Refractive Index Fiber Laser Sensor by Using a Fiber Ball Lens Interferometer with Adjustable Free Spectral Range.

In this work, a fiber laser refractometer based on a fiber ball lens (FBL) interferometer is proposed. The linear cavity erbium-doped fiber laser uses an FBL structure acting as a spectral filter and sensing element for determining the RI of a liquid medium surrounding the fiber. The optical interrogation of the sensor is the wavelength displacement of the generated laser line as a function of the RI variations. For the proposed FBL interferometric filter, the free spectral range of its wavelength-modulated reflection spectrum is adjusted to maximum in order to obtain RI measurements in a range of 1.3939 to 1.4237 RIU, from laser wavelength displacements in a range from 1532.72 to 1565.76 nm. The obtained results show that the wavelength of the generated laser line is a linear function of the RI variations on the medium surrounding the FBL with a sensitivity of 1130.28 nm/RIU. The reliability of the proposed fiber laser RI sensor is analytically and experimentally investigated.

Lossy Mode Resonance Generation on Sputtered Aluminum-Doped Zinc Oxide Thin Films Deposited on Multimode Optical Fiber Structures for Sensing Applications in the 1.55 µm Wavelength Range.

In this work, we demonstrated lossy mode resonance (LMR) generation in optical fiber structures based on multimode fibers coated with aluminum-doped zinc oxide (AZO) films. AZO thin films were deposited by using radio frequency magnetron sputtering. In order to exhibit the usefulness of the LMR effect for sensing applications in optical fiber based systems, the deposition conditions of the AZO film coatings were set to obtain the second LMR order within the 1.55 µm wavelength range. An optical transmission configuration setup was used to investigate the LMR effect on fiber structures based on the use of no-core and cladding-removed multimode fibers coated with AZO films synthesized from metallic sputtering targets with different proportions of Zn:Al, 92:8% and 98:2%, at atomic concentrations. The optical and electrical/chemical features of the AZO films were characterized with UV-vis and XPS spectroscopy, respectively. The optical response of the proposed sensing configuration to refractive index (RI) variations was experimentally demonstrated. For the best approach, the sensitivity of wavelength displacement to RI variations on the liquid surrounding media was found to be 1214.7 nm/RIU.

All-fiber laser with simultaneous Tm3+ passive Q-switched and Ho3+ gain-switched operation.

We experimentally demonstrate simultaneous Tm3+ passive Q-switched (PQS) and Ho3+ gain-switched laser operations at 1888.8 and 2021.2 nm, respectively, in a single-cavity all-fiber laser. The PQS operation of the Tm3+ laser is based on the use of a high-concentration holmium-doped fiber as a fiber saturable absorber. Then the Tm3+ laser emission is used as a pulsed pump source to achieve Ho3+ gain-switched pulses. A high birefringence fiber optical loop mirror used as a spectral filter allows the tuning of both Tm3+ and Ho3+ laser emissions.

Structure and Dynamics of an Intrinsically Disordered Protein Region That Partially Folds upon Binding by Chemical-Exchange NMR.

Many intrinsically disordered proteins (IDPs) and protein regions (IDRs) engage in transient, yet specific, interactions with a variety of protein partners. Often, if not always, interactions with a protein partner lead to partial folding of the IDR. Characterizing the conformational space of such complexes is challenging: in solution-state NMR, signals of the IDR in the interacting region become broad, weak, and often invisible, while X-ray crystallography only provides information on fully ordered regions. There is thus a need for a simple method to characterize both fully and partially ordered regions in the bound state of IDPs. Here, we introduce an approach based on monitoring chemical exchange by NMR to investigate the state of an IDR that folds upon binding through the observation of the free state of the protein. Structural constraints for the bound state are obtained from chemical shifts, and site-specific dynamics of the bound state are characterized by relaxation rates. The conformation of the interacting part of the IDR was determined and subsequently docked onto the structure of the folded partner. We apply the method to investigate the interaction between the disordered C-terminal region of Artemis and the DNA binding domain of Ligase IV. We show that we can accurately reproduce the structure of the core of the complex determined by X-ray crystallography and identify a broader interface. The method is widely applicable to the biophysical investigation of complexes of disordered proteins and folded proteins.

All-Fiber Laser Curvature Sensor Using an In-Fiber Modal Interferometer Based on a Double Clad Fiber and a Multimode Fiber Structure.

