Miracle-dz/UniFAR-FTUs huggingface dataset:
Biosynthesis and Recycling of Nicotinamide Cofactors in Mycobacterium tuberculosis

Despite the presence of genes that apparently encode NAD salvage-specific enzymes in its genome, it has been previously thought that Mycobacterium tuberculosis can only synthesize NAD de novo. Transcriptional analysis of the de novo synthesis and putative salvage pathway genes revealed an up-regulation of the salvage pathway genes in vivo and in vitro under conditions of hypoxia. [14C]Nicotinamide incorporation assays in M. tuberculosis isolated directly from the lungs of infected mice or from infected macrophages revealed that incorporation of exogenous nicotinamide was very efficient in in vivo-adapted cells, in contrast to cells grown aerobically in vitro. Two putative nicotinic acid phosphoribosyltransferases, PncB1 (Rv1330c) and PncB2 (Rv0573c), were examined by a combination of in vitro enzymatic activity assays and allelic exchange studies. These studies revealed that both play a role in cofactor salvage. Mutants in the de novo pathway died upon removal of exogenous nicotinamide during active replication in vitro. Cell death is induced by both cofactor starvation and disruption of cellular redox homeostasis as electron transport is impaired by limiting NAD. Inhibitors of NAD synthetase, an essential enzyme common to both recycling and de novo synthesis pathways, displayed the same bactericidal effect as sudden NAD starvation of the de novo pathway mutant in both actively growing and nonreplicating M. tuberculosis. These studies demonstrate the plasticity of the organism in maintaining NAD levels and establish that the two enzymes of the universal pathway are attractive chemotherapeutic targets for active as well as latent tuberculosis.
A fast and highly adaptive peer-to-peer lookup system for medium-scale network

This paper presents the design and evaluation of FastAd, a fast and highly adaptive peer-to-peer (P2P) lookup system for medium-scale network where the number of nodes is not more than tens of thousands. Using routing tables larger than those of previous schemes, a lookup can be performed at just two hops, while maintenance cost of tables can be minimized by adopting lazy consistency with piggybacking. In addition, assigning dynamic node identifier (nodeId) instead of a fixed nodeId by hashing the node's IP address, FastAd network can be organized more adaptively and adjusted dynamically with system state such as load distribution, node dynamics, and so on. As a result, each node has different responsibility to exploit its heterogeneity.
3D Tumor Segmentation from Volumetric Brain MR Images Using Level-Sets Method

1.1 Statement of the problem Segmentation in volumetric images is a tool allowing a diagnostics automation and as well will assist experts in quantitative and qualitative analysis. It’s an important step in various applications such as visualization, morphometrics and image-guided surgery. In the context of neuro-imaging, brain tumor segmentation from Magnetic Resonance Images (MRI) is extremely important for treatment planning, therapy monitoring, examining efficacy of radiation and drug treatments and studying the difference between healthy subjects and subjects with brain tumor. The task of manually segmentation of brain tumor from MR images is generally time-consuming and difficult. Anyway, the task is done by marking by hand the tumor regions slice-by-slice which generates set of jaggy images, so the practitioner is confronted with a succession of boundary which he mentally stacked up to be made a 3D shape of brain tumor. This shape is inevitably subjective and becomes infeasible when dealing with large data sets, also there is losing of information in the third dimension because is not taken into account in the segmentation process. All this, affect the quality and accuracy of clinical diagnosis. An automatic or semi-automatic segmentation method of brain tumor that takes entire information within the volumetric MR image into account is desirable as it reduces the load on the human raters and generates optimal segmented images (Wang & al., 2004), (Michael & al., 2001), (Lynn & al., 2001). Specially, automatic brain tumor segmentation presents many challenges and involves various disciplines such us pathology, MRI physics and image processing. Brain tumors are difficult to segment because they vary greatly in size and position, may be of any size, may have a variety of shapes and may have overlapping intensities with normal tissue and edema. This leads to numerous segmentation approaches of automatic brain tumor extraction. Low-level segmentation methods, such as pixel-based clustering, region growing, and filter-based edge detection, requires additional pre-processing and post-processing as well as considerable amounts of expert intervention and a priori knowledge on the regions of interest (ROI) (Sahoo & al., 1988). Recently, several attempts have been made to apply deformable models to brain image analysis (Moon & al., 2002). Indeed, deformable models refer to a large class of computer vision methods and have proved to be a successful segmentation technique for a wide range of applications. Deformable models, on the other hand, provide an explicit representation of the boundary and the ROI shape. They combine several desirable features such as inherent connectivity and smoothness, which counteract
Phosphorylation of tau protein over time in rats subjected to transient brain ischemia

