Miracle-dz/UniFAR-FTUs huggingface dataset:
The mouse C-type transient receptor potential 2 (TRPC2) channel: Alternative splicing and calmodulin binding to its N terminus

Channels of the C-type transient receptor potential (TRPC) are involved in agonist-stimulated and capacitative calcium entry. There are seven TRPCs, all of which have a Ca2+-dependent calmodulin (CaM)-binding domain in their C termini. We now tested binding of CaM to TRPC N termini and show that only that of TRPC2 binds CaM in a Ca2+-dependent manner. Four TRPC2 cDNAs have been reported: a (also clone 14), b (also clone 17), α, and β. Sequences responsible for CaM binding in TRPC2 a and b are absent from the α and β isoforms. The α and β cDNAs of TRPC2 were reported as alternative forms, when recloning of TRPC2 a and b proved impossible. Here we analyzed total RNA samples from brain and testis for presence of TRPC2 a and b and describe the splicing patterns responsible for their formation, as well as those leading to the α and β forms of TRPC2. We re-assert existence of RNA encoding the TRPC2 a and b, encoded in 21 exons with an initiator ATG in exon 2 for TRPC2a and in exon 4 for TRCP2b. The analysis of α and β TRPC2 cDNAs indicates that although the TRPC2β mRNA may exist, the TRPC2α cDNA is derived from an incompletely processed TRPC2a mRNA: It includes in its presumed 5′-untranslated sequence, 713 nt of TRPC2a cDNA fused to 291 nt of an incompletely excised intron. While encoding an active channel in the mouse, the human TRPC2 appears to be a pseudogene. We searched for the human gene in the data bank and located approximately one-half of it in a chromosomal region syntenic to that of the mouse, with similar intron–exon structure. We conclude that the human TRPC2 gene may never have been an active gene because of incomplete ancestral duplication or, if it was complete at one point, that it became inactive upon loss of chromosomal sequences.
Hospitalization trends, costs, and risk factors in HIV-infected children on antiretroviral therapy

Objective:To assess hospitalization trends in HIV-infected children on antiretroviral therapy (ART) in Thailand, an important indicator of morbidity, ART effectiveness, and health service utilization. Design:Prospective observational cohort Method:Children initiating ART in 1999–2009 were followed in 40 public hospitals. Hospitalization rate per 100 person-years were calculated from ART initiation to last follow-up/death. Costs to the healthcare provider were calculated using WHO inpatient estimates for Thailand. Zero-inflated Poisson models were used to examine risk factors for early (<12 months of ART) and late hospitalization (≥12 months) and frequency of admissions. Results:A total of 578 children initiated ART, median follow-up being 64 months [interquartile range (IQR) 43–82]; 211 (37%) children were hospitalized with 451 admissions. Hospitalization rates declined from 63 per 100 person-years at less than 6 months to approximately 10 per 100 person-years after 2 years of ART, and costs fell from $35 per patient-month to under $5, respectively. Age less than 2 years, US Centers of Disease Control and Prevention stage B/C, and stunting at ART initiation were associated with early hospitalization. Among those hospitalized, baseline CD4 cell percentage less than 5%, wasting, initiation on dual therapy, late calendar year, and female sex were associated with higher incidence of early admissions (P <0.02). There were no predictors of late hospitalization, although previous hospitalization in less than 12 months of ART was associated with three times higher incidence of late admissions (P < 0.0001). Conclusion:One in three children required hospitalization after ART. Admissions were highest in the first year of therapy and rapidly declined thereafter. Young age, advanced disease stage, and stunting at baseline were predictive of early hospitalization. Treatment initiation before disease progression would likely reduce hospitalization and alleviate demands on healthcare services.
In Cereo and in Silico: Tissue Microarray (TMA) Techniques and Bioinformatics Are Thriving Forces in Medical Science and Personalized Medicine

