bluuebunny/crossref_metadata_2025 huggingface dataset:
SYK inhibition and response prediction in diffuse large B-cell lymphoma
Authors: Cheng Shuhua , Coffey Greg , Zhang X. Hannah , Shaknovich Rita , Song Zibo , Lu Pin , Pandey Anjali , Melnick Ari M. , Sinha Uma , Wang Y. Lynn
Published: October 2011

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and the role of SYK in its pathogenesis is not completely understood. Using tissue microarray, we demonstrated for the first time that SYK protein is activated in 27 of 61 (44%) primary human DLBCL tissues. Among DLBCL cell lines, 7 were sensitive and 3 were resistant to a highly specific SYK inhibitor, PRT060318. In sensitive DLBCL cells, SYK inhibition blocked the G1-S transition and caused cell-cycle arrest. This effect was reproduced by genetic reduction of SYK using siRNA. A detailed analysis of the BCR signaling pathways revealed that the consequence of SYK inhibition on PLCγ2 and AKT, as opposed to ERK1/2, was responsible for cell-cycle arrest. Genetic knock-down of these key molecules decelerated the proliferation of lymphoma cells. In addition, BCR signaling can be blocked by PRT060318 in primary lymphoma cells. Together, these findings provide insights into cellular pathways required for lymphoma cell growth and support the rationale for considering SYK inhibition as a potentially useful therapy for DLBCL. The results further suggest the possibility of using PLCγ2 and AKT as biomarkers to predict therapeutic response in prospective clinical trials of specific SYK inhibitors.
Improving accuracy of protein-protein interaction prediction by considering the converse problem for sequence representation
Authors: Ren Xianwen , Wang Yong-Cui , Wang Yong , Zhang Xiang-Sun , Deng Nai-Yang
Published: October 2011

Background

With the development of genome-sequencing technologies, protein sequences are readily obtained by translating the measured mRNAs. Therefore predicting protein-protein interactions from the sequences is of great demand. The reason lies in the fact that identifying protein-protein interactions is becoming a bottleneck for eventually understanding the functions of proteins, especially for those organisms barely characterized. Although a few methods have been proposed, the converse problem, if the features used extract sufficient and unbiased information from protein sequences, is almost untouched.

Results

In this study, we interrogate this problem theoretically by an optimization scheme. Motivated by the theoretical investigation, we find novel encoding methods for both protein sequences and protein pairs. Our new methods exploit sufficiently the information of protein sequences and reduce artificial bias and computational cost. Thus, it significantly outperforms the available methods regarding sensitivity, specificity, precision, and recall with cross-validation evaluation and reaches ~80% and ~90% accuracy in Escherichia coli and Saccharomyces cerevisiae respectively. Our findings here hold important implication for other sequence-based prediction tasks because representation of biological sequence is always the first step in computational biology.

Conclusions

By considering the converse problem, we propose new representation methods for both protein sequences and protein pairs. The results show that our method significantly improves the accuracy of protein-protein interaction predictions.
In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling
Authors: Becker John VW , van der Merwe Marina M , van Brummelen Anna C , Pillay Pamisha , Crampton Bridget G , Mmutlane Edwin M , Parkinson Chris , van Heerden Fanie R , Crouch Neil R , Smith Peter J , Mancama Dalu T , Maharaj Vinesh J
Published: October 2011

Background

Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile.

Methods

Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis.

Results

The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that were differentially expressed as a result of the treatment and gene ontology analysis identified various biological processes and molecular functions that were significantly affected. Comparison of the dehydrobrachylaenolide treatment transcriptional dataset with a published artesunate (also a sesquiterpene lactone) dataset revealed little overlap. These results strengthen the notion that the isolated compound and the artemisinins have differentiated modes of action.

Conclusions

The novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts.
Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease
Authors: Takahashi Kei , Oharaseki Toshiaki , Nagao Tomokazu , Yokouchi Yuki , Yamada Hitomi , Nagi-Miura Noriko , Ohno Naohito , Saji Tsutomu , Okazaki Tomio , Suzuki Kazuo
Published: October 2011

Background

Intravenous immunoglobulin (IVIg) treatment results in an effective response from patients with acute-phase Kawasaki disease (KD), but 16.5% of them remain nonresponsive to IVIg. To address this therapeutic challenge, we tried a new therapeutic drug, mizoribine (MZR), in a mouse model of KD, which we have established using injections ofCandida albicanswater-soluble fractions (CAWS).

