bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordinating Bacterial Cell Division with Nutrient Availability: a Role for Glycolysis
Authors: Monahan Leigh G. , Hajduk Isabella V. , Blaber Sinead P. , Charles Ian G. , Harry Elizabeth J.
Published: May 2014

Cell division in bacteria is driven by a cytoskeletal ring structure, the Z ring, composed of polymers of the tubulin-like protein FtsZ. Z-ring formation must be tightly regulated to ensure faithful cell division, and several mechanisms that influence the positioning and timing of Z-ring assembly have been described. Another important but as yet poorly understood aspect of cell division regulation is the need to coordinate division with cell growth and nutrient availability. In this study, we demonstrated for the first time that cell division is intimately linked to central carbon metabolism in the model Gram-positive bacterium
Bacillus subtilis
. We showed that a deletion of the gene encoding pyruvate kinase (
pyk
), which produces pyruvate in the final reaction of glycolysis, rescues the assembly defect of a temperature-sensitive
ftsZ
mutant and has significant effects on Z-ring formation in wild-type
B. subtilis
cells. Addition of exogenous pyruvate restores normal division in the absence of the pyruvate kinase enzyme, implicating pyruvate as a key metabolite in the coordination of bacterial growth and division. Our results support a model in which pyruvate levels are coupled to Z-ring assembly via an enzyme that actually metabolizes pyruvate, the E1α subunit of pyruvate dehydrogenase. We have shown that this protein localizes over the nucleoid in a pyruvate-dependent manner and may stimulate more efficient Z-ring formation at the cell center under nutrient-rich conditions, when cells must divide more frequently.

IMPORTANCE
How bacteria coordinate cell cycle processes with nutrient availability and growth is a fundamental yet unresolved question in microbiology. Recent breakthroughs have revealed that nutritional information can be transmitted directly from metabolic pathways to the cell cycle machinery and that this can serve as a mechanism for fine-tuning cell cycle processes in response to changes in environmental conditions. Here we identified a novel link between glycolysis and cell division in
Bacillus subtilis
. We showed that pyruvate, the final product of glycolysis, plays an important role in maintaining normal division. Nutrient-dependent changes in pyruvate levels affect the function of the cell division protein FtsZ, most likely by modifying the activity of an enzyme that metabolizes pyruvate, namely, pyruvate dehydrogenase E1α. Ultimately this system may help to coordinate bacterial division with nutritional conditions to ensure the survival of newborn cells.
The Heterocyst-Specific NsiR1 Small RNA Is an Early Marker of Cell Differentiation in Cyanobacterial Filaments
Authors: Muro-Pastor Alicia M.
Published: May 2014

Differentiation of single cells along filaments of cyanobacteria constitutes one of the simplest developmental patterns in nature. In response to nitrogen deficiency, certain cells located in a semiregular pattern along filaments differentiate into specialized nitrogen-fixing cells called heterocysts. The process involves the sequential activation of many genes whose expression takes place, either exclusively or at least more strongly, in those cells undergoing differentiation. In the model cyanobacterium
Anabaena
(
Nostoc
) sp. strain PCC 7120, increased transcription of
hetR
, considered the earliest detectable heterocyst-specific transcript, has been reported to occur in pairs or even in clusters of cells, thus making it difficult to identify prospective heterocysts during the early stages of differentiation, before any morphological change is detectable. The promoter of
nsiR1
(nitrogen stress inducible RNA1), a heterocyst-specific small RNA, constitutes a minimal sequence promoting heterocyst-specific transcription. Using confocal fluorescence microscopy, I have analyzed expression of a
gfp
reporter transcriptionally fused to P

nsiR1

. The combined analysis of green fluorescence (reporting transcriptional activity from P

nsiR1

) and red fluorescence (an indication of progress in the differentiation of individual cells) shows that expression of P

nsiR1

takes place in single cells located in a semiregular pattern before any other morphological or fluorescence signature of differentiation can be observed, thus providing an early marker for cells undergoing differentiation.

IMPORTANCE
Cyanobacterial filaments containing heterocysts constitute an example of bacterial division of labor. When using atmospheric nitrogen, these filaments behave as multicellular organisms in which two different cell types (vegetative cells and nitrogen-fixing heterocysts) coexist and cooperate to achieve growth of the filament as a whole. The molecular basis governing the differentiation of individual vegetative cells, and thus the establishment of a one-dimensional pattern from cells that are apparently the same, remains one of the most intriguing aspects of this differentiation process. Recent evidence suggests that, at any given time, some cells in the filaments are more likely than others to become heterocysts when nitrogen limitation is encountered. The robust heterocyst-specific
nsiR1
promoter, which is induced very early during differentiation, provides a valuable tool to analyze issues such as early candidacy or the possible role of transcriptional noise in determining the fate of specific cells in cyanobacterial filaments.
Efficient Gene Disruption in Diverse Strains of Toxoplasma gondii Using CRISPR/CAS9
Authors: Shen Bang , Brown Kevin M. , Lee Tobie D. , Sibley L. David
Published: May 2014

