gebhart/patrepeval huggingface dataset:
THE MUTANT mdx: INHERITED MYOPATHY IN THE MOUSE (1987)

The mdx mutant mouse was first observed during a survey of genetic variations of pyruvate kinase in the mouse. Affected mice have high serum levels of this enzyme and although showing little disability they have widespread and severe muscle disease. Light and electron microscopy, muscle enzyme histochemistry and combined cholinesterase-silver impregnations were used for the study of affected and control animals aged 1 day to 1 year. An early ultrastructural abnormality present already at 1 day was scattered focal streaming of Z-lines. Later there was also segmental muscle fibre necrosis and regeneration. The proportion of muscle fibres showing either necrosis, regeneration or internal nuclei was assessed in several muscles, at ages ranging from 10 days to 1 year. Acute segmental necrosis and regeneration were most marked at 1 to 2 months, although they were present at all ages. The number of fibres with internal nuclei increased progressively until 3 months when 70-80% showed this abnormality. Nerve terminals were unaffected but there was a reduction in the number and depth of postsynaptic folds at motor end-plates in adult animals, confirmed by morphometric analysis. Quantitative study of L4 motor root and tibial nerve showed that fibre numbers, axonal calibres and myelin sheath thickness were normal at all ages. No qualitative abnormalities were found in the CNS or other organs. The findings strongly suggest that the mdx mutant has a primary muscle disease and that the nervous system is normal.
Taxol: a review of its preclinical in vivo antitumor activity. (1992)

Taxol has been demonstrated in numerous laboratories worldwide to have broad-spectrum antitumor activity against many tumor models. The susceptible tumors include murine leukemias and solid tumors, and human solid tumor xenografts. The initial findings of taxol's ineffectiveness against most distal site tumor models was probably a consequence of the insolubility of taxol in nearly all the vehicles used in those early studies. On the occasions when an ethanol-based vehicle was used to dissolve taxol, substantial distal site antitumor activity was observed. Although no definitive schedule dependency data have evolved, once-a-day or every-other-day i.v. injections for several treatments have proved to be reproducibly effective in stringent s.c. tumor models. Attempts to discern a therapeutically synergistic cytotoxic drug combination was made on two occasions without success. In the manner evaluated, taxol plus either adriamycin, cisplatin, cyclophosphamide or etoposide (VP-16) were not meaningfully more efficacious than the more effective drug in each of those combination settings.
Pathogenesis of Clostridium difficile infection of the gut (1990)

On the basis of the above findings it is possible to propose a sequence of events following exposure to C. difficile. Exposure of neonates to C. difficile leads to transient colonisation which is almost invariably asymptomatic; the reasons why colonisation is asymptomatic are not known. Exposure of antibiotic-treated adults to C. difficile does not invariably lead to colonisation; however, in those instances where colonisation occurs, it may be transient and asymptomatic or transient and symptomatic. The transient nature of the colonisation could be because the infecting strain is poorly virulent, or because the degree of compromise of the intestinal flora is insufficient to permit establishment and full expression of virulence. It is likely that it is easier to fully compromise the intestinal flora of the elderly so that they more readily become fully susceptible to colonisation by C. difficile. In a fully susceptible host and with a highly virulent strain, the following sequence of events could occur. The organism may associate with the intestinal mucosa possible via fimbriae, and form a microcolony of capsulate cells protected by a glycocalyx. The toxins, or other factors, produced may facilitate the interaction with mucosa and toxin A will result in increased vascular and mucosal permeability resulting in intra-luminal accumulation of serum-albumin-rich fluid. Although C. difficile does not appear to be capable of using serum albumin nutritionally, it may utilise other serum proteins, and the serum proteins in general may compete with host proteases and help prevent degradation of the toxins produced.(ABSTRACT TRUNCATED AT 250 WORDS)
Potential therapeutic applications of decoy oligonucleotides. (2002)

