Miracle-dz/UniFAR-FTUs huggingface dataset:
A Distinct Endosomal Ca2+/Mn2+ Pump Affects Root Growth through the Secretory Process1[C][W][OA]

Ca2+ is required for protein processing, sorting, and secretion in eukaryotic cells, although the particular roles of the transporters involved in the secretory system of plants are obscure. One endomembrane-type Ca-ATPase from Arabidopsis (Arabidopsis thaliana), AtECA3, diverges from AtECA1, AtECA2, and AtECA4 in protein sequence; yet, AtECA3 appears similar in transport activity to the endoplasmic reticulum (ER)-bound AtECA1. Expression of AtECA3 in a yeast (Saccharomyces cerevisiae) mutant defective in its endogenous Ca2+ pumps conferred the ability to grow on Ca2+-depleted medium and tolerance to toxic levels of Mn2+. A green fluorescent protein-tagged AtECA3 was functionally competent and localized to intracellular membranes of yeast, suggesting that Ca2+ and Mn2+ loading into internal compartment(s) enhanced yeast proliferation. In mesophyll protoplasts, AtECA3-green fluorescent protein associated with a subpopulation of endosome/prevacuolar compartments based on partial colocalization with the Ara7 marker. Interestingly, three independent eca3 T-DNA disruption mutants showed severe reduction in root growth normally stimulated by 3 mm Ca2+, indicating that AtECA3 function cannot be replaced by an ER-associated AtECA1. Furthermore, root growth of mutants is sensitive to 50 μm Mn2+, indicating that AtECA3 is also important for the detoxification of excess Mn2+. Curiously, Ateca3 mutant roots produced 65% more apoplastic protein than wild-type roots, as monitored by peroxidase activity, suggesting that the secretory process was altered. Together, these results demonstrate that the role of AtECA3 is distinct from that of the more abundant ER AtECA1. AtECA3 supports Ca2+-stimulated root growth and the detoxification of high Mn2+, possibly through activities mediated by post-Golgi compartments that coordinate membrane traffic and sorting of materials to the vacuole and the cell wall.
Social entrepreneurship in Trujillo, Peru: The case of Nisolo

Abstract This exploratory research examines Nisolo, a social entrepreneurship enterprise based in Trujillo, Peru, where currently its production facility seeks to hire local workers and build the surrounding community. Nisolo produces high-end shoes and tries to distribute its profits to the community of Trujillo. Using a case-study approach, our research intent is to develop a better understanding of this social entrepreneurship enterprise regarding social impact. The research uses a variety of data collection tools, including participatory observation, interviews, and a systematic review of sources consisting of private emails, photographs, videos, and newspaper articles. The findings indicate that Nisolo’s social impact mission positively impacts nearly 400 individuals in the local community. By providing consistent employment, fair wages, health care, livelihood training, and a savings and salary advance program, Nisolo is not only focusing on driving social change, but on creating a sustainable model that highlights potential fashion industry changes.
Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial.

BACKGROUND Depression and anxiety are prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Ketamine has many properties that make it an interesting candidate for rapidly treating depression and anxiety in patients receiving hospice care. To test this hypothesis, a 28-day, open-label, proof-of-concept trial of daily oral ketamine administration was conducted in order to evaluate the tolerability, potential efficacy, and time to potential efficacy in treating depression and anxiety in patients receiving hospice care. METHODS In this open-label study, 14 subjects with symptoms of depression or depression mixed with anxiety warranting psychopharmacological intervention received daily oral doses of ketamine hydrochloride (0.5 mg/kg) over a 28-day period. The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS), which was used to rate overall depression and anxiety symptoms at baseline, and on days 3, 7, 14, 21, and 28. RESULTS Over the 28-day trial there was significant improvement in both depressive symptoms (F5,35=8.03, p=0.002, η(2)=0.534) and symptoms of anxiety (F5,35=14.275, p<0.001, η(2)=0.67) for the eight subjects that completed the trial. One hundred percent of subjects completing the trial responded to ketamine for both anxiety and depression. A significant response in depressive symptoms occurred by day 14 for depression (mean Δ=3.5, d=1.14, 95% CI=1.09-5.9, p=0.01) and day 3 for anxiety (mean Δ=2.4, d=0.67, 95% CI=1.0-3.7, p=0.004). These improvements remained significant through day 28 for both depression (mean Δ=4.0, d=1.34, 95% CI=2.3-5.9, p=0.001) and anxiety (mean Δ=6.09, d=1.34, 95% CI=3.6-8.6, p<0.001). Side effects were rare, the most common being diarrhea, trouble sleeping, and trouble sitting still. CONCLUSIONS Patients who received daily oral ketamine experienced a robust antidepressant and anxiolytic response with few adverse events. The response rate for depression is similar to those found with IV ketamine; however, the time to response is more protracted. The findings of the potential efficacy of oral ketamine for depression and the response of anxiety symptoms are novel. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the efficacy and safety of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care or other subject populations.
β2‐adrenoceptor agonists: current and future direction

