Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrastructural Evidence of Exosome Secretion by Progenitor Cells in Adult Mouse Myocardium and Adult Human Cardiospheres

The demonstration of beneficial effects of cell therapy despite the persistence of only few transplanted cells in vivo suggests secreted factors may be the active component of this treatment. This so-called paracrine hypothesis is supported by observations that culture media conditioned by progenitor cells contain growth factors that mediate proangiogenic and cytoprotective effects. Cardiac progenitor cells in semi-suspension culture form spherical clusters (cardiospheres) that deliver paracrine signals to neighboring cells. A key component of paracrine secretion is exosomes, membrane vesicles that are stored intracellularly in endosomal compartments and are secreted when these structures fuse with the cell plasma membrane. Exosomes have been identified as the active component of proangiogenic effects of bone marrow CD34+ stem cells in mice and the regenerative effects of embryonic mesenchymal stem cells in infarcted hearts in pigs and mice. Here, we provide electron microscopic evidence of exosome secretion by progenitor cells in mouse myocardium and human cardiospheres. Exosomes are emerging as an attractive vector of paracrine signals delivered by progenitor cells. They can be stored as an “off-the-shelf” product. As such, exosomes have the potential for circumventing many of the limitations of viable cells for therapeutic applications in regenerative medicine.
The fight against stigma: An overview of stigma-reduction strategies and interventions

Abstract In many health conditions, people are severely affected by health-related stigma and discrimination. A literature review was conducted to identify stigma-reduction strategies and interventions in the field of HIV/AIDS, mental illness, leprosy, TB and epilepsy. The review identified several levels at which interventions and strategies are being implemented. These are the intrapersonal, interpersonal, organizational/institutional, community and governmental/structural level. Although a lot of work has been carried out on stigma and stigma reduction, far less work has been done on assessing the effectiveness of stigma-reduction strategies. The effective strategies identified mainly concentrated on the individual and the community level. In order to reduce health-related stigma and discrimination significantly, single-level and single-target group approaches are not enough. What is required is a patient-centred approach, which starts with interventions targeting the intrapersonal level, to empower affected persons to assist in the development and implementation of stigma-reduction programmes at other levels.
Peptide cotransmitter potentiates calcium channel activity in crayfish skeletal muscle

The activity of 2 types of Ca2+ channels (38 and 14 pS in 137 mM Ba2+) in the plasma membrane of the crayfish tonic flexor muscle is modulated by the peptide proctolin. This peptide serves as a cotransmitter in 3 of the 5 excitatory tonic flexor motoneurons and greatly enhances tension after depolarization by the conventional neurotransmitter. Proctolin alone has no effect on these channels, but renders them capable of sustained activity following depolarization. After depolarization induces activity, 5 x 10(-9) M proctolin increases the open probability of the larger channel up to 50-fold due to a marked decrease in the mean channel closed time. There is also at least a 4- fold increase in the percentage of patches with active channels for the large channel and a 2-fold increase for the small channel. Proctolin modulation appears to occur via an intracellular messenger, possibly cAMP. The peptide's effect on channel activity is dose dependent in a manner that parallels its effect on tension. These results indicate that the activation of these channels and the resulting influx of Ca2+ into the muscle fiber play a role in the potentiation of tension in this muscle.
The goat domestication process inferred from large-scale mitochondrial DNA analysis of wild and domestic individuals

The emergence of farming during the Neolithic transition, including the domestication of livestock, was a critical point in the evolution of human kind. The goat (Capra hircus) was one of the first domesticated ungulates. In this study, we compared the genetic diversity of domestic goats to that of the modern representatives of their wild ancestor, the bezoar, by analyzing 473 samples collected over the whole distribution range of the latter species. This partly confirms and significantly clarifies the goat domestication scenario already proposed by archaeological evidence. All of the mitochondrial DNA haplogroups found in current domestic goats have also been found in the bezoar. The geographic distribution of these haplogroups in the wild ancestor allowed the localization of the main domestication centers. We found no haplotype that could have been domesticated in the eastern half of the Iranian Plateau, nor further to the east. A signature of population expansion in bezoars of the C haplogroup suggests an early domestication center on the Central Iranian Plateau (Yazd and Kerman Provinces) and in the Southern Zagros (Fars Province), possibly corresponding to the management of wild flocks. However, the contribution of this center to the current domestic goat population is rather low (1.4%). We also found a second domestication center covering a large area in Eastern Anatolia, and possibly in Northern and Central Zagros. This last domestication center is the likely origin of almost all domestic goats today. This finding is consistent with archaeological data identifying Eastern Anatolia as an important domestication center.
Tackling perinatal loss, a participatory action research approach: research protocol.

