Charge distribution in two-dimensional electrostatics

We examine the stability of ringlike configurations of N charges on a plane interacting through the potential $V(z_1,...,z_N)=\sum_i |z_i|^2-\sum_{i<j} ln|z_i-z_j|^2$. We interpret the equilibrium distributions in terms of a shell model and compare predictions of the model with the results of numerical simulations for systems with up to 100 particles.Comment: LaTe

The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

lncRNA requirements for mouse acute myeloid leukemia and normal differentiation

A substantial fraction of the genome is transcribed in a cell type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the c-MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

10. DIAGNÓSTICO DE LA IMPLEMENTACIÓN DE LA NORMA NIIF (NIC 41) EN LAS EMPRESAS GANADERAS DEDICADAS A LA CRÍA DE GANADO BOVINO EN LA REGIÓN DEL BAJO CAUCA ANTIOQUEÑO

El establecimiento de las Normas Internacionales de Información Financiera (NIIF) y la NIC 41 ( Norma Internacional de Contabilidad) en la ley 1314 de 2009, busca determinar la convergencia de los principios y normas de contabilidad e información financiera hacia los estándares internacionales, permitiendo la identificación y reconocimiento de los activos biológicos; por este motivo el grupo de investigación HUTIN (Huellas Tecnológicas de Investigación), desarrolló un proyecto en el cual se diagnosticó las empresas del sector ganadero dedicadas a la cría de ganado bovino de la región del Bajo Cauca Antioqueño implementen esta norma, ya que posibilita el reconocimiento económico de los activos biológicos, valor razonable y deducción de costos que son representativos en los estados financieros. Esto se logró a través de encuestas realizadas a empresas de la subregión del Bajo Cauca Antioqueño dedicadas a la cría de ganado bovino, obteniendo la información necesaria para documentar el proceso y obtener un estándar para ser implementado en el sector siendo una herramienta eficaz para alcanzar mercados globalizados y competitivos. Se percibe un bajo nivel en las empresas ganaderas sobre el proceso de implementación de la NIIF (NIC 41). La implementación de esta norma le permite al empresario del sector ganadero identificar el estado actual de sus activos biológicos e inventarios y poder deducirse costos significativos en el proceso productivo, contando con una información económica, contable y financiera fundamentales en la toma de decisiones

Evaluation of Physical Interaction during Walker-Assisted Gait with the AGoRA Walker: Strategies Based on Virtual Mechanical Stiffness

Smart walkers are commonly used as potential gait assistance devices, to provide physical and cognitive assistance within rehabilitation and clinical scenarios. To understand such rehabilitation processes, several biomechanical studies have been conducted to assess human gait with passive and active walkers. Several sessions were conducted with 11 healthy volunteers to assess three interaction strategies based on passive, low and high mechanical stiffness values on the AGoRA Smart Walker. The trials were carried out in a motion analysis laboratory. Kinematic data were also collected from the smart walker sensory interface. The interaction force between users and the device was recorded. The force required under passive and low stiffness modes was 56.66% and 67.48% smaller than the high stiffness mode, respectively. An increase of 17.03% for the hip range of motion, as well as the highest trunk’s inclination, were obtained under the resistive mode, suggesting a compensating motion to exert a higher impulse force on the device. Kinematic and physical interaction data suggested that the high stiffness mode significantly affected the users’ gait pattern. Results suggested that users compensated their kinematics, tilting their trunk and lower limbs to exert higher impulse forces on the device

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

An Open-Source Social Robot Based on Compliant Soft Robotics for Therapy with Children with ASD

Therapy with robotic tools is a promising way to help improve verbal and nonverbal communication in children. The robotic tools are able to increase aspects such as eye contact and the ability to follow instructions and to empathize with others. This work presents the design methodology, development, and experimental validation of a novel social robot based on CompliAnt SofT Robotics called the CASTOR robot, which intends to be used as an open-source platform for the long-term therapy of children with autism spectrum disorder (CwASD). CASTOR integrates the concepts of soft actuators and compliant mechanisms to create a replicable robotic platform aimed at real therapy scenarios involving physical interaction between the children and the robot. The validation shows promising results in terms of robustness and the safety of the user and robot. Likewise, mechanical tests assess the robot’s response to blocking conditions for two critical modules (i.e., neck and arm) in interaction scenarios. Future works should focus on the validation of the robot’s effectiveness in the therapy of CwASD.</jats:p

Communicating climate change and biodiversity loss with local populations: exploring communicative utopias in eight transdisciplinary case studies

Climate change and biodiversity loss trigger policies targeting and impacting local communities worldwide. However, research and policy implementation often fail to sufficiently consider community responses and to involve them. We present the results of a collective self-assessment exercise for eight case studies of communications with regard to climate change or biodiversity loss between project teams and local communities. We develop eight indicators of good stakeholder communication, reflecting the scope of Verran’s (2002) concept of postcolonial moments as a communicative utopia. We demonstrate that applying our indicators can enhance communication and enable community responses. However, we discover a divergence between timing, complexity and (introspective) effort. Three cases qualify for postcolonial moments, but scrutinising power relations and genuine knowledge co-production remain rare. While we verify the potency of various instruments for deconstructing science, their sophistication cannot substitute trust building and epistemic/transdisciplinary awareness. Lastly, we consider that reforming inadequate funding policies helps improving the work in and with local communities

Real-World Effectiveness and Safety of Dupilumab, Tralokinumab, and Upadacitinib in Patients with Atopic Dermatitis: A 52-Week International, Multicenter Retrospective Cohort Study

Introduction: Evaluating the real-world effectiveness, safety, and tolerability of targeted biologic and non-biologic therapies in patients with atopic dermatitis (AD) treated in routine clinical practice remains crucial. In this international, multicenter, retrospective, comparative study we aimed to evaluate the 52-week effectiveness, safety, and tolerability of dupilumab, tralokinumab, and upadacitinib in patients with AD aged ≥ 12&nbsp;years. Methods: Effectiveness was assessed at weeks&nbsp;16, 24, and 52 using Eczema Area and Severity Index (EASI) and itch Numerical Rating Scale (NRS) scores. Safety was measured via adverse events (AEs). Results: A total of 1286 treatment courses were included: 62.5% received dupilumab, 24.3% received upadacitinib, and 13.1% received tralokinumab. Upadacitinib demonstrated higher effectiveness than dupilumab and tralokinumab across all time points and most evaluated outcomes both on the overall population and the biologic-/JAKi-naïve population, including stringent treatment targets such as EASI&nbsp;90 response and combined EASI&nbsp;90 + itch NRS&nbsp;0/1 response. While upadacitinib demonstrated superior effectiveness, it was associated with a higher incidence of AEs, both leading to and not leading to treatment discontinuation, including thromboembolic events, lipid abnormalities, and hematologic abnormalities. In contrast, conjunctivitis was the most frequently observed AE among patients receiving biologics. Conclusion: This study provides a comprehensive real-world comparison of dupilumab, tralokinumab, and upadacitinib in AD, highlighting upadacitinib’s superior effectiveness in achieving stringent treatment targets, both in the short and long term, but also a higher incidence of AEs. However, the considerable heterogeneity of the study population, an inherent limitation of real-world studies, must be acknowledged when interpreting these findings