Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer’s Disease

Abstract Background Odor identification (OI) dysfunction is an early marker of Alzheimer’s disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. Methods Two hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls. Results From the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants. Conclusion Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.
Solitary Peutz–Jeghers Type Hamartoma in a Nigerian: A Case Report of a Rare Finding and Review of Literature

Background: We report a case of solitary Peutz–Jeghers (P-J) type hamartomatous polyp in the sigmoid colon of an asymptomatic Nigerian without other diagnostic criteria for full-blown P-J syndrome. Case Report: During colonoscopy for a 58-year-old man, a solitary, pedunculated polyp was seen in the sigmoid colon. Histopathological examination of the endoscopically resected mass revealed the classical features of P-J type hamartoma. A search for lentigines on the skin or mucous buccal membranes was negative. There is no family history of such findings. Conclusion: The case here presented is truly rare as a review of the scientific literature appears, to the best of our knowledge, not to contain such a unique presentation from our locality nor indeed from among Black Africans. We conducted a review of the literature and wished to highlight the evolving concept that solitary P-J polyps be considered a distinct disease entity when it appears in the absence of other features of the syndrome complex.
INDUCTION GENERATOR BASED WIND TURBINE FOR ELECTRICAL POWER GENERATION

Nowadays the demand of electricity is going increases every day and to fulfill the requirement of these up growing demands many researchers works on different alternate energy recourses to generates cheap electrical power. The most common and freely available alternate recourses are wind energy and solar energy which can easily be convertible in to usable electrical power. This research article only focused on wind energy alternate resource to generate electrical power. For experimental purposes a three phase induction generator based 5 KW small wind turbine is selected. Metrological wind speed data of Kuala Perlis Malaysia is used for simulation purpose and the performance of wind turbine is tested and verified using MATLAB Simulink Tool. Simulation results verified that small wind turbines can use as an alternate resource to generate electrical power.
Dinucleotide tag‐based parallel reporter gene assay method enables efficient identification of regulatory mutations

The causal single nucleotide polymorphisms (SNPs) leading to increased cancer predisposition mainly function as gene regulatory elements, the evaluation of which largely relies on the parallel reporter gene assay system. However, the common DNA barcodes used in parallel reporter gene assay systems typically because nucleotide composition bias, and many barcodes must be allocated for each sequence to reduce the bias effect.
Detection of food fraud of meat products from the different brands by application of histological methods

In Sohag City, 400 samples were collected from different food markets of different meat products from two companies with high and low prices (e.g., minced meat, kofta sausage, beef burger, and luncheon meat) for determining food fraud. Light, fluorescence, and scanning electron microscopy (SEM) were used to examine the samples. “Special histochemical stains” permit the microscopic examination of different cell types, structures, and/or microorganisms. Histological examination revealed variant tissue types, besides skeletal muscles. Nuchal ligaments, bones, hyaline cartilages, white fibrocartilages, large and medium arteries, cardiac muscles, tendons, and collagenous connective tissues comprised the capsule of a parenchymatous organ. Additionally, a crystal of food additives was recognized using light microscopy and SEM. SEM allows the visualization of bacterial contamination. Using different microscopic anatomy techniques is an efficient methodology for qualitative evaluations of various meat products. No difference in quality was observed between low‐ and high‐priced meat products.
Circularly polarised printed array antennas composed of strips and slots

This letter presents a new type of circularly polarised micro-strip antenna. It is composed of half-wavelength strip conductors and slots arranged along both sides of a microstrip line. Circular polarisation can easily be obtained with this antenna whether the current distribution on the line is a travelling wave or a standing wave. The experimental verification is also presented.
RF/microwave test simulator

