Miracle-dz/UniFAR-FTUs huggingface dataset:
Design of PI Observers for Continuous-Time Descriptor Linear Systems

A parametric design approach for proportional-integral (PI) observers for continuous-time descriptor linear systems is proposed based on a complete general parametric solution to the generalized Sylvester matrix equation. The proposed approach provides complete parameterizations for all the observer gain matrices, gives the parametric expression for the corresponding finite left eigenvector matrix of the observer system matrix, realizes elimination of impulsive responses, and guarantees the regularity of the observer system. The design method offers all the degrees of design freedom, which can be utilized to achieve various desired system specifications and performances and, thus, has great potentials in applications. A numerical example is employed to show the design procedure and illustrate the effect of the proposed approach. Simulation results show a satisfactory tracking performance for descriptor linear systems
Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women

Objective:To describe darunavir (DRV) pharmacokinetics with once-and twice-daily dosing during pregnancy and postpartum in HIV-infected women. Design:Women were enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1026s, a prospective nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included separate cohorts receiving DRV/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg twice daily. Methods:Intensive steady-state 12- or 24-hour pharmacokinetic profiles were performed during the second trimester, third trimester, and postpartum. DRV was measured using high-performance liquid chromatography (detection limit: 0.09 &mgr;g/mL). Results:Pharmacokinetic data were available for 64 women (30 once daily and 34 twice daily dosing). Median DRV area under the concentration–time curve (AUC) and maximum concentration were significantly reduced during pregnancy with both dosing regimens compared with postpartum, whereas the last measurable concentration (Clast) was also reduced during pregnancy with once daily DRV. DRV AUC with once daily dosing was reduced by 38% during the second trimester and by 39% during the third trimester. With twice daily dosing, DRV AUC was reduced by 26% in both trimesters. The median (range) ratio of cord blood/maternal delivery DRV concentration in 32 paired samples was 0.18 (range: 0–0.82). Conclusions:DRV exposure is reduced by pregnancy. To achieve DRV plasma concentrations during pregnancy equivalent to those seen in nonpregnant adults, an increased twice daily dose may be necessary. This may be especially important for treatment-experienced women who may have developed antiretroviral resistance mutations.
Increasing constructive anger verbal behavior decreases resting blood pressure: A secondary analysis of a randomized controlled hostility intervention

We hypothesized that increasing anger verbal behavior in an assertive, constructively motivated style should decrease resting blood pressure (BP) and that this behavior may be one mechanism through which hostility relates to BP. We tested this hypothesis by conducting secondary analyses on a single-blind, matched, randomized controlled study of hostility modification and BP. A total of 22 high-hostile male patients with coronary heart disease were matched on age and hostility level and were randomly assigned to either an 8-week cognitive-behavioral hostility treatment (n = 10) or an information-control group (n = 12). Patients were reassessed after treatment and at 2-month follow-up on hostility, observed anger expression, and resting BP. We found that decreases in hostility predicted increases in constructive anger behavior-verbal component, which in turn predicted decreases in resting BP at follow-up. Thus, one of the mechanisms underlying the hostility-BP association may be the lack of constructive anger expression.
‘Getting to Know Me’: The second phase roll-out of a staff training programme for supporting people with dementia in general hospitals

Objectives The aims were to evaluate a second phase roll-out of a dementia care training programme for general hospital staff and to further develop two outcome scales: the Confidence in Dementia scale for measuring confidence in working with people with dementia and the Knowledge in Dementia scale for measuring knowledge in dementia. Method Following a ‘training the trainers’ phase, the study involved the delivery of the ‘Getting to Know Me’ training programme to a large number of staff (n = 517) across three National Health Service (NHS) Trusts situated in North-West England. The impact of the programme was evaluated using a pre–post design which explored: (i) changes in confidence in dementia, (ii) changes in knowledge in dementia, and (iii) changes in beliefs about behaviours that challenge. Results Statistically significant change was identified between pre–post training on all outcome measures (Confidence in Dementia: eight point increase, p < 0.001; Knowledge in Dementia: two point increase p < 0.001; controllability beliefs scale: four point decrease, p < 0.001). Medium to large effect sizes were demonstrated on all outcome measures. The psychometric properties of the Confidence in Dementia and Knowledge in Dementia scales are reported. Conclusion Staff knowledge in dementia and confidence in working with people with dementia significantly increased following attendance at the training sessions. The findings are consistent with preliminary findings and strengthen current knowledge about the impact of dementia care training in general hospitals. The Confidence in Dementia and Knowledge in Dementia scales continue to demonstrate psychometrically sound properties and demonstrate utility in the field of dementia research.
BCL‐2 Family of Proteins and Mammary Cellular Fate

