bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward Individualized Breast Cancer Therapy: Translating Biological Concepts to the Bedside
Authors: Hortobagyi Gabriel N.
Published: April 2012

The management of breast cancer has changed dramatically over the past 20 years. Based on gene expression profiles, or proteomics of three or four biomarkers, it is apparent that there are multiple subtypes with different clinical characteristics, clinical courses, and sensitivities to existing therapies. This manuscript reviews the management of hormone receptor–positive, human epidermal growth factor receptor 2–positive, and triple-negative breast cancers, emphasizing changes that have occurred in recent years and focusing on potential mechanisms of drug resistance. I also highlight strategies to prevent or overcome resistance to specific therapeutic agents. As a result of enhanced biological understanding of the molecular anomalies that drive the development, progression, and dissemination of breast cancer, a number of novel, molecularly targeted agents have been added to standard therapies. Chemotherapy, endocrine therapy, and targeted treatments have markedly reduced the risk for recurrence and mortality after primary treatment of breast cancer and have increased the 5- and 10-year survival rates. The challenges with novel therapeutics include the absence of accurate predictive biomarkers to identify those patient who will derive substantial benefit and those patients whose tumors are resistant to specific antitumor agents. As we move forward with increasing molecular segmentation of breast cancer and develop new, highly targeted agents, molecular diagnostics must accompany molecular therapeutics to implement the concept of personalized cancer therapy.
Planning for sustainable transport or for people's needs
Authors: Greed Clara
Published: April 2012

This paper reviews and critiques sustainability-driven spatial planning policy from the perspective of ordinary citizens as they seek to travel, live and work, and carry out their daily lives within the environmentally sustainable, green city. The original definition of sustainability contained social, economic and environmental components. This paper argues that there has been an over-emphasis in the UK upon the environmental aspects, at the expense of social considerations, especially gender considerations, creating a dissonance between the sustainability and social equality agendas to the detriment of achieving inclusive urban design. Policy examples from transportation and land-use planning indicate that sustainability-driven planning policy is working against the creation of inclusive, equitable and accessible cities with particular reference to the needs of women. Sustainability policy is set at too high a level to engage with the realities of everyday life. It is concluded that there is a need for a more user-related, social perspective to be integrated into sustainable planning policy.
London's urban heat island: a multi-scaled assessment framework
Authors: Hamilton Ian G. , Davies Michael , Gauthier Stephanie
Published: April 2012

London's urban heat island (UHI) impacts on health, comfort and energy use. Projected higher temperatures due to a change in climate would further exacerbate the effects of London's UHI. It is therefore necessary to understand its net impact and adopt strategies to cope with and mitigate its negative aspects. The Lucid project is addressing both these issues and this paper focuses on the second component. There is currently a lack of practical assessment instruments available to planners, designers and developers that can assess a development's impact on the UHI. This paper thus presents a proposal for a multi-scaled UHI assessment tool framework that could be used in developing relevant planning policy and assessing UHI mitigation design strategies. The paper discusses how a framework of this type could be integrated into the development planning process in London and the UK.
Agreement on Web-based Diagnoses and Severity of Mental Health Problems in Norwegian Child and Adolescent Mental Health Services
Authors: Brøndbo Håkan , Mathiassen Børge , Martinussen Monica , Heiervang Einar , Eriksen Mads , Kvernmo Siv
Published: April 2012

Objective:

This study examined the agreement between diagnoses and severity ratings assigned by clinicians using a structured web-based interview within a child and adolescent mental health outpatient setting.

Method:

Information on 100 youths was obtained from multiple informants through a web-based Development and Well-Being Assessment (DAWBA). Based on this information, four experienced clinicians independently diagnosed (according to the International Classification of Diseases Revision 10) and rated the severity of mental health problems according to the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) and the Children’s Global Assessment Scale (C-GAS).

Results:

Agreement for diagnosis was κ=0.69-0.82. Intra-class correlation for single measures was 0.78 for HoNOSCA and 0.74 for C-GAS, and 0.93 and 0.92, respectively for average measures.

Conclusions:

Agreement was good to excellent for all diagnostic categories. Agreement for severity was moderate, but improved to substantial when the average of the ratings given by all clinicians was considered. Therefore, we conclude that experienced clinicians can assign reliable diagnoses and assess severity based on DAWBA data collected online.
Evaluation of the use of nonesterified fatty acids and β-hydroxybutyrate concentrations in pooled serum samples for herd-based detection of subclinical ketosis in dairy cows during the first week after parturition
Authors: Borchardt Stefan , Staufenbiel Rudolf
Published: April 2012

Objective—To evaluate the use of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) concentrations in pooled serum samples for herd-based detection of subclinical ketosis (SCK) in dairy cows after calving.

Design—Cross-sectional study.

Animals—1,100 dairy cows from 110 herds.

Procedures—Blood samples were collected from 10 healthy cows/herd in the first week after parturition. Aliquots of serum were mixed to create a pooled sample. Concentrations of NEFA and BHBA were measured to estimate prevalence of SCK. Pooled sample test results were compared with those obtained for individual samples. Linear regression and receiver-operating characteristic curve analysis were performed; Bland-Altman plots were used to evaluate agreement between methods.

