Miracle-dz/UniFAR-FTUs huggingface dataset:
The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice

An inhibitor of the transcription factor FOXM1 prevents asthma-associated signaling in mice exposed to a common airborne allergen. Drugging a transcription factor to treat asthma In the lungs of asthma patients, too many goblet cells differentiate (a process called metaplasia) and consequently produce excess mucus in response to various inflammatory signals. The transcription factor FOXM1 is upstream of the transcription factor SPDEF, which is important for airway goblet cell differentiation. Sun et al. identified and characterized a small molecule called RCM-1 that prevented the nuclear translocation of FOXM1 in mice sensitized to house dust mite allergens. In these mice, RCM-1 also prevented airway hyperreactivity and inflammation and improved lung function. IL-13 signaling triggers goblet cell metaplasia, and RCM-1 prevented this response in mice that received IL-13 intranasally. Thus, RCM-1 could be used to treat asthma and other chronic pulmonary disorders associated with goblet cell metaplasia. Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens. RCM-1 blocked the nuclear localization and increased the proteasomal degradation of Forkhead box M1 (FOXM1), a transcription factor critical for the differentiation of goblet cells from airway progenitor cells. RCM-1 reduced airway resistance, increased lung compliance, and decreased proinflammatory cytokine production in mice exposed to the house dust mite and interleukin-13 (IL-13), which triggers goblet cell metaplasia. In cultured airway epithelial cells and in mice, RCM-1 reduced IL-13 and STAT6 (signal transducer and activator of transcription 6) signaling and prevented the expression of the STAT6 target genes Spdef and Foxa3, which are key transcriptional regulators of goblet cell differentiation. These results suggest that RCM-1 is an inhibitor of goblet cell metaplasia and IL-13 signaling, providing a new therapeutic candidate to treat patients with asthma and other chronic airway diseases.
Differentiation of tyrosine hydroxylase‐synthesizing and/or aromatic L‐amino acid decarboxylase‐synthesizing neurons in the rat mediobasal hypothalamus: Quantitative double‐immunofluorescence study

In this double‐immunofluorescence study, we first quantified the neurons of the arcuate nucleus as immunoreactive (+) for tyrosine hydroxylase (TH) and/or aromatic L‐amino acid decarboxylase (AADC) in rats at embryonic day 21 (E21), at postnatal day 9 (P9), and in adulthood by using conventional fluorescent or confocal microscopy. On E21, monoenzymatic (TH+AADC immunonegative (−) and TH−AADC+) neurons and bienzymatic (TH+AADC+) neurons accounted for 99% and 1%, respectively, of the whole neuron population expressing enzymes of dopamine synthesis. Further development was characterized by the dramatic increase in TH+AADC− dorsomedial and TH+AADC+ dorsomedial populations from E21 to P9 as well as by the increase in the TH+AADC+ dorsomedial population (in females) and a drop in the TH+AADC− ventrolateral and TH+AADC− dorsomedial (in males) populations from P9 to adulthood. In contrast to TH+AADC− (in males) and TH+AADC+ neurons, the TH−AADC+ neurons did not change in number from E21 to adulthood. Thus, in rat fetuses, the neurons synthesizing TH and/or AADC were mainly monoenzymatic, whereas during postnatal life the fraction of bienzymatic neurons increased by up to 60%. J. Comp. Neurol. 446:114–122, 2002. © 2002 Wiley‐Liss, Inc.
Comparison of tests of stress‐released cortisol secretion in pituitary disease

OBJECTIVES We wished to compare peak and incremental rise in plasma cortisol in response to insulin induced hypoglycaemia (IIH) stress test, i.m. glucagon stimulation test (IMGST) and short Synacthen test (SST) in patients with pituitary disease, using a modern radioimmunoassay for cortisol. We compared the three stimulants using receiver operator characteristic (ROC) plots, assuming a cortisol threshold of 500 nmol/l or 580 nmol/l for the IIH stress test which we used as the standard from which to evaluate the SST and the IMGST.
Mathematic Analysis of Omnidirectional Wireless Power Transfer—Part-II Three-Dimensional Systems

