bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonbinding Site-Directed Mutants of Transferrin Binding Protein B Exhibit Enhanced Immunogenicity and Protective Capabilities
Authors: Frandoloso Rafael , Martínez-Martínez Sonia , Calmettes Charles , Fegan Jamie , Costa Estela , Curran Dave , Yu Rong-hua , Gutiérrez-Martín César B. , Rodríguez-Ferri Elías F. , Moraes Trevor F. , Schryvers Anthony B. 
Published: December 2014

ABSTRACT

Host-adapted Gram-negative bacterial pathogens from the
Pasteurellaceae
,
Neisseriaceae
, and
Moraxellaceae
families normally reside in the upper respiratory or genitourinary tracts of their hosts and rely on utilizing iron from host transferrin (Tf) for growth and survival. The surface receptor proteins that mediate this critical iron acquisition pathway have been proposed as ideal vaccine targets due to the critical role that they play in survival and disease pathogenesis
in vivo
. In particular, the surface lipoprotein component of the receptor, Tf binding protein B (TbpB), had received considerable attention as a potential antigen for vaccines in humans and food production animals but this has not translated into the series of successful vaccine products originally envisioned. Preliminary immunization experiments suggesting that host Tf could interfere with development of the immune response prompted us to directly address this question with site-directed mutant proteins defective in binding Tf. Site-directed mutants with dramatically reduced binding of porcine transferrin and nearly identical structure to the native proteins were prepared. A mutant
Haemophilus parasuis
TbpB was shown to induce an enhanced B-cell and T-cell response in pigs relative to native TbpB and provide superior protection from infection than the native TbpB or a commercial vaccine product. The results indicate that binding of host transferrin modulates the development of the immune response against TbpBs and that strategies designed to reduce or eliminate binding can be used to generate superior antigens for vaccines.
Monkey Models of Tuberculosis: Lessons Learned
Authors: Peña Juliet C. , Ho Wen-Zhe 
Published: December 2014

ABSTRACT

The use of animal models has been invaluable for studying the pathogenesis of
Mycobacterium tuberculosis
infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research.
Analysis of Metabolism in Dormant Spores of Bacillus Species by
31
P Nuclear Magnetic Resonance Analysis of Low-Molecular-Weight Compounds
Authors: Ghosh Sonali , Korza George , Maciejewski Mark , Setlow Peter 
Published: December 2014

ABSTRACT

This work was undertaken to obtain information on levels of metabolism in dormant spores of
Bacillus
species incubated for weeks at physiological temperatures. Spores of
Bacillus megaterium
and
Bacillus subtilis
strains were harvested shortly after release from sporangia and incubated under various conditions, and dormant spore metabolism was monitored by
31
P nuclear magnetic resonance (NMR) analysis of molecules including 3-phosphoglyceric acid (3PGA) and ribonucleotides. Incubation for up to 30 days at 4, 37, or 50°C in water, at 37 or 50°C in buffer to raise the spore core pH from ∼ 6.3 to 7.8, or at 4°C in spent sporulation medium caused no significant changes in ribonucleotide or 3PGA levels. Stage I germinated spores of
Bacillus megaterium
that had slightly increased core water content and a core pH of 7.8 also did not degrade 3PGA and accumulated no ribonucleotides, including ATP, during incubation for 8 days at 37°C in buffered saline. In contrast, spores incubated for up to 30 days at 37 or 50°C in spent sporulation medium degraded significant amounts of 3PGA and accumulated ribonucleotides, indicative of RNA degradation, and these processes were increased in
B. megaterium
spores with a core pH of ∼7.8. However, no ATP was accumulated in these spores. These data indicate that spores of
Bacillus
species stored in water or buffer at low or high temperatures exhibited minimal, if any, metabolism of endogenous compounds, even when the spore core pH was 7.8 and core water content was increased somewhat. However, there was some metabolism in spores stored in spent sporulation medium.
Z2×Z3Equivariant Bifurcation in Coupled Two Neural Network Rings
Authors: Zheng Baodong , Yin Haidong 
Published: December 2014