Recent progress in molecular biology has provided new techniques with which to inhibit target gene expression. In particular, the application of DNA technologies, such as antisense oligonucleotide (ODN) strategies to regulate the transcription of disease-related genes in vivo, have significant therapeutic potential. Recently, transfection of cis-element double-stranded oligonucleotides (decoy ODNs) has been reported as a new powerful tool in a new class of anti-gene strategies for gene therapy. Transfection of double-stranded ODN corresponding to the cis sequence will result in attenuation of the authentic cis-trans interaction, leading to removal of trans-factors from the endogenous cis-elements with subsequent modulation of gene expression.
Use of Electric Fields to Monitor the Dynamical Aspect of Cell Behavior in Tissue Culture (1986)

Mammalian cells can be cultured and therefore studied in vitro. Normally, the cells' morphology and other static properties are observed with the aid of a light microscope. A method is described here that allows observation of the dynamical aspects of cultured cells. Mammalian fibroblasts are cultured in polystyrene dishes that contain evaporated gold electrodes. As the cells attach to the electrodes, their presence and their motion is directly reflected in the measured impedance.
Therapeutic trials in the murine model of hereditary tyrosinaemia type I: A progress report (1998)

We have studied a knockout mouse with fumarylacetoacetate hydrolase (FAH) deficiency as a model of human hereditary tyrosinaemia type (I (HT1). These mice have a phenotype very similar to the human disease, which is characterized by acute hepatic failure, renal tubular disease and hepatocarcinoma. We have previously reported on the efficacy of 2-(2-nitro-4-trifluoromethylbenzyol)-1,3-cyclohexanedione (NTBC) in preventing acute liver disease in HT1 mice. Here we present a progress report on long-term follow up (> 1 year) of high-dose NTBC therapy in combination with tyrosine restriction. In vivo retroviral gene therapy was also effective in abolishing the acute liver failure of HT1. Retrovirally treated mice remained completely healthy and active for 12 months after retroviral gene transfer. However, hepatocarcinoma developed in 2/3 treated animals after 1 year. Southern blot analysis showed that the tumours did not arise from retrovirally transduced hepatocytes but from non-corrected FAH-deficient cells. These results highlight the extreme danger for tumour formation in HT1 and indicate the need for improved gene therapy that leads to the elimination of endogenous FAH-deficient liver cells.
Imaging of Single Extended DNA Molecules on Flat (Aminopropyl)triethoxysilane−Mica by Atomic Force Microscopy (1996)

Long strands of DNA have been deposited, extended, and immobilized on chemically modified mica for study with an atomic force microscope (AFM). By employing a modified "molecular combing" technique and carefully silanized mica, we show that DNA molecules may be distributed uniformly, adsorbed in extended conformations, and bound with great tenacity. When maintained in a buffer solution, these strands remained stable for >5 h. Scanning the surface with high loads applied to an AFM tip induced fragmentation in the strands, but remaining pieces never relinquished their original positions. Further imaging applications, such as after treatment of the DNA by molecular hybridization or DNA synthesis and labeling in situ, are discussed.
Packaging signals in alphaviruses (1997)

Alphaviruses synthesize large amounts of both genomic and subgenomic RNA in infected cells, but usually only the genomic RNA is packaged. This implies the existence of an encapsidation or packaging signal which would be responsible for selectivity. Previously, we had identified a region of the Sindbis virus genome that interacts specifically with the viral capsid protein. This 132-nucleotide (nt) fragment lies within the coding region of the nsP1 gene (nt 945 to 1076). We proposed that the 132-mer is important for capsid recognition and initiates the formation of the viral nucleocapsid. To study the encapsidation of Sindbis virus RNAs in infected cells, we designed a new assay that uses the self-replicating Sindbis virus genomes (replicons) which lack the viral structural protein genes and contain heterologous sequences under the control of the subgenomic RNA promoter. These replicons can be packaged into viral particles by using defective helper RNAs that contain the structural protein genes (P. Bredenbeek, I. Frolov, C. M. Rice, and S. Schlesinger, J. Virol. 67:6439-6446, 1993). Insertion of the 132-mer into the subgenomic RNA significantly increased the packaging of this RNA into viral particles. We have used this assay and defective helpers that contain the structural protein genes of Ross River virus (RRV) to investigate the location of the encapsidation signal in the RRV genome. Our results show that there are several fragments that could act as packaging signals. They are all located in a different region of the genome than the signal for the Sindbis virus genome. For RRV, the strongest packaging signal lies between nt 2761 and 3062 in the nsP2 gene. This is the same region that was proposed to contain the packaging signal for Semliki Forest virus genomic RNA.
Soluble FLT1 Gene Therapy Alleviates Brain Arteriovenous Malformation Severity (2017)

