gebhart/patrepeval huggingface dataset:
Heterogeneity of chromosome 22 breakpoint in Philadelphia-positive (Ph+) acute lymphocytic leukemia. (1986)

In chronic myelogenous leukemias (CML) with the t(9;22)(q34;q11) chromosome translocation the breakpoints on chromosome 22 occur within a 5.8-kilobase segment of DNA referred to as "breakpoint cluster region" (bcr). The same cytogenetically indistinguishable translocation occurs in approximately 10% of patients with acute lymphocytic leukemias (ALL). In this study we have investigated the chromosome breakpoints in several cases of ALL carrying the t(9;22) translocation. In three of five cases of ALL we found that the bcr region was not involved in the chromosome rearrangement and that the 22q11 chromosome breakpoints were proximal (5') to the bcr region at band 22q11. In addition, we observed normal size bcr and c-abl transcripts in an ALL cell line carrying the t(9;22) translocation. We conclude, therefore, that if c-abl is inappropriately expressed in ALL cells without bcr rearrangements, the genetic mechanism of activation must be different from that reported for CML.
Preclinical and clinical studies with the multi-kinase inhibitor CEP-701 as treatment for prostate cancer demonstrate the inadequacy of PSA response as a primary endpoint (2007)

Evaluation of PSA response is an inadequate indicator of response in CEP-701 treated PC patients. Therefore, the effectiveness of CEP-701 as treatment for prostate cancer has not been adequately tested. Based on a strong preclinical rationale, further clinical studies with CEP-701 using alternative endpoints are indicated.
Peptide/protein–polymer conjugates: synthetic strategies and design concepts (2008)

This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.
Mitigation of Radiation-Induced Epithelial Damage by the TLR5 Agonist Entolimod in a Mouse Model of Fractionated Head and Neck Irradiation (2017)

Radiation treatment of head and neck cancer frequently causes severe collateral damage to normal tissues including mouth mucosa, salivary glands and skin. This toxicity limits the radiation dose that can be delivered and affects the patient's quality of life. Previous studies in mice and nonhuman primates showed that entolimod, a toll-like receptor 5 (TLR5) agonist derived from bacterial flagellin, effectively reduced radiation damage to hematopoietic and gastrointestinal tissues in both total-body and local irradiation scenarios, with no protection of tumors. Here, using a mouse model, we analyzed the efficacy of entolimod administered before or after irradiation in reducing damage to normal tissues. Animals received local fractionated radiation to the head and neck area, thus modeling radiotherapy of head and neck cancer. Tissue damage was evaluated through histomorphological examination of samples collected at different time points up to four weeks, mice were exposed locally to five daily fractions of 5, 6 or 7 Gy. A semiquantitative scoring system was used to assess the severity of observed pathomorphological changes. In this model, radiation damage was most severe in the lips, tongue and skin, moderate in the upper esophagus and minor in salivary glands. The kinetics of injury appearance and recovery of normal morphology varied among tissues, with maximal damage to the tongue, esophagus and salivary glands developing at earlier times (days 8-11 postirradiation) relative to that of lip and skin mucosa (days 11-15 postirradiation). While both tested regimens of entolimod significantly reduced the extent of radiation damage and accelerated restoration of normal structure in all tissues analyzed, administration of entolimod 1 h after each irradiation was more effective than treatment 30 min before irradiation. These results support the potential clinical use of entolimod as an adjuvant for improving the therapeutic index of head and neck cancer radiotherapy by reducing the radiation toxicity in normal tissues.
Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts (2003)

Necrotizing enterocolitis (NEC), a disease affecting predominantly premature infants, is a leading cause of morbidity and mortality in neonatal intensive care units. Although several predisposing factors have been identified, such as prematurity, enteral feeding, and infection, its pathogenesis remains elusive. In the past 20 years, we have established several animal models of NEC in rats and found several endogenous mediators, especially platelet-activating factor (PAF), which may play a pivotal role in NEC. Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The same is true for lesions induced by hypoxia and enteral feeding in neonatal animals. Human patients with NEC show high levels of PAF and decreased plasma PAF-acetylhydrolase, the enzyme degrading PAF. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. Subsequent norepinephrine release and mesenteric vasoconstriction result in splanchnic ischemia and reperfusion. Bacterial products (e.g., endotoxin) enter the intestinal tissue during local mucosal barrier breakdown, and endotoxin synergizes with PAF to amplify the inflammation. Reactive oxygen species produced by the activated leukocytes and by intestinal epithelial xanthine oxidase may be the final pathway for tissue injury. Protective mechanisms include nitric oxide produced by the constitutive (mainly neuronal) nitric oxide synthase, and indigenous probiotics such as Bifidobacteria infantis. The former maintains intestinal perfusion and the integrity of the mucosal barrier, and the latter keep virulent bacteria in check. The development of tissue injury depends on the balance between injurious and protective mechanisms.
Unmasking Disease-Specific Cerebral Blood Flow Abnormalities: Mood Challenge in Patients With Remitted Unipolar Depression (2002)

