Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequential computation of elementary modes and minimal cut sets in genome‐scale metabolic networks using alternate integer linear programming

Motivation: Elementary (flux) modes (EMs) have served as a valuable tool for investigating structural and functional properties of metabolic networks. Identification of the full set of EMs in genome‐scale networks remains challenging due to combinatorial explosion of EMs in complex networks. It is often, however, that only a small subset of relevant EMs needs to be known, for which optimization‐based sequential computation is a useful alternative. Most of the currently available methods along this line are based on the iterative use of mixed integer linear programming (MILP), the effectiveness of which significantly deteriorates as the number of iterations builds up. To alleviate the computational burden associated with the MILP implementation, we here present a novel optimization algorithm termed alternate integer linear programming (AILP). Results: Our algorithm was designed to iteratively solve a pair of integer programming (IP) and linear programming (LP) to compute EMs in a sequential manner. In each step, the IP identifies a minimal subset of reactions, the deletion of which disables all previously identified EMs. Thus, a subsequent LP solution subject to this reaction deletion constraint becomes a distinct EM. In cases where no feasible LP solution is available, IP‐derived reaction deletion sets represent minimal cut sets (MCSs). Despite the additional computation of MCSs, AILP achieved significant time reduction in computing EMs by orders of magnitude. The proposed AILP algorithm not only offers a computational advantage in the EM analysis of genome‐scale networks, but also improves the understanding of the linkage between EMs and MCSs. Availability and Implementation: The software is implemented in Matlab, and is provided as supplementary information. Contact: hyunseob.song@pnnl.gov Supplementary information: Supplementary data are available at Bioinformatics online.
Patients With Renal Dysfunction Require a Longer Duration Until Blood Pressure Dips During the Night

We have postulated that the diminished renal capacity to excrete sodium causes nocturnal blood pressure (BP) elevation, which enhances pressure natriuresis in compensation for impaired daytime natriuresis. If such a mechanism holds, high BP during sleep at night may continue until excess sodium is sufficiently excreted into urine. This study examined whether the duration, defined as “dipping time,” until nocturnal mean arterial pressure began to fall to <90% of daytime average became longer as renal function deteriorated. Ambulatory BP measurements and urinary sodium excretion rates were evaluated for daytime and nighttime to estimate their circadian rhythms in 65 subjects with chronic kidney disease. Dipping time showed an inverse relationship with creatinine clearance (Ccr; &rgr;=−0.61; P<0.0001) and positive relationships with night/day ratios of mean arterial pressure (&rgr;=0.84; P<0.0001) and natriuresis (&rgr;=0.61; P<0.0001), both of which were also inversely correlated with Ccr (mean arterial pressure: r=−0.58, P<0.0001; natriuresis: r=−0.69, P<0.0001). When divided into tertiles by Ccr (mL/min), hazard ratios of nocturnal BP dip adjusted for age, gender, and body mass index were 0.37 (95% CI: 0.17 to 0.79; P=0.01) for the second tertile (Ccr: 50 to 90) and 0.20 (95% CI: 0.08 to 0.55; P=0.002) for the third tertile (Ccr: 5 to 41) compared with the first tertile (Ccr: 91 to 164). These findings demonstrate that patients with renal dysfunction require a longer duration until BP falls during the night. The prolonged duration until BP dip during sleep seems an essential component of the nondipper pattern of the circadian BP rhythm.
Early Renal Dysfunction is Associated with Exposure to Petroleum Products in Petroleum Stations Workers at Khartoum State – Sudan

