gebhart/patrepeval huggingface dataset:
Map location of homologous regions between Marek's disease virus and herpesvirus of turkey and the absence of detectable homology in the putative tumor-inducing gene (1985)

The DNA region having homology between Marek's disease virus and herpesvirus of turkey was assigned to the restriction map of Marek's disease virus by Southern blot hybridization. Under moderate conditions at the level of 15% mismatching, homology was found to be distributed throughout the Marek's disease virus genome. The long inverted-repeat regions (TRL and IRL), which are considered to play a significant role in tumorigenicity, did not show any homology to herpesvirus of turkey DNA.
The Path from Anti Parkinson Drug Selegiline and Rasagiline to Multifunctional Neuroprotective Anti Alzheimer Drugs Ladostigil and M30 (2006)

The therapeutic use of enzyme inhibitors in treatment of neurodegenerative diseases has its origin in the anti Parkinson action of the selective monoamine oxidase (MAO) B inhibitor, l-deprenyl (selegiline ), a failed anti depressant in 1975. This led to further development of MAO- A and B, catechol-O-methyltansferase and cholinestrerase inhibitors as anti Parkinson and Alzheimer drugs. One of the main reasons for the cognitive deficit in dementia of the Alzheimer' type (AD) and in dementia with Lewy bodies (DLB) is degeneration of cholinergic cortical neurones and synaptic plasticity. This led to a correlation that similar to Parkinson's Disease (PD), cholinesterase inhibitors (ChEI) may also have therapeutic activity in AD. Significant percentage of AD and DLB subjects also nigrostriatal dopaminergic, locus ceruleous noradrenergic and raphe nucleus serotoninergic neurones. The present ChEI anti AD drugs have limited symptomatic activity and devoid of neuroprotective property that is needed for disease modifying action. It is becoming clear that there are no magic bullets for neurodegenerative disorders and shut gun approach is needed either as polypharmacology or drugs with multiple activity at different target sites in the CNS. The complex pathology of AD as well as cascade of events that leads to the neurodegenerative process has led us to develop several multifunctional neuroprotective drugs with several CNS targets with possible disease modifying activity. Employing the pharamcophore of our antiparkinson drug rasagiline (Azilect, Agilect, N-propagrgyl-1R-aminoindan) we have developed a novel multifunctional neuroprotective drug, ladostigil [TV-3326 (N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate)], with both cholinesterase-butyrylesterase (Ch-BuE) and brain selective monoamine-oxidase (MAO) AB inhibitory activities possessing the neuroprotective-neurescue propargyl moiety, as potential treatment of AD and DLB and PD with dementias. Since brain MAO and iron increase in AD, PD and ageing, that could lead to iron dependent oxidative stress neurodegeneration, we have developed another series of multifunctional drugs (M30 HLA-20 series) which are brain permeable iron chelators- brain selective MAO inhibitors and possess the propargyl neuroprotective moiety. These series of drugs have the ability of regulating and processing APP (amyloid precursor protein) and reducing Abeta peptide, since APP is a metaloprotein, with an iron responsive element 5d'UTR similar to transferring and ferritin.
The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span (2004)

The highly conserved target-of-rapamycin (TOR) protein kinases control cell growth in response to nutrients and growth factors. In mammals, TOR has been shown to interact with raptor to relay nutrient signals to downstream translation machinery. We report that in C. elegans, mutations in the genes encoding CeTOR and raptor result in dauer-like larval arrest, implying that CeTOR regulates dauer diapause. The daf-15 (raptor) and let-363 (CeTOR) mutants shift metabolism to accumulate fat, and raptor mutations extend adult life span. daf-15 transcription is regulated by DAF-16, a FOXO transcription factor that is in turn regulated by daf-2 insulin/IGF signaling. This is a new mechanism that regulates the TOR pathway. Thus, DAF-2 insulin/IGF signaling and nutrient signaling converge on DAF-15 (raptor) to regulate C. elegans larval development, metabolism and life span.
Family Intervention With Severely Disturbed Inpatients (1977)

