bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical Characterization of a Dihydroneopterin Aldolase Used for Methanopterin Biosynthesis in Methanogens
Authors: Wang Yu , Xu Huimin , Grochowski Laura L. , White Robert H. 
Published: July 2014

ABSTRACT

The gene encoding 7,8-dihydroneopterin aldolase (DHNA) was recently identified in archaea through comparative genomics as being involved in methanopterin biosynthesis (V. Crécy-Lagard, G. Phillips, L. L. Grochowski, B. El Yacoubi, F. Jenney, M. W. Adams, A. G. Murzin, and R. H. White, ACS Chem. Biol. 7:1807–1816, 2012, doi:10.1021/cb300342u). Archaeal DHNA shows a unique secondary and quaternary structure compared with bacterial and plant DHNAs. Here, we report a detailed biochemical examination of DHNA from the methanogen
Methanocaldococcus jannaschii
. Kinetic studies show that
M. jannaschii
DHNA possesses a catalytic capability with a
k
cat

/K
m

above 10
5
M
−1
s
−1
at 70°C, and at room temperature it exhibits a turnover number (0.07 s
−1
) comparable to bacterial DHNAs. We also found that this enzyme follows an acid-base catalytic mechanism similar to the bacterial DHNAs, except when using alternative catalytic residues. We propose that in the absence of lysine, which is considered to be the general base in bacterial DHNAs, an invariant water molecule likely functions as the catalytic base, and the strictly conserved His35 and Gln61 residues serve as the hydrogen bond partners to adjust the basicity of the water molecule. Indeed, substitution of either His35 or Gln61 causes a 20-fold decrease in
k
cat
. An invariant Tyr78 is also shown to be important for catalysis, likely functioning as a general acid. Glu25 plays an important role in substrate binding, since replacing Glu25 by Gln caused a ≥25-fold increase in

K
m

. These results provide important insights into the catalytic mechanism of archaeal DHNAs.
Communication between Binding Sites Is Required for YqjI Regulation of Target Promoters within the
yqjH-yqjI
Intergenic Region
Authors: Wang Suning , Blahut Matthew , Wu Yun , Philipkosky Katherine E. , Outten F. Wayne 
Published: July 2014

ABSTRACT

The nickel-responsive transcription factor YqjI represses its own transcription and transcription of the divergent
yqjH
gene, which encodes a novel ferric siderophore reductase. The intergenic region between the two promoters is complex, with multiple sequence features that may impact YqjI-dependent regulation of its two target promoters. We utilized mutagenesis and DNase I footprinting to characterize YqjI regulation of the
yqjH-yqjI
intergenic region. The results show that YqjI binding results in an extended footprint at the
yqjI
promoter (site II) compared to the
yqjH
promoter (site I). Mutagenesis of
in vivo
gene reporter constructs revealed that the two YqjI binding sites, while separated by nearly 200 bp, appear to communicate in order to provide full YqjI-dependent regulation at the two target promoters. Thus, YqjI binding at both promoters is required for full repression of either promoter, suggesting that the two YqjI binding sites cooperate to control transcription from the divergent promoters. Furthermore, internal deletions that shorten the total length of the intergenic region disrupt the ability of YqjI to regulate the
yqjH
promoter. Finally, mutagenesis of the repetitive extragenic palindromic (REP) elements within the
yqjH-yqjI
intergenic region shows that these sequences are not required for YqjI regulation. These studies provide a complex picture of novel YqjI transcriptional regulation within the
yqjH-yqjI
intergenic region and suggest a possible model for communication between the YqjI binding sites at each target promoter.
Description and implementation of U-Turn Medical, a comprehensive lifestyle intervention programme for chronic disease in the sport and exercise medicine setting: pre–post observations in 210 consecutive patients
Authors: Derman Wayne , Schwellnus Martin , Hope Fallon , Jordaan Esme , Padayachee Trishanta 
Published: July 2014

