Miracle-dz/UniFAR-FTUs huggingface dataset:
Cooperation between HGF and CNTF in Promoting the Survival and Growth of Sensory and Parasympathetic Neurons

Previous studies have shown that hepatocyte growth factor (HGF) enhances the survival and growth of neurons that depend on NGF for survival. To determine if HGF cooperates with other neurotrophic factors in the developing peripheral nervous system, we studied the effect of HGF on parasympathetic ciliary ganglion neurons and proprioceptive trigeminal mesencephalic nucleus (TMN) neurons, both of which survive with CNTF. HGF did not promote the survival of these neurons on its own but did enhance the number that survived with CNTF and increased the length and branching of their neurite arbors. HGF did not, however, enhance the survival and growth of TMN neurons incubated with BDNF, which promoted their survival as effectively as CNTF. These results show that HGF cooperates with CNTF in promoting the survival and growth of parasympathetic and proprioceptive neurons and that within the same neurons, the effects of HGF on survival and growth are selectively dependent on which other signaling pathways are concurrently activated.
Nestin Is a Neuroepithelial Target Gene of Thyroid Transcription Factor-1, a Homeoprotein Required for Forebrain Organogenesis*

Thyroid transcription factor-1 (TTF-1, also known as NKX2.1 and T/EBP), a transcription factor belonging to the NKX-2 family of homeodomain-containing genes, plays an essential role in the organogenesis of the thyroid gland, lung, and ventral forebrain. Nestin is an intermediate filament protein strongly expressed in multipotential neuroepithelial stem cells and rapidly down-regulated during postnatal life. Here we show that stable fibroblastic clones expressing TTF-1 acquire a phenotype reminiscent of neuroepithelial cells in culture and up-regulate the endogenous nestin gene. TTF-1 transactivates in HeLa and NIH3T3 cells a reporter gene driven by a central nervous system-specific enhancer element from the second intron of the rat nestin gene, where it recognizes a DNA-binding site (NestBS) whose sequence resembles a nuclear hormone/cAMP-responsive element very different from canonical TTF-1 binding sites. Nuclear extracts from the head of mouse embryos form a retarded complex with NestBS of the same mobility of the extracts obtained from TTF1-expressing clones, which is either abolished or supershifted in the presence of two different antibodies recognizing the TTF-1 protein. Thus, the neuroepithelial marker nestin is a direct central nervous system-specific target gene of TTF-1, leading to the hypothesis that it might be the effector through which TTF-1 plays its role in the organogenesis of the forebrain.
Antibiotics for bacteremic pneumonia: Improved outcomes with macrolides but not fluoroquinolones.

BACKGROUND The questions of whether the use of antibiotics that are active against atypical organisms is beneficial in the treatment of community-acquired pneumonia and of the potential mechanisms of any beneficial effects remain unresolved. Proposed mechanisms include activity against atypical organisms vs the immunomodulatory effects of these antibiotics. The study of outcomes of a large cohort of patients with bacteremic pneumonia provides a unique opportunity to address these questions by excluding patients with primary atypical infection. METHODS We reviewed data from the charts of 2,209 Medicare patients who were admitted to hospitals across the United States from either home or a nursing facility with bacteremic pneumonia between 1998 and 2001. Patients were stratified according to the type of antibiotic treatment. Multivariate modeling was performed to assess the relationship between the class of antibiotic used and several outcome variables. RESULTS The initial use of any antibiotic active against atypical organisms was independently associated with a decreased risk of 30-day mortality (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.59 to 0.98; p = 0.03) and hospital admission within 30 days of discharge (OR, 0.67; 95% CI, 0.51 to 0.89; p = 0.02). Further analysis revealed that the benefits of atypical treatment were associated with the use of macrolides, but not the use of fluoroquinolones or tetracyclines, with macrolides conferring lower risks of in-hospital mortality (OR, 0.59; 95% CI, 0.40 to 0.88; p = 0.01), 30-day mortality (OR, 0.61; 95% CI, 0.43 to 0.87; p = 0.007), and hospital readmission within 30 days of discharge (OR, 0.59; 95% CI, 0.42 to 0.85; p = 0.004). CONCLUSIONS Initial antibiotic treatment including a macrolide agent is associated with improved outcomes in Medicare patients hospitalized with bacteremic pneumonia. These results have implications regarding the mechanism by which the use of a macrolide for treatment of pneumonia is associated with improved outcomes.
Temperature and myogenic factor transcript levels during early development determines muscle growth potential in rainbow trout (Oncorhynchus mykiss) and sea bass (Dicentrarchus labrax).

