Protein Complexes. 2. Cognate and Noncognate Interactions That Span the Millilmolar to Femptomolar Affinity Range (1995)

The in vivo and in vitro cross-binding of the colicin endonuclease-specific immunity proteins toward the DNase domain of colicin E9 is described. In vivo cross-protection was tested by toxin plate assays in which bacterial cells overexpressing each immunity (Im2, Im7, Im8, and Im9) were challenged with the ColE9 toxin. Im9, the cognate immunity protein, renders cells completely resistant toward very high concentrations of the toxin (> 1 mg/mL), whereas the noncognate immunities display a spectrum of weaker cross-reactivities (< 0.01 mg/mL). The order of biological protection in this assay was Im9 >> Im2 > Im8, with Im7 providing no colicin E9 resistance. In vitro binding between the immunity proteins and the E9 DNase was analyzed by determining the dissociation constants for E9 DNase-Im protein complexes at pH 7.0 in the presence of 200 mM salt and at 25 degrees C. Stopped-flow fluorescence experiments suggest that both Im2 and Im8 associate with the E9 DNase by a two-step mechanism, in which the rate constants for both the bimolecular association (k1 = approximately 6 x 10(7) M-1 s-1) and the subsequent conformational change (k2 + k-2 = 4-5 s-1) are very similar to Im9 binding under the same conditions. Fluorescence chase experiments defined the dissociation rate constants for Im2 and Im8. The estimated values are 10(6)- and 10(8)-fold, respectively, faster than the off-rate for the Im9 protein.(ABSTRACT TRUNCATED AT 250 WORDS)
An overview of the basic principles of the Q-Coder adaptive binary arithmetic coder (1988)

The Q-Coder is a new form of adaptive binary arithmetic coding. The binary arithmetic coding part of the technique is derived from the basic concepts introduced by Rissanen, Pasco, and Langdon, but extends the coding conventions to resolve a conflict between optimal software and hardware implementations. In addition, a robust form of probability estimation is used in which the probability estimate is derived solely from the interval renormalizations that are part of the arithmetic coding process. A brief tutorial of arithmetic coding concepts is presented, followed by a discussion of the compatible optimal hardware and software coding structures and the estimation of symbol probabilities from interval renormalization.
Amycolatopsis echigonensis sp. nov. and Amycolatopsis niigatensis sp. nov., novel actinomycetes isolated from a filtration substrate (2007)

The taxonomic position of two actinomycete strains, LC2(T) and LC11(T), isolated from a filtration substrate made from Japanese volcanic soil, was determined using a polyphasic approach. The strains grew at temperatures from 5 to 45 degrees C, on media of pH between 6 and 11 and in the presence of 7 % NaCl. The major menaquinone was MK-9(H(4)). The major fatty acid was iso-C(16 : 0). A phylogenetic tree based on 16S rRNA gene sequences showed that the two strains formed a distinct evolutionary lineage within the genus Amycolatopsis. On the basis of their morphological, physiological and genotypic characteristics, the isolates are proposed to represent two novel species of the genus Amycolatopsis, for which the names Amycolatopsis echigonensis sp. nov. (type strain LC2(T) =IAM 15387(T) =CCTCC AB206019(T)), and Amycolatopsis niigatensis sp. nov. (type strain LC11(T) =IAM 15388(T) =CCTCC AB206020(T)) are proposed.
Characterization of Torin2, an ATP-Competitive Inhibitor of mTOR, ATM, and ATR (2013)

mTOR is a highly conserved serine/threonine protein kinase that serves as a central regulator of cell growth, survival, and autophagy. Deregulation of the PI3K/Akt/mTOR signaling pathway occurs commonly in cancer and numerous inhibitors targeting the ATP-binding site of these kinases are currently undergoing clinical evaluation. Here, we report the characterization of Torin2, a second-generation ATP-competitive inhibitor that is potent and selective for mTOR with a superior pharmacokinetic profile to previous inhibitors. Torin2 inhibited mTORC1-dependent T389 phosphorylation on S6K (RPS6KB1) with an EC(50) of 250 pmol/L with approximately 800-fold selectivity for cellular mTOR versus phosphoinositide 3-kinase (PI3K). Torin2 also exhibited potent biochemical and cellular activity against phosphatidylinositol-3 kinase-like kinase (PIKK) family kinases including ATM (EC(50), 28 nmol/L), ATR (EC(50), 35 nmol/L), and DNA-PK (EC(50), 118 nmol/L; PRKDC), the inhibition of which sensitized cells to Irradiation. Similar to the earlier generation compound Torin1 and in contrast to other reported mTOR inhibitors, Torin2 inhibited mTOR kinase and mTORC1 signaling activities in a sustained manner suggestive of a slow dissociation from the kinase. Cancer cell treatment with Torin2 for 24 hours resulted in a prolonged block in negative feedback and consequent T308 phosphorylation on Akt. These effects were associated with strong growth inhibition in vitro. Single-agent treatment with Torin2 in vivo did not yield significant efficacy against KRAS-driven lung tumors, but the combination of Torin2 with mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor AZD6244 yielded a significant growth inhibition. Taken together, our findings establish Torin2 as a strong candidate for clinical evaluation in a broad number of oncologic settings where mTOR signaling has a pathogenic role.
<title>Parametric blind deconvolution of fluorescence microscopy images: preliminary results</title> (1996)