BackgroundNon-communicable disease (NCD) is increasing, but management remains mostly curative, disease-centred and focused on single interventions. We describe the development and implementation of a patient-centred, comprehensive, multidisciplinary lifestyle intervention programme (LIP) for patients with NCD in the sport and exercise medicine (SEM) setting (part 1) and present preliminary observational data (part 2).MethodsPart 1 is a description of the programme development and implementation. In part 2, 210 participants with NCD underwent a 12-week LIP (U-Turn Medical). Physiological, functional and metabolic outcomes were assessed at baseline and at completion.Results84% of patients had two or more comorbidities, requiring additional considerations for exercise rehabilitation. On completion, there were decreases in % body fat (29.8±6.7% vs 28.5±6.6%), waist (100.2±16.2 vs 97.3±14.8 cm) and hip circumference (105.4±13 vs 104±12 cm), resting heart rate (74.2±13.4 vs 71.4±11.9 bpm), resting systolic blood pressure (125.7±16.1 vs 120.1±13 mm Hg) and cholesterol (4.7±1.2 vs 4.3±0.9 mmol/L), low-density lipoprotein (3±0.9 vs 2.7±0.8 mmol/L) and triglyceride (1.4±0.7 vs 1.3±0.6 mmol/L), and increases in flexibility (12.1±11.6 vs 16.1±10.8 cm) and 6 min walk distance (559.4±156.6 vs 652.3±193.6 m; all p<0.05).ConclusionsA 12-week comprehensive, patient-centred LIP can be implemented successfully in the SEM setting in patients with NCDs with multiple comorbidities. Observed results show improvements in the majority of outcome variables.
On the energy and performance of commodity hardware transactional memory
Authors: Diegues Nuno , Romano Paolo , Rodrigues Luís 
Published: July 2014

The advent of multi-core architectures has brought concurrent programming to the forefront of software development. In this context, Transactional Memory (TM) has gained increasing popularity as a simpler, attractive alternative to traditional lock-based synchronization. The recent integration of Hardware TM (HTM) in the last generation of Intel commodity processors turned TM into a mainstream technology, raising a number of questions on its future and that of concurrent programming.
To evaluate the potential impact of Intel's HTM, we conducted the largest study on TM to date, comparing different locking techniques, hardware and software TMs, as well as different combinations of these mechanisms, from the dual perspective of performance and power consumption. As a result we perform a workload characterization, to help programmers better exploit the currently available TM facilities, and identify important research directions.
TARDIS
Authors: Clegg Richard G. , Landa Raul , Araújo João Taveira , Mykoniati Eleni , Griffin David , Rio Miguel 
Published: July 2014

This paper describes TARDIS (Traffic Assignment and Retiming Dynamics with Inherent Stability) which is an algorithmic procedure designed to reallocate traffic within Internet Service Provider (ISP) networks. Recent work has investigated the idea of shifting traffic in time (from peak to off-peak) or in space (by using different links). This work gives a unified scheme for both time and space shifting to reduce costs. Particular attention is given to the commonly used 95th percentile pricing scheme.
The work has three main innovations: firstly, introducing the Shapley Gradient, a way of comparing traffic pricing between different links at different times of day; secondly, a unified way of reallocating traffic in time and/or in space; thirdly, a continuous approximation to this system is proved to be stable. A trace-driven investigation using data from two service providers shows that the algorithm can create large savings in transit costs even when only small proportions of the traffic can be shifted.
Open pattern matching for C++
Authors: Solodkyy Yuriy , Dos Reis Gabriel , Stroustrup Bjarne 
Published: July 2014

Pattern matching is an abstraction mechanism that can greatly simplify source code. We present functional-style pattern matching for C++ implemented as a library, called

Mach7
1

. All the patterns are user-definable, can be stored in variables, passed among functions, and allow the use of class hierarchies. As an example, we implement common patterns used in functional languages.

