bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB-516: PDZ-RhoGEF promotes glioblastoma cell invasion, proliferation and survival
Authors: Kwiatkowska Aneta , Dong Zhiwan , Paulino Vincent M. , Tran Nhan L. , Ruggieri Rosamaria , Symons Marc H.
Published: August 2012

Invasion of glioblastoma cells into the surrounding brain parenchyma is a critical parameter of this disease as it hampers complete surgical resection of the tumor mass. Glioblastoma tumors are highly proliferative and resistant to radio- and chemo-therapy, thereby leading to tumor recurrence. Rho family members have been shown to control both the invasive and proliferative behavior of tumor cells. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs). In this study we focused on PDZ-RhoGEF, as its role in glioblastoma is not known. It has been shown that invading glioblastoma cells need contractile force to squeeze their nucleus through narrow spaces that are characteristic of the brain parenchyma (Beadle et al, Mol. Biol. Cell (2008) 19: 3357). We found that depletion of PDZ-RhoGEF in U87 and SNB19 glioblastoma cells strongly inhibits cell migration across a small (3 μm) pore size filter, a process which necessitates nuclear squeezing. PDZ-RhoGEF depletion also inhibits cell migration across a larger (8 μm) pore size filter, albeit to a lesser extent than in the squeezing assay. Interestingly, cells lacking PDZ-RhoGEF display multi-lobed lamellae, suggesting a defect in cell polarization. In addition, PDZ-RhoGEF depletion strongly inhibits glioblastoma cell invasion into ex vivo brain slices. In vitro studies have demonstrated that PDZ-RhoGEF can act on both RhoA and RhoC. The roles of these GTPases in the invasive behavior of glioblastoma have not been reported to date. Interestingly, we found that depletion of RhoC strongly inhibits brain slice invasion and nuclear squeezing, whereas depletion of RhoA has no significant effect on these functions. Thus, taken together, these data suggest that PDZ-RhoGEF largely acts by activating RhoC to stimulate glioma cell invasion. Our preliminary data also indicate that PDZ-RhoGEF mediates glioma cell proliferation and survival. In conclusion, our findings suggest that PDZ-RhoGEF is a potential therapeutic target for glioma therapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-516. doi:1538-7445.AM2012-LB-516
Abstract LB-519: Chemotaxis of acute promyelocytic leukemia cells toward CXCL12 is involved in ATRA syndrome and the requirement of chemotherapy during Induction therapy with ATRA
Authors: Gotoh Akihiko , Aota Yasuo , Miyazawa Keisuke , Kizaki Masahiro , Ohyashiki Kazuma
Published: August 2012

We previously reported that treatment of acute promyelocytic leukemia (APL) cells with all-trans retinoic acid (ATRA) in vitro increases the directed migration towards CXCL12. Here we report the clinical significance of this phenomenon. Bone marrow cells were corrected from 13 de-novo APL patients after obtaining informed consent. Flow-cytometric analysis revealed that all cases expressed CXCR4, the receptor of CXCL12. The CXCR4 expression was enhanced after 24 hour treatment with ATRA in vitro. Chemotaxis analysis using Boyden chamber demonstrated that the directed migration towards CXCL12 increased 1.03 to 4.16 (median 1.65) times in ATRA-treated APL cells as compared to non-treated cells. Four out of 13 APL patients developed ATRA syndrome during induction therapy with ATRA. The chemotaxis towards CXCL12 was enhanced in these four patients (p<0.01). Six cases required chemotherapy with IDR and Ara-C during induction therapy with ATRA. The significant increase in chemotaxis toward CXCL12 was also observed in these patients as compared with those who achieved CR by the induction therapy with ATRA alone (p<0.01). Interestingly, the ability of chemotaxis of APL cells appeared to be more well correlated with the occurrence of ATRA syndrome and the requirement of additional chemotherapy during ATRA treatment as compared with other well known predictable factors such as the APL cell number or white blood cell number in the peripheral blood, and the expression level of CXCR4. To investigate the possible mechanism of the chemotaxis, we used APL cell lines such as ATRA-sensitive NB4 cells and ATRA-resistant UF-1 cells as well as primary APL cells. An inhibitory antibody against CXCR4 and pertussis toxin effectively suppressed chemotaxis of APL cells toward CXCL12. Chemotaxis assay using selective signaling inhibitors demonstrated that activation of phospholipase C but not MAP kinase was strongly involved in the directed migration towards CXCL12 in APL cells. Additionally, the Akt-PI3-kinse pathway was partly participated in this chemotaxis. These results suggest that chemotaxis ability of APL cells toward CXCL12 is involved in the pathogenesis of ATRA syndrome and the requirement of chemotherapy during induction therapy with ATRA. Furthermore, specific signal targeted-therapy might contribute to prevent ATRA syndrome and/or avid administration of excessive chemotherapeutic agents.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-519. doi:1538-7445.AM2012-LB-519
Abstract LB-55: The European Cancer Patient Coalition speaks with a single voice for all cancer patients
Authors: Kossler Ingrid
Published: August 2012