Summary Objectives: Tissue microarray (TMA) techniques are among the most promising developments in biomedicine during the last decade. Bioinformatics techniques are indispensable for storing and processing the masses of data related with tissue archive administration and investigation of raw data. Interrelationship between experimental and computational work will be shown. Methods: Tissue specimen arrays allow parallel analysis of huge amounts of samples. TMA techniques thus produce enormous masses of raw data, and optimal use of data can only be made using modern bioinformatics techniques based on huge storage systems, scalable multilayer software architecture and high-throughput algorithms for retrieval and statistical processing. Further crucial issues addressed by informatics techniques are specimen identification during the whole processing chain, and anonymization whenever scientific work is performed without regard to a certain patient. Results: TMA supported by bioinformatics methods has helped in identification of biomarkers, mainly in cancer diagnosis. Moreover, it provides powerful means of quality assurance and training in histopathology. Conclusions: Further statistical analyses seem to be necessary to detect if certain biomarkers are present in nearly all kinds of specimen of the concerned patient, which would allow effective mass screening based on easily accessible specimen. Some investigations showed low dependence on the specimen localization, whereas others suggest to be extremely careful in material selection for the recipient block.
Effect of Postoperative Complications on Adjuvant Chemotherapy Use for Stage III Colon Cancer

Objective: The National Quality Forum has endorsed a quality metric concerning the use of adjuvant chemotherapy administration in stage III colon cancer, yet a substantial treatment gap exists. Our objective was to evaluate the association of postoperative complications on the use of adjuvant therapy after colectomy for cancer. Patients and Methods: Data from the American College of Surgeons National Surgical Quality Improvement Program and National Cancer Data Base were linked to augment cancer registry information with robust clinical data on comorbidities and postoperative complications (2006–2008). The association of complications on adjuvant chemotherapy use was assessed using hierarchical multivariable regression models. Results: From 126 hospitals, 2368 patients underwent resection for stage III colon adenocarcinoma. Overall utilization of adjuvant chemotherapy was 63.2% (1497/2368). Of the 871 patients who did not receive chemotherapy, 652 met National Quality Forum exclusion criteria: death, severe comorbidity, refusal of care, advanced age (≥80 years), or prior malignancy. Of the remaining 219 patients, 19.1% (42/219) had 1 or more serious postoperative complications (eg, pneumonia, pulmonary failure). After accounting for the aforementioned potential explanations, the utilization rate was 87.2% (1497/1716). The strongest predictors of adjuvant chemotherapy omission were prolonged postoperative ventilation, renal failure, reintubation, and pneumonia (all Ps < 0.05). Superficial surgical site infection did not decrease adjuvant therapy receipt but delayed the time to its use by 3-fold. Serious complications increased time to chemotherapy by 65%. Abscess/anastomotic leak increased time to adjuvant chemotherapy by more than 5-fold. Conclusions: Serious postoperative complications explained nearly 20% of the adjuvant chemotherapy treatment gap for patients with stage III colon cancer. The use of clinical data remains important when judging provider performance.
Inhibition of osteoclast formation and function by bicarbonate: Role of soluble adenylyl cyclase

High ${\rm [HCO}_3^ - ]$ inhibits and low ${\rm [HCO}_3^ - ]$ stimulates bone resorption, which mediates part of the effect of chronic acidosis or acid feeding on bone. Soluble adenylyl cyclase (sAC) is a bicarbonate sensor that can potentially mediate the effect of bicarbonate on osteoclasts. Osteoclasts were incubated in 0, 12, and 24 mM ${\rm HCO}_3^ -$ at pH 7.4 for 7–8 days and assayed for tartrate‐resistant acid phosphatase (TRAP) and vacuolar‐ATPase expression, and H+ accumulation. Total number and area of TRAP (+) multinucleated osteoclasts was decreased by ${\rm HCO}_3^ -$ in a dose‐dependent manner. V‐ATPase expression and H+ accumulation normalized to cell cross‐sectional area or protein were not significantly changed. The ${\rm HCO}_3^ -$‐induced inhibition of osteoclast growth and differentiation was blocked by either 2‐hydroxyestradiol, an inhibitor of sAC or sAC knockdown by sAC specific siRNA. The model of ${\rm HCO}_3^ -$ inhibiting osteoclast via sAC was further supported by the fact that the ${\rm HCO}_3^ -$ dose‐response on osteoclasts is flat when cells were saturated with 8‐bromo‐cAMP, a permeant cAMP analog downstream from sAC thus simulating sAC activation. To confirm our in vitro findings in intact bone, we developed a 1‐week mouse calvaria culture system where osteoclasts were shown to be viable. Bone volume density (BV/TV) determined by micro‐computed tomography (µCT), was higher in 24 mM ${\rm HCO}_3^ -$ compared to 12 mM ${\rm HCO}_3^ -$ treated calvaria. This ${\rm HCO}_3^ -$ effect on BV/TV was blocked by 2‐hydroxyestradiol. In summary, sAC mediates the inhibition of osteoclast function by ${\rm HCO}_3^ -$, by acting as a ${\rm HCO}_3^ -$ sensor. J. Cell. Physiol. 220: 332–340, 2009. © 2009 Wiley‐Liss, Inc.
On human tissue kallikrein activity in urine of Brazilian White and Black primary hypertensive patients.