Part-II of this paper focuses on the mathematical analysis of the 3-D omnidirectional wireless power transfer (WPT) and also addresses the general principle of load detection. It provides the mathematical forms of distributions of the input power vector and output power vector, and demonstrates that the geometry of such 3-D distributed space follows the revolution of the Lemniscate of Bernoulli along its longitudinal axis. It provides the mathematical proof that the direction of energy transfer for the maximum energy efficiency is always in line with that of the maximum load power path in the 3-D space. Experimental verification is included to confirm the 3-D omnidirectional WPT theory.
Effect of different levels of dried sweet orange ( Citrus sinensis ) peel on broiler chickens growth performance

The trial was conducted to evaluate the effect of different levels of dried sweet orange (Citrus sinensis) peel on growth performance in broilers. A total of 400 male broiler chicks (Ross-308) were randomly allocated to treatments varying in supplemental DSOP. The dietary groups consisted of five diets fed for 42 days: control diet without feed additive, diet containing 1.5 % feed additive only in starter phase, diet containing 1.5 % feed additive during whole period (starter + grower), diet containing 3 % feed additive only in starter phase, diet containing 3 % feed additive during whole period. The growth responses achieved by broilers from all groups complied with the standards. However, adding up to 3 % DSOP in diet seems to depress feed intake, body weight gain increasing feed conversion ratio of both starter and growing broilers. Conversely, DSOP in the proportion of 1.5 % of feed seems to promote feed intake and weight gain in the period between the 1-21 days of age, indicating that DSOP can constitute a useful additive in the feeding of broilers. Further research is needed to assess the effects of DSOP to improve its suitability as a feed resource for poultry production.
Expression of the recombination activating genes (RAG1 and RAG2) is not detectable in Epstein‐Barr virus‐associated human lymphomas

The expression of the recombination activating genes (RAG1 and RAG2) is largely restricted to immature lymphoid cells. Previous studies have suggested that Epstein‐Barr virus (EBV) infection may lead to a re‐induction of RAG expression in mature B lymphocytes. To assess the significance of this mechanism for the pathogenesis of malignant lymphomas, we have examined the expression of RAG genes in 11 cases of EBV‐associated endemic Burkitt's lymphoma (BL), 25 cases of Hodgkin's disease (HD, 17 EBV+, 8 EBV‐) and 10 cases of follicular non‐Hodgkin's lymphoma (NHL). Using in situ hybridization, expression of the RAGs was detected in cortical thymocytes in normal thymus and in the tumor cells of 2 of 3 lymphoblastic NHL. By contrast, there was no detectable RAG expression in the BL, HD and follicular NHL cases. Our results indicate that re‐induction of RAG expression does not occur in human lymphomas in vivo. Thus, it is unlikely to play a role in the development of translocations involving immunoglobulin gene loci which are characteristically found in BL and follicular NHL. Moreover, our study shows that in situ hybridization is a suitable method for the analysis of RAG expression in human tissue sections. © 2001 Wiley‐Liss, Inc.
Prophylactic chemotherapy with acyclovir for recurrent herpes simplex labialis

The medical literature was reviewed and 11 clinical trials of prophylactic topical or peroral acyclovir for the suppression of recurrent herpes simplex labialis were identified. The results of these trials showed that prophylactic topical acyclovir was mostly ineffective, but that prophylactic peroral acyclovir, in doses ranging from 400 to 1,000 mg/day, reduced the frequency of herpes labialis during treatment by 50–78%.
Living Drugs for Gastrointestinal Diseases: The Case for Probiotics

Nonpathogenic micro-organisms may contain or produce molecules of potential therapeutic interest. This led to the concept of using ingested living micro-organisms to produce and transport these molecules to targets in the proximal or distal intestine. Several characteristics of this pharmacological approach are very original: potential for in vivo production of active molecules, for targeting immune cells, for presenting immunogenic molecules in a microbial context, for duodenal delivery using bile sensitivity. Probiotics have been studied for some decades and more recently worm eggs have also received some interest. This paper summarizes facts (especially results of randomized controlled trials and pharmacokinetic studies), and ideas about the use of probiotics to treat or prevent gastrointestinal diseases. The safety of this approach (exceptional cases of infections have been observed), and the potential for using new agents or genetically modified micro-organisms (ongoing trials in humans with Crohn’s disease) are also discussed.
Innate immune responses induced by CpG oligodeoxyribonucleotide stimulation of ovine blood mononuclear cells