Methods

CAWS (4 mg/mouse) were injected intraperitoneally into C57BL/6N mice for 5 consecutive days. MZR or IgG was administered for 5 days. After 4 weeks, the mice were sacrificed and autopsied, the hearts were fixed in 10% neutral formalin, and plasma was taken to measure cytokines and chemokines using the Bio-Plex system.

The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α, TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.

Results

The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.

Conclusion

MZR treatment suppressed not only the incidence, range, and degree of vasculitis, but also inflammatory cytokines and chemokines in the plasma of the KD vasculitis model mice, suggesting that MZR may be useful for treatment of KD.
SIR distribution analysis in cellular networks considering the joint impact of path-loss, shadowing and fast fading
Authors: Ben Cheikh Dorra , Kelif Jean-Marc , Coupechoux Marceau , Godlewski Philippe
Published: October 2011

In this paper, we propose an analysis of the joint impact of path-loss, shadowing and fast fading on cellular networks. Two analytical methods are developed to express the outage probability. The first one based on the Fenton-Wilkinson approach, approximates a sum of log-normal random variables by a log-normal random variable and approximates fast fading coefficients in interference terms by their average value. We denote it FWBM for Fenton-Wilkinson based method. The second one is based on the central limit theorem for causal functions. It allows to approximate a sum of positive random variables by a Gamma distribution. We denote it CLCFM for central limit theorem for causal functions method. Each method allows to establish a simple and easily computable outage probability formula, which jointly takes into account path-loss, shadowing and fast fading. We compute the outage probability, for mobile stations located at any distance from their serving BS, by using a fluid model network that considers the cellular network as a continuum of BS. We validate our approach by comparing all results to extensive Monte Carlo simulations performed in a traditional hexagonal network and we provide the limits of the two methods in terms of system parameters. The proposed framework is a powerful tool to study performances of cellular networks, e.g., OFDMA systems (WiMAX, LTE).
Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection
Authors: Branco Luis M , Grove Jessica N , Boisen Matt L , Shaffer Jeffrey G , Goba Augustine , Fullah Mohammed , Momoh Mambu , Grant Donald S , Garry Robert F
Published: October 2011

Background

Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF.

Results

Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa.

Conclusion

Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF.
Not all transmembrane helices are born equal: Towards the extension of the sequence homology concept to membrane proteins
Authors: Wong Wing-Cheong , Maurer-Stroh Sebastian , Eisenhaber Frank
Published: October 2011

Background

Sequence homology considerations widely used to transfer functional annotation to uncharacterized protein sequences require special precautions in the case of non-globular sequence segments including membrane-spanning stretches composed of non-polar residues. Simple, quantitative criteria are desirable for identifying transmembrane helices (TMs) that must be included into or should be excluded from start sequence segments in similarity searches aimed at finding distant homologues.

Results

We found that there are two types of TMs in membrane-associated proteins. On the one hand, there are so-called simple TMs with elevated hydrophobicity, low sequence complexity and extraordinary enrichment in long aliphatic residues. They merely serve as membrane-anchoring device. In contrast, so-called complex TMs have lower hydrophobicity, higher sequence complexity and some functional residues. These TMs have additional roles besides membrane anchoring such as intra-membrane complex formation, ligand binding or a catalytic role. Simple and complex TMs can occur both in single- and multi-membrane-spanning proteins essentially in any type of topology. Whereas simple TMs have the potential to confuse searches for sequence homologues and to generate unrelated hits with seemingly convincing statistical significance, complex TMs contain essential evolutionary information.

Conclusion

For extending the homology concept onto membrane proteins, we provide a necessary quantitative criterion to distinguish simple TMs (and a sufficient criterion for complex TMs) in query sequences prior to their usage in homology searches based on assessment of hydrophobicity and sequence complexity of the TM sequence segments.