The influence of changes in environmental temperature on the mRNA levels of myogenic regulatory factors (MRFs), i.e. MyoD and myogenin, as well as myosin heavy chain (MyHC) were studied during early larval development in rainbow trout and sea bass. Phosphoimager analysis of northern blots indicated that there is an optimum temperature for the RNA transcript levels of MRF and MyHC RNA in trout and in sea bass larvae. In the trout strain studied, the highest concentration for MRF and MyHC transcripts was found at 8 degrees C rather than 4 degrees C or 20 degrees C. In European sea bass, the highest concentrations of MRF and MyHC mRNA were observed at 15-20 degrees C rather than 13 degrees C. Raising sea bass larvae at 15 degrees C was associated with higher MyHC gene expression as well as a trend towards an increase in total muscle fibre number and higher growth rates after transfer at ambient temperature. Results suggest that mRNA levels of MRF and MyHC can be used to optimise early development. An experiment in which the temperature was changed illustrates the consequence of precise temporal expression of MRF genes in specifying muscle fibre number at critical stages during early development.
Compressed-width leaky EH1 mode PBG antenna

The recently developed electric-magnetic-electric (EME) microstrip is successfully used to design a compact leaky-mode antenna with fan beam radiation patterns. The EME microstrip consists of composite metals paralleling the electric and magnetic surfaces, where the magnetic surface is made of an array of coupled inductors. The frequency scanning behavior, experimentally and theoretically confirmed by matrix-pencil analyses, indicates that the line width can be reduced by 20%, compared to that of the conventional microstrip with the identical radiation angle of the first higher order (EH/sub 1/) mode at the same frequency.
An experimental comparison study on indoor localization: RF fingerprinting and Multilateration methods

Due to an increasing number of public and private access points in indoor and urban environments, Wi-Fi positioning becomes more and more attractive. In last ten years different approaches and solutions have been developed and applied. The accuracy of these systems depends on the suitability of the propagation models used for the actual propagation conditions. In this paper, characteristic and analysis of two popular methods for indoor localization named as K-Nearest Neighbour (K-NN) algorithm based RF Fingerprinting and RF Multilateration methods are experimentally evaluated and compared according to received signal strength (RSS) of a mobile Wi-Fi user for getting a better and improved result. Transmitted signal strengths of four fixed Wi-Fi modems are measured by using a mobile Mac Computer with Wi-Fi receiver in the School of Electrical and Electronics Engineering hallways at Yildiz Technical University, Istanbul. Later, accuracy plots and modelling for better solution in small areas and LoS locations has been demonstrated for both methods. An experimental comparison results has been presented to evaluate the performance in localizing accuracy where RF Fingerprinting method shows better results than RF multilateration method while RF multilateration method offers less error rate and better solution for small areas.
Dihydroxy-isosteviol methyl ester of Pulsatilla nigricans extract reduces arsenic-induced DNA damage in testis cells of male mice: its toxicity, drug-DNA interaction and signaling cascades.