Despite the passionate debate over the use of β2‐adrenoceptor agonists in the treatment of airway disorders, these agents are still central in the symptomatic management of asthma and COPD. A variety of β2‐adrenoceptor agonists with long half‐lives, also called ultra long‐acting β2‐adrenoceptor agonists (ultra‐LABAs; indacaterol, olodaterol, vilanterol, carmoterol, LAS100977 and PF‐610355) are currently under development with the hopes of achieving once‐daily dosing. It is likely that the once‐daily dosing of a bronchodilator would be a significant convenience and probably a compliance‐enhancing advantage, leading to improved overall clinical outcomes. As combination therapy with an inhaled corticosteroid (ICS) and a LABA is important for treating patients suffering from asthma, and a combination with an inhaled long‐acting antimuscarinic agent (LAMA) is important for treating COPD patients whose conditions are not sufficiently controlled by monotherapy with a β2‐adrenoceptor agonist, some novel once‐daily combinations of LABAs and ICSs or LAMAs are under development.
Alkaline Phosphatase Knock‐Out Mice Recapitulate the Metabolic and Skeletal Defects of Infantile Hypophosphatasia

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue‐nonspecific isoenzyme of alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization of cartilage and bone matrix. We investigated two independently generated TNSALP gene knock‐out mouse strains as potential models for hypophosphatasia. Homozygous mice (–/–) had < 1% of wild‐type plasma TNSALP activity; heterozygotes had the predicted mean of ∼50%. Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5′‐phosphate are putative natural substrates for TNSALP and all were increased endogenously in the knock‐out mice. Skeletal disease first appeared radiographically at ∼10 days of age and featured worsening rachitic changes, osteopenia, and fracture. Histologic studies revealed developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones. Progressive osteoidosis from defective skeletal matrix mineralization was noted but not associated with features of secondary hyperparathyroidism. Plasma and urine calcium and phosphate levels were unremarkable. Our findings demonstrate that TNSALP knock‐out mice are a good model for the infantile form of hypophosphatasia and provide compelling evidence for an important role for TNSALP in postnatal development and mineralization of the murine skeleton.
Where theory and practice of global health intersect: the developmental history of a Canadian global health initiative

Objective This paper examines the scope of practice of global health, drawing on the practical experience of a global health initiative of the Government of Canada – the Teasdale-Corti Global Health Research Partnership Program. A number of challenges in the practical application of theoretical definitions and understandings of global health are addressed. These challenges are grouped under five areas that form essential characteristics of global health: equity and egalitarian North–South partnerships, interdisciplinary scope, focus on upstream determinants of health, global conceptualization, and global health as an area of both research and practice. Design Information in this paper is based on the results of an external evaluation of the program, which involved analysis of project proposals and technical reports, surveys with grantees and interviews with grantees and program designers, as well as case studies of three projects and a review of relevant literature. Results The philosophy and recent definitions of global health represent a significant and important departure from the international health paradigm. However, the practical applicability of this maturing area of research and practice still faces significant systemic and structural impediments that, if not acknowledged and addressed, will continue to undermine the development of global health as an effective means to addressing health inequities globally and to better understanding, and acting upon, upstream determinants of health toward health for all. Conclusions While it strives to redress global inequities, global health continues to be a construct that is promoted, studied, and dictated mostly by Northern institutions and scholars. Until practical mechanisms are put in place for truly egalitarian partnerships between North and South for both the study and practice of global health, the emerging philosophy of global health cannot be effectively put into practice.
Clinical heterogeneity in lymphoedema-distichiasis withFOXC2 truncating mutations

BACKGROUND Hereditary lymphoedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as lymphoedema of the limbs, with variable age of onset, and extra aberrant growth of eyelashes from the Meibomian gland (distichiasis). Other major reported complications include cardiac defects, cleft palate, and extradural cysts. Photophobia, exotropia, ptosis, congenital ectropion, and congenital cataracts are additional eye findings. Recently, we reported that truncating mutations in the forkhead transcription family member FOXC2resulted in LD in two families. METHODS The clinical findings in seven additional families with LD, including the original family described by Falls and Kertesz, were determined and mutational analyses were performed. RESULTS Distichiasis was the most common clinical feature followed by age dependent lymphoedema. There is a wide variation of associated secondary features including tetralogy of Fallot and cleft palate. The mutational analyses identified truncating mutations in all of the families studied (two nonsense, one deletion, three insertion, and one insertion-deletion), which most likely result in haploinsufficiency ofFOXC2. CONCLUSIONS FOXC2mutations are highly penetrant with variable expressivity which is not explicable by the pattern of mutations.
Failure mechanism and microstructural evolution of Pb-free solder alloys in thermal cycling tests: Effect of solder composition and Sn grain morphology