We study a Hopfield-type network that consists of a pair of one-way rings each with three neurons and two-way coupling between the rings. The rings have symmetric groupΓ=Z3×Z2, which means the global symmetryZ2and internal symmetryZ3. We discuss the spatiotemporal patterns of bifurcating periodic oscillations by using the symmetric bifurcation theory of delay differential equations combined with representation theory of Lie groups. The existence of multiple branches of bifurcating periodic solution is obtained. We also found that the spatiotemporal patterns of bifurcating periodic oscillations alternate according to the change of the propagation time delay in the coupling; that is, different ranges of delays correspond to different patterns of neural network oscillators. The oscillations of corresponding neurons in the two loops can be in phase, antiphase,T/3, 2T/3, 4T/3, 5T/6, or7T/6periods out of phase depending on the delay. Some numerical simulations support our analysis results.
Tyrosine Kinase Inhibition in Leukemia Induces an Altered Metabolic State Sensitive to Mitochondrial Perturbations
Authors: Alvarez-Calderon Francesca , Gregory Mark A. , Pham-Danis Catherine , DeRyckere Deborah , Stevens Brett M. , Zaberezhnyy Vadym , Hill Amanda A. , Gemta Lelisa , Kumar Amit , Kumar Vijay , Wempe Michael F. , Pollyea Daniel A. , Jordan Craig T. , Serkova Natalie J. , Graham Douglas K. , DeGregori James 
Published: December 2014

Abstract
Purpose: Although tyrosine kinase inhibitors (TKI) can be effective therapies for leukemia, they fail to fully eliminate leukemic cells and achieve durable remissions for many patients with advanced BCR-ABL+ leukemias or acute myelogenous leukemia (AML). Through a large-scale synthetic lethal RNAi screen, we identified pyruvate dehydrogenase, the limiting enzyme for pyruvate entry into the mitochondrial tricarboxylic acid cycle, as critical for the survival of chronic myelogenous leukemia (CML) cells upon BCR-ABL inhibition. Here, we examined the role of mitochondrial metabolism in the survival of Ph+ leukemia and AML upon TK inhibition.
Experimental Design: Ph+ cancer cell lines, AML cell lines, leukemia xenografts, cord blood, and patient samples were examined.
Results: We showed that the mitochondrial ATP-synthase inhibitor oligomycin-A greatly sensitized leukemia cells to TKI in vitro. Surprisingly, oligomycin-A sensitized leukemia cells to BCR-ABL inhibition at concentrations of 100- to 1,000-fold below those required for inhibition of respiration. Oligomycin-A treatment rapidly led to mitochondrial membrane depolarization and reduced ATP levels, and promoted superoxide production and leukemia cell apoptosis when combined with TKI. Importantly, oligomycin-A enhanced elimination of BCR-ABL+ leukemia cells by TKI in a mouse model and in primary blast crisis CML samples. Moreover, oligomycin-A also greatly potentiated the elimination of FLT3-dependent AML cells when combined with an FLT3 TKI, both in vitro and in vivo.
Conclusions: TKI therapy in leukemia cells creates a novel metabolic state that is highly sensitive to particular mitochondrial perturbations. Targeting mitochondrial metabolism as an adjuvant therapy could therefore improve therapeutic responses to TKI for patients with BCR-ABL+ and FLT3ITD leukemias. Clin Cancer Res; 21(6); 1360–72. ©2014 AACR.
Membrane-to-Nucleus Signals and Epigenetic Mechanisms for Myofibroblastic Activation and Desmoplastic Stroma: Potential Therapeutic Targets for Liver Metastasis?
Authors: Kang Ningling , Shah Vijay H. , Urrutia Raul 
Published: December 2014