Established in 2003, The European Cancer Patient Coalition is the voice of the European cancer patient community, uniquely representing the interests of all cancer patient groups from the major to the rarer cancers. ECPC is an independent, non-profit “umbrella” organization based in Brussels close to the European institutions, governed by an elected Board of seven members most of whom must be cancer patients, survivors or carers. ECPC maintains close links with EU institutions (Commission, Parliament, Council, and European Medicines Agency). ECPC monitors political development at EU level, identifies those which could impact the field of oncology, informs its member societies and supports European health issues. Priority Areas- • Influence EU policy that has an impact on the prevention, detection and treatment of cancer. • Reach out to national level to support ECPC members in their capacity building efforts on the national level • Build strategic partnerships with key cancer stakeholders to create mutual benefit One of ECPC's key priorities is to make cancer a priority for action on the European health policy agenda. With its policy activities, ECPC aims to effect change in legislative or regulatory policies to help optimize cancer prevention, detection, treatment and care throughout Europe. The policies also need to ensure that gaps within and between Member States are identified and eradicated, and that best practice is shared.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-55. doi:1538-7445.AM2012-LB-55
Abstract LB-57: Susan G. Komen for the Cure- A global breast cancer movement
Authors: Halarewicz Lee
Published: August 2012

Twenty-two Northeast Ohio counties comprise the Northeast Ohio Affiliate for which I volunteer. The Northeast Ohio Affiliate is dedicated to combating breast cancer at every front. Up to 75% of the Affiliate's net income goes toward funding grants to local hospitals and community organizations that provide breast health education and breast cancer screening and treatment programs for medically underserved women. The Affiliate is the only community resource in the Northeast Ohio region positioned to impact the core issues in ways significant enough to improve breast cancer screening rates, which will ultimately lead to a reduction in late stage diagnosis The remaining net income (a minimum of 25%) the Northeast Ohio Affiliate raises supports the national Komen Grants Program, which funds groundbreaking breast cancer research, meritorious awards and educational and scientific programs around the world. The impact of Komen's research investments is evident in every major advance in breast cancer over the past 25 years. Advocate participation in peer review is extended to involvement in many of these ongoing research projects and to other scientific activities through the Advocates in Science program. The Komen Advocates in Science (AIS) program is an inclusive community of dedicated volunteer advocates in scientific breast cancer research. We are brought together and sponsored by Komen to foster excellence in research advocacy and spur greater advocate engagement in research related activities. As an AIS Research Advocate, I participate in a variety of scientific activities to ensure that the unique and valuable perspectives of cancer survivors and others affected by cancer are integrated into scientific dialogue and decisions affecting our progress toward ending breast cancer. Advocates bring a real-world understanding of what most impacts those affected by breast cancer, and they also bring an urgency to find cures and more effective prevention, diagnosis and treatment. Additionally, AIS members engage in ongoing education to enhance our advocacy skills and expand our scientific knowledge.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-57. doi:1538-7445.AM2012-LB-57
Abstract LB-60: Long-term use of hormone therapy and breast cancer incidence and mortality
Authors: Chen Wendy Y. , Willett Walter C. , Hankinson Susan E. , Rosner Bernard A. ,   Nurses Health Study Group
Published: August 2012

