Miracle-dz/UniFAR-FTUs huggingface dataset:
Misfolded endoplasmic reticulum retained subunits cause degradation of wild‐type subunits of arylsulfatase A heteromers

Arylsulfatase A is an oligomeric lysosomal enzyme. In the present study, we use this enzyme as a model protein to examine how heteromerization of wild‐type and misfolded endoplasmic reticulum‐degraded arylsulfatase A polypeptides affects the quality control of wild‐type arylsulfatase A subunits. Using a conformation sensitive monoclonal antibody, we show that, within heteromers of misfolded and wild‐type arylsulfatase A, the wild‐type subunits are not fully folded. The results obtained show that arylsulfatase A polypeptide complexes, rather than the monomers, are subject to endoplasmic reticulum quality control and that, within a heteromer, the misfolded subunit exerts a dominant negative effect on the wild‐type subunit. Although it has been shown that mature lysosomal arylsulfatase A forms dimers at neutral pH, the results obtained in the present study demonstrate that, in the early biosynthetic pathway, arylsulfatase A forms oligomers with more than two subunits.
Enhancement of load flow computation methods to improve the convergence with automated measures based on stability analyses

Future scenarios of generation and load are predicted with market models which consider possible prices and demographic developments. However, nodal reactive powers which are critical in terms of the convergence of load flow calculations can only be estimated. The reactive power demand of heavily stressed power systems differs from regular burdened scenarios, whereby the estimation of the nodal reactive powers is complicated and minor differences affect the convergence characteristics of load flow calculations significantly. The algorithm that is presented in this paper modifies the reactive nodal powers during the load flow calculation if it does not converge. Regions of instability and measures for convergence achievement are determined with a modal stability analysis.
Implant strategies during feeding: impact on carcass grades and consumer acceptability.

Anabolic growth promotants influence beef grade factors and Warner-Bratzler shear force of steaks. No study has assessed the consumer acceptability of beef derived from implanted cattle. This study determined beef carcass grades and consumer acceptability for cooked beef from unimplanted (control) cattle and from cattle implanted with one of seven different implant strategies (initial implant/implant at 59 d = Encore & Component T-S/no implant, Ralgro/Synovex Plus, Ralgro/Revalor-S, Revalor-S/Revalor-S, Revalor-S/no implant, no implant/Synovex Plus, and Synovex Plus/no implant). British crossbred steers (n = 448) were allocated randomly into one of eight pens for each of the control and seven treatment groups. Carcass quality and yield grade (n = 403) and Warner-Bratzler shear force (n = 298) data were collected by trained personnel. Twenty steaks per control or treatment group were selected randomly for use in consumer sensory evaluation. Steaks were evaluated by consumers for overall like, tenderness like, tenderness level, flavor like, flavor intensity, and juiciness level using 9-point, end-anchored hedonic scales. Control carcasses had smaller (P < .05) longissimus muscle areas than carcasses in all treatment groups except those receiving Encore & Component T S/no implant, Ralgro/Synovex Plus, or Revalor S/no implant. Control carcasses had higher (P < .05) marbling scores than carcasses in all treatment groups except those receiving Ralgro/Revalor-S or Encore & Component T-S/no implant. Steaks from control steers had lower (P < .05) Warner-Bratzler shear force values than steaks from steers given Revalor-S/no implant. Consumer ratings for tenderness like and tenderness level were influenced (P < .05) by implant strategy. Effects of implant strategy on overall like, flavor like, and flavor intensity approached significance (P = .07 to .09). Consumers rated steaks from unimplanted steers as more tender (tenderness level; P < .05) than steaks from all treatment groups except that involving Encore & Component T-S/no implant. Consumers rated steaks from unimplanted steers as more desirable (P < .05) for tenderness like than steaks from all treatments except those involving Encore & Component T-S/no implant or Revalor-S/no implant. Although use of implants in this study resulted in heavier hot carcass weights and larger ribeyes, some of the implant strategies reduced consumer preference of tenderness of steaks.
Derivative Pricing Under Strong Persistence

