Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐term, noninvasive imaging of regulated gene expression in living mice

Summary: We describe here an approach for monitoring regulated gene expression by noninvasive imaging in living mice. We have utilized the tetracycline inducible system to simultaneously coregulate the expression of two genes encoding the firefly luciferase and the Cre recombinase, respectively. Results from our model system demonstrate that luciferase can be used as a noninvasive imaging marker for the regulated expression of a second gene in living mice. The integration of noninvasive imaging and inducible gene expression into current approaches of functional genomics should greatly advance our capabilities of carrying out highly controlled long‐term studies of gene function in individual mice. genesis 29:116–122, 2001. © 2001 Wiley‐Liss, Inc.
Reproducibility of a telephone interview assessing cognitive function and depressive symptoms in older adults in Germany

Cognitive tests administered by telephone, such as the Telephone Interview for Cognitive Status (TICS) (Brandt et al., 1988), can detect differences in cognitive function and may be useful for screening for Alzheimer’s disease (AD). Compared with cognitive assessments conducted face-to-face at study centers, telephone-based cognitive tests are more efficient in large epidemiological studies and may reduce selective participation due to disease, immobility, visual impairment or illiteracy. A cognitive telephone interview consisting of a battery of tests including the TICS has been used in the Nurses’ Health Study (NHS) (Tworoger et al., 2006). The original English version of the TICS has been translated and validated in many other languages. For our study in Germany, we translated the cognitive tests used in the NHS into German adding some other tests available in German. The reproducibility of this telephoneadministered cognitive test battery has not been assessed to date. We also included the German version of the 15-item Geriatric Depression Scale (GDS) (Goetz et al., 2001) in the telephone interview as depressive symptoms at the time of cognitive
Adaptive responses to alloxan‐induced mild oxidative stress ameliorate certain tauopathy phenotypes

Oxidative stress is considered to promote aging and age‐related disorders such as tauopathy. Although recent reports suggest that oxidative stress under certain conditions possesses anti‐aging properties, no such conditions have been reported to ameliorate protein‐misfolding diseases. Here, we used neuronal and murine models that overexpress human tau to demonstrate that mild oxidative stress generated by alloxan suppresses several phenotypes of tauopathy. Alloxan treatment reduced HSP90 levels and promoted proteasomal degradation of tau, c‐Jun N‐amino terminal kinase, and histone deacetylase (HDAC) 6. Moreover, reduced soluble tau (phosphorylated tau) levels suppressed the formation of insoluble tau in tau transgenic mice, while reduced HDAC6 levels contributed to microtubule stability by increasing tubulin acetylation. Age‐dependent decreases in HDAC2 and phospho‐tau levels correlated with spatial memory enhancement in alloxan‐injected tau mice. These results suggest that mild oxidative stress, through adaptive stress responses, operates counteractively against some of the tauopathy phenotypes.
Gray matter involvement in multiple sclerosis

Gray matter (GM) involvement is detected even in the earliest stages of multiple sclerosis (MS), and GM atrophy occurs at a faster rate than white matter (WM) atrophy early in the disease course. Studies published to date establish that 1) GM involvement and in particular cortical demyelination can be extensive in MS; 2) GM pathology may occur in part independently of WM lesion formation; 3) a primarily GM-related process may be the earliest manifestation of MS; 4) GM involvement is associated with physical disability, fatigue, and cognitive impairment in MS; and 5) GM disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, WM gadolinium enhancement, WM lesion burden) and disease progression. It remains likely that GM damage is related to WM damage. However, continued studies of GM pathology as well as neuronal and axonal involvement in MS and related experimental models are necessary to better understand the etiology and pathogenesis of the degenerative components.
THE RELATIONSHIP BETWEEN TRADE OPENNESS AND INVESTMENT IN SYRIA

This study attempts to investigate the effect of trade openness, GDP and population on the investment in Syria over the period 1980-2010. The cointegration test indicates that investment is positively and significantly related to the trade openness, GDP and population. Population has the biggest effect on the investment. The Granger causality test indicates bidirectional short-run causality relationships between trade openness, GDP, population and investment. There are also unidirectional long-run causality relationship running from trade openness to investment, and bidirectional long-run causality relationships between GDP, population and investment. The study result indicates that it is vital for the Syrian government to still adopt the economic policy in liberalizing foreign trade in order to motivate the investment in the country.
Multilevel Models for Survival Analysis with Random Effects

Summary. A method for modeling survival data with multilevel clustering is described. The Cox partial likelihood is incorporated into the generalized linear mixed model (GLMM) methodology. Parameter estimation is achieved by maximizing a log likelihood analogous to the likelihood associated with the best linear unbiased prediction (BLUP) at the initial step of estimation and is extended to obtain residual maximum likelihood (REML) estimators of the variance component. Estimating equations for a three‐level hierarchical survival model are developed in detail, and such a model is applied to analyze a set of chronic granulomatous disease (CGD) data on recurrent infections as an illustration with both hospital and patient effects being considered as random. Only the latter gives a significant contribution. A simulation study is carried out to evaluate the performance of the REML estimators. Further extension of the estimation procedure to models with an arbitrary number of levels is also discussed.
Maternal smoking and adverse birth outcomes among singletons and twins.