Our approach to pattern matching is based on compile-time composition of pattern objects through concepts. This is superior (in terms of performance and expressiveness) to approaches based on run-time composition of polymorphic pattern objects. In particular, our solution allows mapping functional code based on pattern matching directly into C++ and produces code that is only a few percent slower than hand-optimized C++ code.
The library uses an efficient type switch construct, further extending it to multiple scrutinees and general patterns. We compare the performance of pattern matching to that of double dispatch and open multi-methods in C++.
Pharmacogenetic Predictors of Outcome in Patients with Stage II and III Colon Cancer Treated with Oxaliplatin and Fluoropyrimidine-Based Adjuvant Chemotherapy
Authors: Custodio Ana , Moreno-Rubio Juan , Aparicio Jorge , Gallego-Plazas Javier , Yaya Ricardo , Maurel Joan , Rodríguez-Salas Nuria , Burgos Emilio , Ramos David , Calatrava Ana , Andrada Encarna , Díaz-López Esther , Sánchez Antonio , Madero Rosario , Cejas Paloma , Feliu Jaime 
Published: July 2014

Abstract
Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with colon cancer who are more likely to benefit from adjuvant chemotherapy. We investigated the effect of single-nucleotide polymorphisms (SNP) within genes involved in oxaliplatin and fluoropyrimidines metabolism, DNA repair mechanisms, drug transport, or angiogenesis pathways on outcome for patients with stage II and III colon cancer treated with adjuvant chemotherapy. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 202 patients with stage II and III colon cancer receiving oxaliplatin-based adjuvant chemotherapy from January 2004 to December 2009. Genotyping was performed for 67 SNPs in 32 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 patients treated with the same chemotherapy regimens. The combination of the selectin E (SELE) rs3917412 G&gt;A G/G and the methylentetrahydrofolate reductase (MTHFR) rs1801133 T/T genotypes was associated with a significantly increased risk for recurrence in both the training [RR = 4.103; 95% confidence interval (CI), 1.803–9.334; P = 0.001] and the validation cohorts (RR = 3.567; 95% CI, 1.253–10.151; P = 0.017) in the multiple regression analysis considering the stage, lymphovascular invasion, and bowel perforation as covariates. The combined analysis of these polymorphisms was also significantly associated with overall survival in both cohorts (RR = 3.388; 95% CI, 0.988–11.623; P = 0.052, and RR = 3.929; 95% CI, 1.144–13.485; P = 0.020, respectively). Our findings suggest that the SELE rs3917412 and MTHFR rs1801133 SNPs could serve as pharmacogenetic predictors of tumor recurrence in patients with early-stage colon cancer treated with oxaliplatin-based adjuvant chemotherapy, thus allowing personalized selection of treatment to optimize clinical outcomes. Mol Cancer Ther; 13(9); 2226–37. ©2014 AACR.
Ethical decision-making in hospice care
Authors: Walker Andreas , Breitsameter Christof 
Published: July 2014

Background: Hospices are based on a holistic approach which places the physical, psychological, social and spiritual welfare of their patients at the forefront of their work. Furthermore, they draw up their own mission statements which they are at pains to follow and seek to conduct their work in accordance with codes of ethics and standards of care. Research question and design: Our study researched what form the processes and degrees of latitude in decision-making take in practice when questions of an ethical and ethically relevant nature arise. We used a qualitative approach. Data collection and evaluation was based on the methods of grounded theory. Ethical considerations: The study was reported to the relevant Ethics Commission who had raised no objections following the submission of the study protocol. The study at the hospices was approved by the directors of the hospices and the nursing teams. The rights of the participants were protected by obtaining informed consent. Results: Medication in the prefinal phase and questions affecting the provision of solids and liquids in the end-of-life phase have an ethical dimension. In the context of these two fields, decisions are taken collectively. A nurse’s individual (and ethically relevant) leeway in decision-making processes is restricted to the nurse’s own style of administering care. The nurse’s decision-making often depends to a far greater degree on her ability to adapt her concept of ideal care to fit the practical realities of her work than to any conceptual framework. Discussion: An adaptive process is necessary for the nurse because she is required to incorporate the four pillars of hospice care – namely, physical, psychological, social and spiritual care – into the practice of her daily work. Conclusion: Ethically relevant decisions are often characterised by nurses adjusting their aspiration levels to the practical conditions with which they are confronted.
Study protocol of the Going to Stay at Home program: evaluation of a residential carer training program to reduce dementia carer distress and burden
Authors: Gresham Meredith , Tsang Ruby S M , Heffernan Megan , Brodaty Henry 
Published: July 2014