An all-fiber curvature laser sensor by using a novel modal interference in-fiber structure is proposed and experimentally demonstrated. The in-fiber device, fabricated by fusion splicing of multimode fiber and double-clad fiber segments, is used as wavelength filter as well as the sensing element. By including a multimode fiber in an ordinary modal interference structure based on a double-clad fiber, the fringe visibility of the filter transmission spectrum is significantly increased. By using the modal interferometer as a curvature sensitive wavelength filter within a ring cavity erbium-doped fiber laser, the spectral quality factor Q is considerably increased. The results demonstrate the reliability of the proposed curvature laser sensor with advantages of robustness, ease of fabrication, low cost, repeatability on the fabrication process and simple operation.

Effectiveness of current disinfection procedures against biofilm on contaminated GI endoscopes.

BACKGROUND AND AIMS: Attention to patient safety has increased recently due to outbreaks of nosocomial infections associated with GI endoscopy. The aim of this study was to evaluate current cleaning and disinfection procedures of endoscope channels with high bioburden and biofilm analysis, including the use of resistant mycobacteria associated with postsurgical infections in Brazil. METHODS: Twenty-seven original endoscope channels were contaminated with organic soil containing 10(8) colony-forming units/mL of Pseudomonas aeruginosa, Staphylococcus aureus, or Mycobacterium abscessus subsp bolletii. Biofilms with the same microorganisms were developed on the inner surface of channels with the initial inoculum of 10(5) colony-forming units/mL. Channels were reprocessed following current protocol, and samples from cleaning and disinfection steps were analyzed by bioluminescence for adenosine triphosphate, cultures for viable microorganisms, and confocal microscopy. RESULTS: After contamination, adenosine triphosphate levels increased dramatically, and high bacterial growth was observed in all cultures. After cleaning, adenosine triphosphate levels decreased to values comparable to precontamination levels, and bacterial growth was demonstrated in 5 of 27 catheters, 2 with P aeruginosa and 3 with M abscessus. With regard to induced biofilm, a remarkable reduction occurred after cleaning, but significant microbial growth inhibition occurred only after disinfection. Nevertheless, viable microorganisms within the biofilm were still detected by confocal microscopy, more so with glutaraldehyde than with peracetic acid or O-phataladehyde. CONCLUSION: After the complete disinfection procedure, viable microorganisms could still be detected within the biofilm on endoscope channels. Prevention of biofilm development within endoscope channels should be a priority in disinfection procedures, particularly for ERCP and EUS.

Recombination-activating gene 1 (Rag1)-deficient mice with severe combined immunodeficiency treated with lentiviral gene therapy demonstrate autoimmune Omenn-like syndrome.

BACKGROUND: Recombination-activating gene 1 (RAG1) deficiency results in severe combined immunodeficiency (SCID) caused by a complete lack of T and B lymphocytes. If untreated, patients succumb to recurrent infections. OBJECTIVES: We sought to develop lentiviral gene therapy for RAG1-induced SCID and to test its safety. METHODS: Constructs containing the viral spleen-focus-forming virus (SF), ubiquitous promoters, or cell type-restricted promoters driving sequence-optimized RAG1 were compared for efficacy and safety in sublethally preconditioned Rag1(-/-) mice undergoing transplantation with transduced bone marrow progenitors. RESULTS: Peripheral blood CD3(+) T-cell reconstitution was achieved with SF, ubiquitous promoters, and cell type-restricted promoters but 3- to 18-fold lower than that seen in wild-type mice, and with a compromised CD4(+)/CD8(+) ratio. Mitogen-mediated T-cell responses and T cell-dependent and T cell-independent B-cell responses were not restored, and T-cell receptor patterns were skewed. Reconstitution of mature peripheral blood B cells was approximately 20-fold less for the SF vector than in wild-type mice and often not detectable with the other promoters, and plasma immunoglobulin levels were abnormal. Two months after transplantation, gene therapy-treated mice had rashes with cellular tissue infiltrates, activated peripheral blood CD44(+)CD69(+) T cells, high plasma IgE levels, antibodies against double-stranded DNA, and increased B cell-activating factor levels. Only rather high SF vector copy numbers could boost T- and B-cell reconstitution, but mRNA expression levels during T- and B-cell progenitor stages consistently remained less than wild-type levels. CONCLUSIONS: These results underline that further development is required for improved expression to successfully treat patients with RAG1-induced SCID while maintaining low vector copy numbers and minimizing potential risks, including autoimmune reactions resembling Omenn syndrome.

A brief tablet-based intervention benefits linguistic and communicative abilities in toddlers and preschoolers.