Reviewers

This article was reviewed by Shamil Sunyaev, L. Aravind and Arcady Mushegian.
Reduction of surgical site infection using a novel intervention (ROSSINI): study protocol for a randomised controlled trial
Authors: Pinkney Thomas D , Bartlett David C , Hawkins William , Mak Tony , Youssef Haney , Futaba Kaori , Harrison Gareth , Gheorghe Adrian , Bradbury Jennifer M , Calvert Melanie J , Dowswell George , Magill Laura , Redman Val , Wilson Sue , Leaper David , Morton Dion G ,   the West Midlands Research Collaborative
Published: October 2011

Background

Surgical site infection (SSI) is a common complication following abdominal surgery. It is associated with considerable morbidity and mortality, and its management results in significant cost to health services within both primary and secondary care. Some surgeons believe that the use of a wound-edge protection device may reduce the incidence of SSI. Whilst there is some encouraging evidence showing that such devices may lead to a reduction in SSI, there are no controlled trials of sufficient size or quality to support their routine use.

Methods/Design

750 patients will be recruited from around 20 surgical units within the United Kingdom. Patients undergoing laparotomy through any major abdominal incision for any indication, elective or emergency, are eligible. Patients under the age of 18, those undergoing a laparoscopic assisted procedure or who have undergone laparotomy within the previous 3 months, and those who are unable to give informed consent will be excluded. Patients will be randomised (1:1 ratio) to the use of a wound-edge protection device or no wound-edge protection device during surgery.

Follow up will consist of blinded clinical wound reviews at 5-7 days and 30-33 days postoperatively with a self-completed questionnaire covering the intervening period. Quality of life questionnaires will be completed prior to surgery and at the subsequent wound review points and information on resource usage will also be captured.

The primary outcome measure is SSI within 30 days of surgery. Secondary outcomes include the impact of the degree of wound contamination, patient comorbidity, and operative characteristics on the efficacy of a wound-edge protection device in reducing SSI and whether the use of a wound-edge protection device has an effect on health-related quality of life or length of hospital stay and is cost-effective.

Discussion

Rossini is the first multicentre observer-blinded randomised controlled trial of sufficient size and quality to establish whether the use of a wound-edge protection device in adult patients undergoing abdominal surgery leads to a lower rate of SSI. The results of this study will be used to inform current surgical practice and may potentially benefit patients undergoing surgery in the future.

Trial registration number

Current Controlled Trials ISRCTN: ISRCTN40402832
The spatiotemporal development of adipose tissue
Authors: Han Jinah , Lee Jung-Eun , Jin Jongho , Lim Joon Seo , Oh Nuri , Kim Kyuho , Chang Soo-Il , Shibuya Masabumi , Kim Honsoul , Koh Gou Young
Published: October 2011

Adipose tissue is a structure highly specialized in energy storage. The adipocyte is the parenchymal component of adipose tissue and is known to be mesoderm or neuroectoderm in origin; however, adipocyte development remains poorly understood. Here, we investigated the development of adipose tissue by analyzing postnatal epididymal adipose tissue (EAT) in mouse. EAT was found to be generated from non-adipose structure during the first 14 postnatal days. From postnatal day 1 (P1) to P4, EAT is composed of multipotent progenitor cells that lack adipogenic differentiation capacity in vitro, and can be regarded as being in the ‘undetermined’ state. However, the progenitor cells isolated from P4 EAT obtain their adipogenic differentiation capacity by physical interaction generated by cell-to-matrix and cell-to-cell contact both in vitro and in vivo. In addition, we show that impaired angiogenesis caused by either VEGFA blockade or macrophage depletion in postnatal mice interferes with adipose tissue development. We conclude that appropriate interaction between the cellular and matrix components along with proper angiogenesis are mandatory for the development of adipose tissue.
Mnemonomics: The Sunk Cost Fallacy as a Memory Kludge
Authors: Baliga Sandeep , Ely Jeffrey C
Published: October 2011

We offer a theory of the sunk cost fallacy as an optimal response to limited memory. As new information arrives, a decision-maker may not remember all the reasons he began a project. The sunk cost gives additional information about future profits and informs subsequent decisions. The Concorde effect makes the investor more eager to complete projects when sunk costs are high and the pro-rata effect makes the investor less eager. In a controlled experiment we had subjects play a simple version of the model. In a baseline treatment subjects exhibit the pro-rata bias. When we induce memory constraints the effect reverses and the subjects exhibit the Concorde bias. (JEL D24, D83, G31)
Did Bankruptcy Reform Cause Mortgage Defaults to Rise?
Authors: Li Wenli , White Michelle J , Zhu Ning
Published: October 2011