Toxoplasma gondii
has become a model for studying the phylum Apicomplexa, in part due to the availability of excellent genetic tools. Although reverse genetic tools are available in a few widely utilized laboratory strains, they rely on special genetic backgrounds that are not easily implemented in natural isolates. Recent progress in modifying CRISPR (clustered regularly interspaced short palindromic repeats), a system of DNA recognition used as a defense mechanism in bacteria and archaea, has led to extremely efficient gene disruption in a variety of organisms. Here we utilized a CRISPR/CAS9-based system with single guide RNAs to disrupt genes in
T. gondii
. CRISPR/CAS9 provided an extremely efficient system for targeted gene disruption and for site-specific insertion of selectable markers through homologous recombination. CRISPR/CAS9 also facilitated site-specific insertion in the absence of homology, thus increasing the utility of this approach over existing technology. We then tested whether CRISPR/CAS9 would enable efficient transformation of a natural isolate. Using CRISPR/CAS9, we were able to rapidly generate both
rop18
knockouts and complemented lines in the type I GT1 strain, which has been used for forward genetic crosses but which remains refractory to reverse genetic approaches. Assessment of their phenotypes
in vivo
revealed that ROP18 contributed a greater proportion to acute pathogenesis in GT1 than in the laboratory type I RH strain. Thus, CRISPR/CAS9 extends reverse genetic techniques to diverse isolates of
T. gondii
, allowing exploration of a much wider spectrum of biological diversity.

IMPORTANCE
Genetic approaches have proven very powerful for studying the biology of organisms, including microbes. However, ease of genetic manipulation varies widely among isolates, with common lab isolates often being the most amenable to such approaches. Unfortunately, such common lab isolates have also been passaged frequently
in vitro
and have thus lost many of the attributes of wild isolates, often affecting important traits, like virulence. On the other hand, wild isolates are often not amenable to standard genetic approaches, thus limiting inquiry about the genetic basis of biological diversity. Here we imported a new genetic system based on CRISPR/CAS9, which allows high efficiency of targeted gene disruption in natural isolates of
T. gondii
. This advance promises to bring the power of genetics to bear on the broad diversity of
T. gondii
strains that have been described recently.
Effect of Acupuncture on Diabetic Peripheral Neuropathy: An Uncontrolled Preliminary Study from Korea
Authors: Jeon Eonju , Kwon Hyojung , Shin Imhee , Kang Seokbong , Shon Hosang
Published: May 2014

Background

Diabetic neuropathic pain can severely influence quality of life, and patients may be dissatisfied with treatment.

Objective

To carry out an observational study of the effects of acupuncture for the treatment of diabetic neuropathic pain, in preparation for a full study.

Methods

Nine patients with diabetic neuropathic pain were recruited from a Korean diabetic clinic and given 12 sessions of acupuncture over 4 weeks. Their symptoms were evaluated using the Total Symptom Score (TSS) and Michigan Neuropathy Screening Instrument (MNSI) at baseline and 4 weeks after the last treatment.

Results

Mean TSS scores reduced from 7.99 (SD 3.55) at baseline to 4.95 (SD 4.41), at the 8-week follow-up—a statistically non-significant change (p=0.057). The MNSI scores improved from 6.33 (SD 1.31) before treatment to 4.33 (SD 3.00) after acupuncture treatment—a significant improvement (p=0.010). One participant experienced an exacerbation of diabetic neuropathy symptoms, but two patients gained complete relief of their diabetic peripheral neuropathy (DPN) symptoms.

Conclusions

The results of this study justify further investigations into the effects of acupuncture on DPN.
Ear Acupuncture for Co-Occurring Substance Abuse and Borderline Personality Disorder: An Aid to Encourage Treatment Retention and Tobacco Cessation
Authors: Stuyt Elizabeth B
Published: May 2014

Objectives

Retention of individuals with co-occurring borderline personality disorder (BPD) and substance use disorders in treatment is known to be difficult. An outcome study of a tobacco-free 90-day inpatient dual-diagnosis treatment programme that uses several evidenced-based treatments in addition to ear acupuncture (acudetox) was undertaken to determine overall treatment effectiveness.

Methods

Between January 2009 and December 2011, 231 patients were treated in the programme, 88% with nicotine dependence and 79% with personality disorder diagnoses. All patients completing the programme were invited to enrol in a 1-year follow-up study in which they responded to monthly questionnaires to assess outcomes.

Results

185 patients (80%) successfully completed the programme. There was no correlation between successful programme completion and gender, race, age, primary drug dependence diagnosis or primary psychiatric diagnosis. The use of acudetox was positively correlated with successful completion (p=0.006). Of the 78 patients with BPD, 100% of men and 83% of women successfully completed the programme. Their use of acudetox was positively correlated with successful completion (p=0.026). At the end of the year, 140 questionnaires were returned: 51 patients with BPD reported outcomes similar to the group as a whole, with 55% sober and doing well.