Three-dimensional microscopy by computational deconvolution methods requires accurate knowledge of the point spread function (PSF) that characterizes the microscope. Experimental PSF's can only be measured over small regions about focus because the small objects necessary for PSF measurement are dim. Theoretical computation of the PSF requires accurate knowledge of all the experimental setup parameters. Some parameters may be difficult or impossible to measure. In blind deconvolution, the PSF and the specimen are estimated simultaneously, an under-determined problem with non-unique solutions. Most existing approaches to blind deconvolution rely on enforcing constraints on the specimen function and PSF, sometimes in ad-hoc ways. We derived a parametric blind deconvolution method by assuming that the PSF follows a mathematical expression with unknown parameters. The parameters are then estimated together with the specimen function. Preliminary results presented here show that this algorithm rapidly estimates the correct PSF.
Effects of Transgalactosylated Disaccharides on the Human Intestinal Microflora and Their Metabolism. (1993)

The effects of transgalactosylated disaccharide (TD) intake on human fecal microflora and their metabolism were investigated in 12 Japanese males. TD is a mixture of sugars, galactosyl galactose, and galactosyl glucose, synthesized from lactose through the transgalactosylation reaction of Streptococcus thermophilus beta-galactosidase. Volunteers took 15 g of the test sugar daily for 6 days. The TD ingestion increased the number of bifidobacteria and lactobacilli, but decreased the number of Bacteroidaceae and Candida spp. in the feces. The ratio of bifidobacteria to total bacteria increased from 0.28 to 0.51. TD decreased the fecal concentrations of propionic acid, isobutyric acid, isovaleric acid, and valeric acid. This sugar also lowered the fecal pH, and the concentrations of fecal ammonia, p-cresol, and indole. Moreover, a positive correlation was found between the concentration of ammonia, and that of branched-chain fatty acids (isobutyric acid and isovaleric acid), p-cresol, and indole. All of these compounds are produced from amino acids through deamination by the intestinal bacteria. The depression of amino acid fermentation by intestinal bacteria may be involved in the reduction of fecal ammonia. These results suggest that a part of the transgalactosylated disaccharides passes into the colon, inducing changes in the colonic microflora composition, hastening carbohydrate fermentation, and depressing amino acid fermentation in the human gut.
Expression of Human Scavenger Receptor B1 on and in Human Platelets (2003)

These findings suggest that determining the level of hSR-B1/CLA-1 expression on the platelets may be a useful clinical marker for atherosclerotic diseases.
Subcytotoxic H2O2 Stress Triggers a Release of Transforming Growth Factor-β1, Which Induces Biomarkers of Cellular Senescence of Human Diploid Fibroblasts (2001)

Stress-induced premature senescence (SIPS) is induced 3 days after exposure of human diploid fibroblasts to subcytotoxic oxidative stress with H(2)O(2), with appearance of several biomarkers of replicative senescence. In this work, we show that transforming growth factor-beta1 (TGF-beta1) regulates the induction of several of these biomarkers in SIPS: cellular morphology, senescence-associated beta-galactosidase activity, increase in the steady-state level of fibronectin, apolipoprotein J, osteonectin, and SM22 mRNA. Indeed, the neutralization of TGF-beta1 or its receptor (TGF-beta RII) using specific antibodies decreases sharply the percentage of cells positive for the senescent-associated beta-galactosidase activity and displaying a senescent morphology. In the presence of each of these antibodies, the steady-state level of fibronectin, osteonectin, apolipoprotein J, and SM22 mRNA is no more increased at 72 h after stress. Results obtained on fibroblasts retrovirally transfected with the human papillomavirus E7 cDNA suggest that retinoblastoma protein (Rb) regulates the expression of TGF-beta1 in stressful conditions, leading to SIPS and overexpression of these four genes.
Thrombotic thrombocytopenic purpura plasma enhances platelet–leucocyte interaction in vitro (1998)