OBJECTIVE To evaluate the possible relationship between the human tissue kallikrein amidase activity with sex and ethnicity in Brazilian primary hypertensive patients. DESIGN Population-based study. PARTICIPANTS One hundred men and women, Black and White primary hypertensive patients aged 20 years and older were selected. Eighty nine healthy individuals, paired according to age, sex, and ethnics were used as controls. METHODS Early-morning midstream urine was used. Human tissue kallikrein amidase activity was estimated with D-Val-Leu-Arg 4-nitroanilide substrate. Creatinine was determined by a method based on Jaffe's reaction. hK1 amidase activity is expressed in microM/(min x mg creatinine) to correct for differences in urine flow rate. Data are expressed as medians. RESULTS Human tissue kallikrein amidase activity was significantly lower in the urine of hypertensive patients (0.210 microM/(min x mg creatinine) than in the urine of control subjects (0.260 microM/(min x mg creatinine) (P = .010). This result supports data from the literature. Contrasting to what was already reported, namely that human tissue kallikrein excretion is higher in females than in males, and especially higher in Caucasians than in African Americans, our results show that, in the urine of Brazilian hypertensive patients and control subjects, no significant effect of sex and ethnicity on human tissue kallikrein amidase activity was observed. CONCLUSIONS The lack of ethnicity effect supports what was already asserted, namely, that, in Brazil, at an individual level, color, as determined by physical evaluation, is a poor predictor of genomic African ancestry, estimated by molecular markers.
Inclusion of Chicory (Cichorium intybus L.) in Pigs' Diets Affects the Intestinal Microenvironment and the Gut Microbiota

ABSTRACT The content and composition of prebiotic plant fiber in the diet is important in promoting gut-related health. This study investigated the effects of the dietary inclusion of chicory forage and roots on the intestinal microenvironment of pigs. Thirty-seven-week-old pigs were fed 1 of 5 diets for 18 days, including a cereal-based control diet and 4 diets with the inclusion of 80 and 160 g kg−1 of body weight chicory forage (CF80 and CF160), 80 g kg−1 chicory root (CR80), and a mix of 80 g kg−1 forage and 80 g kg−1 chicory root (CFR). The animals maintained good performance and health irrespective of diet. Bacterial community structure and diversity in ileal and colonic samples was assessed using terminal restriction fragment length polymorphism (T-RFLP), combined with cloning and sequencing. Samples clustered perfectly according to gut segment with a higher bacterial diversity in colon than ileum. Distal ileum was dominated by lactic acid bacteria (LAB), and the relative amount of this group was increased by the CF160 and CFR diets. The colonic bacterial community was dominated by butyrate-producing bacteria and Prevotella. The increased relative abundance of butyrate-producing bacteria in the colon was positively correlated with the molar proportion of acetic acid and furthermore linked to the chicory forage diets (CF80 and CF160). Diets including chicory roots (CR80 and CFR) were correlated with a higher colonic abundance of Megasphaera elsdenii. The fermentation products and pH in digesta responded to diet type and were correlated with shifts in the microbiota, showing that chicory influences the intestinal microenvironment of pigs.
Visual Development in Very Low Birth Weight Infants