Examples exist in the literature that demonstrate that treatment with immunostimulatory cytosine–phosphate–guanosine (CpG)‐DNA can protect mice against infection by intracellular pathogens. There are, however, few studies reporting that CpG‐DNA offers similar disease protection in other species. In this study, we assessed the potential of a class A and class B CpG oligodeoxynucleotide (ODN) to induce innate immune responses in sheep, an outbred species. Using peripheral blood mononuclear cells, we have for the first time demonstrated CpG‐ODN‐induced innate immune responses, including natural‐killer‐like activity [non‐major histocompatibility complex (MHC)‐restricted cytotoxicity], interferon‐α secretion and 2′‐5′A oligoadenylate synthetase activity, that could contribute to immune protection in sheep. The type and magnitude of these responses were dependent on ODN class and non‐MHC‐restricted killing was not associated with interferon‐γ production. The latter observation is in contrast with observations reported for mice and humans. These observations support the conclusion that differences in CpG‐ODN‐induced responses exist among species and that specific ODN sequences can significantly influence innate immune responses.
Caracterizacion genetica del cerdo iberico mediante marcadores moleculares

Se estudia la estructura genetica del cerdo iberico, tradicionalmente clasificado en diferentes variedades, mediante un analisis de 25 microsatelites sobre un total de 235 animales. Ademas se han incorporado al estudio muestras de Duroc-Jersey y Chato Murciano como poblaciones de referencia. Los microsatelites usados en este trabajo estan incluidos en los recomendados por la ISAG-FAO para estudios de biodiversidad porcina. Se han desarrolado protocolos basados en amplificaciones conjuntas de varios marcadores para facilitar la caracterizacion de gran numero de muestras. La variacion genetica entre las poblaciones se aprecia en las diferencias de las frecuencias alelicas y de las heterocigosidades. Se detecta un significativo desequilibrio Hardy-Weinberg cuando se toma al cerdo iberico como un conjunto homogeneo, sin embargo el desequilibrio apreciado en las poblaciones por separado es mucho menor. Se estudia el grado de subdivision mediante coeficientes de variacion genetica, valores de distancia, arboles geneticos y analisis de componentes principales. Ademas se construye un arbol individual para comprobar la agrupacion de los animales dentro de su propia variedad. A pesar de no encontrar valores de variacion genetica elevados entre algunas de las poblaciones, se puede afirmar que el cerdo Iberico esta constituido por variedades, algunas de ellas bien diferenciadas, por lo que seria conveniente revisar la clasificacion de las mismas. Los resultados muestran que el panel de marcadores empleado para este estudio es adecuado aunque seria interesante sustituir alguno de los marcadores en futuros trabajos con el cerdo Iberico.
La transmisión de los choques a la tasa de cambio sobre la inflación de los bienes importados en presencia de asimetrías

En este documento estimamos el grado de transmision de corto y largo plazo sobre la inflacion de los bienes importados de un choque a la tasa de devaluacion nominal en presencia de asimetrias. Utilizamos una ecuacion estandar de pass-through para modelos con competencia imperfecta, datos trimestrales de Colombia para el periodo 1985 a 2007 y modelos econometricos lineales y no lineales. Los resultados muestran que la transmision es menos que proporcional, sin importar el plazo considerado. Tambien se encuentra que el grado y la dinamica de la transmision son endogenos y asimetricos al signo, tamano y volatilidad de los tasa de cambio y al estado de la economia. La transmision es mayor cuando la economia esta en auge, es mas abierta, las firmas esperan que los movimientos en la tasa de cambio sean permanentes, la tasa de cambio real esta depreciada, la tasa de cambio nominal se devalua y la inflacion es mayor.
Oral inflammatory load and salivary flow rate in morbidly obese patients: relationship with diabetes and effect of bariatric care protocol

Obesity and diabetes promote periodontal disease (PD). The bariatric care protocol, which is a very-low-calorie diet (VLCD) followed by bariatric surgery (BSx), is an effective treatment for obesity and diabetes but little is known about its effect on oral health. Study objectives are: 1) to assess PD prevalence in obese subjects using oral inflammatory load (OIL); 2) to determine the difference in OIL and salivary flow rate (SFR) between obese patients with and without diabetes; and 3) to assess the effects of VLCD, BSx and bariatric care protocol on OIL and SFR. Findings suggest that, based on OIL, PD prevalence is similar to that reported in the literature. Both VLCD and BSx improve glucose metabolism and weight, but have no impact on oral parameters. However, patients with low SFR at baseline are more prone to increased OIL post-surgery, suggesting a higher risk of developing PD.
Advances in Therapy and the Management of Antithrombotic Drugs for Venous Thromboembolism.

