Boundary timelike Liouville theory: bulk 1-point & boundary 2-point functions

We consider timelike Liouville theory with FZZT-like boundary conditions. The bulk one-point and boundary two-point structure constants on a disk are derived using bootstrap. We find that these structure constants are not the analytic continuations of their spacelike counterparts.Comment: 36 pages. Additional comments about normalization in Section 3. Results unchange

Linear cyclodextrin polymer prodrugs as novel yherapeutics for Niemann-Pick type C1 disorder

Niemann-Pick Type C1 disorder (NPC) is a rare lysosomal storage disease characterized by the accumulation of cholesterol in lysosomes. NPC has no FDA approved treatments yet, however 2-hydroxypropyl-β-cyclodextrin (HPβCD) has shown efficacy for treating the disease in both mouse and feline NPC models and is currently being investigated in late stage clinical trials. Despite promising results, therapeutic use of HPβCD is limited by the need for high doses, ototoxicity and intrathecal administration. These limitations can be attributed to its poor pharmacokinetic profile. In the attempt to overcome these limitations, we have designed a β-cyclodextrin (βCD) based polymer prodrugs (ORX-301) for an enhanced pharmacokinetic and biodistribution profile, which in turn can potentially provide an improved efficacy at lower doses. We demonstrated that subcutaneously injected ORX-301 extended the mean lifespan of NPC mice at a dosage 5-fold lower (800 mg/kg, body weight) the HPβCD dose proven efficacious (4000 mg/kg). We also show that ORX-301 penetrates the blood brain barrier and counteracts neurological impairment. These properties represent a substantial improvement and appear to overcome major limitations of presently available βCD-based therapy, demonstrating that this novel prodrug is a valuable alternative/complement for existing therapies

Village Officials’ Competence in Digital-Based Services Using E-Office in Mekarwangi Village, Sumedang Regency

The implementation of new applications to support organizational work, integral to the adoption of SPBE in Indonesia, often encounters a lack of readiness among management officials. This challenge extends to the village level, the lowest tier of government, where the introduction of the E-office as a digital-based administrative service represents both a breakthrough and a formidable hurdle for village officials unfamiliar with information technology. This study aims to assess the competence of the village officials in facilitating the operationalization of the E-office and proposes strategies to enhance their digital service proficiency, focusing on Mekarwangi Village in Tomo District, Sumedang Regency. Employing a descriptive qualitative research approach, data collection involves interviews, observations, and documentation, with data triangulation as the analytical technique. The study reveals that the competence of the Mekarwangi Village officials is currently minimal, primarily due to a lack of adequate education, training, and insufficient support from local or central governments in providing facilities for enhancing the officials' competence in managing village potential data—a critical aspect of E-office operations. In response, the Sumedang government is actively addressing this issue by regularly conducting training and socialization programs on online-based services, specifically the village E-office, for village officials and communities. Efforts have been made to improve the quality and quantity of supporting infrastructure, such as internet network capabilities and the availability of laptops. To foster competitiveness among villages, the government is also instituting awards for those successfully implementing the E-office, accompanied by guidance for villages facing challenges in its optimal operation

Mesoporous Silica Based Protein Release Systems

Mesoporous silica nanoparticles (MSNs) such as MCM41 are effective support carriers with excellent adsorption properties and large surface areas [1-3]. Bioactive molecules like proteins such as albumin, casein and collagen are universally present in nature and products. Interaction of these proteins and MCM41 have not been widely explored. The aim of this study is to assess how these proteins behave in the presence of MCM41 and assess its protein release properties for the purpose of interdisciplinary applications

Optimization of protein extraction and ELISA immunodetection from protein-based paint models with mesoporous silica nanoparticles and MCM41

