Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitric Oxide Inactivation Mechanisms in the Brain: Role in Bioenergetics and Neurodegeneration

During the last decades nitric oxide (•NO) has emerged as a critical physiological signaling molecule in mammalian tissues, notably in the brain. •NO may modify the activity of regulatory proteins via direct reaction with the heme moiety, or indirectly, via S-nitrosylation of thiol groups or nitration of tyrosine residues. However, a conceptual understanding of how •NO bioactivity is carried out in biological systems is hampered by the lack of knowledge on its dynamics in vivo. Key questions still lacking concrete and definitive answers include those related with quantitative issues of its concentration dynamics and diffusion, summarized in the how much, how long, and how far trilogy. For instance, a major problem is the lack of knowledge of what constitutes a physiological •NO concentration and what constitutes a pathological one and how is •NO concentration regulated. The ambient •NO concentration reflects the balance between the rate of synthesis and the rate of breakdown. Much has been learnt about the mechanism of •NO synthesis, but the inactivation pathways of •NO has been almost completely ignored. We have recently addressed these issues in vivo on basis of microelectrode technology that allows a fine-tuned spatial and temporal measurement •NO concentration dynamics in the brain.
Divisorial Valuations via Arcs

This paper shows a finiteness property of a divisorial valuation in terms of arcs. First we show that every divisorial valuation over an algebraic variety corresponds to an irreducible closed subset of the arc space. Then we define the codimension for this subset and give a formula of the codimension in terms of “relative Mather canonical class”. By using this subset, we prove that a divisorial valuation is determined by assigning the values of finite functions. We also have a criterion for a divisorial valuation to be a monomial valuation by assigning the values of finite functions.
Innate immune control and regulation of influenza virus infections

Adaptive immune responses are critical for the control and clearance of influenza A virus (IAV) infection. However, in recent years, it has become increasingly apparent that innate immune cells, including natural killer cells, alveolar macrophages (aMϕ), and dendritic cells (DC) are essential following IAV infection in the direct control of viral replication or in the induction and regulation of virus‐specific adaptive immune responses. This review will discuss the role of these innate immune cells following IAV infection, with a particular focus on DC and their ability to induce and regulate the adaptive IAV‐specific immune response.
Glucose Intolerance During Decreased Physical Activity in Man

Impaired glucose tolerance is a well documented consequence of absolute bedrest in man. Previous studies have shown a decrease in forearm glucose uptake during intravenous glucose infusion after fourteen days of bedrest. Bedrest is associated not only with physical inactivity but with a change in gravitational vector. This study was designed to examine the individual contributions of these factors to the glucose intolerance of bedrest. Thus, glucose tolerance tests were carried out in exercising subjects at bedrest and in rhesus monkeys immobilized in the vertical plane. Exercise in man improved glucose tolerance during bedrest, and vertically immobilized monkeys demonstrated significant glucose intolerance. It is concluded that the glucose intolerance of bedrest is a function of the decrease in physical activity.
Bioconcentration and tissue distribution of perfluorinated acids in rainbow trout (Oncorhynchus mykiss)

Rainbow trout (Oncorhynchus mykiss) were exposed simultaneously to a homologous series of perfluoroalkyl carboxylates and sulfonates in a flow‐through system to determine compound‐specific tissue distribution and bioconcentration parameters for perfluorinated acids (PFAs). In general, PFAs accumulated to the greatest extent in blood > kidney > liver > gall bladder. Carboxylates and sulfonates with perfluoroalkyl chain lengths shorter than seven and six carbons, respectively, could not be detected in most tissues and were considered to have insignificant bioconcentration factors (BCFs). For detectable PFAs, carcass BCFs increased with increasing length of the perfluoroalkyl chain, ranging from 4.0 to 23,000, based on wet weight concentrations. Carboxylate carcass BCFs increased by a factor of eight for each additional carbon in the perfluoroalkyl chain between 8 and 12 carbons, but this relationship deviated from linearity for the longest PFA tested, possibly because of decreased gill permeability. In general, half‐lives (3.9–28 d) and uptake rates (0.053–1,700 L/kg/d) also increased with increasing length of the perfluoroalkyl chain in all tissues. Sulfonates had greater BCFs, half‐lives, and rates of uptake than the corresponding carboxylate of equal perfluoroalkyl chain length, indicating that hydrophobicity, as predicted by the critical micelle concentration, is not the only determinant of PFA bioaccumulation potential and that the acid function must be considered.
Crystal structure of (E)-1-(4-methoxyphenyl)ethanone O-dehydroabietyloxime