Although there is considerable evidence that family variables and interaction patterns affect the duration of hospitalization and frequency of readmission of psychiatric patients, it is rare to find inpatient facilities having psychotherapeutic programs that systematically stress family interventions. This article discusses the difficulties encountered by both families and staff as they cope with the issues of hospitalization, suggests a structured, patient-oriented family approach, and recommends some specific techniques for short-term work with families of severely disturbed inpatients.
Highly efficient gene targeting in embryonic stem cells through homologous recombination with isogenic DNA constructs. (1992)

A vast amount of data suggests that homologous recombination in mammalian cells is relatively rare as compared to random integration, imposing the need for sophisticated selection protocols to enrich for cells in which homologous recombination has occurred. We here show that one of the key factors in efficient homologous recombination is the use of isogenic DNA to prepare the targeting vectors. Homologous recombination at the retinoblastoma susceptibility gene (Rb) in embryonic stem cells derived from mouse strain 129 was 20-fold more efficient with a 129-derived targeting construct than with a BALB/c-derived construct. The two constructs were identical, except for a number of base sequence divergences between 129 and BALB/c DNA, including base-pair substitutions, small deletions/insertions, and a polymorphic CA repeat. Transfection with an isogenic DNA construct, containing 17 kilobases of homology, yielded a targeting frequency of 78% (of a total of 20,000 drug-resistant colonies), without the use of an enrichment protocol for homologous recombination. This result indicates that, also in mammalian cells, homologous recombination rather than random integration can be the predominant event.
The never ripe mutation blocks ethylene perception in tomato. (1994)

Seedlings of tomato fruit ripening mutants were screened for their ability to respond to ethylene. Ethylene induced the triple response in etiolated hypocotyls of all tomato ripening mutants tested except for one, Never ripe (Nr). Our results indicated that the lack of ripening in this mutant is caused by ethylene insensitivity. Segregation analysis indicated that Nr-associated ethylene insensitivity is a single codominant trait and is pleiotropic, blocking senescence and abscission of flowers and the epinastic response of petioles. In normal tomato flowers, petal abscission and senescence occur 4 to 5 days after the flower opens and precede fruit expansion. If fertilization does not occur, pedicel abscission occurs 5 to 8 days after petal senescence. If unfertilized, Nr flowers remained attached to the plant indefinitely, and petals remained viable and turgid more than four times longer than their normal counterparts. Fruit development in Nr plants was not preceded by petal senescence; petals and anthers remained attached until they were physically displaced by the expanding ovary. Analysis of engineered 1-aminocyclopropane-1-carboxylate (ACC) synthase-overexpressing plants indicated that they are phenotypic opposites of Nr plants. Constitutive expression of ACC synthase in tomato plants resulted in high rates of ethylene production by many tissues of the plant and induced petiole epinasty and premature senescence and abscission of flowers, usually before anthesis. There were no obvious effects on senescence in leaves of ACC synthase overexpressers, suggesting that although ethylene may be important, it is not sufficient to cause tomato leaf senescence; other signals are clearly involved.
Generation of dynamic temporal and spatial concentration gradients using microfluidic devices (2004)

This paper describes a microfluidic approach to generate dynamic temporal and spatial concentration gradients using a single microfluidic device. Compared to a previously described method that produced a single fixed gradient shape for each device, this approach combines a simple "mixer module" with gradient generating network to control and manipulate a number of different gradient shapes. The gradient profile is determined by the configuration of fluidic inputs as well as the design of microchannel network. By controlling the relative flow rates of the fluidic inputs using separate syringe pumps, the resulting composition of the inlets that feed the gradient generator can be dynamically controlled to generate temporal and spatial gradients. To demonstrate the concept and illustrate this approach, examples of devices that generate (1) temporal gradients of homogeneous concentrations, (2) linear gradients with dynamically controlled slope, baseline, and direction, and (3) nonlinear gradients with controlled nonlinearity are shown and their limitations are described.
Production of adenovirus vectors and their use as a delivery system for influenza vaccines (2010)

