Miracle-dz/UniFAR-FTUs huggingface dataset:
Human POT1 unfolds G-quadruplexes by conformational selection

The reaction mechanism by which shelterin protein POT1 (Protection of Telomeres) unfolds human telomeric G-quadruplex structures is not fully understood. We report here kinetic, thermodynamic, hydrodynamic and computational studies that show that a conformational selection mechanism, in which POT1 binding is coupled to an obligatory unfolding reaction, is the most plausible mechanism. We show that binding of the single-strand oligonucleotide d[TTAGGGTTAG] to POT1 is fast, with an apparent relaxation time of 80.0 ± 0.4 ms, and strong, with a binding free energy of −10.1 ± 0.3 kcal mol−1. That favourable free energy arises from a large favourable enthalpy contribution of −38.2 ± 0.3 kcal mol−1. In sharp contrast, the binding of POT1 to an initially folded 24 nt G-quadruplex structure is slow, with an average relaxation time of 2000-3000 s. Fluorescence, circular dichroism and analytical ultracentrifugation studies show that POT1 binding is coupled to quadruplex unfolding with a final stoichiometry of 2 POT1 molecules bound per 24 nt DNA. The binding isotherm for the POT1-quadruplex binding interaction is sigmoidal, indicative of a complex reaction. A conformational selection model that includes equilibrium constants for both G-quadruplex unfolding and POT1 binding to the resultant single-strand provides an excellent quantitative fit to the experimental binding data. The overall favourable free energy of the POT1-quadruplex interaction is −7.1 kcal mol−1, which arises from a balance between unfavourable free energy of +3.4 kcal mol−1 for quadruplex unfolding and a large, favorable free energy of −10.5 kcal mol−1 for POT1 binding. We show that POT1 can unfold and bind to any conformational form of human telomeric G-quadruplex (antiparallel, hybrid or parallel), but will not interact with duplex DNA or with a parallel G-quadruplex structure formed by a c-myc promoter sequence. Finally, molecular dynamics simulations provide a detailed structural model of a 2:1 POT1:DNA complex that is fully consistent with experimental biophysical results.
Revisiting the landscape of evolutionary breakpoints across human genome using multi-way comparison

Genome rearrangement is one of the major forces driving the processes of the evolution and disease development. The chromosomal position affected by these rearrangements are called breakpoints. The breakpoints occurring during the evolution of species are known to be non randomly distributed. Detecting their landscape and mapping them to genomic features constitute an important features in both comparative and functional genomics. Several studies have attempted to provide such mapping based on pairwise comparison of genes as conservation anchors. With the availability of more accurate multi-way alignments, we design an approach to identify synteny blocks and evolutionary breakpoints based on UCSC 45-way conservation sequence alignments with 12 selected species. The multi-way designed approach with the mild flexibility of presence of selected species, helped to have a better determination of human lineage-specific evolutionary breakpoints. We identified 261,391 human lineage-specific evolutionary breakpoints across the genome and 2,564 dense regions enriched with biological processes involved in adaptive traits such as response to DNA damage stimulus, cellular response to stress and metabolic process. Moreover, we found 230 regions refractory to evolutionary breakpoints that carry genes associated with crucial developmental process such as organ morphogenesis, skeletal system development, chordate embryonic development, nerve development and regulation of biological process. This initial map of the human genome will help to gain better insight into several studies including developmental studies and cancer rearrangement processes.
Effect of oral spray with Lactobacillus on growth performance, intestinal development and microflora population of ducklings

Objective The aim of this study is to investigate the effect of oral spray with probiotics on the intestinal development and microflora colonization of hatched ducklings. Methods In Exp. 1, an one-way factorial design was used to study the antibacterial activity of the probiotics and metabolites on Escherichia coli (E. coli) without antimicrobial resistance. There were four experimental groups including saline as control and Lactobacillus, Bacillus subtilis, combined Lactobacillus and Bacillus subtilis groups. In Exp. 2, 64-day-old ducklings were allotted to 2 treatments with 4 replicated pens. Birds in the control group were fed a basal diet supplemented with Lactobacillus fermentation in the feed whereas birds in the oral spray group were fed the basal diet and administrated Lactobacillus fermentation by oral spray way during the first week. Results In Exp. 1, the antibacterial activities of probiotics and metabolites on E. coli were determined by the diameter of inhibition zone in order: Lactobacillus>combined Lactobacillus and Bacillus subtilis>Bacillus subtilis. Additionally, compared to E. coli without resistance, E. coli with resistance showed a smaller diameter of inhibition zones. In Exp. 2, compared to control feeding group, oral spray group increased (p<0.05) the final body weight at d 21 and average daily gain for d 1–21 and the absolute weight of the jejunum, ileum and total intestine tract as well as cecum Lactobacillus amount at d 21. Conclusion Lactobacillus exhibited a lower antibacterial activity on E. coli with resistance than E. coli without resistance. Oral spray with Lactobacillus fermentation during the first week of could improve the intestinal development, morphological structure, and microbial balance to promote growth performance of ducklings from hatch to 21 d of age.
Ach and NE : Bayes, uncertainty, attention and learning.