By applying a regulated mechanism to restrict sFLT1 expression to bAVM, AAV9-sFLT1 can potentially be developed into a safer therapy to reduce the bAVM severity.
The soft-output m-algorithm and its applications (2006)

The Soft-Output M-Algorithm (SOMA) is a reduced-complexity trellis decoder based on a sequential decoding technique known as the M-algorithm. Instead of extending all survivors from one trellis depth to the next, it extends only from the best M. The remaining survivors are terminated. The novelty of the SOMA is the use of terminated paths to obtain reliable soft-information. Soft-information is extracted from terminated paths through a simple update-and-discard procedure. It is found that using the M best fully-extended survivors alone is inadequate to deliver soft-information due to their similarity. On the other hand, terminated paths of a pruned trellis carry a significant amount of soft-information which should not be ignored for reliable bit-detection. 
The SOMA is particularly useful in reducing the complexity of an iterative receiver. Applications include turbo equalization of single-input single-output Inter-Symbol Interference (ISI) channels and Multiple-Input Multiple-Output (MIMO) frequency selective fading channels, iterative decoding of MIMO flat fading channels, and multi-user detection and equalization in coded Direct-Sequence Code-Division Multiple-Access (DS-CDMA) systems. 
For turbo equalization of a 16-tap ISI channel with convolutional coding, nearoptimal bit-error-rate is achieved by retaining only 128 (out of 32,768) states. The SOMA is also applicable to reduce the complexity of tree decoding. For a coded MIMO system with 8 antennae transmitting 64-QAM symbols over a flat fading channel, the respective code-tree with 648 hypotheses can be decoded with the SOMA by retaining only 32 paths per tree depth. The complexity of multi-user detection for coded DS-CDMA systems for flat-fading channels can also be significantly reduced using the SOMA. 
High-order trellises with millions of states can also be decoded with modest complexity using the SOMA. The trellis is first expanded into an equivalent trellis/tree structure. Then, the M-algorithm is applied twice, once to reduce the number of states, and the other to reduce the number of branches emanating from each state. The proposed method gives promising results in equalizing a high-order modulated MIMO system with bit-interleaved coded modulation undergoing frequency selective fading. The method is also applicable to reduce the complexity of multi-user equalization of a coded DS-CDMA system undergoing frequency selective fading.
Antibodies to the 45 kDa DEK nuclear antigen in pauciarticular onset juvenile rheumatoid arthritis and iridocyclitis: selective association with MHC gene. (1997)

Antibodies to the 45 kDa DEK protein are characteristic of the pauciarticular onset subtype of JRA, particularly in patients with a history of iridocyclitis. The occurrence of anti-DEK antibodies is significantly but paradoxically associated with the presence of the HLA-A2 allele in such patients.
Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention (2009)