OBJECTIVES This study assessed the effects of maternal smoking on birth outcomes among singletons and twins. METHODS An algorithm was developed to link twins with their siblings in the 1995 Perinatal Mortality Data Set. A random-effects logistic regression model was then used to estimate the association between maternal smoking and several adverse outcomes for a random sample of singletons and for all twins with available maternal smoking information. RESULTS The algorithm successfully linked sibling pairs for 91% of the twin sample. Maternal smoking was associated with a significantly increased risk of low birthweight, very low birthweight, and gestation of less than 33 weeks for both singletons and twins and with an increased risk of gestation of less than 38 weeks, infant mortality, and placental abruption for singletons. Among smokers, negative impacts on the risk of low birthweight, very low birthweight, and extreme premature delivery were significantly higher for women carrying twins. CONCLUSIONS Some of the negative effects of smoking on low birthweight and preterm delivery are greater for twins than for singletons. Women carrying twins should be warned that smoking increases their already high risk of serious infant health problems.
Relative Controllability of Linear Difference Equations

In this paper, we study the relative controllability of linear difference equations with multiple delays in the state by using a suitable formula for the solutions of such systems in terms of their initial conditions, their control inputs, and some matrix-valued coefficients obtained recursively from the matrices defining the system. Thanks to such formula, we characterize relative controllability in time T in terms of an algebraic property of the matrix-valued coefficients, which reduces to the usual Kalman controllability criterion in the case of a single delay. Relative controllability is studied for solutions in the set of all functions and in the function spaces Lp and Ck. We also compare the relative controllability of the system for different delays in terms of their rational dependence structure, proving that relative controllability for some delays implies relative controllability for all delays that are “less rationally dependent” than the original ones, in a sense that we make precise. Finally, we provide an upper bound on the minimal controllability time for a system depending only on its dimension and on its largest delay.
Studies of the Molecular Genetics and Epidemiology of Porcine Rubulavirus Infection

Porcine rubulavirus (PorPV) infection emerged spontaneously in pigs in Mexico in the early 1980s. Since the report of the initial outbreak of the disease, only one full-length genome from a strain isolated in 1984 (PorPV-LPMV/1984) has been sequenced. There is therefore limited information about the genetic variation of this virus. The overall objective of this thesis was to develop molecular techniques to help in the diagnostic field and to investigate in greater detail the full genomes of several isolates, and if possible, gain insights into the persistence, molecular epidemiology and the possible reservoirs of PorPV. In addition, a characterisation of the immune response during acute and persistent infection was included. A real-time RT-PCR was developed for the detection of viral RNA from PorPV in clinical samples using TaqMan technology and primers for the P gene. This assay was highly sensitive (approximately 10 copies per reaction), specific, reproducible and a very useful tool for molecular diagnostics and for enabling studies of various aspects of PorPV throughout this thesis. RT-PCRs based on the NP and P genes were used to study the tissue distribution of the virus. Viral mRNA in the lymph nodes showed that the NP gene was consistently detected in the parotid, submaxilar, cervical and mesenteric nodes and the pancreas. Full-length genomes were sequenced from new isolates obtained from clinical cases of infected swine. The genetic comparison and phylogenetic analysis indicated that three different genetic variants of PorPV had spread in the swine population and that a new generation of circulating virus with a pronounced attenuation has begun to emerge in nature. We also report the isolation of PorPV, or a related virus, from frugivorous, insectivorous, and hematophagous bats. A partial genome sequence analysis showed a 99.97 - 100% amino acid identity to the reference strain isolated from swine. However, larger parts of the genome must be sequenced to ascertain the genetic relationship between these viruses. The study of the immune response during acute and persistent infection revealed enhanced levels of CD8+, CD4+ and CD2+ T-cells in all infected pigs at 10 days PI. CD8+ T-cell subpopulations were signiﬁcantly higher (p<0.05) at 10 and 250 days PI, and CD4+ T-lymphocytes were also signiﬁcant at 250 days PI. In summary, this work developed molecular techniques that can be used to study the pathogenesis and molecular epidemiology of PorPV. The knowledge of the presence of different virus variants in nature, associated with a wildlife reservoir of PorPV can provide greater knowledge regarding the molecular genetic changes and useful data to establish new strategies in the control of this virus in Mexico.
Differences in DNA methylation by extent of breast cancer family history in unaffected women