The time series of stock prices are autocorrelated over short horizons. As described in Bouchaud and Potters, the "first-order" statistical properties of financial time series are well modeled by relative price increments that are independent random variables over the time scale of tens of minutes, but are autocorrelated up to this "decorrelation" time. The distribution from which price increments are drawn is typically much broader than the normal, usually exhibiting power law tails. Whether price increments are best modeled as additive or multiplicative is not clear, but especially at short horizons additive models appear to describe the data better.1 The fact that price movements are not independent over short time horizons contradicts the weak form of the efficient markets hypothesis (Fama 1970) which claims that the returns on an individual stock are not predictable from knowledge of past series of its returns. This violations of the efficient market hypothesis is however consistent with a model in which transaction costs prevent trading in continuous time, and as Bouchaud and Potters note (section 13.1.3) the potential excess returns that such correlations offer traders are of the order of magnitude of the "tick" size in financial markets the smallest unit in which prices are quoted. This suggests that, at least in this respect, most financial markets might be indeed considered efficient up to transaction costs.
An Approach to Context-Aware Service Pushing for Mobile Computing

Context plays an important role for making accurate recommendations in recommendation systems. There are three types of context: network location context, user context and demand context. However, current researches on service recommendation techniques fail to take into consideration all the context. This paper introduces the context-aware recommendation approach which integrates network location context, user context and demand context. An extensible meta-model is proposed in our system, thus the description of class property can be scalable. The consistent representation of service and user demand will provide convenience for service matching and service filtering. In order to ensure real-time update of service information, this paper puts forward three methods: spontaneous service updating, delayed service updating based on accessing, as well as delayed service updating periodically. For service recommendation, we proposed a combined method of three-level service filtering and collaborative recommendation.
Involvement of various amino- and carboxyl-terminal residues in the active site of the histidine-containing protein HPr of the phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus carnosus: site-directed mutagenesis with the ptsH gene, biochemical characterization and NMR studie

The phosphocarrier HPr (heat stable protein) of Staphylococcus carnosus was modified by site-directed mutagenesis of the corresponding ptsH gene in order to analyse the importance of amino acids which were supposed to be part of the active centre of the protein. Three residues which are conserved in all HPrs, Arg17, Pro18 and Glu84, were mutated: Arg17 was changed to His (17RH) and Pro18 and Glu84 were changed into Ala (18PA and 84EA). In addition, Leu86 was changed into Ala (86LA) and one mutant protein was missing the last six residues of the HPr (delta 83). The wild type gene and all mutant genes were overexpressed and the gene products purified to homogeneity. Three-dimensional structures of wild type and mutant proteins were monitored by NMR spectroscopy. All five mutant HPrs had native conformations. The ATP-dependent HPr kinase can phosphorylate all HPr derivatives at Ser46. The PTS activity of the amino-terminal HPr mutant proteins 17RH and 18PA was different compared to wild type HPr. In contrast, the carboxy-terminal mutant HPrs possessed a similar enzyme activity to the wild type HPr. The 17RH and 18PA HPrs with substitution near the active centre His15 showed a very slow phosphorylation by enzyme I but the further transfer of the phosphoryl group to enzyme III was also strongly inhibited. The enzyme activity of the HPr 17RH was significantly improved at low pH. NMR pH-titration experiments showed that Arg17 is not responsible for the low pKa of the active centre His15 but this positively charged residue is essential in this position for the HPr activity.
Cilofungin (LY121019), an antifungal agent with specific activity against Candida albicans and Candida tropicalis