Young children's linguistic and communicative abilities are foundational for their academic achievement and overall well-being. We present the positive outcomes of a brief tablet-based intervention aimed at teaching toddlers and preschoolers new word-object and letter-sound associations. We conducted two experiments, one involving toddlers ( ~ 24 months old, n = 101) and the other with preschoolers ( ~ 42 months old, n = 152). Using a pre-post equivalent group design, we measured the children's improvements in language and communication skills resulting from the intervention. Our results showed that the intervention benefited toddlers' verbal communication and preschoolers' speech comprehension. Additionally, it encouraged vocalizations in preschoolers and enhanced long-term memory for the associations taught in the study for all participants. In summary, our study demonstrates that the use of a ludic tablet-based intervention for teaching new vocabulary and pre-reading skills can improve young children's linguistic and communicative abilities, which are essential for future development.

Multivalent interactions of the disordered regions of XLF and XRCC4 foster robust cellular NHEJ and drive the formation of ligation-boosting condensates in vitro.

In mammalian cells, DNA double-strand breaks are predominantly repaired by non-homologous end joining (NHEJ). During repair, the Ku70-Ku80 heterodimer (Ku), X-ray repair cross complementing 4 (XRCC4) in complex with DNA ligase 4 (X4L4) and XRCC4-like factor (XLF) form a flexible scaffold that holds the broken DNA ends together. Insights into the architectural organization of the NHEJ scaffold and its regulation by the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) were recently obtained by single-particle cryo-electron microscopy analysis. However, several regions, especially the C-terminal regions (CTRs) of the XRCC4 and XLF scaffolding proteins, have largely remained unresolved in experimental structures, which hampers the understanding of their functions. Here we used magnetic resonance techniques and biochemical assays to comprehensively characterize the interactions and dynamics of the XRCC4 and XLF CTRs at residue resolution. We show that the CTRs of XRCC4 and XLF are intrinsically disordered and form a network of multivalent heterotypic and homotypic interactions that promotes robust cellular NHEJ activity. Importantly, we demonstrate that the multivalent interactions of these CTRs lead to the formation of XLF and X4L4 condensates in vitro, which can recruit relevant effectors and critically stimulate DNA end ligation. Our work highlights the role of disordered regions in the mechanism and dynamics of NHEJ and lays the groundwork for the investigation of NHEJ protein disorder and its associated condensates inside cells with implications in cancer biology, immunology and the development of genome-editing strategies.

The DNA binding domain and the C-terminal region of DNA Ligase IV specify its role in V(D)J recombination.

DNA Ligase IV is responsible for the repair of DNA double-strand breaks (DSB), including DSBs that are generated during V(D)J recombination. Like other DNA ligases, Ligase IV contains a catalytic core with three subdomains-the DNA binding (DBD), the nucleotidyltransferase (NTD), and the oligonucleotide/oligosaccharide-fold subdomain (OBD). Ligase IV also has a unique C-terminal region that includes two BRCT domains, a nuclear localization signal sequence and a stretch of amino acid that participate in its interaction with XRCC4. Out of the three mammalian ligases, Ligase IV is the only ligase that participates in and is required for V(D)J recombination. Identification of the minimal domains within DNA Ligase IV that contribute to V(D)J recombination has remained unresolved. The interaction of the Ligase IV DNA binding domain with Artemis, and the interaction of its C-terminal region with XRCC4, suggest that both of these regions that also interact with the Ku70/80 heterodimer are important and might be sufficient for mediating participation of DNA Ligase IV in V(D)J recombination. This hypothesis was investigated by generating chimeric ligase proteins by swapping domains, and testing their ability to rescue V(D)J recombination in Ligase IV-deficient cells. We demonstrate that a fusion protein containing Ligase I NTD and OBDs flanked by DNA Ligase IV DBD and C-terminal region is sufficient to support V(D)J recombination. This chimeric protein, which we named Ligase 37, complemented formation of coding and signal joints. Coding joints generated with Ligase 37 were shorter than those observed with wild type DNA Ligase IV. The shorter length was due to increased nucleotide deletions and decreased nucleotide insertions. Additionally, overexpression of Ligase 37 in a mouse pro-B cell line supported a shift towards shorter coding joints. Our findings demonstrate that the ability of DNA Ligase IV to participate in V(D)J recombination is in large part mediated by its DBD and C-terminal region.

Multivalent interactions of the disordered regions of XLF and XRCC4 foster robust cellular NHEJ and drive the formation of ligation-boosting condensates in vitro.