OBJECTIVE To evaluate the ameliorative efficacy of dihydroxy-isosteviol methyl ester (DIME) of Pulsatilla nigricans extract in arsenic-induced DNA damage in testis cells of mice. METHODS The mice were treated with sodium arsenite (SA) solution intragastrically at a dose of 20 mg/kg per day and examined at 30, 60, and 90 d after treatment. We divided SA-intoxicated mice into two sub-groups: one fed with DIME at a dose of 35 mg/kg and the other with 85% alcohol. We analyzed the expressions of apoptotic signal proteins like CYP1A1, p53 and caspase 3, ascertained the level of cellular and DNA damage and estimated the level of testicular-toxicity biomarkers. We studied the interaction of DIME with calf thymus DNA as target through circular dichroism spectra and melting temperature profiles. RESULTS We observed an elevation in all apoptotic and toxicity biomarkers leading to cellular and DNA damage in the SA-intoxicated mice which showed significant inhibition or reversal on administration of DIME. Results also showed that DIME interacted with DNA, bringing in discernible changes in structure and conformation. CONCLUSION DIME has potentials for therapeutic use in amelioration of arsenic-induced reproductive toxicity.
Increased salivary acetaldehyde levels in heavy drinkers and smokers: a microbiological approach to oral cavity cancer.

The pathogenetic mechanisms behind alcohol-associated carcinogenesis in the upper digestive tract remain unclear, as alcohol is not carcinogenic. However, there is increasing evidence that a major part of the tumour-promoting action of alcohol might be mediated via its first, toxic and carcinogenic metabolite acetaldehyde. Acetaldehyde is produced from ethanol in the epithelia by mucosal alcohol dehydrogenases, but much higher levels derive from microbial oxidation of ethanol by the oral microflora. In this study we investigated factors that might alter the composition and quantities of the oral microflora and, consequently, influence microbial acetaldehyde production. Information about dental health, smoking habits, alcohol consumption and other factors was obtained by a questionnaire from 326 volunteers with varying social backgrounds and health status, e.g. oral cavity malignancy. Paraffin-induced saliva was collected and the microbial production of acetaldehyde from ethanol was measured. Smoking and heavy drinking were the strongest factors increasing microbial acetaldehyde production. Whether poor dental status may alter local acetaldehyde production from ethanol remained unanswered. Bacterial analysis revealed that mainly gram-positive aerobic bacteria and yeasts were associated with higher acetaldehyde production. Increased local microbial salivary acetaldehyde production due to ethanol among smokers and heavy drinkers could be a biological explanation for the observed synergistic carcinogenic action of alcohol and smoking on upper gastrointestinal tract cancer. It offers a new microbiological approach to ethanol-associated carcinogenesis at these anatomic sites.
Ensemble of Constraint Handling Techniques

During the last three decades, several constraint handling techniques have been developed to be used with evolutionary algorithms (EAs). According to the no free lunch theorem, it is impossible for a single constraint handling technique to outperform all other techniques on every problem. In other words, depending on several factors such as the ratio between feasible search space and the whole search space, multimodality of the problem, the chosen EA, and global exploration/local exploitation stages of the search process, different constraint handling methods can be effective during different stages of the search process. Motivated by these observations, we propose an ensemble of constraint handling techniques (ECHT) to solve constrained real-parameter optimization problems, where each constraint handling method has its own population. A distinguishing feature of the ECHT is the usage of every function call by each population associated with each constraint handling technique. Being a general concept, the ECHT can be realized with any existing EA. In this paper, we present two instantiations of the ECHT using four constraint handling methods with the evolutionary programming and differential evolution as the EAs. Experimental results show that the performance of ECHT is better than each single constraint handling method used to form the ensemble with the respective EA, and competitive to the state-of-the-art algorithms.
A Single Amino Acid Exchange Inverts Susceptibility of Related Receptor Tyrosine Kinases for the ATP Site Inhibitor STI-571* 210

The tyrosine kinase inhibitor STI-571 potently blocks BCR-Abl, platelet-derived growth factor (PDGF) α- and β-receptors, and c-Kit kinase activity. Flt3, a receptor tyrosine kinase closely related to PDGF receptors and c-Kit is, however, not inhibited by STI-571. Sequence alignments of different kinases and indications from the crystal structure of the STI-571 Abl kinase complex revealed amino acid residues that are probably crucial for this activity profile. It was predicted that Flt3 Phe-691 in the β5 strand may sterically prevent interaction with STI-571. The point mutants Flt3 F691T and PDGFβ-receptor T681F were constructed, and kinase assays showed that the Flt3 mutant but not the PDGFβ-receptor mutant is inhibited by STI-571. Docking of STI-571 into computer models of the PDGFβ-receptor and Flt3 kinase domains and comparison with the crystal structure of the STI-571 Abl kinase complex indicated very similar binding sites among the three nonphosphorylated kinases, suggesting corresponding courses of their Asp-Phe-Gly motifs and activation loops. Accordingly, we observed reduced sensitivity of preactivated compared with nonactivated PDGFR-β for the inhibition by STI-571. Courses of the activation loop that collide with STI-571 binding explain its inactivity at other kinases as the insulin receptor. The binding site models of PDGFR-β and Flt3 were applied to predict structural approaches for more selective PDGFβ-receptor inhibitors.
Human Growth Hormone-regulated HOXA1 Is a Human Mammary Epithelial Oncogene*