Cilofungin (LY121019) is an antifungal agent that interferes with beta-glucan synthesis in the cells walls of fungi. The activity of this agent against 256 clinical isolates of yeasts was determined. It was found to be very active in vitro against Candida albicans (MIC for 90% of isolates [MIC90], less than or equal to 0.31 microgram/ml; minimal fungicidal concentration for 90% of isolates [MFC90], less than or equal to 0.31 micrograms/ml) and C. tropicalis (MIC90, less than or equal to 0.31 microgram/ml; MFC90, less than or equal to 0.31 microgram/ml) and moderately active against Torulopsis glabrata (MIC90 and MFC90, less than or equal to 20 micrograms/ml). All C. parapsilosis, Cryptococcus, and Saccharomyces cerevisiae strains were resistant. The activity of cilofungin was affected by medium and inoculum size. Antibiotic medium no. 3 was used as the standard medium. Isolates of C. albicans and C. tropicalis demonstrated a paradoxical effect in Sabouraud dextrose broth and yeast nitrogen base broth in that growth was partially inhibited at MICs equivalent to those in antibiotic medium no. 3, but growth continued, in many instances, throughout all concentrations tested. There was decreased activity of cilofungin with inocula greater than 10(5) CFU/ml. The temperature and duration of incubation did not affect its activity.
Ultrasound-guided therapeutic focused ultrasound: Current status and future directions

Abstract This paper reviews ultrasound imaging methods for the guidance of therapeutic focused ultrasound (USgFUS), with emphasis on real-time preclinical methods. Guidance is interpreted in the broadest sense to include pretreatment planning, siting of the FUS focus, real-time monitoring of FUS-tissue interactions, and real-time control of exposure and damage assessment. The paper begins with an overview and brief historical background of the early methods used for monitoring FUS-tissue interactions. Current imaging methods are described, and discussed in terms of sensitivity and specificity of the localisation of the FUS effects in both therapeutic and sub-therapeutic modes. Thermal and non-thermal effects are considered. These include cavitation-enhanced heating, tissue water boiling and cavitation. Where appropriate, USgFUS methods are compared with similar methods implemented using other guidance modalities, e.g. magnetic resonance imaging. Conclusions are drawn regarding the clinical potential of the various guidance methods, and the feasibility and current status of real-time implementation.
Impact of weight status on physical and psychological outcomes of a comprehensive pain rehabilitation programme.

OBJECTIVE To examine the impact of weight status on physical and psychological outcomes of patients enrolled in a comprehensive pain rehabilitation programme. METHODS Participants (n = 314; mean body mass index 30.34) were administered measures of pain perception, depression, and physical functioning. Analyses included (Group: healthy weight, overweight, obese) × 2 (Time: admission, discharge) mixed-model analysis of variance (ANOVA) models for variables of interest. RESULTS All 3 groups of participants evidenced improved pain severity [F(1,311) = 228.94, p < 0.001], pain interference [F(1,311) = 305.93, p < 0.001], pain catastrophizing [F(1,311) = 318.78, p < 0.001], depression [F(1,311) = 191.21, p < 0.001], and physical functioning [F(1,278) = 156.12, p < 0.001] from pre- to post-treatment. No impact of weight status on treatment outcomes emerged. Patients with obesity had lower physical therapy performance scores at both pre- and post-treatment [F(2,278) = 5.98, p = 0.003]; however, results suggested a similar magnitude of physical improvement across all weight ranges. CONCLUSION Regardless of weight status, patients achieved improvement in physical and psychological functioning following comprehensive pain rehabilitation. The multidisciplinary nature of this intervention probably resulted in improvements for all patients, including those of higher weight.
Anterior lumbar inter-body fusion with instrumentation compared with posterolateral fusion for low grade isthmic-spondylolisthesis.