In the title compound, C29H37NO3 {systematic name: (E)-1-(4-methoxyphenyl)ethanone O-[(1R,4aS,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carbonyl]oxime}, a new derivative of dehydroabietic acid, the two cyclohexane rings exhibit a trans-ring junction and are in chair and half-chair conformations. The C=N double bond exhibits an E conformation.
Over-Rotating Black Holes, Godel Holography and the Hypertube

We demonstrate how a five dimensional Godel universe appears as the core of resolved two-charge and three-charge over-rotating BMPV black holes. A smeared generalized supertube acts as a domain wall and removes regions of closed timelike curves by cutting off both the inside and outside solution before causality violations appear, effectively allowing the Godel universe and the over-rotating black hole to solve each other's causality problems. This mechanism suggests a novel form of holography between the compact Godel region and the diverse vacua and excitations of the bound state of a finite number of D0 and D4-branes with fundamental strings.
Insight Into the Origin and Evolution of the Vibrio parahaemolyticus Pandemic Strain

A strain of Vibrio parahaemolyticus that emerged in 1995 caused the first known pandemic involving this species. This strain comprises clonal autochthonous ocean-dwelling bacteria whose evolution has occurred in the ocean environment. The low sequence diversity in this population enabled the discovery of information on its origin and evolution that has been hidden in bacterial clones that have evolved over a long period. Multilocus sequencing and microarray analysis, together with phylogenetic analysis, of pandemic and pre-pandemic isolates has suggested that the founder clone was an O3:K6 non-pathogenic strain that initially acquired a toxRS/new region and subsequently acquired at least seven novel genomic islands. Sequencing and comparison of whole genomes later confirmed these early observations, and it confirmed that most of the genetic changes occurred via gene conversion involving horizontally transmitted DNA. The highly clonal population rapidly diversified, especially in terms of antigenicity, and 27 serotypes have already been reported. Comparisons of the core genomes derived from the founder clone indicate that there are only a few hundred single-nucleotide variations between isolates. However, when the whole genome is considered (the core plus non-core genome and from any clonal frame), the amount of DNA with a different clonal frame can reach up to 4.2% and the number of single-nucleotide variations can reach several hundred thousand. Altogether, these and previous observations based on multilocus sequence typing, microarray analysis, and whole-genome sequencing indicate the large contribution made by DNA with different clonal genealogy to genome diversification. The evidence also indicates that horizontal gene transfer (HGT) caused the emergence of new pathogens. Furthermore, the extent of HGT seems to depend on the vicissitudes of the life of each bacterium, as exemplified by differences in thousands of base pairs acquired by HGT among almost identical genetic isolates.
Genetic Analysis of Variation in Gene Expression in Arabidopsis thaliana

In Arabidopsis thaliana, significant efforts to determine the extent of genomic variation between phenotypically divergent accessions are under way, but virtually nothing is known about variation at the transcription level. We used microarrays to examine variation in transcript abundance among three inbred lines and two pairs of reciprocal F1 hybrids of the highly self-fertilizing species Arabidopsis. Composite additive genetic effects for gene expression were estimated from pairwise comparisons of the three accessions Columbia (Col), Landsberg erecta (Ler), and Cape Verde Islands (Cvi). For the pair Col and Ler, 27.0% of the 4876 genes exhibited additive genetic effects in their expression (α = 0.001) vs. 32.2 and 37.5% for Cvi with Ler and Col, respectively. Significant differential expression ranged from 32.45 down to 1.10 in fold change and typically differed by a factor of 1.56. Maternal or paternal transmission affected only a few genes, suggesting that the reciprocal effects observed in the two crosses analyzed were minimal. Dominance effects were estimated from the comparisons of hybrids with the corresponding midparent value. The percentage of genes showing dominance at the expression level in the F1 hybrids ranged from 6.4 to 21.1% (α = 0.001). Breakdown of these numbers of genes according to the magnitude of the dominance ratio revealed heterosis for expression for on average 9% of the genes. Further advances in the genetic analysis of gene expression variation may contribute to a better understanding of its role in affecting quantitative trait variation at the phenotypic level.
Age‐Related Changes in the Prevalence of Smell/Taste Problems among the United States Adult Population: Results of the 1994 Disability Supplement to the National Health Interview Survey (NHIS)

