Molecular Hydrogen Kinematics in Cepheus A

We present the radial velocity structure of the molecular hydrogen outflows associated to the star forming region Cepheus A. This structure is derived from doppler shift of the H_2 v=1-0 S(1) emission line obtained by Fabry-Perot spectroscopy. The East and West regions of emission, called Cep A(E) and Cep A(W), show radial velocities in the range -20 to 0 km/s with respect to the molecular cloud. Cep A(W) shows an increasing velocity with position offset from the core indicating the existence of a possible accelarating machanism. Cep A(E) has an almost constant mean radial velocity of -18 km/s along the region although with a large dispersion in velocity, indicating the possibility of a turbulent outflow. A detailed analysis of the Cep A(E) region shows evidence for the presence of a Mach disk on that outflow. Also, we argue that the presence of a velocity gradient in Cep A(W) is indicative of a C-shock in this region. Following Riera et al. (2003), we analyzed the data using wavelet analysis to study the line width and the central radial velocity distributions. We found that both outflows have complex spatial and velocity structures characteristic of a turbulent flow.Comment: 24 pages, 15 figure

A Multiple System of Radio Sources at the Core of the L723 Multipolar Outflow

We present high angular resolution Very Large Array multi-epoch continuum observations at 3.6 cm and 7 mm towards the core of the L723 multipolar outflow revealing a multiple system of four radio sources suspected to be YSOs in a region of only ~4 arcsecs (1200 AU) in extent. The 3.6 cm observations show that the previously detected source VLA 2 contains a close (separation ~0.29 arcsecs or ~90 AU) radio binary, with components (A and B) along a position angle of ~150 degrees. The northern component (VLA 2A) of this binary system is also detected in the 7 mm observations, with a positive spectral index between 3.6 cm and 7 mm. In addition, the source VLA 2A is associated with extended emission along a position angle of ~115 degrees, that we interpret as outflowing shock-ionized gas that is exciting a system of HH objects with the same position angle. A third, weak 3.6 cm source, VLA 2C, that is detected also at 7 mm, is located ~0.7 arcsecs northeast of VLA 2A, and is possibly associated with the water maser emission in the region. The 7 mm observations reveal the presence of an additional source, VLA 2D, located ~3.5 arcsecs southeast of VLA 2A, and with a 1.35 mm counterpart. All these radio continuum sources have a positive spectral index, compatible with them being YSOs. We also propose that the high velocity CO emission observed in the region could be the superposition of multiple outflows (at least three independent bipolar outflows) excited by the YSOs located at the core, instead of the previous interpretations in terms of only one or two outflows.Comment: Accepted for publication in The Astrophysical Journal (2007 December 6

Reverse-flow anterolateral thigh flap for knee soft-tissue reconstruction: case report

The reconstruction of the injured tissue around the knee is a complex procedure for the plastic and orthopaedic surgeon. The objective is to provide an acceptable function and aesthetic result. Successful wound management includes meticulous debridement, planning and proper execution of the surgical procedure. An 11-year-old male patient with a right patellar fracture using an anterolateral thigh flap with reverse flow to cover the skin defect. For such purposes, the reverse flow anterolateral flap is an effective, trustworthy and well-documented option. The correct obtaining and implantation of the flap reduces the morbidity of the donor site, offers options in size and design, an adequate length of the pedicle and the possible combination with the fascia lata in case it is required. The versatility of the reverse flow anterolateral flap makes it a possible therapeutic alternative in reconstructive surgery since it is aesthetic and functional for the reconstruction of tissue near the knee joint

Characterization of the platelet phenotype caused by a germline RUNX1 Variant in a CRISPR/Cas9-generated murine model