This review focuses on the pro‐apoptotic and anti‐apoptotic Bcl‐2 family members involved in apoptosis, which is the predominant process controlling cell remodelling during post‐lactational mammary gland involution. The members of the Bcl‐2 protein family, whose expression levels are under the control of lactogenic hormones, internally control this mechanism also during lactation. They can physically interact with each other, sometimes in an antagonistic manner. Mammary glands undergo repeated cycles of structural development, functional differentiation and regression, therefore provide a unique model for investigating this family of proteins that regulate the fate of the secretory cells and consequently milk yield. The involvement of Bcl‐2 family members is reviewed in mammary tissue during morphogenesis, at different stages of lactation cycle and in comparison with dairy and laboratory animals.
Islet isolation and transplantation from an annular pancreas: a case report.

CONTEXT Annular pancreas is an uncommon congenital anomaly formed by a thin band of normal pancreatic tissue encircling the duodenum. CASE REPORT We report the first case of an islet isolation and transplantation from an annular pancreas. The pancreas together with duodenum was procured from a 32-year-old previously healthy man after diagnosis of brain death. The pancreas including the annular portion was distended well after intraductal collagenase perfusion. A total of 276,064 islet equivalent was recovered and transplanted into a type 1 diabetic patient. CONCLUSIONS Bearing in mind the shortage of donors, patients with this anomalous condition should not be excluded as potential organ donors.
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Potentiator VX-770 (Ivacaftor) Opens the Defective Channel Gate of Mutant CFTR in a Phosphorylation-dependent but ATP-independent Manner* ♦

Background: VX-770 (ivacaftor), approved for therapy in CF patients bearing the G551D mutation, has an unknown mode of action. Results: Potentiation of purified WT and mutant CFTR by VX-770 did not require the normal activating ligand ATP. Conclusion: VX-770 binds WT and mutant CFTR channels directly to induce a nonconventional mode of gating. Significance: These findings will enable discovery of the VX-770-binding site. The cystic fibrosis transmembrane conductance regulator (CFTR) acts as a channel on the apical membrane of epithelia. Disease-causing mutations in the cystic fibrosis gene can lead to CFTR protein misfolding as in the case of the F508del mutation and/or channel dysfunction. Recently, a small molecule, VX-770 (ivacaftor), has shown efficacy in restoring lung function in patients bearing the G551D mutation, and this has been linked to repair of its channel gating defect. However, these studies did not reveal the mechanism of action of VX-770 in detail. Normally, CFTR channel activity is regulated by phosphorylation, ATP binding, and hydrolysis. Hence, it has been hypothesized that VX-770 modifies one or more of these metabolic events. In this study, we examined VX-770 activity using a reconstitution system for purified CFTR protein, a system that enables control of known regulatory factors. We studied the consequences of VX-770 interaction with CFTR incorporated in planar lipid bilayers and in proteoliposomes, using a novel flux-based assay. We found that purified and phosphorylated CFTR was potentiated in the presence of Mg-ATP, suggesting that VX-770 bound directly to the CFTR protein, rather than associated kinases or phosphatases. Interestingly, we also found that VX-770 enhanced the channel activity of purified and mutant CFTR in the nominal absence of Mg-ATP. These findings suggest that VX-770 can cause CFTR channel opening through a nonconventional ATP-independent mechanism. This work sets the stage for future studies of the structural properties that mediate CFTR gating using VX-770 as a probe.
Ganglioside biosynthesis in mouse embryos: sialyltransferase IV and the asialo pathway.