Increased mammary epithelial expression of the human growth hormone (hGH) gene is associated with the acquisition of pathological proliferation. We report here that autocrine hGH production by human mammary carcinoma cells increased the expression and transcriptional activity of the homeobox domain containing protein HOXA1. Forced expression of HOXA1 in human mammary carcinoma cells resulted in increased total cell number primarily by the promotion of cell survival mediated by the transcriptional up-regulation of Bcl-2. HOXA1 also abrogated the apoptotic response of mammary carcinoma cells to doxorubicin. Forced expression of HOXA1 in mammary carcinoma cells, in a Bcl-2-dependent manner, resulted in dramatic enhancement of anchorage-independent proliferation and colony formation in soft agar. Finally, forced expression of HOXA1 was sufficient to result in the oncogenic transformation of immortalized human mammary epithelial cells with aggressive in vivo tumor formation. Herein, we have therefore provided a molecular mechanism by which autocrine hGH stimulation of human mammary epithelial cells may result in oncogenic transformation.
Biologic Measures as Epidemiological Indicators of Risk for the Development of Hypertension in an African American Adolescent Population

&NA;Globally, the health disparity of hypertension is disproportionately greater within the African American population and develops at an earlier age. Elevated and continuous interaction of biologic measures during adolescence may be precursors and indicators of risk for blood pressure changes and the subsequent development of adult essential hypertension. The purpose of this study was to describe (1) the prevalence of biologic measures of risk of hypertension, specifically family history of hypertension, prehypertension, elevated salivary cortisol, and hyperresponsive cortisol and cardiovascular reactivity, and (2) the gender difference in the prevalence of biologic risk factors of hypertension. Subjects and Method:This was an exploratory descriptive design with a nonrandom purposive sample. Participants (N = 106) were high school, African American adolescents, aged 14 to 18 years. Data, including family history of hypertension, resting blood pressure, and blood pressure and cortisol levels before and after induced physiologic stress by cold water hand immersion, were measured. Results:One hundred six African American participants (49 males and 57 females) completed the study. Data described that 71% had a positive family history of hypertension. Overall, the resting blood pressures were 120 mm Hg for systolic and 68 mm Hg for diastolic. Forty-one percent of the patients had prehypertensive blood pressures; 86% had elevated cortisol; 49% had hyperresponsive blood pressure reactivity; and 35% had cortisol hyperresponsivity. Excluding ethnicity, 65% had 3 or more biologic measures of risk of hypertension. Statistically significant gender differences included male systolic pressure and number of males with prehypertension. Conclusion:This study provides evidence of the high prevalence of multiple physiologic biologic measures of risk of hypertension factors within a vulnerable population. The continuous interaction of biologic measures over time may increase the susceptibility and risk of essential hypertension development and supports the development of appropriate physiologically based behavioral interventions.
Drug resistance in Indian visceral leishmaniasis