AIM The aim of this study was to promote changes to improve the care provided to parents who have experienced a perinatal loss through participatory action research. BACKGROUND The birth of a child is a joyful event for most families, however, unfortunately some pregnancies end in loss. Perinatal loss creates a heavy emotional impact not only on parents but also on health professionals, where in most cases there is an evident lack of skills, strategies and resources to cope with these kinds of situations. DESIGN Participatory action research is the methodology proposed to achieve the purpose of this study. METHODS Participatory action research consists of five stages: outreach and awareness, induction, interaction, implementation and systematization. The working group will include professionals from the Mother and Child Unit for patients at a tertiary level public hospital in Spain. The duration of the study will be 3 years since the approval of the protocol in January 2011. The qualitative techniques used will include group dynamics such as the SWOT analysis the nominal group technique, focus groups and brainstorming, among others that will be recorded and transcribed, generating reports throughout the evolution of the group sessions and about the consensus reached. Content analysis will be conducted on the field diaries kept by the participants and researchers. This project has been funded by the Andalusian Regional Ministry of Health. DISCUSSION Participatory action research is a methodological strategy that allows changes in clinical practice to conduct a comprehensive transformative action in the care process for perinatal loss.
On the optimization of heterogeneous MDDs

This paper proposes minimization algorithms for the memory size and the average path length (APL) of heterogeneous multivalued decision diagrams (MDDs). In a heterogeneous MDD, each multivalued variable can take different domains. To represent a binary logic function using a heterogeneous MDD, we partition the binary variables into groups with different numbers of binary variables and treat the groups as multivalued variables. Since memory size and APL of a heterogeneous MDD depend on the partition of binary variables as well as the ordering of binary variables, the memory size and the APL of a heterogeneous MDD can be minimized by considering both orderings and partitions of binary variables. The experimental results show that heterogeneous MDDs can represent logic functions with smaller memory sizes than free binary decision diagrams (FBDDs) and smaller APLs than reduced ordered BDDs (ROBDDs); the APLs of heterogeneous MDDs can be reduced by half of the ROBDDs without increasing memory size; and heterogeneous MDDs have smaller area-time complexities than MDD(k)s.
Diagnostic test accuracy: methods for systematic review and meta-analysis

ABSTRACTSystematic reviews are carried out to provide an answer to a clinical question based on all available evidence (published and unpublished), to critically appraise the quality of studies, and account for and explain variations between the results of studies. The Joanna Briggs Institute specializes in providing methodological guidance for the conduct of systematic reviews and has developed methods and guidance for reviewers conducting systematic reviews of studies of diagnostic test accuracy. Diagnostic tests are used to identify the presence or absence of a condition for the purpose of developing an appropriate treatment plan. Owing to demands for improvements in speed, cost, ease of performance, patient safety, and accuracy, new diagnostic tests are continuously developed, and there are often several tests available for the diagnosis of a particular condition. In order to provide the evidence necessary for clinicians and other healthcare professionals to make informed decisions regarding the optimum test to use, primary studies need to be carried out on the accuracy of diagnostic tests and the results of these studies synthesized through systematic review. The Joanna Briggs Institute and its international collaboration have updated, revised, and developed new guidance for systematic reviews, including systematic reviews of diagnostic test accuracy. This methodological article summarizes that guidance and provides detailed advice on the effective conduct of systematic reviews of diagnostic test accuracy.
Crossing the taxonomic divide: conflict and its resolution in societies of reproductively totipotent individuals

