Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased PHGDH expression uncouples hair follicle cycle progression and promotes inappropriate melanin accumulation

Copy number gain of the PHGDH gene that encodes the first enzyme of the serine biosynthesis pathway is found in some human cancers, including a subset of melanomas. In order to study the effect of increased PHGDH expression in tissues in vivo, we generated mice harboring a PHGDHtetO allele that allows tissue-specific, doxycycline-inducible PHGDH expression. Tissues and cells derived from PHGDHtetO mice exhibit increased serine biosynthesis. Histological examination of skin tissue from PHGDHtetO mice reveals the presence of melanin granules in anagen II hair follicles, despite the fact that melanin synthesis is normally closely coupled to the hair follicle cycle and does not begin until later in the cycle. This phenotype occurs in the absence of any global change in hair follicle cycle timing. The inappropriate presence of melanin early in the hair follicle cycle following PHGDH expression is also accompanied by increased melanocyte abundance in anagen II skin. Together, these data support a model in which PHGDH expression affects melanocyte proliferation and/or differentiation and may provide insight into how PHGDH expression impacts normal melanocyte biology to promote melanoma. SIGNIFICANCE The significance behind copy number gain of PHGDH in human cancers is unclear. In this study, we generate a mouse model that mimics PHGDH gene copy number gain and characterize its effect on normal tissues. Increased PHGDH expression yields a phenotype of aberrant melanin production, which indicates that PHGDH expression may play a role in normal melanocyte biology. This result may provide insight into why PHGDH copy number gain is observed in melanoma more frequently than in most other tumor types.
Mutagenesis induced by the tumor microenvironment: implications of increased DNA damage and diminished DNA repair

Mutagenesis Induced by the Tumor Microenvironment Implications of Increased DNA Damage and Diminished DNA Repair May 2002 Tumors are characterized by microenvironmental heterogeneity, with regions of hypoxia, low pH, and nutrient deprivation. It has been proposed that such conditions may be an important factor contributing to cancer genetic instability. Using a chromosomally based lambda phage shuttle vector as a mutation reporter, we show that growth of cells in hypoxia and/or at low pH results in elevated mutation frequencies in two different reporter genes. To elucidate the mechanism of the tumor microenvironment-induced genetic instability, we first measured the production of DNA damage upon hypoxia and re-oxygenation in culture. We found that under such conditions, the intracellular level of a premutagenic lesion, 8-oxo-dG, was increased by 2to 3fold, consistent with the frequent G to T transversions observed among the hypoxia-induced mutation spectrum. We next examined the effect of the tumor microenvironment on two important cellular DNA repair pathways, i.e., the nucleotide excision repair (NER) and the mismatch repair (MMR) pathways. Using an assay for repair based on host cell reactivation of UV-damaged plasmid DNA, cells exposed to hypoxia and low pH were found to have a diminished capacity for DNA NER compared to control cells grown under standard conditions. Furthermore, the expression of the MMR gene, M lhl, was specifically reduced under hypoxia, along with secondary decrease in Pms2 protein. On a functional level, instability of simple dinucleotide repeats, a hallmark of MMR deficiency, was detected in hypoxic cells. Taken together, our work suggests that the tumor microenvironment may lead to conditions that either cause DNA damage or compromise DNA repair processes, and consequently contribute to mutagenesis and genomic instability. This may constitute a fundamental mechanism of tumor progression in vivo.
Recent Advances in Angiogenesis Assessment Methods and their Clinical Applications

