Miracle-dz/UniFAR-FTUs huggingface dataset:
A study on the modulation of alpha-synuclein fibrillation by Scutellaria pinnatifida extracts and its neuroprotective properties

Aggregation of alpha-synuclein (α-SN) is a key pathogenic event in Parkinson’s disease (PD) leading to dopaminergic degeneration. The identification of natural compounds inhibiting α-SN aggregation may have a major role in treating PD. Different Scutellaria species are known as valuable medicinal plants, primarily due to their high flavonoid levels. Scutellaria pinnatifida (S. pinnatifida) is endemic to Iran; however, the knowledge of its pharmaceutical properties is limited. Here we report that S. pinnatifida extracts have an anti-fibrillation effect on α-SN aggregation and neuroprotective properties on PC12 and primary dopaminergic neurons. Treatment during α-SN fibril formation with S. pinnatifida extracts showed that the extractions performed with dichloromethane (DCMEx) and n-butanol (BuOHEx) strongly inhibited α-SN fibrillation. TLC-based analysis revealed that S. pinnatifida contains a great amount of flavonoids with high antioxidant properties as shown using a radical scavenging assay. Further analysis using HPLC and Mass spectroscopy on the DCMEx revealed the presence of baicalein in this extract. We then selected the more efficient extracts based on cell viability and ROS scavenging on PC12 cells and tested their neuroprotective properties on primary dopaminergic neurons. Our results showed the extracts strongly protected against α-SN oligomers. Surprisingly, they also neutralized the severe toxicity of paraquat. Therefore, S. pinnatifida may be a potential valuable medicinal herb for further studies related to the treatment of PD.
Criminal Responsibility of the Pharmacist in the Pharmaceutical Services in Indonesia

Medical malpractice has a long history in Indonesia, with fatal consequences for patients due to negligence from the health practitioner. This study aims to ensure legal certainty in pharmaceutical practice according to laws and regulations. Also, to provide criminal law sanctions for pharmacists in pharmaceutical practices that lead to criminal acts. The method used was qualitative empirical normative research with a literature study. This research was conducted qualitatively based on data triangulation which resulted from three ways: interview, participant to observation, and review of organizational records (document records). Data collection usually uses qualitative research observation, documentation, and interview methods. This study discusses legal provisions related to health and pharmaceutical services and interviews with ten people at Dr. Wahidin Sudirohusodo Regional General Hospital, Makassar, and five people from Wamena Regional General Hospital, Jayawijaya Regency, Papua. Our study exhibited that implementing a pharmacist's practice was based on the prevailing laws and regulations. The pharmaceutical practice in question starts from planning, procurement, storage, distribution, evaluation, and provision of drug information and monitoring of drug side effects. These practices are based on Government Regulation No. 51 of 2009 article 4. This regulation is stated to protect patients and the public in obtaining and stipulating pharmaceutical preparations and pharmaceutical services. In addition, to maintain and improve the quality of implementation of pharmaceutical work by using developments in science and technology as well as laws and regulations; and provide legal certainty for patients, communities, and pharmaceutical workers. In the criminal responsibility of pharmacists in pharmaceutical services that have resulted in illegal acts, there have not been cases that have reached court proceedings. Nevertheless, there are cases where actions that have resulted in criminal acts have occurred in the field. Still, mediation can resolve them to reach a consensus with unique mediation.
Procedural Modeling for Digital Cultural Heritage

The rapid development of computer graphics and imaging provides the modern archeologist with several tools to realistically model and visualize archeological sites in 3D. This, however, creates a tension between veridical and realistic modeling. Visually compelling models may lead people to falsely believe that there exists very precise knowledge about the past appearance of a site. In order to make the underlying uncertainty visible, it has been proposed to encode this uncertainty with different levels of transparency in the rendering, or of decoloration of the textures. We argue that procedural modeling technology based on shape grammars provides an interesting alternative to such measures, as they tend to spoil the experience for the observer. Both its efficiency and compactness make procedural modeling a tool to produce multiple models, which together sample the space of possibilities. Variations between the different models express levels of uncertainty implicitly, while letting each individual model keeping its realistic appearance. The underlying, structural description makes the uncertainty explicit. Additionally, procedural modeling also yields the flexibility to incorporate changes as knowledge of an archeological site gets refined. Annotations explaining modeling decisions can be included. We demonstrate our procedural modeling implementation with several recent examples.
An evaluation of approaches to federated query processing over linked data