Results—Overall prevalence of SCK was 30.7%, 19.3%, and 13.6%, as determined by use of BHBA threshold concentrations of 1,000, 1,200, and 1,400 μmol/L, respectively. Pooled sample concentrations of NEFA and BHBA were significantly correlated (r = 0.98 and 0.97, respectively) with individual sample means and with the number of cows that had NEFA (R2 range, 0.81 to 0.84) or BHBA (R2 range, 0.65 to 0.76) concentrations above predefined thresholds. Pooled sample concentrations of NEFA and BHBA were very accurate to highly accurate for herd-based detection of SCK.

Conclusions and Clinical Relevance—Analysis of NEFA and BHBA concentrations in pooled serum samples was useful for herd-based detection of SCK. A sample size of 10 cows/herd was deemed adequate for monitoring dairy herds for SCK. Reference criteria specific to pooled samples should be used for this type of herd-based testing.
Comparison of arterial blood pressure measurements and hypertension scores obtained by use of three indirect measurement devices in hospitalized dogs
Authors: Wernick Morena B. , Höpfner Robert M. , Francey Thierry , Howard Judith
Published: April 2012

Objective—To evaluate the agreement of blood pressure measurements and hypertension scores obtained by use of 3 indirect arterial blood pressure measurement devices in hospitalized dogs.

Design—Diagnostic test evaluation.

Animals—29 client-owned dogs.

Procedures—5 to 7 consecutive blood pressure readings were obtained from each dog on each of 3 occasions with a Doppler ultrasonic flow detector, a standard oscillometric device (STO), and a high-definition oscillometric device (HDO).

Results—When the individual sets of 5 to 7 readings were evaluated, the coefficient of variation for systolic arterial blood pressure (SAP) exceeded 20% for 0% (Doppler), 11 % (STO), and 28% (HDO) of the sets of readings. After readings that exceeded a 20% coefficient of variation were discarded, repeatability was within 25 (Doppler), 37 (STO), and 39 (HDO) mm Hg for SAP. Correlation of mean values among the devices was between 0.47 and 0.63. Compared with Doppler readings, STO underestimated and HDO overestimated SAP. Limits of agreement between mean readings of any 2 devices were wide. With the hypertension scale used to score SAP, the intraclass correlation of scores was 0.48. Linear-weighted inter-rater reliability between scores was 0.40 (Doppler vs STO), 0.38 (Doppler vs HDO), and 0.29 (STO vs HDO).

Conclusions and Clinical Relevance—Results of this study suggested that no meaningful clinical comparison can be made between blood pressure readings obtained from the same dog with different indirect blood pressure measurement devices.
Transdiaphragmatic extension of a retroperitoneal lipoma into the intrathoracic extrapleural space via the lumbocostal trigone in a dog
Authors: Klosterman Emily S. , Heng Hock Gan , Freeman Lynetta J. , Childress Michael O.
Published: April 2012

Case Description—An 8-year-old 12.2-kg (26.9-lb) spayed female American Cocker Spaniel was referred for evaluation of abdominal discomfort and a suspected intra-abdominal lipoma with possible invasion into the thorax.

Clinical Findings—Physical examination revealed a tense abdomen, and the margins of a large abdominal mass could be appreciated. Abdominal imaging revealed a mass of fat opacity in the abdominal and thoracic cavities. Computed tomography with precontrast and postcontrast peritoneograms was used to determine whether the masses connected via a diaphragmatic defect.

Treatment and Outcome—Exploratory laparotomy revealed a retroperitoneal lipomatous mass that had focally invaded the hypaxial musculature and had extended across the dorsolateral aspect of the diaphragm via the lumbocostal trigone into the intrathoracic extrapleural space. Surgical resection required transdiaphragmatic thoracotomy. Histologic examination of excised tissue confirmed the preoperative diagnosis of a lipoma. The dog recovered from surgery with no complications and had no disease recurrence for at least 32 months after surgical resection.

Clinical Relevance—The defect of the lumbocostal trigone is also called the foramen of Bochdalek in humans, and it is recognized as a common location for congenital diaphragmatic hernia. A lumbocostal trigone hernia may be considered as a differential diagnosis for bicavitary masses in dogs, particularly in the absence of a history of trauma.
Variations of clinical SPECT/CT operations
Authors: Wieder H. , Czernin J. , Navar B. N. , Israel O. , Beyer T. , Freudenberg L. S.
Published: April 2012

Aim: This survey gathers information about clinical SPECT/CT operations worldwide to help guide standardization of clinical SPECT/ CT imaging. Methods: An international, webbased survey of SPECT/CT users was initiated in 12/2010 through an e-mail distribution. Users were asked 71 questions related to (A) demographics, (B) SPECT/CT operations/utilization and (C) variations in imaging protocols. Results: Collected responses originated from 117 imaging centers in the Americas (66%), Europe (20%), Asia-Pacific (11%) and the Middle-East (3%), with the majority of responding sites representing public health care institutions (69%). Most sites operate 1–2 SPECT/CT-systems (74%), typically installed in Nuclear Medicine departments (84%) with extensive prior SPECT-only experience (82%). Only 14% of SPECT/CTs are installed in Radiology departments. Clinical SPECT/CT imaging is performed either as routine (51%) or ad-hoc “add-on” procedure (49%) with a high inter-site and inter-examination variability. The main application of the integrated CT is to provide anatomical localization of the tracer uptake rather than to produce contrast enhanced or other high-quality CT images. Consequently, in only 22% of the sites a CT contrast injector is installed. Only 6% of centers use SPECT/CT devices for stand-alone CT procedures. Conclusion: An international survey among clinical SPECT/CT users revealed that SPECT/CT is a not a routine component of nuclear medicine procedures. The majority of the centers responding do not fully utilize the diagnostic potential of the CT components. Significant variations in standard imaging protocols were observed. These findings illustrate the need for training and standardization and underscore the need for revisiting the role of SPECT/CT in diagnostic imaging.
Guiding Differentiation of Stem Cells in Vivo by Tetracycline-Controlled Expression of Key Transcription Factors
Authors: Kozlova Elena N. , Berens Christian
Published: April 2012