Uncertainty in various forms plagues our interactions with the environment. In a Bayesian statistical framework, optimal inference and learning, based on imperfect observation in changing contexts, require the representation and manipulation of different forms of uncertainty. We propose that the neuromodulatory systems such as acetylcholine (ACh) and norepinephrine (NE) play a major role in the brain's implementation of these uncertainty computations. ACh and NE have long been supposed to be critically involved in cognitive processes such as attention and learning. However, there has been little consensus on their precise computational functions. We propose that acetylcholine reports expected uncertainty; norepinephrine signals unexpected uncertainty. The interaction between these formally distinct sorts of uncertainty is suggested as playing a important role in mediating the interaction between top-down and bottom-up processing in inference and learning. The generative models we use to describe probabilistic relationships in the environment belong to the class of noisy dynamical systems related to the Hidden Markov Model (HMM). At any given time point, the animal has uncertainty about the hidden state of the world that arises from two sources: the noisy relationship between the true state and imperfect sensory observations, and the inherent non- stationarity of these hidden states. The former gives rise to expected uncertainty, the latter to unexpected uncertainty. These theoretical concepts are illustrated by applications to several attentional tasks. When ACh and NE are identified with the proposed uncertainty measures in these specific tasks, they exhibit properties that are consistent with a diverse body of pharmacological, behavioral, electrophysiological, and neurological findings. In addition, numerical and analytical analyses for these models give rise to novel experimental predictions. Preliminary data from several experimental studies engendered by this set of theoretical work will also be discussed.
Influence of Drought on Foliar Water Uptake Capacity of Temperate Tree Species

Foliar water uptake (FWU) has been investigated in an increasing number of species from a variety of areas but has remained largely understudied in deciduous, temperate tree species from non-foggy regions. As leaf wetting events frequently occur in temperate regions, FWU might be more important than previously thought and should be investigated. As climate change progresses, the number of drought events is expected to increase, basically resulting in a decreasing number of leaf wetting events, which might make FWU a seemingly less important mechanism. However, the impact of drought on FWU might not be that unidirectional because drought will also cause a more negative tree water potential, which is expected to result in more FWU. It yet remains unclear whether drought results in a general increase or decrease in the amount of water absorbed by leaves. The main objectives of this study are, therefore: (i) to assess FWU-capacity in nine widely distributed key tree species from temperate regions, and (ii) to investigate the effect of drought on FWU in these species. Based on measurements of leaf and soil water potential and FWU-capacity, the effect of drought on FWU in temperate tree species was assessed. Eight out of nine temperate tree species were able to absorb water via their leaves. The amount of water absorbed by leaves and the response of this plant trait to drought were species-dependent, with a general increase in the amount of water absorbed as leaf water potential decreased. This relationship was less pronounced when using soil water potential as an independent variable. We were able to classify species according to their response in FWU to drought at the leaf level, but this classification changed when using drought at the soil level, and was driven by iso- and anisohydric behavior. FWU hence occurred in several key tree species from temperate regions, be it with some variability, which potentially allows these species to partly reduce the effects of drought stress. We recommend including this mechanism in future research regarding plant–water relations and to investigate the impact of different pathways used for FWU.
Non-cardiac transthoracic ultrasonography in sloth bear (Melursus ursinus); Bear’s-Blue