An improved understanding of how materials and processing affect solder joint microstructure provides insight into how to enhance the fatigue performance of Pb free solder joints. Our previous results showed that differences in solder volume can alter the Sn grain morphology of a near eutectic, SnAgCu Pb-free solder joint and change the lifetime in thermal cycling test. Solder composition and PCB surface finish were also shown to influence Pb free solder joint microstructure and the lifetimes of package interconnects in an ATC test. However, the effects of those parameters on failure mechanisms, particularly recrystallization behavior and crack propagation, are not well understood. Thus, in the current work, Pb-free solder joints were assembled with a range of materials, and the microstructure and reliability of those solder joints were characterized and correlated with the different fabrication parameters. In each case, the failure mechanism was examined. Solder joints of various sizes were assembled onto test boards with Cu-OSP, ENIG or ENEPIG PCB surface finishes using commercial solders alloys with different microalloying elements, such as Ni and Mn. For comparison, Sn3Ag0.5Cu (SAC 305) and eutectic SnPb alloys were included in the sample set. Accelerated thermal cycling testing was performed on the assembled vehicles. Microstructural analysis was performed on as-reflowed, on partially cycled samples, and on samples after electrical failure, to understand the initial microstructure and its evolution during the test. Thus, selected samples were taken out of the thermal cycling chamber at specific intervals of characteristic life (i.e., 20% and 50% of their characteristic life) for microstructural analysis. Polarized light microscopy and electron backscatter diffraction (EBSD) techniques were used to assess the Sn grain morphology of solder joints. The effect of solder composition, Sn grain morphology and PCB surface finish on solder joint microstructure and lifetime was evaluated. The effect of microstructure on the recrystallization behavior and on crack initiation, and thus the failure mechanism of joints in thermal cycling test is reported.
Changes in force and cytosolic Ca2+ concentration after length changes in isolated rat ventricular trabeculae

1 Changes in cytosolic [Ca2+] ([Ca2+]i) were measured in isolated rat trabeculae that had been micro‐injected with fura‐2 salt, in order to investigate the mechanism by which twitch force changes following an alteration of muscle length. 2 A step increase in length of the muscle produced a rapid potentiation of twitch force but not of the Ca2+ transient. The rapid rise of force was unaffected by inhibiting the sarcoplasmic reticulum (SR) with ryanodine and cyclopiazonic acid. 3 The force‐[Ca2+]i relationship of the myofibrils in situ, determined from twitches and tetanic contractions in SR‐inhibited muscles, showed that the rapid rise of force was due primarily to an increase in myofibrillar Ca2+ sensitivity, with a contribution from an increase in the maximum force production of the myofibrils. 4 After stretch of the muscle there was a further, slow increase of twitch force which was due entirely to a slow increase of the Ca2+ transient, since there was no change in the myofibrillar force‐[Ca2+]i relationship. SR inhibition slowed down, but did not alter the magnitude of, the slow force response. 5 During the slow rise of force there was no slow increase of diastolic [Ca2+]i, whether or not the SR was inhibited. The same was true in unstimulated muscles. 6 We conclude that the rapid increase in twitch force after muscle stretch is due to the length‐ dependent properties of the myofibrils. The slow force increase is not explained by length dependence of the myofibrils or the SR, or by a rise in diastolic [Ca2+]i. Evidence from tetani suggests the slow force responses result from increased Ca2+ loading of the cell during the action potential.
A three‐dimensional geometric morphometrics view of the cranial shape variation and population history in the New World

Craniofacial variation in past and present Amerindians has been attributed to the effect of multiple founder events, or to one major migration followed by in situ differentiation and possibly recurrent contacts among Circum‐Arctic groups. Our study aims to: (i) detect morphological differences that may indicate several migrations; (ii) test for the presence of genetic isolation; and (iii) test the correlation between shape data and competing settlement hypotheses by taking into account geography, chronology, climate effects, the presence of genetic isolation and recurrent gene flow.
Cardiovascular and Immune Responses to Acute Psychological Stress in Young and Old Women: A Meta-Analysis