Transplantation of stem or progenitor cells is an attractive strategy for cell replacement therapy. However, poor long-term survival and insufficiently reproducible differentiation to functionally appropriate cells in vivo still present major obstacles for translation of this methodology to clinical applications. Numerous experimental studies have revealed that the expression of just a few transcription factors can be sufficient to drive stem cell differentiation toward a specific cell type, to transdifferentiate cells from one fate to another, or to dedifferentiate mature cells to pluripotent stem/progenitor cells (iPSCs). We thus propose here to apply the strategy of expressing the relevant key transcription factors to guide the differentiation of transplanted cells to the desired cell fate in vivo. To achieve this requires tools allowing us to control the expression of these genes in the transplant. Here, we describe drug-inducible systems that allow us to sequentially and timely activate gene expression from the outside, with a particular emphasis on the Tet system, which has been widely and successfully used in stem cells. These regulatory systems offer a tool for strictly limiting gene expression to the respective optimal stage after transplantation. This approach will direct the differentiation of the immature stem/progenitor cells in vivo to the desired cell type.
Development of 198 novel EST‐derived microsatellites in Eucalyptus (Myrtaceae)
Authors: He Xudong , Wang Yu , Li Fagen , Weng Qijie , Li Mei , Xu Li‐an , Shi Jisen , Gan Siming
Published: April 2012

• Premise of the study: Expressed sequence tag (EST)–derived microsatellites were identified in Eucalyptus through screening the GenBank database. The loci were sequence‐verified and explored for polymorphism among 20 genotypes.

• Methods and Results: In total, 198 novel microsatellites were developed from 8262 unigenes, with the identity of 73.6–100% to the original sequences and presence of the expected repeat motifs. One hundred and eighty‐four markers proved to be polymorphic among 10 E. urophylla and 10 E. tereticornis genotypes, with the number of alleles per locus, observed heterozygosity, and polymorphic information content being 2–17 (mean: 7.11), 0–1.0 (mean: 0.4511), and 0.0940–0.9131 (mean: 0.6571), respectively.

• Conclusions: These markers will be useful for germplasm characterization, genome mapping, and gene tagging for economic traits in the two species examined and may have potential for genetic applications in Eucalyptus.
The Plasma Permeability Factor in Nephrotic Syndrome: Indirect Evidence in Pediatric Peritoneal Dialysis
Authors: Azocar Marta , Quiroz Lily , Delucchi Angela , Dinamarca Hector , Emilfork Marcos , Cano Francisco
Published: April 2012

Background

Nephrotic syndrome (NS) in children has been associated with a systemic circulating permeability factor. Therefore, once peritoneal dialysis (PD) has been started, peritoneal protein losses should be higher in the nephrotic than in the non-nephrotic population.

Objective

We compared peritoneal protein losses in children with and without NS on PD.

Methods

Our retrospective 4-year study analyzed Hispanic patients with NS under PD. Data at dialysis entry and 6 months later were compared. Nutritional support was given according to recommended dietary allowances and recommendations from the Kidney Disease Outcomes Quality Initiative. Clinical and biochemical data were obtained, and 24-hour dialysate and urine samples were collected to measure protein losses. Dialysis dose (Kt/V), daily protein intake (DPI), normalized protein equivalent of nitrogen appearance (nPNA), peritoneal equilibration test (PET), and peritonitis rate were determined. All measurements took place at least 4 weeks after resolution of a peritonitis episode. All patients received automated PD using a HomeChoice PD System cycler (Baxter Healthcare Corporation, Deerfield, IL, USA), with an exchange volume of 1100 mL/m2 and a dextrose concentration of 1.5% – 2.5%. A control group of non-NS children on PD matched by age and sex were also studied. Data are reported as mean ± standard deviation. Differences between groups were calculated using the Mann–Whitney U-test, and p < 0.05 was considered significant.

Results

Each study group consisted of 10 patients [NS patients: 4 boys, mean age of 7.3 ± 4.1 years; control patients: 6 boys, mean age of 7.2 ± 4.7 years ( p = nonsignificant)]. In the group with NS, 8 patients were diagnosed by biopsy as having focal segmental glomerulosclerosis, and 2 as having minimal-change disease. At study entry, patients with NS had hourly urinary protein losses of 398 ± 313 mg/m2 and daily peritoneal protein losses of 3.4 ± 1.9 g/m2, compared with 29.9 ± 31 mg/m2 and 1.5 ± 1.1 g/m2 respectively in the control group ( p < 0.05). The same statistical difference was found 6 months later. We observed no statistical differences in PET results, daily exchange volume, and mean dextrose concentration of dialysate. Similarly, no significant between-group differences were observed for Kt/V, DPI, nPNA, and biochemical parameters.