In thrombotic thrombocytopenic purpura (TTP), intravascular platelet aggregation and formation of platelet-rich thrombi impair the microcirculation. TTP plasma has been shown to induce aggregation of normal platelets in vitro. The present study investigates the formation of activated platelet aggregates (aPAg) induced by TTP plasma, with particular attention to their binding to leucocytes (LPAg). Results were compared with the effects of plasmas from normal controls (CTL) and from patients with immune thrombocytopenic purpura (ITP) or thrombosis (THR). Following addition of test plasma to normal whole blood (WB), aPAg and LPAg were assayed by flow cytometry using mAbs against CD41 (platelet marker), CD62p (platelet activation marker) and CD45 (pan-leucocyte marker), Compared to control plasma, TTP plasma was more potent than ITP or THR plasma in increasing aPAg: only TTP plasma significantly promoted leucocyte binding to give increased LPAg. Prior removal of neutrophils (PMN) from WB by beads coated with anti-CD15 mAb largely prevented formation of aPAg and LPAg. However, TTP plasma added to normal platelet-rich plasma significantly increased aPAg, which suggested possible hindrance of aPAg formation by erythrocytes and other leucocytes in PMN-depleted blood. We concluded that TTP plasma was most potent in the induction of aPAg and unique in promoting LPAg formation in WB. Neutrophils, and not other leucocytes, appear to be essential for LPAg formation. Enhanced PMN-platelet interaction in the microcirculation may facilitate platelet adhesion to vessel walls and promote the formation of platelet-rich microthrombi in TTP.
A low-power CMOS time-to-digital converter (1995)

A time-to-digital converter, TDC, with 780 ps lsb and 10-/spl mu/s input range has been integrated in a 1.2-/spl mu/m CMOS technology. The circuit is based on the interpolation time interval measurement principle and contains an amplitude regulated crystal oscillator, a counter, two pulse-shrinking delay lines, and a delay-locked loop for stabilization of the delay. The TDC is designed for a portable, low-power laser range-finding device. The supply voltage is 5/spl plusmn/0.5 V, and the operating temperature range is -40 to +60/spl deg/C. Single-shot accuracy is 3 ns and accuracy after averaging is /spl plusmn/120 ps with input time intervals 5-500 ns. In the total input range of 10 /spl mu/s, the final accuracy after averaging is /spl plusmn/200 ps. Current consumption is 3 mA, and the chip size is 2.9 mm/spl times/2.5 mm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Histamine Release by Contrast Media (1971)

The blood draining organs with a high histamine content was sampled and elevation of plasma histamine was found to result from injections of certain contrast media. All methylglucamine contrast media tested to date (acetrizoate, diatrizoate, and iodipamide) produced such elevations. Methylglucamine chloride also caused elevation of plasma histamine. Some “allergic” reactions to contrast media may be explained on this basis.
Design of a reversible biotin analog and applications in protein labeling, detection, and isolation (2011)

To expand the applicability of the biotin-(strept)avidin system, a biotin analog with reversible binding under non-denaturing conditions has been designed, and its applications in protein labeling, detection, and isolation have been evaluated.
Update on the therapeutic approaches to brain tumors (2003)

Neuro-oncology is a rapidly growing field of study. The understanding of brain tumors has expanded in pace with advances in the field of molecular biology and genetics. Diagnoses are more accurate, biopsy and surgical intervention safer, radiotherapy more focused and chemotherapy safer and better tolerated. Novel strategies based on the understanding of brain tumor biology are emerging as targeted approaches to therapy. Despite all this, only a minority of patients with certain subsets of brain tumors have experienced prolonged survival. This review focuses on the standard and emerging therapies for the two most common categories of brain tumors: gliomas and meningiomas. Primary CNS lymphoma, while a relatively rare tumor, is also included as a topic of discussion as the achievements in its treatment represent the principal strides in the evolution of neuro-oncology.
A case of multiple sclerosis demonstrating vertigo (2011)

A 27-year-old woman who was referred to our hospital 5 days after an episode of vertigo had experienced right facial palsy 2 days earlier and a feeling of numbness in her left hand one year earlier. Ocular movement showed rotatory nystagmus in the positioning nystagmus, and the abduction of the right eye was impaired. A T2-weighted magnetic resonance imaging (MRI) study showed multiple high-intensity lesions in the dorsal pons and white matter close to the lateral ventricles, supporting a diagnosis of multiple sclerosis. Methylprednisolone pulse therapy effectively alleviated the patient's complaints except for the feeling of numbness in the left hand, and the patient's ocular movements normalized within one month. A neuro-otology examination, such as the observation of eye movements, is a key study for suspected brain lesion symptoms.