UNLABELLED Spondylolisthesis presenting as low back pain is not an uncommon condition. Many of such patients are treated conservatively. For those that require surgical management, various treatment options are in vogue e.g. Postero-lateral fusion (PLF) with decompression or posterior fusion with instrumentation and anterior lumbar inter-body fusion (ALIF). Each technique has produced satisfactory outcome with benefits and disadvantages. AIM OF THE STUDY To compare the outcome of surgical management of low grade spondylolisthesis with two treatments modalities--Postero-lateral fusion (PLF) and Anterior lumbar inter-body fusion (ALIF) with posterior instrumentation in similar patient profile. SETTINGS AND DESIGN Prospective study to compare the results of two surgical treatment modalities. MATERIAL AND METHODS The selected group of patients for surgery based on definite criteria was operated by the same surgeon by two modalities: Postero-lateral fusion with decompression and Anterior Lumbar Inter-body fusion with posterior instrumentation. The outcomes were compared. STATISTICAL ANALYSIS USED Analysis of variance (ANOVA) test. RESULTS Follow up was done at twelve weekly intervals up to 2 years. Both groups showed good recovery in pain as seen in Visual analogue scale (VAS) and Oswestry low back pain scoring. Intra-operative bleeding was observed to be higher in Postero-lateral fusion group. Average length of hospital stay for the patients of PLF group was 6.6 days (Range: 4-7 days) as compared to 12.5 days (Range: 10-16 days) in case of ALIF group. Treatment cost was found to be higher in patients who undergone ALIF with instrumentation. CONCLUSIONS ALIF with posterior instrumentation in low grade isthmic spondylolisthesis provides satisfactory outcome in patients requiring surgical treatment. The results of pain relief and disability index are comparable to time tested posterolateral fusion. ALIF shows a tendency to faster pain relief and return to activity with less intraoperative blood requirement in low grade isthmic spondylolisthesis.
When Policy Gets It Right: Variability in U.S. Hospitals’ Diagnosis of Ventilator-Associated Pneumonia*

Objective:The Centers for Disease Control has recently proposed a major change in how ventilator-associated pneumonia is defined. This has profound implications for public reporting, reimbursement, and accountability measures for ICUs. We sought to provide evidence for or against this change by quantifying limitations of the national definition of ventilator-associated pneumonia that was in place until January 2013, particularly with regard to comparisons between, and ranking of, hospitals and ICUs. Design:A prospective survey of a nationally representative group of 43 hospitals, randomly selected from the American Hospital Association Guide (2009). Subjects classified six standardized vignettes of possible cases of ventilator-associated pneumonia as pneumonia or no pneumonia. Subjects:Individuals responsible for ventilator-associated pneumonia surveillance at 43 U.S. hospitals. Interventions:None. Measurements and Main Results:We measured the proportion of standardized cases classified as ventilator-associated pneumonia. Of 138 hospitals consented, 61 partially completed the survey and 43 fully completed the survey (response rate 44% and 31%, respectively). Agreement among hospitals about classification of cases as ventilator-associated pneumonia/not ventilator-associated pneumonia was nearly random (Fleiss &kgr; 0.13). Some hospitals rated 0% of cases as having pneumonia; others classified 100% as having pneumonia (median, 50%; interquartile range, 33–66%). Although region of the country did not predict case assignment, respondents who described their region as “rural” were more likely to judge a case to be pneumonia than respondents elsewhere (relative risk, 1.25, Kruskal-Wallis chi-square, p = 0.03). Conclusions:In this nationally representative study of hospitals, assignment of ventilator-associated pneumonia is extremely variable, enough to render comparisons between hospitals worthless, even when standardized cases eliminate variability in clinical data abstraction. The magnitude of this variability highlights the limitations of using poorly performing surveillance definitions as methods of hospital evaluation and comparison, and our study provides very strong support for moving to a more objective definition of ventilator-associated complications.
Macrolide resistance in Helicobacter pylori: rapid detection of point mutations and assays of macrolide binding to ribosomes