Transient brain ischemia has been shown to induce hyperphosphorylation of the microtubule-associated protein tau. To further determine the mechanisms underlying these processes, we investigated the interaction between tau, glycogen synthase kinase (GSK)-3β and protein phos-phatase 2A. The results confirmed that tau protein was dephosphorylated during brain ischemia; in addition, the activity of GSK-3β was increased and the activity of protein phosphatase 2A was decreased. After reperfusion, tau protein was hyperphosphorylated, the activity of GSK-3β was decreased and the activity of protein phosphatase 2A remained low. Importantly, the interaction of tau with GSK-3β and protein phosphatase 2A was altered during ischemia and reperfusion. Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3β and protein phosphatase 2A, and improve learning and memory ability of rats after transient brain ischemia. The present study demonstrated that it was the interaction of tau with GSK-3β and protein phosphatase 2A, rather than their individual activities, that dominates the phosphorylation of tau in transient brain ischemia. Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke. The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.
Low-Power and High Speed 128-Point Pipline FFT/IFFT Processor for OFDM Applications

This paper represents low power and high speed 128-point pipelined Fast Fourier Transform (FFT) and its inverse Fast Fourier Transform (IFFT) processor for OFDM. The Modified architecture also provides concept of ROM module and variable length support from 128~2048 point for FFT/IFFT for OFDM applications such as digital audio broadcasting (DAB), digital video broadcasting-terrestrial (DVB-T), asymmetric digital subscriber loop (ADSL) and very-high-speed digital subscriber loop (VDSL). The 128-point architecture consists of an optimized pipeline implementation based on Radix-2 butterfly processor Element. To reduce power consumption and chip area, special current-mode SRAMs are adopted to replace shift registers in the delay lines. In low-power operation, when the supply voltage is scaled down to 2.3 V, the processor consumes 176mW when it runs at 17.8 MHz.
Right-sided transperitoneal hand-assisted laparoscopic donor nephrectomy: is there an issue with the renal vessels?

OBJECTIVE Short right renal vessels might complicate kidney transplantation, thus causing traction and difficulties during anastomosis. Single-center prospective comparison of right- and left-sided transperitoneal hand-assisted laparoscopic donor nephrectomy (HALDN) is presented. PATIENTS AND METHODS Eighty-two living kidney donors underwent HALDN between 2003 and 2008. Right-sided HALDN was performed in 46 living kidney donors. The operative technique of right-sided HALDN was modified to obtain the maximum length of right renal vessels. Outcome data in donors including quality of life as well as graft outcome in recipients were prospectively collected. RESULTS All procedures were laparoscopically completed with no conversion. Mean operative time was 127 minutes (vs. 138 minutes in left HALDN, p = 0.08). The mean warm ischemia time was 41 seconds (vs. 39 seconds in left HALDN, p = 0.23). There was no renal artery or vein thrombosis in any of the grafts. Mean blood loss was 81 mL (vs. 92 mL in left HALDN, p = 0.09). Hospital discharge was on an average of 3.6 days postoperative. Delayed graft function occurred in two recipients: one in the left group and the other in the right group. One-year graft survival rate was 95% in the left group versus 96.9% in the right group (p = 0.08). Further, no statistically significant difference in serum levels of creatinine was seen between the groups 1 year after the transplantation. CONCLUSIONS Right HALDN is technically safe and feasible and results in convenient extension of right renal vessels to full length with no increased incidence of vascular thrombosis.
[Nutrition recommendations].