Mood challenge in unipolar euthymic patients in full remission unmasks an apparent depression trait marker. The pattern of acute CBF changes is distinct from that seen in euthymic healthy volunteers and mirrors the untreated depressed state seen during a major depressive episode and the pattern of change seen in depressed patients. These findings suggest that disease-specific modifications of pathways mediating transient mood changes are present in unipolar depression independent of clinical illness status. These findings have implications for understanding the vulnerability of remitted patients for illness relapse.
Elasticity of high-porosity sandstones; theory for two North Sea data sets (1996)

Abstract We have analyzed two laboratory data sets obtained on high-porosity rock samples from the North Sea. The velocities observed are unusual in that they seem to disagree with some simple models based on porosity. On the other hand, the rocks are unusually poorly-cemented (for laboratory studies, at least), and we investigate the likelihood that this is the cause of the disagreement. One set of rocks, from the Oseberg Field, is made of slightly cemented quartz sands. We find that we can model their dry-rock velocities using a cementation theory where the grains mechanically interact through cement at the grain boundaries. This model does not allow for pressure dependence. The other set of rocks, from the Troll Field, is almost completely uncemented. The grains are held together by the applied confining pressure. In this case, a lower bound for the velocities can be found by using the Hertz-Mindlin contact theory (interaction of uncemented spheres) to predict velocities at a critical porosity, combined with the modified Hashin-Strikman lower bound for other porosities. This model, which allows for pressure-dependence, also predicts fairly large Poisson's ratios for saturated rocks, such as those observed in the measurements. The usefulness of these theories may be in estimating the nature of cement in rocks from measurements such as sonic logs. The theories could help indicate sand strength in poorly consolidated formations and predict the likelihood of sand production. Both theoretical methods have analytical expressions and are ready for practical use.
Decoupled automated rotational and translational registration for functional MRI time series data: The dart registration algorithm (1997)

A rapid, in-plane image registration algorithm that accurately estimates and corrects for rotational and translational motion is described. This automated, one-pass method achieves its computational efficiency by decoupling the estimation of rotation and translation, allowing the application of rapid cross-correlation and cross-spectrum techniques for the determination of displacement parameters. k-space regridding and modulation techniques are used for image correction as alternatives to linear interpolation. The performance of this method was analyzed with simulations and echo-planar image data from both phantoms and human subjects. The processing time for image registration on a Hewlett-Packard 735/125 is 7.5 s for a 128 x 128 pixel image and 1.7 s for a 64 x 64 pixel image. Imaging phantom data demonstrate the accuracy of the method (mean rotational error, -0.09 degrees; standard deviation = 0.17 degrees; range, -0.44 degrees to +0.31 degrees; mean translational error = -0.035 pixels; standard deviation = 0.054 pixels; range, -0.16 to +0.06 pixels). Registered human functional imaging data demonstrate a significant reduction in motion artifacts such as linear trends in pixel time series and activation artifacts due to stimulus-correlated motion. The advantages of this technique are its noniterative one-pass nature, the reduction in image degradation as compared to previous methods, and the speed of computation.
Efficient anaerobic whole cell stereoselective bioreduction with recombinant saccharomyces cerevisiae (2003)