Combination chemoprevention for cancer was proposed a quarter of a century ago, but has not been implemented in standard medical practice owing to limited efficacy and toxicity. Recent trials have targeted inflammation and polyamine biosynthesis, both of which are increased in carcinogenesis. Preclinical studies have demonstrated that DFMO (difluoromethylornithine), an irreversible inhibitor of ODC (ornithine decarboxylase) which is the first enzyme in polyamine biosynthesis, combined with NSAIDs (non-steroidal anti-inflammatory drugs) suppresses colorectal carcinogenesis in murine models. The preclinical rationale for combination chemoprevention with DFMO and the NSAID sulindac, was strengthened by the observation that a SNP (single nucleotide polymorphism) in the ODC promoter was prognostic for adenoma recurrence in patients with prior sporadic colon polyps and predicted reduced risk of adenoma in those patients taking aspirin. Recent results from a phase III clinical trial showed a dramatic reduction in metachronous adenoma number, size and grade. Combination chemoprevention with DFMO and sulindac was not associated with any serious toxicity. A non-significant trend in subclinical ototoxicity was detected by quantitative audiology in a subset of patients identified by a genetic marker. These preclinical, translational and clinical data provide compelling evidence for the efficacy of combination chemoprevention. DFMO and sulindac is a rational strategy for the prevention of metachronous adenomas, especially in patients with significant risk for colorectal cancer. Toxicities from this combination may be limited to subsets of patients identified by either past medical history or clinical tests.
Genomic Expression Programs in the Response of Yeast Cells to Environmental Changes (2000)

We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. A large set of genes (approximately 900) showed a similar drastic response to almost all of these environmental changes. Additional features of the genomic responses were specialized for specific conditions. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators. Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell.
Actin Cytoskeletal Disruption following Cryopreservation Alters the Biodistribution of Human Mesenchymal Stromal Cells In Vivo (2014)

Mesenchymal stromal cells have shown clinical promise; however, variations in treatment responses are an ongoing concern. We previously demonstrated that MSCs are functionally stunned after thawing. Here, we investigated whether this cryopreservation/thawing defect also impacts the postinfusion biodistribution properties of MSCs. Under both static and physiologic flow, compared with live MSCs in active culture, MSCs thawed from cryopreservation bound poorly to fibronectin (40% reduction) and human endothelial cells (80% reduction), respectively. This reduction correlated with a reduced cytoskeletal F-actin content in post-thaw MSCs (60% reduction). In vivo, live human MSCs could be detected in murine lung tissues for up to 24 hr, whereas thawed MSCs were undetectable. Similarly, live MSCs whose actin cytoskeleton was chemically disrupted were undetectable at 24 hr postinfusion. Our data suggest that post-thaw cryopreserved MSCs are distinct from live MSCs. This distinction could significantly affect the utility of MSCs as a cellular therapeutic.
Complex Information Processing and Intelligence (2000)

Theories of human intelligence must explain those complex human behaviors that are most commonly understood as its indicants. Thus, the central facts to be explained by a theory of intelligence must go beyond faster or more efficient processing of elementary tasks, for example, or the efficiency of biological processes and inherited structures, or the influence of other individuals, environments, or even cultures on abilities. Rather, a theory of intelligence must explain the writing of novels, the solving of complex mathematical problems, the designing of skyscrapers and microchips, and the myriad other forms of complex cognition valued by society. In short, an understanding of how individuals solve complex tasks and an explanation of why they differ so markedly in their ability to do so are in fact central to any theory of intelligence.
Phase retrieval, error reduction algorithm, and Fienup variants: a view from convex optimization (2002)

The phase retrieval problem is of paramount importance in various areas of applied physics and engineering. The state of the art for solving this problem in two dimensions relies heavily on the pioneering work of Gerchberg, Saxton, and Fienup. Despite the widespread use of the algorithms proposed by these three researchers, current mathematical theory cannot explain their remarkable success. Nevertheless, great insight can be gained into the behavior, the shortcomings, and the performance of these algorithms from their possible counterparts in convex optimization theory. An important step in this direction was made two decades ago when the error reduction algorithm was identified as a nonconvex alternating projection algorithm. Our purpose is to formulate the phase retrieval problem with mathematical care and to establish new connections between well-established numerical phase retrieval schemes and classical convex optimization methods. Specifically, it is shown that Fienup's basic input-output algorithm corresponds to Dykstra's algorithm and that Fienup's hybrid input-output algorithm can be viewed as an instance of the Douglas-Rachford algorithm. We provide a theoretical framework to better understand and, potentially, to improve existing phase recovery algorithms.
Stimulation of glycogen synthesis by proglycosyn (LY177507) by isolated hepatocytes of normal and streptozotocin diabetic rats. (1991)