Homeowners in financial distress can use bankruptcy to avoid defaulting on their mortgages, since filing loosens their budget constraints. But the 2005 bankruptcy reform made bankruptcy less favorable to homeowners and therefore caused mortgage defaults to rise. We test this relationship and find that the reform caused prime and subprime mortgage default rates to rise by 23% and 14%, respectively. Default rates rose even more for homeowners who were particularly negatively affected by the reform. We calculate that bankruptcy reform caused mortgage default rates to rise by one percentage point even before the start of the financial crisis. (JEL D14, G01, G21, K35)
Do genome-wide association scans have potential for translation?
Authors: Lopes Margarida C. , Zeggini Eleftheria , Panoutsopoulou Kalliope
Published: October 2011

The success of genome-wide association studies (GWAS) in identifying replicating associations has greatly contributed to understanding of the genetic aetiology of complex diseases. This review discusses and provides examples of the potential of GWAS findings to be translated into clinical practice, i.e., diagnosis, prediction, prognosis, novel treatments and response to treatment of common diseases. The biological insights afforded by newly-identified robust associations represent the largest, albeit indirect, translational contribution of GWAS.
Heart type fatty acid binding protein in relation to pharmacologic scintigraphy in coronary artery disease
Authors: Sbarouni Eftihia , Georgiadou Panagiota , Koutelou Maria , Constantinos Mihas , Chaidaroglou Antigoni , Degiannis Demitris , Voudris Vassilis
Published: October 2011

Heart-type fatty acid-binding protein (H-FABP) is a marker of myocardial necrosis, but whether it increases during myocardial ischemia is not known. This study investigated whether serum levels of H-FABP change during adenosine stress testing and nuclear imaging in patients with stable coronary artery disease.

Thirty stable patients with established coronary artery disease on their medications were studied. Sampling was performed before the stress test, at the end of adenosine infusion, as well as 1, 2 and 3 h after the completion of the infusion.

No difference in H-FABP serum levels were found at the five pre-specified time points in the overall group (p=0.99); furthermore, there was no significant difference regardless of the test result – positive (p=1) or negative (p=0.98).

It is concluded that H-FABP does not change significantly during pharmacologic stress testing in patients with known coronary artery disease and there is no difference whether there is inducible ischemia or not.
Evaluation of nucleated red blood cells in the peripheral blood of hematological diseases
Authors: Danise Paolo , Maconi Mariacaterina , Barrella Fabio , Di Palma Anna , Avino Daniela , Rovetti Adele , Gioia Maria , Amendola Giovanni
Published: October 2011

Nucleated red blood cells (NRBCs) are present in the peripheral blood of several hematological and non-hematological conditions, usually associated with bad prognosis. The lack of an easy, rapid and reliable NRBCs count method did no’t allow one to know the incidence of NRBCs and to quantify them: the count was usually done during the microscopic revision of a blood smear; this is the reason we found few studies on NRBCs automated count in the literature. The aim of this study was the evaluation of the presence and the quantification of NRBCs in some onco-hematological disorders.

This study analyzed 478 patients with the automated hematology analyzer Sysmex XE2100. The range of NRBCs were calculated in the peripheral blood at diagnosis, at hematological remission and during therapy.

NRBCs are present in the peripheral blood of a high number of hematological diseases and are related to ineffective erythropoiesis or stress erythropoiesis or primary alterations of hematopoiesis. NRBCs were found in nearly all onco-hematological diseases at diagnosis, but not in all patients. NRBCs were frequently found during chemotherapy and absent at remission.

To the authors’ knowledge, this is the first study that gives a range for NRBCs count in the peripheral blood of these diseases.
Funktionale Kategorien in der PP und deren Zweitspracherwerb
Authors: Gutzmann Daniel , Turgay Katharina
Published: October 2011