The Web has evolved from a global information space of linked documents to a web of linked data. The Web of Data enables answering complex, structured queries that could not be answered by a single data source alone. While the current procedure to work with multiple, distributed linked data sources is to load the desired data into a single RDF store and process queries in a centralized way against the merged data set, such an approach may not always be practically feasible or desired. In this paper, we analyze alternative approaches to federated query processing over linked data and how different design alternatives affect the performance and practicality of query processing. To this end, we define a benchmark for federated query processing, comprising a selection of data sources in various domains and representative queries. Using the benchmark, we perform experiments with different federation alternatives and provide insights about their advantages and disadvantages.
No-jump-into-basic-block: Enforce basic block CFI on the fly for real-world binaries

Code-reuse attack is a growing threat to computing systems as it can circumvent existing security defenses. Fortunately, control flow integrity (CFI) is promising in defending such attack. However, former implementations generally suffer from two major drawbacks: 1) complex pre-processing to obtain control flow graph; 2) high overhead. In this paper, we propose a cross-layer approach that employs basic block information inside the binary code and read-only data to enforce fine-grained control-flow integrity. Our approach demonstrates high applicability and thorough attack detection coverage without static analysis or recompilation. Meanwhile, it can effectively protect even striped programs, while incurring negligible 0.13% performance overhead.
A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression

Objective To compare response and remission rates in depressed patients with chronic treatment-resistant depression (TRD) treated with vagus nerve stimulation (VNS) Therapy® plus treatment as usual (VNS + TAU) or TAU alone in a meta-analysis using Bayesian hierarchical models. Data sources and study selection Six outpatient, multicenter, clinical trials that have evaluated VNS + TAU or TAU in TRD, including two single-arm studies of VNS + TAU (n = 60 and n = 74), a randomized study of VNS + TAU versus TAU (n = 235), a randomized study of VNS + TAU comparing different VNS stimulation intensities (n = 331), a nonrandomized registry of VNS + TAU versus TAU (n = 636), and a single-arm study of TAU (n = 124) to provide longer-term, control data for comparison with VNS-treated patients. Data extraction A systematic review of individual patient-level data based on the intent-to-treat principle, including all patients who contributed more than one post-baseline visit. Response was based on the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions scale’s Improvement subscale (CGI-I), as these were the two clinician-rated measures common across all or most studies. Remission was based on the MADRS. Results Outcomes were compared from baseline up to 96 weeks of treatment with VNS + TAU (n = 1035) versus TAU (n = 425). The MADRS response rate for VNS + TAU at 12, 24, 48, and 96 weeks were 12%, 18%, 28%, and 32% versus 4%, 7%, 12%, and 14% for TAU. The MADRS remission rate for VNS + TAU at 12, 24, 48, and 96 weeks were 3%, 5%, 10%, and 14% versus 1%, 1%, 2%, and 4%, for TAU. Adjunctive VNS Therapy was associated with a greater likelihood of response (odds ratio [OR] = 3.19, 95% confidence interval [CI]: 2.12, 4.66) and remission (OR = 4.99, CI: 2.93, 7.76), compared with TAU. For patients who had responded to VNS + TAU at 24 weeks, sustained response was more likely at 48 weeks (OR = 1.98, CI: 1.34, 3.01) and at 96 weeks (OR = 3.42, CI: 1.78, 7.31). Similar results were observed for CGI-I response. Conclusion For patients with chronic TRD, VNS + TAU has greater response and remission rates that are more likely to persist than TAU.
Localization of the Kar3 kinesin heavy chain-related protein requires the Cik1 interacting protein