The generation of quality RF/Microwave Test Program Sets (TPS) has always been a technically challenging and expensive task. The lack of an RF/microwave test simulator makes the generation of test and diagnostic vectors a very time consuming task. RF/microwave components exhibit multiple fault modes, i.e. gain, noise figure, etc., as compared to the "1" or "0" fault mode of digital circuitry. Also, due to the parametric nature of an RF/microwave device, each failure mode is application specific and forces the development of multiple fault classes. The result has increased TPS costs and stretched schedules when compared to digital testing where test simulators do exist. This paper outlines an approach to developing an RF/microwave Test Simulator. Design simulation software is utilized to provide a behavioral model of the Unit Under Test (UUT). A multi-dimensional fault dictionary is generated based on this behavioral knowledge which enables the tester to consider the multiple fault modes and fault classes in order to achieve "probeless" diagnostics. <<ETX>>
Fast algorithm for Traffic Sign Recognition

Information technology improves convenience, safety, and performance of automobiles. Recently, a lot of algorithms are studied to provide safety and environment information for driving, and traffic sign recognition is one of them. It can provide important information for safety driving. In this paper, we propose a method for traffic sign detection and identification concentrating on reducing the computation time. First, potential traffic signs are segmented by color threshold, and a polygon approximation algorithm is used to detect appropriate polygons. The potential signs are compared with the template signs in the database using SURF and ORB feature matching method.
Molecular mechanism of glycolytic flux control intrinsic to human phosphoglycerate kinase

Significance Control of glycolytic flux plays an important role in energy production and metabolic homeostasis in cells. Phosphoglycerate kinase (PGK), a glycolytic enzyme, catalyzes reversible phosphotransfer to generate 3-phosphoglycerate (3PG) and adenosine triophosphate (ATP) in glycolysis. PGK controls glycolytic flux according to the intracellular [ATP]/[ADP] (adenosine diphosphate) ratio; however, its molecular mechanism remains unknown. Here, we report a protein-level regulation of the human PGK reaction by switching ligand-binding cooperativities between adenine nucleotides and 3PG, which is finely tuned to appropriately respond to changes in the intracellular [ATP]/[ADP] ratio. Our findings reveal a molecular mechanism intrinsic to human PGK that controls glycolytic flux by rapid adaptation to changes in the intracellular environment to avoid critical damage. Glycolysis plays a fundamental role in energy production and metabolic homeostasis. The intracellular [adenosine triphosphate]/[adenosine diphosphate] ([ATP]/[ADP]) ratio controls glycolytic flux; however, the regulatory mechanism underlying reactions catalyzed by individual glycolytic enzymes enabling flux adaptation remains incompletely understood. Phosphoglycerate kinase (PGK) catalyzes the reversible phosphotransfer reaction, which directly produces ATP in a near-equilibrium step of glycolysis. Despite extensive studies on the transcriptional regulation of PGK expression, the mechanism in response to changes in the [ATP]/[ADP] ratio remains obscure. Here, we report a protein-level regulation of human PGK (hPGK) by utilizing the switching ligand-binding cooperativities between adenine nucleotides and 3-phosphoglycerate (3PG). This was revealed by nuclear magnetic resonance (NMR) spectroscopy at physiological salt concentrations. MgADP and 3PG bind to hPGK with negative cooperativity, whereas MgAMPPNP (a nonhydrolyzable ATP analog) and 3PG bind to hPGK with positive cooperativity. These opposite cooperativities enable a shift between different ligand-bound states depending on the intracellular [ATP]/[ADP] ratio. Based on these findings, we present an atomic-scale description of the reaction scheme for hPGK under physiological conditions. Our results indicate that hPGK intrinsically modulates its function via ligand-binding cooperativities that are finely tuned to respond to changes in the [ATP]/[ADP] ratio. The alteration of ligand-binding cooperativities could be one of the self-regulatory mechanisms for enzymes in bidirectional pathways, which enables rapid adaptation to changes in the intracellular environment.
Clinical outcomes and cardiac rehabilitation in underrepresented groups after percutaneous coronary intervention: an observational study.