Learn about Carbohydrates ♦ When you have diabetes it is important to know which foods contain carbohydrates: • Sugars (e.g. table sugar, honey, syrup, corn syrup) are pure carbohydrates • Fruit juice and fruit are primarily carbohydrate • Starches (e.g. bread, cereal, rice, pasta, tortillas, beans) are high in carbohydrates • Milk, yogurt and ice cream contain carbohydrates or “milk sugars” • Some vegetables (like white potatoes, yams, corn, peas) have a high carbohydrate content while others (like broccoli and green beans) are low in carbohydrates ♦ During digestion all carbohydrates (except for fiber) break down into sugars ♦ Because carbohydrates cause blood sugar levels to rise, carbohydrate intake usually needs to be reduced and spread evenly throughout the day
Parathyroid hormone concentration in geriatric cats with various degrees of renal function.

OBJECTIVE To determine whether cats in the nonazotemic stages of chronic kidney disease have increased plasma parathyroid hormone (PTH) concentrations as a compensatory physiologic mechanism to maintain plasma phosphate concentration within the reference interval. DESIGN Prospective longitudinal study. ANIMALS 118 client-owned geriatric cats with various degrees of renal function. PROCEDURES For each cat, a blood sample was obtained for plasma biochemical analysis and determination of plasma PTH concentration, and a urine sample was obtained for determination of urine specific gravity at study entry (baseline) and after 12 months. For a subset of 30 cats, plasma calcitriol concentration was determined at baseline. Cats were categorized into 1 of 3 groups on the basis of kidney function at the end of 12 months. At baseline and after 12 months, plasma concentrations of variables associated with calcium homeostasis were compared between the 3 groups and also within groups over time. Multivariable linear regression was used to identify variables associated with plasma PTH concentration. RESULTS Plasma PTH concentration was significantly increased in cats that developed azotemia, compared with PTH concentration in cats that remained nonazotemic, and PTH concentration increased before changes in plasma calcium and phosphate concentrations were detected. A moderate positive association between plasma calcitriol and PTH concentrations was identified. Plasma PTH concentration was associated with age and plasma urea, creatinine, and total calcium concentrations in the final multivariable model. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that renal secondary hyperparathyroidism can develop prior to azotemia in cats, even in the absence of hyperphosphatemia and hypocalcemia.
Phylogeny-Aware Gap Placement Prevents Errors in Sequence Alignment and Evolutionary Analysis

Genetic sequence alignment is the basis of many evolutionary and comparative studies, and errors in alignments lead to errors in the interpretation of evolutionary information in genomes. Traditional multiple sequence alignment methods disregard the phylogenetic implications of gap patterns that they create and infer systematically biased alignments with excess deletions and substitutions, too few insertions, and implausible insertion-deletion–event histories. We present a method that prevents these systematic errors by recognizing insertions and deletions as distinct evolutionary events. We show theoretically and practically that this improves the quality of sequence alignments and downstream analyses over a wide range of realistic alignment problems. These results suggest that insertions and sequence turnover are more common than is currently thought and challenge the conventional picture of sequence evolution and mechanisms of functional and structural changes.
Regulation of breathing by CO2 requires the proton-activated receptor GPR4 in retrotrapezoid nucleus neurons

Receptor in the brain controls breathing Control of breathing in mammals depends primarily not on sensing oxygen, but rather on detecting concentrations of carbon dioxide in the blood. Failure of this system can cause potentially deadly sleep apnias. Taking a hint from insects, which use a heterotrimeric guanine nucleotide–binding protein-coupled receptor (GPCR) to sense carbon dioxide, Kumar et al. demonstrate that the GPCR GPR4 is essential to control breathing in mice. GPR4 senses protons generated by the formation of carbonic acid in the blood and works with a pH-sensitive potassium channel called TASK-2 in a set of brain cells that control breathing. Science, this issue p. 1255 A G protein–coupled receptor in the brain controls respiration. Blood gas and tissue pH regulation depend on the ability of the brain to sense CO2 and/or H+ and alter breathing appropriately, a homeostatic process called central respiratory chemosensitivity. We show that selective expression of the proton-activated receptor GPR4 in chemosensory neurons of the mouse retrotrapezoid nucleus (RTN) is required for CO2-stimulated breathing. Genetic deletion of GPR4 disrupted acidosis-dependent activation of RTN neurons, increased apnea frequency, and blunted ventilatory responses to CO2. Reintroduction of GPR4 into RTN neurons restored CO2-dependent RTN neuronal activation and rescued the ventilatory phenotype. Additional elimination of TASK-2 (K2P5), a pH-sensitive K+ channel expressed in RTN neurons, essentially abolished the ventilatory response to CO2. The data identify GPR4 and TASK-2 as distinct, parallel, and essential central mediators of respiratory chemosensitivity.
Core of communities in bipartite networks

