Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel NTRK1 Frameshift Mutation in Congenital Insensitivity to Pain With Anhidrosis

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder. It has been reported that the defect in the NTRK1 gene encoding tropomyosin-related kinase A (TrkA) can cause congenital insensitivity to pain with anhidrosis. Nerve growth factor (NGF), the product of NGFB, mediates biological effects by binding to and activating tropomyosin-related kinase A. In addition, necdin (encoded by NDN) is also essential in nerve growth factor–tropomyosin-related kinase A pathway. We performed mutation analysis in NTRK1, NGFB, and NDN genes in a Chinese Han 17-year-old female patient with congenital insensitivity to pain with anhidrosis and her healthy family members. As a result, the patient was found to have a novel insertion in exon 7 (c.727insT) of NTRK1, which causes premature termination, and a single nucleotide polymorphism (rs2192206 G>A) in NDN. Our findings imply that the genetic variations of the nerve growth factor–tropomyosin-related kinase A pathway play an important role in congenital insensitivity to pain with anhidrosis.
Tensional homeostasis in dermal fibroblasts: Mechanical responses to mechanical loading in three‐dimensional substrates

Many soft connective tissues are under endogenous tension, and their resident cells generate considerable contractile forces on the extracellular matrix. The present work was aimed to determine quantitatively how fibroblasts, grown within three‐dimensional collagen lattices, respond mechanically to precisely defined tensional loads. Forces generated in response to changes in applied load were measured using a tensional culture force monitor. In a number of variant systems, resident cells consistently reacted to modify the endogenous matrix tension in the opposite direction to externally applied loads. That is, increased external loading was followed immediately by a reduction in cell‐mediated contraction whilst decreased external loading elicited increased contraction. Responses were cell‐mediated and not a result of material properties of the matrices. This is the first detailed characterisation of a tensional homeostatic response in cells. The maintained force, after 8 h in culture, was typically around 40–60 dynes/million cells. Maintenance of an active tensional homeostasis has widespread implications for cells in culture and forwhole tissue function. J. Cell. Physiol. 175:323–332, 1998. © 1998 Wiley‐Liss, Inc.
Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study

This study utilizes 2D‐DIGE (difference gel etrophoresis), isotope‐coded protein labeling and biochemical assays to characterize protein alteration in ulcerative colitis (UC) and Crohn's disease (CD) in human epithelial cell and mucosal biopsies in inflammatory bowel disease (IBD)‐affected patients. The aim of this study is to identify the key molecular signatures involved in epithelial cell structure of IBDs. In non‐inflamed UC (QUC) keratins, vimentin, and focal adhesion kinase (7) increased, whereas vinculin and de‐tyrosinated α‐tubulin decreased; inflammation (IUC) exacerbated molecular changes, being collagen type VI alpha 1 chain (COL6A1), tenascin‐C and vimentin increased. In non‐inflamed CD (QCD), tenascin C, de‐tyrosinated α‐tubulin, vinculin, FAK, and Rho‐associated protein kinase 1 (ROCK1) decreased while vimentin increased. In inflamed CD (ICD), COL6A1, vimentin and integrin alpha 4 increased. In QUC, cell metabolism is characterized by a decrease of the tricarboxylic acid cycle enzymes and a decrease of short/branched chain specific acyl‐CoA dehydrogenase, fatty acid synthase, proliferator‐activated receptors alpha, and proliferator‐activated receptors gamma. In QCD a metabolic rewiring occurs, as suggested by glycerol‐3‐phosphate dehydrogenase (GPD2), pyruvate dehydrogenase E1 component subunit beta, NADH dehydrogenase [ubiquinone] iron‐sulfur protein 3, and 4‐trimethylaminobutyraldehyde dehydrogenase increment, while dihydrolipoyl dehydrogenase decreased. Macroautophagy is activated in QUC and IUC, with increased levels of p62, HSC70, major vault protein, myosin heavy chain 9, whereas it is blunted in QCD and ICD. The differing pattern of extracellular matrix, cytoskeletal derangements, cellular metabolism, and autophagy in UC and CD may contribute to the pathophysiological understanding of these disorders and serve as diagnostic markers in IBD patients.
Chromosome replication during the division cycle in slowly growing, steady-state cultures of three Escherichia coli B/r strains