RUNX1-related disorder (RUNX1-RD) is caused by germline variants affecting the RUNX1 gene. This rare, heterogeneous disorder has no specific clinical or laboratory phenotype, making genetic diagnosis necessary. Although international recommendations have been established to classify the pathogenicity of variants, identifying the causative alteration remains a challenge in RUNX1-RD. Murine models may be useful not only for definitively settling the controversy about the pathogenicity of certain RUNX1 variants, but also for elucidating the mechanisms of molecular pathogenesis. Therefore, we developed a knock-in murine model, using the CRISPR/Cas9 system, carrying the RUNX1 p.Leu43Ser variant (mimicking human p.Leu56Ser) to study its pathogenic potential and mechanisms of platelet dysfunction. A total number of 75 mice were generated; 25 per genotype (RUNX1WT/WT, RUNX1WT/L43S, and RUNX1L43S/L43S). Platelet phenotype was assessed by flow cytometry and confocal microscopy. On average, RUNX1L43S/L43S and RUNX1WT/L43S mice had a significantly longer tail-bleeding time than RUNX1WT/WT mice, indicating the variant's involvement in hemostasis. However, only homozygous mice displayed mild thrombocytopenia. RUNX1L43S/L43S and RUNX1WT/L43S displayed impaired agonist-induced spreading and α-granule release, with no differences in δ-granule secretion. Levels of integrin αIIbβ3 activation, fibrinogen binding, and aggregation were significantly lower in platelets from RUNX1L43S/L43S and RUNX1WT/L43S using phorbol 12-myristate 13-acetate (PMA), adenosine diphosphate (ADP), and high thrombin doses. Lower levels of PKC phosphorylation in RUNX1L43S/L43S and RUNX1WT/L43S suggested that the PKC-signaling pathway was impaired. Overall, we demonstrated the deleterious effect of the RUNX1 p.Leu56Ser variant in mice via the impairment of integrin αIIbβ3 activation, aggregation, α-granule secretion, and platelet spreading, mimicking the phenotype associated with RUNX1 variants in the clinical setting.This work was partially supported by grants from Instituto de Salud Carlos III (ISCIII) and Feder (PI17/01311, PI17/01966, and CB15/00055), Fundación Séneca (19873/GERM/15), Gerencia Regional de Salud (GRS 2061A/19 and 1647/A/17), Fundación Mutua Madrileña (FMM, AP172142019), and Sociedad Española de Trombosis y Hemostasia (SETH-FETH; Premio López Borrasca 2019 and Ayuda a Grupos de Trabajo en Patología Hemorrágica 2019). The authors' research on IPDs is conducted in accordance with the aims of the Functional and Molecular Characterization of Patients with Inherited Platelet Disorders Project, which is supported by the Hemorrhagic Diathesis Working Group of the Spanish Society of Thrombosis and Haemostasis. A.M.-Q., C.F.-I., and L.H.-C. were supported by predoctoral grants from the Junta de Castilla y León, Spain. E.V. was supported by the predoctoral grant from the University of Salamanca, Spain. IG-T and RB were supported by "Contratos postdoctorales Programa II) from the University of Salamanca, Spain

Damaging variants in FOXI3 cause microtia and craniofacial microsomia

Q1Q1Pacientes con Microtia y Microsomía craneofacialPurpose: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. Methods: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. Results: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. Conclusion: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.https://orcid.org/0000-0003-3822-7780https://orcid.org/0000-0002-0729-6866Revista Internacional - IndexadaA1N

Archaeological perspectives for northern Patagonia: Cueva Huenul 1 Site (Neuquen Province, Argentina)

Northern Neuquén Province (Pehuenches Dept., Argentina) is barely known from an archaeological perspective, though it is centrally placed in terms of several large-scale key issues in the peopling of South America: the extinction of the megafauna and its causes, early human presence, and the existence of archaeological discontinuities during the Mid-Holocene. In this paper we present the first body of paleoecological and archaeological data for Cueva Huenul 1 site, recently excavated, which offers a sedimentary sequence extending during the last of 16.000 calendar years. Initially, we present a chrono-stratigraphic frame for the site, including new tephro-chronological information. On this basis, four temporal components are defined, providing the historical scheme for the analysis of the recovered evidences that include: archaeofaunas (paleontological and archaeological), archaeobotany, lithic and ceramic technology, and rockart. These results at a site scale provide a first approach to a discussion of macro-regional processes, as well as the basis for the continuation of our research.El norte de la provincia de Neuquén (Depto. Pehuenches, Argentina) es muy poco conocido a nivel arqueológico, a pesar de estar ubicado en una posición central en relación con distintos temas clave del poblamiento humano de Sudamérica, incluyendo la extinción de la megafauna y sus causas, el poblamiento humano inicial y la existencia de discontinuidades arqueológicas en el Holoceno medio. En este trabajo se presenta el primer cuerpo de resultados paleoecológicos y arqueológicos para el sitio Cueva Huenul 1, recientemente excavado, que ofrece una secuencia sedimentaria que se extiende durante los últimos 16.000 años calendáricos. Estas evidencias incluyen el desarrollo de un marco crono-estratigráfico para el sitio, que aporta novedosa información tefro-cronológica. A partir de este análisis, se definen cuatro componentes temporales, sobre los cuales se asienta el estudio de los materiales recuperados: evidencias faunísticas (paleontológicas y arqueológicas), arqueobotánicas, líticas, cerámicas y de arte rupestre. Estos resultados en escala de sitio proveen una primera instancia de evaluación de procesos en escala macro-regional, así como las bases para la continuación de este proyecto.Facultad de Ciencias Naturales y Muse

Economía y finanzas sociales: avances en la investigación

Esta obra colectiva propone un cambio de paradigma en la investigación científica, financiera y económica, cuyo centro de atención es reducir las desigualdades sociales y económicas, mejorar la sostenibilidad ambiental y la creación eficiente de valor económico. Desde un punto de vista crítico y mediante diversos enfoques teóricos, metodológicos y disciplinares, los autores analizan el esquema financiero predominante en las economías de mercado, al tiempo que abordan temas como la inclusión financiera, la banca ética o las experiencias e intervenciones en y sobre la economía social.ITESO, A.C

