Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms Regulating Epidermal Innervation in Pruritus of Atopic Dermatitis

Histamine, the best-known pruritogen in humans, is also regarded as an experimental itch-causing substance. Clinically, antihistamines, i.e., H1-receptor blockers, are used to treat all types of itch resulting from renal and liver diseases, as well as from serious skin diseases such as atopic dermatitis. Antihistamines, however, often lack efficacy in patients with chronic itch involving other agonists, including proteases, neuropeptides, cytokines, and opioids, as well as their cognate receptors, including thermoreceptors, PAR-2, and opioid receptors. Release of these pruritogenic mediators and modulators into the periphery may directly activate itch-sensitive C-fibers by binding to specific receptors on the nerve terminals (Ikoma et al., 2006; Paus et al., 2006). Nerve fibers can also be activated by exogenous mechanical, chemical, or biological stimuli, resulting in itch responses (Tominaga and Takamori, 2010). Histological examination has shown increased epidermal nerve densities in patients with atopic dermatitis (AD), suggesting that this higher density may be at least partly responsible for the intense itching in the skin. Such hyperinnervation is probably caused by an imbalance of nerve elongation factors (e.g. nerve growth factor, amphiregulin, and gelatinase) and nerve repulsion factors (e.g. semaphorin 3A and anosmin-1) produced by keratinocytes (Tominaga and Takamori, 2010; Tengara et al., 2010). Using a unique system of culturing rat dorsal root ganglion (DRG) neurons, consisting of Boyden chambers and extracellular matrix (ECM), we recently demonstrated that neuronal matrix metalloproteinase-2 (MMP-2) is involved in the penetration of sensory nerve fibers into basement membrane through modulation by axonal guidance molecules and/or ECM (Tominaga et al., 2009a). Clinically, psoralenUVA (PUVA) therapy may reduce epidermal hyperinnervation in patients with AD by normalizing abnormal Sema3A and NGF expression in the epidermis, decreasing in visual analog scale (VAS) scores of pruritus severity (Tominaga et al., 2009c). Such anti-nerve growth effects have been observed in the dry skin of acetone-treated mice following exposure to narrowband-UVB and excimer lamps (Kamo et al., 2011a). These findings may help understand the mechanisms by which UV-based therapy modulate epidermal innervation. This chapter presents recent knowledge regarding the relationship between pruritus and epidermal nerve density, especially in AD.
In Honor of Nobel Laureate

W hen Gary Becker asked me to introduce Franco Modigliani on this occasion celebrating Franco's Nobel Prize, he noted that, by tradition, the honoree does not speak. Instead, he listens. It is the introducer who speaks, devoting 30 minutes or so to the laureate's chief contributions to economics. Now, I know of no meeting of economists attended by Franco where he didn't speak. Beyond feasibility, however, rational and optimal considerations would seem to dictate that tradition be broken, for Modigliani is surely his own best synthesizer. Such a departure seems especially apt given the central role of rationality and optimization in Modigliani's economic models. But then, of course, he has also written much about the limits of unconstrained optimization and the complexity of rationality in action. And so it is with us here. Adopting the untraditional alternative would indeed be dubiously optimal, since this occasion is designed to do Franco Modigliani honor, rather than delegate him to perform still another feat of critical summary for the enduring benefit of his fellow economists. After this proper rationalization of my undertaking a summary, rather than imposing that task upon Franco, where shall I begin? Franco Modigliani is a great macroeconomist. He is also a great microeconomist. Rare as this composite is, there are a few others in economics with such wide-ranging
Effects of slow and rapid cooling on catecholamine concentration in arterial plasma and the skin