Like the trans-abdominal ultrasonography examination technique used to examine the visceral organs in the abdominal cavity, the non-cardiac trans-thoracic ultrasonography technique will help to examine the lungs. The lungs are located within the thoracic cavity of all mammals and are the only organs in the body to be filled with air under normal conditions. In the past, the belief was that the lung is not optimal for ultrasonography imaging because the aerated lungs creates insurmountable obstacles; therefore, people concentrated more on trans-abdominal, trans-rectal and trans-thoracic echocardiography. These methods became well established in human medicine and were gradually adopted into veterinary medicine as well. However, the ultrasonography examination of pulmonary system remained a grey area. Recent advancements and continued development in medical science has surmounted the previously thought impossible and has proven that ultrasonography is an excellent diagnostic model in regard to the anatomy of all mammalian species. Rantanen was the first veterinarian to use the ultrasonography to diagnose pulmonary disease in horses, and successfully diagnosed pneumothorax in 1986. Following this discovery, awareness in the field increased and resulted in the establishment of the Bed side Lung Ultrasound Examination (BLUE) protocol in human medicine and the Vet-BLUE protocol in small animal veterinary medicine. However, these advanced technologies are not as well established or effectively utilized in wild animal medicine as they are in small animal veterinary practice globally, except for in a few research institutions and teaching universities. Therefore, adopting this advanced diagnostic procedure in wildlife is pertinent for providing the utmost care in these species. During the study, we were able to clearly document the examination of the pulmonary system of sloth bears by adopting the non-cardiac, trans-thoracic ultrasonography technique. This technique includes patient preparation, positioning, probe selection, and recording of the ultrasonography image to compare and interpret normal versus abnormal lung and its radiographs. Thus, we developed the BLUE protocol for bears (Bear’s-BLUE). The aim of this article is to disseminate the knowledge of sloth bear lung ultrasonography to wildlife veterinarians at field level, and to encourage the neophytes to adopt this practice and improve their diagnostic ability to provide better care to the animals and develop a more effective therapeutic plan.
Selection of Native Non-Saccharomyces Yeasts with Biocontrol Activity against Spoilage Yeasts in Order to Produce Healthy Regional Wines

Two major spoilage yeasts in the wine industry, Brettanomyces bruxellensis and Zygosaccharomyces rouxii, produce off-flavors and gas, causing considerable economic losses. Traditionally, SO2 has been used in winemaking to prevent spoilage, but strict regulations are in place regarding its use due to its toxic and allergenic effects. To reduce its usage researchers have been searching for alternative techniques. One alternative is biocontrol, which can be used either independently or in a complementary way to chemical control (SO2). The present study analyzed 122 native non-Saccharomyces yeasts for their biocontrol activity and their ability to be employed under fermentation conditions, as well as certain enological traits. After the native non-Saccharomyces yeasts were assayed for their biocontrol activity, 10 biocontroller yeasts were selected and assayed for their ability to prevail in the fermentation medium, as well as with respect to their corresponding positive/negative contribution to the wine. Two yeasts that satisfy these characteristics were Wickerhamomyces anomalus BWa156 and Metschnikowia pulcherrima BMp29, which were selected for further research in application to mixed fermentations.
Mononuclear phagocytes drive Mertk-dependent T cell regulation at autoimmune and tumor sites

Understanding mechanisms of immune regulation is key to developing effective immunotherapies for autoimmunity and cancer. We examined the role of mononuclear phagocytes (MNPs) in regulating effector T cells in type 1 diabetes and melanoma. MNPs in the islets impaired T cell responsiveness to antigen by preventing antigen-mediated T cell arrest. MNPs in the autoimmune lesion express the TAM family receptor tyrosine kinase Mertk which functions in efferocytosis. Inhibition or deficiency of Mertk led to a release from T cell regulation characterized by enhanced T cell arrest in pre-diabetic islets and at the tumor site. T cell arrest was accompanied by increased T cell-antigen presenting cell interactions as well as increased antigen experience and effector function by T cells in the islets. Single cell RNA-seq analysis of islet MNPs identified multiple myeloid subsets. Inhibition of Mertk induced the most significant changes in gene expression among the islet resident macrophages including upregulation of inflammatory cytokine and adhesion genes. In the NOD mouse model, inhibition of Mertk-dependent T cell regulation culminated in the rapid acceleration of autoimmune pathology and disease. In human islets, the number of Mertk-expressing cells were increased in remaining insulin-containing islets from type 1 diabetic patients, suggesting that they might have a protective role in human disease. These data indicate that Mertk signaling in MNPs drives T cell regulation that functions specifically at the disease site in peripheral tissues through a mechanism that prevents T cell arrest and response to antigen.
Investigation of the influence of the thermal effects on the FeCrAl alloys Kh15Yu5 and Kh23Yu5

FeCrAl alloys having the composition of chromium added to iron is peculiar by in the increased corrosion resistance of the new metallic alloy compared to pure iron. Such FeChAl alloys are used in numerous different applications as a corrosion resistant, oxidation resistant and heat resistant material. Owing to their resistance and good mechanical characteristics, FeCrAl alloys are regarded as one of the main structural materials for use in nuclear power plants. They are commonly used within industrial applications where high-temperature oxidation resistance is needed. The good resistance to oxidation, sulfur resistance and corrosion resistance are attained due to a dense oxide film formed on the surface that prevents the rapid further degradation of the material. In this study, two FeCrAl alloys are investigated - Kh15Yu5 (15%Cr5%Al) and Kh23Yu5 (23%Cr5%Al). Using the method of Mossbauer spectroscopy, the study was conducted on the influence of temperature and period of heating on the cold-rolled ribbon of FeCrAl alloys Kh15Yu5 and Kh23Yu5 with the thickness of 50 µm. It is shown that these alloys, as a result of thermal effect, are prone to the layering in solid solution, forming the areas depleted and enriched with chromium and aluminum.
Effects of Studying Tasks Compatibility with Tablets on Their Acceptance