In mammalian cells, DNA double-strand breaks are predominantly repaired by non-homologous end joining (NHEJ). During repair, the Ku70/80 heterodimer (Ku), XRCC4 in complex with DNA Ligase 4 (X4L4), and XLF form a flexible scaffold that holds the broken DNA ends together. Insights into the architectural organization of the NHEJ scaffold and its regulation by the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) have recently been obtained by single-particle cryo-electron microscopy analysis. However, several regions, especially the C-terminal regions (CTRs) of the XRCC4 and XLF scaffolding proteins, have largely remained unresolved in experimental structures, which hampers the understanding of their functions. Here, we used magnetic resonance techniques and biochemical assays to comprehensively characterize the interactions and dynamics of the XRCC4 and XLF CTRs at atomic resolution. We show that the CTRs of XRCC4 and XLF are intrinsically disordered and form a network of multivalent heterotypic and homotypic interactions that promotes robust cellular NHEJ activity. Importantly, we demonstrate that the multivalent interactions of these CTRs led to the formation of XLF and X4L4 condensates in vitro which can recruit relevant effectors and critically stimulate DNA end ligation. Our work highlights the role of disordered regions in the mechanism and dynamics of NHEJ and lays the groundwork for the investigation of NHEJ protein disorder and its associated condensates inside cells with implications in cancer biology, immunology and the development of genome editing strategies.

[Role of creative discussion in the learning of critical reading of scientific articles]. / Papel de la discusión creadora en el aprendizaje de la lectura crítica de artículos científicos.

OBJECTIVE: To compare two active educational strategies on critical reading (two and three stages) for research learning in medical students. MATERIAL AND METHODS: Four groups were conformed in a quasi-experimental design. The medical student group, related to three stages (critical reading guide resolution, creative discussion, group discussion) g1, n = 9 with school marks > 90 and g2, n = 19 with a < 90, respectively. The two-stage groups (guide resolution and group discussion) were conformed by pre-graduate interns, g3, n = 17 and g4, n = 12, who attended social security general hospitals. A validated and consistent survey with 144 items was applied to the four groups before and after educational strategies. Critical reading with its subcomponents: interpretation, judgment and proposal were evaluated with 47, 49 and 48 items, respectively. The case control studies, cohort studies, diagnostic test and clinical trial designs were evaluated. Nonparametric significance tests were performed to compare the groups and their results. A bias calculation was performed for each group. RESULTS: The highest median was obtained by the three-stage groups (g1 and g2) and so were the medians in interpretation, judgment and proposal. The several research design results were higher in the same groups. CONCLUSIONS: An active educational strategy with three stages is superior to another with two stages in medical students. It is advisable to perform these activities in goal of better learning in our students.

[Drug use among students of the Faculty of Medical Sciences of the National Autonomous University of Nicaragua, Leon, Nicaragua]. / Uso de drogas entre estudiantes de la Facultad de Ciencias Médicas de la Universidad Nacional Autónoma de Nicaragua, León, Nicaragua.

The aim of this study was to characterize the relationships of students of the Faculty of Medical Sciences of UNAN León, with licit and illicit drugs. This was accomplished by means of a traversal, descriptive study carried out in the year 2008 in the City of León, Nicaragua. The SAMSHA (Substance Abuse and Mental Health Services Administration) questionnaire, adapted for the Nicaraguan context, was applied anonymously. The questionnaire was completed by a total of 954 students, between 17 and 35 years old, of both sexes. It was found that 52.6% of the students used alcohol, 25.3% tobacco, 48.7% medication and 2.6% cocaine. It is necessary to develop other studies to guide prevention and intervention in the university context.

[Nutritional indicators in children with acute lymphoblastic leukemia]. / Indicadores nutricionales en niños con leucemia linfoblástica aguda.

BACKGROUND: A nutritional assessment allows to determine the state of nutrition and to predict the possibility of displaying additional risks for a disease. Previous investigations have verified that it is not sufficient for children with acute lymphoblastic leukemia (ALL) to have registry of anthropometric measurements such as age, weight, and height. Given the previous information, it is necessary to conduct studies with nutritional indicators that contribute to understanding their importance in children with ALL. OBJECTIVE: To compare the nutritional values of five indicators of children with and without ALL. METHODS: A sample of 21 children with a diagnosis of ALL and 54 children without ALL (control) participated in the study; the children's ages ranged between 1.3 to 10 years. Comparisons between cases and controls were performed. RESULTS: Indicators of albumin and triceps skin fold showed differences between the groups (p < 0.005). CONCLUSIONS: Children with ALL at time of diagnosis had nutritional deficiencies of subcutaneous fat reserve and protein. These indicators could be part of the prognostic and standard of care for children with this cancer.

TiOxNy Thin Film Sputtered on a Fiber Ball Lens as Saturable Absorber for Passive Q-Switched Generation of a Single-Tunable/Dual-Wavelength Er-Yb Double Clad Fiber Laser.