Reproduction in groups may be unequal, with one or a few individuals monopolizing direct reproduction assisted by nonbreeding helpers. In social insects this has frequently led to a pronounced queen‐worker dichotomy and a loss of reproductive totipotency among workers. However, in some invertebrate and all vertebrate societies, all or most individuals remain reproductively totipotent. In these groups, conflicts of interest over reproduction are potentially greatest. Here, we synthesize previous analyses of reproductive conflict, aggression and breeder replacement in haplodiploid societies of totipotent individuals and extend them to cover diploid (vertebrate) examples. We test predictions arising from this approach using the best‐studied invertebrate (Dinoponera queenless ants) and vertebrate (naked mole‐rat, Heterocephalus glaber) examples, although in principle our analysis applies to all similar groups. We find that premature replacement of a parent breeder by nonbreeders (overthrow) is rare. Dominant coercive control of nonbreeders by the breeder is often unnecessary and honest signalling of breeder vitality can maintain group stability and resolve conflicts over reproduction. We hope that by providing an explicit transfer of social theory between ants and naked mole‐rats we will stimulate further cross‐taxonomic studies that will greatly broaden our understanding of sociality.
A novel family 9 endoglucanase gene (celD), whose product cleaves substrates mainly to glucose, and its adjacent upstream homolog (celE) from Fibrobacter succinogenes S85

Two adjacent, highly homologous endoglucanase genes, celD and celE from Fibrobacter succinogenes S85, which were separated by an AT-rich 223-nucleotide intergenic region were characterized. The celD gene codes for endoglucanase D (EGD), a protein of 668 residues with a molecular mass of 71.7 kDa, while the celE gene encodes endoglucanase E, a protein of 467 amino acids with a molecular mass of 50.7 kDa. Both gene products belong to family 9 of glycosyl hydrolases. EGD displays an array of serine-rich periodic sequences (SRPS) near its C terminus which separate the catalytic domain from a basic terminal domain (BTD) rich in positively charged amino acids. Endoglucanase E has a BTD which is homologous to that of EGD, but it lacks the SRPS and 151 residues present at the N terminus of EGD. The SRPS structures may function as flexible linkers which facilitate interactions between the BTDs and acidic membrane proteins from F. succinogenes S85. The recombinant EGD showed pH and temperature optima of 5.5 and 35 degrees C, respectively. The enzyme cleaved barley-beta-glucan, carboxymethyl cellulose, and acid-swollen cellulose with specific activities of 19.1, 11.5 and 1.7 micromol x min-1 x mg of protein-1, respectively. There was a rapid drop in viscosity during hydrolyses of carboxymethyl cellulose, which is characteristic of an endoglucanase. Glucose was the main hydrolysis product of acid-swollen cellulose. Monospecific polyclonal antibodies against EGD detected the expression of a 68-kDa cellulose-inducible protein corresponding in size to the recombinant EGD in the culture fluid of F. succinogenes S85 and several larger proteins. The celE gene appeared to have little activity when expressed from the beta-galactosidase promoter in pBluescript in Escherichia coli; however, reverse transcriptase PCR analysis with internal primers for the gene revealed that a cellulose-inducible message was made in F. succinogenes, thereby documenting expression of the gene.
A Predictive Display With Force Feedback And Its Application To Remote Manipulation System With Transmission Time Delay

This paper discusses the design of a predictive display system with force feedback and its application to a remote manipulation system with transmission time delay. In the field of telerobotics, it has been found that an operator's performance is enhanced by the ability to obtain the information of remote environment with high fidelity. However, the transmission time delay produces one of the most crucial problems in space telerobotics. It is not practical to feed back force data continuously to the operator's hands because the delayed feedback may cause instability. In order to improve the manipulability, a system that presents the information of environments pre- cisely to the operator without time delay is re- quired. In this paper, a method for virtual genera- tion of the constraining forces in the model world is proposed. As a first step, a simple robot and its environment model are constructed. It is assumed that the environment model consists of several polyhedral objects without friction on the surface and that the slave robot is a point object. The spring effects are assumed at the surface of the ob- jects and then the constraining forces are produced in the direction normal to the surface, and those magnitudes are in proportion to the amount of the penetrations. A predictive display remote manipu- lation system with a force generation function is implemented. Some experiments were performed to confirm the effectiveness of the proposed method.
Is there a Relationship between Bone Morphology and Injured Ligament on Imaging Studies and Laxity on Ankle Stress Radiographs?

