Miracle-dz/UniFAR-FTUs huggingface dataset:
Reductive Metabolism Influences the Toxicity and Pharmacokinetics of the Hypoxia-Targeted Benzotriazine Di-Oxide Anticancer Agent SN30000 in Mice

3-(3-Morpholinopropyl)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (SN30- 000), an analog of the well-studied bioreductive prodrug tirapazamine (TPZ), has improved activity against hypoxic cells in tumor xenografts. However, little is known about its biotransformation in normal tissues. Here, we evaluate implications of biotransformation of SN30000 for its toxicokinetics in NIH-III mice. The metabolite profile demonstrated reduction to the 1-N-oxide (M14), oxidation of the morpholine side-chain (predominantly to the alkanoic acid M18) and chromophore, and subsequent glucuronidation. Plasma pharmacokinetics of SN30000 and its reduced metabolites was unaffected by the presence of HT29 tumor xenografts, indicating extensive reduction in normal tissues. This bioreductive metabolism, as modeled by hepatic S9 preparations, was strongly inhibited by oxygen indicating that it proceeds via the one-electron (radical) intermediate previously implicated in induction of DNA double strand breaks and cytotoxicity by SN30000. Plasma pharmacokinetics of SN30000 and M14 (but not M18) corresponded closely to the timing of reversible acute clinical signs (reduced mobility) and marked hypothermia (rectal temperature drop of ∼8°C at nadir following the maximum tolerated dose). Similar acute toxicity was elicited by dosing with TPZ or M14, although M14 did not induce the kidney and lung histopathology caused by SN30000. M14 also lacked antiproliferative potency in hypoxic cell cultures. In addition M14 showed much slower redox cycling than SN30000 in oxic cultures. Thus a non-bioreductive mechanism, mediated through M14, appears to be responsible for the acute toxicity of SN30000 while late toxicities are consistent with DNA damage resulting from its one-electron reduction. A two-compartment pharmacokinetic model, in which clearance of SN30000 is determined by temperature-dependent bioreductive metabolism to M14, was shown to describe the non-linear PK of SN30000 in mice. This study demonstrates the importance of non-tumor bioreductive metabolism in the toxicology and pharmacokinetics of benzotriazine di-oxides designed to target tumor hypoxia.
Increased Hydrolysis of Oximino-β-Lactams by CMY-107, a Tyr199Cys Mutant Form of CMY-2 Produced by Escherichia coli

ABSTRACT The cephalosporinase CMY-107, a Tyr199Cys mutant form of CMY-2 encoded by an IncI self-transferable plasmid carried by an Escherichia coli clinical strain, was characterized. The enzyme hydrolyzed oximino-cephalosporins and aztreonam more efficiently than CMY-2 did.
The extended disc and halo of the Andromeda galaxy observed with Spitzer-IRAC

We present the first results from an extended survey of the Andromeda galaxy (M31) using 41.1 h of observations by Spitzer-IRAC at 3.6 and 4.5 µm. This survey extends previous observations to the outer disc and halo, covering total lengths of 4°. 4 and 6°. 6 along the minor and major axes, respectively. We have produced surface brightness profiles by combining the integrated light from background-corrected maps with stellar counts from a new catalogue of point sources. Using auxiliary catalogues, we have carried out a statistical analysis in colour–magnitude space to discriminate M31 objects from foreground Milky Way stars and background galaxies. The catalogue includes 426 529 sources, of which 66 per cent have been assigned probability values to identify M31 objects with magnitude depths of [3.6] = 19.0 ± 0.2, [4.5] = 18.7 ± 0.2. We discuss applications of our data for constraining the stellar mass and characterizing point sources in the outer radii.
Adenovirus Endocytosis Requires Actin Cytoskeleton Reorganization Mediated by Rho Family GTPases

ABSTRACT Adenovirus (Ad) endocytosis via αv integrins requires activation of the lipid kinase phosphatidylinositol-3-OH kinase (PI3K). Previous studies have linked PI3K activity to both the Ras and Rho signaling cascades, each of which has the capacity to alter the host cell actin cytoskeleton. Ad interaction with cells also stimulates reorganization of cortical actin filaments and the formation of membrane ruffles (lamellipodia). We demonstrate here that members of the Rho family of small GTP binding proteins, Rac and CDC42, act downstream of PI3K to promote Ad endocytosis. Ad internalization was significantly reduced in cells treated with Clostridium difficile toxin B and in cells expressing a dominant-negative Rac or CDC42 but not a H-Ras protein. Viral endocytosis was also inhibited by cytochalasin D as well as by expression of effector domain mutants of Rac or CDC42 that impair cytoskeletal function but not JNK/MAP kinase pathway activation. Thus, Ad endocytosis requires assembly of the actin cytoskeleton, an event initiated by activation of PI3K and, subsequently, Rac and CDC42.
Mathematical Modelling of Mooring Systems for Wave Energy Converters—A Review