We use the information present in a bipartite network to detect cores of communities of each set of the bipartite system. Cores of communities are found by investigating statistically validated projected networks obtained using information present in the bipartite network. Cores of communities are highly informative and robust with respect to the presence of errors or missing entries in the bipartite network. We assess the statistical robustness of cores by investigating an artificial benchmark network, the coauthorship network, and the actor-movie network. The accuracy and precision of the partition obtained with respect to the reference partition are measured in terms of the adjusted Rand index and the adjusted Wallace index, respectively. The detection of cores is highly precise, although the accuracy of the methodology can be limited in some cases.
Kuskokwim Syndrome, a Recessive Congenital Contracture Disorder, Extends the Phenotype of FKBP10  Mutations

Recessive mutations in FKBP10 at 17q21.2, encoding FKBP65, cause both osteogenesis imperfecta (OI) and Bruck syndrome (OI plus congenital contractures). Contractures are a variable manifestation of null/missense FKBP10 mutations. Kuskokwim syndrome (KS) is an autosomal recessive congenital contracture disorder found among Yup'ik Eskimos. Linkage mapping of KS to chromosome 17q21, together with contractures as a feature of FKBP10 mutations, made FKBP10 a candidate gene. We identified a homozygous three‐nucleotide deletion in FKBP10 (c.877_879delTAC) in multiple Kuskokwim pedigrees; 3% of regional controls are carriers. The mutation deletes the highly conserved p.Tyr293 residue in FKBP65's third peptidyl‐prolyl cis–trans isomerase domain. FKBP10 transcripts are normal, but mutant FKBP65 is destabilized to a residual 5%. Collagen synthesized by KS fibroblasts has substantially decreased hydroxylation of the telopeptide lysine crucial for collagen cross‐linking, with 2%–10% hydroxylation in probands versus 60% in controls. Matrix deposited by KS fibroblasts has marked reduction in maturely cross‐linked collagen. KS collagen is disorganized in matrix, and fibrils formed in vitro had subtle loosening of monomer packing. Our results imply that FKBP10 mutations affect collagen indirectly, by ablating FKBP65 support for collagen telopeptide hydroxylation by lysyl hydroxylase 2, thus decreasing collagen cross‐links in tendon and bone matrix. FKBP10 mutations may also underlie other arthrogryposis syndromes.
A six-gene phylogeny reveals the evolution of mode of infection in the rice blast fungus and allied species

The family Magnaporthaceae contains devastating fungal cereal and grass pathogens, such as Magnaporthe oryzae (rice blast fungus, formerly known as M. grisea), M. poae (summer patch pathogen of turf grasses) and Gaeumannomyces graminis (take-all fungus of various cereals and grasses), which are popular model organisms in fungal biology and host-pathogen interaction studies. Despite their ecological and economic importance, the phylogenetic relationships among the constituent species remain ambiguous due to the lack of convincing morphological characters and paucity of molecular data for the majority of the non-model species in the family. In this study our multilocus phylogeny suggests that both Magnaporthe and Gaeumannomyces are polyphyletic genera. The phylogeny also provides insights into fungal biology and pathogenesis. Magnaporthe oryzae formed a basal clade, while M. poae and M. rhizophila formed another well supported clade with G. incrustans and G. graminis. The basal species infect both root and aerial parts of the plant host, while the aerial infection capacity seems to be lost in the taxa of the latter clade. The phylogeny is corroborated by evolution of the anamorphs and a cAMP-dependent protein kinase (CPKA) gene. Magnaporthe oryzae produces Pyricularia, while taxa in the latter clade all produce Phialophora-like anamorphs. CPKA is present in animals and many fungal lineages with various functions. In M. oryzae CPKA is essential for the formation of functional appressoria for leaf penetration. In root-infecting G. graminis var. tritici and M. poae however only non-functional CPKA homologous pseudogenes were found in their genomes. The study indicates that anamorphic and ecological features are more informative than the teleomorphic characters in defining monophyletic groups among these taxa.
A consensus review on malignancy‐associated hemophagocytic lymphohistiocytosis in adults

