Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of the hematopoietic stem cell lifecycle by the endothelial niche.

PURPOSE OF REVIEW Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions. RECENT FINDINGS Studies employing genetic vascular models have unequivocally confirmed that ECs provide the essential instructive cues for HSC emergence during embryonic development as well as adult HSC maintenance during homeostasis and regeneration. Aging of ECs may impair their ability to maintain HSC function contributing to the development of aging-associated hematopoietic deficiencies. These findings have opened up new avenues to explore the therapeutic application of ECs. ECs can be adapted to serve as an instructive platform to expand bona fide HSCs and also utilized as a cellular therapy to promote regeneration of the hematopoietic system following myelosuppressive and myeloablative injuries. SUMMARY ECs provide a fertile niche for maintenance of functional HSCs throughout their lifecycle. An improved understanding of the EC-HSC cross-talk will pave the way for development of EC-directed strategies for improving HSC function during aging.
Epidemiología de las sibilancias en el primer año de vida: Estudio multicéntrico

[ES] Con la siguiente tesis se pretende describir la prevalencia y gravedad de las sibilancias y SR en los lactantes durante el primer ano de vida, procedentes de diferentes Centros de Salud del area de Salamanca y hacer comparacion entre ellos y entre los resultados obtenidos en otras areas geograficas espanolas. Tambien dar a conocer los factores de riesgo que puedan asociarse a las sibilancias, con especial atencion a la historia familiar y personal y factores ambientales considerados como de riesgo de asma en edades posteriores. Ademas se intenta proporcionar un marco para una posterior investigacion etiologica en relacion a los factores que afectan a estas enfermedades, de tipo genetico, de estilo de vida, de ambiente y de cuidados medicos, y asi obtener una medicion basal para poder valorar la tendencia futura en la prevalencia y gravedad de esta patologia. Finalmente se quiere detectar factores de riesgo sobre los que fuera posible actuar para variar la evolucion de las sibilancias recurrentes en los primeros meses de vida.
Knee kinematics and joint moments during gait following anterior cruciate ligament reconstruction: a systematic review and meta-analysis

Background Abnormal gait after anterior cruciate ligament reconstruction (ACLR) may contribute to development and/or progression of knee osteoarthritis. Objective To conduct a systematic review and meta-analysis of knee kinematics and joint moments during walking after ACLR. Methods We searched seven electronic databases and reference lists of relevant papers, for cross-sectional, human-based observational studies comparing knee joint kinematics and moments during level walking in individuals with ACLR, with the uninjured contralateral knee or healthy individuals as a control. Two independent reviewers appraised methodological quality (modified Downs and Black scale). Where possible, data were pooled by time post-ACLR (RevMan), otherwise narrative synthesis was undertaken. Results Thirty-four studies were included. Meta-analysis revealed significant sagittal plane deficits in ACLR knees. We found greater knee flexion angles (standardised mean difference: 1.06; 95% CI 0.39 to 1.74) and joint moments (1.61; 0.87 to 2.35) <6 months post-ACLR, compared to healthy controls. However, lower peak knee flexion angles were identified 1–3 years (−2.21; −3.16 to −1.26) and ≥3 years post-ACLR (−1.38, −2.14 to −0.62), and lower knee flexion moment 6–12 months post-ACLR (−0.76; −1.40 to −0.12). Pooled data provided strong evidence of no difference in peak knee adduction moment >3 years after ACLR (vs healthy controls) (0.09; −0.63 to 0.81). No transverse plane conclusions could be drawn. Conclusions Sagittal plane biomechanics, rather than the knee adduction moment, appear to be more relevant post-ACLR. Better understanding of sagittal plane biomechanics is necessary for optimal post-operative recovery, and to potentially prevent early onset and progression of knee OA after ACLR. Trial registration number PROSPERO systematic review protocol registration number CRD4201400882 2.
Deletion of Smgpi1 encoding a GPI‐anchored protein suppresses sterility of the STRIPAK mutant ΔSmmob3 in the filamentous ascomycete Sordaria macrospora