The period of DNA synthesis C during the cell cycle was determined over a broad range of generation times in slowly growing, steady-state batch cultures in the exponential phase and in chemostat cultures of three strains of Escherichia coli, strains B/r A, B/r K, and B/r TT, utilizing measurements of average amounts of DNA per cell and cell survival after radioactive decay of 125I incorporated into the DNA of synthesizing cells. At each growth rate, values for cell survival and for C periods were the same within experimental errors for the three strains. The length of the DNA synthesis period increased linearly with generation (doubling) time T of the culture and approached a limiting value of C = 0.36T at very long generation times. In very slowly growing cultures, DNA replication was limited almost entirely to the final third of the cell cycle. D periods, between termination of DNA replication and cell division, were found to be relatively short at all growth rates for each strain. Average amounts of DNA per cell measured in slowly growing cultures of strains B/r A and B/r TT were indistinguishable from results for strain B/r K at the same growth rates. Amounts of DNA per cell calculated from the cell survival values alone are completely consistent with the measured DNA per cell.
Cellular interactions with biodegradable polyurethanes formulated from L-tyrosine

L-Tyrosine polyurethanes (LTUs) have been synthesized by structural modification of the poly (amino acid) backbone to circumvent the problems associated with the processing of poly (amino acids) arising from their high crystallinity, insolubility in common organic solvents, and high glass-transition and melting temperatures. Additionally, problems such as unpredictable swelling characteristics, change in conformation, and uncontrolled enzymatic degradation have severely restricted the use of poly (amino acids). In contrast, LTUs are designed to retain their superior physico-chemical properties, while incorporating biodegradability through enzymatic, hydrolytic, and oxidative pathways. The aim of this study is to evaluate initially the biocompatibility of LTUs and their degradation products. Studies involving primary dermal human fibroblasts cultured in contact with LTU films or degradation products suggest a lack of toxicity (cell viabilities >93% with p < 0.05 compared to the control for all studies). The diversity of LTU polymer chemistry and the ability of LTUs to phase separate seem to present a heterogeneous surface with variable wettability. This phenomenon influences the adhesion and proliferation of human fibroblasts on polymeric surfaces, wherein fibroblast adhesion on polycaprolactone diol (PCL) based LTUs is characterized by higher cell counts (81,250 ± 18,390 for PCL-C-DTH (desaminotyrosine–tyrosyl hexyl, DTH), 58,360 ± 7370 for PCL-L-DTH, 38,480 ± 12,680 for PEG-C-DTH (polyethylene glycol, PEG), and 46,430 ± 16,000 for PEG-L-DTH at 120 h with p < 0.001 for comparison between PCL-C-DTH and all other LTUs), more rapid cellular proliferation (doubling time of 37–49 h for PCL-based LTUs compared to 68–90 h for PEG-based LTUs), and a uniform cell distribution compared to PEG-based LTUs. However, immunofluorescence assay for F-actin suggests that the cells are well attached. Thus, the lack of cytotoxicity and the ability to control cellular adhesion through polymer chemistry make LTUs attractive candidates for tissue-engineering applications that require elastomeric, biodegradable, and biocompatible polymers.
A linear programming model for optimizing HDR brachytherapy dose distributions with respect to mean dose in the DVH-tail.

PURPOSE Recent research has shown that the optimization model hitherto used in high-dose-rate (HDR) brachytherapy corresponds weakly to the dosimetric indices used to evaluate the quality of a dose distribution. Although alternative models that explicitly include such dosimetric indices have been presented, the inclusion of the dosimetric indices explicitly yields intractable models. The purpose of this paper is to develop a model for optimizing dosimetric indices that is easier to solve than those proposed earlier. METHODS In this paper, the authors present an alternative approach for optimizing dose distributions for HDR brachytherapy where dosimetric indices are taken into account through surrogates based on the conditional value-at-risk concept. This yields a linear optimization model that is easy to solve, and has the advantage that the constraints are easy to interpret and modify to obtain satisfactory dose distributions. RESULTS The authors show by experimental comparisons, carried out retrospectively for a set of prostate cancer patients, that their proposed model corresponds well with constraining dosimetric indices. All modifications of the parameters in the authors' model yield the expected result. The dose distributions generated are also comparable to those generated by the standard model with respect to the dosimetric indices that are used for evaluating quality. CONCLUSIONS The authors' new model is a viable surrogate to optimizing dosimetric indices and quickly and easily yields high quality dose distributions.
Redes sociales: una herramienta para la comunicación estratégica. Uso de las redes sociales en la comunicación de la defensa