Angiogenesis, a natural phenomenon of developing new blood vessels, is an integral part of normal developmental processes as well as numerous pathological states in humans. The angiogenic assays are reliable predictors of certain pathologies in particular tumor growth, metastasis, inflammation, wound healing, tissue regeneration, isch - emia, cardiovascular, and ocular diseases. The angiogenic inducer and inhibitor studies rely on both in vivo and in vitro angiogenesis methods, and various animal models are also standardized to assess qualitative and quantitative angiogenesis. Analogously, the discovery and development of anti-angiogenic agents are also based on the choice of suitable angiogenic assays and potential drug targeted sites within the angiogenic process. Similarly, the selection of cell types and compatible experimental conditions resembling the angiogenic disease being studied are also potential challenging tasks in recent angiogenesis studies. The imaging analysis systems for data acquisition from in vivo, in vitro, and in ova angiogenesis assay to preclinic, and clinical research also requires novel but easy-to-use tools and well-established protocols. The proposition of this pragmatic book chapter overviews the recent advances in angiogenesis assessment methods and discusses their applications in numerous disease pathogenesis. proteins (SMAD and and cause cell cycle arrest and apoptosis. However, TGF-β stimulates other molecular pathways in transformed cells to inhibit cell apoptosis and accelerates cell migration and metastasis. In contrast, a second type 1 receptor (ALK1) is expressed in ECs which stimulates cell proliferation and migration via activating SMADs 1 and 5 genes. to the test compound. In vitro angiogenesis assays may perform in a short provide the accurate and reliable outcome of angiogenic processes. Mouse models based angiogenesis assays have also standardized to an improved understanding of tumor angiogenesis and lymphangiogenesis. Similarly, such models also used to assess vasculogenesis and arteriogenesis in ischemic heart diseases, psoriasis, and arthri-tis. assessment focal role to determine the pathogenesis and progression of certain challenging diseases in human populations in human cancer. progression, the molecular mechanisms and cellular pathways, to develop anti-angiogenic inhibitors. The manipulation of the a and molecular new gates for the of more reliable models for angiogenesis studies testing new therapeutic
Assessment of Metagenomic MinION and Illumina sequencing as an approach for the recovery of whole genome sequences of chikungunya and dengue viruses directly from clinical samples

The recent global emergence and re-emergence of arboviruses has caused significant human disease. Common vectors, symptoms and geographical distribution make differential diagnosis both important and challenging. We performed metagenomic sequencing using both the Illumina MiSeq and the portable Oxford Nanopore MinION to study the feasibility of whole genome sequencing from clinical samples containing chikungunya or dengue virus, two of the most important arboviruses. Direct metagenomic sequencing of nucleic acid extracts from serum and plasma without viral enrichment allowed for virus and coinfection identification, subtype determination and in the majority of cases elucidated complete or near-complete genomes adequate for phylogenetic analysis. This work demonstrates that metagenomic whole genome sequencing is feasible for over 90% and 80% of chikungunya and dengue virus PCR-positive patient samples respectively. It confirms the feasibility of field metagenomic sequencing for these and likely other RNA viruses, highlighting the applicability of this approach to front-line public health.
Genome editing in poultry - opportunities and impacts

Poultry products (meat and eggs) are a major source of animal protein on which the world is increasingly reliant to feed a rapidly growing population. Improved breeds and advances in farm management practices have had a large impact on the poultry industry. For example, using current genetic stock and production practices, broiler chickens can weigh 2 kg in about 34 days. Forty-five years ago it would have typically taken over 60 days. These impressive advances have been made using traditional selective breeding methods and more recently by using genomics. Now, with the availability of precision genome engineering tools there are new opportunities to improve poultry production above and beyond those achievable by traditional means. One major opportunity is disease resilience, particularly for viral diseases such as avian influenza that has devastating impacts on the poultry industry. Resilience to specific diseases can be a notoriously difficult trait to select for using traditional breeding and the latest technologies that precisely edit the genome have created new ways to address this challenge.
Speckle Noise Reduction from Ultrasound Fetus Images