Conclusions

The use of acudetox was positively correlated with both successful completion of the programme for those with BPD as well as successful tobacco cessation, which ultimately improves the ability to maintain sobriety.
Positional convulsant syncope in a pacemaker patient following insulation break of the right ventricular lead
Authors: Ben Lassoued Mehdi , Baatour Makram , Haggui Abdeddayem , Lamine Khaled
Published: May 2014

In spite of the advances made in the technology of pacemakers which resulted in a decrease in the incidence of pacemaker lead fracture, the latter remains a potential complication of implanted pacemakers manufactured in the early days. In this report, we present a case of fracture of the unipolar electrode diagnosed by an emergency physician in a patient on a pacemaker for 10 years who presented to the emergency department with positional convulsant syncopes.
Chronic empyema thoracis after percutaneous nephrolithotomy
Authors: Kumar Sanjeev , Gautam Shefali , Kumar Suresh , Rai Anurag
Published: May 2014

Percutaneous nephrolithotomy (PCNL) is presently the treatment of choice for large or multiple kidney stones or stones in the calyx. PCNL is generally safe and associated with low but indisputable complication rate. Pleural injury in PCNL is a rare but severe complication which can occur during or immediately after operation. Pleural injury may lead to chronic empyema thoracis. Until now no such case has been reported in literature.
Spontaneous external fistula: the rarest presentation of hydatid cyst
Authors: Jayant Kumar , Agrawal Swati , Agarwal Rajendra , Dayama Krishna Gopal
Published: May 2014

A 65-year-old man with hydatid disease of the liver presented with a spontaneous cutaneous rupture draining about 10 L of fluid with daughter cysts. Contrast-enhanced CT showed multiple hypodense areas in the residual right lobe of the liver and abdominal wall with compensatory hypertrophy of the left lobe, confirming the diagnosis of a hydatid cyst presenting as external fistulisation which represents a very advanced stage of hydatid disease. Once the patient's nutritional status improved he was taken for surgery. On laparotomy there were multiple cysts seen in the residual right lobe of the liver and inflammatory changes in the abdominal wall with an external fistulous opening. Right-lobe hepatectomy was carried out along with excision of the fistulous tract. The specimen showed multiple degenerated contents of the cyst with numerous daughter cysts along the fistulous tract and examination of cyst fluid demonstrated protoscolices. The postoperative period was uneventful. He was regularly followed and was doing well.
An incidental talonavicular coalition in a diabetic patient: a podiatric perspective
Authors: Shtofmakher Garry , Rozenstrauch Adam , Cohen Randy
Published: May 2014

A tarsal coalition is a pathological union of two or more tarsal bones. The authors present an incidental finding of a unilateral talonavicular (TN) coalition that was overlooked in a 57-year-old diabetic female with signs and symptoms of peripheral neuropathy. This case highlights the clinical implications and important teaching points in recognising a TN coalition. This is particularly relevant for new, upcoming clinicians who may have never been exposed to this diagnostic rarity during clinical training.
A small-area analysis of inequalities in chronic disease prevalence across urban and non-urban communities in the Province of Nova Scotia, Canada, 2007–2011
Authors: Terashima Mikiko , Rainham Daniel G C , Levy Adrian R
Published: May 2014

Background

Small-area studies of health inequalities often have an urban focus, and may be limited in their translatability to non-urban settings. Using small-area units representing communities, this study assessed the influence of living in different settlement types (urban, town and rural) on the prevalence of four chronic diseases (heart disease, cancer, diabetes and stroke) and compared the degrees of associations with individual-level and community-level factors among the settlement types.

Methods

The associations between community-level and individual-level characteristics and prevalence of the chronic diseases were assessed using logistic regression (multilevel and non-multilevel) models. Individual-level data were extracted from the Canadian Community Health Survey (2007–2011). Indices of material deprivation and social isolation and the settlement type classification were created using the Canadian Census.

Results

Respondents living in towns were 21% more likely to report one of the diseases than respondents living in urban communities even after accounting for individual-level and community-level characteristics. Having dependent children appeared to have protective effects in towns, especially for males (OR: 0.49 (95% CI 0.27 to 0.90)). Unemployment had a strong association for all types of communities, but being unemployed appeared to be particularly damaging to health of males in urban communities (OR: 2.48 (95% CI 1.43 to 4.30)).

Conclusions

The study showed that those living in non-urban settings, particularly towns, experience extra challenges in maintaining health above and beyond the socioeconomic condition and social isolation of the communities, and individual demographic, behavioural and socioeconomic attributes. Our findings also suggest that health inequality studies based on urban-only settings may underestimate the risks by some factors. Ways to devise meaningful small-area units comparable in all settlement types are necessary to help plan effective provision of chronic disease-related health services and programmes on a regional scale.
Exposure to Leadership WalkRounds in neonatal intensive care units is associated with a better patient safety culture and less caregiver burnout
Authors: Sexton J Bryan , Sharek Paul J , Thomas Eric J , Gould Jeffrey B , Nisbet Courtney C , Amspoker Amber B , Kowalkowski Mark A , Schwendimann René , Profit Jochen
Published: May 2014

Background

Leadership WalkRounds(WR) are widely used in healthcare organisations to improve patient safety. The relationship between WR and caregiver assessments of patient safety culture, and healthcare worker burnout is unknown.

Methods

This cross-sectional survey study evaluated the association between receiving feedback about actions taken as a result of WR and healthcare worker assessments of patient safety culture and burnout across 44 neonatal intensive care units (NICUs) actively participating in a structured delivery room management quality improvement initiative.