Extremely preterm infants are at risk for neurodevelopmental problems and the visual system is particularly vulnerable. However, development of visual function in preterm infants with little or no retinal or neurologic injury has not been well defined. This study compared development of visual function in preterm infants without severe retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) to that of term infants at 5–7 mo corrected age. Twenty-one very low birth weight (VLBW) preterm infants (24–32 wk gestational age, weighing < 1500 g), and 22 healthy term infants were tested at 5–7 mo corrected age. Infants with any IVH/PVL and > Stage II ROP or Plus disease were excluded. Contrast sensitivity, grating acuity, and vernier acuity were measured using swept-parameter visual evoked potentials. Thresholds and maximum amplitudes were compared between groups. VLBW and term infants showed no differences in sensitivity for contrast (67.5 versus 63.8), grating resolution (12.4 versus 12.5 cpd) or vernier acuity (1.2 versus 1.0 arcmin). However, the amplitudes for swept contrast (p < 0.03) and swept vernier offset (p < 0.04) stimuli were higher in VLBW infants. Visual thresholds in VLBW infants without serious retinal or neurologic abnormalities were not significantly different from those of term infants, suggesting that increased visual experience does not influence visual sensitivity. The higher amplitudes in VLBW infants, suggests that visual experience may affect responses to suprathreshold stimuli.
Cutaneous manifestations of primary immunodeficiency

Purpose of review To show that skin symptoms help in the recognition of primary immunodeficiencies (PIDs). To analyze whether recent molecular data help in understanding genotype/phenotype relations. Recent findings Erythroderma in Omenn syndrome may be caused by either mutations in genes associated with severe combined immunodeficiency (SCID) in which the generation of some T cells is possible, which results in potentially autoreactive lymphoid clones, or by selective proliferation of revertant CD8+ T cells in the skin due to clonal expansion in response to infections or autoantigens. The newborn eczematous eruption, which occurs mainly in the signal-transducer-and-activator-of-transcription-3 (STAT3) variant, helps to differentiate STAT3 from Dedicator of Cytokinesis 8-related Hyper-IgE-syndrome (HIES). Impaired T helper 17 cell (TH17) immunity [HIES and defects of autoimmune regulator element (AIRE), STAT-1, and interleukin17 receptor(IL17(R))] may give rise to localized chronic mucocutaneous candidiasis, whereas a defective innate immune system predisposes to systemic candidiasis [congenital neutropenia, neutrophil dysfunction, and caspase recruitment domain 9 (CARD9) deficiency]. Noninfectious granulomas may be the presenting symptom in innate immunity defects [such as chronic granulomatous disease (CGD) or in predominantly humoral immunodeficiencies such as common variable immunodeficiency], as well as ataxia teleangiectasia or rare recombination-activating gene-deficient cases. Summary The skin is important in the diagnosis of PIDs. In particular eczematous lesions, erythroderma, noninfectious granuloma, and microbial manifestations may help to direct further diagnostic laboratory analysis.
NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells

NKp46 is a novel triggering receptor expressed by all human NK cells that is involved in natural cytotoxicity. In this study we show that the surface density of NKp46 may vary in different NK cells and that a precise correlation exists between the NKp46 phenotype of NK clones and their natural cytotoxicity against HLA‐class I‐unprotected allogeneic or xenogeneic cells. Thus, NKp46bright clones efficiently lysed human and murine tumor cells while NKp46dull clones were poorly cytolytic against both types of target cells. We also show that the NKp46 phenotype of NK clones correlates with their ability to lyse HLA‐class I‐unprotected autologous cells. Finally, NKp46 was found to be deeply involved in the natural cytotoxicity mediated by freshly derived NK cells. This was indicated both by the inhibition of cytolysis after monoclonal antibody‐mediated masking of NKp46 and by the correlation existing between the natural cytotoxicity of fresh NK cells derived from different donors and their NKp46 phenotype. In conclusion, these studies strongly support the concept that NKp46 plays a central role in the physiological triggering of NK cells and, as a consequence (in concert with killer inhibitory receptors), in the NK‐mediated clearance of abnormal cells expressing inadequate amounts of HLA‐class I molecules.
Serverless protocols for inventory and tracking with a UAV

It is widely acknowledged that the proliferation of Unmanned Aerial Vehicles (UAVs) may lead to serious concerns regarding avionics safety, particularly when end-users are not adhering to air safety regulations. There are, however, domains in which UAVs may help to increase the safety of airplanes and the management of flights and airport resources that often require substantial human resources. For instance, Paris Charles de Gaulle airport (CDG) has more than 7,000 staff and supports 30,000 direct jobs for more than 60 million passengers per year (as of 2016). Indeed, these new systems can be used beneficially for several purposes, even in sensitive areas like airports. Among the considered applications are those that suggest using UAVs to enhance safety of on-ground airplanes; for instance, by collecting (once the aircraft has landed) data recorded by different systems during the flight (like the sensors of the Aircraft Data Networks — ADN) or by examining the state of airplane structure. In this paper, our proposal is to use UAVs, under the control of the airport authorities, to inventory and track various tagged assets, such as luggage, supplies required for the flights, and maintenance tools. The aim of our proposal is to make airport management systems more efficient for operations requiring inventory and tracking, along with increasing safety (sensitive assets such as refueling tanks, or sensitive pieces of luggage can be tracked), thus raising financial profit.
Foscarnet Salvage Therapy for Patients with Late-Stage HIV Disease and Multiple Drug Resistance