Background: The risk of breast cancer associated with longer-term use of both estrogen (ET) or estrogen + progesterone (E+P) hormone therapy (HT) cannot be determine from existing randomized controlled trials. Methods: The Nurses’ Health Study included 121,700 female registered nurses aged 30-55 in 1976 who have been followed with biennial questionnaires to medication use, risk factors and cancer incidence. Only postmenopausal women were included in this analysis. The main outcome was incidence of invasive breast cancer. We additionally evaluated the risk of fatal breast cancer (breast cancer diagnosis that resulted in breast cancer death). Results: During 1.57 million person-years of follow-up from 1980 through 2008, 5631 incident invasive breast cancers were diagnosed and 884 died of breast cancer. Breast cancer risk increased with duration of current E+P use without evidence for a plateau (e.g. RR 1.88 (95% CI 1.64-2.16) for 10-14.9 years and RR 2.35 (95% CI 1.90-2.92) for 15-19.9 years of use). More than 10 years of current ET use was also associated with increased breast cancer risk (RR 1.22 (95% CI 1.06-1.40) for 10-14.9 years and RR 1.43 (95% CI 1.22-1.68) for 15-19.9 years of use). Past E+P was also weakly associated with breast cancer risk. When the population was restricted to the same entry criteria as the Women's Health Initiative trial, we also observed a non-significant deceased risk of breast cancer HT with current ET use similar in magnitude to that seen in the trial (RR 0.61 (95% CI 0.63-1.05) for < 5 years and RR 0.93 (95% CI 0.76-1.14) for 5-9.9 years), but still observed an increased risk with current ET users of 15-19.9 years (RR 1.30 (95% CI 1.07-1.59). Effects were stronger for ER positive tumors and among thinner women. Results were similar when limited to women who underwent regular screening. Although breast cancer incidence was increased in these groups, there was no increase in the risk of fatal breast cancer with either E+P or ET use (RR 1.05 (95% CI 0.67-1.68) and RR 1.08 (0.80-1.46) for 10-19.9 years of current use respectively). Conclusions: Both past and current E + P users and current long-term ET users were at increased breast cancer risk. We did not observe an increase in fatal breast cancer with HT use.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-60. doi:1538-7445.AM2012-LB-60
Abstract SY10-04: Delineating cellular targets of transformation in breast cancer
Authors: Fu Nai Yang , Vaillant François , Lindeman Geoffrey J. , Visvader Jane E.
Published: August 2012

To understand relationships between the mammary epithelia, ‘cells of origin’ and cancer stem cells in breast tumors, it is necessary to dissect the normal mammary epithelial hierarchy. We have isolated discrete populations of mouse and human mammary epithelial cells on the basis of cell-surface markers and identified cell subsets that are highly enriched for mammary stem (MaSC), luminal progenitor and mature luminal cells. Analysis of different mouse models of mammary tumorigenesis using syngeneic transplantation assays and interrogation of molecular profiles has revealed potential ‘cells of origin’ in preneoplastic tissue and the presence of a definitive cancer stem cell subset in different mouse mammary tumors. Cell lineage tracing studies in the mouse provide the current gold standard for identifying cells of origin. Towards this end, we have constructed a series of transgenic mice harboring lineage-specific gene regulatory regions (180 kB) that can be used to direct the expression of specific mammary oncogenes to discrete epithelial cell types. This will allow us to address the contribution of ‘cells of origin’ and the nature of the oncogene itself to mouse mammary tumorigenesis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY10-04. doi:1538-7445.AM2012-SY10-04
Abstract SY20-01: CHD5: Chromosome engineering, chromatin dynamics and cancer
Authors: Mills Alea A.
Published: August 2012