Conclusions

Hispanic children with NS on PD show higher peritoneal protein losses than do their control counterparts. Such differences could be secondary to increased peritoneal permeability caused by a systemic permeability factor.
Du rire de sarah à l'enfant du rire ou le désir des âges dans la bible
Authors: Gibert Pierre
Published: April 2012

La Bible dans son ensemble, Ancien et Nouveau Testament, n’est pas bégueule et ne recule pas devant la sexualité, jusqu’au paradoxe. Ainsi n’hésite-t-elle pas à mettre en scène, Sarah, une vieille femme promise au plaisir et à la maternité ; pas plus qu’elle n’hésite au seuil de notre ère à raconter la surprise incrédule du vieux Zacharie et l’émerveillement de sa femme, la vieille Elisabeth. Un enfant du rire, Isaac, en rit encore dans la triomphante nudité que nous en offre Le Caravage.
Fuzzy-Rule Based Adaptive Data Warehouse
Authors: Tiwari Rajdev , Tiwari Anubhav , Singh Manu Pratap
Published: April 2012

Data Warehouses (DWs) are aimed to empower the knowledge workers with information and knowledge which helps them in decision making. Technically, the DW is a large reservoir of integrated data that does not provide the intelligence or the knowledge demanded by users. The burden of data analysis and extraction of information and knowledge from integrated data still lies upon the analyst’s shoulder. The overhead of analysts can be taken off by architecting a new generation data warehouses systems those shall be capable of capturing, organizing and representing knowledge along with the data and information in it. This new generation DW may be called as Knowledge Warehouse (KW) shall exhibit decision making capabilities themselves and can also supplement the Decision Support Systems (DSS) in making decisions quickly and effortlessly. This paper proposes and simulates a fuzzy-rule based adaptive knowledge warehouse with capabilities to learn and represent implicit knowledge by means of adaptive neuro fuzzy inference system (ANFIS).
Reference Point Based Multi-Objective Optimization to Workflow Grid Scheduling
Authors: Garg Ritu , Singh Awadhesh Kumar
Published: April 2012

Grid provides global computing infrastructure for users to avail the services supported by the network. The task scheduling decision is a major concern in heterogeneous grid computing environment. The scheduling being an NP-hard problem, meta-heuristic approaches are preferred option. In order to optimize the performance of workflow execution two conflicting objectives, namely makespan (execution time) and total cost, have been considered here. In this paper, reference point based multi-objective evolutionary algorithms, R-NSGA-II and R-e-MOEA, are used to solve the workflow grid scheduling problem. The algorithms provide the preferred set of solutions simultaneously, near the multiple regions of interest that are specified by the user. To improve the diversity of solutions we used the modified form of R-NSGA-II (represented as M-R-NSGA-II). From the simulation analysis it is observed that, compared to other algorithms, R-e-MOEA delivers better convergence, uniform spacing among solutions keeping the computation time limited.
Cloud Computing Security
Authors: Arshad Junaid , Townend Paul , Xu Jie , Jie Wei
Published: April 2012

The evolution of modern computing systems has lead to the emergence of Cloud computing. Cloud computing facilitates on-demand establishment of dynamic, large scale, flexible, and highly scalable computing infrastructures. However, as with any other emerging technology, security underpins widespread adoption of Cloud computing. This paper presents the state-of-the-art about Cloud computing along with its different deployment models. The authors also describe various security challenges that can affect an organization’s decision to adopt Cloud computing. Finally, the authors list recommendations to mitigate with these challenges. Such review of state-of-the-art about Cloud computing security can serve as a useful barometer for an organization to make an informed decision about Cloud computing adoption.
Effective Service Composition in Large Scale Service Market
Authors: Wang Xianzhi , Wang Zhongjie , Xu Xiaofei
Published: April 2012

The web has undergone a tremendous shift from information repository to the provisioning capacity of services. As an effective means of constructing coarse-grained solutions by dynamically aggregating a set of services to satisfy complex requirements, traditional service composition suffers from dramatic decrease on the efficiency of determining the optimal solution when large scale services are available in the Internet based service market. Most current approaches look for the optimal composition solution by real-time computation, and the composition efficiency greatly depends on the adopted algorithms. To eliminate such deficiency, this paper proposes a semi-empirical composition approach which incorporates the extraction of empirical evidence from historical experiences to provide guidance to solution space reduction to real-time service selection. Service communities and historical requirements are further organized into clusters based on similarity measurement, and then the probabilistic correspondences between the two types of clusters are identified by statistical analysis. For each new request, its hosting requirement cluster would be identified and corresponding service clusters would be determined by leveraging Bayesian inference. Concrete services would be selected from the reduced solution space to constitute the final composition. Timing strategies for re-clustering and consideration to special cases in clustering ensures continual adaption of the approach to changing environment. Instead of relying solely on pure real-time computation, the approach distinguishes from traditional methods by combining the two perspectives together.
IL-2 Simultaneously Expands Foxp3+ T Regulatory and T Effector Cells and Confers Resistance to Severe Tuberculosis (TB): Implicative Treg–T Effector Cooperation in Immunity to TB
Authors: Chen Crystal Y. , Huang Dan , Yao Shuyu , Halliday Lisa , Zeng Gucheng , Wang Richard C. , Chen Zheng W.
Published: April 2012