Results

Of 3294 administered surveys, 2073 were returned for an overall response rate of 62.9%. More WR feedback was associated with better safety culture results and lower burnout rates in the NICUs. Participation in WR and receiving feedback about WR were less common in NICUs than in a benchmarking comparison of adult clinical areas.

Conclusions

WR are linked to patient safety and burnout. In NICUs, where they occurred more often, the workplace appears to be a better place to deliver and to receive care.
‘I'll continue as long as I can, and die when I can't help it’: a qualitative exploration of the views of end-of-life care by those affected by head and neck cancer (HNC)
Authors: O'Sullivan E M , Higginson I J
Published: May 2014

Background

Evidence currently suggests that many people would prefer to die at home. However, optimal end-of-life homecare depends on the patient's ability to express their care preferences, prognostic awareness, complexity of care, concordance of patient/carer preferences and availability of appropriate services/support. This study explores Irish Head and Neck Cancer (HNC) patient and caregivers’ views on end-of-life care (EoLC), an area hitherto little studied.

Methods

Qualitative data were collected using semistructured, one-to-one interviews with HNC patients with therapeutic experience and their nearest caregivers (n=10, 7 patients, 3 carers). Interview topic guide was developed from the PRISMA EoLC survey. Thematic content analysis was employed to interpret findings.

Results

Thematic analysis identified five broad EoLC themes: prognostication, decision making, preferred focus of care/advanced care planning (ACP), preferred place of care/death, perceived barriers/supports to home death. Participants were very willing to discuss most aspects of EoLC, exhibiting no signs of distress. Patients were reluctant to discuss preferred focus-of-care and ACP. This seemed linked to an overly optimistic view of aggressive medical intervention. While carers favoured full patient involvement in decision making, patients were divided between wanting autonomy and those preferring a more passive approach. All expressed a preference for homecare, and most felt they wouldideallyprefer to die at home. However, decision making was considered a complex process intertwined with risks, responsibilities and commitments to others. Carer burden and symptom control were major concerns.

Conclusions

Normalising discussions on EoLC may benefit those affected by HNC. However, in HNC, this needs to be done alongside discussions regarding potentially life-extending treatment, symptom management and support.
Incidence trends of injury among the elderly in Spain, 2000–2010
Authors: Cirera Eva , Pérez Katherine , Santamariña-Rubio Elena , Novoa Ana M , Olabarria Marta
Published: May 2014

Background

The significant growth in the elderly population expected in the coming years demands a thorough and up-to-date understanding of the incidence of injuries in this group for purposes of prevention polices and their evaluation. The aim of this study was to describe the incidence of injuries in hospital inpatients over 64 years of age in Spain, stratified by sex, age group, and the severity and mechanism of injury, and to analyse trends in incidence during the period 2000–2010.

Methods

Descriptive trends study using data from the National Hospital Discharge Register. The dependent variable was the number of hospital discharges with injury. Stratified incidence rates were calculated per 100 000 inhabitants. Trends, in terms of annual per cent change, were assessed using Poisson regression with discharge year as the independent variable.

Results

Rates of injury were higher among women than men, increased with age in both sexes, with individuals aged ≥85 years having a fivefold greater risk than those aged 65–69 years. During the period 2000–2010, incidence increased annually by 1.1% in men and 0.9% in women aged 75–79 years, 2.3% and 1.6% in 80–84-year-olds and 3.3% and 2.4% in ≥85-year-olds, respectively. The incidence of all levels of injury severity and all mechanisms of injury increased during the study period, except for traffic injuries, which decreased.

Conclusions

Incidence of injury in the elderly is rising, particularly in older individuals, indicating that the increase in the number of hospitalisations is not a consequence of population aging only.
ERBB3 as an independent prognostic marker for nasopharyngeal carcinoma
Authors: Tulalamba Warut , Larbcharoensub Noppadol , Janvilisri Tavan
Published: May 2014

Aim

Although the ERBB proteins have been shown to be associated in many types of human tumours and serve as important cancer therapeutic targets, however, data regarding the expression and clinical relevance of ERBBs in nasopharyngeal carcinoma (NPC) are still conflicting. The aim of this study is to investigate the expression pattern of all ERBB members simultaneously in NPC tissues using immunohistochemistry and determine their clinical relevance.

Methods

The expression of all members of ERBB proteins was evaluated using immunohistochemistry on 82 NPC tissue samples. Relationship between the ERBB protein expression, clinicopathological parameters and patient outcome was assessed using univariate and multivariate analyses.

Results

We found that ERBB1, ERBB2 and ERBB3 were strongly expressed in the normal nasopharyngeal epithelial cells. A marked reduction of ERBB1 and ERBB2 expression in NPC was observed compared with the non-cancerous tissues. 76 of 82 (92.7%) cases were ERBB3-positive, while ERBB4 was not expressed in both normal and NPC. The univariate log-rank analysis showed that regional lymph node metastasis, systemic metastasis, recurrence and ERBB3 expression were associated with patient survival. The ERBB3 expression was not correlated to other clinicopathological factors. Furthermore, multivariate analysis revealed that ERBB3 expression was an independent prognostic factor influencing patient survival.