espanolLas redes sociales han llegado para quedarse. Desde mediados del ano 2012 las redes sociales son unas herramientas plenamente integradas en el dia a dia de la comunicacion del Ministerio de Defensa. De hecho, se han convertido en el primer canal oficial de comunicacion entre el departamento y la sociedad espanola. La inmediatez en la difusion de la informacion y el contacto directo con el ciudadano son la principal aportacion a la proyeccion publica de la actividad del Ministerio de Defensa y el trabajo de las Fuerzas Armadas. El futuro inmediato para las redes sociales en el ambito de la defensa pasa por dotar a esta area de un fundamento normativo asi como seguir exprimiendo su potencial creativo. EnglishSocial Media is here to stay. From mid-2012 social media accounts have become fully integrated communication tools in the Ministry of Defense. As a matter of fact, they are the first official channel of communication between the department and the Spanish public opinion. The immediacy in the release of information and the direct contact with the citizens are the two main contributions of social media to the broadcasting of the ministry of Defense and the Armed Forces’ activity. The immediate future of social media in the Defense field includes establishing clear policy guidelines and developing its creative potential.
Properties of Ba2+ currents arising from human alpha1E and alpha1Ebeta3 constructs expressed in HEK293 cells: physiology, pharmacology, and comparison to native T-type Ba2+ currents.

Currents arising from human alpha1E and alpha1Ebeta3 Ca2+ channel subunits expressed in HEK-293 cells were examined with whole-cell recording methods and compared to properties of T-current in DRG neurons studied under identical ionic conditions. Coexpression of alpha1E subunit with the beta3 subunit shifted activation to more negative potentials. Activation and deactivation of both variants were comparable at most voltages, with deactivation becoming faster, but less voltage-dependent, at more negative potentials. The inactivation time course for alpha1E and alpha1Ebeta3 currents was best described by at least two exponential components. Recovery from inactivation was markedly voltage-dependent and similar for both constructs. In comparison to alpha1E and alpha1Ebeta3 constructs, T current activation was shifted to more negative potentials, activation was typically slower, deactivation exhibited a steeper voltage-dependence, and recovery from inactivation was less voltage-dependent. Over most of the activation range, native T current inactivated more completely and in a single exponential fashion. Despite some pharmacological similarities (e.g. octanol, barbiturates) between alpha1E and T-type currents, aspects of blockade by amiloride and phenytoin appear to distinguish alpha1E current from T-type currents. The results define several distinguishing features of alpha1E currents that distinguish them from native T-type currents.
Protective Neighborhoods: Neighborhood Proportion of Mexican Americans and Depressive Symptoms in Very Old Mexican Americans

Research indicates that neighborhood context can have a significant effect on the health of older adults. The evidence suggests that there may be physical health benefits afforded to Mexican Americans living in ethnically homogenous neighborhoods, despite the relatively high economic risk in such neighborhoods, but few studies have considered the effect of neighborhood ethnic density on mental health outcomes in older adults. This study evaluated the association between neighborhoods with a high proportion of Mexican Americans and depressive symptoms in very old Mexican Americans. Hierarchical linear modeling was used to examine data from Wave 5 (2004/05) of the Hispanic Established Populations for the Epidemiologic Study of the Elderly. Subjects included 1,875 community‐dwelling Mexican Americans aged 75 and older living in 386 neighborhoods in five states in the southwestern United States (Arizona, California, Colorado, New Mexico, Texas). Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (α=0.88). Results showed that, in very old men, there was a significant negative association between percentage of Mexican Americans in the neighborhood and depressive symptoms (P=.01). In women, the direction of the association was the same, but the effect was not significant. These findings suggest that the proportion of Mexican Americans in the neighborhood matter more for very old Mexican American men than women. Further research may inform screening and treatment for depressive symptoms based on differences in neighborhood composition. Recommendations include culturally customized programs that offer older Mexican Americans greater mobility and access to programs and opportunities in culturally identifiable neighborhoods.
Measurement of response to methacholine inhalation challenge in asthma and allergic rhinitis. PC20 or PC35FEV1?