The striatin interacting phosphatase and kinase (STRIPAK) complex, which is composed of striatin, protein phosphatase PP2A and kinases, is required for fruiting‐body development and cell fusion in the filamentous ascomycete Sordaria macrospora. Here, we report on the interplay of the glycosylphosphatidylinositol (GPI)‐anchored protein SmGPI1 with the kinase activator SmMOB3, a core component of human and fungal STRIPAK complexes. SmGPI1 is conserved among filamentous ascomycetes and was first identified in a yeast two‐hybrid screen using SmMOB3 as bait. The physical interaction of SmMOB3 and SmGPI1 was verified by co‐immunoprecipitation. In vivo localization and differential centrifugation revealed that SmGPI1 is predominantly secreted and attached to the cell wall but is also associated with mitochondria and appears to be a dual‐targeted protein. Deletion of Smgpi1 led to an increased number of fruiting bodies that were normally shaped but reduced in size. In addition, Smmob3 and Smgpi1 genetically interact. In the sterile ΔSmmob3 background deletion of Smgpi1 restores fertility, vegetative growth as well as hyphal‐fusion defects. The suppression effect was specific for the ΔSmmob3 mutant as deletion of Smgpi1 in other STRIPAK mutants does not restore fertility.
Compiler and Runtime Supports for Efficient and Scalable Big Data Systems Research Statement

Big Data analytics applications such as social network analysis and web analysis have revolutionized modern computing. The processing demand posed by an unprecedented amount of data challenges both industrial practitioners and academia researchers to design and implement highly efficient and scalable system infrastructures. Unfortunately, Big Data processing is fundamentally limited by memory inefficiencies inherent with the underlying programming languages. While offering several invaluable benefits, a managed runtime comes with time and space overheads. In large-scale systems, the memory management cost can be easily magnified and become the critical performance bottleneck. Throughout my Ph.D., I have designed and developed a series of system optimizations to enable scalable Big Data processing including a new programming model, and several novel compiler and runtime supports. In the future, I plan to continue addressing the low-performance issue in data-intensive systems by developing practical solutions across the whole software stack, spanning from the processing model to language extensions.
Census of brown lemurs (Eulemur fulvus sspp.) in southeastern Madagascar: Methods‐testing and conservation implications

Four forest areas were censused in southeastern Madagascar from June–August 1995 to estimate local population densities and habitat conditions for two threatened subspecies of brown lemur (Eulemur fulvus collaris and Eulemur fulvus albocollaris). Survey transects varied in length (1–3.5 km) and in surveillance frequency (three to seven times). Additional test surveys were conducted at the Parc National de Ranomafana to compare transect methods in an area with known population densities of Eulemur fulvus. Based on these tests, we demonstrate that the use of existing trails for transects can result in a close estimate of local population size, although more replications and longer transects increase precision. Results from regional surveys indicate considerably smaller population densities for E. f. albocollaris (0.086 animals/ha). In contrast, E. f. collaris densities were relatively high (.107 animals/ha) at Midongy‐Sud. We also noted variation among sites in the density of lianas, which was positively correlated with local population density (a possible indication of habitat degradation). More generally, habitats in E. f. albocollaris's range suffered from fragmentation, reduction in forest area, logging, and potentially greater hunting pressure. Based on these results, it is apparent that more immediate steps are necessary to preserve E. f. albocollaris populations and habitats. Am. J. Primatol. 47:51–60, 1999. © 1999 Wiley‐Liss, Inc.
Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

N. Girard1, E. Ruffini2, A. Marx3, C. Faivre-Finn4 & S. Peters5, on behalf of the ESMO Guidelines Committee* Department of Respiratory Medicine, Expert Centre for Thymic Malignancies, Reference Centre for Orphan Pulmonary Diseases, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France; Department of Thoracic Surgery, University of Torino, Turin, Italy; Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany; Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK; Department of Medical Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
Relational Sustainability: Environments for Long-term Critical Care Patients

Patients undergoing bone marrow transplant, using spinal cord services, and with traumatic brain injury represent a relatively new patient type, requiring both intense care and long-term care in the same facility. As medical advances allow these patients the opportunity to recover from their critical illnesses or injuries, designers and caregivers must give increased attention to the long-term critical care environment. Designing for this type of care requires an understanding of new technologies and the potential for the built environment to address the wide range of physical, sensory, and psychological issues long-term inpatients face. Recent work by SmithGroupJJR has provided valuable insights into the ways in which lighting, patient room and unit layouts, spatial volumes, and other design elements can contribute to the recovery of patients who must spend weeks or months in a critical care environment. This knowledge was gained through an approach that allows design professionals to immerse themselves in a health care institution's values, culture, and work processes. By mapping both operational flow and patients' experiences, project teams can develop design solutions that sustain the well-being of higher-acuity patients and their family members and caregivers.
Deconstructing mammalian thermoregulation