The Kar3 protein (Kar3p), a protein related to kinesin heavy chain, and the Cik1 protein (Cik1p) appear to participate in the same cellular processes in S. cerevisiae. Phenotypic analysis of mutants indicates that both CIK1 and KAR3 participate in spindle formation and karyogamy. In addition, the expression of both genes is induced by pheromone treatment. In vegetatively growing cells, both Cik1::beta-gal and Kar3::beta-gal fusions localize to the spindle pole body (SPB), and after pheromone treatment both fusion proteins localize to the spindle pole body and cytoplasmic microtubules. The dependence of Cik1p and Kar3p localization upon one another was investigated by indirect immunofluorescence of fusion proteins in pheromone-treated cells. The Cik1p::beta-gal fusion does not localize to the SPB or microtubules in a kar3 delta strain, and the Kar3p::beta-gal fusion protein does not localize to microtubule-associated structures in a cik1 delta strain. Thus, these proteins appear to be interdependent for localization to the SPB and microtubules. Analysis by both the two-hybrid system and co- immunoprecipitation experiments indicates that Cik1p and kar3p interact, suggesting that they are part of the same protein complex. These data indicate that interaction between a putative kinesin heavy chain-related protein and another protein can determine the localization of motor activity and thereby affect the functional specificity of the motor complex.
Assessment of the Relationship between Periodontitis and Cardiac Parameters in Patients with Early Chronic Heart Failure: A Cross-Sectional Study

Periodontal disease (PD) is considered a risk factor for cardiovascular events. However, its relationship to chronic heart failure (CHF) is unclear. The aim was to compare cardiac and inflammatory parameters in CHF patients with (PG) versus without periodontitis (NPG). The following parameters were recorded in 58 patients: periodontal screening and recording (PSR), troponin T, NT-proBNP, C-reactive protein (CRP), interleukin-6 (IL-6), blood pressure, heart rate, ejection fraction (EF), ventricular systolic and diastolic function parameters, incremental test, and three questionnaires (Mediterranean Diet Adherence Screener, MEDAS; Oral Health Impact Profile, OHIP-14; Patient Health Questionnaire, PHQ). The serum levels of NT-proBNP and troponin T were significantly higher in the PG, and the left ventricular systolic and diastolic function parameters were significantly lower. The correlation analysis showed age as the only independent risk factor for periodontitis and cardiac biomarkers. No significant group differences were found in the MEDAS, OHIP-14, and PHQ scores, or in CRP, IL-6, and cardiocirculatory parameters. Overall, the BMI correlated significantly with the mean PSR and total cholesterol. The occurrence of increased PSR together with increased age and cardiac risk parameters does not exclude an association between periodontitis and CHF, though no positive correlation was calculated. Periodontitis may be a modifiable risk factor for CHF. Its treatment may help to control the inflammatory burden.
A Pyramidal Approach to Content-Based Image Retrieval

Search based on image contents is an important issue in large image and video databases. In this paper, two methods for a better content-based image retrieval (CBIR) are presented, namely, the use of recognition kernel and locales. Features of model objects are extracted at levels that are most appropriate to yield only the necessary yet sufficient details, together they form the kernel. Instead of relying on image segmentation, a method of feature localization based on locales is developed. It is shown that the deployment of the recognition kernel and locales in a pyramidal (multiresolution) framework delivers good retrieval results.
Specification and morphogenesis of the zebrafish larval head skeleton.