Throughout the world, pentavalent antimonial compounds (Sbv) have been the mainstay of antileishmanial therapy for more than 50 years. Sbv has been highly effective in the treatment of Indian visceral leishmaniasis (VL: kala‐azar) at a low dose (10 mg/kg) for short durations (6–10 days). But in the early 1980s reports of its ineffectiveness emerged, and the dose of Sbv was eventually raised to 20 mg/kg for 30–40 days. This regimen cures most patients with VL except in India, where the proportion of patients unresponsive to Sbv has steadily increased. In hyperendemic districts of north Bihar, 50–65% patients fail treatment with Sbv. Important reasons are rampant use of subtherapeutic doses, incomplete duration of treatment and substandard drugs. In vitro experiments have established emergence of Sbv resistant strains of Leishmania donovani, as isolates from unresponsive patients require 3–5 times more Sbv to reach similarly effectiveness against the parasite as in Sbv responders. Anthroponotic transmission in India has been an important factor in rapid increase in the Sbv refractoriness. Pentamidine was the first drug to be used and cured 99% of these refractory patients, but over time even with double the amount of initial doses, it cures only 69–78% patients now and its use has largely been abandoned in India. Despite several disadvantages, amphotericin B is the only drug available for use in these areas and should be used as first‐line drug instead of Sbv. The new oral antileishmanial drug miltefosine is likely to be the first‐line drug in future. Unfortunately, development of newer antileishmanial drugs is rare; two promising drugs, aminosidine and sitamaquine, may be developed for use in the treatment of VL. Lipid associated amphotericin B has an excellent safety and efficacy profile, but remains out of reach for most patients because of its high cost.
Validity, reliability, and responsiveness of the fingertip-to-floor test.

OBJECTIVE To evaluate the validity, reliability, and responsiveness of the fingertip-to-floor test to assess total mobility when bending forward in standing position. DESIGN Experimental, prospective, correlational. SETTING Rehabilitation and radiology departments in a university hospital in France. PARTICIPANTS Ten patients (6 women, 4 men; mean age, 42yr) with chronic low back pain (LBP) in the validity study; 32 LBP patients (16 women, 16 men; mean age, 52yr) in the reliability study; and 72 LBP patients (22 women, 50 men; mean age, 30yr) in the responsiveness study. INTERVENTIONS Dynamic radiographs and fingertip-to-floor test. MAIN OUTCOME MEASURES For the validity study, 2 lateral radiographs of the upper dorsal spine, 1 in neutral position, and then 1 in full trunk flexion, were made. Validity was assessed by means of Spearman's correlation coefficient. Reliability was studied by using intraclass correlation coefficient (ICC) and the Bland and Altman method. Responsiveness was assessed by the effect size and the standardized response mean (SRM). RESULTS The Spearman's correlation coefficient for trunk flexion assessed by the test and the radiologic measure was excellent (r(s) = -. 96). The intra- and interobserver reliability were excellent (ICC = .99). The Bland and Altman method showed no systematic trend. The values observed for the test were . 97 for SRM and . 87 for effect size. CONCLUSIONS Because the fingertip-to-floor test has excellent validity, reliability, and responsiveness, it can be used in clinical practice and therapeutic trials.
Organisation of Xanthophyll-Lipid Membranes Studied by Means of Specific Pigment Antisera, Spectrophotometry and Monomolecular Layer Technique Lutein versus Zeaxanthin

Abstract The structure of the xanthophyll pigments lutein and zeaxanthin differs in the position of one double bond and refers to one of the ionon rings. Specific antibodies to zeaxanthin were used to analyse the localisation and orientation of these two xanthophyll pigments in lipid membranes formed with egg yolk lecithin. Bimolecular and monomolecular layers were used. Antibody-antigen interaction was demonstrated and analysed by the bathochromic shift of the absorption spectra of both pigments and by the increase of light-scattering of the pig- mented liposome suspension. It appeared that the extent of the spectral effects accompanying the interaction of the antiserum to zeaxanthin, injected to the liposome suspension which was pigmented with either zeaxanthin or lutein, was different in spite of their similar molecular structures. The results are interpreted in terms of a localisation and distribution of lutein, in the hydrophobic phase of liposomes within two essentially different pigment pools, one oriented horizontally and the other vertically with respect to the membrane plane. This inter- pretation is supported by the analysis of isotherms of the compression of monomolecular layers of lutein and zeaxanthin formed at the air-water interface and of mixed xanthophyll- lipid monolayers as well as by analysis of the penetration of antibody proteins dissolved in the subphase into the mixed xanthophyll-lipid films.