Ad vector-based influenza vaccines for pandemic preparedness are under development to meet global vaccine demand.
Synthesis and Biological Evaluation of Novel Chloroethylaminoanthraquinones with Potent Cytotoxic Activity against Cisplatin-Resistant Tumor Cells (2004)

Novel 1- and 1,4-substituted chloroethylaminoanthraquinones with DNA binding and alkylating properties along with their respective hydroxyethylaminoanthraquinone intermediates were synthesized. Selected chloroethylaminoanthraquinones were shown to cross-link DNA and alkylate guanines (at low nM concentration) with a preference for reaction sites containing 5'-PyG. A compound (Alchemix) with the bis-chloroethyl functionality confined to one side chain alkylated but did not cross-link DNA. All the 1,4-disubstituted chloroethylaminoanthraquinones were potently cytotoxic (nM IC(50)s) against cisplatin-resistant ovarian cancer cell lines.
Genetic Predisposition to Respiratory Diseases: Infiltrative Lung Diseases (2006)

The availability of high-throughput genotyping and large collaborative clinical networks creating well-characterized patient populations with DNA repositories has facilitated genome-wide scans and candidate gene studies to identify susceptibility alleles for the development of interstitial lung disease. The association of pulmonary fibrosis with rare inherited disorders, and the variable susceptibility of inbred mouse strains to this disease indicate that pulmonary fibrosis is determined by genetic factors. Sarcoidosis represents a complex disease with racial and ethnic differences in disease prevalence, and evidence of familial clustering. Familial aggregation of sarcoidosis from 'A Case-Control Etiologic Study of Sarcoidosis' (ACCESS) reveals a familial odds ratio (OR) of sarcoidosis of 5.8 (95% CI 2.1-15.9) for sibs and 3.8 (95% CI 1.2-11.3) for parents. Several HLA class II alleles have been associated with either increased or decreased risk of sarcoidosis, and results vary depending on study populations of different ethnicity. Genome-wide screening has conclusively identified linkage to chromosome 5q11and the development of sarcoidosis, and HLA genes and BTNL2 are susceptibility genes located in this region. Familial aggregation of idiopathic interstitial pneumonia (IIP) has been established by several groups, and a large US-based study suggests autosomal dominant inheritance with reduced penetrance; furthermore, cigarette smoking was associated with affection status among siblings (OR = 3.6, 95% CI 1.3-9.8, p = 0.01). Families demonstrate more than one type of IIP, suggesting various subtypes of IIP may share a common pathogenesis. Genome-wide linkage scans in familial interstitial pneumonia demonstrate linkage to chromosomes 4, 5 and 11. Candidate gene studies indicate that surfactant protein C and telomerase are susceptibility genes for the development of pulmonary fibrosis. Future challenges include determining how multiple susceptibility alleles interact with each other and environmental factors resulting in disease risk and multiple phenotypes, and determining the mechanism of action and cellular pathways involving susceptibility alleles. Further insight into these areas may lead to new therapeutic interventions.
A short history of sweat gland biology (2007)

The axilla, especially its microflora and axillary sweat glands as well as their secretions, is the main target of cosmetic compositions such as deodorants or antiperspirants. There are three types of sweat glands present in the axillary skin, namely apocrine, eccrine and apoeccrine sweat glands. Here, we provide an overview of the morphological, structural and functional characteristics of the different gland types and present techniques that allow their clear distinction. Moreover, we describe different forms of perspiration as physical reactions to external and internal stimuli.
Organoids direct systemic expression of erythropoietin in mice. (1995)