Conclusions

Our results suggested that the expression of ERBB3 is associated with patient survival and could serve as a novel and valuable predictor for prognostic evaluation of patients with NPC.
Flexural ductility of reinforced concrete beams with lap-spliced bars
Authors: Rakhshanimehr Mehrollah , Esfahani M. Reza , Kianoush M. Reza , Mohammadzadeh B. Ali , Mousavi S. Roohollah
Published: May 2014

In this paper, the flexural ductility of lap-spliced reinforced concrete (RC) beams is experimentally investigated. Twenty-four specimens were designed and manufactured for laboratory experiments. Concrete compressive strength, amount of transverse reinforcement over the splice length, and the diameter of longitudinal bars were selected as the main variables. The ductility of tested specimens is evaluated based on a previously defined ductility ratio. Results show that concrete strength and amount of transverse reinforcement over the splice have major effects on ductility. With an appropriate amount of transverse reinforcement, a satisfactory ductility response for different concrete strengths can be obtained. The CSA-A23.3-04 Standard provisions on bond strength and ductility of lap-spliced RC beams are evaluated and discussed. This study shows that the provisions in predicting the bond strength of lap-spliced concrete beams are adequate but may not achieve a satisfactory performance for ductility. An equation is proposed to achieve the appropriate ductility.
Experimental Study on Impact-Induced Damage Detection Using an Improved Extended Kalman Filter
Authors: Lei Ying , Lai Zhilu , Zhu Songye , Zhang Xiao-Hua
Published: May 2014

This paper presents an experimental study on using an improved extended Kalman filter (EKF) to identify impact-induced structural damage. By introducing the optimization of estimated residual error into the classical EKF, this real-time approach demonstrates an excellent capability to identify the abrupt changes of structural parameters instantly and accurately. The optimization procedure is activated when a prescribed threshold is exceeded. A shaking table test of a three-story steel frame subjected to abrupt damage induced by impact load was conducted to validate the improved EKF approach. The results clearly reveal its improved performance and good anti-noise ability in identifying time-variant structural parameters.
Wireless Sensor Placement for Bridge Health Monitoring Using a Generalized Genetic Algorithm
Authors: Zhou Guang-Dong , Yi Ting-Hua , Li Hong-Nan
Published: May 2014

The optimal placement of wireless sensors is very different from conventional wired sensor placement due to the limited transmission range of the wireless sensors. This constraint on the inter-sensor distance makes the optimization problem difficult to solve with conventional gradient-based methods. In this paper, an improved generalized genetic algorithm (GGA) based on a self-adaptive dynamic penalty function (SADPF) is proposed for the optimal wireless sensor placement (OWSP) in bridge vibration monitoring. The mathematical model of the OWSP problem is established, and it considers both the bridge vibration monitoring requirements and the constraints of the data transmission range in wireless sensor networks (WSNs). SADPF, which can automatically adjust the amount of penalization for constraint violations according to the evolution generation number and the degree of violation, is then developed so that the wireless sensor placement can be optimized using GGA. Subsequently, the GGA is improved by implementing an elite conservation strategy, a worst elimination policy and a dual-structure coding system. Finally, a numerical experiment is presented with a long-span suspension bridge to demonstrate the feasibility and efficiency of the proposed method, and some indispensible discussions are also given. The results indicate that the wireless sensor configurations that are optimized by the improved SADPF-based GGA can simultaneously meet the data transmission demands in a WSN and fulfill the requirements for structural condition assessment. The developed SADPF can minimize the influence of the limited data transmission range on the search process for the OWSP. The improved SADPF-based GGA quickly and robustly converges to the global optimal solution.
Sensor Placement Optimization in Structural Health Monitoring Using Niching Monkey Algorithm
Authors: Yi Ting-Hua , Li Hong-Nan , Gu Ming , Zhang Xu-Dong
Published: May 2014

Optimal sensor placement (OSP) method plays a key role in setting up a health monitoring system for large-scale structures. This paper describes the implementation of monkey algorithm (MA) as a strategy for the optimal placement of a predefined number of sensors. To effectively maintain the population diversity while enhancing the exploitation capacities during the optimization process, a novel niching monkey algorithm (NMA) by combining the MA with the niching techniques is developed in this paper. In the NMA, the dual-structure coding method is adopted to code the design variables and a chaos-based approach instead of a pure random initialization is employed to initialize the monkey population. Meanwhile, the niche generation operation and fitness sharing mechanism are modified and incorporated to alleviate the premature convergence problem while enhancing the exploration of new search domain. In addition, to promote interactions and share the available resources, the replacement scheme is proposed and adopted among the niches. Finally, numerical experiments are conducted on a high-rise structure to evaluate the performance of the proposed NMA. It is found that the innovations in the proposed NMA can effectively improve the convergence of algorithm and generate superior sensor configurations when compared to the original MA.
An Intermittent Poisson Process Generating 1/f Noise with Possible Application to Fluorescence Intermittency
Authors: Grüneis Ferdinand
Published: May 2014