Abstract

Background
Caring for a person with dementia has profound physical, psychological, social and financial impacts on the carer, while morbidity in carers has detrimental effects on outcomes in people with dementia. A 10-day hospital-based residential carer training program (BMJ 299(6712):1375–1379, 1989) delayed residential care placement, delayed mortality, reduced carer’s psychological morbidity and lowered care costs. This study aims to evaluate the effects of a similar program adapted for use with residential respite.

Methods/Design
This is a single-arm longitudinal study conducted at a residential aged care facility involving 100 people with dementia and their primary carers. In a 7-day residential program, carers will attend intensive training sessions while the people with dementia are engaged in daily activities. Data will be collected at the start of the residential program (baseline), at 6 months (post 1) and at 12 months (post 2) after completion of the program. The primary outcome is carer psychological distress. Secondary outcomes include carer burden, carer quality of life and time to residential care placement.

Discussion
This study will provide evidence on the effectiveness of the program in reducing carer distress and burden as well as delaying institutionalisation of the person with dementia, which may have important implications for policy.
Cyclin-dependent kinases
Authors: Malumbres Marcos 
Published: July 2014

SummaryCyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific members has generated very encouraging results in clinical trials.
Psychodynamic psychotherapy: developing the evidence base
Authors: Yakeley Jessica 
Published: July 2014

SummaryPsychodynamic psychotherapy has been criticised as being based on outdated principles of psychoanalysis and lacking an adequate evidence base to convincingly demonstrate its efficacy. This article summarises the recent evidence from high-quality outcome studies to show that psychodynamic psychotherapy is as effective in the treatment of a range of mental disorders as other psychological treatment modalities such as cognitive-behavioural therapy, as well as reviewing process-outcome research aiming to elucidate mechanisms of therapeutic change. A paradigm for psychodynamic psychotherapy research based on attachment theory is introduced, which may inform the development of psychodynamic therapeutic modalities tailored for specific conditions.LEARNING OBJECTIVESUnderstand the basic principles and techniques of psychodynamic psychotherapy.Be able to summarise the recent evidence base for the efficacy of psychodynamic psychotherapy.Appreciate process-outcome research that elucidates therapeutic mechanisms underpinning psychodynamic psychotherapy.
Improved Survival After Transplantation of More Donor Plasmacytoid Dendritic or Naïve T Cells From Unrelated-Donor Marrow Grafts: Results From BMTCTN 0201
Authors: Waller Edmund K. , Logan Brent R. , Harris Wayne A.C. , Devine Steven M. , Porter David L. , Mineishi Shin , McCarty John M. , Gonzalez Corina E. , Spitzer Thomas R. , Krijanovski Oleg I. , Linenberger Michael L. , Woolfrey Ann , Howard Alan , Wu Juan , Confer Dennis L. , Anasetti Claudio 
Published: July 2014

Purpose To characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor–mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201. Patients and Methods Fresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD). Results Patients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naïve T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naïve CD8+ T cells (CD8Tns), or naïve CD4+ T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD. Conclusion Donor immune cells in BM but not PB stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation.
Adaptive Dose-Finding Studies: A Review of Model-Guided Phase I Clinical Trials
Authors: Iasonos Alexia , O'Quigley John 
Published: July 2014