Abstract This study aimed to investigate the relationship between bone morphology and injured ligaments on imaging studies and laxity on ankle stress radiographs in patients with lateral ankle instability. In total, 115 patients who had undergone ankle MRI, ankle radiography, and stress radiography were included. Distal tibial articular surface angle, bimalleolar tilt, medial and lateral malleolar relative length, medial malleolar slip angle, anterior inclination of the tibia, and fibular position were measured on ankle radiographs. Tibiotalar tilt angle and anterior translation of the talus were measured on ankle stress radiographs. Degree of ligament injury was evaluated on ankle MRIs. Multiple regression analysis was performed using the following independent variables: age, sex, and factors significantly associated with ankle stress view on univariate linear regression analysis. Age (p=0.041), sex (p=0.014), degree of anterior talofibular ligament injury (p<0.001), and bimalleolar tilt (p=0.016) were correlated with tibiotalar tilt angle. Fibular position and degree of posterior talofibular ligament injury were factors significantly related to anterior translation of the talus. Differences in patient characteristics might predispose ankle stress radiograph results. Comparison of both ankles on stress radiographs is superior to applying fixed numerical values to the injured side in order to reduce the influence of patient factors.
Complexes between C1-inhibitor, kallikrein, high molecular weight kininogen, plasma thromboplastin antecedent, and plasmin in normal human plasma and hereditary angioneurotic edema plasmas containing dysmorphic C1-inhibitors: role of cold activation.

When normal human plasma was adsorbed at 4°C with monospecific antibody globulins to human C -INH inhibitor (anti-C -INH), CC -INH was removed from the plasma in proportion to the amount of antibody globulins used. Clotting activity attributable to Fletcher factor (prekallikrein), high molecular weight kininogen (HMW-K), and irregularly, plasma thromboplastin antecedent (PTA, factor XI) were also removed by these antibody globulins, and the removal of PTA and HMW-K was dependent on the presence of the prekallikrein. Plasma kallikrein and HMW-K antigen concentrations were also reduced by adsorption with anti-CC -INH. Neither prekallikrein, high molecular weight kininogen, nor PTA was removed from plasma of persons with hereditary angioneurotic edemacontaining any of three different types of dysmorphic CC -INH proteins. Hageman factor was not removed from normal plasma by this immune adsorption procedure, even after the plasma was activated with glass or ellagic acid, but it was required for immune depletion of kallikrein and HMW-K, for neither was reduced by adsorption of Hageman trait plasma. In the presence of Hageman factor, prekallikrein was apparently activated at 4°C, the kallikrein formed complexes with CC -INH, and this complex was then removed by the anti-C -INH. Plasminogen was not removed from normal plasma by adsorption with anti-CC -INH globulins, but plasmin was removed once generated by treating plasma with streptokinase. Similarly, after exposure of hereditary angioneurotic edema plasmas containing dysmorphic CC -INH proteins to streptokinase, the plasminogen concentration was reduced and some plasmin was removed by the anti-C -INH.
Lower Bounds for the Minimax Risk Using $f$-Divergences, and Applications

Lower bounds involving f-divergences between the underlying probability measures are proved for the minimax risk in estimation problems. Our proofs just use simple convexity facts. Special cases and straightforward corollaries of our bounds include well known inequalities for establishing minimax lower bounds such as Fano's inequality, Pinsker's inequality and inequalities based on global entropy conditions. Two applications are provided: a new minimax lower bound for the reconstruction of convex bodies from noisy support function measurements and a different proof of a recent minimax lower bound for the estimation of a covariance matrix.
The Acetazolamide Challenge: Techniques and Applications in the Evaluation of Chronic Cerebral Ischemia