Forward genetic analyses can reveal important developmental regulatory genes and how they function to pattern morphology. This is because a mutated gene can produce a novel, sometimes beautiful, phenotype that, like the normal phenotype, immediately seems worth understanding. Generally the loss-of-function mutant phenotype is simplified from the wild-type one, and often the nature of the pattern simplification allows one to deduce how the wild-type gene contributes to patterning the normal, more complex, morphology. This truism seems no less valid for the vertebrate head skeleton than for other and simpler cases of patterning in multicellular plants and animals. To show this, we review selected zebrafish craniofacial mutants. "Midline group" mutations, in genes functioning in one of at least three signal transduction pathways, lead to neurocranial pattern truncations that are primarily along the mediolateral axis. Mutation of lazarus/pbx4, encoding a hox gene partner, and mutation of valentino/kreisler, a hox gene regulator, produce anterior-posterior axis disruptions of pharyngeal cartilages. Dorsoventral axis patterning of the same cartilages is disrupted in sucker/endothelin-1 mutants. We infer that different signal transduction pathways pattern cartilage development along these three separate axes. Patterning of at least the anterior-posterior and dorsoventral axes have been broadly conserved, e.g., reduced Endothelin-1 signaling similarly perturbs cartilage specification in chick, mouse, and zebrafish. We hypothesize that Endothelin-1 also is an upstream organizer of the patterns of cellular interactions during cartilage morphogenesis.
What do game developers expect from development and design tools?

Context: Development of software is a complex process with several stakeholders and their varying practices. The game industry has also additional requirements such as artistic presentation, an interesting story and high quality sound effects that further complicate the process. Objective: The objective of this paper is to understand what kind of requirements and expectations are attached to the technical infrastructure of game development in practice. Method: This study observed and qualitatively analyzed seven game-developing organizations, from recent startups to established organizations to allow comparison of their use of technical infrastructure. Results: Based on our study, the game organizations, regardless of their size, are generally pleased with the tools they apply. The selections of the applied tools are based on their ability to test concepts and build prototypes to help design. Conclusion: In general, the game development organizations expect their tools to allow adaptability to changes during the development process. The case companies did not seem to have many problems with their current technical infrastructure, and ability to test different solutions was considered very important feature.
RUQYAH: LISTENING TO QURANIC VERSES, A DISEASE TREATMENT STRATEGY

The global Muslim population has surpassed two million, and Islamic principles emphasize accepting teachings from the Holy Quran and Sunnah for theoretical and practical guidance. Among these teachings is the recommendation to seek healing through reciting the Quran, known as 'Ruqyah Shar'iyya. ' Despite its significance, medical professionals in Muslim-majority countries often need more awareness of Ruqyah, leading to an overreliance on pharmacological treatments with potential side effects. This study aims to increase awareness among healthcare providers about authentic and updated knowledge regarding Islamic teachings related to disease treatment through listening to the Quran and supplications. Through a descriptive literature review, the research explores critical terms such as Ruqyah, shifa (healing), treatment by Quran, spiritual treatment, Islamic treatment, and supplication in various sources, including the Quran, Hadith books, Google Scholar, and PubMed. While pharmacological treatments remain the primary approach for many diseases, this study suggests that non-pharmacological strategies, such as Quran recitation (Ruqyah) and specific supplications, align with the recommendations of Prophet Mohammad (ﷺ). Training doctors, nurses, and healthcare providers in the Muslim community to incorporate Ruqyah into their practice or involving Ruqyah professionals for Muslim patients can offer additional treatment options. This approach promotes healing without side effects and enhances patients' patience, satisfaction, and overall well-being. Such practices improve quality of life and foster trust in the doctor-patient relationship.
Proteomic analysis reveals Hrs ubiquitin‐interacting motif‐mediated ubiquitin signaling in multiple cellular processes