The use of titanium oxynitride (TiOxNy) thin films as a saturable absorber (SA) element for generation of passive Q-switched (PQS) laser pulses, from a linear cavity Er-Yb double-clad fiber (EYDCF) laser, is demonstrated. Additionally, the deposition of the material as a thin film covering a fiber micro-ball lens (MBL) structure is reported for the first time. The TiOxNy coating is deposited by a direct current (DC) magnetron-sputtering technique. The MBL is inserted within the laser cavity in a reflection configuration, alongside a reflecting mirror. As a result, the coated fiber MBL simultaneously acts as a SA element for PQS laser pulses generation and as an interference filter for wavelength selection and tuning of the generated laser line. Tunable single-laser emission in a wavelength range limited by dual-wavelength laser generation at 1541.96 and 1547.04 nm is obtained. PQS laser pulses with a repetition rate from 18.67 to 124.04 kHz, minimum pulse duration of 3.57 µs, maximum peak power of 0.359 W, and pulse energy of 1.28 µJ were obtained in a pump power range from 1 to 1.712 W.

[Summarized real clinical cases use to learn clinical aptitude]. / Resúmenes clínicos problematizados para el aprendizaje de la clínica.

OBJECTIVE: to evaluate clinical skills indicators (CSI) with summarized real clinical cases (SRCC) by two generations of pregraduates interns. METHODS: with a descriptive survey design 430 SRCC were elaborated according to the CSI: risk factors, clinical diagnosis, laboratory and x-ray diagnosis, commission and omission iatrogenesis procedures, therapeutics, nosology and peer critical medical actions. An evaluation scale for the clinical cases included: a relationship with the clinical experience, and the CSI selected. The final evaluation was considered as adequate or inadequate and was performed independently by three medical social service students. RESULTS: except for family medicine, the SRCC were related to the clinical experience of the students. A 62 % of the total was considered as adequate. The CSI assessed were related to risk factors (18 %), clinical diagnosis (32 %), omission and commission iatrogenesis (9 %), laboratory and x-ray diagnosis resources (16 %), therapeutics (17 %), nosology (9 %) and a critical to peer medical actions (3 %). CONCLUSIONS: the SRCC patients studied from different points of view by the interns included the CSI. Therefore, this action is advisable for the improvement of the patients' clinical approach.

Bilateral enucleation at birth modifies calcium spike amplitude, but not frequency, in neurons of the somatosensory thalamus and cortex: Implications for developmental cross-modal plasticity.

Bilateral eye enucleation at birth (BE) leads to an expansion of the primary somatosensory cortex (S1) in rat pups. Although increased growth of the somatosensory thalamo-cortical afferents (STCAs) in part explains S1 expansion, timing mechanisms governing S1 formation are also involved. In this work, we begin the search of a developmental clock by intending to document the existence of putative clock neurons in the somatosensory thalamus (VPM) and S1 based upon changes of spontaneous spike amplitude; a biophysical property sensitive to circadian regulation; the latter known to be shifted by enucleation. In addition, we also evaluated whether STCAs growth rate and segregation timing were modified, as parameters the clock might time. We found that spontaneous spike amplitude transiently, but significantly, increased or decreased in VPM and S1 neurons of BE rat pups, respectively, as compared to their control counterparts. The growth rate and segregation timing of STCAs was, however, unaffected by BE. These results support the existence of a developmental clock that ticks differently in the VPM and S1 after BE. This observation, together with the fact that STCAs growth rate and segregation timing is unchanged, suggests that S1 expansion in BE rats may in part be controlled at the cortical level.

Biallelic mutations in DNA ligase 1 underlie a spectrum of immune deficiencies.

We report the molecular, cellular, and clinical features of 5 patients from 3 kindreds with biallelic mutations in the autosomal LIG1 gene encoding DNA ligase 1. The patients exhibited hypogammaglobulinemia, lymphopenia, increased proportions of circulating γδT cells, and erythrocyte macrocytosis. Clinical severity ranged from a mild antibody deficiency to a combined immunodeficiency requiring hematopoietic stem cell transplantation. Using engineered LIG1-deficient cell lines, we demonstrated chemical and radiation defects associated with the mutant alleles, which variably impaired the DNA repair pathway. We further showed that these LIG1 mutant alleles are amorphic or hypomorphic, and exhibited variably decreased enzymatic activities, which lead to premature release of unligated adenylated DNA. The variability of the LIG1 genotypes in the patients was consistent with that of their immunological and clinical phenotypes. These data suggest that different forms of autosomal recessive, partial DNA ligase 1 deficiency underlie an immunodeficiency of variable severity.