gebhart/patrepeval huggingface dataset:
The TACAN4TGCA motif upstream from the -35 region in the sigma70-sigmaS-dependent Pm promoter of the TOL plasmid is the minimum DNA segment required for transcription stimulation by XylS regulators (1996)

Transcription from the TOL plasmid meta-cleavage pathway operon promoter Pm is dependent on the XylS regulator activated by benzoate effectors or after XylS overproduction. We have generated 5' deletions in Pm and have analyzed expression from wild-type and mutant promoters with the wild-type XylS regulator and XylS mutant regulators that stimulated transcription constitutively. We have found that the motifs T(C or A)CAN4TGCA located between -46 and -57 and -67 and -78 with respect to the main transcription initiation point are required for maximal stimulation of transcription from Pm with effector-activated wild-type XylS. Deletion of the farthest TCCA submotif decreased but did not abolish transcription mediated by the pair XylS with 3-methylbenzoate; however, removal of the motif between -67 and -78 resulted in the loss of stimulation by the wild-type regulator. XylSG44S and XylSS229I stimulated high levels of transcription in the absence of effectors from the wild-type promoter and from a mutant promoter exhibiting only the -46 to -57 motif only when an effector was present. The point mutation Pm5U (with C-47 replaced by G [C-47-->G]) and Pm4 (C-68-->G), located in each 3' TGCA submotif of each motif, resulted in a 90% decrease in transcription stimulation with wild-type XylS; however, the mutant XylSS229I stimulated high levels of transcription from the point mutation promoters both in the presence and in the absence of effectors, while mutant XylSG44S suppressed the two point mutations only with 3-methylbenzoate. Overexpression of XylS and XylSG44S allowed the two regulators to stimulate high levels of transcription from the wild-type promoter, the point mutation Pm4 and Pm5U promoters, and deltaPm promoters exhibiting at least the -46 to -57 motif. Therefore the TACAN4TGCA motif between -46 and -57 represents the minimal DNA segment required for stimulation of transcription from Pm.
CD28-negative cytolytic effector T cells frequently express NK receptors and are present at variable proportions in circulating lymphocytes from healthy donors and melanoma patients (1999)

In humans, NK receptors are expressed by natural killer cells and some T cells, the latter of which are preferentially α βTCR+ CD8+ cytolytic T lymphocytes (CTL). In this study we analyzed the expression of nine NK receptors (p58.1, p58.2, p70, p140, ILT2, NKRP1A, ZIN176, CD94 and CD94/NKG2A) in PBL from both healthy donors and melanoma patients. The percentages of NK receptor-positive T cells (NKT cells) varied strongly, and this variation was more important between individual patients than between individual healthy donors. In all the individuals, the NKT cells were preferentially CD28–, and a significant correlation was found between the percentage of CD28– T cells and the percentage of NK receptor+ T cells. Based on these data and the known activated phenotype of CD28– T cells, we propose that the CD28– CD8+ T cell pool represents or contains the currently active CTL population, and that the frequent expression of NK receptors reflects regulatory mechanisms modulating the extent of CTL effector function. Preliminary results indicate that some tumor antigen-specific T cells may indeed be CD28– and express NK receptors in vivo.
How does it sound? [voice clarity analysis] (2001)

In this paper, the author describes how, in order to check voice quality, designers of compressed and packetized data networks are enlisting computer-based techniques.
Endovascular treatment for M2 occlusions in the era of stentrievers: a descriptive multicenter experience (2014)

Endovascular treatment of M2 MCA occlusion with stentrievers seems safe. Induced recanalization may double the chances of achieving a favorable outcome, especially for patients with moderate or severe deficit.
Curcumin improves sclerosing cholangitis in Mdr2 −/− mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation (2010)

These results show that curcumin may have multiple targets in liver including activation of PPARgamma in cholangiocytes and inhibition of ERK1/2 signalling in MFBs, thereby modulating several central cellular events in a mouse model of cholangiopathy. Targeting these pathways may be a promising therapeutic approach to cholangiopathies.
An Algorithm for the Grading of Activity in Chronic Hepatitis C (1996)