Breast cancer clusters within families but genetic factors identified to date explain only a portion of this clustering. Lower global DNA methylation in white blood cells (WBC) has been associated with increased breast cancer risk. We examined whether WBC DNA methylation varies by extent of breast cancer family history in unaffected women from high-risk breast cancer families. We evaluated DNA methylation levels in LINE-1, Alu and Sat2 in 333 cancer-free female family members of the New York site of the Breast Cancer Family Registry, the minority of which were known BRCA1 or BRCA2 mutation carriers. We used generalized estimated equation models to test for differences in DNA methylation levels by extent of their breast cancer family history after adjusting for age. All unaffected women had at least one sister affected with breast cancer. LINE-1 and Sat2 DNA methylation levels were lower in individuals with 3 or more (3+) first-degree relatives with breast cancer relative to women with only one first-degree relative. For LINE-1, Alu, and Sat2, having 3+ affected first-degree relatives was associated with a decrease of 23.4% (95%CI = −46.8%, 0.1%), 17.9% (95%CI = −39.5%, 3.7%) and 11.4% (95% CI = −20.3%, −2.5%), respectively, relative to individuals with only one affected first-degree relative, but the results were only statistically significant for Sat2. Individuals having an affected mother had 17.9% lower LINE-1 DNA methylation levels (95% CI = −28.8%, −7.1%) when compared with those not having an affected mother. No associations were observed for Alu or Sat2 by maternal breast cancer status. If replicated, these results indicate that lower global WBC DNA methylation levels in families with extensive cancer histories may be one explanation for the clustering of cancers in these families. Family clustering of disease may reflect epigenetic as well as genetic and shared environmental factors.
Neurotrophin and Neurotrophin Receptor Involvement in Human Neuroblastoma

Neuroblastoma (NB) is an embryonic tumour that originates from cells of the neural crest (NC) arrested in their differentiation at different stages along the sympatho-adrenal lineage and, less frequently, from precursors of sensory neurons [1, 2]. As a consequence, NB can occur throughout the sympathetic chain from thoracic, abdominal and pelvic sites to the adrenal medulla, which accounts for the majority of NBs. Consistent with this, NBs exhibit a high degree of genetic heterogeneity and biological variability, including differences in catechola‐ mine expression, according to their differentiation state along the sympathoadrenal lineage, with a small number of primitive midline and spinal NBs that do not secrete catecholamines considered to be of dorsal root sensory origin [1, 2].
Combined Physical and Psychosexual Therapy for Provoked Vestibulodynia—An Evaluation of a Multidisciplinary Treatment Model

Our objective is to standardize and evaluate a combined physical and psychosexual therapy for women with provoked vestibulodynia. Twenty-four patients underwent the treatment program. Sessions with a psychosexual counselor included issues on sexual functioning, psychological adjustments, and stress elimination. Exercises for mucosal desensitization and reestablishment of pelvic floor function were supervised by a midwife. A questionnaire was used for evaluation at a minimum of 6 months after the treatment. The mean number of appointments to the counselor was 12 (4–24) and 15 (9–26) to the midwife during a mean period of 53 weeks (19–92). Nineteen women (79%) considered themselves to be cured or having greatly improved. Intercourse frequency was increased (p = 0.001) and coital pain was reduced (p = 0.02) after completing the treatment. Improvements in sexual functioning and coping strategies for psychological impairment and stress were reported. Women with provoked vestibulodynia benefit from a multidisciplinary treatment model including desensitization of the vestibular mucosa, rehabilitation of the pelvic floor, and psychosexual adjustments.
Pathological observations of an experimental infection of geese with goose circovirus

There is so far no report describing the pathogenicity of goose circovirus (GoCV) following experimental infection. We report here an experimental inoculation of 21-day-old geese with a GoCV polymerase chain reaction (PCR)-positive sample of bursa of Fabricius (BF) homogenate, and the results of clinicopathological changes. Forty geese were randomly assigned to two groups: the inoculated group (n=30) receiving tissue homogenate and the uninoculated group (n=10) receiving a placebo (physiological saline). Tissue samples were collected for histopathological examination and GoCV detection. The main clinical signs in the GoCV-inoculated geese included diarrhoea at 17 to 30 days post inoculation, marked differences of growth rate and feather disorders in three of the geese. Viraemia was detected by PCR only at 14 days post inoculation. The BF, thymus, spleen, duodenum and liver of some inoculated geese were also PCR-positive. Real-time PCR showed that there was relatively more viral load in the BF. Histological examination revealed lymphocytic depletion and histiocytosis in the BF and inflammation characterized by lymphatic infiltration in the lung, liver and kidney. Immunohistochemistry applied to PCR-positive samples showed that in only three BF samples was GoCV antigen detected in lymphocytes in both the cortex and medulla. In situ apoptosis detection of all BF samples indicated that GoCV inoculation was associated with an increase in bursal lymphocytic apoptotic events.
Accidental Exposure to UV Radiation Produced by Germicidal Lamp: Case Report and Risk Assessment