Organoids are adenoviral vector transduced cells embedded ex vivo in a collagen-polytetrafluoroethylene lattice that is saturated with angiogenic factors. Organoids provide an alternative method of cell mediated gene transfer following implantation in the donor/recipient. The feasibility of adenovirally mediated delivery via organoids using the erythropoietin (Epo) cDNA was tested. Fibroblasts were transduced by two recombinant adenoviral vectors encoding the Macaca cynomolgus Epo cDNA, driven by a viral (RSV LTR) or a murine housekeeping gene promoter (PGK-1). A functional in vivo assay was used to monitor Epo production via the rise in hematocrit(s) (hct). The hct remained elevated for as long as 6 weeks after implantation. Subcutaneous implants gave consistently higher hct than intraperitoneal implants, while organoids made with a greater number of cells, or an equal number of cells transduced at higher multiplicities of infection (MOI) also produced a larger increase in hct. AdPGKEpo-organoids produced a greater increase in hct than AdRSVEpo-organoids under comparable conditions, but the duration of expression was similar. A 10- to 50-fold lower input of AdRSVEpo using organoids versus direct intravenous injections resulted in an equal to, or greater than hct response in mice. Explanted organoids caused a rapid decrease in the hct of mice. Organoid supernatant had little or no detectable free viral particles making this method safe from unwanted recombinant adenovirus dissemination.
Retrovirus packaging cells based on 10A1 murine leukemia virus for production of vectors that use multiple receptors for cell entry (1996)

10A1 murine leukemia virus can enter cells by using either of two different cell surface phosphate transport proteins, the gibbon ape leukemia virus receptor Glvr-1 (Pit-1) or the amphotropic retrovirus receptor Ram-1 (Pit-2). Glvr-1 and Ram-1 are widely expressed in different tissues, but the relative amounts of each are highly variable. We have developed retrovirus packaging cell lines based on 10A1 virus to take advantage of this dual receptor utilization to improve gene transfer rates in somatic cells of animals and humans, in which the relative levels of the two receptors are not always known. Optimization of the Env expression vector allowed the generation of packaging lines that produce helper-free vector titers up to 10(7)/ml. By interference analysis, we found that a 10A1 pseudotype retroviral vector can utilize Ram-1 for efficient entry into mouse, rat, and human cells and can utilize Glvr-1 for entry into mouse and human cells but not for entry into rat cells. The 10A1 pseudotype vector efficiently enters mouse cells by using Glvr-1, while entry into human cells is much less efficient. Thus, the 10A1 pseudotype packaging cells may be advantageous compared with the standard amphotropic packaging cells because vectors produced by the cells can use an additional receptor for cell entry. These packaging cells will also be useful to further explore the complicated pattern of receptor usage conferred by the 10A1 viral surface protein.
VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells (2002)

Despite considerable advances in medicine, the incidence of heart failure remains high in patients after myocardial infarction (MI). This study investigated the effects of engrafted early-differentiated cells (EDCs) from mouse embryonic stem cells, with or without transfection of vascular endothelial growth factor (VEGF) cDNA (phVEGF(165)), on cardiac function in postinfarcted mice. EDCs were transfected with green fluorescent protein (GFP) cDNA and transplanted into infarcted myocardium. Compared with the MI mice receiving cell-free medium, cardiac function was significantly improved in the MI mice 6 wk after transplantation of EDCs. Moreover, improvement of heart function was significantly greater in the mice implanted with EDCs overexpressing VEGF (EDCs-VEGF) than with EDCs alone. Frozen sections of infarcted myocardium with EDCs or EDCs-VEGF transplantation showed GFP-positive tissue. The area with positive immunostaining for cardiac troponin I and alpha-myosin heavy chain was larger in injured myocardium with EDCs or EDCs-VEGF transplantation than with medium injection. Transplantation of EDCs or EDCs-VEGF significantly increased the number of blood vessels in the MI area. However, the density of capillaries was significantly higher in the EDCs-VEGF animals than in the EDC mice. Double staining for GFP and connexin-43 was positive in injured myocardium with EDC transplantation. Our data demonstrate that engrafted EDCs or EDCs-VEGF regenerated cardiac tissue and significantly improved cardiac function in postinfarcted hearts. The novel EDCs-VEGF synergistic approach may have an important impact on future cell therapy for patients experiencing MI or heart failure.
Scaling the issue window with look-ahead latency prediction (2004)