Histological activity reflects the global assessment of basic necroinflammatory lesions and is a criterion of major importance in chronic hepatitis C. The aim of this study was to propose and test the accuracy of a simple algorithm that generates a single activity score based on basic pathological features. A panel of 10 pathologists reviewed 363 chronic hepatitis C liver biopsies and graded the activity of hepatitis according to their own experience (reference activity). Then, a consensual algorithm on the grading of activity was established by the 10 experts in a panel discussion. Finally, stepwise discriminant analysis was performed to define which basic features had been intuitively used in the reference activity (statistical activity). To test the accuracy of the algorithm, concordance between the activity defined by the algorithm and the reference activity was assessed. It was compared with concordance between the activity defined by the statistical model and the reference activity. The algorithm proposed by the panel for the grading of activity included piecemeal necrosis and lobular necrosis. Concordance between reference activity and activity defined by the algorithm was substantial (305 cases, 84%, kappa = .75). Discriminant analysis showed that piecemeal necrosis, lobular necrosis, and portal inflammation were independently used to grade the activity. Concordance between reference activity and activity defined by the statistical model was substantial (300 cases, 83%, kappa = .73), virtually identical to the concordance between reference activity and activity defined by algorithm. This study proposes a simple algorithm for the grading of activity in chronic hepatitis. Its accuracy is as high as that obtained using a statistical approach.
A novel method for high-throughput detection and quantification of neutrophil extracellular traps reveals ROS-independent NET release with immune complexes (2016)

A newly-described first-line immune defence mechanism of neutrophils is the release of neutrophil extracellular traps (NETs). Immune complexes (ICxs) induce low level NET release. As such, the in vitro quantification of NETs is challenging with current methodologies. In order to investigate the role of NET release in ICx-mediated autoimmune diseases, we developed a highly sensitive and automated method for quantification of NETs. After labelling human neutrophils with PKH26 and extracellular DNA with Sytox green, cells are fixed and automatically imaged with 3-dimensional confocal laser scanning microscopy (3D-CLSM). NET release is then quantified with digital image analysis whereby the NET amount (Sytox green area) is corrected for the number of imaged neutrophils (PKH26 area). A high sensitivity of the assay is achieved by a) significantly augmenting the area of the well imaged (11%) as compared to conventional assays (0.5%) and b) using a 3D imaging technique for optimal capture of NETs, which are topologically superimposed on neutrophils. In this assay, we confirmed low levels of NET release upon human ICx stimulation which were positive for citrullinated histones and neutrophil elastase. In contrast to PMA-induced NET release, ICx-induced NET release was unchanged when co-incubated with diphenyleneiodonium (DPI). We were able to quantify NET release upon stimulation with serum from RA and SLE patients, which was not observed with normal human serum. To our knowledge, this is the first semi-automated assay capable of sensitive detection and quantification of NET release at a low threshold by using 3D CLSM. The assay is applicable in a high-throughput manner and allows the in vitro analysis of NET release in ICx-mediated autoimmune diseases.
Muscle-Specific SIRT1 Gain-of-Function Increases Slow-Twitch Fibers and Ameliorates Pathophysiology in a Mouse Model of Duchenne Muscular Dystrophy (2014)

SIRT1 is a metabolic sensor and regulator in various mammalian tissues and functions to counteract metabolic and age-related diseases. Here we generated and analyzed mice that express SIRT1 at high levels specifically in skeletal muscle. We show that SIRT1 transgenic muscle exhibits a fiber shift from fast-to-slow twitch, increased levels of PGC-1α, markers of oxidative metabolism and mitochondrial biogenesis, and decreased expression of the atrophy gene program. To examine whether increased activity of SIRT1 protects from muscular dystrophy, a muscle degenerative disease, we crossed SIRT1 muscle transgenic mice to mdx mice, a genetic model of Duchenne muscular dystrophy. SIRT1 overexpression in muscle reverses the phenotype of mdx mice, as determined by histology, creatine kinase release into the blood, and endurance in treadmill exercise. In addition, SIRT1 overexpression also results in increased levels of utrophin, a functional analogue of dystrophin, as well as increased expression of PGC-1α targets and neuromuscular junction genes. Based on these findings, we suggest that pharmacological interventions that activate SIRT1 in skeletal muscle might offer a new approach for treating muscle diseases.
Chronic Obstructive Pulmonary Disease in Men and Women: Myths and Reality (2009)