The possibility that simultaneous expansion of T regulatory cells (Treg) and T effector cells early postinfection can confer some immunological benefits has not been studied. In this study, we tested the hypothesis that early, simultaneous cytokine expansion of Treg and T effector cells in a tissue infection site can allow these T cell populations to act in concert to control tissue inflammation/damage while containing infection. IL-2 treatments early after Mycobacterium tuberculosis infection of macaques induced simultaneous expansion of CD4+CD25+Foxp3+ Treg, CD8+CD25+Foxp3+ T cells, and CD4+ T effector/CD8+ T effector/Vγ2Vδ2 T effector populations producing anti-M. tuberculosis cytokines IFN-γ and perforin, and conferred resistance to severe TB inflammation and lesions. IL-2–expanded Foxp3+ Treg readily accumulated in pulmonary compartment, but despite this, rapid pulmonary trafficking/accumulation of IL-2–activated T effector populations still occurred. Such simultaneous recruitments of IL-2–expanded Treg and T effector populations to pulmonary compartment during M. tuberculosis infection correlated with IL-2–induced resistance to TB lesions without causing Treg-associated increases in M. tuberculosis burdens. In vivo depletion of IL-2–expanded CD4+Foxp3+ Treg and CD4+ T effectors during IL-2 treatment of M. tuberculosis-infected macaques significantly reduced IL-2–induced resistance to TB lesions, suggesting that IL-2–expanded CD4+ T effector cells and Treg contributed to anti-TB immunity. Thus, IL-2 can simultaneously activate and expand T effector cells and Foxp3+ Treg populations and confer resistance to severe TB without enhancing M. tuberculosis infection.
Surfactant Protein A Modulates Induction of Regulatory T Cells via TGF-β
Authors: Mukherjee Sambuddho , Giamberardino Charles , Thomas Joseph M. , Gowdy Kymberly , Pastva Amy M. , Wright Jo Rae
Published: April 2012

TCR signaling plays a critical role in regulatory T cell (Treg) development. However, the mechanism for tissue-specific induction of Tregs in the periphery remains unclear. We observed that surfactant protein A (SP-A)–deficient mice have impaired expression of Foxp3 and fewer CD25+Foxp3+ Tregs after ex vivo stimulation and after stimulation with LPS in vivo. The addition of exogenous SP-A completely reversed this phenotype. Although SP-A is known to inhibit T cell proliferation under certain activation conditions, both IL-2 levels as well as active TGF-β levels increase on extended culture with exogenous SP-A, providing a key mechanism for the maintenance and induction of Tregs. In addition, kinetic suppression assays demonstrate that SP-A enhances the frequency of functional Foxp3+ Tregs in responder T cell populations in a TGF-β–dependent manner. In mice treated with LPS in vivo, Tregs increased ∼160% in wild-type mice compared with only a 50% increase in LPS-treated SP-A−/− mice 8 d after exposure. Taken together, these findings support the hypothesis that SP-A affects T cell immune function by the induction of Tregs during activation.
Pulmonary Inflammation Induced by Subacute Ozone Is Augmented in Adiponectin-Deficient Mice: Role of IL-17A
Authors: Kasahara David I. , Kim Hye Y. , Williams Alison S. , Verbout Norah G. , Tran Jennifer , Si Huiqing , Wurmbrand Allison P. , Jastrab Jordan , Hug Christopher , Umetsu Dale T. , Shore Stephanie A.
Published: April 2012

Pulmonary responses to ozone, a common air pollutant, are augmented in obese individuals. Adiponectin, an adipose-derived hormone that declines in obesity, has regulatory effects on the immune system. To determine the role of adiponectin in the pulmonary inflammation induced by extended (48–72 h) low-dose (0.3 parts per million) exposure to ozone, adiponectin-deficient (Adipo−/−) and wild-type mice were exposed to ozone or to room air. In wild-type mice, ozone exposure increased total bronchoalveolar lavage (BAL) adiponectin. Ozone-induced lung inflammation, including increases in BAL neutrophils, protein (an index of lung injury), IL-6, keratinocyte-derived chemokine, LPS-induced CXC chemokine, and G-CSF were augmented in Adipo−/− versus wild-type mice. Ozone also increased IL-17A mRNA expression to a greater extent in Adipo−/− versus wild-type mice. Moreover, compared with control Ab, anti–IL-17A Ab attenuated ozone-induced increases in BAL neutrophils and G-CSF in Adipo−/− but not in wild-type mice, suggesting that IL-17A, by promoting G-CSF release, contributed to augmented neutrophilia in Adipo−/− mice. Flow cytometric analysis of lung cells revealed that the number of CD45+/F4/80+/IL-17A+ macrophages and γδ T cells expressing IL-17A increased after ozone exposure in wild-type mice and further increased in Adipo−/− mice. The IL-17+ macrophages were CD11c− (interstitial macrophages), whereas CD11c+ macrophages (alveolar macrophages) did not express IL-17A. Taken together, the data are consistent with the hypothesis that adiponectin protects against neutrophil recruitment induced by extended low-dose ozone exposure by inhibiting the induction and/or recruitment of IL-17A in interstitial macrophages and/or γδ T cells.
Functional Changes in Myeloid-Derived Suppressor Cells (MDSCs) during Tumor Growth: FKBP51 Contributes to the Regulation of the Immunosuppressive Function of MDSCs
Authors: Kim Yun-Sun , Kim Yeon-Jeong , Lee Jung-Mi , Kim Eun-Kyung , Park Young-Jun , Choe Su-Kyong , Ko Hyun-Jeong , Kang Chang-Yuil
Published: April 2012