The in vitro activity of sialyltransferase IV (SAT-IV), which catalyzes the transfer of sialic acid to the terminal galactose of different gangliotetraosylceramides (GA1, GM1a and GD1b), was examined in membrane-enriched preparations from mouse embryos at embryonic day 12 (E-12). Gangliosides GD1a and GT1b were the only reaction products using GM1a and GD1b as substrates, respectively. The Km values for GM1a and GD1b were 53 microM and 42 microM, respectively. Competitive inhibition experiments showed that the same enzyme (SAT-IV) catalyzed sialic acid transfer to the terminal galactose residues of both GM1a and GD1b. Two labeled ganglioside products were obtained, however, using GA1 as a substrate. One product was identified as ganglioside GM1b and the enzymatic reaction for its formation was maximal at pH 6.0, similar to that for GD1a and GT1b formation. The second product, synthesized by a different sialyltransferase, was identified as GD1 alpha based on results from TLC immunostaining, neuraminidase digestion, and periodate oxidation-borohydride reduction. The pH dependence curve for GD1 alpha formation had a different shape than that for GM1b formation with a maximum at pH 6.3. GD1 alpha is apparently synthesized from GM1b by an endosialyltransferase that catalyzes the transfer of a second sialic acid to the internal N-acetylgalactosamine of GM1b. The formation of both GM1b and GD1 alpha was linear over protein concentration. The ratio of GD1 alpha/GM1b formation varied from 0.25 to 1.20 depending on the GA1 substrate concentration. (ABSTRACT TRUNCATED AT 250 WORDS)
The Agrobacterium tumefaciens vir gene transcriptional activator virG is transcriptionally induced by acid pH and other stress stimuli

A set of Agrobacterium tumefaciens operons required for pathogenesis is coordinately induced during plant infection by the VirA and VirG proteins. The intracellular concentration of VirG increases in response to acidic media, and this response was proposed to be regulated at the level of transcription at a promoter (P2) that resembles the Escherichia coli heat shock promoters. To test this hypothesis, we first constructed a virG-lacZ transcriptional fusion. A strain containing this fusion had higher levels of beta-galactosidase activity in acidic media than in media at neutral pH. Second, primer extension analysis of virG indicated that acidic media stimulated the transcription of this promoter. To determine whether P2 is a member of a heat shock-like regulon in A. tumefaciens, five agents that induce E. coli heat shock genes were tested for their abilities to induce a P2-lacZ fusion in A. tumefaciens. P2 was most strongly induced by low pH, was moderately stimulated by CdCl2 or mitomycin C, and was slightly induced by P2 as measured by beta-galactosidase activity and primer extension analysis. Induction by these treatments did not require any Ti plasmid-encoded function or the chromosomally encoded RecA protein. We also pulse-labeled cellular proteins after a shift to low pH and detected several proteins whose synthesis was induced by these conditions. We conclude that P2 is primarily induced by acid pH and secondarily by certain other stimuli, each of which is stressful to cell growth. This stress induction is at least partly independent of the heat shock and SOS responses.
So what shall we do about assertive community treatment?

Abstract The usefulness of Assertive Community Treatment (ACT) in European countries with well-developed community care systems has been disputed, despite considerable relevant literature. This paper aims to assess reasons for and against implementing ACT in such countries. ACT may not be useful where generic community mental health teams are not yet well-developed, where admission rates are already low, or where an alternative model based on close integration of a full range of types of care is in place. Good reasons for introducing ACT include listening to patients' preferences, being able to monitor a high risk group of patients more successfully, good staff satisfaction, and the potential for using ACT teams as a platform for delivering interventions for difficult to treat psychosis. The ACT model is more likely to thrive in future if a recovery orientation can be adopted.
Superantigen Enhancement of Specific Immunity: Antibody Production and Signaling Pathways1