ABSTRACT: Information about the prevalence of disorders of the chemical senses has been limited. In the late 1970s, the consensus among experts convened by the National Institutes of Health (NIH) was that more than 2 million adults in the United States had a disorder of smell or taste. A large, nonrandom survey conducted by the National Geographic Society in 1987 found that 1% of their 1.2 million respondents could not smell 3 or more of 6 odorants using a 'scratch and sniff' test. Age was an important factor, with a decline beginning in the second decade of life. No comparable data have been available for taste, although it has been suggested that the sense of taste remains more robust with age. The National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, began collaborating with the National Center for Health Statistics (NCHS) in 1993 to acquire information on the prevalence of smell/taste problems using the Disability Supplement to the National Health Interview Survey (NHIS). This survey was administered to approximately 42,000 randomly‐selected households (representing about 80,000 adults over 18 years of age) in 1994. Adjusted national estimates derived from this survey showed a prevalence of 2.7 million (1.4%) U.S. adults with an olfactory problem. Also, 1.1 million (0.6%) adults reported a gustatory problem. When smell or taste problems were combined, 3.2 million (1.65%) adults indicated a chronic chemosensory problem. The prevalence rates increased exponentially with age. Almost 40% with a chemosensory problem (1.5 million) were 65 years of age or greater. In a multivariate analysis, the individual's overall health status, other sensory impairments, functional limitations (including difficulty standing or bending), depression, phobia, and several other health‐related characteristics were associated with an increase in the rate of chemosensory disorders.
Higher order spectral analysis of heart rate variability in pregnancy and postpartum

This paper presents the study of bispectrum analysis methods of heart rate variability in normotensive pregnant and postpartum women. The self and cross spectral components are estimated from bispectrum of ECG of pregnant and postpartum women. It is observed that, very low frequency (VLF) and low frequency (LF) component coupling increases while the high frequency (HF) coupling and cross coupling between VLF-LF, VLF-HF and LF-HF decreases throughout the pregnancy. The power at very high frequencies decreases as gestation age progresses. Significant differences are found in similar and cross coupling frequency components in all three trimesters and postpartum. The results indicate that one possible discriminating dynamics for the pregnant women in all three trimesters is the absence of nonlinear interactions between the sympathetic and parasympathetic nervous systems.
The phytoene synthase gene family in the Grasses

Carotenoids are a complex class of isoprenoid pigments playing diverse roles in plants and providing nutritional value. Metabolic engineering of the biosynthetic pathway has been of interest to specifically address global vitamin A deficiency by breeding cereal crop staples in the Poaceae (Grass family) for elevated levels of provitamin A carotenoids. However, there remain open questions about the rate-controlling steps that limit predictability of metabolic engineering in plants, whether by transgenic or nontransgenic means. We decided to focus on the first committed biosynthetic step which is mediated by phytoene synthase. Our studies revealed that in the Grasses, PSY is encoded by three genes. Maize transcript profiling, together with carotenoid and ABA analysis, revealed that the three PSY copies have subfunctionalized and provide the Grasses with a fine tine control of carotenogenesis in response to various developmental and external cues. Promoter analysis supports subfunctionalization; cis-element analysis of maize PSY1 alleles and comparison with Grass orthologs suggests that man’s selection of yellow maize endosperm has occurred at the expense of a change of gene regulation in photosynthetic tissue as compared to the progenitor white endosperm PSY1 allele.
The metabolism and toxicity of hemin in astrocytes