Several recent ground-breaking papers address the deconstruction of neural circuits that regulate mammalian thermoregulation (1⇓–3), including “A hypothalamic circuit that controls body temperature,” by Zhao et al. (3) from Wei Shen’s new laboratory at ShanghaiTech University, recently published in PNAS. In this study, Zhao et al. define neural circuit mechanisms that are novel and critically relevant for mammalian thermoregulation. Thermoregulation is essential in all organisms, an evolutionary conditio sine qua non . In mammals and other warm-blooded animals, homeothermy became an essential physiologic feature during evolution. Homeothermy, the physiologic capability to maintain a constant core body temperature with minimal deviation from the set point, provided a critical survival advantage to mammalian and avian phyla because it brought about a thermally equilibrated internal environment for cells and organs. This in turn rendered nutrition, metabolism, and excretion more robust and efficient, and permitted more precise and powerful functioning of excitable cells in the nervous system, as well as for contractile cells in heart, muscle, and smooth muscle, and evolutionary honing of an immune-defense and wound-healing system. This change led to animals being more competitive to defend against external stress and at the same time more efficient at procreation. Thermal homeostasis coevolved with other vital homeostatic systems (4) and thermoregulation and homeothermy represent primordial–physiologic functions that have long aroused the interest of physiologists and bio-medical researchers (5). However, ground-breaking progress toward elucidation of molecular and neural-circuit mechanisms accounting for thermoregulation and homeothermy has, until recently, been elusive. As such, significant nonincremental progress toward elucidation of neural circuit mechanisms of mammalian thermoregulation, recently provided in the paper by Zhao et al., represents an important milestone (3). In this study (3), using cutting-edge mouse methodology to untangle neural circuitry that regulates core body temperature, Zhao et al. show that: ( i ) GABAergic … [↵][1]1Email: wolfgang{at}neuro.duke. edu. [1]: #xref-corresp-1-1
Transport proteins (carriers) of mitochondria

Mitochondria are subcellular structures essential to the aerobic eukaryotic cell. Their role extends much beyond their basic reactions of oxidative phosphorylation. It encompasses the steps critical for cellular metabolic pathways, for apoptosis, and for other processes such as antiviral signaling. This short review is limited to transport proteins (carriers) that catalyze the transport of metabolites across the inner mitochondrial membrane and thus link metabolic pathway reactions in the cytosol and the mitochondrial matrix. Such transport must minimally affect the electrochemical proton gradient essential for oxidative phosphorylation (chemiosmotic mechanism of oxidative phosphorylation). Many of these transport proteins belong to a family of membrane proteins, and the major part of this review will consider their structures and functions. First studies of these transporters were carried out with intact mitochondria and with inhibitors that appeared transporter‐specific. Such an inhibitor was then utilized in the first purification of one of these transporter proteins. Its substrate‐specificity was then established after functionally active incorporation into liposomes. Questions about copurification of other transporters and thus a definitive identification of transported substrate with the purified protein were resolved definitively only after heterologous expression in bacteria, most generally as inclusion bodies, and followed by reconstitution in liposomes. Site‐specific mutations permitted the identification of amino acids essential to their transport function. These mutagenesis studies then also helped interpret human diseases with mutations in these transport proteins. The high‐resolution structure of a member of this transporter protein family dramatically advanced these studies. It raised new questions because this structure complexed with a high‐affinity inhibitor showed a monomeric protein, while purification and inhibitor stoichiometry studies suggest a functional homodimeric transport protein. Remaining key questions need to address: the homodimeric nature of the transporters, details of their transport mechanism, and the functional identification of many members of this family whose existence has only been suggested from genomic data. © 2008 IUBMB IUBMB Life, 61(1): 40–46, 2009
[Clinical Dementia Rating (CDR)].

Anvendelse: Clinical Dementia Rating (CDR) tilstræber en global vurdering af det kognitive og praktiske funktionsniveau med henblik på at fastsætte graden af demens ved især Alzheimers sygdom. Vurderingen er baseret på relativt detaljerede, separate semistrukturerede interviews med henholdsvis patienten og en informant (pårørende eller plejepersonale). Anvendelse af CDR forudsætter et forudgående træningsprogram af ca. 6-8 timers varighed.
Lesions of the fornix but not the entorhinal or perirhinal cortex interfere with contextual fear conditioning