Petrol and its derivatives are the most important sources of energy in the world, and they have many benefits and uses however they have hematological and biochemical adverse effects on human health. The primary purpose of this study is to determine the effect of petroleum products exposure on renal function. This study carried out at Khartoum state on petroleum stations workers during the period from March to May 2016. Spot urine samples were collected from 50 individuals exposed to petroleum products at petroleum stations and 50 non exposed individuals as control. The urine Albumin and urine creatinine was estimated by using cobas Integra 400 analyzer and then the albumin/creatinine ratio was calculated. The mean of albumin/creatinine ratio was higher in exposed group (43.56±43.00 mg/g) compared to non exposed group (19.58±3.9 mg/g); p.value<0.05 and there was no correlation of albumin/creatinine ratio(ACR) results with age, body mass index (BMI) and duration of exposure to petroleum products at petroleum stations per year. The exposure to petroleum products at petroleum stations has risk of renal dysfunction, but the severity of renal damage was not correlated with duration of exposure to petroleum products. That indicates increase the probability of chronic kidney disease in petroleum stations workers in the area of study.
Reproducibility of Newly Developed Spinal Topography Measurements for Scoliosis

Objective: In an effort to limit exposure to ionizing radiation and fully characterize three dimensional changes in the spine of patients with scoliosis reliable non-invasive methods of spinal back contour analysis (Milwaukee Topographic Scanner) (MTS) have been developed. Study Design: The current study compares spinal topography measurements among different subject positions and evaluates the reproducibility of the system for both inter-rater and intra-rater reliability. Methods: A dummy cast (plastic cast) of one patient with adolescent idiopathic scoliosis was created in order to test the reliability of the MTS. The dummy cast was positioned and rotated in 3D while scanned by two investigators using the MTS. A total of twelve parameters including Q-angle (an analog to X-ray’s Cobb angle) were extracted. Results: All measurements of intra-rater and inter-rater reliability were excellent (Intraclass Correlation Coefficients ranging from 0.89 to 0.99) with the exception of Pelvic Tilt (intra-rater ICC is 0.61) and lordosis angle (inter-rater ICC is 0.82). No significant variability among investigators was observed for all tested metrics. No significant variability due to position was observed for the majority of back contour measurements but there were significant changes in the T1-S1 angle, T1-S1 deviation, T1-NC angle, T1-NC deviation, and Back Height metric (p< 0.05). Conclusions: The MTS is a reliable method of raster stereography in the measurement of the back contour, which will help monitor the progression of children with idiopathic scoliosis and reduce the use of X-rays.
MIMO indoor WLAN channel measurements and parameter modeling at 5.25 GHz

We present measurement results of indoor multiple-input multiple-output (MIMO) multipath wireless channels in the unlicensed national information infrastructure (U-NII) 5.25 GHz band for wireless local area network (WLAN) applications. MIMO channel impulse responses were measured at different locations using co-polarized (copol) and cross-polarized (crosspol) antennas under line-of-sight (LOS) and non-line-of-sight (NLOS) channel conditions in office and cafeteria type environments. Ricean k-factors, correlations, crosspol discriminations (XPD), pathloss (PL) and RMS delay spread (/spl tau//sub rms/) were computed for different antenna configurations (copol/crosspol) and different channel conditions (LOS/NLOS). Models were developed to characterize the distance dependent variation and the statistical deviations of these parameters.
Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis

The mechanism of tumor cell killing by OXI4503 was investigated by studying vascular functional and morphological changes post drug administration. SCID mice bearing MHEC5‐T hemangioendothelioma were given a single dose of OXI4503 at 100 mg/kg. Tumor blood flow, measured by microsphere fluorescence, was reduced by 50% at 1 hr, and reached a maximum level 6–24 hr post drug treatment. Tumor vascular permeability, measured by Evan's blue and hemoglobin, increased significantly from 3 hr and peaked at 18 hr. The elevated tumor vessel permeability was accompanied by an increase in vascular endothelial growth factor (VEGF) from 1 hr post drug treatment. Immunohistochemical staining for CD31 and laminin showed that tumor blood vessels were affected as early as 3 hr but more prominent from 6 hr. From 12 hr, the vessel structure was completely destroyed. Histopathological and double immunohistochemical staining showed morphological change and induction of apoptosis in endothelial cells at 1–3 hr, followed by tumor cell necrosis from 6–72 hr. There were no statistically significant changes of Evan's blue and hemoglobin contents in liver tissue over the time course. These results suggest that OXI4503 selectively targets tumor blood vessels, and induces blood flow shutdown while it enhances tumor blood vessel permeability. The early induction of endothelial cell apoptosis leads to functional changes of tumor blood vessels and finally to the collapse of tumor vasculature, resulting in massive tumor cell necrosis. The time course of the tumor vascular response observed with OXI4503 treatment supports this drug for development as a stand alone therapy, and also lends support for the use of the drug in combination with other cancer therapies. © 2004 Wiley‐Liss, Inc.
The physical mechanism of dispersion caused by AlGaN/GaN buffers on Si and optimization for low dispersion

