Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic and molecular analyses reveal an evolutionary trajectory for glycan synthesis in a bacterial protein glycosylation system

Although protein glycosylation systems are becoming widely recognized in bacteria, little is known about the mechanisms and evolutionary forces shaping glycan composition. Species within the genus Neisseria display remarkable glycoform variability associated with their O-linked protein glycosylation (pgl) systems and provide a well developed model system to study these phenomena. By examining the potential influence of two ORFs linked to the core pgl gene locus, we discovered that one of these, previously designated as pglH, encodes a glucosyltransferase that generates unique disaccharide products by using polyprenyl diphosphate-linked monosaccharide substrates. By defining the function of PglH in the glycosylation pathway, we identified a metabolic conflict related to competition for a shared substrate between the opposing glycosyltransferases PglA and PglH. Accordingly, we propose that the presence of a stereotypic, conserved deletion mutation inactivating pglH in strains of Neisseria gonorrhoeae, Neisseria meningitidis, and related commensals, reflects a resolution of this conflict with the consequence of reduced glycan diversity. This model of genetic détente is supported by the characterization of pglH “missense” alleles encoding proteins devoid of activity or reduced in activity such that they cannot exert their effect in the presence of PglA. Thus, glucose-containing glycans appear to be a trait undergoing regression at the genus level. Together, these findings document a role for intrinsic genetic interactions in shaping glycan evolution in protein glycosylation systems.
A Mathematical Theory of Co-Design

One of the challenges of modern engineering, and robotics in particular, is designing complex systems, composed of many subsystems, rigorously and with optimality guarantees. This paper introduces a theory of co-design that describes "design problems", defined as tuples of "functionality space", "implementation space", and "resources space", together with a feasibility relation that relates the three spaces. Design problems can be interconnected together to create "co-design problems", which describe possibly recursive co-design constraints among subsystems. A co-design problem induces a family of optimization problems of the type "find the minimal resources needed to implement a given functionality"; the solution is an antichain (Pareto front) of resources. A special class of co-design problems are Monotone Co-Design Problems (MCDPs), for which functionality and resources are complete partial orders and the feasibility relation is monotone and Scott continuous. The induced optimization problems are multi-objective, nonconvex, nondifferentiable, noncontinuous, and not even defined on continuous spaces; yet, there exists a complete solution. The antichain of minimal resources can be characterized as a least fixed point, and it can be computed using Kleene's algorithm. The computation needed to solve a co-design problem can be bounded by a function of a graph property that quantifies the interdependence of the subproblems. These results make us much more optimistic about the problem of designing complex systems in a rigorous way.
The Effect of Live Streaming Quality on Purchase Intention through Immersive Experience, Consumer Trust, and Perceived Value (Study of This is April Consumers on TikTok)

Live-streaming shopping has become a new trend since the pandemic in 2020 where live streamers promote and sell products to consumers via social media channels by increasing intimacy and communication. This Is April is one of the leading fashion brands in Indonesia that focuses on fulfilling women's desires for fashionable, affordable and high-quality clothes, shoes, and bags. This Is April also continues to carry out promotions by keeping up with developments in consumer behavior that continues to change, one of which is by carrying out promotions by selling via live streaming on one of the e-commerce sites (TikTok). This study aims to investigate the effect of live streaming quality (LSQ) on purchase intention (PI) through immersive experience (IE), consumer trust (CT), and perceived value (PV) at This is April consumers on TikTok by answering 10 (ten) hypotheses. This research uses a quantitative approach using partial least squares equation model (PLS-SEM). The samples in this study were respondents who had experience in watching live streaming of This is April fashion products on TikTok within the last 3 (three) months and respondents who lived in the city of Malang using a non-probability sampling technique. The analysis results show that LSQ has a positive and significant effect on PI. Furthermore, the research results show that IE, CT, and PV are able to mediate the relationship between LSQ and PI. The implication of this finding can provide a theoretical basis and reference for seller of fashion clothing products to focus their attention on the important of effectively leverage live streaming quality to develop immersive experience, consumer trust, and perceived value to influence purchase intention
Effect of Rivastigmine Augmentation in Treatment of Male Patients With Combat-Related Chronic Posttraumatic Stress Disorder: A Randomized Controlled Trial