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe immune activation and dysregulation resulting in extreme and often life‐threatening inflammation. HLH has been well recognized in pediatric populations, and most current diagnostic and therapeutic guidelines are based on pediatric HLH. Recently there has been recognition of HLH in adults, especially secondary to immune deregulation by an underlying rheumatologic, infectious, or malignant condition. This review is focused on malignancy‐associated HLH (M‐HLH), in which possible mechanisms of pathogenesis include severe inflammation, persistent antigen stimulation by the tumor cells, and loss of immune homeostasis because of chemotherapy, hematopoietic stem cell transplantation, or infection. Previously considered rare, M‐HLH may occur in up to 1% of patients with hematologic malignancies. M‐HLH is often missed or diagnosed late in most published studies, and it has been associated with a poor median survival of less than 2 months. Identification of the clinical and laboratory features specific to M‐HLH in adults may allow early detection, consultation with HLH experts, and intervention. Improved management of adult M‐HLH with optimal combinations of T‐lympholytic and immunosuppressive agents and the incorporation of novel agents based on the pediatric experience hopefully will improve outcomes in adults with M‐HLH. Cancer 2017;123:3229‐40. © 2017 American Cancer Society.
Reverse spatial and textual k nearest neighbor search

Geographic objects associated with descriptive texts are becoming prevalent. This gives prominence to spatial keyword queries that take into account both the locations and textual descriptions of content. Specifically, the relevance of an object to a query is measured by spatial-textual similarity that is based on both spatial proximity and textual similarity. In this paper, we define Reverse Spatial Textual k Nearest Neighbor (RSTkNN) query, i.e., finding objects that take the query object as one of their k most spatial-textual similar objects. Existing works on reverse kNN queries focus solely on spatial locations but ignore text relevance. To answer RSTkNN queries efficiently, we propose a hybrid index tree called IUR-tree (Intersection-Union R-Tree) that effectively combines location proximity with textual similarity. Based on the IUR-tree, we design a branch-and-bound search algorithm. To further accelerate the query processing, we propose an enhanced variant of the IUR-tree called clustered IUR-tree and two corresponding optimization algorithms. Empirical studies show that the proposed algorithms offer scalability and are capable of excellent performance.
Unique spatial and cellular expression patterns of Hoxa5, Hoxb4, and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia.

BACKGROUND Hox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern-specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial, and cellular expression of Hoxa5, Hoxb4, and Hoxb6 proteins compared to normal lung development. METHODS Temporal, spatial, and cellular Hoxa5, Hoxb4, and Hoxb6 expression was studied in normal (untreated) and nitrofen-induced hypoplastic (NT-PH) lungs from gestational day 13.5, 16, and 19 fetuses and neonates using Western blot and immunohistochemistry. RESULTS Modification of protein levels and spatial and cellular Hox expression patterns in NT-PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 protein isoforms changed with development and were altered further in NT-PH lungs. Compared to normal lungs, GD19 and neonatal NT-PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways. CONCLUSIONS Unique spatial and cellular expression of Hoxa5, Hoxb4, and Hoxb6 participates in branching morphogenesis and terminal sac formation. Altered Hox protein temporal and cellular balance of expression either contributes to pulmonary hypoplasia or functions as a compensatory mechanism attempting to correct abnormal lung development and maturation in this condition.