This review focuses on antithrombotic therapy for venous thromboembolism and covers a diverse range of topics including a discussion of emerging anticoagulant drugs, a renewed focus on thrombolytic agents for selected patients, and an analysis of the factors leading to adverse events in patients on warfarin, and how to optimize therapy. In Section I Dr. Weitz discusses new anticoagulant drugs focusing on those that are in the advanced stages of development. These will include drugs that (a) target factor VIIa/tissue factor, including tissue factor pathway inhibitor and NAPc2; (b) block factor Xa, including the synthetic pentasaccharide and DX9065a; (c) inhibit factors Va and VIIIa, i.e., activated protein C; and (d) block thrombin, including hirudin, argatroban, bivalirudin and H376/95. Oral formulations of heparin will also be reviewed. In Section II, Dr. Comerota will discuss the use of thrombolysis for selected patients with venous thromboembolism. Fibrinolytic therapy, which has suffered from a high risk/benefit ratio for routine deep venous thrombosis, may have an important role to play in patients with iliofemoral venous thrombosis. Dr. Comerota presents his own results with catheter-directed thrombolytic therapy and the results from a large national registry showing long-term outcomes and the impact on quality of life. In Section III, Dr. Ansell presents a critical analysis of the factors responsible for adverse events with oral anticoagulants and the optimum means of improving outcomes. The poor status of present day anticoagulant management is reviewed and the importance of achieving a high rate of "time in therapeutic range," is emphasized. Models of care to optimize outcomes are described, with an emphasis on models that utilize patient self-testing and patient self-management of oral anticoagulation which are considered to be the ultimate in anticoagulation care. The treatment of venous and arterial thromboembolism is undergoing rapid change with respect to the development of new antithrombotic agents, an expanding list of new indications, and new methods of drug delivery and management. In spite of these changes, many of the traditional therapeutics are still with us and continue to play a vital role in the treatment of thromboembolic disease. The following discussion touches on a wide range of therapeutic interventions, from old to new, exploring the status of anticoagulant drug development, describing a new intervention for iliofemoral venous thrombosis, and analyzing the critical factors for safe and effective therapy with oral anticoagulants.
The c-Myc Transactivation Domain Is a Direct Modulator of Apoptotic versus Proliferative Signals

ABSTRACT We have assayed the oncogenic, proliferative, and apoptotic activities of the frequent mutations that occur in the c-myc gene in Burkitt's lymphomas. Some alleles have a modest (50 to 60%) increase in transforming activity; however, the most frequent Burkitt's lymphoma allele (T58I) had an unexpected substantial decrease in transforming activity (85%). All alleles restored the proliferation function of c-Myc in cells that grow slowly due to a c-myc knockout. There was discordance for some alleles between apoptotic and oncogenic activities, but only the T58A allele had elevated transforming activity with a concomitant reduced apoptotic potential. We discovered a novel missense mutation, MycS71F, that had a very low apoptotic activity compared to wild-type Myc, yet this mutation has never been found in lymphomas, suggesting that there is no strong selection for antiapoptotic c-Myc alleles. MycS71F also induced very low levels of cytochrome c release from mitochondria, suggesting a mechanism of action for this mutation. Phosphopeptide mapping provided a biochemical basis for the dramatically different biological activities of the transformation-defective T58I and transformation-enhanced T58A c-Myc alleles. Furthermore, the antiapoptotic survival factor insulin-like growth factor 1 was found to suppress phosphorylation of T58, suggesting that the c-Myc transactivation domain is a direct target of survival signals.
LITHIUM TREATMENT IN AFFECTIVE DISORDERS