Myeloid-derived suppressor cells (MDSCs) are increased by tumor-derived factors and suppress anti-tumor immunity. MDSCs obtained at a late time point after tumor injection had stronger suppressive activity than MDSCs obtained at an early time point, as measured by T cell proliferation assays. To find factors in MDSCs that change during tumor growth, we analyzed gene expression profiles from MDSCs at different time points after tumor injection. We found that immune response-related genes were downregulated but protumor function-related genes were upregulated in both monocytic MDSCs (Mo-MDSCs) and polymorphonuclear granulocytic MDSCs (PMN-MDSCs) at the late time point. Among differentially expressed genes, FK506 binding protein 51 (FKBP51), which is a member of the immunophilin protein family and plays a role in immunoregulation, was increased in the Mo-MDSCs and PMN-MDSCs isolated from the late time points. Experiments using small interfering RNA and a chemical inhibitor of FKBP51 revealed that FKBP51 contributes to the regulation of the suppressive function of MDSCs by increasing inducible NO synthase, arginase-1, and reactive oxygen species levels and enhancing NF-κB activity. Collectively, our data suggest that FKBP51 is a novel molecule that can be targeted to regulate the immunosuppressive function of MDSCs.
The Asp299Gly Polymorphism Alters TLR4 Signaling by Interfering with Recruitment of MyD88 and TRIF
Authors: Figueroa Leandra , Xiong Yanbao , Song Chang , Piao Wenji , Vogel Stefanie N. , Medvedev Andrei E.
Published: April 2012

Asp299Gly (D299G) and, to a lesser extent, Thr399Ile (T399I) TLR4 polymorphisms have been associated with Gram-negative sepsis and other infectious diseases, but the mechanisms by which they affect TLR4 signaling are unclear. In this study, we determined the impact of the D299G and T399I polymorphisms on TLR4 expression, interactions with myeloid differentiation factor 2 (MD2), LPS binding, and LPS-mediated activation of the MyD88- and Toll/IL-1R resistance domain-containing adapter inducing IFN-β (TRIF) signaling pathways. Complementation of human embryonic kidney 293/CD14/MD2 transfectants with wild-type (WT) or mutant yellow fluorescent protein-tagged TLR4 variants revealed comparable total TLR4 expression, TLR4–MD2 interactions, and LPS binding. FACS analyses with anti-TLR4 Ab showed only minimal changes in the cell-surface levels of the D299G TLR4. Cells transfected with D299G TLR4 exhibited impaired LPS-induced phosphorylation of p38 and TANK-binding kinase 1, activation of NF-κB and IFN regulatory factor 3, and induction of IL-8 and IFN-β mRNA, whereas T399I TLR4 did not cause statistically significant inhibition. In contrast to WT TLR4, expression of the D299G mutants in TLR4−/− mouse macrophages failed to elicit LPS-mediated induction of TNF-α and IFN-β mRNA. Coimmunoprecipitation revealed diminished LPS-driven interaction of MyD88 and TRIF with the D299G TLR4 species, in contrast to robust adapter recruitment exhibited by WT TLR4. Thus, the D299G polymorphism compromises recruitment of MyD88 and TRIF to TLR4 without affecting TLR4 expression, TLR4–MD2 interaction, or LPS binding, suggesting that it interferes with TLR4 dimerization and assembly of intracellular docking platforms for adapter recruitment.
Tuberculous Spondylitis Presenting as Severe Chest Pain
Authors: Kaeser Martha A. , Kettner Norman W. , Albastaki Usama , Kotb Hossam Ahmed , Eldesouky Ibrahim M.A. , Pierre-Jerome Claude
Published: April 2012

This case report describes a 32-year-old male who presented to an emergency department with severe chest pain and a history of cough, fever, night sweats, loss of appetite and weight. Chest radiography revealed a left upper lobe consolidation and multiple compression deformities in the thoracic spine. Magnetic resonance imaging demonstrated significant kyphosis and vertebral plana at two thoracic levels. Anterior compression of the spinal cord and adjacent soft tissue masses were also noted.
Case study to evaluate the influence of the SolarBees and dossage on the water quality of the Rietvlei Dam Water Treatment Plant.
Authors: Booyens S. , De Vos D. , Barnard Sandra , Coetzee Leanne
Published: April 2012

The aim of this project was to investigate the influence of the SolarBees and dosage on the water quality at Rietvlei Dam WTP. The difference between the raw and final water samples was less than anticipated due to the drastic improvement in raw water quality of Rietvlei Dam.
Evaluation of BAER surface model for aerosol optical thickness retrieval over land surface
Authors: Chiang Y. S. , von Hoyningen-Huene W. , Chen K. S. , Ladstätter-Weißenmayer A. , Burrows J. P.
Published: April 2012

