gebhart/patrepeval huggingface dataset:
An exploration of the association between frailty and muscle fatigue (2008)

Frailty is increasingly recognized as a geriatric syndrome that shares common biomedical determinants with rapid muscle fatigue: aging, disease, inflammation, physical inactivity, malnutrition, hormone deficiencies, subjective fatigue, and changes in neuromuscular function and structure. In addition, there is an established relationship between muscle fatigue and core elements of the cycle of frailty as proposed by Fried and colleagues (sarcopenia, neuroendocrine dysregulation and immunologic dysfunction, muscle weakness, subjective fatigue, reduced physical activity, low gait speed, and weight loss). These relationships suggest that frailty and muscle fatigue are closely related and that low tolerance for muscular work may be an indicator of frailty phenotype.
Asthma severity in childhood, untangling clinical phenotypes* (2010)

Assessment of childhood asthma severity and asthma control encompasses heterogeneous clinical presentations. The relationship between patterns of asthma symptoms and objective measurements is poorly defined in paediatric asthma. This study includes 115 asthmatic schoolchildren, of which 31 were at inclusion defined as Problematic severe asthma because of inadequate asthma control in the presence of high-dose inhaled corticosteroid (HD-ICS) treatment and at least one other asthma controller drug. Two partially overlapping clinical outcomes were defined irrespective of severity classification (Exacerbations and Chronic persistent asthma) in patients with uncontrolled asthma. The same symptom criteria were used as for Problematic severe asthma, but disregarding current medication. Lung function, exhaled nitric oxide (FE(NO)), bronchial hyperresponsiveness, allergic sensitization and Quality of life (QoL) in the symptom subgroups were compared to children with well-controlled asthma. Multifactor analysis was performed to assess the relative explanatory power of clinical asthma presentations and of HD-ICS treatment on objective measurements. Whereas children included in the Exacerbations subgroup had objective features similar to patients with well-controlled asthma, the Chronic persistent asthma subgroup demonstrated significantly reduced lung function, increased immunoglobin E, allergic poly-sensitization and impaired QoL, similar to that in patients pre-defined as Problematic severe asthma. The presence of chronic asthma symptoms was a significant explanatory factor for reduced lung function, QoL and increased FE(NO) in multifactor analysis. Differences in objective measurements suggest that children with Chronic persistent asthma and those who are symptomatic predominantly during exacerbations may represent distinct phenotypes of childhood asthma with different clinical prognoses.
Growth of native oxide on a silicon surface (1990)

The control factors controlling the growth of native silicon oxide on silicon (Si) surfaces have been identified. The coexistence of oxygen and water or moisture is required for growth of native oxide both in air and in ultrapure water at room temperature. Layer-by-layer growth of native oxide films occurs on Si surfaces exposed to air. Growth of native oxides on n-Si in ultrapure water is described by a parabolic law, while the native oxide film thickness on n+-Si in ultrapure water saturates at 10 Å. The native oxide growth on n-Si in ultrapure water is continuously accompanied by a dissolution of Si into the water and degrades the atomic flatness at the oxide-Si interface, producing a rough oxide surface. A dissolution of Si into the water has not been observed for the Si wafer having surface covered by the native oxide grown in air. Native oxides grown in air and in ultrapure de-ionized water have been demonstrated experimentally to exhibit remarkable differences such as contact angles of ultrapure water drops and chemical binding energy. These chemical bond structures for native oxide films grown in air and in ultrapure water are also discussed.
Haptics in computer-mediated simulation: Training in vertebroplasty surgery (2006)

Surgical simulators and computer games share the enabling technologies in the human-machine interface. With appropriate design and development, the computer-game-like medical training simulator could be used in surgical training. The authors describe a PC-based system for the simulation of the vertebroplasty procedure. In vertebroplasty, the surgeon or radiologist relies on sight and feel to properly insert the bone needle through various tissue types and densities and monitor the injection and reflux of the polymethylmethacrylate (PMMA), or cement, into the vertebra. This article focuses on the provision of a near-realistic haptic feel in bone needle insertion and manual PMMA injection. This involves an efficient biomechanical modeling of bone needle insertion and PMMA flow in bone for haptic rendering, as well as reliable delivery of forces via haptic devices. The authors show that with virtual reality gaming technologies, the surgical simulator can become a virtual trainer for a potentially risky spinal interventional procedure.
Automatic parallelization of an adaptive generalized predictive control algorithm using MAPS 1.0 environment (2000)