Mathematical analysis is an essential tool for the successful development and operation of wave energy converters (WECs). Mathematical models of moorings systems are therefore a requisite in the overall techno-economic design and operation of floating WECs. Mooring models (MMs) can be applied to a range of areas, such as WEC simulation, performance evaluation and optimisation, control design and implementation, extreme load calculation, mooring line fatigue life evaluation, mooring design, and array layout optimisation. The mathematical modelling of mooring systems is a venture from physics to numerics, and as such, there are a broad range of details to consider when applying MMs to WEC analysis. A large body of work exists on MMs, developed within other related ocean engineering fields, due to the common requirement of mooring floating bodies, such as vessels and offshore oil and gas platforms. This paper reviews the mathematical modelling of the mooring systems for WECs, detailing the relevant material developed in other offshore industries and presenting the published usage of MMs for WEC analysis.
Pna Probability, Networks and Algorithms Probability, Networks and Algorithms Self-destructive Percolation Self-destructive Percolation

CWI's research has a theme-oriented structure and is grouped into four clusters. Listed below are the names of the clusters and in parentheses their acronyms. ABSTRACT Consider ordinary site percolation on an infinite graph in which the sites, independent of each other, are occupied with probability p and vacant with probability 1−p. Now suppose that, by some 'catastrophe', all sites which are in an infinite occupied cluster become vacant. Finally, each vacant site gets an extra enhancement to become occupied. More precisely, each site that was already vacant or that was made vacant by the catastrophe, becomes occupied with probability δ (independent of the other sites). When p is larger than but close to the critical value p c one might believe (for 'nice' graphs) that only a small δ is needed to have an infinite occupied cluster in the final configuration. This appears to be indeed the case for the binary tree. However, on the square lattice we strongly conjecture that this is not true. We discuss the background for these problems and also show that the conjecture, if true, has some remarkable consequences. Note: This report has been submitted for publication elsewere. This work has been done under project PNA 3.1.
A coupling between a non-linear 1D compressible-incompressible limit and the 1D $p$-system in the non smooth case

We consider two compressible immiscible fluids in one space dimension and in the isentropic approximation. The first fluid is surrounded and in contact with the second one. As the sound speed of the first fluid diverges to infinity, we present the proof of rigorous convergence for the fully non--linear compressible to incompressible limit of the coupled dynamics of the two fluids. A linear example is considered in detail, where fully explicit computations are possible.
SDSS J090152.05+624342.6: A NEW “OVERLAPPING-TROUGH” FeLoBAL QUASAR AT Z ~ 2

We here report an identification of SDSS J090152.04+624342.6 as a new "overlapping-trough" iron low-ionization broad absorption line quasar at redshift of $z\sim2.1$. No strong variation of the broad absorption lines can be revealed through the two spectra taken by the Sloan Digital Sky Survey with a time interval of $\sim6$yr. Further optical and infrared spectroscopic study on this object is suggested.
Behavioral Anomalies in Consumer Wait-or-Buy Decisions and Their Implications for Markdown Management

A decision to buy an item at a regular price or wait for a possible markdown involves a multi-dimensional trade-off between the value of the item, the delay in getting it, the likelihood of getting it, and the magnitude of the price discount. Such trade-offs are prone to behavioral anomalies by which human decision makers deviate from the discounted expected utility model. We build an axiomatic preference model that accounts for three well-known anomalies, and produces a parsimonious generalization of discounted expected utility. We then plug this behavioral model into a Stackelberg-Nash game between a firm that decides the price discount and a continuum of consumers who decide to wait or buy, anticipating other consumers' decisions and the resultant likelihood of product availability. We solve the markdown management problem and contrast the results of our model with those under discounted expected utility. We analytically show that accounting for the behavioral anomalies can result in larger markdowns and higher revenues. Finally, we calibrate our model via a laboratory experiment, and validate its predictions out-of-sample.
Differences in risk factors according to the site of intracranial aneurysms