In this study we investigate the NADPH-dependent stereoselective reduction of the bicyclic diketone bicyclo[2.2.2]octane-2,6-dione (BCO2,6D) to the chiral ketoalcohol (1R,4S,6S)-6-hydroxybicyclo[2.2.2]octane-2-one (BCO2one6ol). Our aim was to develop a whole cell batch process for reduction of carbonyl substrates with (i) a high cosubstrate yield (formed product/consumed cosubstrate) and (ii) a high conversion rate under anaerobic conditions with Saccharomyces cerevisiae as biocatalyst and glucose as cosubstrate. Five open reading frames (ORFs), YMR226c, YDR368w, YOR120w, YGL157w, and YGL039w, encoding reductases involved in the conversion of BCO2,6D were identified using cell-free extract from strains belonging to the ExClone collection (yeast ORF expression clones; ResGen, Invitrogen Corp., UK). We report the one-step purification and characterization of three major BCO2,6D reductases, YMR226cp, YDR368wp (YPR1p), and YOR120wp (GCY1p). The reductases were overexpressed under a strong constitutive promoter and the impact on cosubstrate yield, conversion time, glucose consumption rate, and reduction rate was investigated when reductases were overexpressed either alone or in combination with low phosphoglucose isomerase activity (encoded by YBR196c). Combining overexpression of BCO2,6D reductase with reduced glycolytic rate (low phosphoglucose isomerase activity) offers a fast whole cell stereoselective bioreduction system useful for facilitated anaerobic batch conversions.
Changes of Cerebrospinal Fluid Peptides due to Tauopathy (2017)

Alzheimer's disease (AD) and progressive supranuclear palsy are two common neurodegenerative tauopathies, and the most common cause of progressive brain dementia in elderly affecting more than 35 million people. The tauopathies are characterized by abnormal deposition of microtubule associated protein tau into intracellular neurofibrillary tangles composed mainly of the hyperphosphorylated form of the protein. The diagnosis of tauopathies is based on the presence of clinical features and pathological changes. Over the last decade, there has been an intensive search for novel biochemical markers for clinical diagnosis of AD and other tauopathies. In the present study, we used transgenic rat model for tauopathy expressing human truncated tau protein (aa 151-391/4R) to analyze the cerebrospinal fluid (CSF) peptidome using liquid chromatography - matrix assisted laser desorption/ionization mass spectrometry (LC-MALDI TOF/TOF). From 345 peptides, we identified a total of 175 proteins. Among them, 17 proteins were significantly altered in the CSF of transgenic rats. The following proteins were elevated in the CSF of transgenic rats when compared to the control animals: neurofilament light and medium chain, apolipoprotein E, gamma-synuclein, chromogranin A, reticulon-4, secretogranin-2, calsyntein-1 and -3, endothelin-3, neuroendocrine protein B72A, alpha-1-macroglobulin, and augurin. Interestingly most of the identified proteins were previously linked to AD and other tauopathies, indicating the significance of transgenic animals in biomarker validation.
Land-use data integration based on knowledge (2010)

Te high subjective degree of subjective factors appears while integrating land-use maps by manual work,and the integrated rules are difficult to express with precise mathematical language and form,this paper introduced the concepts of integrated knowledge database and inference engine.It proposed the method of automatic integrating land-use data based on knowledge-studying,and then achieved the functions of integration of sporadic surface features,linear features and polygons by inference engine based on integrated knowledge database.At the same time,the importance of man-machine synergy has been also taken into account.It made the computer participate in map integrating process to improve the integration efficiency.
Optical inhibition of motor nerve and muscle activity in vivo (2012)

This demonstration of optical inhibition of motor nerves is an important advancement toward novel optogenetics-based therapies for spastic hypertonia.
Glatiramer Acetate in Multiple Sclerosis: A Review (2007)

ABSTRACT Multiple sclerosis (MS) is considered to be primarily an inflammatory autoimmune disease. Over the last 5 years, our view of the pathogenesis of MS has evolved considerably. The axonal damage was recognized as an early event in the disease process and as an important determinant of long‐term disability. Therefore, the antiinflammatory and neuroprotective strategies are thought to represent promising approach to the therapy of MS. The therapeutic potential of glatiramer acetate (GA), a synthetic amino acid polymer composed of a mixture of l ‐glutamic acid, l ‐lysine, l ‐alanine, and l ‐tyrosine in defined proportions, in MS has been apparent for many years. GA has been shown to be effective in preventing and suppressing experimental allergic encephalomyelitis (EAE), the animal model of MS. GA has been, therefore, evaluated in several clinical studies and found to alter the natural history of relapsing‐remitting (RR)MS by reducing the relapse rate and affecting disability. These findings were confirmed in open‐label follow‐up trials covering more than 10 years of treatment. The trials demonstrated sustained efficacy for GA in slowing the progression of disability. The clinical therapeutic effect of GA is consistent with the results of magnetic resonance imaging (MRI) findings from various clinical centers. At a daily standard dose of 20 mg, s.c., GA was generally well tolerated. The induction of GA‐reactive T‐helper 2‐like regulatory suppressor cells is thought to be the main mechanism of the therapeutic action of this drug. In addition, it was recently shown that GA‐reactive T cells produce neurotrophic factors (e.g., brain‐derived neurotrophic factor [BDNF]) that protect neurons and axons in the area of injury.
Integrated micro heat sink for power multichip module (2000)