Abstract. Estimation of surface reflectance is essential for an accurate retrieval of aerosol optical thickness (AOT) by satellite remote sensing approach. Due to the variability of surface reflectance over land surfaces, a surface model is required to take into account the crucial factor controlling this variability. In the present study, we attempted to simulate surface reflectance in the short-wave channels with two methods, namely the land cover type dependent method and a two-source linear model. In the two-source linear model, we assumed that the spectral property can be described by a mixture of vegetated and non-vegetated area, and both the normalized difference vegetation index (NDVI), and the vegetation continuous field (VCF) was applied to summarize this surface characteristic. By comparing our estimation with surface reflectance data derived from Moderate Resolution Imaging Spectroradiometer (MODIS), it indicated that the land cover type approach did not provide a better estimation because of inhomogeneous land cover pattern and the mixing pixel properties. For the two-source linear method, the study suggested that the use of NDVI as parameterization for vegetation fraction can reflect the spectral behavior of shortwave surface reflectance, despite of some deviation due to the averaging characteristics in our linear combination process. A channel-dependent offset and scalar factor could enhance reflectance estimation and further improve AOT retrieval by the current Bremen AErosol Retrieval (BAER) approach.
Activity and abundance of denitrifying bacteria in the subsurface biosphere of diffuse hydrothermal vents of the Juan de Fuca Ridge
Authors: Bourbonnais A. , Juniper S. K. , Butterfield D. A. , Devol A. H. , Kuypers M. M. M. , Lavik G. , Hallam S. J. , Wenk C. B. , Chang B. X. , Murdock S. A. , Lehmann M. F.
Published: April 2012

Abstract. Little is known about nitrogen (N) transformations in general, and the elimination of N in particular, at diffuse vents where anoxic hydrothermal fluids have mixed with oxygenated crustal seawater prior to discharge. Oceanic N sinks that remove bio-available N ultimately affect chemosynthetic primary productivity in these ecosystems. Using 15N paired isotope techniques, we determined potential rates of fixed N-loss pathways (denitrification, anammox) and dissimilative nitrate reduction to ammonium (DNRA) in sulfidic hydrothermal vent fluids discharging from the subsurface at several sites at Axial Volcano and the Endeavour Segment on the Juan de Fuca Ridge. We also measured physico-chemical parameters (i.e. temperature, pH, nutrients, H2S and N2O concentrations) as well as the biodiversity and abundance of chemolithotrophic nitrate-reducing, sulfur-oxidizing γ-proteobacteria (SUP05 cluster) using sequence analysis of amplified small subunit ribosomal RNA (16S rRNA) genes in combination with taxon-specific quantitative polymerase chain reaction (qPCR) assays. Denitrification was the dominant N-loss pathway in the subsurface biosphere of the Juan de Fuca Ridge, with rates of up to ~1000 nmol N l−1 day−1. In comparison, anammox rates were always <5 nmol N l−1 day−1 and below the detection limit at most of the sites. DNRA rates were up to 152 nmol N l−1 day−1. These results suggest that bacterial denitrification out-competes anammox in sulfidic hydrothermal vent waters. Taxon-specific qPCR revealed that γ-proteobacteria of the SUP05 cluster sometimes dominated the microbial community (SUP05/total bacteria up to 38%). Significant correlation existed between fixed N-loss (i.e., denitrification, anammox) rates and in-situ nitrate and dissolved inorganic nitrogen (DIN) deficits in the fluids, indicating that DIN availability may ultimately regulate N-loss in the subsurface. Based on our rate measurements, and on published data on hydrothermal fluid fluxes and residence times, we estimated that, on average, ~10 Tg N yr−1 could globally be removed in the subsurface biosphere of hydrothermal vents systems, and could thus represent a small, but significant, fraction of the total marine N loss (240–400 Tg N yr−1).
Monsoonal response to mid-holocene orbital forcing in a high resolution GCM
Authors: Bosmans J. H. C. , Drijfhout S. S. , Tuenter E. , Lourens L. J. , Hilgen F. J. , Weber S. L.
Published: April 2012

Abstract. In this study, we use a sophisticated high-resolution atmosphere-ocean coupled climate model, EC-Earth, to investigate the effect of Mid-Holocene orbital forcing on summer monsoons on both hemispheres. During the Mid-Holocene (6 ka), there was more summer insolation on the Northern Hemisphere than today, which intensified the meridional temperature and pressure gradients. Over North Africa, monsoonal precipitation is intensified through increased landward monsoon winds and moisture advection as well as decreased moisture convergence over the oceans and more convergence over land compared to the pre-industrial simulation. Precipitation also extends further north as the ITCZ shifts northward in response to the stronger poleward gradient of insolation. This increase and poleward extent is stronger than in most previous ocean-atmosphere GCM simulations. In north-westernmost Africa, precipitation extends up to 35° N. Over tropical Africa, internal feedbacks completely overcome the direct warming effect of increased insolation. We also find a weakened African Easterly Jet. Over Asia, monsoonal precipitation during the Mid-Holocene is increased as well, but the response is different than over North-Africa. There is more convection over land at the expense of convection over the ocean, but precipitation does not extend further northward, monsoon winds over the ocean are weaker and the surrounding ocean does not provide more moisture. On the Southern Hemisphere, summer insolation and the poleward insolation gradient were weaker during the Mid-Holocene, resulting in a reduced South American monsoon through decreased monsoon winds and less convection, as well as an equatorward shift in the ITCZ. This study corroborates the findings of paleodata research as well as previous model studies, while giving a more detailed account of Mid-Holocene monsoons.
A channel transmission losses model for different dryland rivers
Authors: Costa A. C. , Bronstert A. , de Araújo J. C.
Published: April 2012