It has been widely accepted that significant bronchial responsiveness is demonstrated by a 20% fall in the FEV1 during the course of a methacholine challenge (PC20 or PD20FEV1). However, many subjects with allergic rhinitis may have a positive reaction, as evidenced by attaining a PC20 or PD20FEV1, and then demonstrate a plateau. When the PC35FEV1 is used, individuals with this plateau versus individuals with asthma can clearly be differentiated. We thus decided to assess bronchial responsiveness to methacholine with PC20 and PC35FEV1 in asthmatics and patients with allergic rhinitis. Bronchial challenge with methacholine by the method described by Cockcroft et al., with a Hudson 1720 nebulizer (output: 0.198 +/- 0.017 ml/min) was performed on 57 asthmatics and on 56 patients with allergic rhinitis. At the time of the study, they had an FEV1 and FVC greater than or equal to 80% of their predicted normal value and a FEV1FVC% greater than or equal to 70%. Results were expressed as the provocative concentration of methacholine required to produce a 20% and 35% fall in FEV1 (PC20 and PC35FEV1). A plateau was considered if 3 or more consecutive doses of methacholine produced no fall in FEV1 greater than 5%. By the PC20FEV1, bronchial responsiveness was increased (PC20 less than or equal to 18 mg/ml) in 98% of patients with bronchial asthma and in 28% of patients with allergic rhinitis. By the PC35FEV1, bronchial hyperexcitability (PC35FEV1 less than or equal to 40 mg/ml) was detected in 93% of patients with bronchial asthma and in 12% of patients with allergic rhinitis. (ABSTRACT TRUNCATED AT 250 WORDS)
Cross-Presentation of Listeria monocytogenes-Derived CD4 T Cell Epitopes1

Listeriolysin O (LLO) mediates the evasion of Listeria monocytogenes from the phagolysosome into the cytoplasm of the host cell. The recognition of infected cells by CD4 T cells is thought to be limited by the evasion of bacteria from the phagolysosome and also by the direct LLO-mediated inhibition of CD4 T cell activation. To analyze the influence of these immunoevasive mechanisms on the antilisterial CD4 T cell response, the expansion of L. monocytogenes-specific CD4 and CD8 T cells was monitored in infected mice. It was found that expansion of L. monocytogenes-specific CD4 T cells occurred synchronously with CD8 T cell expansion. The analysis of Ag presentation by macrophages and dendritic cells isolated from spleens of infected mice revealed efficient presentation of L. monocytogenes-derived CD4 T cell epitopes that was not dependent on the actA-mediated intercellular spread of bacteria. The further in vitro Ag presentation analysis revealed that although L. monocytogenes-infected macrophages and dendritic cells were poor presenters of CD4 T cell epitopes, more efficient presentation occurred after cocultivation of noninfected dendritic cells or macrophages with infected cells. These data indicate that the suppressive effect of LLO on the antilisterial CD4 T cell response is maintained only in infected APC and support the hypothesis that cross-priming plays a role in the induction of the strong CD4 T cell response in Listeria-infected mice.
Targeted IL-24 gene therapy inhibits cancer recurrence after liver tumor resection by inducing tumor cell apoptosis in nude mice.

BACKGROUND Interleukin-24 (IL-24) is a novel candidate tumor suppressor that induces tumor cell apoptosis experimentally in a variety of human malignant cells including liver cancer cells. The present study was conducted to investigate the potential effect of recombinant adeno-associated virus (rAAV)-mediated IL-24 gene therapy on tumor recurrence and metastasis by inducing tumor cell apoptosis in a hepatocellular carcinoma (HCC) model in nude mice. METHODS We established a recurrent and metastatic HCC model in nude mice and constructed an rAAV vector carrying alpha-fetoprotein (AFP) promoter for expressing the IL-24 gene (rAVV/AFP/IL-24). The vector was administered by regional injection (liver incisal margin). AFP was detected by radiation immunoassay. Histological evaluation of tumor recurrence and metastasis was performed for the liver and lung. The effect of tumor cell apoptosis was confirmed by TUNEL analysis. RESULTS IL-24 gene therapy prevented tumor recurrence and metastasis, as evidenced by marked decreases in the number of metastatic tumor nodules and tumor volume in the liver and lung. At the same time, serum AFP concentration decreased markedly in the IL-24 group compared with the control or rAAV groups (P<0.05). IL-24 gene therapy inhibited tumor recurrence and metastasis as evidenced by the induction of tumor cell apoptosis. CONCLUSION The results demonstrated that targeted IL-24 gene therapy was effective in the prevention of postoperative recurrence and metastasis in an HCC nude mice model by induction of tumor cells apoptosis with potential minimum tumor burden.
Free money, but not tax-free: a proposal for the tax treatment of cryptocurrency hard forks