Although 1p36 loss has been documented for decades and a variety of malignancies have this particular lesion, the tumor suppressor mapping to this genomic interval had not been identified. Using chromosome engineering to create models with gain and loss of the region of the mouse genome corresponding to human 1p36, we pinpointed a potent tumor suppressive interval, identified Chromodomain Helicase DNA-binding domain protein 5 (CHD5) as the causative gene in the region, elucidated molecular pathways induced by CHD5, and demonstrated that CHD5 is frequently deleted in human cancer. The discovery of CHD5 as a tumor suppressor has had a major impact in the cancer field. Indeed, it is now appreciated that CHD5 is mutated in cancers of the breast, ovary, colon, and prostate, as well as in melanoma, glioma, and neuroblastoma. Furthermore, CHD5 status is a prognostic indicator of patient survival following anti-cancer therapy.

Still, the mechanism by which CHD5 exerts its tumor suppressive role is barely understood. CHD5 belongs to the CHD family of SWI-SNF-like ATP dependent-chromatin remodeling proteins; however, the role of CHD5 in modulating chromatin dynamics has not been reported. Here, we show that CHD5's tumor suppressive function is dependent on its tandem plant homeodomains (PHDs)—modules that in several other chromatin-remodeling proteins regulate transcription by binding to specific covalent modifications on histone tails. Each of the two PHDs of CHD5 preferentially bind unmethylated H3K4 (H3K4me0), an interaction abrogated by methylation of H3K4 but unaffected by modification of H3K9. Consistent with its binding specificity in vitro, genome-wide ChIP-sequencing indicates that CHD5 binds loci lacking highly methylated H3K4 marks in vivo. Both loss- and gain-of-function studies reveal that CHD5 modulates transcription, and furthermore, that CHD5 is a potent inhibitor of cellular proliferation. Mutation of residues within the PHDs of CHD5 that abolish H3K4me0 binding effectively abrogate the ability of CHD5 to modulate expression of target genes as well as to inhibit proliferation, leading to tumorigenesis in vivo.

These findings identify CHD5 as a member of a newly appreciated class of H3K4me0-binding PHD containing proteins and reveal a critical role for this interaction in facilitating CHD5's cellular function, providing new insight into the molecular mechanism responsible for the tumor suppressive role of CHD5.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY20-01. doi:1538-7445.AM2012-SY20-01
Abstract SY29-03: Regulation and function of the Hippo-YAP pathway in organ size, tumorigenesis, and metastasis
Authors: Guan Kun-Liang Liang
Published: August 2012

Regulation and function of the Hippo-YAP pathway in organ size, tumorigenesis and metastasis Kun-Liang Guan, Department of Pharmacology and Moores Cancer Center, University of California at San Diego, USA The Yes-associated protein (YAP) is a transcription co-activator that plays a critical role in organ size control by promoting cell proliferation and inhibiting apoptosis. YAP is a human oncogene amplified or overexpressed in some human cancers. YAP represents the major downstream of the Hippo tumor suppressor pathway. The Lats tumor suppressor kinase in the Hippo pathway phosphorylates and inactivates YAP. Recent studies have demonstrated regulation of the Hippo pathway by cell-cell contact, cell adhesion, and mechanical stress. Cell attachment to extracellular matrix (ECM) is crucial to cell physiology such as cell polarity, cell motility, and cell proliferation. In normal cells, loss of attachment to ECM induces a specific type of apoptosis, termed anoikis. In metastatic cancer cells, resistance to anoikis allows their survival in circulation and dispersion to distant anatomic sites leading to tumor metastasis. We have observed that cell detachment activates the Hippo pathway kinases Lats1/2 and leads to YAP phosphorylation and inhibition. The detachment-induced YAP inactivation is required for anoikis. Furthermore, actin and microtubule organization mediates Lats1/2 activation in response to cell detachment. Moreover, Lats2 downregulation is tightly associated with metastatic prostate cancer, indicating a role of the Hippo pathway in tumor metastasis. Our findings provide an important connection from cell attachment and cytoskeleton organization to cell proliferation, anoikis, and cancer metastasis through the Hippo pathway.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY29-03. doi:1538-7445.AM2012-SY29-03
Antibodies against Carbonic Anhydrase in Patients with Aplastic Anemia
Authors: Lakota Jan , Lanz Annika , Dubrovcakova Maria , Jankovicova Barbora , Gonzalez Asensio , Stern Martin
Published: August 2012