SUMMARY: The acetazolamide (ACZ) challenge test is a useful clinical tool and a reliable predictor of critically reduced perfusion. In patients with chronic steno-occlusive disease, the ability to maintain normal cerebral blood flow by reducing vascular resistance secondary to autoregulatory vasodilation is compromised. Identification of the presence and degree of autoregulatory vasodilation (reflecting the cerebrovascular reserve) is a significant prognostic factor in patients with chronic cerebrovascular disease. The pharmacologic challenge of a vasodilatory stimulus such as ACZ can also be used to optimize the treatment strategies for these patients. The pathophysiology, methods, and clinical applications of the ACZ challenge test are discussed in this article.
A C-Terminal Acidic Domain Regulates Degradation of the Transcriptional Coactivator Bob1

ABSTRACT Bob1 (Obf-1 or OCA-B) is a 34-kDa transcriptional coactivator encoded by the Pou2af1 gene that is essential for normal B-cell development and immune responses in mice. During lymphocyte activation, Bob1 protein levels dramatically increase independently of mRNA levels, suggesting that the stability of Bob1 is regulated. We used a fluorescent protein-based reporter system to analyze protein stability in response to genetic and physiological perturbations and show that, while Bob1 degradation is proteasome mediated, it does not require ubiquitination of Bob1. Furthermore, degradation of Bob1 in B cells appears to be largely independent of the E3 ubiquitin ligase Siah. We propose a novel mechanism of Bob1 turnover in B cells, whereby an acidic region in the C terminus of Bob1 regulates the activity of degron signals elsewhere in the protein. Changes that make the C terminus more acidic, including tyrosine phosphorylation-mimetic mutations, stabilize the instable murine Bob1 protein, indicating that B cells may regulate Bob1 stability and activity via signaling pathways. Finally, we show that expressing a stable Bob1 mutant in B cells suppresses cell proliferation and induces changes in surface marker expression commonly seen during B-cell differentiation.
Acoustic observation for English speakers' perception of a three-way laryngeal contrast of Korean stops

While the two-way voicing contrast of English stops can be distinguished by VOT alone, the three-way laryngeal contrast of Korean stops requires additional acoustic parameter, f0, together with VOT for its realization (Chang, 2010; M. Kim, 2004). The distinct acoustic characteristics of the Korean and English stops may create difficulties in English speakers’ discrimination of the non-native Korean contrasts. To confirm this hypothesis, the current study examines English speakers’ discrimination of a three-way laryngeal distinction of Korean stops /p t k/ in word-initial position of disyllabic minimal pairs. The result supports the hypothetical link between acoustic patterns and perceptual discrimination to a large extent by displaying a relatively low correct discrimination level on the lenis fortis contrast. This leads to a conclusion that f0 is as important as VOT for non-native listeners to fully perceive the three-way contrast of Korean stops.
Spreading of Thermonuclear Flames on the Neutron Star in SAX J1808.4-3658: An Observational Tool

We analyze archival Rossi X-Ray Timing Explorer (RXTE) proportional counter array (PCA) data of thermonuclear X-ray bursts from the 2002 outburst of the accreting millisecond pulsar SAX J1808.4-3658. We present evidence of nonmonotonic variations of oscillation frequency during burst rise, and correlations among the time evolution of the oscillation frequency, amplitude, and the inferred burning region area. We also find that the amplitude and burning region area evolutions are consistent with thermonuclear flames spreading on the neutron star surface. Based on this discussion, we infer that for the 2002 October 15 thermonuclear burst, the ignition likely occurred in the midlatitudes, the burning region took ~0.2 s to nearly encircle the equatorial region of the neutron star, and after that the lower amplitude oscillation originated from the remaining asymmetry of the burning front in the same hemisphere where the burst ignited. Our observational findings and theoretical discussion indicate that studies of the evolution of burst oscillation properties during burst rise can provide a powerful tool to understand thermonuclear flame spreading on neutron star surfaces under extreme physical conditions.