Parallelization of real time control algorithms is a problem that the control engineer must consider to meet tighter specifications in terms of plant sampling time. However, due to the lack of appropriate tools, the development time and prototyping of an efficient parallel algorithm is much higher than its sequential equivalent. It is also common that such implementation requires knowledge of system programming. Assuming that a control engineer must concentrate in implementing an efficient control strategy, rather than work around system dependent issues, the Matrix Algorithms Automatic Parallelization System –MAPS- programming environment was developed. If the control algorithm can be represented in a matricial form, as is the case of many, this programming environment puts in the hands of the control engineer the power of parallel processing at the cost of the sequential programming model. In this paper the automatic parallelization of an Adaptive Generalized Predictive Control - AGPC – algorithm is employed as an example, using the MAPS environment. It will be shown that, as long as MAPS supports the target hardware, porting an algorithm is just a matter of describing the parallel network topology in a simple block diagram. Finally, the performance of this parallel AGPC algorithm, mapped over some network topologies will be presented and discussed.
Cryptic loxP sites in mammalian genomes: genome-wide distribution and relevance for the efficiency of BAC/PAC recombineering techniques (2007)

Cre is widely used for DNA tailoring and, in combination with recombineering techniques, to modify BAC/PAC sequences for generating transgenic animals. However, mammalian genomes contain recombinase recognition sites (cryptic loxP sites) that can promote illegitimate DNA recombination and damage when cells express the Cre recombinase gene. We have created a new bioinformatic tool, FuzznucComparator, which searches for cryptic loxP sites and we have applied it to the analysis of the whole mouse genome. We found that cryptic loxP sites occur frequently and are homogeneously distributed in the genome. Given the mammalian nature of BAC/PAC genomic inserts, we hypothesised that the presence of cryptic loxP sites may affect the ability to grow and modify BAC and PAC clones in E. coli expressing Cre recombinase. We have observed a defect in bacterial growth when some BACs and PACs were transformed into EL350, a DH10B-derived bacterial strain that expresses Cre recombinase under the control of an arabinose-inducible promoter. In this study, we have demonstrated that Cre recombinase expression is leaky in un-induced EL350 cells and that some BAC/PAC sequences contain cryptic loxP sites, which are active and mediate the introduction of single-strand nicks in BAC/PAC genomic inserts.
EGF regulates plasminogen activator inhibitor‐1 (PAI‐1) by a pathway involving c‐Src, PKCδ, and sphingosine kinase 1 in glioblastoma cells (2007)

Patients with gliomas expressing high levels of epidermal growth factor receptor (EGFR) and plasminogen activator inhibitor-1 (PAI-1) have a shorter overall survival prognosis. Moreover, EGF enhances PAI-1 expression in glioma cells. Although multiple known signaling cascades are activated by EGF in glioma cells, we show for the first time that EGF enhances expression of PAI-1 via sequential activation of c-Src, protein kinase C delta (PKCdelta), and sphingosine kinase 1 (SphK1), the enzyme that produces sphingosine-1-phosphate. EGF induced rapid phosphorylation of c-Src and PKCdelta and concomitant translocation of PKCdelta as well as SphK1 to the plasma membrane. Down-regulation of PKCdelta abolished EGF-induced SphK1 translocation and up-regulation of PAI-1 by EGF; whereas, down-regulation of PKCalpha had no effect on the EGF-induced PAI-1 activation but enhanced its basal expression. Similarly, inhibition of c-Src activity by PP2 blocked both EGF-induced translocation of SphK1 and PKCdelta to the plasma membrane and up-regulation of PAI-1 expression. Furthermore, SphK1 was indispensable for both EGF-induced c-Jun phosphorylation and PAI-1 expression. Collectively, our results provide a functional link between three critical downstream targets of EGF, c-Src, PKCdelta, and SphK1 that have all been implicated in regulating motility and invasion of glioma cells.
A comprehensive BAC resource (2001)