AIMS Underrepresentation of migrants, women, and older adults in cardiovascular disease (CVD) trials may contribute to disparate care and survival. Among patients who underwent percutaneous coronary intervention (PCI), we aimed to investigate the associations of (i) underrepresented groups with major adverse cardiac events (MACE), CVD mortality, and non-CVD mortality, (ii) underrepresented groups with cardiac rehabilitation (CR) uptake, and (iii) CR uptake with outcomes. METHODS AND RESULTS We included 15 211 consecutive patients from the CARDIOBASE Bern PCI registry (2009-18). In multi-state models comparing transition probabilities of events, sex was not associated with increased risk of any event. For each year increase in age, the increased risk of non-CVD and CVD mortality was 8% [95% confidence interval (CI) 6-9%]. Being migrant was associated with a lower risk of non-CVD mortality [hazard ratio (HR) (95% CI) 0.49 (0.27-0.90)] but not with CVD mortality. In logistic regression analysis, CR uptake was lower among women [odds ratio (95% CI) = 0.72 (0.57-0.86)] and older adults [0.32 (0.27-0.38)], but not among migrants. In cox regression, CR was independently associated with lower all-cause [HR (95% CI) = 0.12 (0.03-0.37)] and CVD mortality [0.1 (0.02-0.7)], but not with MACE [1.08 (0.8-1.4)]. CONCLUSION Among underrepresented groups undergoing PCI, age, but not migration status nor sex, contributed to disparities in mortality. Migrant status did not result in lower attendance of CR. Considering the protective associations of CR on CVD mortality independent of age, sex, and migration status, the lower uptake in women and older adults is noteworthy.
Effect of reinforcements and heat treatment on tensile strength of Al-Si-Mg based hybrid composites

Metal Matrix Composites (MMCs) constitute an important class of design and weight-efficient structural materials that are encouraging every sphere of engineering applications and mainly in aerospace applications. The present investigation is focused on formation of a hybrid composite by using industrial waste fly ash and E glass short fibers by dispersing them into AA7075 alloy by Stir casting method. The MMC is obtained for the different compositions of E-glass and Fly ash particulates. The test specimens are prepared to the standard size by turning and facing operations to conduct tensile test and the specimens are subjected to heat treatment. The specimens were tested for tensile test at different loads by using Universal Test Machine. The results are plotted and it is concluded that the MMC obtained has got better tensile strength compared to Aluminum alloy (7075) alone. Further, tensile strength slightly increased with I hour aging heat treatment.
Evaluation of Remote Categorical Loudness Scaling.

PURPOSE The aims of this study were to (a) demonstrate the feasibility of administering categorical loudness scaling (CLS) tests in a remote setting, (b) assess the reliability of remote compared with laboratory CLS results, and (c) provide preliminary evidence of the validity of remote CLS testing. METHOD CLS data from 21 adult participants collected in a home setting were compared to CLS data collected in a laboratory setting from previous studies. Five participants took part in studies in both settings. Precalibrated equipment was delivered to participants who performed headphone output level checks and measured ambient noise levels. After a practice run, CLS measurements were collected for two runs at 1 and 4 kHz. RESULTS Mean headphone output levels were within 1.5 dB of the target calibration level. Mean ambient noise levels were below the target level. Within-run variability was similar between the two settings, but across-run bias was smaller for data collected in the laboratory setting compared with the remote setting. Systematic differences in CLS functions were not observed for the five individuals who participated in both settings. CONCLUSIONS This study demonstrated that precise stimulus levels can be delivered and background noise levels can be controlled in a home environment. Across-run bias for remote CLS was larger than for in-laboratory CLS, indicating that further work is needed to improve the reliability of CLS data collected in remote settings. Supplemental Material https://doi.org/10.23641/asha.17131856.
Characterisation of the genetic relationship between the domains of sleep and circadian‐related behaviours with substance use phenotypes