Kozyreva, T. V. , E. Y. Tkachenko, V. P. Kozaruk, T. V. Latysheva, and M. A. Gilinsky. Effects of slow and rapid cooling on catecholamine concentration in arterial plasma and the skin. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R1668–R1672, 1999. —Norepinephrine (NE) and epinephrine (Epi) concentrations in arterial plasma and in skin tissue were measured chromatographically before and after external cooling. Urethan-anesthetized rats were cooled either slowly (0.004–0.006°C/s) or rapidly (0.03– 0.05°C/s). Blood samples were drawn three times from each animal: 1) before cooling and at a rectal temperature decreased 2) by 0.5°C and 3) by 3–4°C. Skin samples were taken from controls and from rapidly or slowly cooled rats at a rectal temperature lowered by 0.5°C. The resting mean values were 36.7 6 0.3°C for rectal temperature, 0.62 6 0.079 and 1.09 6 0.203 ng/ml for plasma NE and Epi, and 85.6 6 4.1 and 137.6 6 34.3 ng/g for skin NE and Epi. A decrease in rectal temperature by 0.5°C at rapid cooling produced a 2.6-fold increase of NE and a 2.8-fold increase of Epi in plasma. Concomitantly, there was a significant decrease in skin NE concentration by 28% and Epi by 86%. At a rectal temperature decreased by 0.5°C after slow cooling, plasma catecholamines did not change; at unaltered skin NE concentration, there was a reduction in skin Epi concentration (60%). When rectal temperature was lowered by 3–4°C, the increase in plasma NE was virtually the same at both cooling rates and only plasma Epi increased more after deep rapid cooling than slow cooling. Thus the sympathoadrenal system may be differently activated depending on cooling rate. Rapid cooling, when the dynamic activity of the skin cold receptors is involved in the cold response, may provide conditions for an earlier activation of the sympathoadrenal system. This may evidence the functional significance of the dynamic activity of the skin cold receptors in the formation of the cold defense responses.
Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes.

BACKGROUND The relationship between symptoms, intestinal mucosal histology, and disaccharidase activities is not well defined. An analysis of disaccharidase activities was performed in children grouped by age, symptoms, and intestinal mucosal histology and normal values established. METHODS Disaccharidase activities and histology of 246 endoscopically obtained duodenal biopsies in 232 patients (121 girls; age range, 0.08-17 years; mean, 5.9 years) in a 3-year period were reviewed. Patients were divided into two groups based on absence (group 1; n = 142) or presence (group 2; n = 90) of diarrhea and were subdivided by age into, less than 24 months of age and 24 months of age or more. Histologic changes within groups were classified as (A) normal, (B) mild, or (C) moderate to severe based on villus height abnormalities. A questionnaire was sent to 34 patients with hypolactasia to assess the efficacy of lactose avoidance and/or lactase supplementation. RESULTS All group 1 patients had normal findings in analysis of mucosal specimens, and their disaccharidase activities showed normal values because they had no diarrhea. The geometric means (95% confidence interval) in children aged less than 24 months are (in micromoles of substrate hydrolyzed per minute at 37 degrees C per gram protein) (units [U]) lactase, 36.7 (13.4-100.4); maltase, 178.5 (88.9-356.3); palatinase, 12.7 (3.8-41.5); and sucrase 60.0 (24.0-148.1). In children 24 months of age or more, the values are 23.2 (3.9-108.1), 167.6 (78.8-355.9), 12.7 (4.9-32.9), and 51.0 (20.5-126.0), respectively. Only lactase activity decreased with age (p < 0.05). No differences in disaccharidase activities were noted in patients with and without diarrhea if the mucosal histology was normal (group 1A vs. 2A). In patients with diarrhea, values were commensurate with the degree of mucosal injury, especially in the older group. Twenty-two of 27 patients (81%) who responded to the questionnaire had benefited from lactase supplementation and/or lactose avoidance. CONCLUSIONS We have established normal values for disaccharidase activities in the pediatric population. Although the disaccharidase activities correlate more with degree of intestinal mucosal injury than with symptoms, their activities are difficult to predict accurately based on these criteria. If required, disaccharidase activities should be measured biochemically.
A relation-based services management mechanism for service computing

In this paper we propose a service management mechanism based on a relational model, in which all services to be managed are represented, and operations for services are relational operations using SQL. To define the model, we use Web Services Description Language (WSDL) descriptions and extract information. To use SQL for relational operations for service management, we introduce a new operator to check assignability. Through this definition and introduction we can manage services by relational operations, such as service invoke, service collaboration, and service composition. It also becomes easy to collaborate services and data in relational databases since users can access both via a single SQL query. We present an example of implementation built on the Knowledge Cluster System, a type of service computing environment we are developing.
Effects of island-distribution of mid-cardiomyocytes on ventricular electrical excitation associated with the KCNQ1-linked short QT syndrome