Hemin is cytotoxic, and contributes to the brain damage that accompanies hemorrhagic stroke. In order to better understand the basis of hemin toxicity in astrocytes, the present study quantified hemin metabolism and compared it to the pattern of cell death. Heme oxygenase‐1 (HO‐1) expression was first evident after 2 h incubation with hemin, with maximal expression being observed by 24 h. Despite the induction of HO‐1, it was found that the proportion of hemin metabolized by astrocytes remained fairly constant throughout the 24 h period, with 70–80% of intracellular hemin remaining intact. A period of cell loss began after 2 h exposure to hemin, which gradually increased in severity to reach a maximum by 24 h. This cell loss could not be attenuated by the iron chelator, 1,10‐phenanthroline, or by several antioxidant compounds (Trolox, N‐acetyl‐L‐cysteine and N‐tert‐butyl‐α‐phenylnitrone), indicating that the mechanism of hemin toxicity does not involve iron. While these results make it unlikely that hemin toxicity is due to interactions with endogenous H2O2, hemin toxicity was increased in the presence of supraphysiological levels of H2O2 and this increase was ameliorated by PHEN, indicating that the iron released from hemin can be toxic under some pathological conditions. However, when H2O2 is present at physiological levels, the toxicity of hemin appears to be caused by other mechanisms that may involve bilirubin and carbon monoxide in this model system. © 2011 Wiley‐Liss, Inc.
Data Center Fault-Tolerant Routing and Forwarding: An Approach Based on Encoded Paths

Traditional layer 2 and layer 3 network designs face some limitations on data center networks such as lack of scalability, difficult management and inflexible communication. We observe that data center networks are often managed as a single logical network fabric with a well-controlled baseline topology and growth model. This paper describes a data center networking approach based on encoded paths carried in the packet header. We present an Open Flow-based test bed implementation of a data center architecture governed by a logically centralized Network Manager, which is responsible to transparently provide the networking and support functions to operate the data center network. We evaluate the proposal in terms of fail recovery time, state requirements, and load balancing capabilities. The results of the experiments show that our proposal improves the fail recovery time, while preserving scalability requirements.
Reassessing selection criteria prior to liver transplantation for hepatocellular carcinoma utilizing the scientific registry of transplant recipients database

The current model of liver graft allocation in place in the United States favors transplantation of patients with small hepatocellular carcinomas (HCCs) within the Milan criteria (a single tumor up to 5 cm in diameter or up to three lesions, none larger than 3 cm). Although several reports have suggested that these criteria could be extended, there is currently no agreement on new selection tools. In this study, we performed an overview of 6478 adult recipients of an isolated first liver transplant registered in the Scientific Registry of Transplant Recipients (SRTR) database. From March 2002 to January 2008, increasing numbers of patients outside Milan criteria (P ≤ 0.001) have been registered for a transplant, but they still represent less than 5% of the transplants performed for HCC. Of all the tested variables (tumor number, largest tumor size, and Milan and University of California San Francisco criteria), only total tumor volume (TTV; P ≤ 0.05) and alpha fetoprotein (AFP; P ≤ 0.001) could predict patient survival. While these two parameters demonstrated independent behaviors (no patient demonstrated an increase in both values), a composite score was defined, with patients with a TTV > 115 cm3 or an AFP > 400 ng/mL being outside criteria. The combined TTV/AFP score efficiently predicted posttransplant survival (hazard ratio = 2, 95% confidence interval = 1.7‐2.4, P ≤ 0.001); patients not meeting these criteria had a survival below 50% at 3 years. Conclusion: According to the present SRTR data, Milan criteria are too restrictive, and patients with larger TTV can enjoy satisfactory posttransplant survivals. A composite patient selection score combining TTV and AFP was the most effective of all tested staging criteria for the prediction of posttransplant patient survival for candidates with HCC. (HEPATOLOGY 2009.)
Natural selection and glucocorticoid physiology