Background/Aims: Antibodies against carbonic anhydrase (CA) have been detected in patients with an aplastic anemia (AA)-like syndrome after autologous stem cell transplantation. Methods: We analyzed sera of 53 bona fide AA patients before and after treatment with anti-thymocyte globulin (ATG) or bone marrow transplantation for the presence of anti-CA antibodies. Results: Anti-CA antibodies were detected in 20 patients (38%) and were associated with older age at diagnosis of AA. Antibody-positive patients showed poor response to ATG treatment (complete response 14%) and inferior long-term survival (36% at 10 years), when compared to antibody-negative patients (complete response and 10-year survival both 64%). Two thirds of patients with antibodies at diagnosis of AA became antibody negative after treatment with ATG. Clearance of the antibody did not appear to be associated with hematological improvement. Conclusion: Antibodies against CA are detected frequently at diagnosis of AA, and their presence identifies a subset of patients with poor response to immunosuppressive treatment.
The 34,XY1,der(13) Chromosome Constitution with Loss of Y2 Is Associated with Unilateral Testicular Hypoplasia in the Endangered Indian Blackbuck Antelope (Antilope cervicapra)
Authors: Sontakke S.D. , Kandukuri L.R. , Umapathy G. , Kulashekaran K.M. , Venkata P.O. , Shivaji S. , Singh L.
Published: August 2012

The present study is the first report of unilateral testicular hypoplasia in 3 of 15 (20%) Indian blackbuck antelopes (Antilope cervicapra). Interestingly, the condition was restricted to only the right testis in all cases. Cytogenetic analysis revealed chromosomal aneuploidy in the affected individuals which had a 34,XY1,der(13) karyotype with loss of the acrocentric (autosomal) Y2 and an aberrant chromosome 13. We further determined that the semen output and the circulating testosterone levels were markedly low in the males with hypoplastic testes as compared to fertile males.
Applying Genomic Analysis to Newborn Screening
Authors: Solomon B.D. , Pineda-Alvarez D.E. , Bear K.A. , Mullikin J.C. , Evans J.P. ,   NISC Comparative Sequencing Programc
Published: August 2012

Large-scale genomic analysis such as whole-exome and whole-genome sequencing is becoming increasingly prevalent in the research arena. Clinically, many potential uses of this technology have been proposed. One such application is the extension or augmentation of newborn screening. In order to explore this application, we examined data from 3 children with normal newborn screens who underwent whole-exome sequencing as part of research participation. We analyzed sequence information for 151 selected genes associated with conditions ascertained by newborn screening. We compared findings with publicly available databases and results from over 500 individuals who underwent whole-exome sequencing at the same facility. Novel variants were confirmed through bidirectional dideoxynucleotide sequencing. High-density microarrays (Illumina Omni1-Quad) were also performed to detect potential copy number variations affecting these genes. We detected an average of 87 genetic variants per individual. After excluding artifacts, 96% of the variants were found to be reported in public databases and have no evidence of pathogenicity. No variants were identified that would predict disease in the tested individuals, which is in accordance with their normal newborn screens. However, we identified 6 previously reported variants and 2 novel variants that, according to published literature, could result in affected offspring if the reproductive partner were also a mutation carrier; other specific molecular findings highlight additional means by which genomic testing could augment newborn screening.
Does Charter Status Determine Preferences? Comparing the Hiring Preferences of Charter and Traditional Public School Principals
Authors: Cannata Marisa , Engel Mimi
Published: August 2012