Background and purpose: Several risk factors for aneurysmal subarachnoid haemorrhage have been identified but it is not known whether some sites of aneurysms are linked to a specific risk factor. In a series of patients with aneurysmal subarachnoid haemorrhage, we compared risk factors according to the site of the ruptured aneurysm at the circle of Willis. Methods: From our prospectively collected database of patients with aneurysmal subarachnoid haemorrhage admitted to our hospital between 2003 and 2007, we retrieved 304 patients with saccular aneurysms on the anterior communicating artery, middle cerebral artery, posterior communicating artery, basilar artery and vertebral artery. Risk factors (age, gender, smoking, no or excessive alcohol intake, hypertension and familial preponderance) were assessed per aneurysm location and compared with the anterior communicating artery as reference. We calculated odds ratios (ORs) and corresponding 95% CI. Results: In comparison with aneurysms at the anterior communicating artery, those at the middle cerebral artery were less associated with age >55 years (OR 0.4; 95% CI 0.2 to 0.8), those at the posterior communicating artery were less associated with male gender (OR 0.4; 95% CI 0.2 to 0.9) and those at the basilar artery were more associated with no alcohol consumption (OR 5.8; 95% CI 1.1 to 29.9). Conclusion: Risk factors differ according to the site of aneurysm. This heterogeneity should be kept in mind in studies on the aetiology of aneurysms, such as genetic studies.
Increasing Incidence of Linezolid-Intermediate or -Resistant, Vancomycin-Resistant Enterococcus faecium Strains Parallels Increasing Linezolid Consumption

ABSTRACT Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r2 = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.
Exosome Function: From Tumor Immunology to Pathogen Biology

Exosomes are the newest family member of ‘bioactive vesicles’ that function to promote intercellular communication. Exosomes are derived from the fusion of multivesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non‐hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell‐to‐cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intracellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates.
Urbanization in China in the 1990s: New Definition, Different Series, and Revised Trends *

This paper tackles new problems concerning China’s urban population figures and the annual urban population series arising from the use of a new Census 2000 urban definition. The paper extends existing research and incorporates crucial findings not available or previously overlooked. The paper assesses major competing urban annual series for the 1990s, including the latest released in the Zhongguo tongji nianjian 2002 and checks empirically the different series of urban population estimates, by
Comment on Elejalde syndrome and relationship with Griscelli syndrome

In their interesting report about Elejalde syndrome (ES), Ivanovich et al. [2001] discussed the complex relationship of this disease with Griscelli syndrome (GS). Unfortunately, their report was submitted shortly before the publication of new data about molecular genetics of GS that have by now defined the relationship of ES and GS [Menasché et al., 2000]. GS is a rare autosomal recessive disease with hypopigmentation and hemophagocytic lymphohistiocytosis underlied by deficient lymphocyte cytotoxicity and variable neurological defects [Klein et al., 1994]. ES, or melanolysosomal neurocutaneous syndrome, is a rare autosomal recessive disease, which as its name indicates, associates hypopigmentation and profound central nervous system dysfunction [Elejalde et al., 1979; DuranMcKinster et al., 1999]. ES and GS bear a striking resemblance in that, in both diseases, hypopigmentation manifests as silvery hair, and is underlied by defective melanosome transport in melanocytes. The myosin Va gene (MYOVA) was the first gene involved in GS [Pastural et al., 1997]. Noticeably, these MYOVA mutations were found in patients, who, apart from silvery hair, presented early-onset severe psychomotor retardation, but no immune deficiency [Menasché et al., 2000]. The murine dilute phenotype, consisting of coat color dilution and severe neurological defects is also caused by mutations of MYOVA [Mercer et al., 1991]. Confirming genetic data, it was shown that myosin Va regulates organelle transport in melanocytes and in neuronal cells [Reck-Peterson et al., 2000]. However, in other GS patients, it was demonstrated that the Rab27a gene (RAB27A) is mutated. Noticeably, apart from partial albinism, patients with RAB27A mutations presented hemophagocytic lymphohistiocytosis, but no primary neurological disease [Menasché et al., 2000]. The murine ashen phenotype, consisting of coat color dilution and deficient cytotoxic lymphocyte activity, is also caused by a mutation in RAB27A [Wilson et al., 2000]. Confirming genetic data we studied the melanocytes of a GS patient with a nonsense mutation in RAB27A and established the key-role of Rab27a in melanosome transport [Menasché et al., 2000], while others showed that Rab27a is required for cytotoxic granule exocytosis [Menasché et al., 2000;Haddad et al., 2001; Stinchcombe et al., 2001]. These data shed a new light on the relationship of ES and GS. Mutations of MYOVA result in the cutaneousandneurological formof Griscelli syndrome or Griscelli syndrome type 1 that likely corresponds to Elejalde syndrome, and dilute is the corresponding mouse model. On the other hand, mutations in RAB27A account for the cutaneous and immunological form of Griscelli syndrome or Griscelli syndrome type 2, and ashen is the corresponding mouse model. The possible occurrence of neurological symptoms caused by hemophagocytic syndrome in the second subset of patients probably explains why this clarification could not be made before molecular data became available.
QoS-oriented Admission Control in HSDPA networks