Despite the critical importance of protein ubiquitination in the regulation of diverse cellular processes, the molecular mechanisms by which cells recognize and transmit ubiquitin signals remain poorly understood. The endosomal sorting machinery component hepatocyte growth factor‐regulated tyrosine kinase substrate (Hrs) contains a ubiquitin‐interacting motif (UIM), which is believed to bind ubiquitinated membrane cargo proteins and mediate their sorting to the lysosomal degradation pathway. To gain insight into the role of Hrs UIM‐mediated ubiquitin signaling in cells, we performed a proteomic screen for Hrs UIM‐interacting ubiquitinated proteins in human brain by using an in vitro expression cloning screening approach. We have identified 48 ubiquitinated proteins that are specifically recognized by the UIM domain of Hrs. Among them, 12 are membrane proteins that are likely to be Hrs cargo proteins, and four are membrane protein‐associated adaptor proteins whose ubiquitination may act as a signal to target their associated membrane cargo for Hrs‐mediated endosomal sorting. Other classes of the identified proteins include components of the vesicular trafficking machinery, cell signaling molecules, proteins associated with the cytoskeleton and cytoskeleton‐dependent transport, and enzymes involved in ubiquitination and metabolism, suggesting the involvement of Hrs UIM‐mediated ubiquitin signaling in the regulation of multiple cellular processes. We have characterized the ubiquitination of two identified proteins, Munc18‐1 and Hsc70, and their interaction with Hrs UIM, and provided functional evidence supporting a role for Hsc70 in the regulation of Hrs‐mediated endosome‐to‐lysosome trafficking.
Augmenting the Efficacy of a Polyvinyl Alcohol Selective Layer Coated on Polyvinylidene Fluoride Support Membranes with Kaolinite Introduction for Improved Pervaporation Dehydration of Epichlorohydrin/Isopropanol/Water Ternary Systems

Composite membranes with a polyvinyl alcohol (PVA) selective layer composed of well-dispersed hydrophilic kaolinite particles coated on a polyvinylidene fluoride (PVDF) support were developed. They were applied to the pervaporation dehydration of the industrially important epichlorohydrin (ECH)/isopropanol (IPA)/water ternary mixture. In comparison with raw kaolinite (RK), hydrophilic kaolinite (HK) enhanced the mechanical properties, hydrophilicity, and thermal stability of the PVA selective layer, as confirmed by universal testing, the contact angle, and TGA analyses, respectively. The pervaporation results revealed that the addition of HK particles significantly enhanced the separation factor (3-fold). Only a marginal reduction in flux was observed with ECH/IPA/water, 50/30/20 (w/w %) at 40 °C. An HK particle concentration of 4 wt. % with respect to PVA delivered the highest flux performance of 0.86 kg/m2h and achieved a separation factor of 116. The PVA–kaolinite composite membrane exhibited pronounced resistance to the ECH-containing feed, demonstrating a sustained flux and separation factor throughout an extended pervaporation stability test lasting 250 h.
When it Rains , it Pours : Capital Flows with Twin External Crises ∗

This paper examines the joint dynamics of private and public external debt for countries. We develop a model with the co-occurrence of banking crisis and sovereign debt crisis in open economies, formalizing Reinhart and Rogoff (2011) findings “from financial crash to debt crisis". External interest rate spikes or sudden stop shocks force banks to cut down debt position and fire-sale capital. The existence of frictions in bank equity market creates incentives for the government to initiate a bailout. The government bails out banks by increasing external borrowing and implementing fiscal austerity to undo inefficiencies in the private sector. Under optimal bailout scheme, the model generates diverging external debt dynamics for the private sector and the government during a crisis, as we document in the European data. Finally, we investigate two rationales for ex-ante macro-prudential regulations on private external debt: fire-sale externalities between banks and moral hazard by banks. JEL classification: F34 F41 G01 G21 G28
Floating Points: A Method for Computing Stipple Drawings

We present a method for computer generated pen‐and‐ink illustrations by the simulation of stippling. In a stipple drawing, dots are used to represent tone and also material of surfaces. We create such drawings by generating an initial dot set which is then processed by a relaxation method based on Voronoi diagrams. The point patterns generated are approximations of Poisson disc distributions and can also be used for integrating functions or the positioning of objects. We provide an editor similar to paint systems for interactively creating stipple drawings. This makes it possible to create such drawings within a matter of hours, instead of days or even weeks when the drawing is done manually.