Cryptocurrency has attracted extraordinary attention as one of the greatest financial innovations in recent years. Equally noticeable are the increasingly frequent cryptocurrency events, such as hard forks. Put simply, a cryptocurrency hard fork happens when a single cryptocurrency splits in two, which results in original coin owners receiving free forked coins. Such hard forks have resulted in billions of dollars distributed to U.S. taxpayers. Despite ongoing regulatory efforts, to date, the Internal Revenue Service (IRS) has yet to take a clear position on the tax treatment of cryptocurrency hard forks. The lack of useful guidance when filing tax returns has left taxpayers genuinely confused in the past few years. To fill this regulatory gap, this Note proposes a framework for cryptocurrency hard fork taxation. It explains the underlying technology of cryptocurrency hard forks, examines the recommended guidelines from the American Bar Association and the Association of International Certified Professional Accountants on cryptocurrency hard fork taxation, and references the current practices in Japan and the United Kingdom to lay a solid foundation for the proposed framework. Ultimately, this Note proposes a two-pronged tax on cryptocurrency hard forks. The first tax is levied on the profit made from the receipt of forked coins, and the second tax is levied on the profit made from the disposition of forked coins. A concrete proposal is provided for the applicable coin valuation, tax basis, holding period, and tax rate for the two prongs. Aiming to propose a tax treatment that is closest to the nature of cryptocurrency hard forks, this proposal considers various practical concerns, such as the inefficiency of the cryptocurrency market, the indirect possession of forked coins through third-party exchanges, and the fluctuating trading prices of forked coins when determining the valuation, tax basis, and holding period. This proposal not only provides clarity for taxpayers in filing
A differential printed antenna design for multiband impulse radio transmitter at 60 GHz

We propose in this paper two microtrip planar antennas dedicated to a 60 GHz high data rate Impulse Radio Multi-band On Off Keying (IR-MBOOK) low power consumption transmitter architecture. The planar antennas were designed and simulated on a conventional and low-cost RT/Duroid 5880 substrate, and then are connected after two differential Power Amplifiers. The antennas serve for radiation as well as an out-of-phase power combiner. In this solution, the 57.05-63.7GHz dedicated band is separated into four balanced sub-bands. We propose the use of two differential planar antennas to cover the dedicated bandwidth on the transmitter architecture. An antenna covers the first 57.05-60.257GHz sub-band (band 1 and 2) and a second antenna covers the 60.257-63.7GHz sub-band (band 3 and 4). The planar antennas 1 and 2 were designed and simulated using the electromagnetic HFSS software and they give a maximum gain of 9.81 dBi and 10.03 dBi, respectively.
Economic crisis and consumption: an almost ideal demand system estimation for Turkey with time-varying parameters

ABSTRACT This paper proposes an alternative approach for analyzing the impacts of economic crises on consumption demand patterns in the absence of household consumption or price data. To do so, an Almost Ideal Demand System (AIDS) which incorporates time dummies corresponding to the periods of economic crises is estimated by using Turkish household final consumption data derived from national accounts. All findings are plausible and coherent with the theoretical framework and show that the crises significantly affect consumption demand patterns in Turkey. The study also reveals tax cuts of 2009 were designed on the basis of economic efficiency, although they were shown to be regressive by Albayrak ([2011. “Finansal Krizde Uygulanan Vergi Politikalarının Gelir Dağilimi Etkileri: 2004-2009.” Ankara Üniversitesi SBF Dergisi 66 (2): 001–034).