Objective To evaluate the efficacy of foscarnet on HIV infection in patients with late-stage HIV disease and multiple drug resistance. Methods Three drugs experienced patients with plasma viral load (pVL) >50,000 copies/ml and CD4+ T-cell counts <100/mm3 were eligible for this open-label, single-arm, add-on pilot study. Foscarnet induction therapy consisted of 5 g intravenously twice daily for 6 weeks, in addition to a stable antiretroviral regimen. Patients with at least 1 log10 decrease in pVL at week 6 (W6), were given foscarnet 5 g intravenously twice daily on two consecutive days each week. Primary endpoint was the virological response rate at W6. Results Eleven patients were enrolled with a median baseline pVL at 5.16 log10 copies/ml, median CD4+ T-cell count at 10/mm3 and median number of mutations of 9, 2 and 12 associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs and protease inhibitors, respectively. One patient discontinued foscarnet at W2 because of renal toxicity. In an intent-to-treat analysis, the median change in pVL from baseline was -1.99 log10 copies/ml at W2 and -1.79 log10 copies/ml at W6. Eight out of eleven patients had a fall in pVL of at least 1 log10 at W6, and six started maintenance therapy. The median fall in pVL after 12 weeks of maintenance therapy was -0.85 log10 copies/ml in the four patients who reached W12, and the median increase of CD4+ T-cell count was 60/mm3. Conclusion In patients with HIV mutations conferring resistance to all antiretroviral drug classes, foscarnet markedly reduced plasma HIV load and improved immunological status.
Estudio de causalidad entre la inversión extranjera directa y la solicitud de patentes por mexicanos como mecanismo de la derrama tecnológica (Study of causality between foreign direct investment and patent application by Mexicans, as a mechanism of technology spill)

El presente documento analiza la relacion entre la Inversion Extranjera Directa (IED) y la solicitud de patentes (P) en Mexico, como mecanismo de derrama tecnologica hacia el pais receptor. Parte de un marco teorico contemporaneo que relaciona ambas variables e identifica la conveniencia de empresas multinacionales de gestionar o resguardar el conocimiento. Posteriormente mediante la causalidad de Granger, se muestra que no existe en nuestro pais una causalidad bidireccional ni un idireccional entre ambas variables. Clasificacion JEL: O32, O33. Abstract This paper analyzes the relationship between Foreign Direct Investment (FDI) and the application of patents (P) in Mexico as a mechanism of technological spill to the host country. Part of a contemporary and theoretical framework that relates both variables and identifies the convenience of multinational companies to manage or safeguard knowledge. Subsequently through the Granger causality, it is shown there is no bidirectional or unidirectional causality in our country between both variables.
Accurate architecture-level thermal analysis methods for MPSoC with consideration for leakage power dependence on temperature

Efficient thermal analysis plays a key role in the temperature-aware floorplan design for MultiProcessor System-on-Chip (MPSoC) and Dynamic Power& Temperature Management (DPTM). This work adopts the bottom-up modeling method to study architecture-level MPSoC thermal analysis. First, it extracts relative thermal resistance between functional modules with HotSpot software. Then, based on these parameters, this work further proposes three analysis methods with different accuracy and algorithm complexity: Block-level Temperature Analysis Method (BloTAM), Core-level Temperature Analysis Method (CorTAM) and Block-Improving Core Temperature Analysis Method (BiCorTAM). Experiments show that BloTAM and BiCorTAM can substantially reduce the time for MPSoC thermal analysis with the high accuracy. Compared with HotSpot, both methods achieve 50+ times speedup in analysis with average temperature error as low as 3%. They are ideal architecture-level thermal analysis method for MPSoCs.