Abstract
Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment (TME), are a key source of the extracellular matrix (ECM) that constitutes the desmoplastic stroma. Through remodeling of the reactive tumor stroma and paracrine actions, CAFs regulate cancer initiation, progression, and metastasis, as well as tumor resistance to therapies. The CAFs found in stroma-rich primary hepatocellular carcinomas (HCC) and liver metastases of primary cancers of other organs predominantly originate from hepatic stellate cells (HSTC), which are pericytes associated with hepatic sinusoids. During tumor invasion, HSTCs transdifferentiate into myofibroblasts in response to paracrine signals emanating from either tumor cells or a heterogeneous cell population within the hepatic tumor microenvironment. Mechanistically, HSTC-to-myofibroblast transdifferentiation, also known as, HSTC activation, requires cell surface receptor activation, intracellular signal transduction, gene transcription, and epigenetic signals, which combined ultimately modulate distinct gene expression profiles that give rise to and maintain a new phenotype. The current review defines a paradigm that explains how HSTCs are activated into CAFs to promote liver metastasis. Furthermore, a focus on the most relevant intracellular signaling networks and epigenetic mechanisms that control HSTC activation is provided. Finally, we discuss the feasibility of targeting CAF/activated HSTCs, in isolation or in conjunction with targeting cancer cells, which constitutes a promising and viable therapeutic approach for the treatment of primary stroma-rich liver cancers and liver metastasis. Mol Cancer Res; 13(4); 604–12. ©2014 AACR.
Cloud Trails Past the Lesser Antilles
Authors: Kirshbaum Daniel J. , Fairman Jonathan G. 
Published: December 2014

Abstract
Observations and cloud-resolving simulations of elongated cloud plumes (or “cloud trails”) past the Lesser Antilles islands in the Caribbean Sea are presented. Analysis of one year of visible satellite images reveals that each island forms cloud trails on 30%–40% of days, typically in the afternoon in response to diurnal island heating. On around 10% of days the cloud bands are very well organized, with lengths of and durations of min. Radiosonde analysis suggests that the well-organized events are favored by moderate-to-strong trade winds (6–10 m s−1) and stronger trade inversions. The simulated cloud trails, which are consistent with observations in their morphology and diurnal cycle, are organized by quasi-linear bands of thermally forced convergence within the heated island wake. They are sensitive to overland surface fluxes, inversion strength and height, terrain height, and trade-wind speed. While surface fluxes control the strength of the wake thermal circulations, the inversion controls precipitation and the disruption of cloud trails by subcloud cold pools. The impacts of terrain height and wind speed are multifaceted, including control over (i) the mechanical flow regime, (ii) the intensity of wake turbulence, (iii) the cloud-trail length, (iv) the wake thermal anomaly, and (v) elevated-heating effects (which strengthen the thermal convergence). Dimensional analysis is used to develop empirical scalings for the wake thermal circulation, which describe the suite of numerical sensitivity tests reasonably well.
Cultural orientation and social capital as predictors of condom use among internal migrants in China
Authors: Du Hongfei , Li Xiaoming , Lin Danhua , Tam Cheuk Chi 
Published: December 2014

Background: The global literature has revealed that cultural orientation, adaptation and social capital may influence HIV-related sexual behaviours among migrants. However, whether cultural orientations influence adaptation and social capital and thereby affect sexual behaviour is not well understood. Method: This study examined whether individualistic and collectivistic orientations, adaptation and social capital have direct and indirect effects on condom use among rural-to-urban migrants in China. We collected data from 641 migrants aged 17 to 30 years, in Beijing, China. Participants completed scales on individualistic orientation, collectivistic orientation, adaptation, social capital and condom use. Structural equation modelling was used for model testing. Results: Condom use was positively associated with an individualistic orientation and social capital. An individualistic orientation had an indirect effect on condom use via social capital. Women reported higher levels of condom use than men. Conclusion: Future sexual risk prevention and intervention programmes to improve sexual health should pay more attention to building social capital and engaging with relevant cultural factors.
Individual Differences in the Calibration of Trust in Automation
Authors: Pop Vlad L. , Shrewsbury Alex , Durso Francis T. 
Published: December 2014

Objective: The objective was to determine whether operators with an expectancy that automation is trustworthy are better at calibrating their trust to changes in the capabilities of automation, and if so, why. Background: Studies suggest that individual differences in automation expectancy may be able to account for why changes in the capabilities of automation lead to a substantial change in trust for some, yet only a small change for others. Method: In a baggage screening task, 225 participants searched for weapons in 200 X-ray images of luggage. Participants were assisted by an automated decision aid exhibiting different levels of reliability. Measures of expectancy that automation is trustworthy were used in conjunction with subjective measures of trust and perceived reliability to identify individual differences in trust calibration. Results: Operators with high expectancy that automation is trustworthy were more sensitive to changes (both increases and decreases) in automation reliability. This difference was eliminated by manipulating the causal attribution of automation errors. Conclusion: Attributing the cause of automation errors to factors external to the automation fosters an understanding of tasks and situations in which automation differs in reliability and may lead to more appropriate trust. Application: The development of interventions can lead to calibrated trust in automation.
Reducing the Disruptive Effects of Interruptions With Noninvasive Brain Stimulation
Authors: Blumberg Eric J. , Foroughi Cyrus K. , Scheldrup Melissa R. , Peterson Matthew S. , Boehm-Davis Debbie A. , Parasuraman Raja 
Published: December 2014