Today, more and more compact converters with high current are required. The thermal environment is a key point to meet these requirements: the heat sink must be integrated as closely as possible to heat sources. Liquid-cooled microchannel heat sinks are very efficient and well adapted to the cooling of power components. Thus, a high-performance micro heat sink was made and tested under a power multichip module. First, the principle of the microchannel heat sink and a three-dimensional approach are presented. Then, a prototype and results are described. Composed of eight insulated gate bipolar transistor chips, the prototype has a current rating as high as 1200 A.
Hospital design Innovation on show at Queensland facility. (2015)

In a follow-up to an article on the hospital that first appeared in the autumn 2010 issue of The Australian Hospital Engineer, and was then republished with the help of the magazine. The Institute of Hospital Engineering Australia, and the IFHE in the November 2011 edition of HEJ, principals at architectural firm, Hassell, Kieren Morgan and Megan Reading, explain how the new Gold Coast University Hospital (GCUH) in Southport, Queensland, 'demonstrates how good design can improve delivery of care, as well as staff retention and attraction'.
Protection against homologous but not heterologous challenge induced by inactivated feline immunodeficiency virus vaccines (1995)

Whole inactivated virus vaccines from the FL4 cell line protected against challenge with homologous feline immunodeficiency virus (Petaluma strain) but not against a heterologous FIV isolate (GL-8) which is distinct from the Petaluma strain in virus neutralization. Protection was associated with a type-specific neutralizing antibody response and was retained when the challenge virus was propagated in an unrelated cell line.
Dinaciclib (SCH 727965), a Novel and Potent Cyclin-Dependent Kinase Inhibitor (2010)

Cyclin-dependent kinases (CDK) are key positive regulators of cell cycle progression and attractive targets in oncology. SCH 727965 inhibits CDK2, CDK5, CDK1, and CDK9 activity in vitro with IC(50) values of 1, 1, 3, and 4 nmol/L, respectively. SCH 727965 was selected as a clinical candidate using a functional screen in vivo that integrated both efficacy and safety parameters. Compared with flavopiridol, SCH 727965 exhibits superior activity with an improved therapeutic index. In cell-based assays, SCH 727965 completely suppressed retinoblastoma phosphorylation, which correlated with apoptosis onset and total inhibition of bromodeoxyuridine incorporation in >100 tumor cell lines of diverse origin and background. Moreover, short exposures to SCH 727965 were sufficient for long-lasting cellular effects. SCH 727965 induced regression of established solid tumors in a range of mouse models following intermittent scheduling of doses below the maximally tolerated level. This was associated with modulation of pharmacodynamic biomarkers in skin punch biopsies and rapidly reversible, mechanism-based effects on hematologic parameters. These results suggest that SCH 727965 is a potent and selective CDK inhibitor and a novel cytotoxic agent.
The Nor-D3 locus of Triticum tauschii: natural variation and genetic linkage to markers in chromosome 5 (1991)

Variation in the intergenic spacer region of the ribosomal RNA genes (located at the Nor locus) was assayed in a collection of 411 accessions of Triticum tauschii from Turkey, USSR, Iran, Afghanisan, Pakistan, and China. Twenty rDNA genotypes were identified and it was demonstrated that T. tauschii accessions from the USSR and Iran have the highest diversity at the Nor locus. At least four of the rDNA genotypes were demonstrated to be alleles of a single major locus, in segregating F 2 progeny analyses. The TaqI restriction fragment associated with rDNA genotype 7 was shown to be the same as the Nor-D3a allele present in all bread wheats (based on chromosome location and length of the intergenic spacer region). This genotype was significantly associated with T. t. ssp. strangulata, previously argued to be the donor of the D genome to hexaploid wheat. The Nor locus showed a high level of recombination with the 5SDna-2 locus, which was also located on chromosome 5D. The Nor locus is placed distal to the 5SDna-2 locus but proximal to the grain softness protein gene (XGsp) on the short arm of chromosome 5D.Key words: D genome, Nor-D3, rDNA polymorphism, chromosomal location.