Miracle-dz/UniFAR-FTUs huggingface dataset:
Basolateral uptake of inorganic mercury in the kidney.

Renal disposition of administered inorganic mercury was studied in rats that had undergone an acute bilateral ureteral ligation shortly before being injected with a nontoxic 0.5-micromol/kg iv dose of inorganic mercury with or without 2.0 micromol/kg glutathione (GSH) or cysteine. Ureteral ligation and induction of "stop-flow" conditions were carried out to decrease glomerular filtration rate to negligible levels prior to the administration of inorganic mercury. The disposition of mercury was studied in the kidneys, liver, and blood 1 h after treatment. In rats given only mercuric chloride, the renal burden of mercury was approximately 20-25% of the administered dose of mercury, which is approximately 50% of the renal burden of mercury detected on average in normal rats. Coadministration of inorganic mercury with GSH or cysteine caused a significant increase in the renal uptake of mercury 1 h after treatment. The enhanced uptake of mercury in the kidneys was due to increased uptake of mercury in the renal cortex and outer stripe of the outer medulla. Pretreatment with para-aminohippuric acid caused significant reductions in the renal concentration and burden of inorganic mercury in all the rats administered inorganic mercury, regardless of whether the inorganic mercury was coadministered with GSH or cysteine. Overall, the findings from the present study provide additional evidence that there is basolateral uptake of inorganic mercury in the kidneys and that the primary mechanism involved in this basolateral uptake is dependent on the activity of the organic anion transporter. More importantly, the present findings also show that GSH and cysteine enhance the basolateral uptake of mercuric ions in the kidney when they are coadministered with inorganic mercury (presumably in the form of mercuric conjugates). On the basis of the present findings, one is led to believe that mercuric conjugates of GSH and cysteine are taken up at the basolateral membrane following exposure to inorganic forms of mercury.
The Mitochondrial Permeability Transition, Release of Cytochrome c and Cell Death

We investigated the relationship between opening of the permeability transition pore (PTP), mitochondrial depolarization, cytochrome c release, and occurrence of cell death in rat hepatoma MH1C1 cells. Treatment with arachidonic acid or A23187 induces PTP opening in situ with similar kinetics, as assessed by the calcein loading-Co2+ quenching technique (Petronilli, V., Miotto, G., Canton, M., Colonna, R., Bernardi, P., and Di Lisa, F. (1999) Biophys. J. 76, 725–734). Yet depolarization, as assessed from the changes of mitochondrial tetramethylrhodamine methyl ester (TMRM) fluorescence, is rapid and extensive with arachidonic acid and slow and partial withA23187. Cyclosporin A-inhibitable release of cytochrome cand cell death correlate with the changes of TMRM fluorescence but not with those of calcein fluorescence. Since pore opening must be accompanied by depolarization, we conclude that short PTP openings are detected only by trapped calcein and may have little impact on cell viability, while changes of TMRM distribution require longer PTP openings, which cause release of cytochrome c and may result in cell death. Modulation of the open time appears to be the key element in determining the outcome of stimuli that converge on the PTP.
Analysis of surgeon-controlled variables in the treatment of limb-threatening type-III open tibial diaphyseal fractures.

BACKGROUND The open tibial diaphyseal fracture remains a treatment challenge. The purpose of the present analysis of the long-term follow-up data on a previously reported cohort of patients was to identify surgeon-controlled variables that affected fracture union, complications, and final outcome in patients who had sustained a severe open tibial shaft fracture. METHODS A cohort of 156 patients with a limb-threatening open tibial diaphyseal fracture was identified from the Lower Extremity Assessment Project (LEAP) study group. The patients were prospectively followed for two to seven years. In addition to the Sickness Impact Profile, other outcome metrics included the time to fracture union as well as the occurrence of infection and other complications that required rehospitalization. Statistical differences between groups were calculated. RESULTS Within the parameters of the present study, the timing of débridement, the timing of soft-tissue coverage, and the timing of bone-graft placement had no effect on outcome. Patients in whom the fracture was definitively treated with an external fixator had more surgical procedures, took longer to achieve full weight-bearing status, and had more readmissions to the hospital for the treatment of infection and nonunion than did those in whom the fracture was treated with an intramedullary nail. Patients undergoing external fixation who also had a muscle flap for wound coverage had more physical impairment and a worse functional outcome than did patients who had an amputation. CONCLUSIONS Surgeons should carefully consider alternative treatment options for patients who have a severe open tibial fracture when limb salvage is perceived to require the combination of external fixation for fracture fixation and a muscle flap for wound coverage.
Correlates of Untreated Hypercholesterolemia in Older Adults: A Community-Based Household Survey in China

Hypercholesterolemia is common in older adults and less treated, but little is known about correlates of untreated hypercholesterolemia. Using a standard interview method we examined a random sample of 7,572 participants aged ≥60 years in a community-based household survey across 7 provinces of China during 2007–2012, and documented 328 cases of hypercholesterolemia from self-reported doctor diagnosis. Compared to participants with normal cholesterol, older adults with hypercholesterolemia had higher socioeconomic position and larger body mass index. In patients with hypercholesterolemia, 209 were not treated using lipid-lowering medications (63.7%, 95% confidence interval (CI) 58.5%–68.9%). Untreated hypercholesterolemia was significantly associated with female sex (adjusted odds ratio 2.13, 95%CI 1.17–3.89), current smoking (3.48, 1.44–8.44), heavy alcohol drinking (3.13,1.11–8.84), chronic bronchitis (2.37,1.14–4.90) and high level of meat consumptions (2.85,1.22–6.65). Although having coronary heart disease exposed participants for treatment, half of participants with coronary heart disease did not receive lipid-lowering medications. Among hypercholesterolemia participants with stroke, hypertension or diabetes, more than half of them did not receive lipid-lowering medications. The high proportion of untreated hypercholesterolemia in older, high-risk Chinese adults needs to be mitigated through multi-faceted primary and secondary prevention strategies to increase population opportunities of treating hypercholesterolemia.
Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy.

PURPOSE Current standard therapy for children and adolescents with Hodgkin's disease includes combination chemotherapy and low-dose involved-field radiation (LD-IFRT). Because radiation may be associated with adverse late effects, the Children's Cancer Group (CCG) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy. PATIENTS AND METHODS Between January 1995 and December 1998, 829 eligible patients were enrolled onto CCG 5942. A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were randomized to receive LD-IFRT or no further treatment. Event-free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate. RESULTS The projected 3-year EFS from study entry for the entire cohort was 87% +/- 1.2%. Among patients who achieved a complete response to initial chemotherapy, 92% +/- 1.9% of those randomized to receive LD-IFRT were alive and disease free 3 years after randomization, versus 87% +/- 2.2% for patients randomized to receive no further therapy (stratified log-rank test; P =.057). With an "as-treated" analysis, 3-year EFS after randomization for the radiation cohort was 93% +/- 1.7% versus 85% +/- 2.3% for patients receiving no further therapy (stratified log-rank test; P =.0024). Three-year survival estimates for patients treated with and without LD-IFRT were 98% +/- 1.1% for patients who received radiation and 99% +/- 0.5% for patients who did not receive radiation. CONCLUSION LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS. At this time, there is no survival advantage for LD-IFRT, but follow-up remains short.
The Return of the Wheelbarrow Men; or, the Arrival of Postmodern Penality?

This paper examines a range of new penal trends and attempts to assess their significance, in the context of the growing debate on modernist and postmodernist penality. It argues that they can be seen as early indicators of an emerging postmodern penality, even if its contours may still be unclear and unmarked. The paper then goes on to discuss the empirical and theoretical significance of this contention. This paper is written as a contribution to a growing debate on the significance of a range of new penal initiatives to be found to a greater or lesser extent across most English based jurisdictions at the present time. While all contributors to this debate are in agreement that we are currently experiencing quite significant penal change, there are considerable differences between them as to its implications (see, for example, Feeley and Simon 1992; Garland 1995, 1996; Sparks 1996; Simon 1995, 1997; Lucken 1998). At the heart of the matter is the issue of whether or not these initiatives, however different in form they might seem and however different the cultural values that seem to inform them may be to much of the penal development that has taken place during the course of this century at least, still operate within the parameters of modernity itself: or whether they go beyond its parameters and thereby signal the arrival of a postmodern penality. Such distinctions are a matter of far greater import than mere semantics: how it is possible to punish within the one framework will be very different from how it is possible to punish within the other. Furthermore, if it is possible to see the emergence of a postmodern penality (albeit still in embryonic form) on the empirical basis of the discontinuities from modernity represented in the new penal arrangements, this then raises important theoretical issues about the adequacy of the sociology of modernity to provide an analytical framework in which to situate these current trends (Brodeur 1994). To explore these issues further, the position I want to take in this paper is informed by but ultimately reverses that taken by Garland (1995) in his authoritative contribution to this debate. A detailed analysis of the range of new penal initiatives is provided. I then go on to examine critically the case that can be made for situating them within the modernist framework, before suggesting how and why they may be pointers to the emergence of a postmodern penal world, even if its exact contours are still somewhat vague and ill defined.
Biological and Biochemical Characteristics of Prion Strains Conserved in Persistently Infected Cell Cultures

ABSTRACT Abnormal prion protein (PrPSc) plays a central role in the transmission of prion diseases, but the molecular basis of prion strains with distinct biological characteristics remains to be elucidated. We analyzed the characteristics of prion disease by using mice inoculated with the Chandler and Fukuoka-1 strains propagated in a cultured mouse neuronal cell line, GT1-7, which is highly permissive to replication of the infectious agents. Strain-specific biological characteristics, including clinical manifestations, incubation period as related to the infectious unit, and pathological profiles, remained unchanged after passages in the cell cultures. We noted some differences in the biochemical aspects of PrPSc between brain tissues and GT1-7 cells which were unlikely to affect the strain phenotypes. On the other hand, the proteinase K-resistant PrP core fragments derived from Fukuoka-1-infected tissues and cells were slightly larger than those from Chandler-infected versions. Moreover, Fukuoka-1 infection, but not Chandler infection, gave an extra fragment with a low molecular weight, ∼13 kDa, in both brain tissues and GT1-7 cells. This cell culture model persistently infected with different strains will provide a new insight into the understanding of the molecular basis of prion diversity.
Attitude and perception of rural women towards the formation and membership of self-help groups in Kaduna state, Nigeria

This study was carried out to elicit the attitude and perception of rural women in Kaduna State, Nigeria, towards the formation and membership of self-help groups (SHGs). Multistage random sampling was adopted and a total of 176 respondents from two (2) local government areas were interviewed using a pre-tested structured questionnaire. Two sets of questions based on a 5-point Likert-type scale were used to generate primary data. The respondents expressed over whelming positive attitude to the formation and membership of SHGs as indicated by the aggregate and mean scores which ranged from 607 to 719 and 345 to 4.08 respectively. Age (r = 0.310, P
Anaphase lagging mainly explains chromosomal mosaicism in human preimplantation embryos.

BACKGROUND Cleavage stage embryos as well as postimplantation embryos have been studied extensively over the years. However, our knowledge with respect to the chromosomal constitution of human embryos at the blastocyst stage is still rudimentary. METHODS In the present paper, a large series of human blastocysts was examined by means of fluorescent in situ hybridization (FISH). RESULTS It was found that only one in four blastocysts (25%) displayed a normal chromosomal pattern. We defined a group of blastocysts (26%) displaying a simple mosaic chromosome pattern (different cell lines resulting from one chromosomal error), an about equally large group of blastocysts (31%) displaying a complex mosaic chromosome pattern, and a smaller group of blastocysts (11%) showing a chaotic chromosome distribution pattern. Six per cent of all blastocysts analysed could not be assigned one of the previously mentioned chromosomal patterns. CONCLUSION Anaphase lagging appeared to be the major mechanism through which human embryos acquire a mosaic chromosome pattern during preimplantation development to the blastocyst stage.
Amino Acid 316 of Hemagglutinin and the Neuraminidase Stalk Length Influence Virulence of H9N2 Influenza Virus in Chickens and Mice

ABSTRACT H9N2 influenza viruses with an A316S substitution in hemagglutinin (HA) and a shorter neuraminidase (NA) stalk have become predominant in China. The A316S was shown to increase HA cleavage efficiency when combined with short stalk NA, and the short stalk NA improved NA enzyme activity and release of virus from erythrocytes. Single mutations or combinations of these mutations strengthened the virulence of H9N2 virus in chickens and mice.
Temperature-Aware Floorplanning of Microarchitecture Blocks with IPC-Power Dependence Modeling and Transient Analysis

Operating temperatures have become an important concern in high performance microprocessors. Floorplanning or block-level placement offers excellent potential for thermal optimization through better heat spreading between the blocks, but these optimizations can also impact the throughput of a microarchitecture, measured in terms of the number of instructions per cycle (IPC). In nanometer technologies, global buses can have multicycle delays that depend on the positions of the blocks, and it is important for a floorplanner to be microarchitecturally-aware to be sure that thermal and IPC considerations are appropriately balanced. This paper proposes a methodology for thermally-aware microarchitecture floorplanning. The approach models the interactions between the IPC and the temperature distribution, and incorporates both factors in the floorplanning cost function. Our approach uses transient modeling and optimizes both the peak and the average temperatures, and employs a design of experiments (DOE) based strategy, which effectively captures the huge exponential search space with a small number of cycle-accurate simulations. A comparison with a technique based on previous work indicates that the proposed approach results in good reductions both in the average and the peak temperatures for a range of SPEC benchmarks
Role of Mechanical Cues in Cell Differentiation and Proliferation: A 3D Numerical Model

Cell differentiation, proliferation and migration are essential processes in tissue regeneration. Experimental evidence confirms that cell differentiation or proliferation can be regulated according to the extracellular matrix stiffness. For instance, mesenchymal stem cells (MSCs) can differentiate to neuroblast, chondrocyte or osteoblast within matrices mimicking the stiffness of their native substrate. However, the precise mechanisms by which the substrate stiffness governs cell differentiation or proliferation are not well known. Therefore, a mechano-sensing computational model is here developed to elucidate how substrate stiffness regulates cell differentiation and/or proliferation during cell migration. In agreement with experimental observations, it is assumed that internal deformation of the cell (a mechanical signal) together with the cell maturation state directly coordinates cell differentiation and/or proliferation. Our findings indicate that MSC differentiation to neurogenic, chondrogenic or osteogenic lineage specifications occurs within soft (0.1-1 kPa), intermediate (20-25 kPa) or hard (30-45 kPa) substrates, respectively. These results are consistent with well-known experimental observations. Remarkably, when a MSC differentiate to a compatible phenotype, the average net traction force depends on the substrate stiffness in such a way that it might increase in intermediate and hard substrates but it would reduce in a soft matrix. However, in all cases the average net traction force considerably increases at the instant of cell proliferation because of cell-cell interaction. Moreover cell differentiation and proliferation accelerate with increasing substrate stiffness due to the decrease in the cell maturation time. Thus, the model provides insights to explain the hypothesis that substrate stiffness plays a key role in regulating cell fate during mechanotaxis.
Facilitation of glutamate release by nicotine involves the activation of a Ca2+/calmodulin signaling pathway in rat prefrontal cortex nerve terminals