Purpose We provide a comprehensive review of adaptive phase I clinical trials in oncology that used a statistical model to guide dose escalation to identify the maximum-tolerated dose (MTD). We describe the clinical setting, practical implications, and safety of such applications, with the aim of understanding how these designs work in practice. Methods We identified 53 phase I trials published between January 2003 and September 2013 that used the continual reassessment method (CRM), CRM using escalation with overdose control, or time-to-event CRM for late-onset toxicities. Study characteristics, design parameters, dose-limiting toxicity (DLT) definition, DLT rate, patient-dose allocation, overdose, underdose, sample size, and trial duration were abstracted from each study. In addition, we examined all studies in terms of safety, and we outlined the reasons why escalations occur and under what circumstances. Results On average, trials accrued 25 to 35 patients over a 2-year period and tested five dose levels. The average DLT rate was 18%, which is lower than in previous reports, whereas all levels above the MTD had an average DLT rate of 36%. On average, 39% of patients were treated at the MTD, and 74% were treated at either the MTD or an adjacent level (one level above or below). Conclusion This review of completed phase I studies confirms the safety and generalizability of model-guided, adaptive dose-escalation designs, and it provides an approach for using, interpreting, and understanding such designs to guide dose escalation in phase I trials.
An Alternative Carbon Dioxide Capture by Electrochemical Method
Authors: Taniguchi Ikuo , Ioh Daichi , Fujikawa Shigenori , Watanabe Takayuki , Matsukuma Yosuke , Minemoto Masaki 
Published: July 2014

Abstract
CO2 capture with liquid amine scrubbing has received current acceptance; however, the energy intensive heating process in CO2 recovery requires alternate effective CO2 separation methods. Condensation of CO2-trapping solutions by electrodialysis and successive CO2 recovery under reduced pressure would decrease the required energy in the CO2 capture drastically. Energy calculations and basic experiments reveal that the required energy can be reduced to less than 2.0 GJ (t-CO2)−1, which is about a half of the energy required for aqueous monoethanolamine.
A comparative assessment of small-head metal-on-metal and ceramic-on-polyethylene total hip replacement
Authors: Lübbeke A. , Gonzalez A. , Garavaglia G. , Roussos C. , Bonvin A. , Stern R. , Peter R. , Hoffmeyer P. 
Published: July 2014

Large-head metal-on-metal (MoM) total hip replacements (THR) have given rise to concern. Comparative studies of small-head MoM THRs over a longer follow-up period are lacking. Our objective was to compare the incidence of complications such as infection, dislocation, revision, adverse local tissue reactions, mortality and radiological and clinical outcomes in small-head (28 mm) MoM and ceramic-on-polyethylene (CoP) THRs up to 12 years post-operatively. A prospective cohort study included 3341 THRs in 2714 patients. The mean age was 69.1 years (range 24 to 98) and 1848 (55.3%) were performed in women, with a mean follow-up of 115 months (18 to 201). There were 883 MoM and 2458 CoP bearings. Crude incidence rates (cases/1000 person-years) were: infection 1.3 vs 0.8; dislocation 3.3 vs 3.1 and all-cause revision 4.3 vs 2.2, respectively. There was a significantly higher revision rate after ten years (adjusted hazard ratio 9.4; 95% CI 2.6 to 33.6) in the MoM group, and ten of 26 patients presented with an adverse local tissue reaction at revision. No differences in mortality, osteolysis or clinical outcome were seen. In conclusion, we found similar results for small-head MoM and CoP bearings up to ten years post-operatively, but after ten years MoM THRs had a higher risk of all-cause revision. Furthermore, the presence of an adverse response to metal debris seen in the small-head MOM group at revision is a cause for concern. Cite this article: Bone Joint J 2014; 96-B:868–75.