SUMMARY 50 manic patients of unipolar and bipolar affective illness were placed on oral lithium 600-1500 mg daily and serum levels in the range of 0.49-1.23 mEq/L. A better response in bipolar disorders than unipolar was observed. Besides, a much better response to lithium therapy is observed in patients with disease of longer duration and a positive history of affective illness in blood relations. Therapeutic effect had no relationship in terms of age or sex of the patients.
Migration in India: A Review

Migration in India has received increased scholarly attention in the past forty years, assisted by additional categories of data collected through the National Census. Considering the volume of both internal and international migration, the Indian population is relatively immobile. Most movements occur locally; 60 percent of internal migration is rural-rural on an intra-district level, consisting primarily of women moving with their husbands after marriage. Next in importance is the rural-urban migration of males seeking economic gain. The few studies done on migrants' characteristics show migration to be highly selective of age, sex, marital status, education, occupation and caste. The specific role of poverty in causing migration is still under debate. Key areas for further research include a greater focus on immobility; the social and demographic consequences of migration on sending and receiving communities; and the social, economic and demographic behavior of the migrants.
The Time is Crucial for Ex Vivo Expansion of T Regulatory Cells for Therapy

Ex vivo expanded CD4+CD25highCD127- T regulatory cells (Tregs) are recognized as a promising candidate for immunosuppressive therapy in humans. However, due to the plasticity of Tregs lineage and artificial environment present during ex vivo expansion, Tregs easily lose suppressive activity. Here, we followed expanding CD4+CD25highCD127- Tregs and their naive (CD45RA+) and memory-like (CD45RA-) subsets in order to establish the best conditions of the expansion. We found that, regardless of the phenotype sorted, expanding Tregs were undergoing changes resembling homeostatic proliferation and transformed into effector memory-like cells which produced not only suppressive interleukin-10 (IL-10) but also IL-6, IL-17, and interferon-γ (IFN-γ). With the time ex vivo, Tregs were losing the expression of FoxP3 and suppressive activity both when stimulated and when at rest. The only variable that helped preserve suppressive abilities of Tregs was the limitation of the time of ex vivo cultures to 2 weeks only. According to our study, the highest number of highly suppressive Tregs could be yielded with CD4+CD25highCD127- Tregs cultured no longer than 2 weeks. Thorough quality check, preferentially with the assessment of FoxP3 expression and IFN-γ suppression assay, should be applied to assess suppressive activity of the cells.
Risk of hospitalization during influenza season among a cohort of patients with congestive heart failure

SUMMARY It is uncertain whether hospitalization among patients with congestive heart failure (CHF) increases during the influenza season. This retrospective cohort study used influenza surveillance data from the United States (1986–1987 to 1990–1991), clinical information from the Studies of Left Ventricular Dysfunction (SOLVD) database, and daily temperature data from the National Climatic Data Center to assess the effect of influenza season on hospitalizations in this cohort of patients. The overall hospitalization rate was higher during influenza seasons compared to non-influenza seasons [relative risk (RR) 1·08, 95% confidence interval (CI) 1·01–1·16]. Multivariable Cox modelling revealed an adjusted hazard ratio (HR) of 1·11 for hospitalization during the influenza season (95% CI 1·03–1·20, P=0·005). Overall death rates were also higher during influenza seasons than non-influenza seasons (RR 1·09, 95% CI 0·97–1·21), but the corresponding adjusted HR for death was not significant (HR 1·01, 95% CI 0·98–1·24, P=0·11). Patients with CHF have a greater risk of hospitalization during the influenza season than in the non-influenza season, supporting the current belief that patients with CHF should be regarded as a high-risk group.
Violin Bridge Mobility Analysis under In-Plane Excitation

The vibration of a violin bridge is a dynamic contact vibration with two interfaces: strings-bridge, and bridge feet-top plate. In this paper, the mobility of an isolated bridge under in-plane excitation is explored using finite element modeling based on the contact vibration model. Numerical results show that the dynamic contact stiffness in the two contact interfaces has a great impact on the bridge mobility. A main resonance peak is observed in the frequency range of 2–3 kHz in the frequency response of the isolated bridge when the contact stiffness is smaller than a critical threshold. The main resonance peak frequency is affected by the contact stiffness as well. In order to verify the numerical findings, a novel experimental system is then designed on the basis of a piezoelectric dynamometer for bridge mobility analysis. Experimental results confirm the impact of the dynamic contact stiffness on the bridge mobility.