Abstract. Channel transmission losses in drylands take place normally in extensive alluvial channels or streambeds underlain by fractured rocks. They can play an important role in streamflow rates, groundwater recharge, freshwater supply and channel-associated ecosystems. We aim to develop a process-oriented, semi-distributed channel transmission losses model, using process formulations which are suitable for data-scarce dryland environments and applicable to both hydraulically disconnected losing streams and hydraulically connected losing(/gaining) streams. This approach should be able to cover a large variation in climate and hydro-geologic controls, which are typically found in dryland regions of the Earth. Our model was first evaluated for a losing/gaining, hydraulically connected 30 km reach of the Middle Jaguaribe River (MJR), Ceará, Brazil, which drains a catchment area of 20 000 km2. Secondly, we applied it to a small losing, hydraulically disconnected 1.5 km channel reach in the Walnut Gulch Experimental Watershed (WGEW), Arizona, USA. The model was able to predict reliably the streamflow volume and peak for both case studies without using any parameter calibration procedure. We have shown that the evaluation of the hypotheses on the dominant hydrological processes was fundamental for reducing structural model uncertainties and improving the streamflow prediction. For instance, in the case of the large river reach (MJR), it was shown that both lateral stream-aquifer water fluxes and groundwater flow in the underlying alluvium parallel to the river course are necessary to predict streamflow volume and channel transmission losses, the former process being more relevant than the latter. Regarding model uncertainty, it was shown that the approaches, which were applied for the unsaturated zone processes (highly nonlinear with elaborate numerical solutions), are much more sensitive to parameter variability than those approaches which were used for the saturated zone (mathematically simple water budgeting in aquifer columns, including backwater effects). In case of the MJR-application, we have seen that structural uncertainties due to the limited knowledge of the subsurface saturated system interactions (i.e. groundwater coupling with channel water; possible groundwater flow parallel to the river) were more relevant than those related to the subsurface parameter variability. In case of the WEGW application we have seen that the non-linearity involved in the unsaturated flow processes in disconnected dryland river systems (controlled by the unsaturated zone) generally contain far more model uncertainties than do connected systems controlled by the saturated flow. Therefore, the degree of aridity of a dryland river may be an indicator of potential model uncertainty and subsequent attainable predictability of the system.
Modeling water resources trends in Middle East and North Africa towards 2050
Authors: Droogers P. , Immerzeel W. W. , Terink W. , Hoogeveen J. , Bierkens M. F. P. , van Beek L. P. H. , Negewo B. D.
Published: April 2012

Abstract. Changes in water resources availability can be expected as consequences of climate change, population growth, economic development and environmental considerations. A two-stage modeling approach is used to explore the impact of these changes in the Middle East and North Africa (MENA) region. An advanced physical based distributed hydrological model is applied to determine the internal and external renewable water resources for the current situation and under future changes. Subsequently, a water allocation model is used to combine the renewable water resources with sectorial water demands. Results show that total demand in the region will increase to 132 km3 yr−1 in 2050, while total water shortage will grow to 199 km3 yr−1 in 2050 for the average climate change projection; an increase of 157 km3. This increase in shortage is the combined impact of an increase in water demand by 50% with a decrease in water supply by 12%. Uncertainty based on the output of the nine GCMs applied, reveals that expected water shortage ranges from 85 km3 to 283 km3 in 2050. The analysis shows that 22% of the water shortage can be attributed to climate change and 78% to changes in socio-economic factors.
Multi-criteria parameter estimation for the unified land model
Authors: Livneh B. , Lettenmaier D. P.
Published: April 2012

Abstract. We describe a parameter estimation framework for the Unified Land Model (ULM) that utilizes multiple independent data sets over the Continental United States. These include a satellite-based evapotranspiration (ET) product based on MODerate resolution Imaging Spectroradiometer (MODIS) and Geostationary Operation Environmental Satellites (GOES) imagery, an atmospheric-water balance based ET estimate that utilizes North American Regional Reanalysis (NARR) atmospheric fields, terrestrial water storage content (TWSC) data from the Gravity Recovery and Climate Experiment (GRACE), and streamflow (Q) primarily from the United States Geological Survey (USGS) stream gauges. The study domain includes 10 large-scale (≥105 km2) river basins and 250 smaller-scale (<104 km2) tributary basins. ULM, which is essentially a merger of the Noah Land Surface Model and Sacramento Soil Moisture Accounting model, is the basis for these experiments. Calibrations were made using each of the criteria individually, in addition to combinations of multiple criteria, with multi-criteria skill scores computed for all cases. At large-scales calibration to Q resulted in the best overall performance, whereas certain combinations of ET and TWSC calibrations lead to large errors in other criteria. At small scales, about one-third of the basins had their highest Q performance from multi-criteria calibrations (to Q and ET) suggesting that traditional calibration to Q may benefit by supplementing observed Q with remote sensing estimates of ET. Model streamflow errors using optimized parameters were mostly due to over (under) estimation of low (high) flows. Overall, uncertainties in remote-sensing data proved to be a limiting factor in the utility of multi-criteria parameter estimation.