Ultrasound imaging is widely used in medical diagnosis, because of its noninvasive nature, low cost, capability of forming real time imaging and continuing improvement in image quality. The main problem during diagnosis is the distortion of visual signals . These distortions are termed as (speckle noise), this makes the image unclear. The success of ultrasonic examination depends on the image quality which is usually retarded due to speckle noise. Therefore, noise reduction is very important process. Many denoising techniques have been proposed for effective suppression of speckle noise. In this paper three adaptive filers are used for effective suppression of speckle noise present in ultrasounds fetus images.
The Effect of Retailer’s Perceived Service Innovation and Value Co-Creation Behavior on SME’s Brand Equity

The purpose of this study is to examine the predictive effect of value-co creation, and service innovation on SME’s brand equity in Malaysia. 529 questionnaires were collected via judgemental sampling from customers who patronizing SMEs involved in Food and Beverages (F & B) services. The findings show that the impact of value co-creation on SME’s brand equity is positive. Moreover, the retailer’s perceived service innovation is positively related to SME’s brand equity. This study provides theoretical, empirical and managerial contributions to the field of brand and service management from consumers’ perspective. The outcome of the study will benefit SME retailers’ particular to F & B operators to manage their customers in a more excellent manner.
Emergence of a thermal equilibrium in a subsystem of a pure ground state by quantum entanglement

By numerically exact calculations of spin-1/2 antiferromagnetic Heisenberg models on small clusters, we demonstrate that quantum entanglement between subsystems $A$ and $B$ in a pure ground state of a whole system $A+B$ can induce thermal equilibrium in subsystem $A$. Here, the whole system is bipartitoned with the entanglement cut that covers the entire volume of subsystem $A$. Temperature ${\cal T}_{A}$ of subsystem $A$ is not a parameter but can be determined from the entanglement von Neumann entropy ${\cal S}_{A}$ and the total energy ${\cal E}_{A}$ of subsystem $A$ calculated for the ground state of the whole system. We show that temperature ${\cal T}_{A}$ can be derived by minimizing the relative entropy for the reduced density matrix operator of subsystem $A$ and the Gibbs state (i.e., thermodynamic density matrix operator) of subsystem $A$ with respect to the coupling strength between subsystems $A$ and $B$. Temperature ${\cal T}_{A}$ is essentially identical to the thermodynamic temperature, for which the entropy and the internal energy evaluated using the canonical ensemble in statistical mechanics for the isolated subsystem $A$ agree numerically with the entanglement entropy ${\cal S}_{A}$ and the total energy ${\cal E}_{A}$ of subsystem $A$. Fidelity calculations ascertain that the reduced density matrix operator of subsystem $A$ for the pure but entangled ground state of the whole system $A+B$ matches, within a maximally $1.5\%$ error in the finite size clusters studied, the thermodynamic density matrix operator of subsystem $A$ at temperature ${\cal T}_{A}$. We argue that quantum fluctuation in an entangled pure state can mimic thermal fluctuation in a subsystem. We also provide two simple but nontrivial analytical examples of free bosons and free fermions for which these statements are exact. We furthermore discuss implications and possible applications of our finding.
Two types of densification scaling in the evolution of temporal networks.

Many real-world social networks constantly change their global properties over time, such as the number of edges, size, and density. While temporal and local properties of social networks have been extensively studied, the origin of their dynamical nature is not yet well understood. Networks may grow or shrink if (a) the total population of nodes changes and/or (b) the chance of two nodes being connected varies over time. Here, we develop a method that allows us to classify the source of time-varying nature of temporal networks. In doing so, we first show empirical evidence that real-world dynamical systems could be categorized into two classes, the difference of which is characterized by the way the number of edges grows with the number of active nodes, i.e., densification scaling. We develop a dynamic hidden-variable model to formally characterize the two dynamical classes. The model is fitted to the empirical data to identify whether the origin of scaling comes from a changing population in the system or shifts in the connecting probabilities.
Security Analysis of Android Application by Using Reverse Engineering