The Human Genome Project has generated extensive map and sequence data for a large number of Bacterial Artificial Chromosome (BAC) clones. In order to maximize the efficient use of the data and to minimize the redundant work for the research community, The Institute for Genomic Research (TIGR) comprehensive BAC resource (cBACr) (http://www.tigr.org/tdb/BacResource/BAC_resourc e_intro. html) was built as an expansion of the TIGR human BAC ends database. This resource collects, integrates and reports the information on library, maps, sequence, annotation and functions for each human and mouse BAC. The current database contains 635 016 human BACs and 265 617 mouse BACs that were characterized by various approaches, among which 22 705 human clones and 1000 mouse clones have sequence and annotation data.
Induction of Robust B Cell Responses after Influenza mRNA Vaccination Is Accompanied by Circulating Hemagglutinin-Specific ICOS+ PD-1+ CXCR3+ T Follicular Helper Cells (2017)

Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable and precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by mRNA vaccines are largely unknown. In this study, we demonstrate that protective levels of antibodies to hemagglutinin were induced after two immunizations of modified non-replicating mRNA encoding influenza H10 encapsulated in lipid nanoparticles (LNP) in non-human primates. While both intradermal (ID) and intramuscular (IM) administration induced protective titers, ID delivery generated this response more rapidly. Circulating H10-specific memory B cells expanded after each immunization, along with a transient appearance of plasmablasts. The memory B cell pool waned over time but remained detectable throughout the 25-week study. Following prime immunization, H10-specific plasma cells were found in the bone marrow and persisted over time. Germinal centers were formed in vaccine-draining lymph nodes along with an increase in circulating H10-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells, a population shown to correlate with high avidity antibody responses after seasonal influenza vaccination in humans. Collectively, this study demonstrates that mRNA/LNP vaccines potently induce an immunological repertoire associated with the generation of high magnitude and quality antibodies.
An Insulated Coaxial Probe for EM Local Heating (1985)

An insulated miniature coaxial probe with a modified geometry has been developed for EM local heating of a biological (or conducting) medium. This probe is basically a lossy coaxial cavity, and its input impedance, current distribution, and power dissipation pattern can be controlled by the selection of terminal impedances, insulating sheath, and the dimensions of the probe. An approximate theory and an experimental study on the probe are presented.
Stress-relaxation behavior in gels with ionic and covalent crosslinks (2010)

Long-chained polymers in alginate hydrogels can form networks by either ionic or covalent crosslinks. This paper shows that the type of crosslinks can markedly affect the stress-relaxation behavior of the gels. In gels with only ionic crosslinks, stress relaxes mainly through breaking and subsequent reforming of the ionic crosslinks, and the time scale of the relaxation is independent of the size of the sample. By contrast, in gels with only covalent crosslinks, stress relaxes mainly through migration of water, and the relaxation slows down as the size of the sample increases. Implications of these observations are discussed.
Correlating In Vitro Splice Switching Activity With Systemic In Vivo Delivery Using Novel ZEN-modified Oligonucleotides (2014)

Splice switching oligonucleotides (SSOs) induce alternative splicing of pre-mRNA and typically employ chemical modifications to increase nuclease resistance and binding affinity to target pre-mRNA. Here we describe a new SSO non-base modifier (a naphthyl-azo group, "ZEN™") to direct exon exclusion in mutant dystrophin pre-mRNA to generate functional dystrophin protein. The ZEN modifier is placed near the ends of a 2'-O-methyl (2'OMe) oligonucleotide, increasing melting temperature and potency over unmodified 2'OMe oligonucleotides. In cultured H2K cells, a ZEN-modified 2'OMe phosphorothioate (PS) oligonucleotide delivered by lipid transfection greatly enhanced dystrophin exon skipping over the same 2'OMePS SSO lacking ZEN. However, when tested using free gymnotic uptake in vitro and following systemic delivery in vivo in dystrophin deficient mdx mice, the same ZEN-modified SSO failed to enhance potency. Importantly, we show for the first time that in vivo activity of anionic SSOs is modelled in vitro only when using gymnotic delivery. ZEN is thus a novel modifier that enhances activity of SSOs in vitro but will require improved delivery methods before its in vivo clinical potential can be realized.
Chemical Radiosensitizers in Cancer Therapy (1992)