The prepositional phrase (PP) in German has complex morpho-syntactic properties and therefore constitutes a challenge for children both in first and in second language acquisition. The prototypical German PP is headed by a preposition selecting for a determiner phrase (DP). Beside using a determiner and correctly marking the morpho-syntactic features inside the DP, the children have to learn that there is a prepositional element that is the head of the PP. Since the structure of the PP can be divided further into functional projections for local and directional PPs, there are at least three functional elements for the children to be learned. We conducted an empirical study with 40 Turkish speaking primary school children in L2 acquisition together with two control groups of children in L1 acquisition to examine how the functional categories inside the PP are acquired and whether their acquisition concurs to the hierarchical ordering and acquisition pattern attested for the first language acquisition of German, or whether a transfer from their L1 can be observed. Our data shows similarities to the attested acquisition order, at least to its later stages, but does not concur to the hierarchical ordering since local PPs seem to be acquired later than directional ones even if the latter are ordered higher in the phrasal hierarchy. Furthermore, we observe no transfer from the subjects' L1 regarding the linearization of the preposition, even though Turkish PPs are head final.
Natural History of Infantile GM2 Gangliosidosis
Authors: Bley Annette E. , Giannikopoulos Ourania A. , Hayden Doug , Kubilus Kim , Tifft Cynthia J. , Eichler Florian S.
Published: October 2011

OBJECTIVE:

GM2 gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile GM2 gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature.

METHODS:

Patients with infantile GM2 gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature.

RESULTS:

Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival.

CONCLUSIONS:

We studied the timing of regression in 97 cases of infantile GM2 gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions.
Combination Antibiotic Therapy for Empiric and Definitive Treatment of Gram‐Negative Infections: Insights from the Society of Infectious Diseases Pharmacists
Authors: Boyd Natalie , Nailor Michael D.
Published: October 2011

The widespread emergence of antibiotic‐resistant gram‐negative organisms has compromised the utility of current treatment options for severe infections caused by these pathogens. The rate of gram‐negative multidrug resistance is worsening, threatening the effectiveness of newer broad‐spectrum antibiotic agents. Infections associated with multidrug‐resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae are having a substantial impact on hospital costs and mortality rates. The potential for these resistant gram‐negative nosocomial pathogens must always be a primary consideration when selecting antibiotic therapy for critically ill patients. Empiric combination therapy directed at gram‐negative pathogens is a logical approach for patients with suspected health care‐associated infections, particularly those with risk factors for infections caused by multidrug‐resistant pathogens. Although in vitro synergy tests have shown potential benefits of continued combination therapy, convincing clinical data that demonstrate a need for combination therapy once susceptibilities are known are lacking. Thus, deescalation to a single agent once susceptibilities are known is recommended for most patients and pathogens. Use of polymyxins, often in combination with other antimicrobials, may be necessary for salvage therapy.
Novel simulation-based algorithms for optimal open-loop and closed-loop scheduling of deficit irrigation systems
Authors: Schütze N. , de Paly M. , Shamir U.
Published: October 2011

The scarcity of water compared with the abundance of land constitutes the main drawback within agricultural production. Besides the improvement of irrigation techniques a task of primary importance is solving the problem of intra-seasonal irrigation scheduling under limited seasonal water supply. An efficient scheduling algorithm has to take into account the crops' response to water stress at different stages throughout the growing season. Furthermore, for large-scale planning tools compact presentations of the relationship between irrigation practices and grain yield, such as crop water production functions, are often used which also rely on an optimal scheduling of the considered irrigation systems. In this study, two new optimization algorithms for single-crop intra-seasonal scheduling of deficit irrigation systems are introduced which are able to operate with general crop growth simulation models. First, a tailored evolutionary optimization technique (EA) searches for optimal schedules over a whole growing season within an open-loop optimization framework. Second, a neuro-dynamic programming technique (NDP) is used for determining optimal irrigation policy. In this paper, different management schemes are considered and crop-yield functions generated with both the EA and the NDP optimization algorithms compared.
Temporal and spatial characteristics of precipitation and droughts in the upper reaches of the Yangtze river basin (China) in recent five decades
Authors: Zhang Nan , Xia Ziqiang , Zhang Shaofeng , Jiang Hong
Published: October 2011