Protein-based biological materials such as albumin, casein and collagen are found in various cultural heritage (CH) artefacts. This study focuses on the study of protein binders from easel paintings media. Proteins have complex structures which are difficult to identify with non-invasive spectroscopic methods (FT-IR, Raman, UV). Immunoassays such as ELISA determine the protein’s source of origin which is necessary for art objects. To increase the detection and identification of proteins by immunoassays, the efficiency of micro-extraction of proteins from heritage materials is a crucial step. Extractions mediated by cycles of orbital agitation and ultrasonic radiation give the possibility to extract proteins from easel painting sample. In this work, protein-based paint models coupled with silica nanoparticles were used for micro-extraction. Nanoparticles possess high surface-to-volume ratios that can attach bioactive molecules such as proteins and increase the total protein recovered from microsamples. Protein extracts were quantified with Bradford Assay in the presence of Coomassie blue. The protein recovery results were statistically computed, and the SPSS analysis shows significant (p <0.05) increase in protein recovery, above 1.3 times for NPSiO2 and above 1.6 times for MCM-41. The statistical data shows evidence that silica nanoparticles intensify the total protein recovered from paint microsamples. Finally, ELISA was realized on the protein extracts to verify and compare the immunodetection of protein from the paint models with and without the use of silica nanoparticles

Prenatal Isotretinoin Exposure Reduces the Neuronal Population of Hippocampus in Rats

ABSTRACT Isotretinoin is a drug used in the treatment of acne. Teratogenic effects of isotretinoin are well known. It is causes craniofacial abnormalities like cleft palate in animal model studies. There are very few studies focusing on its effect on the developing brain specially hippocampus concerned with memory. In the present study we investigate teratogenic effect on neuronal population of the hippocampus during postnatal development. Pregnant Wistar rats were exposed to either 8 or 16mg/kg dose of body weight of isotretinoin during early or mid-gestation of pregnancy. Pups were sacrificed at postnatal day 7 or day 21, brains were removed and processed for histological studies. Coronal sections o brain were taken and stained with cresyl violet and viable neurons were counted for 250 μm length in different regions of the hippocampus. At postnatal day 7neurons belonging to CA1 region of the hippocampus was severely affected at both the doses tested and also in early &amp; mid-gestation treatment regime. At postnatal day 21, neurons of the CA2 &amp; CA1 regions were severely affected. It is also observed that mid-gestational effect had more severe effect compared to early gestational treatment. This study clearly demonstrates the teratogenic effect of isotretinoin on hippocampal neuronal population of developing brain. Care must be taken while prescribing this drug to women of reproductive age

Surface modification of a polyethersulfone microfiltration membrane with graphene oxide for reactive dyes removal

Polyethersulfone microfiltration membranes (mPES) were modified with polyethilenimine (PEI) and graphene oxide (GO) by layer-by-layer self-assembly method via electrostatic interaction using a pressurized filtration system. The high positively charge of PEI allowed it to be easily assembled on the polyethersulfone substrate, and also to receive the negative layer of GO. Several techniques were applied to characterize the modified membranes (i.e. ATR-FTIR, SEM, water angle contact and zeta potential), and proved that the modification was successfully achieved. The effect of PEI and GO concentrations in the modification was investigated, and the best performance of all membranes was achieved with a Blue Corazol (BC) dye rejection of 97.8% and a pure water permeability of 99.4 L m−2 h−1 bar−1. The membrane also presented a flux recovery ratio of >80% after being hydraulically cleaned for 30 min. Moreover, the membrane performance was evaluated in terms of rejection of BC dye in a real dye bath wastewater, and an excellent performance with a maximum rejection rate of 96% was observed. Therefore, the proposed study may provide an efficient alternative to feasible the use of microfiltration membranes, by modifying them, in order to improve its surface characteristics and its filtration capacity, aiming to apply it in the removal of dyes of textile industries wastewater.This work was funded by the Fundação para a Ciência e a Tecnologia (FCT), project n° POCI-01-0145-FEDER-007136 (UID/CTM/00264/2013). The authors would also like to thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the financial support and for scholarships awarded, and Universidade do Minho (UMinho) for the availability of laboratories and equipment

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline