Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene

Background. Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. Methods. The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. Results. High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. Conclusion. It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.
Unearthing ectomycorrhizal dynamics.

We are in the midst of a revolution in field research of microbial ecology (Horton & Bruns, 2001). Historically, soil biologists have been hampered by difficulties inherent with working on microscopic organisms below ground. However, recent advances in molecular approaches have greatly facilitated our ability to survey microbial communities in situ. These techniques have become relatively inexpensive, and the capacity to process large numbers of samples has increased. Together, these two trends allow investigators to conduct field studies of ever-increasing scope. In this issue, Izzo et al. (pp. 619– 629) demonstrate how these new capabilities can be used to glean foundational knowledge regarding microbial community structure – their work addresses the question as to what extent ectomycorrhizal communities change over time in an otherwise stable ecosystem. The research is groundbreaking in terms of its comprehensive and simultaneous measurement of spatial and temporal variability in ectomycorrhizal community composition. Izzo et al. sampled at intervals ranging from 5 cm to 200 m at two depths over 3 yr. This combined approach was useful, because the authors found that the ectomycorrhizal community turns over frequently at smaller scales, but much less so than at larger scales. These results indicate that the pool of available ectomycorrhizal species within an ecosystem may remain more or less constant, whereas the exact location of individual species may shift over time. Had the authors focused on the contribution of either time or space, but not both, they would not have detected this pattern. The project of Izzo et al., which was initiated in 1999, required the genetic analysis of a total of 1300 ectomycorrhizal root tips in all. Current macroand microarray approaches now allow us to characterize thousands of samples at a time in runs lasting one month or less (e.g. Valinsky et al., 2002). Molecular techniques are now a tractable tool for in-depth study of mycorrhizal communities.
Simulation of Convective Heat Loss through Mineral Wool in a Rainscreen Facade

This study applied Computational Fluid Dynamics (CFD) to determine the effects of windinduced convection through mineral wool in a ventilated rainscreen system. Wind studies of a conceptual low-rise building subject to a wind speed of 6.7 m/s demonstrated dynamic airflows and rainscreen velocities ranging from 0.1 to over 3 m/s. Localized pressure fields near cladding support framing increased air velocities within the mineral wool by one to two orders of magnitude. These high pressure regions, together with increased surface flows at corner domains, represented the primary pathways governing convective heat loss. Simulated convection through mineral wool slabs showed that even high density materials are prone to increased heat transfer due to air permeability into the open pore volume. Vertical and horizontal flow regimes at 1 to 2 m/s increased heat transfer by 4 to 42% over the range of simulated mineral wool densities. Gaps between and behind insulation slabs further increased the convective effects, resulting in heat flux densities that were up to 62% higher than non-gapped, impermeable insulation. The results of this study support growing recognition that exterior mineral wool must be protected from the detriments of convective forces. Alternatively, adjustments in effective Rvalues should be made when using un-faced mineral wool slabs.
Macrophage migration inhibitory factor (MIF) modulates innate immune responses induced by endotoxin and Gram-negative bacteria

Discovered in the early 1960s as a T-cell cytokine, MIF has emerged to be an important mediator of the innate immune system. MIF was identified recently to be released by a vast array of cells, including monocytes/macrophages, T-cells, B-cells, endocrine cells and epithelial cells in response to infection and stress. Bacteria, microbial toxins and cytokines have been shown to be powerful inducers of MIF secretion by macrophages. MIF stimulates the expression of pro-inflammatory mediators by immune cells and functions to counterbalance the anti-inflammatory and immunosuppressive effects of glucocorticoids. Like TNF and IL-1, MIF plays an important role in host responses to infection. Recombinant MIF was found to exacerbate lethal endotoxemia or bacterial sepsis when co-injected with LPS or Escherichia coli in mice. Conversely, MIF knockout mice or mice treated with anti-MIF antibodies were protected from shock induced by LPS, staphylococcal exotoxins or bacterial peritonitis, even when anti-MIF therapy was started after the onset of infection. Given the central role played by MIF in innate immune responses against microbial pathogens and in the regulation of inflammatory responses, pharmacological modulation of MIF production or neutralization of MIF activity could have broad clinical applications and may offer new treatment options for the management of patients with severe sepsis or septic shock.
From the National Institutes of Health. Summary of a workshop on cytomegalovirus infections during organ transplantation.

Over the past decade a growing number of reports have appeared in the literature attesting to the frequent occurrence and clinical significance of cytomegalovirus (CMV) infection in recipients of tissue transplants. Although such infections have been most extensively studied among recipients of kidney and bone marrow transplants, recent studies have confirmed the ubiquity and potential seriousness of this infection among cardiac transplant patients as well. Two patterns of CMV disease have been noted: (1) primary CMV disease, in which the transplant recipient has had no previous experience with the virus (and is seronegative for CMV before the transplant) and develops infection with virus that appears to be transmitted in latent fashion with an allograft from a seropositive donor; and (2) reactivation disease, in which the transplant recipient, who has been infected with CMV previously (and is seropositive for CMV before the transplant), reactivates endogenous latent virus. In both instances, the immunosuppressive therapy required for transplantation and the rejection processes that follow placement of an allograft appear to activate latent virus and make it clinically manifest. Currently available data would
The single-ring Thermoanaerobacter brockii chaperonin 60 (Tbr-EL7) dimerizes to Tbr-EL14.Tbr-ES7 under protein folding conditions.

Chaperone proteins assist in the folding of some newly synthesized proteins and inhibit protein aggregation. The Thermoanaerobacter brockii chaperonin proteins (Tbr-EL and Tbr-ES) have recently been purified and characterized [Truscott, W.N. , Høj, P. B. , & Scopes, R. K. (1994) Eur. J. Biochem. 222, 277-284]; Tbr-EL was a single seven-membered toroid, unlike most GroELs which exist as double toroids. Using high-resolution gel filtration chromatography, we have resolved the purified Tbr-EL into single ringed (Tbr-EL7) and double ringed (Tbr-EL14) species. The latter contained tightly bound Tbr-ES co-chaperonin (Tbr-EL14.Tbr-ES7). In the presence of Mg.ATP and either Escherichia coli GroES (Eco-ES) or Tbr-ES (i.e., under protein folding conditions), the isolated Tbr-EL7 rapidly dimerized to the Tbr-EL14.Eco-ES7 or Tbr-EL14.Tbr-ES7 complexes. The doubly toroidal species thus formed contained > or = 6 molecules tightly bound ADP and one GroES7 and are similar to the asymmetric chaperonin complex isolated from Thermus thermophilus [Taguch, H. , Konishi, J., Ishii, N. , & Yoshida, M. (1991) J. Biol. Chem. 266, 22411-22418]. The isolated Tbr-EL7 and Tbr-EL14.Tbr-ES7 hydrolyzed ATP at approximate to 2 and 1 min-1, respectively. Addition of a molar excess of Eco-ES7 to the isolated Tbr-EL7 reduced the ATPase activity to 1 min-1, consistent with the formation of Tbr-EL14.Eco-ES7. Eco-ES7 failed to inhibit the Tbr-El14.Tbr-ES7 complex. The isolated Tbr-EL14.Tbr-ES7 complex did not support the folding of Rubisco under nonpermissive conditions. Only when the complex was supplemental with additional GroES was folding of Rubisco observed; i.e., one molar equivalent of GroES was not sufficient for folding. Both Tbr-EL7 and Tbr-EL14.Tbr-ES7 bound on unfolded [35S] Rhodospirillum rubrum Rubisco per mole particle. In contrast, Eco-EL14 bound 2 mol of protein per mole particle, consistent with each toroid having a peptide binding site. Eco-EL14.Eco-ES7 complex only bound one unfolded protein, thus GroES binding blocks one GroEL peptide binding site. Addition of Eco-ES7 to a Eco-EL14.Rubisco2 complex did not result in the displacement of one molecule of Rubisco but in the formation of a ternary Eco-EL14.Rubisco2. Eco-ES7 complex.
Affine cellularity of Khovanov–Lauda–Rouquier algebras in type A

We prove that the Khovanov–Lauda–Rouquier algebras Rα of type A∞ are (graded) affine cellular in the sense of Koenig and Xi. In fact, we establish a stronger property, namely that the affine cell ideals in Rα are generated by idempotents. This, in particular, implies the (known) result that the global dimension of Rα is finite, and yields a theory of standard and proper standard modules for Rα.
Bedside Ultrasound Reduces Diagnostic Uncertainty and Guides Resuscitation in Patients With Undifferentiated Hypotension*

Objectives:Utilization of ultrasound in the evaluation of patients with undifferentiated hypotension has been proposed in several protocols. We sought to assess the impact of an ultrasound hypotension protocol on physicians’ diagnostic certainty, diagnostic ability, and treatment and resource utilization. Design:Prospective observational study. Setting:Emergency department in a single, academic tertiary care hospital. Subjects:A convenience sample of patients with a systolic blood pressure less than 90 mm Hg after an initial fluid resuscitation, who lacked an obvious source of hypotension. Interventions:An ultrasound-trained physician performed an ultrasound on each patient using a standardized hypotension protocol. Differential diagnosis and management plan was solicited from the treating physician immediately before and after the ultrasound. Blinded chart review was conducted for management and diagnosis during the emergency department and inpatient hospital stay. Measurements and Main Results:The primary endpoints were the identification of an accurate cause for hypotension and change in physicians’ diagnostic uncertainty. The secondary endpoints were changes in treatment plan, use of resources, and changes in disposition after performing the ultrasound. One hundred eighteen patients with a mean age of 62 years were enrolled. There was a significant 27.7% decrease in the mean aggregate complexity of diagnostic uncertainty before and after the ultrasound hypotension protocol (1.85–1.34; –0.51 [95% CI, –0.41 to –0.62]) as well as a significant increase in the absolute proportion of patients with a definitive diagnosis from 0.8% to 12.7%. Overall, the leading diagnosis after the ultrasound hypotension protocol demonstrated excellent concordance with the blinded consensus final diagnosis (Cohen k = 0.80). Twenty-nine patients (24.6%) had a significant change in the use of IV fluids, vasoactive agents, or blood products. There were also significant changes in major diagnostic imaging (30.5%), consultation (13.6%), and emergency department disposition (11.9%). Conclusions:Clinical management involving the early use of ultrasound in patients with hypotension accurately guides diagnosis, significantly reduces physicians’ diagnostic uncertainty, and substantially changes management and resource utilization in the emergency department.
Theorising about gender and computing interventions through an evaluation framework

Despite over 20 years of intervention programmes, the gender balance in the computing profession is not improving. It has been suggested that the problem with much of the research on gender and computing is that it is under‐theorised. The contribution of this study is an evaluation framework, designed to evaluate gender and computing interventions, which will advance the theorisation of research through programme evaluation. This study was undertaken in three phases: The first involved theory building through an extensive review of the literature resulting in a conceptual framework for intervention programme evaluation. The second phase consisted of a multiple‐case study of 14 major intervention programmes in Australia. Subsequent modifications to the conceptual framework resulted in the gender and computing intervention evaluation framework. The value of the framework was confirmed in phase three by intervention experts and showed that applying the framework will help programme champions to evaluate their programmes more thoroughly. The dissemination of sound evaluation results will then enable a deeper theorisation of the issues surrounding gender and computing interventions.
The psychological refractory period: evidence for age differences in attentional time-sharing.

The authors report 2 psychological refractory period (PRP) experiments in which the stimulus onset asynchrony (SOA) between Task 1 and Task 2 was 150 ms, 250 ms, 600 ms, and 1,100 ms for both younger and older adults. H. Pashler's (1994a) response-selection bottleneck theory predicts that SOA manipulations should not affect Task 1 performance, but that reaction time (RT) for Task 2 should increase as the SOA between the 2 tasks decreases (i.e., the classical PRP effect). In Experiment 1 (Task 1 = tone discrimination, Task 2 = dot location), older adults showed a larger PRP effect than younger adults did, although Task 1 RT was affected by SOA, suggesting that participants were grouping their responses on some trials. That is, participants were holding their response for Task 1 until they had completed processing Task 2, and then they responded to both tasks almost simultaneously. However, a subset of participants (11 younger adults and 11 older adults) who showed no evidence of response grouping on Task 1 continued to show a larger PRP effect for older adults on Task 2. In Experiment 2 (Task 1 = dot location, Task 2 = simultaneous letter matching), older adults continued to show a larger PRP effect than younger adults for Task 2, and Task 1 performance was unaffected by SOA. Consequently, these experiments provide evidence that older adults (relative to younger adults) exhibit a decrement in time-sharing at the response-selection stage of processing. These results suggest that attentional time-sharing needs to be added to the list of topics examined in aging research on varieties of attention.
Social networks and their relationship to mental health service use and expenditures among Medicaid beneficiaries.

OBJECTIVE This study examined the relationship between social networks and mental health services utilization and expenditures. METHODS A sample of 522 Medicaid mental health consumers was randomly selected from the administrative records of Colorado's Department of Health Care Policy and Financing. The administrative records contain information on utilization of services and expenditures of Medicaid beneficiaries within Colorado's Mental Health Services. In addition to the administrative records, social network and psychosocial data were gathered through longitudinal survey interviews. The interviews were conducted at six-month intervals between 1994 and 1997. Measures used in the regression analysis included demographic characteristics, clinical diagnoses, the social network index, expenditures, and utilization variables. RESULTS The social network index was positively associated with utilization of and expenditures for inpatient services in local hospitals but negatively associated with expenditures for inpatient services in state hospitals or outpatient services. Relationships with family were negatively related to expenditures for outpatient services. Relationships with friends were positively associated with utilization of and expenditures for psychiatric inpatient services in local hospitals. CONCLUSIONS Consumers who had higher social network index scores utilized more inpatient psychiatric services in local hospitals and had higher expenditures than those who had lower scores. Consumers who had higher social network index scores also had lower expenditures for inpatient services in state hospitals and outpatient services than those who have lower scores. Findings suggest that social network is associated with mental health utilization and expenditures in various ways, associations that need to be researched further.
Comparison of single- and triple-dose contrast material in the MR screening of brain metastases.

PURPOSE Although studies obtained with triple-dose contrast administration can show more brain metastases than those obtained with single-dose contrast material in patients with multiple metastases, such studies are costly and of limited clinical benefit. Since most patients who undergo screening have negative findings or a single metastasis, this study was performed to compare the clinical utility of single-dose versus triple-dose contrast administration in this large group of patients who could benefit from the possible increased sensitivity in lesion detection. METHODS Ninety-two consecutive patients with negative or equivocal findings or a solitary metastasis on single-dose contrast-enhanced MR images underwent triple-dose studies. Findings were compared with a standard of reference composed of panel review and long-term follow-up. Further analysis was performed by comparing results with those obtained by two blinded readers. RESULTS In all 70 negative single-dose studies, the triple-dose studies depicted no additional metastases in terms of the standard of reference. No statistically significant difference was seen between the results of the single- and triple-dose studies. For 10 equivocal single-dose studies, the triple-dose study helped clarify the presence or absence of metastases in 50% of the cases. In 12 patients with a solitary metastasis seen on the single-dose study, the triple-dose study depicted additional metastases in 25% of the cases. In the results of one of the two blinded readers, use of triple-dose contrast led to a statistical difference by decreasing the number of equivocal readings but at the expense of increasing the number of false-positive readings. CONCLUSION Routine triple-dose contrast administration in all cases of suspected brain metastasis is not helpful. On the basis of our investigation, we conclude that the use of triple-dose contrast material is beneficial in selected cases with equivocal findings or solitary metastasis, although with the disadvantage of increasing the number of false-positive results.
The calcium transient in sea urchin eggs during fertilization requires the production of inositol 1,4,5-trisphosphate.

The production of inositol 1,4,5-trisphosphate (InsP3) has been reported to mediate the transient rise in intracellular Ca2+ activity ([Ca2+]i) in sea urchin eggs during fertilization. However, direct evidence of an absolute requirement for generation of InsP3 during fertilization is still lacking. We investigated this question by blocking the InsP3 synthesizing enzyme phospholipase C (PLC) during fertilization with U73122, an aminosteroid. U73122 inhibited the sperm-induced Ca2+ release in a dose-dependent manner, although above 15 microM U73122 eggs showed an elevated resting [Ca2+]i and a lower fertilization rate. The inhibition of Ca2+ transient by U73122 was not due to a failure of fertilization, since incorporated sperm nuclei were evident in eggs used to measure the Ca2+ response. U73122 also prevented the accompanying rise in intracellular pH (pHi), which is mediated by the activation of the Na+-H+ antiporter. The antiporter is regulated through activation of protein kinase C by 1,2-diacylglycerol, which is the other hydrolytic product of phosphatidylinositol 4,5-bisphosphate by PLC. Further evidence of the specificity of U73122 action was inhibition of the increase in InsP3 mass during the first 2 min of fertilization. In addition, U73122 inhibited the GTPgammaS-induced Ca2+ release and pHi rise in unfertilized eggs. These results suggested that the transient rise in Ca2+ in sea urchin during fertilization requires the production of InsP3.
Demographics and Parasitism of American Eels in the Chesapeake Bay, USA

Abstract The Chesapeake Bay supports the largest U.S. harvest of American eels Anguilla rostrata, yet little is known about the underlying demographics and production rates that sustain these harvests. Chesapeake Bay subestuaries (Sassafras, Chester, Choptank, Patuxent, Potomac, and James rivers) are expected to provide productive but varying growth habitats for yellow-stage American eels due to differences in land use, prey availability, and salinity. We compared length, age, growth, mortality, condition, and health (prevalence and incidence of parasitism by the swim bladder nematode Anguillicola crassus) of yellow American eels (n = 850) in the six principal subestuaries. As has been observed for other systems, female American eels in the Chesapeake Bay were larger, older, and heavier and had higher growth rates than male, intersexual, or undifferentiated American eels. Prevalence of male and intersexual individuals in the upper bay region was higher than that in the lower bay and higher than that repor.