Sleep problems and substance use frequently co‐occur. While substance use can result in specific sleep deficits, genetic pleiotropy could explain part of the relationship between sleep and substance use and use disorders. Here we use the largest publicly available genome‐wide summary statistics of substance use behaviours (N = 79,729–632,802) and sleep/activity phenotypes to date (N = 85,502–449,734) to (1) assess the genetic overlap between substance use behaviours and both sleep and circadian‐related activity measures, (2) estimate clusters from genetic correlations and (3) test processes of causality versus genetic pleiotropy. We found 31 genetic correlations between substance use and sleep/activity after Bonferroni correction. These patterns of overlap were represented by two genetic clusters: (1) tobacco use severity (age of first regular tobacco use and smoking cessation) and sleep health (sleep duration, sleep efficiency and chronotype) and (2) substance consumption/problematic use (drinks per day and cigarettes per day, cannabis use disorder, opioid use disorder and problematic alcohol use) and sleep problems (insomnia, self‐reported short sleep duration, increased number of sleep episodes, increased sleep duration variability and diurnal inactivity) and measures of circadian‐related activity (L5, M10 and sleep midpoint). Latent causal variable analyses determined that horizontal pleiotropy (rather than genetic causality) underlies a majority of the associations between substance use and sleep/circadian related measures, except one plausible genetically causal relationship for opioid use disorder on self‐reported long sleep duration. Results show that shared genetics are likely a mechanism that is at least partly responsible for the overlap between sleep and substance use traits.
CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regulating the SIRT1-FOXO3-BNIP3 axis and enhances the therapeutic effects involving mitochondrial dysfunction in hepatocellular carcinoma

ABSTRACT Mitophagy is a type of selective macroautophagy/autophagy that degrades dysfunctional or excessive mitochondria. Regulation of this process is critical for maintaining cellular homeostasis and has been closely implicated in acquired drug resistance. However, the regulatory mechanisms and influences of mitophagy in cancer are still unclear. Here, we reported that inhibition of CDK9 blocked PINK1-PRKN-mediated mitophagy in HCC (hepatocellular carcinoma) by interrupting mitophagy initiation. We demonstrated that CDK9 inhibitors promoted dephosphorylation of SIRT1 and promoted FOXO3 protein degradation, which was regulated by its acetylation, leading to the transcriptional repression of FOXO3-driven BNIP3 and impairing the BNIP3-mediated stability of the PINK1 protein. Lysosomal degradation inhibitors could not rescue mitophagy flux blocked by CDK9 inhibitors. Thus, CDK9 inhibitors inactivated the SIRT1-FOXO3-BNIP3 axis and PINK1-PRKN pathway to subsequently block mitophagy initiation. Moreover, CDK9 inhibitors facilitated mitochondrial dysfunction. The dual effects of CDK9 inhibitors resulted in the destruction of mitochondrial homeostasis and cell death in HCC. Importantly, a novel CDK9 inhibitor, oroxylin A (OA), from Scutellaria baicalensis was investigated, and it showed strong therapeutic potential against HCC and a striking capacity to overcome drug resistance by downregulating PINK1-PRKN-mediated mitophagy. Additionally, because of the moderate and controlled inhibition of CDK9, OA not led to extreme repression of general transcription and appeared to overcome the inconsistent anti-HCC efficacy and high normal tissue toxicity that was associated with existing CDK9 inhibitors. All of the findings reveal that mitophagy disruption is a promising strategy for HCC treatment and OA is a potential candidate for the development of mitophagy inhibitors. Abbreviations: BNIP3: BCL2 interacting protein 3; CCCP: carbonyl cyanide p-trichloromethoxy-phenylhydrazone; CDK9: cyclin dependent kinase 9; CHX: cycloheximide; CQ, chloroquine; DFP: deferiprone; DOX: doxorubicin; EBSS: Earle’s balanced salt solution; E64d: aloxistatin; FOXO3: forkhead box O3; HCC: hepatocellular carcinoma; HepG2/ADR: adriamycin-resistant HepG2 cells; MMP: mitochondrial membrane potential; mito-Keima: mitochondria-targeted and pH-sensitive fluorescent protein; MitoSOX: mitochondrial reactive oxygen species; OA: oroxylin A; PB: phosphate buffer; PDX: patient-derived tumor xenograft; PINK1: PTEN induced kinase 1; POLR2A: RNA polymerase II subunit A; p-POLR2A-S2: Ser2 phosphorylation of RNA polymerase II subunit A; PRKN: parkin RBR E3 ubiquitin protein ligase; SIRT1: sirtuin 1.
Diverse molecular mechanisms of transcription regulation by the bacterial alarmone ppGpp