Cross section measurements of 155,157Gd(n, γ) induced by thermal and epithermal neutrons

Neutron capture cross section measurements on Gd and Gd were performed using the time-of-flight technique at the n_TOF facility at CERN on isotopically enriched samples. The measurements were carried out in the n_TOF experimental area EAR1, at 185 m from the neutron source, with an array of 4 CD liquid scintillation detectors. At a neutron kinetic energy of 0.0253 eV, capture cross sections of 62.2(2.2) and 239.8(8.4) kilobarn have been derived for Gd and Gd, respectively, with up to 6% deviation relative to values presently reported in nuclear data libraries, but consistent with those values within 1.6 standard deviations. A resonance shape analysis has been performed in the resolved resonance region up to 181 eV and 307 eV, respectively for Gd and Gd, where on average, resonance parameters have been found in good agreement with evaluations. Above these energies and up to 1 keV, the observed resonance-like structure of the cross section has been analysed and characterised. From a statistical analysis of the observed neutron resonances we deduced: neutron strength function of 2. 01 (28) × 10 and 2. 17 (41) × 10 ; average total radiative width of 106.8(14) meV and 101.1(20) meV and s-wave resonance spacing 1.6(2) eV and 4.8(5) eV for n + Gd and n + Gd systems, respectively

Detection of Alpha-Rod Protein Repeats Using a Neural Network and Application to Huntingtin

A growing number of solved protein structures display an elongated structural domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel alpha-helices. Alpha-rods are flexible and expose a large surface, which makes them suitable for protein interaction. Although most likely originating by tandem duplication of a two-helix unit, their detection using sequence similarity between repeats is poor. Here, we show that alpha-rod repeats can be detected using a neural network. The network detects more repeats than are identified by domain databases using multiple profiles, with a low level of false positives (<10%). We identify alpha-rod repeats in approximately 0.4% of proteins in eukaryotic genomes. We then investigate the results for all human proteins, identifying alpha-rod repeats for the first time in six protein families, including proteins STAG1-3, SERAC1, and PSMD1-2 & 5. We also characterize a short version of these repeats in eight protein families of Archaeal, Bacterial, and Fungal species. Finally, we demonstrate the utility of these predictions in directing experimental work to demarcate three alpha-rods in huntingtin, a protein mutated in Huntington's disease. Using yeast two hybrid analysis and an immunoprecipitation technique, we show that the huntingtin fragments containing alpha-rods associate with each other. This is the first definition of domains in huntingtin and the first validation of predicted interactions between fragments of huntingtin, which sets up directions toward functional characterization of this protein. An implementation of the repeat detection algorithm is available as a Web server with a simple graphical output: http://www.ogic.ca/projects/ard. This can be further visualized using BiasViz, a graphic tool for representation of multiple sequence alignments

Attending to warning signs of primary immunodeficiencies disease across the range of clinical practices

Purpose: Patients with primary immunodeficiency diseases (PIDD) may present with recurrent infections affecting different organs, organ-specific inflammation/autoimmunity, and also increased cancer risk, particularly hematopoietic malignancies. The diversity of PIDD and the wide age range over which these clinical occurrences become apparent often make the identification of patients difficult for physicians other than immunologists. The aim of this report is to develop a tool for educative programs targeted to specialists and applied by clinical immunologists. Methods: Considering the data from national surveys and clinical reports of experiences with specific PIDD patients, an evidence-based list of symptoms, signs, and corresponding laboratory tests were elaborated to help physicians other than immunologists look for PIDD. Results: Tables including main clinical manifestations, restricted immunological evaluation, and possible related diagnosis were organized for general practitioners and 5 specialties. Tables include information on specific warning signs of PIDD for pulmonologists, gastroenterologists, dermatologists, hematologists, and infectious disease specialists. Conclusions: This report provides clinical immunologists with an instrument they can use to introduce specialists in other areas of medicine to the warning signs of PIDD and increase early diagnosis. Educational programs should be developed attending the needs of each specialty.Fil: Costa Carvalho, Beatriz Tavares. Universidade Federal de São Paulo; BrasilFil: Sevciovic Grumach, Anete. Fundação ABC. Faculdade de Medicina; BrasilFil: Franco, José Luis. Universidad de Antioquia; ColombiaFil: Espinosa Rosales, Francisco Javier. Instituto Nacional de Pediatría. Unidad de Investigación en Inmunodeficiencias; MéxicoFil: Leiva, Lily E.. State University of Louisiana; Estados UnidosFil: King, Alejandra. Hospital de Niños Doctor Luis Calvo Mackenna. Unidad de Inmunología; ChileFil: Porras, Oscar. Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera”; Costa RicaFil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Oleastro, Mathias. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sorensen, Ricardo U.. State University of Louisiana; Estados Unidos. Universidad de La Frontera. Facultad de Medicina; MéxicoFil: Condino Neto, Antonio. Universidade de Sao Paulo; Brasi