Aims: Short QT syndrome (SQTS) is a new genetic disorder of the electrical system of the heart. To date, there are six gene mutations in ion channels underlying SQTS. However, functional effects of spatial heterogeneities, such as island-distribution of mid-cardiomyocytes (M island) on ventricular electrical excitation in SQTS condition are poorly understood or even not understood at all. Therefore, this study used computational modelling to investigate such possible effects.
Preponderance of Fis-binding sites in the R6K gamma origin and the curious effect of the penicillin resistance marker on replication of this origin in the absence of Fis

Fis protein is shown here to bind to 10 sites in the gamma origin of plasmid R6K. The Fis-binding sites overlap all the previously identified binding sites in the gamma origin for the plasmid-encoded pi initiator protein and three host-encoded proteins, DnaA, integration host factor, and RNA polymerase. However, the requirement of Fis for R6K replication depends on the use of copy-up pi-protein variants and, oddly, the antibiotic resistance marker on the plasmid. In Fis-deficient cells, copy-up pi variants cannot drive replication of R6K gamma-origin plasmids carrying the bla gene encoding resistance to penicillin (Penr) but can drive replication of plasmids with the same origin but carrying the chloramphenicol acetyltransferase gene encoding chloramphenicol resistance (Cmr). In contrast, R6K replication driven by wild-type pi is unaffected by the antibiotic resistance marker in the absence of Fis protein. Individually, none of these elements (copy-up pi, Fis deficiency, or drug markers) prevents R6K replication. The replication defect is not caused by penicillin in the medium or runaway replication and is unaffected by the orientation of the bla gene relative to the origin. Replication remains inhibited when part of the bla coding segment is deleted but the bla promoter is left intact. However, replication is restored by insertion of transcriptional terminators on either side of the gamma origin, suggesting that excess transcription from the bla gene may inactivate replication driven by pi copy-up mutants in the absence of Fis. This study suggests that vector sequences such as drug markers may not be inconsequential in replication studies, as is generally assumed.
Interactions between Herpesvirus Entry Mediator (TNFRSF14) and Latency-Associated Transcript during Herpes Simplex Virus 1 Latency

ABSTRACT Herpesvirus entry mediator (HVEM) is one of several cell surface proteins herpes simplex virus (HSV) uses for attachment/entry. HVEM regulates cellular immune responses and can also increase cell survival. Interestingly, latency-associated transcript (LAT), the only viral gene consistently expressed during neuronal latency, enhances latency and reactivation by promoting cell survival and by helping the virus evade the host immune response. However, the mechanisms of these LAT activities are not well understood. We show here for the first time that one mechanism by which LAT enhances latency and reactivation appears to be by upregulating HVEM expression. HSV-1 latency/reactivation was significantly reduced in Hvem −/− mice, indicating that HVEM plays a significant role in HSV-1 latency/reactivation. Furthermore, LAT upregulated HVEM expression during latency in vivo and also when expressed in vitro in the absence of other viral factors. This study suggests a mechanism whereby LAT upregulates HVEM expression potentially through binding of two LAT small noncoding RNAs to the HVEM promoter and that the increased HVEM then leads to downregulation of immune responses in the latent microenvironment and increased survival of latently infected cells. Thus, one of the mechanisms by which LAT enhances latency/reactivation appears to be through increasing expression of HVEM.
Chemosensitivity enhancement toward arsenic trioxide by inhibition of histone deacetylase in NB4 cell line

Objective To investigate the cytotoxic effects of suberanilohydroxamic acid (vorinostat) in combination with arsenic trioxide (ATO) on the human NB4 cell line in vitro. Methods The rates of cell proliferation following treatment with vorinostat with or without ATO were measured. Flow cytometry of Annexin-V/propidium iodide double-stained cells was used to measure apoptosis. Acridine Orange and ethidium bromide staining was used to observe morphological changes characteristic of apoptosis. Western blot analysis was used to measure protein levels. Results Vorinostat and ATO, alone and in combination, inhibited the proliferation of NB4 cells in a time- and dose-dependent manner and the effect was additive. NB4 cells treated with vorinostat + ATO demonstrated greater levels of apoptosis compared with cells treated with either drug alone. Both vorinostat and ATO alone and in combination resulted in lower levels of promyelocytic leukaemia/retinoic acid receptor alpha fusion protein and increased levels of acetyl-histone H3 and acetyl-histone H4 proteins compared with controls. Vorinostat + ATO resulted in lower levels of Akt protein compared with either drug alone. Conclusion The combination of vorinostat and ATO inhibited cell proliferation, induced apoptosis, and enhanced the chemosensitivity of NB4 cells. The mechanism might be associated with increasing histone acetylation levels as well as downregulation of the Akt signalling pathway.
Reversible Cysteine Protease Inhibitors Show Promise for a Chagas Disease Cure