The development of effective low-LET radiation therapy for cancer has been hindered by the lack of consistent differential responses to radiation between tumor and normal tissues. One major difference between many solid tumors and the surrounding normal stroma is the presence of hypoxic foci in solid tumors due to the inadequate supply of nutritional needs as a result of the breakdown of microvasculature. Consequently, failure of conventional radiotherapy and local recurrences are in part attributed to the radioresistant hypoxic cell populations, present in the tumor. Local cure/control rates of a tumor can be increased only by an effective increase in the radiation dose. At the same time, an increase in such a dose would damage the oxic normal stroma, more than the hypoxic tumor cells. Hence, specific modification of tumor radiosensitivity by the use of chemical radiosensitizers, in combination with conventional radiotherapy, is an attractive alternative. Many clinicians and radiotherapists are skeptical about the outcome of using radiosensitizers in patients. Nevertheless, a vast amount of information is currently available regarding the first- and second-generation radiosensitizers both in murine and in human tumors. As a result, it is hoped that eventually a radiosensitizing drug would be discovered/synthesized that will overcome the drawbacks so far encountered in their use in the clinic. In this article, the development of chemical radiosensitizers since the early sixties, the basis for their selection, their mechanism(s) of action, and the results obtained with the various groups of radiosensitizers are reviewed.
Characterization and comparative profiling of the small RNA transcriptomes in two phases of locust (2009)

The abundance of small RNAs in the locust might indicate a long evolutionary history of post-transcriptional gene expression regulation, and differential expression of small RNAs between the two phases might further disclose the molecular mechanism of phase changes.
Fluorometric Studies on the Light Chains of Skeletal Muscle Myosin (1977)

Light chains of skeletal muscle myosin were studied through the reactivity of their SH groups with a fluorescent thiol reagent, N-(7-dimethylamino-4-methylcoumarinyl) maleimide (DACM). The experiments were carried out by reacting the reagent with myosin for a short time and measuring the amounts of reacted dye by fluorometry after separating light chains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The two classes of light chains, alkali light chains and DTNB light chain, were clearly distinguished by their manner of reactivity change, and differences in their environment and in their function were suggested. Although we found that the SH groups of the DTNB light chain were susceptible to very low concentrations of Mg ions (of the order of 10-5 M), we could not observe Ca2+-induced conformational change by our technique. We also estimated the stoichiometry of light chains in skeletal muscle myosin to be 1.37 mol alkali light chain 1, 1.95 mol of DTNB light chain and 0.77 mol of alkali light chain 2 per mole of myosin from the total amounts of our reagent that reacted with each light chain.
Repeated Occurrence of Skin Necrosis Twice Following Coumarin Intake and Subsequently During Decrease of Vitamin K Dependent Coagulation Factors Associated with Cholestasis (1982)

A female patient is described who developed skin and subcutaneous fat necrosis on two occasions after intake of acenocoumarol. Several months later identical skin changes occurred during an episode of cholestasis associated with a prolongation of the prothrombin time to an extent comparable with therapeutic anticoagulation; intake of oral anticoagulants could be excluded. This association gives new insights in the pathogenetic mechanisms responsible for the so-called coumarin necrosis and indicates that it may be not due to drug toxicity or allergy.
Synthesis of DNA/RNA and Their Analogs via Phosphoramidite and H-Phosphonate Chemistries (2013)