The academic success of any school depends on its teachers. However, relatively little research exists on the qualities principals value in teacher hiring, and we know almost nothing about charter school principals’ preferences. This article addresses this gap in the literature using survey results for a matched sample of charter and traditional public school principals. We compare regression-adjusted survey responses of charter and traditional public school principals to examine whether charter school principals report placing more emphasis on teacher hiring than principals in traditional public schools and whether principals’ preferences for teacher qualifications and characteristics vary between charter and traditional public schools. While we find some mean differences in principals’ reported hiring focus and preferences across charter and traditional public schools, regression results indicate that these differences are driven not by charter status but by school characteristics, such as average teacher experience and school enrollment.
The Scope for Promoting Equal Opportunity in Education: Evidence from the Kibbutz
Authors: Justman Moshe , Gilboa Yaakov
Published: August 2012

We compare the link between parents’ schooling and their children’s college-entrance test scores in Israeli kibbutzim (communal villages) and in the general population. Though kibbutzim are committed to an egalitarian ethos and provide all kibbutz children with similar need-based access to educational resources, we still find a substantial link between kibbutz parents’ schooling and their children’s test scores—roughly three-fifths its size in the general population. This confirms the importance of non-pecuniary channels of parental influence on education and provides an informative reference point on the practical scope for reducing origin dependence in education through public policy.
A Variational Approach for Retrieving Raindrop Size Distribution from Polarimetric Radar Measurements in the Presence of Attenuation
Authors: Cao Qing , Zhang Guifu , Xue Ming
Published: August 2012

This study presents a two-dimensional variational approach to retrieving raindrop size distributions (DSDs) from polarimetric radar data in the presence of attenuation. A two-parameter DSD model, the constrained-gamma model, is used to represent rain DSDs. Three polarimetric radar measurements—reflectivity ZH, differential reflectivity ZDR, and specific differential phase KDP—are optimally used to correct for the attenuation and retrieve DSDs by taking into account measurement error effects. Retrieval results with simulated data demonstrate that the proposed algorithm performs well. Applications to real data collected by the X-band Center for Collaborative Adaptive Sensing of the Atmosphere (CASA) radars and the C-band University of Oklahoma–Polarimetric Radar for Innovations in Meteorology and Engineering (OU-PRIME) also demonstrate the efficacy of this approach.
Documenting Wind Speed and Power Deficits behind a Utility-Scale Wind Turbine
Authors: Hirth Brian D. , Schroeder John L.
Published: August 2012

High-spatial-and-temporal-resolution radial velocity measurements surrounding a single utility-scale wind turbine were collected using the Texas Tech University Ka-band mobile research radars. The measurements were synthesized to construct the first known dual-Doppler analyses of the mean structure and variability of a single turbine wake. The observations revealed a wake length that subjectively exceeded 20 rotor diameters, which far exceeds the typically employed turbine spacing of 7–10 rotor diameters. The mean horizontal wind speed deficits found within the turbine wake region relative to the free streamflow were related to potential reductions in the available power for a downwind turbine. Mean wind speed reductions of 17.4% (14.8%) were found at 7 (10) rotor diameters downwind, corresponding to a potential power output reduction of 43.6% (38.2%). The wind speed deficits found within the wake also exhibit large variability over short time intervals; this variability would have an appreciable impact on the inflow of a downstream turbine. The full understanding and application of these newly collected data have the potential to alter current wind-farm design and layout practices and to affect the cost of energy.
Constraints on the Profiles of Total Water PDF in AGCMs from AIRS and a High-Resolution Model
Authors: Molod Andrea
Published: August 2012

Atmospheric general circulation model (AGCM) cloud parameterizations generally include an assumption about the subgrid-scale probability distribution function (PDF) of total water and its vertical profile. In the present study, the Atmospheric Infrared Sounder (AIRS) monthly-mean cloud amount and relative humidity fields are used to compute a proxy for the second moment of an AGCM total water PDF called the “RH01 diagnostic,” which is the AIRS mean relative humidity for cloud fractions of 0.1 or less. The dependence of the second moment on horizontal grid resolution is analyzed using results from a high-resolution global model simulation.