Objective To describe the relationships between cardiovascular and natural killer (NK) cell number changes on acute psychological stress in women. Method Data from eight different studies were analyzed. A total of 128 healthy female subjects, 85 younger (18-45 years) and 43 older (49-87 years), had been subjected to a speech stressor (N = 80) or a mental effort stressor (N = 48), mental arithmetic, or the Stroop test. Correlations between changes in NK cell numbers, systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) were computed. Meta-analysis programs were used to study correlations across studies and to examine whether correlations differed with stressors or age. Results In all studies, significant increases over baseline were observed for each variable. Across studies, the mean weighted r between changes in HR, DBP, and SBP was medium (rw = .25) to large (rw = .64). A medium to large average correlation between HR and NK changes (rw = .37) was observed, whereas average correlations of changes in NK cell numbers with blood pressure changes were small to medium (rw <or=to .23). Correlations between changes in NK cell numbers and cardiovascular variables were homogeneous across studies, whereas mutual correlations between cardiovascular variables were heterogeneous. One moderator variable showed itself: correlations between HR and DBP reactions were larger in studies with older than younger subjects. Conclusion NK cell changes and HR responses induced by acute stress in women are regulated, to some extent, by the same mechanisms. Neither the type of stressor nor age seem to be very important when considering correlations between NK cell and cardiovascular changes. This study integrates information about NK cell and cardiovascular responses in women that can be used as reference material in future studies.
Identification of rhesus macaques with spontaneous endometriosis

Abstract: Rhesus macaques (Macaca mulatta) with endometriosis were identified using reproductive histories, serum levels CA‐125, pelvic ultrasonography, laparoscopy, and histopathology. All animals were evaluated from a large breeding colony and had a history of infertility and/or spontaneous abortions. Laparoscopy and ultrasonography were performed on 40 macaques: 27 macaques from the breeding colony with elevated CA‐125 levels, ten macaques from the breeding colony with normal or low serum CA‐125 levels, and three macaques from another facility with previously diagnosed spontaneous endometriosis. Clinical endometriosis was diagnosed by laparoscopy in 16/37 (43%) macaques from the breeding colony and was confirmed by histologic examination in all animals biopsied. The disease was classified as minimal (40%), mild (25%), moderate (10%), or severe (25%). The most common sites of endometriosis were the serosal surface of the uterus (75%) and the posterior cul‐de‐sac (75%). In this study, CA‐125 levels were useful in identifying animals from the breeding colony with endometriosis. The rhesus macaque provides a valuable animal model to study endometriosis and potentially to assess efficacy of therapeutic agents for this disease condition.
Predictors of early response to infliximab in patients with ulcerative colitis

Background Our objective is to report the outcome of infliximab (IFX) in ulcerative colitis (UC) patients from a single center and to identify predictors of early clinical response. Methods The first 100 UC patients (45 female; median age, 37.9 years) who received IFX at a single center were included. Eighty‐four patients received 5 mg/kg IFX, and 37 patients received a 3‐dose IFX induction at weeks 0, 2, and 6. The Mayo endoscopic subscore, assessed by sigmoidoscopy before inclusion, was 1, 2, and 3 in 5%, 52%, and 43% of patients, respectively. Sixty percent had pancolitis, 63% were on concomitant immunosuppressive therapy, 9% were active smokers, 64% had C‐reactive protein ≥5 mg/dL, and 44% were pANCA+/ASCA−. Five patients received IFX because of severe acute colitis refractory to intravenous corticosteroids. Results Early complete and partial clinical responses were observed in 41% and 24% of patients. Patients with early clinical response were significantly younger than nonresponders (median age, 35.7 versus 41.6 years, P = 0.041). Patients who were pANCA+/ASCA− had a significantly lower early clinical response (55% versus 76%; odds ratio [OR] = 0.40 (0.16–0.99), P = 0.049). Concomitant immunosuppressive therapy and the use of an IFX induction scheme did not influence early clinical response. Only 1 of 5 patients who received IFX for acute steroid‐refractory colitis required colectomy within 2 months. Conclusions IFX is an efficient therapy in UC, as shown by 65% early clinical response. A pANCA+/ASCA− serotype and an older age at first IFX infusion are associated with a suboptimal early clinical response. (Inflamm Bowel Dis 2006)
Perception of Kinematic Characteristics of Tennis Strokes for Anticipating Stroke Type and Direction

The purpose of this study was to determine the sources of visual information used by highly skilled tennis players in anticipating their opponent's shots. In Experiment 1, motion analysis of the strokes showed that the relative motion between the racquet and forearm was different between the ground strokes and lobs, but there were no reliable kinematic differences when shot direction was varied. In Experiment 2, 12 skilled tennis players observed the opponent hitting strokes in a normal video or in a point-light display with different segments occluded. Players' anticipation accuracy was not degraded by the use of the point-light display. Occluding the racquet and forearm significantly reduced the participant's ability to determine the type of stroke produced.
Dry electrodes for monitoring of vital signs in functional textiles

Wearable electronics may become a key element in the future to measure a patient's physiological parameters not only in a clinical environment. This work describes dry electrodes based on conductive rubber, which can be integrated into clothing for monitoring purposes. Characteristic electrical properties like warm up time, skin-electrode impedance and motion artefacts will be discussed.