Drought is one of the most harmful natural hazards in the Upper Reaches of the Yangtze River basin (URYR) in the mid-west part of China. Alterations in precipitation will affect the severity of drought. The nonparametric Mann–Kendall (MK) test was used in this paper to examine the trend of precipitation and the standardized precipitation index (SPI) was adopted to analyze the spatial–temporal variations of meteorological drought over different time scales in the last 50 years. The MK test value of precipitation indicated that, for most of the URYR showed an increasing trend of precipitation in the months of January, February, March and June, mainly in the Min-Tuojiang, Jialingjiang and Wujiang sub-basins and a decreasing trend was observed in August to December. The most obvious decreasing trend of precipitation occurred in the Jialingjiang, upper mainstream and Wujiang sub-basins in September, with a rate ranging from –7.89mm/10 years to –39.36mm/10 years. The results show that the SPI is applicable in the URYR basin. The number of severe droughts differed among the six sub-basins, i.e., a more obvious 3-month drought takes place in the middle of the upper mainstream, Wujiang sub-basins and the southeast of Jialingjiang sub-basin and other droughts in 6, 9 and 12 month timescales have the same effect in these three sub-basins. The outcomes of the paper could provide references for droughts mitigation, local water resources management and agriculture decision making.
Optimization study of a hybrid alum coagulation-membrane filtration system for virus removal
Authors: Guo H. , Hu J. Y.
Published: October 2011

Due to the intrinsically small sizes of enteric viruses (20–100 nm) and their relatively high resistance to most disinfectants, detection of viruses in treated drinking water is not a rare phenomenon. This study therefore evaluates various aspects involved in a hybrid alum coagulation-ultrafiltration (UF) system for virus removal. Coagulant doses (0, 1 and 10 mg Al3+/L) and pH conditions relevant to drinking water (pH 6–8) were investigated. With this hybrid system, removal was not attributable merely to MS2 adsorption to flocs and subsequent retention by UF membranes. MS2 removal comprises of inactivation by the effect of pH and coagulant and subsequently, rejection of virus-associated flocs by UF membrane. Coagulation with 1 mg Al3+/L at pH 6 and 7 resulted in an overall reduction brought about by an average of 0.62 log inactivation via the pH effect, 1.2 log inactivation by alum coagulant, and >5.4 log rejection by the 100 kDa polyethersulfone UF membrane. In contrast, negligible upstream inactivation was noted with a coagulant dose of 1 mg Al3+/L at pH 8, but 5.8 log rejection was attained with downstream UF filtration. By optimizing the conditions appropriate for upstream inactivation and subsequent membrane rejection, virus removal efficiencies can be enhanced.
Development of adsorbent for the simultaneous removal of organic and inorganic contaminants from aqueous solution
Authors: Choi J. W. , Chung S. G. , Hong S. W. , Kim D. J. , Lee S. H.
Published: October 2011

In this study, a modified adsorbent, alginate complex beads, was prepared and applied to the removal of mixed contaminants from wastewater. The alginate complex beads were generated by the immobilization of powdered activated carbon and synthetic zeolites onto alginate gel beads, which were then dried at 110 °C for 20 h until the diameter had been reduced to 1 mm. This dry technique increased the hardness of the adsorbent to assure its durability and application. The adsorption onto the alginate complex beads of organic and inorganic compounds, as target contaminants, was investigated by performing both equilibrium and kinetic batch experiments. From the adsorption isotherms, according to the Langmuir equation, the alginate complex bead was capable of effectively removing benzene, toluene, zinc and cadmium. From kinetic batch experiments, the removal efficiencies of benzene, toluene, zinc and cadmium were found to be 66.5, 92.4, 74.1 and 76.7%, respectively, for initial solution concentrations of 100 mg L−1. The results indicated that the adsorbent developed in this study has the potential to be a promising material for the removal of mixed pollutants from industrial wastewater or contaminated groundwater.
Mathematical modeling of heavy metals contamination from MSW landfill site in Khon Kaen, Thailand
Authors: Tantemsapya N. , Naksakul Y. , Wirojanagud W.
Published: October 2011