The AIRS-derived RH01 diagnostic is generally larger near the surface than aloft, indicating a narrower PDF near the surface, and varies with the type of underlying surface. High-resolution model results show that the vertical structure of profiles of the AGCM PDF second moment is unchanged as the grid resolution changes from 200 to 100 to 50 km, and that the second-moment profiles shift toward higher values with decreasing grid spacing.

Several Goddard Earth Observing System, version 5 (GEOS-5), AGCM simulations were performed with several choices for the profile of the PDF second moment. The resulting cloud and relative humidity fields were shown to be quite sensitive to the prescribed profile, and the use of a profile based on the AIRS-derived proxy results in improvements relative to observational estimates. The AIRS-guided total water PDF profiles, including their dependence on underlying surface type and on horizontal resolution, have been implemented in the version of the GEOS-5 AGCM used for publicly released simulations.
High-Resolution Monthly Rainfall Database for Ethiopia: Homogenization, Reconstruction, and Gridding
Authors: Tsidu G. Mengistu
Published: August 2012

Recent heightened concern regarding possible consequences of anthropogenically induced global warming has spurred analyses of data aimed at detection of climate change and more thorough characterization of the natural climate variability. However, there is greater concern regarding the extent and especially quality of the historical climate data. In this paper, rainfall records of 233 gauge stations over Ethiopia for the 1978–2007 period are employed in an analysis that involves homogenization, reconstruction, and gridding onto a regular 0.5° × 0.5° resolution grid. Inhomogeneity is detected and adjusted based on quantile matching. The regularized expectation-maximization and multichannel singular spectrum analysis algorithms are then utilized for imputation of missing values, and the latter has been determined to have a marginal advantage. Ordinary kriging is used to create a gridded monthly rainfall dataset. The spatial and temporal coherence of this dataset are assessed using harmonic analysis, self-organizing maps, and intercomparison with global datasets. The self-organizing map delineates Ethiopia into nine homogeneous rainfall regimes, which is consistent with seasonal and interannual rainfall variations. The harmonic analysis of the dataset reveals that the annual mode accounts for 55%–85% of the seasonal rainfall variability over western Ethiopia while the semiannual mode accounts for up to 40% over southern Ethiopia. The dataset is also intercompared with Global Precipitation Climatology Project (GPCP), Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP), Climatic Research Unit time series version 3 (CRUTS3.0), Tropical Rainfall Measuring Mission (TRMM), and interim ECMWF Re-Analysis (ERA-Interim) rainfall. The correlation of the dataset with global datasets ranges from 0.52 to 0.95 over sparse to dense rain gauge regions. The GPCP rainfall has a small bias and good correlation with the new dataset whereas TRMM and ERA-Interim have relatively large dry and wet biases, respectively.
The Winter Rainfall of Malaysia
Authors: Chen Tsing-Chang , Tsay Jenq-Dar , Yen Ming-Cheng , Matsumoto Jun
Published: August 2012