Mobile devices have developed tremendous popularity over the last few years. The most popular usage is the smart phones because they are capable of providing services such as banking, social network, and so on. The Android platform is the fastest growing market in smart phone operating systems to date. The malicious applications targeting the Android system have exploded in recent years. It needs to detect the malicious code on Android applications. This paper focus on the analysis of the android apps by using the reverse engineering tools for checking the malicious activities. There are mainly two parts this analysis such as permissions and java source codes analysis. The results show that most of malware apps are located the unnecessary permission on AndroidManifest.xml to inject the malicious codes in the apps.
Starch Content in Citrus Leaves: A Test with Seasonal Accuracy

One of the most prominent characteristics of huanglongbing (HLB or citrus greening)-affected citrus trees is the abundant starch accumulation in photosynthetic cells and all other remaining parenchyma cells of aerial parts. Under natural conditions, citrus leaves store very low levels of starch, and detectable amounts are only seen as a result of zinc deficiency or accidental girdling of branches. Therefore, leaf starch concentrations over a threshold level should indicate the presence of HLB. In this report, we detail both frequentist and Bayesian statistical approaches to predict HLB using starch levels in citrus leaves. Real-time PCR detection of the presumptive causing agent Candidatus Liberibacter asiaticus was used as a proxy for HLB status, but we also present a competing analysis that does not use PCR as a gold standard. Starch content was found to reliably predict the PCR results (the proxy for HLB presence) during the “warm season” (June through November), but not in the “cool season” (December through May). During the cool season, starch levels for HLB positive trees tend to be lower, and 43% of samples were incorrectly classified using linear discriminant analysis (LDA). In contrast, during the warm season, only 8% were misclassified. Further, assuming PCR possibly has error, the total probability of misclassification for HLB status could be controlled using an “uncertain” classification. Analysis of the biotic conditions surrounding HLB in terms of bacteria life cycle and the plant development provides insights into these patterns.
Analysis of Quadrilateral Out-of-Step Protection Relay Operation

-Generally, electrical torque in synchronous generator is balanced with the rotor mechanical torque under steady-state condition. Thus, the synchronous generator rotor rotates at constant speed. However, under fault condition, the electrical torque output is suddenly decreased and the sum of both torques does not remain constant. If the mechanical torque is not decreased at the same time, the generator rotor would accelerate. Therefore, this accelerating generator rotates at different speeds with respect to other generators in the power system. This phenomena is called as Out-of-Step (OOS). In this paper, we presented a certain two-step type quadrilateral OOS relay setting, which is applicable in actual field, and examined the validity of its setting value with OOS simulation conditions due to delayed fault clearing in transmission line. In order to conduct the study of OOS relay characteristics, we checked the impedance locus and generator output characteristics under the various delayed fault clearing conditions. Moreover, we proposed a countermeasure for avoiding the mis-operation of OOS relay during the stable swing by modifying the setting values.
An Efficient Super-Resolution DOA Estimator Based on Grid Learning

Direction-of-arrival (DOA) estimation based on sparse signal reconstruction (SSR) is always vulnerable to off-grid error. To address this issue, an efficient superresolution DOA estimation algorithm is proposed in this work. Utilizing the Taylor series expansion, the sparse dictionary matrix is constructed under the off-grid model. Then, a polynomial optimization function is established based on the orthogonality principle. By minimizing the given objective function, we derive an efficient closed-form solution of the off-grid errors. Using the estimated off-grid errors, the discretized grid can be iteratively learned and approaches the true DOAs. With the newly learned grid, accurate DOA estimations can be achieved through the SSR scheme. The proposed algorithm converges fast and achieves precise DOA estimations even the step size of the discretized grid is large. The superior performance of the proposed algorithm is demonstrated by the simulation results.
Tumor-specific Causal Inference (TCI): A Bayesian Method for Identifying Causative Genome Alterations within Individual Tumors