Resistance of Helicobacter pylori to macrolides is a major cause of failure of eradication therapies. Single base substitutions in the H. pylori 23S rRNA genes have been associated with macrolide resistance in the United States. Our goal was to extend this work to European strains, to determine the consequence of this mutation on erythromycin binding to H. pylori ribosomes, and to find a quick method to detect the mutation. Seven pairs of H. pylori strains were used, the parent strain being naturally susceptible to macrolides and the second strain having acquired an in vivo resistance during a treatment regimen that included clarithromycin. The identity of the strains was confirmed by random amplified polymorphic DNA testing with two different primers, indicating that resistance was the result of the selection of variants of the infecting strain. All resistant strains were found to have point mutations at position 2143 (three cases) or 2144 (four cases) but never on the opposite DNA fragment of domain V of the 23S rRNA gene. The mutation was A-->G in all cases except one (A-->C) at position 2143. Using BsaI and BbsI restriction enzymes on the amplified products, we confirmed the mutations of A-->G at positions 2144 and 2143, respectively. Macrolide binding was tested on purified ribosomes isolated from four pairs of strains with [14C]erythromycin. Erythromycin binding increased in a dose-dependent manner for the susceptible strain but not for the resistant one. In conclusion we suggest that the limited disruption of the peptidyltransferase loop conformation, caused by a point mutation, reduces drug binding and consequently confers resistance to macrolides. Finally, the macrolide resistance could be detected without sequencing by performing restriction fragment length polymorphism with appropriate restriction enzymes.
Selection on knockdown performance in Drosophila melanogaster impacts thermotolerance and heat-shock response differently in females and males

SUMMARY We studied adaptive thermotolerance in replicate populations of Drosophila melanogaster artificially selected for high and low knockdown temperature (TKD), the upper temperature at which flies can no longer remain upright or locomote effectively. Responses to selection have generated High TKD populations capable of maintaining locomotor function at ∼40°C, and Low TKD populations with TKD of∼ 35°C. We examined inducible knockdown thermotolerance, as well as inducible thermal survivorship, following a pretreatment heat-shock (known to induce heat-shock proteins) for males and females from the TKD selected lines. Both selection for knockdown and sex influenced inducible knockdown thermotolerance, whereas inducible thermal survivorship was influenced only by sex, and not by selection. Overall, our findings suggest that the relationships between basal and inducible thermotolerance are contingent upon the methods used to gauge thermotolerance, as well as the sex of the flies. Finally, we compared temporal profiles of the combined expression of two major heat-shock proteins, HSC70 and HSP70, during heat stress among the females and males from the selected TKD lines. The temporal profiles of the proteins differed between High and Low TKD females, suggesting divergence of the heat-shock response. We discuss a possible mechanism that may lead to the heat-shock protein patterns observed in the selected females.
Net Present Value Analysis and the Wealth Creation Process: A Case Illustration

This case is intended to help students on accounting undergraduate and postgraduate courses deepen their understanding of capital budgeting. We introduce a working example and hypothetical case to show that knowing an investment project’s net present value (NPV) is important but is not sufficient. Shareholders would also like to know how and when a project pays the excess wealth it generates. In the case we show in monetary amounts, how much each group receives in every time period; how much is received in the form of excess wealth by the existing shareholders; and, when does that excess wealth starts to accrue. The case can be used specifically in the final year undergraduate and postgraduate accounting study programmes.
MDR1 gene expression and treatment outcome in acute myeloid leukemia.

To prospectively assess the role of MDR1 gene expression in patients with de novo acute myeloid leukemia (AML), levels of MDR1 RNA in blast cells were determined at diagnosis and correlated with treatment outcome in 63 patients. MDR1 RNA levels were negative in 29% and positive in 71% of the patients. The complete remission rate in response to induction chemotherapy was 89% for MDR1 RNA-negative patients and 53% for MDR1 RNA-positive patients (P = .008). Expression of the MDR1 gene was observed in most patients who died early or had resistant disease. Kaplan-Meier curves revealed a decrease in both disease-free survival and overall survival of patients with detectable MDR1 gene expression compared with the disease-free survival and overall survival of MDR1 RNA-negative patients (P = .029 and P = .009, respectively). These data indicate that MDR1 gene expression is an unfavorable prognostic factor and suggest that multidrug resistance is important in AML.