ABSTRACT The cysteine protease cruzipain is essential for the viability, infectivity, and virulence of Trypanosoma cruzi, the causative agent of Chagas disease. Thus, inhibitors of cruzipain are considered promising anti-T. cruzi chemotherapeutic agents. Reversible cruzipain inhibitors containing a nitrile “warhead” were prepared and demonstrated 50% inhibitory concentrations (IC50s) as potent as 1 nM in baculovirus-generated cruzipain enzyme assays. In epimastigote and intracellular amastigote in vitro assays, the most potent compounds demonstrated antiparasitic behavior in the 5 to 10 μM IC50 range; however, trypomastigote production from the amastigote form was ∼90 to 95% inhibited at 2 μM. Two key compounds, Cz007 and Cz008, with IC50s of 1.1 and 1.8 nM, respectively, against the recombinant enzyme were tested in a murine model of acute T. cruzi infection, with oral dosing in chow for 28 days at doses from 3 to 50 mg/kg of body weight. At 3 mg/kg of Cz007 and 3 mg/kg of Cz008, the blood parasitemia areas under the concentration-time curves were 16% and 25% of the untreated group, respectively. At sacrifice, 24 days after immunosuppression with cyclophosphamide, parasite presence in blood, heart, and esophagus was evaluated. Based on negative quantitative PCR results in all three tissues, cure rates in surviving animals were 90% for Cz007 at 3 mg/kg, 78% for Cz008 at 3 mg/kg, and 71% for benznidazole, the control compound, at 50 mg/kg.
Familial adult motor neuron disease: amyotrophic lateral sclerosis

We analyzed the medical records of 103 patients with familial adult motor neuron disease (MND). In the 72 families, 329 members were known to be affected. Observations were compared with the sporadic and Mariana forms of MND. Clinical and laboratory examinations of all three forms were similar in clinical course and findings, but there were minor variations in age at onset, sex ratio, survival, and the frequency with which onset occurred in the lower extremities. Recognition of the familial form still depends on diagnosis of the disease in more than one member of a family.
Dual-port output control of isolated DC/DC converter focusing on duty cycle and frequency of primary inverter

This paper proposes a new approach of an isolated DC/DC converter with dual-port outputs. The converter has two outputs, i.e., a 12-V port and a 48-V port for automotive applications. The dual-port output control can independently be achieved by using only a single primary inverter and a single high-frequency transformer. The duty cycle and the frequency of the inverter are used to control the two output voltages at the same time. The both port voltages are regulated by means of manipulating the duty cycle and the frequency, respectively. In the paper, a technique to achieve the dual-port output voltage control of the isolated DC/DC converter is described and their control characteristics are investigated to confirm validity of the proposed technique.
Strong coupling of predation intensity and diversity in the Phanerozoic fossil record

The importance of ecological interactions in driving the evolution of animals has been the focus of intense debate among paleontologists, evolutionary biologists, and macroecologists. To test whether the intensity of such interactions covaries with the secular evolutionary trend in global biodiversity, we compiled a species-level database of predation intensity, as measured by the frequency of common predation traces (drillings and repair scars ranging in age from Ediacaran to Holocene). The results indicate that the frequency of predation traces increased notably by the Ordovician, and not in the mid-Paleozoic as suggested by multiple previous studies. Importantly, these estimates of predation intensity and global diversity of marine metazoans correlate throughout the Phanerozoic fossil record regardless of corrections and methods applied. This concordance may represent (i) an ecological signal: long-term coupling of diversity and predation; (ii) a diversity-driven diffusion of predatory behaviors: an increased probability of more complex predatory strategies to appear at higher diversity levels; or (iii) a spurious concordance in signal capture: an artifact where rare species and less-frequent (e.g., trace-producing) predatory behaviors are both more detectable at times when sampling improves. The coupling of predation and diversity records suggests that macroevolutionary and macroecological patterns share common causative mechanisms that may reflect either historical processes or sampling artifacts.
Task Demands, Task Interest, and Task Performance: Implications for Human Subjects Research and Practicing What We Preach