Chronic diseases have a variable impact on men and women due to the complex interaction between biological sex and environmental risk factors to which men and women are differentially exposed. Sex differences have not been adequately explored in chronic obstructive pulmonary disease (COPD), as most studies have either had small sample sizes or not enough women to allow for accurate comparisons. This article will address sex differences in susceptibility, expression of COPD subtypes, and activity-related breathlessness, and will identify key areas for further investigation.
Poly(isoglycerol methacrylate)-b-poly(d or l-lactide) Copolymers: A Novel Hydrophilic Methacrylate as Building Block for Supramolecular Aggregates (2010)

On the basis of a new acetal-protected glycerol monomethacrylate monomer (cis-1,3-benzylidene glycerol methacrylate/BGMA) a series of potentially biocompatible and partially biodegradable homo- and block copolymers were synthesized. ATRP polymerization of BGMA yielded well-defined polyacrylates with pendant benzylidene acetal groups and high glass transition temperatures (115−130 °C). This hydrophobic poly(cis-1,3-benzylidene glycerol methacrylate) could be readily transformed into the hydrophilic and water-soluble poly(1,3-dihydroxypropyl methacrylate), referred to as poly(isoglycerol methacrylate) (PIGMA). It exclusively contains primary hydroxyl groups and therefore differs significantly from the commonly known poly(glycerol methacrylate) (PGMA). Block copolymer systems based on poly(lactide) and BGMA were realized via two orthogonal living polymerization techniques starting from a bifunctional initiator, employing first atom transfer radical polymerization (ATRP) of BGMA and in the second step organo-base catalyzed polymerization of l- or d-lactide. This route provides well-defined block copolymers of low polydispersity (PDI 1.12−1.17) and molecular weights in the range of 7000 to 30 000 g/mol (NMR). Rapid and highly selective acetal hydrolysis of the PBGMA block resulted in the release of the hydrophilic and water-soluble poly(1,3-dihydroxypropyl methacrylate) (poly(isoglycerol methacrylate), PIGMA). Acidic hydrolysis of the acetal protecting groups of poly(BGMA)-b-poly(lactide) copolymers proceeded smoothly to amphiphilic structures, notably without affecting the potentially labile polyester block. The novel PIGMA-b-PLLA copolymers are capable of supramolecular self-assembly to spherical aggregate structures in aqueous environment. The polymers generally exhibited low aggregation constants (CAC: 8−20 mg/L). Because of the unique feature of stereocomplex formation of poly(lactide), the corresponding aggregate morphology could be adjusted by mixing two nearly identical PIGMA-b-PLA copolymers with enantiomeric poly(lactide blocks) in a 1:1 ratio. In this case the uniformly shaped micelles (20 nm) changed to large vesicles with diameters ranging from 600 to 1400 nm. These features render this new type of amphiphilic block copolymers promising for drug delivery applications.
Genetic Improvement of Sorghum as a Biofuel Feedstock: I. QTL for Stem Sugar and Grain Nonstructural Carbohydrates (2008)