The phenacylimidazolium compound LY177507 was shown by Harris et al. (Harris, R. A., Yamanuchi, K., Roach, P. J., Yen, T. T., Dominiani, S. J., and Stephens, T. W. (1989) J. Biol. Chem. 264, 14674-14680) to stimulate glycogen synthesis greatly in isolated rat hepatocytes. We extended studies with this compound, designated proglycosyn (Yamaguchi, K., Stephens, T. W., Chikadar, K., Depaoli-Roach, A., And Harris, R. A. (1991) Diabetes 40, (Suppl. 1) 102 (abstr.] employing hepatocytes from normal and streptozotocin diabetic rats. Proglycosyn is more effective than amino acids in stimulating glycogen synthesis. In cells incubated with glucose, lactate, or dihydroxyacetone the effect of glutamine and proglycosyn was synergistic. In cells incubated with glucose plus lactate, or glucose plus dihydroxyacetone, the stimulation by the two agonists was additive. Proglycosyn diverted the gluconeogenic flux from glucose to glycogen. The maximal rates of glycogen deposition attained in the presence of glutamine and proglycosyn from cells incubated with glucose plus lactate, or glucose plus dihydroxyacetone, where about 80 and 110 mumols/h/g of liver, respectively. Proglycosyn depressed glycogenolysis in hepatocytes of fed rats and stimulated glycogen synthesis from lactate and dihydroxyacetone. The incorporation of [U-14C]glucose and [U-14C]lactate in these cells occurred in the presence of glycogen breakdown or exceeded net production, indicating the occurrence of recycling of glycogen in hepatocytes of fed rats. Hepatocytes from fasted streptozotocin diabetic rats contained high levels of glycogen. Glycogenolysis was markedly depressed by proglycosyn. Glycogen synthesis from lactate and dihydroxyacetone in these cells was stimulated by glutamine and proglycosyn in a fashion similar to that in cells from fasted control rats, and the rates of glycogen synthesis were similar in cells of control and diabetic rats. With glucose as sole substrate, glutamine did not stimulate glycogen synthesis. When both agonists were present, there was a marked synergism and substantial glycogen formation. Streptozotocin diabetic rats prior to the onset of cachexia have a normal capacity for glycogen synthesis.
A New Triterpene Saponin from Pittosporum viridiflorum from the Madagascar Rainforest (2001)

A novel triterpenoid saponin, pittoviridoside (1), which possesses an unusual 2,3,4-trisubstituted glycosidic linkage, has been isolated from Pittosporum viridiflorum using the engineered yeast strains 1138, 1140, 1353, and Sc-7 for bioactivity-guided fractionation. The structure of this compound was determined to be 3-O-[beta-D-glucopyranosyl(1-->2)]-[alpha-D-arabinopyranosyl(1-->3)],[alpha-l-arabinofuranosyl(1-->4)-beta-D-glucuronopyranosyl-21-angeloyl-22-senecioylolean-12-en-3beta,15alpha,16alpha,21beta,22alpha,28-hexol by spectral, chemical, and GC analyses. This compound showed weak cytotoxicity against the A2780 human ovarian cancer cell line.
Characterization of mouse parvovirus infection by in situ hybridization (1995)

Infection of young adult BALB/cByJ mice with mouse parvovirus-1, a newly recognized, lymphocytotropic, nonpathogenic parvovirus, was examined by in situ hybridization. Virus appeared to enter through the small intestine and was disseminated to the liver and lymphoid tissues. Strand-specific probes detected virion DNA in a consistently larger number of cells than replicative forms of viral DNA and/or viral mRNA. The number of signal-positive cells in the intestinal mucosa, lymph nodes, spleen, and thymus increased through day 10 after oral inoculation but decreased after seroconversion. Positive cells were still detected, however, in peripheral lymphoid tissues of mice examined at 9 weeks postinoculation. The results underscore the need to assess potential effects of persistent mouse parvovirus-1 infection on immune function in mice.