Glucocorticoid hormones are considered potent modulators of trade‐offs between reproduction and survival. As such, selection should affect glucocorticoid physiology, although relatively little is known about how selection may act on glucocorticoid profiles. In general, the evolution of physiology is less studied and less well understood than morphological or life history traits. Here, we used a long‐term data set from a population of mountain white‐crowned sparrows to estimate natural selection on glucocorticoid profiles. Our study suggests that survival selection favours higher hormone concentrations for multiple components of glucocorticoid physiology (both baseline and stress‐induced glucocorticoid levels). Fecundity selection varies depending on the component of hypothalamic–pituitary–adrenal physiology; greater reproductive output was associated with higher baseline glucocorticoid levels, but lower stress‐induced glucocorticoid levels. Additionally, the selection gradient was greater for glucocorticoids than for a morphological trait (wing length). These results support the hypothesis that stress‐induced glucocorticoids increase survival over reproduction within a wild population (the CORT‐trade‐off hypothesis). Taken together, these results add to our knowledge of how selection operates on physiological traits and also provide an evolutionary and ecological perspective on several key open issues in the field of glucocorticoid physiology.
The N-Terminal Transmembrane Domain of λ S Is Required for Holin but Not Antiholin Function

ABSTRACT The λ S gene encodes a holin, S105, and an antiholin, S107, which differs by its Met-Lys N-terminal extension. The model for the lysis-defective character of S107 stipulates that the additional N-terminal basic residue keeps S107 from assuming the topology of S105, which is N-out, C-in, with three transmembrane domains (TMDs). Here we show that the N terminus of S105 retains its fMet residue but that the N terminus of S107 is fully deformylated. This supports the model that in S105, TMD1 inserts into the membrane very rapidly but that in S107, it is retained in the cytoplasm. Further, it reveals that, compared to S105, S107 has two extra positively charged moieties, Lys2 and the free N-terminal amino group, to hinder its penetration into an energized membrane. Moreover, an allele, S105ΔTMD1 , with TMD1 deleted, was found to be defective in lysis, insensitive to membrane depolarization, and dominant to the wild-type allele, indicating that the lysis-defective, antiholin character of S107 is due to the absence of TMD1 from the bilayer rather than to its ectopic localization at the inner face of the cytoplasmic membrane. Finally, the antiholin function of the deletion protein was compromised by the substitution of early-lysis missense mutations in either the deletion protein or parental S105 but restored when both S105ΔTMD1 and holin carried the substitution.
The diagnostic efficacy and safety of endobronchial ultrasound-guided transbronchial needle aspiration as an initial diagnostic tool

Background/Aims Real-time, convex probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used for the staging of malignant mediastinal lymph nodes. We evaluated the diagnostic efficacy and safety of EBUS-TBNA when used as an initial diagnostic tool. Methods We retrospectively studied 56 patients who underwent EBUS-TBNA as an initial diagnostic tool between August 2010 and December 2011. Procedure purpose were classified into four categories: 1) intrathoracic masses adjacent to the central airway; 2) enlarged lymph nodes for concurrent diagnosis and staging in suspected malignancy; 3) enlarged lymph nodes in suspected malignancy cases with inability to perform percutaneous core needle biopsy (PCNB); and 4) solely mediastinal masses/lymph nodes in lieu of mediastinoscopy. Results The diagnostic accuracy of EBUS-TBNA regardless of procedure purpose was calculated to be 83.9%. Furthermore, the diagnostic accuracy of malignant disease was significantly higher than benign disease (93.9% vs. 70.6%, p < 0.001). The diagnostic accuracy of EBUS-TBNA for each disease is as follows: tuberculosis, 50%; sarcoidosis, 60%; aspergillosis, 100%; lung abscess, 100%; lung cancer, 93%; and lymphoma, 100%. There were minor complications in seven patients during the EBUS-TBNA procedure. The complications included mild hypoxia and bleeding. Conclusions In conclusion, EBUS-TBNA is a useful initial diagnostic tool for both benign and malignant diseases. EBUS-TBAN is also a very safe procedure and less invasive compared to mediastinoscopy or PCNB.