Through the continuous investigation of humans in organizations, we have learned much about motivation, attitudes, and performance. For example, Yukl and others have helped increase our understanding of influence tactics and the effect they have on the performance of subordinates, supervisors, and peers. Some tactics (and combinations of tactics) lead to resistance, some lead to compliance, and some lead to commitment. In this study, we raise the question of whether or not we incorporate our knowledge of these research findings into the design, implementation, and interpretation of our own research studies that require the participation of human subjects. In a survey of 134 subjects from a previous social science study, we found that performance varied across the sample, consistent with the concepts of resistance, compliance, and commitment. In addition, the variance in performance could be explained, in part, by task interest and perceived task demands. Implications are discussed.
The relationship between unplanned pregnancy and maternal body mass index 2009–2012

Abstract Objective To analyse the relationship between unplanned pregnancy and maternal Body Mass Index (BMI). Methods A prospective case-control study of planned vs. unplanned pregnancies among women who delivered an infant weighing ≥ 500 g during the four years 2009–2012 in a large maternity hospital in Ireland. Maternal weight and height were measured at the first antenatal visit before calculation of BMI. Clinical and sociodemographic details were computerised. BMI was categorised according to the World Health Organization. The epidemiological associations were examined using logistic regression, adjusted for confounding variables. Results Between 2009 and 2012, 34,377 women were included, 31.7% (n = 10,894) reported an unplanned pregnancy and 16.6% (n = 5647) were obese. The odds ratios of unplanned pregnancy were greater among obese women compared with those of normal BMI (unadjusted Odds Ratio (OR) 1.3; 95% Confidence Interval (CI) 1.3–1.4 p < 0.001). These ratios increased with increasing BMI (mild unadjusted OR 1.3; CI 1.2–1.4 p < 0.001; moderate unadjusted OR 1.4; CI 1.2–1.6 p < 0.001; severe obesity unadjusted OR 1.7; CI 1.4–2.0 p < 0.001). The higher rate of unplanned pregnancy among obese women was associated with a lower rate of contraception usage and a higher rate of contraceptive failure. Only 37.6% (n = 2112) of obese women took preconceptional folic acid to prevent neural tube defects compared with 46.1% (n = 8176) of women with a normal BMI (p < 0.001). Conclusion Higher rates of unplanned pregnancy among obese women compared with women with a normal BMI is associated with compromised prepregnancy care in this high-risk population. Chinese Abstract 摘要： 目的 分析意外怀孕和孕妇体重指数(BMI)之间的关系。 方法 对在爱尔兰的一个大型妇产科医院里，从2009 - 2012年四年间，生产婴儿的体重≥500 g的计划内和计划外怀孕的女性，进行前瞻性病例对照研究。 在计算体重指数之前的第一次产前随访时，测量孕妇的体重和身高。 临床和社会人口的详细资料已用电脑处理。 体重指数是根据世界卫生组织进行的分类。 使用逻辑回归进行了流行病学关联调查，同时调整混杂变量。 结果 从2009年至2012年期间， 34377名女性被纳入研究。 据报道， 31.7%(n=10894)的意外怀孕女性中有16.6%(n=5647)为肥胖女性。 肥胖女性意外怀孕的比值比比体重指数(BMI)正常的女性意外怀孕的比值比大(未调整的比值比为1.3；95%可信区间：1.3-1.4， p < 0.001)。 这些比值随着体重指数的增加而增大(轻微调整的比值比为1.3；可信区间：1.2-1.2， p < 0.001；适度调整的比值比为1.4；可信区间；1.2-1.6 ，p < 0.001；严重肥胖未经调整的比值比为1.7；可信区间；1.4-2.0 ，p < 1.4)。 肥胖女性中较高的意外怀孕率与较低的避孕率及较高的避孕失败率有关。 与46.1%(n=8176)的体重指数正常的女性相比，只有37.6%(n=2112) 的肥胖女性服用叶酸来预防神经管缺陷(p < 0.001)。 结论 肥胖女性意外怀孕的几率比体重指数正常的女性高，这个结论与肥胖女性放弃孕前保健有关。 关键词： 肥胖孕妇；意外怀孕；避孕