Kham Bon landfill site is one of many municipality waste disposal sites in Thailand which are in an unsanitary condition. The site has been receiving municipality wastes without separating hazardous waste since 1968. Heavy metals including, Pb, Cr and Cd are found in soil and groundwater around the site, posing a health risk to people living nearby. In this research, contamination transport modelling of Pb, Cr and Cd was simulated using MODFLOW for two periods, at the present (2010) and 20 years prediction (2030). Model results showed that heavy metals, especially Pb and Cr migrated toward the north-eastern and south-eastern direction. The 20 years prediction showed that, heavy metals tend to move from the top soil to the deeper aquifer. The migration would not exceed 500 m radius from the landfill centre in the next 20 years, which is considered to be a slow process. From the simulation model, it is recommended that a mitigation measure should be performed to reduce the risk from landfill contamination. Hazardous waste should be separated for proper management. Groundwater contamination in the aquifer should be closely monitored. Consumption of groundwater in a 500 m radius must be avoided. In addition, rehabilitation of the landfill site should be undertaken to prevent further mobilization of pollutants.
Characterization of the potential impact of retention tank emptying on wastewater primary treatment: a new element for CSO management
Authors: Maruejouls T. , Lessard P. , Wipliez B. , Pelletier G. , Vanrolleghem P. A.
Published: October 2011

Theoretical studies have shown that discharges from retention tanks could have a negative impact on the WWTP's (Wastewater Treatment Plant) effluent. Characterization of such discharges is necessary to better understand these impacts. This study aims at: (1) characterizing water quality during emptying of a tank; and (2) characterizing the temporal variation of settling velocities of the waters released to the WWTP. Two full-scale sampling campaigns (18 rain events) have been realized in Quebec City and laboratory analyses have shown a wide variability of total suspended solids (TSS) and Chemical Oxygen Demand (COD) concentrations in the water released from the tank. Suspended solids seem to settle quickly because they are only found in large amounts during the first 15 min of pumping to the WWTP. These solids are hypothesized to come from the pumping in which solids remained after a previous event. When these solids are evacuated, low TSS containing waters are pumped from the retention tank. A second concentration peak occurs at the end of the emptying period when the tank is cleaned with wash water. Finally, settling velocity studies allowed characterizing combined sewer wastewaters by separating three main fractions of pollutants which correspond to the beginning, middle and end of emptying. In most cases, it is noticed that particle settling velocities increase as the pollutant load increases.
Chicken Meat Rich in Selenium and Omega-3 Fatty Acids
Authors: Haug Anna , Christophersen Olav A. , Sogn Trine
Published: October 2011

The concentration of selenium (Se) in food is in many countries too low and the ratio between omega-6 and
omega-3 fatty acids too high implying more non-communicable diseases, e.g. cancer, cardiac disease, impaired immune
defense, pain, enhanced non-infectious inflammatory response. Meat from animals supplemented with Se and omega-3
fatty acids makes a good source of these nutrients in human nutrition. The worldwide demand for several nutrients is increasing,
and food with optimal composition is required. The objective of the present study was to produce chicken meat
especially high in Se and with a favorable ratio between omega-6 and omega-3 fatty acids. Sixty newly hatched chickens
were fed wheat-based diets containing 40 g rapeseed oil/kg, 10 g linseed oil/kg and varying amounts of selenium enriched
yeast for three weeks, resulting in meat with a favorable ratio between omega-6 and omega-3 fatty acids and with selenium
concentration ranging from 0.2 to 0.6 mg/kg. This meat would be expected to give health benefits both in prophylactic
and therapeutic contexts. It represents a better strategy for increasing the intake of Se and very long chain omega-3
fatty acids at a population basis rather than relying on Se supplements or only on fish resources that are already overexploited
and can not cover EPA and DHA requirements (for ensuring optimal health) for more than a fraction of the
world’s total population. The meat from the highest Se supplementation treatment groups might be useful for some groups
of patients (e.g. with ischemic pain) who might benefit from especially high Se intake.
Sample Size for a Binomial Proportion with Autocorrelation
Authors: Magaret Amalia S. , Stanaway Jeffrey
Published: October 2011

A flexible sample size computation is desired for a binomial outcome consisting of repeated binary measures with autocorrelation over time. This type of outcome is common in viral shedding studies, in which each individual's outcome is a proportion: the number of samples on which virus is detected out of number of samples assessed. Autocorrelation between proximal samples occurs in some conditions such as herpes infection, in which reactivation is episodic. We determine a sample size computation that accounts for: (1) participant-level differences in outcome frequency, (2) autocorrelation in time between samples, and (3) varying number of samples per participant. In addition, we develop a computation appropriate for crossover designs that accounts for the dependence of the investigational treatment effect on the pre-treatment detection frequency. The computations are validated through comparison with real and simulated data, and sensitivity to misspecification of parameter values is examined graphically.
Application of analytic hierarchy process in landscape management: Case study area Kosutnjak park-forest
Authors: Lakicevic Milena , Srdjevic Bojan
Published: October 2011