Background Posttraumatic stress disorder (PTSD) is one of the chronic and disabling psychiatric disorders, particularly in combat veterans. In a case series, rivastigmine was suggested to be an effective augmentation in treatment of PTSD. The aim of the present study was to evaluate this finding in a randomized controlled trial. Method A 12-week, double-blind, placebo-controlled clinical trial was performed on 36 male patients (aged 42–60 years) diagnosed with chronic, combat-related PTSD. Subjects were screened for apparent cognitive deficits by means of Mini-Mental State Examination. All patients received selective serotonin reuptake inhibitors plus sodium valproate for 4 weeks and then reevaluated. Subjects who did not show adequate response were randomly assigned into 3 groups receiving rivastigmine (up to 6 mg/d), placebo, or the prior treatment regimen. Efficacy of medication was measured by administering PTSD Check List–Military Version at baseline and weeks 2, 4, 8, and 12. Collected data were analyzed by analysis of variance and repeated measurement. Reported differences were considered significant at the level of 0.05 or less. Results The 3 groups showed statistically significant reductions in the total PTSD Check List–Military Version, avoidance subscale, and the reexperience subscale but not in the hyperarousal subscale. No significant differences were found between the 3 groups. Conclusions In contrast to the previous case series, findings of the current study did not support the efficacy of adjunctive rivastigmine in treatment of PTSD. This hypothetically could be due to the fact that all the study's subjects scored higher than 25 on Mini-Mental State Examination.
Ideal closures of Busemann space and singular Minkowski space

We discuss two different in general natural approaches to the ideal closure and ideal boundary of Busemann nonpositively curved metric space. It is shown that the identity map of the space admits surjective continuation from its coarse ideal closure to the weak one. We consider some situations when these closures coincide, and when they are essentially different. In particular, the singular Minkowski space is studied as flat Busemann space, and some types of its ideal points are described.
Application of modified multi-objective particle swarm optimisation algorithm for flexible process planning problem

Process planning belongs to one of the most essential functions of the modern manufacturing system. Moreover, flexible process planning implies the ability of a system to adapt to changing requirements and thereby provide alternative ways of performing manufacturing operations on a part. Variety of manufacturing resources including variety of alternative machines, alternative tools, as well as tool access direction (TAD) leads to the fact that most of the parts in modern manufacturing systems have various flexible process plans. Therefore, obtaining optimal process plan from all available alternatives has become a very important task in the domain of flexible process planning research. In this article, a method based on modified particle swarm optimisation (mPSO) has been developed to solve this nondeterministic polynomial-hard combinatorial optimisation problem, and the following issues have been addressed: (i) the AND/OR network representation has been adopted to describe various types of flexibility, i.e. machine flexibility, tool flexibility, TAD flexibility, process flexibility and sequence flexibility; (ii) the particle encoding/decoding scheme has been proposed and traditional PSO algorithm has been modified with crossover, mutation and shift operator and (iii) optimal operation sequence has been found by performing multi-objective optimisation procedure concerning minimisation of the production time and production cost. In order to verify the performance of the proposed mPSO algorithm, five independent experiments have been carried out and comparisons with other meta-heuristic algorithms have been made. The experimental results show that the proposed algorithm has achieved satisfactory improvement in terms of efficiency and effectiveness.
Permian tectonic evolution of the eastern section of the northern margin of the North China Plate:Constraints from zircon U-Pb geochronology and geochemistry of the volcanic rocks