Superantigens are microbial proteins that induce massive activation, proliferation, and cytokine production by CD4+ T cells via specific Vβ elements on the TCR. In this study we examine superantigen enhancement of Ag-specific CD4+ T cell activity for humoral B cell responses to T-dependent Ags BSA and HIV gp120 envelope, type I T-independent Ag LPS, and type II T-independent Ag pneumococcal polysaccharides. Injection of BSA followed by a combination of superantigens staphylococcal enterotoxin A and staphylococcal enterotoxin B (SEB) 7 days later enhanced the anti-BSA Ab response in mice ∼4-fold as compared with mice given BSA alone. The anti-gp120 response was enhanced ∼3-fold by superantigens. The type II T-independent Ag pneumococcal polysaccharide response was enhanced ∼2.3-fold by superantigens, whereas no effect was observed on the response to the type I T-independent Ag LPS. The superantigen effect was completely blocked by the CD4+ T cell inhibitory cytokine IL-10. SEB-stimulated human CD4+ T cells were examined to determine the role of the mitogen-activated protein (MAP) kinase signal transduction pathway in superantigen activation of T cells. Inhibitors of the mitogen pathway of MAP kinase blocked SEB-induced proliferation and IFN-γ production, while an inhibitor of the p38 stress pathway had no effect. Consistent with this, SEB activated extracellular signal-regulated kinase/MAP kinase as well as MAP kinase-interacting kinase, a kinase that phosphorylates eIF4E, which is an important component of the eukaryotic protein synthesis initiation complex. Both kinases were inhibited by IL-10. Thus, superantigens enhance humoral immunity via Ag-specific CD4+ T cells involving the stress-independent pathway of MAP kinase.
Mixed dust fibrosis and tuberculosis in comparison with silicosis and macular pneumoconiosis.

BACKGROUND To assess the relationship between mixed dust fibrosis (MDF) and tuberculosis. METHODS We performed a comparative analysis with MDF, silicosis, and macular pneumoconiosis (Mac), using autopsy records from 1975 to 1994. RESULTS Prevalences of having tuberculosis among MDF, silicosis, and Mac were not significantly different, albeit a tendency of higher prevalence in silicosis. Cure rates of tuberculosis were, in order, silicosis < MDF < Mac (P=0. 085). Death rates associated with tuberculosis were, in order, silicosis > MDF=Mac (P=0.911). With respect to the two types of association with tuberculosis, i.e., combined type (tuberculopneumoconiosis) and complicated one (pneumoconiosis with tuberculosis); the former was significantly dominant in silicosis, the latter was significantly dominant in Mac, and intermediate in MDF. As a whole, the complicated type had a tendency of a higher cure rate than the combined type (P=0.071). Although the differences of profiles between the combined and complicated types were not statistically significant, the combined type had a tendency to have longer duration of exposure to dusts, earlier registration for treatment, higher profusion score, and earlier death compared with the complicated type. CONCLUSIONS From our findings, MDF takes an intermediate position between silicosis and Mac regarding the relationship with tuberculosis. The type of association with tuberculosis rather than the kind of background pneumoconiosis seemed to be more important in light of responsiveness to the treatment.
Effect of Naturally Occurring nif Reiterations on Symbiotic Effectiveness in Rhizobium phaseoli

Most naturally occurring strains of Rhizobium phaseoli possess reiteration of the nif genes. Three regions contain nitrogenase structural genes in strain CFN42. Two of these regions (a and b) have copies of nifH, nifD, and nifK, whereas the third region (c) contains only nifH. Strains containing mutations in either nif region a or nif region b had significantly diminished symbiotic effectiveness compared with the wild-type strain on the basis of nodule mass, total nitrogenase activity per plant, nitrogenase specific activity, total nitrogen in the shoot, and percentage of nitrogen. A strain containing mutations in both nif region a and nif region b was totally ineffective. These data indicate that both nif region a and nif region b are needed for full symbiotic effectiveness in R. phaseoli.
Influences of Dietary and Environmental Stress on Microbial Populations in the Murine Gastrointestinal Tract