Ultraviolet radiation is known to cause both benefits and harmful effects on humans. The adverse effects mainly involve two target organs, skin and eye, and can be further divided into short‐ and long‐term effects. The present case report describes an accidental exposure of two health‐care workers to ultraviolet radiation produced by a germicidal lamp in a hospital pharmacy. The germicidal lamp presented a spectrum with an intense UV‐C component as well as a modest UV‐B contribution. Overexposure to UV‐C radiation was over 100 times as large as the ICNIRP exposure limits. A few hours after the exposure, the two subjects reported symptoms of acute UV injury and both of them continued having significant clinical signs for over 2 years. In this study, we describe acute and potentially irreversible effects caused by high UV exposure. In addition, we present the results of risk assessment by occupational exposure to germicidal lamps.
Platelet lysates promote mesenchymal stem cell expansion: A safety substitute for animal serum in cell‐based therapy applications

Mesenchymal stem cells (MSCs) are considered as emergent “universal” cells and various tissue repair programs using MSCs are in development. In vitro expansion of MSCs is conventionally achieved in medium containing fetal calf serum (FCS) and is increased by addition of growth factors. However, for widespread clinical applications, contact of MSCs with FCS must be minimized since it is a putative source of prion or virus transmission. Therefore, because platelets are a natural source of growth factors, we sought to investigate in vitro MSC expansion in response to platelet lysates (PL) obtained from platelet‐rich plasma. Human MSCs were expanded in FCS (±bFGF)‐ or PL‐supplemented medium through a process of subculture. We demonstrated that PL‐containing medium is enriched by growth factors (platelet‐derived growth factors (PDGFs), basic fibroblast growth factor (bFGF), transforming growth factor (TGF‐β), insulin‐like growth factor‐1 (IGF‐1) …) and showed that PL is able to promote MSC expansion, to decrease the time required to reach confluence, and to increase CFU‐F size, as compared to the FCS medium. Furthermore, we demonstrated that MSCs cultured in the presence of PL maintain their osteogenic, chondrogenic, and adipogenic differentiation properties and retain their immunosuppressive activity. Therefore, we propose that PL may be a powerful and safe substitute for FCS in development of tissue‐ and cellular‐engineered products in clinical settings using MSCs. © 2005 Wiley‐Liss, Inc.
The Role of Intercultural Communicative Competence in the Development of World Englishes and Lingua Francas

There is a tendency to think of World Englishes in the noun form; as products rather than as processes (implying that one receives both ready-made, controlling the development of neither). Conceptualising World Englishes as processes in which one can participate as an agent raises the question of what skills are needed in their active construction. The author will argue that since culture resides partly in language, the development of intercultural communicative competence (Byram 1997) should play a pivotal role in foreign language education both to preserve cultural and linguistic diversity, facilitating and enhancing intercultural communication in the process. A range of skills considered central to intercultural communicative competence will be presented and illustrated showing how language students can learn to take control over the development not only of language, but of their own identities.
Development toward rapid and efficient screening for high performance hydrolysate lots in a recombinant monoclonal antibody manufacturing process

Plant‐derived hydrolysates are widely used in mammalian cell culture media to increase yields of recombinant proteins and monoclonal antibodies (mAbs). However, these chemically varied and undefined raw materials can have negative impact on yield and/or product quality in large‐scale cell culture processes. Traditional methods that rely on fractionation of hydrolysates yielded little success in improving hydrolysate quality. We took a holistic approach to develop an efficient and reliable method to screen intact soy hydrolysate lots for commercial recombinant mAb manufacturing. Combined high‐resolution 1H nuclear magnetic resonance (NMR) spectroscopy and partial least squares (PLS) analysis led to a prediction model between product titer and NMR fingerprinting of soy hydrolysate with cross‐validated correlation coefficient R2 of 0.87 and root‐mean‐squared‐error of cross‐validation RMSECV% of 11.2%. This approach screens for high performance hydrolysate lots, therefore ensuring process consistency and product quality in the mAb manufacturing process. Furthermore, PLS analysis was successful in discerning multiple markers (DL‐lactate, soy saccharides, citrate and succinate) among hydrolysate components that positively and negatively correlate with titer. Interestingly, these markers correlate to the metabolic characteristics of some strains of taxonomically diverse lactic acid bacteria (LAB). Thus our findings indicate that LAB strains may exist during hydrolysate manufacturing steps and their biochemical activities may attribute to the titer enhancement effect of soy hydrolysates. © 2012 American Institute of Chemical Engineers Biotechnol. Prog. , 28: 1061–1068, 2012