LA-ICP-MS zircon U-Pb dating and geochemical data have been obtained for the volcanic rocks from the Daheshen and Guanmenzuizi formations in the middle-eastern parts of Jilin Province, with the aim of constraining the tectonic nature of the eastern section of the northern margin of the North China Plate in Late Paleozoic. Zircons from the volcanic rocks in the Daheshen and Guanmenzuizi formations are euhedral-subhedral in shape and display fine-scale oscillatory zoning and striped absorption (basaltic andesite) as well as high Th/U ratios (0.31 similar to 1.56), implying their magmatic origin. LA-ICP-MS zircon U-Pb age data indicate that the dacite and rhyolites from the Daheshen Formation in Hunchun County formed in the Early Permian (279 +/- 3Ma similar to 293 +/- 2Ma), whereas the basaltic andesite and basalt from the Guanmenzuizi Formation in the Hunchun and Tumen areas formed in the Early Permian (275 +/- 7Ma) and Late Pennian (250 +/- 5Ma), respectively. The volcanic rocks from the Daheshen Formation have SiO2 = 64.9% similar to 75.4%, Mg-# = 0.21 similar to 0.57, belonging chemically to medium-to high-K calc-alkaline series, and display an enrichment in LREEs and LILEs and depletion in HFSEs (such as Nb, Ta, and Ti) and P, similar chemically to those from an active continental margin setting. Their initial Elf isotopic ratios and Hf two-stage model ages range from +0.9 to +10.37 and from 785Ma to 1240Ma, respectively, suggesting that their primary magmas could be mainly derived from partial melting of the Meso-Neoproterozoic accretted lower crust. The Early Permian basaltic andesites from the Cuanmenzurzi Formation in Hunchun area, belonging chemically to medium-K calc-alkaline series, are poor in SiO2 (53.4% similar to 53.7%) and HFSEs, rich in Al2O3 (16.4% similar to 16.8%) and LILEs, and display low REE abundances and flat REE pattern, similar to those from an island arc setting. The primary magma of the basaltic andesites could be mainly derived from partial melting of the depleted mantle wedge metasomatized by the subducted slab-derived fluid. The Late Permian basalts from the Guanmenzuizi Formation in Tumen area have SiO2 =48.7% similar to 49.6%, Mg-# = 0.64 similar to 0.72, and are enriched in LREEs and LILEs, and depleted in HREEs and HFSEs, similar chemically to those from a volcanic arc setting. Combined with its Nd isotopic ratios (+6.01), we consider that its primary magma could be derived from partial melting of a depleted lithospheric mantle. Taken together, we conclude that the subduction of the Paleo-Asian oceanic plate happened in both the eastern section of the northern margin of the North China Plate (in middle part of Jilin Province) and the southwestern margin of the Khanka Massif from Early Permian to Late Permian.
The Efficacy of Photodynamic Therapy in Actinic Cheilitis of the Lower Lip: A Prospective Study of 15 Patients

BACKGROUND Photodynamic therapy (PDT) has been developed into a widely used method to treat actinic keratoses and basal cell carcinoma. OBJECTIVE The objective was to assess the efficacy of PDT in the treatment of actinic cheilitis of the lower lip. METHODS In this prospective, uncontrolled study at a university dermatology department, 15 patients with actinic cheilitis received two sessions of PDT of the lower lip at an interval of 1 week using methylaminoxopentanoate and red light. Clinical and histopathologic evaluation was performed 3 months after therapy. RESULTS Complete clinical cure was observed in 47% (7/15) and partial cure in another 47% (7/15) of the patients. By histopathologic analysis, residual disease was found in 62% (8/13). Cosmetic results and patients' satisfaction were good to excellent in most cases. Local pain was sufficiently controlled by local anesthesia. CONCLUSION PDT can be an effective noninvasive method to treat actinic cheilitis of the lower lip.
Investigation on Polylactide (PLA)/Poly(butylene adipate-co-terephthalate) (PBAT)/Bark Flour of Plane Tree (PF) Eco-Composites