Genetic improvement of sorghum [ Sorghum bicolor (L.) Moench] has traditionally focused on a single nonstructural carbohydrate, either grain starch or stem sugar. Sorghum starch and sugar may both be used as feedstocks for biofuel production. To investigate genetic tradeoffs between grain and stem sugar, a population derived from sweet sorghum cultivar Rio and grain sorghum ‘BTx623’ was evaluated for 27 traits related to grain and stem sugar yield and composition. Across three environments, a total of 129 quantitative trait loci (QTL) were identified. Tradeoffs identified between grain and stem sugar yield QTL colocalized with height and flowering time QTL. Most importantly, QTL were identified that increased yield and altered the composition of stem sugar and grain without pleiotropic effects. For example, a QTL on chromosome 3 that explained 25% of the genetic variance for stem sugar concentration did not colocalize with any grain QTL. These results suggest that total nonstructural carbohydrate yield could be increased by selecting for major QTL from both grain and sweet sorghum types. We conclude that altering grain and stem sugar genetic potential for yield traits should lead to greater feedstock improvement than altering composition traits.
Chromosomal and Gene Amplification in Diffuse Large B-Cell Lymphoma (1998)

Chromosomal translocations leading to deregulation of specific oncogenes characterize approximately 50% of cases of diffuse large B-cell lymphomas (DLBL). To characterize additional genetic features that may be of value in delineating the clinical characteristics of DLBL, we studied a panel of 96 cases at diagnosis consecutively ascertained at the Memorial Sloan-Kettering Cancer Center (MSKCC) for incidence of gene amplification, a genetic abnormality previously shown to be associated with tumor progression and clinical outcome. A subset of 20 cases was subjected to comparative genomic hybridization (CGH) analysis, which identified nine sites of chromosomal amplification (1q21-23, 2p12-16, 8q24, 9q34, 12q12-14, 13q32, 16p12, 18q21-22, and 22q12). Candidate amplified genes mapped to these sites were selected for further analysis based on their known roles in lymphoid cell and lymphoma development, and/or history of amplification in tumors. Probes for six genes, which fulfilled these criteria, REL (2p12-16), MYC (8q24), BCL2 (18q21), GLI, CDK4, and MDM2 (12q13-14), were used in a quantitative Southern blotting analysis of the 96 DLBL DNAs. Each of these genes was amplified (four or more copies) with incidence ranging from 11% to 23%. This analysis is consistent with our previous finding that REL amplification is associated with extranodal presentation. In addition, BCL2 rearrangement and/or REL, MYC, BCL2, GLI, CDK4, and MDM2 amplification was associated with advanced stage disease. These data show, for the first time, that amplification of chromosomal regions and genes is a frequent phenomenon in DLBL and demonstrates their potential significance in lymphomagenesis.
Preventive effect of ritodrine hydrochloride and/or urinary trypsin inhibitor against lipopolysaccharide‐induced preterm delivery in mice (1997)

Combination therapy with ritodrine plus UTI may be helpful for preventing preterm delivery in humans without the cardiovascular side effects that often accompany treatment with ritodrine alone.
Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors (2014)

The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that resistance to FGFR inhibitors can be acquired through mutations in the FGFR gatekeeper residue, as clinically observed for FGFR4 in embryonal rhabdomyosarcoma and neuroendocrine breast carcinomas. Here we report on the use of a structure-based drug design to develop two selective, next-generation covalent FGFR inhibitors, the FGFR irreversible inhibitors 2 (FIIN-2) and 3 (FIIN-3). To our knowledge, FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. Because of the conformational flexibility of the reactive acrylamide substituent, FIIN-3 has the unprecedented ability to inhibit both the EGF receptor (EGFR) and FGFR covalently by targeting two distinct cysteine residues. We report the cocrystal structure of FGFR4 with FIIN-2, which unexpectedly exhibits a "DFG-out" covalent binding mode. The structural basis for dual FGFR and EGFR targeting by FIIN3 also is illustrated by crystal structures of FIIN-3 bound with FGFR4 V550L and EGFR L858R. These results have important implications for the design of covalent FGFR inhibitors that can overcome clinical resistance and provide the first example, to our knowledge, of a kinase inhibitor that covalently targets cysteines located in different positions within the ATP-binding pocket.
Asymmetric Reduction of Ketones with Catecholborane Using 2,6-BODOL Complexes of Titanium(IV) as Catalysts (2001)