The effects of entorhinal cortex lesions, combined entorhinal and perirhinal cortex lesions, and fornix lesions on the conditioning of fear responses (freezing) to contextual stimuli were examined using a conditioning procedure known to produce hippocampal-dependent contextual conditioning. Lesions of the entorhinal and or entorhinal plus perirhinal cortex did not disrupt contextual conditioning, but lesions of the fornix did. None of the lesions affected conditioning to an explicit conditioned stimulus. Given that the entorhinal cortex is the primary linkage between the neocortex and the hippocampus and that the fornix is the primary linkage with subcortical structures, subcortical inputs to and outputs of the hippocampus appear to be sufficient to mediate contextual fear conditioning. As a result, the presumption that neocortical information is required for contextual fear conditioning, and perhaps other hippocampal-dependent functions, should be reevaluated.
Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation

Background/Aims: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-β/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. Methods: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes. The condition of cartilage and ossification were measured by a series of staining methods. Subcutaneous injection of mesenchymal stem cells (MSCs) into nude rats was performed. Results: After transfection, compared to the AdGFP group, the corresponding target mRNAs were overexpressed in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups, and overexpression of BMP2 at the mRNA and protein expression was observed in the AdSmad1 and AdCx43 + AdSmad1 groups. The mRNA expressions of aggrecan (ACAN) and collagen type II alpha 1 (Col2a1), the glycosaminoglycan content of the extracellular matrix and the expression of type II collagen, Col2a1, osteopontin (OPN) and osteocalcin (OC) were higher in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups than in the AdGFP group; alkaline phosphatase (ALP) activity and mRNA and protein expressions of Runx2 were also higher in these groups than in the AdGFP group. Heterotopic osteogenesis tests demonstrated evident cartilage differentiation ability in the AdCx43 + AdSmad1 + AdBMP2 groups. In comparison, the AdCx43 + AdSmad1 and AdSmad1 groups exhibited weaker cartilage differentiation abilities. Conclusion: Cx43 and Smad1 promote BMP-induced cartilage differentiation of BMSCs and inhibit osteoblast differentiation, which provide a new strategy for cartilage tissue engineering using exogenous Cx43 and Smad1.
Understanding passenger reaction to dynamic prices in ride-on-demand service

In recent years emerging ride-on-demand services (eg., Uber or Didi) are penetrating into the market of traditional taxi service. In these new services mobile devices are a key enabler: they serve as the intermediary between passengers/drivers and the service provider, tracking the locations and behavior of both passengers and drivers. On the other hand, the use of mobile devices also help us to capture huge amount of data for analysis. Through collaboration with a leading service provider in China, we collect vast amount of accurate data and analyze, in this paper, passenger reaction to dynamic prices in such a service. We consider the analysis as an important step towards making the service more efficient and more attractive to the passengers. We present the patterns of passengers' reaction, and discuss if it is useful to estimate the trip fare for multiple times in order to get a lower price. Our findings pave the way for future study on system optimization and policy considerations.
A potentially preventable case of serious influenza infection in a pregnant patient

The case: A 16-year-old pregnant teenager (gravida 1, para 0) presented at 32 weeks' gestation to a local emergency department in late December 2006 with a 5-day history of increasing dyspnea, low-grade fever, nausea and vomiting. She had taken amoxicillin for 3 days based on a presumptive diagnosis
Advances in the therapy of Alzheimer’s disease: targeting amyloid beta and tau and perspectives for the future

Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer’s disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD.
Control system design of robotic manipulator for testing of shifting system

The paper deals with robotic manipulator for automated testing of shifting system which was developed for automotive industry. Procedure of modelling and control design for hybrid force/position motion control as well as construction of the test stand and experimental results are presented. The proposed control structure with minimum set of feature-based parameters allows rapid online tuning in case of variable testing conditions even by an unskilled operator.
The True Story and Advantages of RNA Phage Capsids as Nanotools

RNA phages are often used as prototypes for modern recombinant virus-like particle (VLP) technologies. Icosahedral RNA phage VLPs can be formed from coat proteins (CPs) and are efficiently produced in bacteria and yeast. Both genetic fusion and chemical coupling have been successfully used for the production of numerous chimeras based on RNA phage VLPs. In this review, we describe advances in RNA phage VLP technology along with the history of the Leviviridae family, including its taxonomical organization, genomic structure, and important role in the development of molecular biology. Comparative 3D structures of different RNA phage VLPs are used to explain the level of VLP tolerance to foreign elements displayed on VLP surfaces. We also summarize data that demonstrate the ability of CPs to tolerate different organic (peptides, oligonucleotides, and carbohydrates) and inorganic (metal ions) compounds either chemically coupled or noncovalently added to the outer and/or inner surfaces of VLPs. Finally, we present lists of nanotechnological RNA phage VLP applications, such as experimental vaccines constructed by genetic fusion and chemical coupling methodologies, nanocontainers for targeted drug delivery, and bioimaging tools.