Polylactide (PLA)/poly(butylene adipate-co-terephthalate) (PBAT)/bark flour of plane tree (PF) eco-composites were prepared via melt blending. The morphologies, mechanical properties, crystal structures and melting and crystallization behaviors of the eco-composites were investigated by means of scanning electron microscopy (SEM), mechanical tests, polarized light microscopy (PLM), wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC), respectively. It is shown that the interfacial adhesion between PLA matrix and PF is weak and the mechanical properties of PLA/PF eco-composites are poor. The titanate treatment improves the adhesion between the matrix and the filler and enhances the stiffness of the eco-composites. The toughness is improved by PBAT and ductile fractured surfaces can be found. The spherulitic size of PLA is decreased by the addition of PF. The α crystalline form of PLA remains in the composites. Compared with PF, T-PF (PF treated by a titanate coupling agent) and PBAT have negative effects on the crystallization of PLA.
Oral Absorption, Intestinal Metabolism and Human Oral Bioavailability

Most of the drugs that are available in the marketplace are administered via the oral route, which is a convenient and cost effective route of administration (Lipinski 1995; Lipinski 2000; Lipinski et al. 2001; Lipinski 2004; Abrahamsson and Lennernas 2005). Thus, oral bioavailability is one of the key considerations for discovery and development of a new chemical entity (NCE). It is well recognized that poor oral bioavailability is one of the major causes of therapeutic variability, associated with the variable drug exposure (Beierle et al. 1999; Bardelmeijer et al. 2000; Katsura and Inui 2003). This is particularly important for drugs with narrow therapeutic window or potential for resistance development such as antibiotics and cytotoxic drugs (Bardelmeijer et al. 2000). Hellriegel et al. reported a significant inverse relationship between the oral bioavailability of drugs from several therapeutic classes and the coefficient of inter-individual variability in their oral bioavailability (Hellriegel et al. 1996).
Serotonin induces the increase in intracellular Ca2+ that enhances neurite outgrowth in PC12 cells via activation of 5‐HT3 receptors and voltage‐gated calcium channels

As a neurotransmitter and neuromodulator, serotonin (5‐HT) influences neuronal outgrowth in the nervous systems of several species. In PC12 cells, 5‐HT is known to have neuritogenic effects, although the signal transduction pathway responsible for these effects is not understood. In this study, we hypothesized that a 5‐HT‐induced increase in intracellular Ca2+ concentration ([Ca2+]i) could be involved in mediating the effects of 5‐HT. Application of 5‐HT to PC12 cells enhanced nerve growth factor (NGF)‐induced neurite outgrowth in a dose‐dependent manner, and the sensitivity of this neuritogenic effect was increased in differentiated PC12 cells. In accordance, an increase in [Ca2+]i was observed following application of 5‐HT in differentiated PC12 cells. This increase was amplified by further NGF treatment. 5‐HT‐induced increases in [Ca2+]i were inhibited by MDL 72222, a selective 5‐HT3 receptor antagonist, and nifedipine, an L‐type calcium channel blocker, but not by ketanserin, a 5‐HT2 receptor antagonist, or thapsigargin, a specific inhibitor of endoplasmic reticulum Ca2+‐ATPase. These pharmacological tests indicated that 5‐HT‐induced increases in [Ca2+]i are mediated by activation of voltage‐gated calcium channels via 5‐HT3 receptors and that 5‐HT‐induced increases in [Ca2+]i are likely to be independent of activation of 5‐HT2 receptors in PC12 cells. Furthermore, the neuritogenic effect of 5‐HT was suppressed by MDL 72222, nifedipine, calmodulin (CaM) inhibitor, and calcineurin inhibitors. Taken together, our results indicate that 5‐HT‐induced increases in [Ca2+]i, which are mediated via 5‐HT3 receptors and L‐type calcium channels in PC12 cells, and subsequent activation of CaM and calcineurin enhance NGF‐induced neurite outgrowth. © 2006 Wiley‐Liss, Inc.
Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial.