Quantum dots (QD) and other nanoparticles exhibit fluorescence intermittency switching irregularly between bright ("on") and dark ("off") states. On- and off-times follow a power-law statistics with exponents ranging from -1 to -2. The empirical power spectral density of this two-state process shows a 1/fx shape with an exponent x reverting from ≈1 at low frequencies to ≈2 at high frequency. Based on theoretical considerations, the low frequency region can be attributed to the on-state; however, there are some discrepancies in attributing the off-states to the high frequency region. This difficulty can be overcome by introducing a Poisson process which is gated by the two-state process giving rise to an intermittent Poisson process (IPP); in this way, the statistical features of the two-state process are transferred to the IPP. The power spectral density of the IPP can be derived in closed form for arbitrarily distributed on/off-states. Besides shot noise the power spectrum of the IPP exhibits excess noise with two scaling regions which can be attributed to the respective on/off-states. The results are applied to interpret the power spectrum of fluorescence intermittency in QDs.
Applying Agile Project Management to Predevelopment Stages of Innovation
Authors: Gonzalez Winston
Published: May 2014

This study explores the early stages of innovation: the predevelopment stages leading to development. The paper examines the agile project management approach as a flexible and dynamic approach to manage the predevelopment stages of innovation. Scholarly sources reveal insufficient findings, signaling a gap in the literature in the areas of fuzzy front end of innovations and the applicability of modern approaches such as the agile project management approach. As a result, this paper introduces a theoretical model, advancing concepts on agile project management, management innovation, and how these concepts can be applied to the predevelopment stages of innovation.
Application Path for Promoting Technology Commercialization
Authors: Kato Kensuke , Miyazaki Kumiko
Published: May 2014

Even though candidate applications of emerging technologies cover a broad field of markets, new businesses do not progress as expected at all. Commercialization faces several deadlocks during the process. In this study, setting application paths for emerging technologies to overcome deadlocks is examined. In order to analyze it, a "shotgun approach" is proposed as a methodology and applied to the cases of DMFC and fluid MEMS. Based on the analyses, it has been shown that establishing "paths to create a final market" is significant not only for overcoming deadlocks but also for accumulating knowledge, and building technology competences.
Effect of neodymium doping on structural, microscopic and electrical properties of barium phosphate system
Authors: Suri Shivani , Singh Vishal , Bamzai K. K.
Published: May 2014

Neodymium-doped barium phosphate (NdBP) was prepared as single crystal by room temperature solution technique known as gel encapsulation technique. Single crystal X-ray diffraction shows that the crystal belongs to orthorhombic system. The flower type morphology was observed by scanning electron microscope (SEM) and the stoichiometric composition of the prepared crystal was observed by energy dispersive X-ray analysis (EDAX). The presence of functional group and other groups was studied by Fourier transform infrared spectroscopy (FTIR). The electrical properties of these materials like dielectric constant (ε′), dielectric loss (tanδ) and ac conductivity [ln(σac)] was studied at different temperatures ranging from 40°C to 420°C in the frequency range of 5 kHz to 1 MHz. The activation energy values decreases with increase in frequency suggesting that the conduction mechanism is because of hopping of charge carriers.
Coastal products of marine transgression in cold-temperate and high-latitude coastal-plain settings: Gulf of St Lawrence and Beaufort Sea
Authors: Forbes D. L. , Manson G. K. , Whalen D. J. R. , Couture N. J. , Hill P. R.
Published: May 2014

Cold climate exerts a clear influence on the processes of marine transgression in mid- and high-latitude coastal-plain settings, but its signature in the depositional record is much clearer at high latitude. Both cases selected for this study are influenced by the legacy of past glaciation and the pervasive effects of ongoing Holocene marine transgression. Both are affected by sea ice. The high-latitude site lies within the zone of continuous permafrost and the abundance of excess ground ice along the Beaufort coast is the dominant factor distinguishing it from the mid-latitude Gulf of St Lawrence (GSL) setting and standard models of transgressive coasts elsewhere. In the southern GSL, the transgressive unconformity (TU) is at the seabed (or buried by a very thin veneer) across the inner shelf; shoreface sand moves landward, keeping pace with the transgressive front through deposition in barriers, dunes and estuaries. The pace of transgression in the Beaufort Sea is influenced by a number of distinctive periglacial erosion processes, including thermal abrasion and thaw subsidence. Marine transgression across this landscape creates intricate breached-lake estuaries and low sandy barrier beaches with limited dunes, leaving distinctive facies suites and geometry, while seaward sediment transport buries the TU on the inner shelf.
Megalandslides in the Andes of central Chile and Argentina (32°–34°S) and potential hazards
Authors: Moreiras Stella M. , Sepúlveda Sergio A.
Published: May 2014

This review deals with an integration and update of the knowledge about large-volume landslides in the Central Andes at 32–34°S. An integrated landslide inventory for megalandslides in central Chilean and Argentinean Andean basins was developed, and dispersed chronological data on palaeolandslides were compiled, showing a dominance of Late Pleistocene and Holocene ages. Traditional hypotheses adopted for explaining landslide occurrence in the Central Andes are contrasted. Whereas seismic tremors have been widely suggested as the main triggering mechanism in Chilean collapses, palaeoclimatic conditions are considered as the main cause of Argentinean giant landslides. These different approaches denote the lack of multidisciplinary studies focused on the controversy about seismic or climate trigger mechanisms in the Central Andes. These studies are also essential to understand failure mechanisms and assessment of the related hazard and risk, which are essential to reduce social and economic impacts on vulnerable communities from future landslide events.
Mitochondrial respiration and microRNA expression in right and left atrium of patients with atrial fibrillation
Authors: Slagsvold Katrine Hordnes , Johnsen Anne Berit , Rognmo Øivind , Høydal Morten Andre , Wisløff Ulrik , Wahba Alexander
Published: May 2014