Objective: The authors determine whether transcranial direct current stimulation (tDCS) can reduce resumption time when an ongoing task is interrupted. Background: Interruptions are common and disruptive. Working memory capacity has been shown to predict resumption lag (i.e., time to successfully resume a task after interruption). Given that tDCS applied to brain areas associated with working memory can enhance performance, tDCS has the potential to improve resumption lag when a task is interrupted. Method: Participants were randomly assigned to one of four groups that received anodal (active) stimulation of 2 mA tDCS to one of two target brain regions, left and right dorsolateral prefrontal cortex (DLPFC), or to one of two control areas, active stimulation of the left primary motor cortex or sham stimulation of the right DLPFC, while completing a financial management task that was intermittently interrupted with math problem solving. Results: Anodal stimulation to the right and left DLPFC significantly reduced resumption lags compared to the control conditions (sham and left motor cortex stimulation). Additionally, there was no speed-accuracy tradeoff (i.e., the improvement in resumption time was not accompanied by an increased error rate). Conclusion: Noninvasive brain stimulation can significantly decrease resumption lag (improve performance) after a task is interrupted. Application: Noninvasive brain stimulation offers an easy-to-apply tool that can significantly improve interrupted task performance.
Effectiveness of a training package for implementing a community-based occupational therapy program in dementia: a cluster randomized controlled trial
Authors: Döpp Carola ME , Graff Maud JL , Teerenstra Steven , Olde Rikkert Marcel GM , Nijhuis–van der Sanden Maria WG , Vernooij-Dassen Myrra JFJ 
Published: December 2014

Objective: Evaluate the effectiveness of a training package to implement a community occupational therapy program for people with dementia and their caregiver (COTiD). Design: Cluster randomized controlled trial. Subjects: A total of 45 service units including 94 occupational therapists, 48 managers, 80 physicians, treating 71 client-caregiver couples. Interventions: Control intervention: A postgraduate course for occupational therapists only. Experimental intervention: A training package including the usual postgraduate course, additional training days, outreach visits, regional meetings, and access to a reporting system for occupational therapists. Physicians and managers received newsletters, had access to a website, and were approached by telephone. Main measures: Primary outcome: The intended adherence of therapists to the COTiD program. This was assessed using vignettes. Secondary outcomes: clients’ daily functioning, caregivers’ sense of competence, quality of life, and self-perceived performance of daily activities of both clients and caregivers. Between-group differences were assessed using multilevel analyses with therapist and intervention factors as covariates. Results: No significant between-group differences between baseline and 12 months were found for adherence (1.58, 95% CI −0.10 to 3.25), nor for any client or caregiver outcome. A higher number of coaching sessions and higher self-perceived knowledge of dementia at baseline positively correlated with adherence scores. In contrast, experiencing more support from occupational therapy colleagues or having conducted more COTiD treatments at baseline negatively affected adherence scores. Conclusion: The training package was not effective in increasing therapist adherence and client–caregiver outcomes. This study suggests that coaching sessions and increasing therapist knowledge on dementia positively affect adherence. Clinical trial number: NCT01117285
Risk Factors Associated With Revision and Contralateral Anterior Cruciate Ligament Reconstructions in the Kaiser Permanente ACLR Registry
Authors: Maletis Gregory B. , Inacio Maria C.S. , Funahashi Tadashi T. 
Published: December 2014