CONTEXT Nondystrophic myotonias (NDMs) are rare diseases caused by mutations in skeletal muscle ion channels. Patients experience delayed muscle relaxation causing functionally limiting stiffness and pain. Mexiletine-induced sodium channel blockade reduced myotonia in small studies; however, as is common in rare diseases, larger studies of safety and efficacy have not previously been considered feasible. OBJECTIVE To determine the effects of mexiletine for symptoms and signs of myotonia in patients with NDMs. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled 2-period crossover study at 7 neuromuscular referral centers in 4 countries of 59 patients with NDMs conducted between December 23, 2008, and March 30, 2011, as part of the National Institutes of Health-funded Rare Disease Clinical Research Network. INTERVENTION Oral 200-mg mexiletine or placebo capsules 3 times daily for 4 weeks, followed by the opposite intervention for 4 weeks, with 1-week washout in between. MAIN OUTCOME MEASURES Patient-reported severity score of stiffness recorded on an interactive voice response (IVR) diary (scale of 1 = minimal to 9 = worst ever experienced). Secondary end points included IVR-reported changes in pain, weakness, and tiredness; clinical myotonia assessment; quantitative measure of handgrip myotonia; and Individualized Neuromuscular Quality of Life summary quality of life score (INQOL-QOL, percentage of maximal detrimental impact). RESULTS Mexiletine significantly improved patient-reported severity score stiffness on the IVR diary. Because of a statistically significant interaction between treatment and period for this outcome, primary end point is presented by period (period 1 means were 2.53 for mexiletine and 4.21 for placebo; difference, -1.68; 95% CI, -2.66 to -0.706; P < .001; period 2 means were 1.60 for mexiletine and 5.27 for placebo; difference, -3.68; 95% CI, -3.85 to -0.139; P = .04). Mexiletine improved the INQOL-QOL score (mexiletine, 14.0 vs placebo, 16.7; difference, -2.69; 95% CI, -4.07 to -1.30; P < .001) and decreased handgrip myotonia on clinical examination (mexiletine, 0.164 seconds vs placebo, 0.494 seconds; difference, -0.330; 95% CI, -0.633 to -0.142; P < .001). The most common adverse effect was gastrointestinal (9 mexiletine and 1 placebo). Two participants experienced transient cardiac effects that did not require stopping the study (1 in each group). One serious adverse event was determined to be not study related. CONCLUSION In this preliminary study of patients with NDMs, the use of mexiletine compared with placebo resulted in improved patient-reported stiffness over 4 weeks of treatment, despite some concern about the maintenance of blinding. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00832000.
Look for evidence that place of residence influenced visitor attitudes to feeding wild dolphins

Purpose – To ascertain if place attachment or experiential norms influence visitor attitudes to the feeding of wild dolphins. Design/Methodology/Approach – A cross section of beach based visitors at a popular Australian marine tourism destination were opportunistically sampled using pen and paper questionnaires. Findings – Visitors expressed strong support for the strictly controlled minimalist reward feeding that accompanies beach based wild dolphin interactions at the Bunbury Dolphin Discovery Centre and visitors believe there are tourism benefits to be gained from the regulated feeding of wild dolphins. Results also suggest that neither place attachment nor experiential norms influence visitor attitudes to feeding of the Koombana Bay dolphin population. Originality of the research – This location specific, snapshot, case study suggests that contrary to published theory, place attachment and experiential norms do not influence tourist attitudes to wildlife feeding, especially for charismatic iconic wildlife such as dolphins.
Pharmacokinetic-Pharmacodynamic Analyses for Efficacy of Ceftaroline Fosamil in Patients with Community-Acquired Bacterial Pneumonia

ABSTRACT Pharmacokinetic-pharmacodynamic (PK-PD) analyses for efficacy using phase III trial data from patients treated with a ceftaroline fosamil dosing regimen of 600 mg intravenously (i.v.) every 12 h (q12h) for 5 to 7 days for community-acquired bacterial pneumonia (CABP) were conducted. High clinical and microbiological success rates (84.7 and 86.3%, respectively) and percentages of time during the dosing interval that free-drug steady-state concentrations remained above the MIC (f%T>MIC) (98.4% had f%T>MIC values of ≥63.3) were observed among 124 microbiologically evaluable patients. As a result, significant PK-PD relationships could not be identified. These data provide support for the use of a ceftaroline fosamil dosing regimen of 600 mg i.v. q12h to treat patients with CABP.