Precision medicine for cancer involves identifying and targeting the somatic genome alterations (SGAs) that drive the development of an individual tumor. Much of current efforts at finding driver SGAs have involved identifying the genes that are mutated more frequently than expected among a collection of tumors. When these population-derived driver genes are altered (perhaps in particular ways) in a given tumor, they are posited as driver genes for that tumor. In this technical report, we introduce an alternative approach for identifying causative SGAs, also known as “drivers”, by inferring causal relationships between SGAs and molecular phenotypes at the individual tumor level. Our tumor-specific causal inference (TCI) algorithm uses a Bayesian method to identify the SGAs in a given tumor that have a high probability of regulating transcriptomic changes observed in that specific tumor. Thus, the method is focused on identifying the tumor specific SGAs that are causing expression changes that are specific to the tumor. Those SGAs that have a high probability of regulating transcriptomic changes related to oncogenic processes are then designated to be the putative drivers of the tumor. In this paper, we describe in detail the TCI algorithm and its implementation.
Characterization of single vesicle recycling kinetics and other presynaptic properties at small central terminals

Sustained neural activity critically relies on the ongoing function of small central synapses. In particular, activity-driven fusion and recycling of neurotransmitter-filled vesicles at presynaptic terminals are key processes responsible for information transfer. Despite the fact that vesicle exocytosis and endocytosis are of great interest, the mechanisms of their regulation are still poorly understood. Moreover, hippocampal synapses exhibit high levels of variability in their structure and function, but the basis for this remains unclear. The aim of this work was to investigate these fundamental properties and establish key rules of regulation. Specifically, we wanted to test whether the timing of endocytosis of single synaptic vesicles was characteristic at individual boutons, and to investigate structural and molecular properties of synapses that underlie their particular behaviour. To explore this, we used a variety of optical imaging techniques in rat hippocampal neurons based on acutely applied probes such as FM1-43 dye, fluorescently tagged antibodies and genetically encoded reporters of presynaptic function, as well as ultrastructural readouts using electron microscopy. We found that although the timing of vesicle retrieval, measured with the optical reporter sypHy2x, was highly variable across the population of synapses, individual boutons showed signature endocytic kinetics. We also uncovered the properties of synapses that determine this behaviour, and demonstrated that these could be modulated, leading to predictable changes in the timing of recycling. These findings offer new insights into the rules that govern the function of presynaptic terminals. A second related objective examined was whether amyloid beta, the misfolding protein implicated in Alzheimer’s disease, causes changes that are detrimental for efficient vesicle recycling. We showed that oligomeric amyloid beta 1-42 impaired endocytosis and disrupted other related presynaptic processes. We suggest that vesicle recycling mechanisms are important target substrates in Alzheimer’s disease providing potential new avenues for development of therapeutic approaches.
The ACE Gene I/D Polymorphism and Physical Performance Correlations Among Community-Dwelling Older Adults

Angiotensin converting enzyme (ACE) (EC 3.4.15.1) plays a vital role in maintaining blood pressure and cardiovascular health as part of the renin-angiotensinaldosterone system (RAAS) (Schmieder et al., 2007). ACE functions by cleaving angiotensin I (Ang I) to produce angiotensin II (Ang II), an active vasoconstrictor and important part of RAAS regulation, and also by inactivating brandykinin, a vasodilator (Harrison and Acharya, 2014). A major polymorphism of ACE occurs in intron 16, where there can be an Alu sequence inserted, resulting in two different alleles: one containing the insertion (Iinsertion) and one without it(Ddeletion) (Harrison and Acharya, 2014). The D allele of ACE has been shown to produce more mRNA than the I allele (Suehiro et al., 2004), while the I/D polymorphism has been linked with nearly half the variance in serum ACE levels between individuals (Rigat et al., 1990). The brain has independent ACE expression, and the I allele has been linked with a 70% increase in ACE promoter transcription in neuro (Wu enst al., 2013). This apparent difference in ACE expression between the brain and the periphery within the same genotype, and the differences in expression between genotypes, likely have an effect on the cardiovascular and musculoskeletal systems where ACE activity is involved. This study attempted to examine these effects through the differential significant correlations of physical performance and strength measurements seen between the genotype groups.