Reductions performed with Ti(IV) complexes of ligands based on bicyclo[2.2.2]octane diols 5 and 6 are effective catalysts in the reduction of prochiral ketones to optically active alcohols, with catecholborane as the reducing agent. Methyl ketones are favored and enantiomeric excesses (ee) of < or =98% have been achieved with acetophenone as the substrate. Several other substrates were tested, among them 2-octanone, which gave 2-octanol in 87% ee. Further details of the method were examined, for example, temperature, solvent composition, amount of molecular sieves (4 A), and catecholborane quality, as well as the sensitivity of the ligands towards acids. NMR spectroscopic methods were used to gain some insight into the complexes formed between the ligands and [Ti(OiPr)4]. A dimeric structure is proposed for the pre-catalyst.
Human factor VII deficiency caused by S339C mutation located adjacent to the specificity pocket of the catalytic domain (2002)

This report documents our identification of a novel factor VII (FVII) gene mutation in a Japanese boy with FVII deficiency. The proband's FVII activity was 34% and his FVII antigen level was 40% of normal controls. DNA sequence analysis of the proband's FVII gene identified a C to G point mutation at nucleotide position 10 933 in exon 8, which results in the substitution of Cys (TGC) for Ser339 (TCC). Hinf I digestion results indicate the proband and his mother were heterozygous for the mutation. Both wild-type and mutant FVIIs were transiently expressed in COS-1 cells. FVII levels measured in the culture medium of FVII Ser339Cys mutants were markedly reduced as compared to those of cells with FVII wild-type. The amount of intracellular FVII in FVII Ser339Cys mutants was 80% of that in wild-type. In the wild-type FVII, Ser339 is juxtaposed to Asp338, which is positioned at the bottom of the substrate-binding pocket in the protease domain and located adjacent to FVII Cys340, that forms a disulphide bond with Cys368. We suspect that the creation of a novel unpaired cysteine through this mutation leads to abnormal disulphide bonding during protein folding, thereby reducing the secretion of FVII.
Multi-hypothesis motion planning for visual object tracking (2011)

In this paper, we propose a long-term motion model for visual object tracking. In crowded street scenes, persistent occlusions are a frequent challenge for tracking algorithm and a robust, long-term motion model could help in these situations. Motivated by progresses in robot motion planning, we propose to construct a set of `plausible' plans for each person, which are composed of multiple long-term motion prediction hypotheses that do not include redundancies, unnecessary loops or collisions with other objects. Constructing plausible plan is the key step in utilizing motion planning in object tracking, which has not been fully investigate in robot motion planning. We propose a novel method of efficiently constructing disjoint plans in different homotopy classes, based on winding numbers and winding angles of planned paths around all obstacles. As the goals can be specified by winding numbers and winding angles, we can avoid redundant plans in the same homotopy class and multiple whirls or loops around a single obstacle. We test our algorithm on a challenging, real-world dataset, and compare our algorithm with Linear Trajectory Avoidance and a simplified linear planning model. We find that our algorithm outperforms both algorithms in most sequences.
A miniature all-optical photoacoustic imaging probe (2011)

A miniature (250 &mu;m outer diameter) photoacoustic probe for endoscopic applications has been developed. It comprises a single delivery optical fibre with a transparent Fabry Perot (FP) ultrasound sensor at its distal end. The fabrication of the sensor was achieved by depositing a thin film multilayer structure comprising a polymer spacer sandwiched between a pair of dichroic dielectric mirrors on to the tip of a single mode fiber. The probe was evaluated in terms of its acoustic bandwidth and sensitivity. Ultra high acoustic sensitivity has been achieved with a concave FP interferometer cavity design, which effectively suppresses the phase dispersion of multiple reflected beam within the cavity to achieve high finesse. The noise equivalent noise (NEP) achieved is 8 Pa over a 20 MHz bandwidth. Backward mode operation of the probe is demonstrated by detecting photoacoustic signals in a variety of phantoms designed to simulate endoscopic applications. A side-viewing probe is also demonstrated illustrating an all-optical design for intravascular imaging applications.