In this paper a measurement methodology, using a two-dimensional electron gas (2DEG) resistor, is used to evaluate the dispersion of three different type of buffers, namely a step graded buffer, a buffer with low temperature (LT) AlN interlayers and a superlattice buffer. Together with a dedicated Design of Experiments (DOE), these measurements allowed us to identify the physical origin of the dispersion and identify the key parts of the buffer which influence the buffer-induced dispersion of the 2DEG.
A Simplified Binet Formula for k-Generalized Fibonacci Numbers

We present a particularly nice Binet-style formula that can be used to produce the k-generalized Fibonacci numbers (that is, the Tribonaccis, Tetranaccis, etc). Furthermore, we show that in fact one needs only take the integer closest to the first term of this Binet-style formula to generate the desired sequence. These results were also found (independently) at about the same time by Zhaohui Du of Singapore, China. We are working on a joint paper.
Antiplatelet therapy attenuates subcellular remodelling in congestive heart failure

Antiplatelet agents, sarpogrelate (SAR), a 5‐HT2A receptor antagonist, and cilostazol (CIL), a phosphodiesterase III (PDE‐III) inhibitor, are used for the treatment of peripheral vascular disease. We tested whether these agents affect cardiac function and subcellular remodelling in congestive heart failure (CHF) induced by myocardial infarction (MI). Three weeks after MI, rats were treated daily with 5 mg/kg SAR or CIL as well as vehicle for 5 weeks. Sham‐operated animals served as controls. At end of the treatment period, haemodynamic measurements were performed and the left ventricle was processed for the determination of sarcoplasmic reticulum (SR) Ca2+‐uptake and ‐release activities, and expression of SR Ca2+‐pump, phospholamban and ryanodine receptors, as well as myofibrillar ATPase activities, expression of α‐ and β‐myosin heavy chain (MHC) isoforms, and phosphorylation of phospholamban and cardiac troponin‐I (c Tn‐I). Marked haemodynamic changes in the MI‐induced CHF were associated with depressions in SR Ca +‐uptake and ‐release activities as well as in protein content and gene expression for SR proteins. Furthermore, myofibrillar Ca2+‐stimulated ATPase activity, as well as protein content and gene expression for α‐MHC were decreased whereas those for β‐MHC were increased in the failing heart. Also, phosphorylation levels of phospholamban and cTn‐I were reduced in failing hearts. The MI‐associated changes in cardiac function, SR and myofibillar activities, as well as SR and myofibrillar protein and gene expression were attenuated by treatment with SAR or CIL. The results suggest that SAR and CIL improve cardiac function by ameliorating subcellular remodelling in the failing heart and indicate the potential therapy of CHF with antiplatelet agents.
Distributed maintenance of resource reservation paths in multihop 802.11 networks

Supporting applications with high quality-of-service requirements in wireless multihop networks is challenging, mainly due to uncertainties about the packet forwarding times introduced by the data link layer at every node on the path to the destination. For instance, networks based on IEEE 802.11 exhibit such variable forwarding times due to their CSMA (carrier sense multiple access) mechanism. Previously, we designed a fully distributed reservation protocol that introduces time slots into this CSMA mechanism. We now analyze the performance of our protocol in scenarios where nodes randomly switch on and off. We show, by simulation, that our protocol achieves a lower average and less variable end-to-end delay.
Adjunctive cognitive behavioural treatment for chronic pain couples improves marital satisfaction but not pain management outcomes