The chemical synthesis of DNA and RNA is universally carried out using nucleoside phosphoramidites or H-phosphonates as synthons. This review focuses on the phosphorus chemistry behind these synthons and how it has been developed to generate procedures whereby yields per condensation approach 100% with very few side products. Additionally the synthesis and properties of certain DNA and RNA analogs that are modified at phosphorus will also be discussed. These analogs include boranephosphonates, metallophosphonates, and alkylboranephosphines.
Using diode lasers for atomic physics (1991)

We present a review of the use of diode lasers in atomic physics with an extensive list of references. We discuss the relevant characteristics of diode lasers and explain how to purchase and use them. We also review the various techniques that have been used to control and narrow the spectral outputs of diode lasers. Finally we present a number of examples illustrating the use of diode lasers in atomic physics experiments.
Evaluation of Acute Corneal Barrier Change Induced by Topically Applied Preservatives Using Corneal Transepithelial Electric Resistance In Vivo (2009)

Instillation with BAC immediately disrupted the corneal epithelium. Corneal epithelial cell death is supposed to be associated with a decline in barrier function; thus, corneal TER measurement in vivo can assess the acute toxicity of preservatives added to ophthalmic drugs.
Targeted for drug delivery (2005)

The concept of targeted drugs is not new, but dates back to 1906 when Ehrlich1 first postulated the ‘magic bullet’. The durability of this concept is a strong indication of its appeal, but the ‘magic bullet’ continues to be a challenge to implement in the clinic. The challenge has been on three fronts: finding the proper target for a particular disease state; finding a drug that effectively treats this disease; and finding a means of carrying the drug in a stable form to specific sites while avoiding the immunogenic and nonspecific interactions that efficiently clear foreign material from the body. Nanoparticles are potentially useful as carriers of active drugs and, when coupled with targeting ligands, may fulfill many attributes of a ‘magic bullet’. This review focuses on targeted drug delivery using nanoparticles as a modality that couples a ligand to a nanosized, drug-loaded vehicle as a potential means to achieve increased efficacy of a drug at the site of interest.
Recent advances in the diagnosis and management of migraine (2006)

The World Health Organization considers that severe migraine can be as disabling as quadriplegia. The disorder affects as many of 15% of adults in North America and Western Europe and is probably one of the commonest reasons for patients to see their doctors. Traditionally, headache is given little time in medical teaching, but headache science is advancing rapidly, fuelled by developments in treatment and neuroscience, and there is a sense of excitement perhaps unrivalled in neurology. Many recent advances have particular relevance to clinical practice in terms of both diagnosis and management; I will highlight these. Interested readers should see recent monographs listed in the Further reading box for more detailed accounts of the management of headache disorders.
Conditional deletion of the Bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly (2000)

Bcl-x is a member of the Bcl2 family and has been suggested to be important for the survival and maturation of various cell types including the erythroid lineage. To define the consequences of Bcl-x loss in erythroid cells and other adult tissues, we have generated mice conditionally deficient in the Bcl-x gene using the Cre-loxP recombination system. The temporal and spatial excision of the floxed Bcl-x locus was achieved by expressing the Cre recombinase gene under control of the MMTV-LTR. By the age of five weeks, Bcl-x conditional mutant mice exhibited hyperproliferation of megakaryocytes and a decline in the number of circulating platelets. Three-month-old animals suffered from severe hemolytic anemia, hyperplasia of immature erythroid cells and profound enlargement of the spleen. We demonstrate that Bcl-x is only required for the survival of erythroid cells at the end of maturation, which includes enucleated reticulocytes in circulation. The extensive proliferation of immature erythroid cells in the spleen and bone marrow might be the result of a fast turnover of late red blood cell precursors and accelerated erythropoiesis in response to tissue hypoxia. The increase in cell death of late erythroid cells is independent from the proapoptotic factor Bax, as demonstrated in conditional double mutant mice for Bcl-x and Bax. Mice conditionally deficient in Bcl-x permitted us for the first time to study the effects of Bcl-x deficiency on cell proliferation, maturation and survival under physiological conditions in an adult animal.