Bacteria must rapidly detect and respond to stressful environmental conditions. Guanosine tetraphosphate (ppGpp) is a universal stress signal that, in most bacteria, drives the reprograming of transcription at a global level. However, recent studies have revealed that the molecular mechanisms utilized by ppGpp to rewire bacterial transcriptomes are unexpectedly diverse. In Proteobacteria, ppGpp regulates the expression of hundreds of genes by directly binding to two sites on RNA polymerase (RNAP), one in combination with the transcription factor, DksA. Conversely, ppGpp indirectly regulates transcription in Firmicutes by controlling GTP levels. In this case, ppGpp inhibits enzymes that salvage and synthesize GTP, which indirectly represses transcription from rRNA and other promoters that use GTP for initiation. More recently, two different mechanisms of transcription regulation involving the direct binding of transcription factors by ppGpp have been described. First, in Francisella tularensis, ppGpp was shown to modulate the formation of a tripartite transcription factor complex that binds RNAP and activates virulence genes. Second, in Firmicutes, ppGpp allosterically regulates the transcription repressor, PurR, which controls purine biosynthesis genes. The diversity in bacterial ppGpp signaling revealed in these studies suggests the likelihood that additional paradigms in ppGpp‐mediated transcription regulation await discovery.
An Adjustable Adaptive Subdivision Surface Modeling Based on Triangle Meshes

Subdivision surfaces have become a standard technique for free shape modeling. But tradition subdivision scheme does not adjust the shape of subdivision results. In this paper, We introd uce adjustable adaptive subdivision as a new adaptive subdivision method for triangle meshes. This method applied to the method of adaptive subdivision constructs a new subdivision rule by introducing adjustable parameter to the traditional Loop scheme. The experiment shows that this method not only use fewer meshes to obtain the performance good surface but also can adjust the hape of subdivision surface to satisfy the actual need.
Understanding the Process of Economic Change

Preface vii CHAPTER ONE: An Outline of the Process of Economic Change 1 PART I: THE ISSUES INVOLVED IN UNDERSTANDING ECONOMIC CHANGE 9 INTRODUCTION 11 CHAPTER TWO: Uncertainty in a Non-ergodic World 13 CHAPTER THREE: Belief Systems, Culture, and Cognitive Science 23 CHAPTER FOUR: Consciousness and Human Intentionality 38 CHAPTER FIVE: The Scaffolds Humans Erect 48 CHAPTER SIX: Taking Stock 65 PART II: THE ROAD AHEAD 81 INTRODUCTION 83 CHAPTER SEVEN: The Evolving Human Environment 87 CHAPTER EIGHT: The Sources of Order and Disorder 103 CHAPTER NINE: Getting It Right and Getting It Wrong 116 CHAPTER TEN: The Rise of the Western World 127 CHAPTER ELEVEN: The Rise and Fall of the Soviet Union 146 CHAPTER TWELVE: Improving Economic Performance 155 CHAPTER THIRTEEN: Where Are We Going? 166 Bibliography 171 Index 183
Structural basis of DNA methylation-dependent site selectivity of the Epstein–Barr virus lytic switch protein ZEBRA/Zta/BZLF1

Abstract In infected cells, Epstein–Barr virus (EBV) alternates between latency and lytic replication. The viral bZIP transcription factor ZEBRA (Zta, BZLF1) regulates this cycle by binding to two classes of ZEBRA response elements (ZREs): CpG-free motifs resembling the consensus AP-1 site recognized by cellular bZIP proteins and CpG-containing motifs that are selectively bound by ZEBRA upon cytosine methylation. We report structural and mutational analysis of ZEBRA bound to a CpG-methylated ZRE (meZRE) from a viral lytic promoter. ZEBRA recognizes the CpG methylation marks through a ZEBRA-specific serine and a methylcytosine-arginine-guanine triad resembling that found in canonical methyl-CpG binding proteins. ZEBRA preferentially binds the meZRE over the AP-1 site but mutating the ZEBRA-specific serine to alanine inverts this selectivity and abrogates viral replication. Our findings elucidate a DNA methylation-dependent switch in ZEBRA’s transactivation function that enables ZEBRA to bind AP-1 sites and promote viral latency early during infection and subsequently, under appropriate conditions, to trigger EBV lytic replication by binding meZREs.