Data have consistently shown that patient coping with chronic pain can be affected by various factors associated with the primary relationship, and hence efforts to include the patient's partner in the treatment process have merit. This study evaluated the benefit of adding an adjunctive, couples‐based, cognitive behavioural treatment (CBT) for chronic pain to a standard cognitive behavioural pain management programme.
Multiple maxima of likelihood in phylogenetic trees: an analytic approach

Maximum likelihood (ML) is a widely used criterion for selecting optimal evolutionary trees. However, little is known on the nature of the likelihood surface for trees, especially as to the frequency of multiple optima. We initiate an analytic study for identifying sequences that generate multiple optima. We report a new approach to calculating ML directly, which we have used to find large families of sequences that have multiple optima, including sequences with a continuum of optimal points. Such datasets are best supported by different (two or more) phylogenies that vary significantly in their timings of evolutionary events Some standard biological processes can lead to data with multiple optima and consequently the field needs further investigation. Our results imply that hill climbing techniques, as currently implemented in various software packages, cannot guarantee to find the global ML point, even if it is unique.
Emergence and Spread in French Hospitals of Methicillin-Resistant Staphylococcus aureus with Increasing Susceptibility to Gentamicin and Other Antibiotics

ABSTRACT Oxacillin (methicillin) resistance in methicillin-resistantStaphylococcus aureus (MRSA) is associated with an increased incidence of resistance to other antibiotics, which has increased since it was first reported in 1969. In 1992 a new phenotype of MRSA arose in France; this was characterized by a heterogeneous expression of resistance to oxacillin and susceptibility to various antibiotics, including gentamicin but also tetracycline, minocycline, lincomycin, pristinamycin, co-trimoxazole, rifampin, and fusidic acid. In French hospitals a longitudinal nationwide surveillance of antibiotic resistance in S. aureus has allowed for the detection of changes in antibiotic susceptibility profiles. Seven French clinical laboratories (six from the mainland and one from the West Indies) reported the results of susceptibility testing of 57,347 S. aureus strains isolated in their institutes between 1992 and 1998. Over a 7-year period the incidence of isolation of gentamicin-susceptible MRSA (GS-MRSA) strains has steadily increased to represent, in 1998, 46.8 to 94.4% of the MRSA strains, irrespective of the overall incidence of MRSA. Two predominant types recognized by pulsed-field gel electrophoresis (PFGE) accounted for the majority of the GS-MRSA in different mainland hospitals, both differing from the predominant type observed in the French West Indies. Some GS-MRSA and gentamicin-resistant MRSA (GR-MRSA) strains had closely related PFGE profiles, and hybridization studies confirmed the lack in GS-MRSA of the aac6′-aph2" gene, which confers resistance to all aminoglycosides, with conservation of the ant4′ gene, which confers resistance to kanamycin, tobramycin, and amikacin. Thus, it is likely that certain GS-MRSA strains could have emerged from GR-MRSA strains by excision or deletion of the aac6′-aph2" gene.
Promoter Hypermethylation of KLF4 Inactivates Its Tumor Suppressor Function in Cervical Carcinogenesis

Objective The KLF4 gene has been shown to be inactivated in cervical carcinogenesis as a tumor suppressor. However, the mechanism of KLF4 silencing in cervical carcinomas has not yet been identified. DNA methylation plays a key role in stable suppression of gene expression. Methods The methylation status of the KLF4 promoter CpG islands was analyzed by bisulfite sequencing (BSQ) in tissues of normal cervix and cervical cancer. KLF4 gene expression was detected by RT-PCR, immunohistochemistry and western blot. KLF4 promoter methylation in cervical cancer cell line was determined by BSQ and methylation-specific polymerase chain reaction (MS-PCR). Cell proliferation ability was detected by cell growth curve and MTT assay. Results The methylated allele was found in 41.90% of 24 cervical cancer tissues but only in 11.11% of 11 normal cervix tissues (P<0.005). KLF4 mRNA levels were significantly reduced in cervical cancer tissues compared with normal cervix tissues (P<0.01) and KLF4 mRNA expression showed a significant negative correlation with the promoter hypermethylation (r = −0.486, P = 0.003). Cervical cancer cell lines also showed a significant negative correlation between KLF4 expression and hypermethylation. After treatment with the demethylating agent 5-Azacytidine (5-Aza), the expression of KLF4 in the cervical cancer cell lines at both mRNA and protein levels was drastically increased, the cell proliferation ability was inhibited and the chemosensitivity for cisplatin was significantly increased. Conclusion KLF4 gene is inactivated by methylation-induced silencing mechanisms in a large subset of cervical carcinomas and KLF4 promoter hypermethylation inactivates the gene’s function as a tumor suppressor in cervical carcinogenesis.
Diverse supramolecular structures formed by self‐assembling proteins of the B acillus subtilis spore coat