The effect of nicotine on evoked glutamate release from isolated nerve terminals (synaptosomes) from rat prefrontal cortex was examined. We found that nicotine significantly potentiated 4‐aminopyridine (4AP)‐evoked glutamate release, and this potentiatory effect was mimicked by the selective α7 nicotinic receptor agonist choline and was blocked by the selective α7 nicotinic receptor antagonist methyllycaconitine, indicating its mediation by α7 nicotinic receptors. Examination of the effect of nicotine on cytosolic [Ca2+] revealed that the potentiation of glutamate release was associated with an increase in voltage‐dependent Ca2+ influx through N‐ and P/Q‐type Ca2+ channels. The potentiatory effect of nicotine on Ca2+ influx seems to be attributed to its increasing synaptosomal excitability because nicotine significantly increased depolarization‐evoked increase in the intrasynaptosomal free Na+ concentration and 4AP‐evoked depolarization of the synaptosomal plasma membrane potential. Also, Ca2+ ionophore ionomycin‐induced glutamate release was enhanced by nicotine, and this action was blocked by methyllycaconitine. These results suggest that nicotine exerts its potentiatory effect presynaptically, likely through the activation of α7 nicotinic receptors, resulting in Na+ influx and local depolarization, which subsequently enhances the CaK+ entry through voltage‐dependent N‐and P/Q‐type Ca2+ channels as well as the vesicular release machinery to cause an increase in evoked glutamate release from rat prefrontocortical nerve terminals. Moreover, in this release potentiation may involve an activation of Ca2+/calmodulin signaling pathway as nicotine‐mediated potentiation of 4AP‐ and ionomycin‐evoked glutamate release were significantly attenuated by KN62, a selective inhibitor of Ca2+/calmodulin‐dependent kinase II. Synapse 59:491–501, 2006. © 2006 Wiley‐Liss, Inc.
Kernelization Algorithms for Packing Problems Allowing Overlaps (Extended Version)

We consider the problem of discovering overlapping communities in networks which we model as generalizations of Graph Packing problems with overlap. We seek a collection $\mathcal{S}' \subseteq \mathcal{S}$ consisting of at least $k$ sets subject to certain disjointness restrictions. In the $r$-Set Packing with $t$-Membership, each element of $\mathcal{U}$ belongs to at most $t$ sets of $\mathcal{S'}$ while in $t$-Overlap each pair of sets in $\mathcal{S'}$ overlaps in at most $t$ elements. Each set of $\mathcal{S}$ has at most $r$ elements. Similarly, both of our graph packing problems seek a collection $\mathcal{K}$ of at least $k$ subgraphs in a graph $G$ each isomorphic to a graph $H \in \mathcal{H}$. In $\mathcal{H}$-Packing with $t$-Membership, each vertex of $G$ belongs to at most $t$ subgraphs of $\mathcal{K}$ while in $t$-Overlap each pair of subgraphs in $\mathcal{K}$ overlaps in at most $t$ vertices. Each member of $\mathcal{H}$ has at most $r$ vertices and $m$ edges. We show NP-Completeness results for all of our packing problems and we give a dichotomy result for the $\mathcal{H}$-Packing with $t$-Membership problem analogous to the Kirkpatrick and Hell \cite{Kirk78}. We reduce the $r$-Set Packing with $t$-Membership to a problem kernel with $O((r+1)^r k^{r})$ elements while we achieve a kernel with $O(r^r k^{r-t-1})$ elements for the $r$-Set Packing with $t$-Overlap. In addition, we reduce the $\mathcal{H}$-Packing with $t$-Membership and its edge version to problem kernels with $O((r+1)^r k^{r})$ and $O((m+1)^{m} k^{{m}})$ vertices, respectively. On the other hand, we achieve kernels with $O(r^r k^{r-t-1})$ and $O(m^{m} k^{m-t-1})$ vertices for the $\mathcal{H}$-Packing with $t$-Overlap and its edge version, respectively. In all cases, $k$ is the input parameter while $t$, $r$, and $m$ are constants.
Early transverse decoherence of bunches with space charge

The transverse decoherence of injected bunches is an important phenomenon in synchrotrons and storage rings. The initial stage of this process determines the transverse emittance blowup, which should be taken into account for the design of feedback systems, for example. The interplay of different high-intensity effects can strongly affect the initial decoherence stage. We present a model that explains decoherence and emittance growth with chromaticity, space charge, and image charges within the first synchrotron period. We compare the model for different combinations of parameters with self-consistent particle tracking simulations and measurements in the SIS18 synchrotron at GSI Darmstadt. Generally, space charge slows down the decoherence process and can cause the loss of decoherence. Chromaticity and image charges can partly compensate this loss and restore the decoherence. We also analyze the single-particle excitation driven by space charge during the decoherence process. Particles gain large amplitudes from the coherent beam oscillation, which leads to halo buildup and losses.