Background: Patients generally choose to undergo anterior cruciate ligament reconstruction (ACLR) to return to their active lifestyles. However, returning to their previous activity level may result in a retear of their reconstructed knee or an injury to their contralateral anterior cruciate ligament (CACL). Purpose: To determine the risk factors associated with revision ACLR and contralateral ACLR (CACLR), compare the survival of the reconstructed ACL with the CACL, and determine how the risk factors associated with revision ACLR compare with those for CACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective cohort study of prospectively collected data from the Kaiser Permanente ACLR registry between February 1, 2005, and September 30, 2012, was conducted. Primary ACLR cases without history of contralateral knee ACL injury were included. The study endpoints included revision ACLR and CACLR. Graft type (bone–patellar tendon–bone [BPTB] autograft, hamstring autograft, and allograft) was the main exposure of interest, and patient characteristics were evaluated as risk factors for revision ACLR and CACLR. Survival analyses were conducted. Results: A total of 17,436 ACLRs were evaluated. The median age was 27.2 years (interquartile range, 18.7-37.7 years), and 64% were males. The 5-year survival for index ACLR was 95.1% (95% CI, 94.5%-95.6%), and for CACL it was 95.8% (95% CI, 95.2%-96.3%). Overall, the cohort had a mean of 2.4 ± 1.7 years of follow-up; 18.2% were lost to follow-up. There were fewer CACLRs per 100 years of observation (0.83) than there were revision ACLRs (1.05) during the study period ( P < .001). There was a statistically significant difference in the density of revision ACLR and CACL in BPTB autografts (0.74 vs 1.06, respectively; P = .010), hamstring autografts (1.07 vs 0.81; P = .042), and allografts (1.26 vs 0.67; P < .001). The risk factors for revision ACLR and contralateral surgery were different ( P < .05). After adjusting for covariates, factors associated with higher risk of revision ACLR were as follows: allografts, hamstring autografts, male sex, younger age, lower body mass index (BMI), and being white as opposed to black. Factors associated with higher risk of CACLR were as follows: younger age, female sex, and lower BMI. Conclusion: The 5-year revision-free and CACLR-free survival rate in this study was 95.1% and 95.8%, respectively. Allografts and hamstring autografts had a higher risk of revision ACLR surgery, and BPTB autografts had a higher risk of CACLR. Males were found to have a higher risk of revision ACLR, and females had a higher risk of CACLR. Increasing age and increasing BMI decreased the risk of both revision and CACLR.
Hamstring Tendon Regeneration After Harvesting
Authors: Suijkerbuijk Mathijs A.M. , Reijman Max , Lodewijks Susanne J.M. , Punt Jorien , Meuffels Duncan E. 
Published: December 2014

Background: Hamstring tendons are often used as autografts for anterior cruciate ligament (ACL) reconstruction. However, no systematic review has been performed describing consequences such as hamstring tendon regeneration rate and determinants of hamstring tendon regeneration. Purpose: To summarize the current literature regarding hamstring tendon rate regeneration, the time course of regeneration, and determinants of hamstring regeneration. Study design: Systematic review. Methods: A search was performed in the Embase, Medline (OvidSP), Web of Science, Cochrane, PubMed, and Google Scholar databases up to June 2014 to identify relevant articles. A study was eligible if it met the following inclusion criteria: tendons were harvested, regeneration at harvest site was assessed, population size was at least 10 human subjects, full-text article was available, and the study design was either a randomized controlled trial, prospective cohort study, retrospective cohort study, or case control study. A risk of bias assessment of the eligible articles was determined. Data describing hamstring tendon regeneration rates were pooled per time period. Results: A total of 18 publications met the inclusion criteria. The mean regeneration rate for the semitendinosus and gracilis tendons was, in all cases, 70% or higher. More than 1 year after harvesting, 79% (median [IQR], 80 [75.5-90]) of the semitendinosus tendons and 72% (median [IQR], 80 [61-88.5]) of the gracilis tendons were regenerated. No significant differences in regeneration rate could be found considering patient sex, age, height, weight, or duration of immobilization. Results did not clearly show whether absence of regeneration disadvantages the subsequent hamstring function. Five studies measured the regeneration rate at different moments in time. Conclusion: Hamstring tendons regenerated in the majority of patients after ACL reconstruction. The majority of the hamstring tendon regeneration was found to occur between 1 month and 1 year after harvest. No significant determinants for hamstring tendon regeneration could be identified because of a lack of research. The function and strength of the regenerated hamstring remained unclear.