In contemporary out-of-order superscalar design, high IPC is mainly achieved by exposing high instruction level parallelism (ILP). Scaling issue window size can certainly provide more ILP; however, future processor scaling demands threaten to limit the size of the issue window.In this study, we propose a dynamic instruction sorting mechanism that provides more ILP without increasing the size of the issue window. In our approach, early in the pipeline, we predict how long an instruction needs to wait before it can be issued, i.e. the waiting time for its operands to be produced. Using this knowledge, the instructions are placed into a sorting structure, which allows instructions with shorter waiting times enter the issue window ahead of those instructions with longer waiting times, preventing long-waiting instructions from clogging the issue queue.The accuracy in predicting instruction waiting times directly determines the effectiveness of our sorting mechanism. While most instructions have deterministic execution latencies, predicting load execution times is more difficult due to cache misses and in-flight loads. Loads are particularly challenging since their execution time can vary significantly. In this study, we examine techniques to predict load execution time accurately, based on data reference history.
Immobilization of denatured DNA to macroporous supports: II. Steric and kinetic parameters of heterogeneous hybridization reactions (1982)

The accessibility of immobilized DNA has been shown to depend more crucially on the method of immobilization than on the type of support used for fixation. When sonicated denatured DNA is coupled via diazotization or via cyanogen bromide reaction to solid Sephadex G-25 and Cellex 410 or to macroporous Sephacryl S-500 and Sepharose C1-6B its accessibility varies from 100 to 24 percent. Generally the loss of accessibility is linked to a depression of the melting temperature of DNA helices formed on the support. This correlation shows a characteristic course for a particular coupling method. DNA coupled under denaturing conditions may become totally inaccessible when only 3 percent of its bases are involved in the covalent linkage. Kinetic experiments with sonicated E.coli DNA have shown that the rate constants for renaturation or hybridization reactions are very similar for DNA immobilized by different methods to solid or macroporous supports. Generally the second order rate constant for a heterogeneous reaction (between mobile and immobilized DNA) is about one order of magnitude smaller than that of the analogous homogeneous reaction (in solution).
Radiofrequency Ablation of Unresectable Primary and Metastatic Hepatic Malignancies (1999)

RFA is a safe, well-tolerated, and effective treatment to achieve tumor destruction in patients with unresectable hepatic malignancies. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA should be investigated.
Advanced amorphous materials for photovoltaic conversion. Semiannual report, October 1, 1979-March 31, 1980 (1980)

The primary objectives of this project are twofold: (i) to investigate new amorphous semiconductor (a-Sc) materials, in which recombination centers are passivated, using plasma deposition techniques; and (ii) to characterize the optoelectronic properties pertaining to both majority-carrier and minority-carrier transport in as-deposited films and in devices. The specific goals in FY 1980 are: (i) to continue investigations of the effects of atmospheric impurities, i.e., nitrogen and oxygen, on the optoelectronic properties of a-Si:H alloys; and (ii) to initiate a study of the effects of these impurities upon the photovoltaic conversion efficiencies of diagnostic devices that are fabricated using such alloys. The following activities were emphasized in the program: (i) an expansion of plasma studies using optical emission spectroscopy in order to identify emitting reactive species due to impurities; and (ii) electrical and optical measurements on alloys with calibrated impurity levels by measurments of photoconductivity, photoluminescence, vibrational spectroscopy, etc.; and (iii) completing the apparatus for device measurements of spectral response, dark I-V characteristics, illuminated I-V characteristics, etc. Associated with the last activity, the fabrication of solar cells was begun using low-impurity a-Si:H materials and various a-Si:(H,O,N) alloys. Progress is reported. (WHK)