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a potential to cause serious complications. Mitochondria play central roles in cardiomyocyte function and have been implicated in AF pathophysiology. MicroRNA (miR) are suggested to influence both mitochondrial function and the development of AF. Yet mitochondrial function and miR expression remain largely unexplored in human atrial tissue. This study aims to investigate mitochondrial function and miR expression in the right (RA) and left atria (LA) of patients with AF and sinus rhythm (SR). Myocardial tissue from the RA and LA appendages was investigated in 37 patients with AF ( n = 21) or SR ( n = 16) undergoing coronary artery bypass surgery and/or heart valve surgery. Mitochondrial respiration was measured in situ after tissue permeabilization by saponin. MiR expression was assessed by miR array and real-time quantitative reverse-transcription polymerase chain reaction. Maximal mitochondrial respiratory rate was increased in both RA and LA tissue of patients with AF vs. SR. Biatrial downregulation of miR-208a and upregulation of miR-106b, -144, and -451 were observed in AF vs. SR. In addition, miR-15b was upregulated in AF within RA only, and miR-106a, -18a, -18b, -19a, -19b, -23a, -25, -30a, -363, -486-5p, -590-5p, and -93 were upregulated in AF within LA only. These findings suggest that mitochondrial function and miR are involved in AF pathophysiology and should be areas of focus in the exploration for potential novel therapeutic targets.
R270C polymorphism leads to loss of function of the canine P2X7 receptor
Authors: Spildrejorde Mari , Bartlett Rachael , Stokes Leanne , Jalilian Iman , Peranec Michelle , Sluyter Vanessa , Curtis Belinda L. , Skarratt Kristen K. , Skora Amanda , Bakhsh Tahani , Seavers Aine , McArthur Jason D. , Dowton Mark , Sluyter Ronald
Published: May 2014

The relative function of the P2X7 receptor, an ATP-gated ion channel, varies between humans due to polymorphisms in the P2RX7 gene. This study aimed to assess the functional impact of P2X7 variation in a random sample of the canine population. Blood and genomic DNA were obtained from 69 dogs selected as representatives of a cross section of different breeds. P2X7 function was determined by flow cytometric measurements of dye uptake and patch-clamp measurements of inward currents. P2X7 expression was determined by immunoblotting and immunocytochemistry. Sequencing was used to identify P2RX7 gene polymorphisms. P2X7 was cloned from an English springer spaniel, and point mutations were introduced into this receptor by site-directed mutagenesis. The relative function of P2X7 on monocytes varied between individual dogs. The canine P2RX7 gene encoded four missense polymorphisms: F103L and P452S, found in heterozygous and homozygous dosage, and R270C and R365Q, found only in heterozygous dosage. Moreover, R270C and R365Q were associated with the cocker spaniel and Labrador retriever, respectively. F103L, R270C, and R365Q but not P452S corresponded to decreased P2X7 function in monocytes but did not explain the majority of differences in P2X7 function between dogs, indicating that other factors contribute to this variability. Heterologous expression of site-directed mutants of P2X7 in human embryonic kidney-293 cells indicated that the R270C mutant was nonfunctional, the F103L and R365Q mutants had partly reduced function, and the P452S mutant functioned normally. Taken together, these data highlight that a R270C polymorphism has major functional impact on canine P2X7.
Discovery of Mesothelin and Exploiting It as a Target for Immunotherapy
Authors: Pastan Ira , Hassan Raffit
Published: May 2014

We have recently reported that an immunotoxin targeting mesothelin produced durable major tumor regressions in patients with extensive treatment-refractory mesothelioma. These unprecedented tumor responses have prompted us to review how mesothelin was discovered and the advances that led to these tumor responses. This review is not comprehensive but focuses on major developments over the past 20 years since mesothelin was first identified in our laboratory. Mesothelin is a cell-surface glycoprotein whose expression in normal human tissues is restricted to mesothelial cells. Because it is highly expressed by many solid tumors, it is an attractive immunotherapy target. Antibody-based therapies currently in clinical trials include an immunotoxin, a chimeric monoclonal antibody, and an antibody drug conjugate. In addition, a mesothelin tumor vaccine and a mesothelin- chimeric antigen receptor are being evaluated in the clinic. SS1P, an anti-mesothelin immunotoxin, was the first mesothelin-directed therapy to enter the clinic, and its use showed that mesothelin-targeted therapy was safe in patients. More importantly, our recent work has shown that SS1P in combination with pentostatin and cyclophosphamide can result in durable tumor regression in patients with advanced mesothelioma and opens up the possibility that such an approach can benefit patients with many common cancers. Cancer Res; 74(11); 2907–12. ©2014 AACR.
Phosphoproteomics of MAPK Inhibition in BRAF-Mutated Cells and a Role for the Lethal Synergism of Dual BRAF and CK2 Inhibition
Authors: Parker Robert , Clifton-Bligh Roderick , Molloy Mark P.
Published: May 2014