This chapter addresses the issue of tablets acceptance for studying. An experiment was carried out to test the effects of specific studying tasks experienced by students with no previous experiences with tablets on the perceived usability and usefulness of tablets. Students had to perform a high-compatible task (i.e. navigation/reading task) and a low-compatible task (i.e. writing task) for tablets. Subjective measures of usability, usefulness and use intention were designed to be more specific to the type of task than the classical measures used in the Technology Acceptance Model approach (Davis, 1989). Participants rated their answers before and after performing the tasks with a tablet. The results showed that the perceived usability and usefulness of tablets increased after the high-compatible task while their decreased with the low-compatible task. The findings stressed the need to consider the real user experience and to use more task-oriented measures to investigate the acceptance of mobile devices for studying.
AMELIORATIVE EFFECT OF ALLIUM CEPA ON OXIDATIVE STRESS AND NEURONAL DAMAGE AFTER ISCHEMIA AND REPERFUSION-INDUCED CEREBRAL INJURY

Background: Stroke is the second most common cause of death and major cause of disability worldwide. Because of the ageing population, the burden will increase greatly during the next 20 years, especially in developing countries. Antioxidants have been the focus of studies for developing neuroprotective agents to be used in the therapy for stroke, which is an acute and progressive neurodegenerative disorder. Allium cepa (Linn.) has been greatly valued, commercially as well as medicinally, since ancient times. A. cepa is reported to be potent antioxidants and neuroprotective agent. Our previous work demonstrated that pretreatment with methanol extract of A. cepa prevents ischemia-reperfusion (I/R) induced cerebral injury. Objective: The present study was designed to investigate the effect of methanol extract and flavonoid-rich fraction of outer scales of A. cepa bulbs post-cerebral injury. Materials and methods: Global cerebral ischemia was induced in mice by bilateral carotid artery occlusion followed by reperfusion. Treatment with extracts of A. cepa, was carried out for 28 days after I/R. Cerebral infract size was estimated using triphenyltetrazolium chloride staining. TBARS assay was employed to measure oxidative stress. Morris water maze was employed to assess memory, and inclined-beam walking test was employed to evaluate motor coordination. Phytochemical screening tests showed the presence of flavonoids in the bioactive extract, hence flavonoid-rich fraction was prepared and biological studies were carried out. Results: The flavonoid-rich fraction of the outer scales of A. cepa demonstrated the most significant reduction in cerebral damage and oxidative stress. It also ameliorated the damage to memory and motor coordination. This bioactive fraction found to contain high amount of total phenolics and total flavonoid content. Conclusion: The standardized flavonoid-rich fraction of the outer scales of allium cepa may be a potential candidate for the treatment of post-cerebral damage.
Learning from minimally labeled data with accelerated convolutional neural networks

Dundar, Aysegul Ph.D., Purdue University, May 2016. Learning from Minimally Labeled Data with Accelerated Convolutional Neural Networks. Major Professor: Eugenio Culurciello. The main objective of an Artificial Vision Algorithm is to design a mapping function that takes an image as an input and correctly classifies it into one of the user-determined categories. There are several important properties to be satisfied by the mapping function for visual understanding. First, the function should produce good representations of the visual world which will be able to recognize images independently of pose, scale and illumination. Furthermore, the designed artificial vision system has to learn these representations by itself. Recent studies on Convolutional Neural Networks (ConvNets) produced promising advancements in visual understanding. These networks attain significant performance upgrades by relying on hierarchical structures inspired by biological vision systems. In my research, I work mainly in two areas: 1) how ConvNets can be programmed to learn the optimal mapping function using the minimum amount of labeled data, and 2) how these networks can be accelerated for practical purposes. 1) The task of labeling data for training deep neural networks is daunting and tedious work. It requires millions of labels to achieve the current state-of-the-art accuracy. The dependency on large amounts of labeled data can be mitigated by exploiting hierarchical features via unsupervised learning techniques. Unsupervised learning algorithms explore patterns in datasets consisting only of input data without labeled targets. It is believed that this is akin to how humans learn to recognize objects, because unlike traditional computer learning algorithms, humans do not need thousands of examples of an object to learn it. In this thesis, algorithms that learn from unlabeled data are studied, and state-of-the-art results on common benchmarks are achieved.