Bacterial spores (endospores), such as those of the pathogens Clostridium difficile and Bacillus anthracis, are uniquely stable cell forms, highly resistant to harsh environmental insults. Bacillus subtilis is the best studied spore‐former and we have used it to address the question of how the spore coat is assembled from multiple components to form a robust, protective superstructure. B. subtilis coat proteins (CotY, CotE, CotV and CotW) expressed in Escherichia coli can arrange intracellularly into highly stable macro‐structures through processes of self‐assembly. Using electron microscopy, we demonstrate the capacity of these proteins to generate ordered one‐dimensional fibres, two‐dimensional sheets and three‐dimensional stacks. In one case (CotY), the high degree of order favours strong, cooperative intracellular disulfide cross‐linking. Assemblies of this kind could form exquisitely adapted building blocks for higher‐order assembly across all spore‐formers. These physically robust arrayed units could also have novel applications in nano‐biotechnology processes.
Human Milk

Entero-mammary pathway The presence of obligate anaerobic bacteria was not compatible with the traditional view that human milk is sterile by nature. Bacteria detected in milk were thought to stem exclusively from the breast skin or from the baby’s mouth colonizing the mammary gland, said Jiménez. In another study the same lactic acid bacteria were found in locally fermented food, maternal milk, and fecal samples of breastfeeding mothers and their babies [5]. This observation supports the hypothesis that bacteria are transferred from the mother’s gastrointestinal tract to her milk and through the milk to the infant’s gastrointestinal tract. As Jiménez reported, evidence has increased that a mother’s gastrointestinal bacteria are able to reach the mammary gland via an endogenous route. For this bacterial The first studies investigating the bacterial content of human milk were undertaken in the 1970s and 1980s because of concerns that bacteria might affect preterm babies fed with human milk. At that time, the only bacteria that had been detected in human milk were Staphylococci and Streptococci, reported Dr. Esther Jiménez, Madrid (Spain). It was not until 2003 that lactic acid bacteria were isolated from human milk [1]; these were regarded as beneficial because they were able to suppress the growth of Staphylococcus aureus in the laboratory [2].
The Tumor Suppressor PTEN Is Phosphorylated by the Protein Kinase CK2 at Its C Terminus

The tumor suppressor phosphatase PTEN regulates cell migration, growth, and survival by dephosphorylating phosphatidylinositol second messengers and signaling phosphoproteins. PTEN possesses a C-terminal noncatalytic regulatory domain that contains multiple putative phosphorylation sites, which could play an important role in the control of its biological activity. The protein kinase CK2 phosphorylated, in a constitutive manner, a cluster of Ser/Thr residues located at the PTEN C terminus. PTEN-phosphorylated defective mutants showed decreased stability in comparison with wild type PTEN and were more rapidly degraded by the proteasome. Inhibition of PTEN phosphorylation by the CK2 inhibitor 5,6-dichloro-1-β-d-ribofuranosyl-benzimidazole also diminished the PTEN protein content. Our results support the notion that proper phosphorylation of PTEN by CK2 is important for PTEN protein stability to proteasome-mediated degradation.
Evaluation of Organic Anion Transporting Polypeptide 1B1 and 1B3 Humanized Mice as a Translational Model to Study the Pharmacokinetics of Statins

Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.