Activating mutations in the MAPK pathway are prevalent drivers of several cancers. The chief consequence of these mutations is a hyperactive ERK1/2 MAPK able to promote cell proliferation, producing a critical hallmark of metastatic disease. The biochemistry of the ERK pathway is well characterized; however, how the pathway achieves different outcomes in the face of genetic aberrations of cancer and subsequent treatment with chemical inhibitors is not clear. To investigate this, we used mass spectrometry to complete a global phosphoproteomic analysis of a BRAFV600E thyroid cancer cell line (SW1736) after treatment with the mutation-selective inhibitor vemurafenib (PLX4032) and MEK1/2 inhibitor selumetinib (AZD6244). We identified thousands of phosphorylation events orchestrated in BRAFV600E cells and performed kinase landscape analysis to identify putative kinases regulated in response to MAPK blockade. The abundance of phosphopeptides containing consensus motifs for acidophilic kinases increased after short-term inhibition with these compounds. We showed that coinhibition of the pleiotropic acidophilic protein kinase CK2 (CK2) and BRAFV600E synergistically reduced proliferation in patient-derived melanomas and thyroid cancer cells harboring the BRAF lesion. We investigated this mechanism and show a role for CK2 in controlling AKT activation that was not reliant on changes to PTEN or PDK1 phosphorylation. These findings highlight a role for CK2 blockade in potentiating the antiproliferative effects of BRAF and MEK inhibition in BRAF cancers. Mol Cancer Ther; 13(7); 1894–906. ©2014 AACR.
Combination of Conventional Chemotherapeutics with Redox-Active Cerium Oxide Nanoparticles—A Novel Aspect in Cancer Therapy
Authors: Sack Maren , Alili Lirija , Karaman Elif , Das Soumen , Gupta Ankur , Seal Sudipta , Brenneisen Peter
Published: May 2014

Nanotechnology is becoming an important field of biomedical and clinical research and the application of nanoparticles in disease may offer promising advances in treatment of many diseases, especially cancer. Malignant melanoma is one of the most aggressive forms of cancer and its incidence is rapidly increasing. Redox-active cerium oxide nanoparticles (CNP) are known to exhibit significant antitumor activity in cells derived from human skin tumors in vitro and in vivo, whereas CNP is nontoxic and beyond that even protective (antioxidative) in normal, healthy cells of the skin. As the application of conventional chemotherapeutics is associated with harmful side effects on healthy cells and tissues, the clinical use is restricted. In this study, we addressed the question of whether CNP supplement a classical chemotherapy, thereby enhancing its efficiency without additional damage to normal cells. The anthracycline doxorubicin, one of the most effective cancer drugs, was chosen as reference for a classical chemotherapeutic agent in this study. Herein, we show that CNP enhance the antitumor activity of doxorubicin in human melanoma cells. Synergistic effects on cytotoxicity, reactive oxygen species generation, and oxidative damage in tumor cells were observed after co-incubation. In contrast to doxorubicin, CNP do not cause DNA damage and even protect human dermal fibroblasts from doxorubicin-induced cytotoxicity. A combination of classical chemotherapeutics with nongenotoxic but antitumor active CNP may provide a new strategy against cancer by improving therapeutic outcome and benefit for patients. Mol Cancer Ther; 13(7); 1740–9. ©2014 AACR.
Anti-miR182 Reduces Ovarian Cancer Burden, Invasion, and Metastasis: An In Vivo Study in Orthotopic Xenografts of Nude Mice
Authors: Xu Xiaofei , Ayub Bushra , Liu Zhaojian , Serna Vanida Ann , Qiang Wenan , Liu Yugang , Hernando Eva , Zabludoff Sonya , Kurita Takeshi , Kong Beihua , Wei Jian-Jun
Published: May 2014

High-grade serous ovarian carcinoma (HGSOC) is a fatal disease, and its grave outcome is largely because of widespread metastasis at the time of diagnosis. Current chemotherapies reduce tumor burden, but they do not provide long-term benefits for patients with cancer. The aggressive tumor growth and metastatic behavior characteristic of these tumors demand novel treatment options such as anti-microRNA treatment, which is emerging as a potential modality for cancer therapy. MicroRNA-182 (miR182) overexpression contributes to aggressive ovarian cancer, largely by its negative regulation of multiple tumor suppressor genes involved in tumor growth, invasion, metastasis, and DNA instability. In this study, we examined the therapeutic potential of anti-miR182 utilizing the animal orthotopic model to mimic human ovarian cancer using ovarian cancer cells SKOV3 (intrabursal xenografts) and OVCAR3 (intraperitoneal injection). These models provide a valuable model system for the investigation of ovarian cancer therapy in vivo. Through a combination of imaging, histological, and molecular analyses, we found that anti-miR182 treatment can significantly reduce tumor burden (size), local invasion, and distant metastasis compared with its control in both models. The bases of anti-miR182 treatment are mainly through the restoration of miR182 target expression, including but not limited to BRCA1, FOXO3a, HMGA2, and MTSS1. Overall, our results strongly suggest that anti-miR182 can potentially be used as a therapeutic modality in treating HGSOC. Mol Cancer Ther; 13(7); 1729–39. ©2014 AACR.