HSDPA defines a new High Speed Shared Channel (HS-DSCH) which allows for practical speeds up to 10 Mbps. Among all the changes introduced by HSDPA, the most prominent ones regarding QoS are the inclusion of “link adaptation”, “Hybrid ARQ” and the quick “Scheduling” algorithms. In HSDPA the Radio Network Controller (RNC) is still the responsible for admitting new users but also for handling different kinds of traffics of different users over the same channel. One of the mostly adopted solutions for admitting new users assuring QoS comprises an admission control algorithm based on performance, with the cells power as the limiting resource. This kind of algorithms makes use of a static “guard power offset” for users whose channel conditions worsen in the course of the connection. In this paper, we propose two admission control algorithms that take into account that this guard power varies according to the channel conditions of each user, the number of allowed users, the service and the transmission speed that they require, and the power used by the cell on each Transmission Time Interval (TTI). The coverage radius of the cell will be divided into three concentric rings, and those users with better channel conditions (the ones nearer to the Node-B) will be assigned with higher priority. Since they will need less power than those farther they will have a better chance on satisfying their needs. Simulation scenario in Matlab shows the behavior of these proposals by comparing how many users are admitted and how many of them are satisfied.
Chronology and Culture Change in the San Juan Islands, Washington

Abstract The archaeological sequence in the San Juan Islands is known best from two phases: the Marpole phase which occurs within the first millennium B.C., and the San Juan phase which lasts from at least A.D. 1300 to historic times. More difficult to place culturally and chronologically are: (1) the previously excavated bluff areas of Cattle Point which contain components similar to Whalen I and II and would thus occupy the time period between about 500 B.C. and A.D. 400; and (2) the Argyle Lagoon site which, though early, cannot be related definitely to other components because of insufficient excavation. Culture change is shown by increasing maritime adaptation through time and by the gradual replacement of the chipped stone industry by one using abrading and polishing techniques as the result of influence from the Old World.
Impact of Risk Factors on Indicators of Behavioral Problems according to Parents ’ and Children ’ s Reports

Multiple informants in the evaluation process and the identification of the relationship between risk factors and children's behavioral problems could help mental health professionals planning necessary strategies for preventing and managing behavioral problems. This study examined the relationship between risk factors and behavioral problems in a group of 25Brazilian children and their parents. Parents evaluated their children's problems (CBCL), their own problems (ASR), and the Family Adversity Index. Children provided information about themselves through a semi-structured interview (SCICA). Elevated family adversity indexes correlated positively with high scores for Internalizing Problems (CBCL) and Total Self-Report Problems (SCICA). The marital discord factor was associated with the presence of externalizing, internalizing and total problems. These results reinforces the need of multiple informants, suggest that several factors are associated with the presence of childhood psychopathology, and that public policies are needed to reduce risk factors, in order to promote mental health in childhood.
A Mobile Health Approach to Tuberculosis Contact Tracing in Resource-Limited Settings

Tuberculosis remains a leading cause of morbidity and mortality worldwide. In 2011, there were 8.7 million new cases and 1.4 million deaths from the disease, with >95% of these deaths taking place in low- and middle-income countries [1]. Contact tracing prevents the spread of tuberculosis by identifying and screening a case's contacts and referring symptomatic individuals to health care providers. Traditionally, contact tracing has been conducted with paper forms, which can lead to considerable inefficiencies in data collection, storage, and retrieval. These inefficiencies are problematic as tuberculosis can continue to spread if disruption of disease transmission is delayed. Mobile health approaches to tuberculosis contact tracing remain largely unaddressed and limited to management and monitoring of multidrug-resistant tuberculosis [2]. To address these limitations, a mobile health application that digitizes and automates contact tracing was developed. This poster presents work currently underway to evaluate this new approach in Botswana, which has the tenth highest incidence rate of tuberculosis in the world [3]. Operational considerations for implementing a mobile health approach to contact tracing in resource-limited settings are also presented.
Physical Symptoms in Young Adults and Their Use of Different Computers and Mobile Phones

This paper presents the use of new technical equipment by young adults (30 years old or younger), and the physical symptoms they have. The paper then analyses how the symptoms are associated with the use of computers and mobile phones, taking into account the background information. The study is based on a survey of 15000 working-age ( 18-65) Finns. The responses (1563) covering young adults’ physical symptoms were analysed. Altogether 53.3% of all young adults had pretty often or more frequently pain, numbness or aches in the neck and 32.2% had aches in the hip and lower back. Women experienced more pain, numbness or aches in the neck (65.0%) than men (34.5%). The use of different computers at leisure quite often had an association with some symptoms in different parts of the body. In addition, exhaustion at work had associations with some physical symptoms. In the future, it is essential to note ergonomic reasons and exhaustion at work when young adults experience pain, numbness or aches.