Aerobic and anaerobic cultural techniques and histological methods were used in a study of the effects of environmental and dietary stress on the indigenous microbiota of the gastrointestinal tract of mice. Mice previously inoculated with Salmonella typhimurium were examined in a similar manner. Three strains of mice (CD-1, Ha/ICr, and C57BL) were used. Control animals previously inoculated with S. typhimurium had low population levels of Salmonella bacteria in the small and large bowel. Mice previously inoculated with Salmonella and then deprived of food, water, and bedding for 48 h harbored high population levels of these bacteria in their small and large bowels. Coliforms increased in numbers in the large bowel of stressed mice inoculated with Salmonella and in the jejunum-ileum and cecum of stressed mice not previously inoculated with Salmonella. Control mice had high population levels of lactobacilli inhabiting the keratinized squamous epithelium of the stomach. Stressed mice showed dramatic reductions in these populations of lactobacilli. Populations of fusiform-shaped bacteria associated with the mucosal epithelium of the cecum and colon in control mice were reduced in stressed mice as determined by microscope examination of histological sections. Total anaerobic counts were similar, however, in both stressed and control animals. Environmental and dietary stress markedly alter the gastrointestinal microbiota in mice. Therefore, such stressful conditions profoundly affect the factors that regulate the localization and population levels of microorganisms in the stomach and intestines.
Management of Ptosis in Chronic Progressive External Ophthalmoplegia

Patients with chronic progressive external ophthalmoplegia (CPEO) are often disabled by ptosis; however, conventional ptosis surgery may induce lagophthalmos and exposure keratitis. Ten patients with CPEO underwent ptosis correction via bilateral frontalis suspensions, using monofilament synthetic material. Three of these patients were also treated with lower eyelid horizontal tightening. The frontalis sling was adjusted to provide a firm linkage between the eyebrow and eyelid, but was loose enough to allow eyelid closure when the frontalis muscle is relaxed. All patients experienced lessening of ptosis and relief from visual obstruction. One patient required reoperation of one eyelid for undercorrection. No lagophthalmos or corneal complications occurred. The rationale for treatment, preoperative evaluation, and operative procedure in CPEO is discussed herein.
Assessing the risk of de novo malignancy in kidney transplant recipients: role for monitoring of peripheral blood lymphocyte populations.

Role for Monitoring of Peripheral Blood Lymphocyte Populations We have read with interest the recent article by Lim et al., assessing the impact of the use of T-cellYdepleting antibodies as antirejection therapy on the development of de novo malignancy after kidney transplantation (KT) (1). They found that recipients who experienced acute rejection (AR) and were treated with T-cellYdepleting antibodies exhibited a 1.4-fold increase in the adjusted risk of incident cancer as compared to those who did not experience AR. Interestingly, such an effect was not observed in patients with rejection episodes that did not require therapy with T-cellYdepleting agents (1). Following the suggestion made by Snanoudj and Legendre in their editorial (2), we attempted to analyze whether the use of such agents as induction therapy also increases the risk of posttransplant malignancy. In addition, in view that the decrease in antitumor and antiviral T-cellYmediated immune surveillance seems to be the most relevant mechanism underlying the association reported by Lim et al. (1), we explored the potential utility of a monitoring strategy based on some easily available proxy for the posttransplant status of the cell-mediated immunity in an attempt to individualize cancer prevention in this population. All patients undergoing KT at our institution from November 2008 are being enrolled in an ongoing immunemonitoring study in which data on major posttransplant complications are prospectively collected (3, 4). Peripheral blood lymphocyte subpopulations (PBLSs) counts are enumerated at baseline and posttransplant months 1 and 6 using a six-color flow cytometric assay (4). In this substudy, we included patients with a minimum posttransplant follow-up of 90 days, unless death or graft loss occurred earlier. The study outcome was the occurrence of de novo cancer (excluding nonmelanocytic skin cancer) after transplantation. We preestablished two subgroups: those patients who received antithymocyte globulin (ATG) as induction therapy (ATG group), and those who received anti-CD25 monoclonal antibodies or no induction therapy (non-ATG group). Areas under receiver operating characteristic curves (auROC) were used to assess the accuracy of each PBLS count in predicting the development of de novo malignancy. The best cutoff values were then assessed through the calculations of sensitivity and specificity. Survival curves were plotted by the Kaplan-Meier method, and univariate and multivariate Cox regression models were used to evaluate the association between the most predictive parameter identified by auROC analysis and the study outcome. We analyzed 297 patients (162 and 135 in the non-ATG and ATG groups, respectively) throughout a median follow-up of 72.7 months (interquartile rank, 32.8Y53.5 months; risk exposure period, 360,248 transplant days). At the end of this period, 255 of them (85.9%) were still alive and with a functioning graft. Seventeen patients (5.7%)