Proper management is one of key elements of the natural landscape protection
strategy. Park-forests with protected and conserved natural elements
represent attractive eco-tourism urban zones. Kosutnjak is the most visited
park-forest in Serbian capitol Belgrade, unfortunately with increasing number
of degraded and devastated areas as a consequence of negative human impacts
in the past. In order to conserve natural values in this popular forested
city area, and to improve its tourism potential, we found that in achieving
that goal, it is meaningful to asses possible management practices and
identify the most desired one by applying the analytic hierarchy process
(AHP), scientifically sound multi-criteria decision making tool. Based on the
obtained results, a recommended strategy is to renovate natural vegetation
and to promote recreational and tourism offer in Kosutnjak with respect of
the sustainability principle.
The role of rural population in agricultural development in the Pcinja district
Authors: Jovanovic Slavoljub , Zivkovic Ljiljana
Published: October 2011

Research results presented in this paper refer to changes in the structure of
the agricultural population of the Pcinja District in the period from 1971 to
2002. They point to markedly decrease in the agricultural population, the
share of agricultural population in total population, the share of rural
population in total population, as well as the share of active agricultural
population in total active population. The process of deagrarianization in
this area is a constraining factor for the development of agriculture and
causes spontaneous abandonment by working-age population who is employing in
other sectors. Transfer of agricultural population in non-agricultural
activities takes place either by moving into the city centre or by remaining
in agricultural households and employing in non-agricultural activities
(which causes daily rural-urban migration). The process of depopulation and
deruralization caused ageing population to be involved in agriculture in many
rural settlements so that the effects of agricultural production have become
significantly decreasing. To eliminate the negative effects of the regional
development of the Pcinja District, it is necessary to establish and
implement a functional demographic policy and concept of the revitalization
of rural area.
The new institutionalism and international relations: A step forward
Authors: Baker Rudy
Published: October 2011

The behavioral revolution of the 1960s which engulfed the social sciences,
and particularly Political Science and Sociology, led to a large-scale
disinterest in the study and structure of institutions. The 1980s saw a new
movement emerge upon the social sciences, which stressed the centrality of
institutional analysis in the study of politics and society and resurrected
the study of institutions as key variables. Dubbed the New Institutionalism,
this movement would have profound effects on the direction of research in
Political Science and Sociology. Unfortunately, the New Institutionalist
movement has been largely ignored by International Relations theorists and
practitioners, even though it has generated both a useful toolkit of methods,
and a rich source of findings that could be of much use to International
Relations theory.
Monitoring of 7Be atmospheric activity concentration using short term measurements
Authors: Papandreou Sotiria , Savva Marilia , Karfopoulos Konstantinos , Karangelos Dimitrios , Anagnostakis Marios , Simopoulos Simos
Published: October 2011

The activity concentration of 7Be in atmospheric aerosol can exhibit seasonal
variations due to various physical processes taking place in the troposphere
and stratosphere, as well as due to solar activity. An investigation of these
variations has been carried out at the Nuclear Engineering Department of the
National Technical University of Athens over a two year period
(3/2008-4/2010). In the framework of this study, sampling and analysis
methods were appropriately selected to allow for the observation of
short-term 7Be air activity concentration variations, using a 4-hour sampling
interval, while taking in consideration type A and type B uncertainties
introduced in the measurements. In order to study the role of precipitation
in surface air 7Be activity concentration variations, a procedure for
collecting and analyzing rainwater was developed. The techniques used in the
present study allowed for the observation of seasonal and diurnal 7Be
concentration variations, as well as correlations between 7Be activity
concentration and the meteorological parameters of air temperature and
relative humidity.
New method for determination of temperature in spallation reactions
Authors: Jordanov Dragana , Grabez Bojana , Subotic Krunoslav , Nadjdjerdj Laslo
Published: October 2011

We propose a new method for determination of temperature in spallation
events. It is shown that temperature can be determined by applying the
friction model of energy dissipation in participant-spectator model of a
spallation process. First order estimate of temperature dependence of the
participant zone on reaction Q-value is obtained from the Fermi gas model
considerations. The heat diffusion process is also discussed.