Malaysia is geographically separated into Peninsular Malaysia and west Borneo. The rainfall maximum in the former region occurs during November–December, whereas that in the latter region occurs during December–February. This difference of maximum rainfall period indicates that the formation mechanism is different for the rainfall centers in these two parts of Malaysia. Since rainfall is primarily produced by severe weather systems, the formation of a climatological rainfall center is explored through synoptic activity and the rainfall amount of this center is estimated through contributions by rain-producing disturbances. The major cause of the rainfall maximum of Peninsular Malaysia is cold surge vortices (CSVs) and heavy rainfall/flood (HRF) events propagating from the Philippine area and Borneo. In contrast, the major cause of the rainfall maximum of Borneo is these rain-producing disturbances trapped in Borneo. Disturbances of the former group are formed by the cold surge flows of the Philippine Sea type, whereas disturbances of the latter group are formed by cold surge flows of the South China Sea (SCS) type. The population of HRF events is about one-fourth of the rain-producing disturbances in both Peninsular Malaysia and Borneo, but they produce less than ~60% rainfall for these two regions. It is revealed from the synoptic and dynamic analyses that the major Borneo rain-producing disturbances propagate westward before December by strong tropical easterlies, but they are trapped after December by strong northeasterlies of the SCS-type cold surge flow.
Tornadoes in the New York Metropolitan Region: Climatology and Multiscale Analysis of Two Events
Authors: Colle Brian A. , Lombardo Kelly A. , Tongue Jeffrey S. , Goodman William , Vaz Nelson
Published: August 2012

This paper describes the climatology of tornadoes around New York City (NYC) and Long Island (LI), New York, and the structural evolution of two tornadic events that affected NYC on 8 August 2007 and 16 September 2010. Nearly half (18 of 34 events from 1950 to 2010) of NYC–LI tornadoes developed between 0500 and 1300 EDT, and August is the peak tornado month as compared to July for most of the northeast United States. A spatial composite highlights the approaching midlevel trough, moderate most unstable convective available potential energy (MUCAPE), and frontogenesis along a low-level baroclinic zone. Shortly before the early morning tornadoes on 8 August 2007, a mesoscale convective system intensified in the lee of the Appalachians in a region of low-level frontogenesis and moderate MUCAPE (~1500 J kg−1). Warm advection at low levels and evaporative cooling within an elevated mixed layer (EML) ahead of the mesoscale convective system (MCS) helped steepen the low-level lapse rates. Meanwhile, a surface mesolow along a quasi-stationary frontal zone enhanced the warm advection and low-level shear. The late afternoon event on 16 September 2010 was characterized by a quasi-linear convective system (QLCS) that also featured an EML aloft, a surface mesolow just west of NYC, low-level frontogenesis, and a southerly low-level jet ahead of an approaching midlevel trough. The QLCS intensified approaching NYC and generated mesovortices as the QLCS bowed outward. These cases illustrate the benefit of high-density surface observations, terminal Doppler radars, and sounding profiles from commercial aircraft for nowcasting these events.
City and Nation in an African Context
Authors: Freund Bill
Published: August 2012

Despite the manifest failings of the Congolese state since independence, its inability to deliver services or to promote the status or prestige of its population, the educated minority of citizens of the capital city, Kinshasa, continue to cling to a notion of the unified state as an ideal that is closely tied to their own sense of self in the world. At its peak, it was a city especially of display and consumption that nourished this sense. The city was the site of the creation of this class par excellence. The particular hold of the state as an ideal comes not out of some inherently African trait but in consequence of the conjuncture of class plus the particular way in which Kinshasa has evolved by contrast with other African capital cities and the DRC by contrast with other African countries.
‘Give the Devil His Due’: The Satanic Agenda and Social Justice in the Book of Job
Authors: Aimers Geoffrey J.
Published: August 2012

In this article the status of the Joban satan is revised in connection to the Divine Wager. The broadened scope of the wager sees a test of Job's and the Friends’ fear of God in the sense of self-conceit about God's will for genuine social justice. Is it obscured by presumption of grace and the ‘Just World’ delusion? The disillusionment of this self-conceit in the God speeches paves the way for repentance and restoration in the Epilogue. Thus the Joban satan is seen as adopting a more central role which is more consistent with that of a primary character. Fear of God, in connection to God's will for social justice, is seen as a major unifying theme in the overall composition.
Moving Beyond Achievement Data
Authors: Burger John M. , Nadirova Anna , Keefer Kateryna V.
Published: August 2012

The Student Orientation to School Questionnaire (SOS-Q) is a multidimensional student-centered assessment tool for measuring psychosocial facilitators of student engagement. The SOS-Q is based in research on the self-system models of motivation and direct student input on perceived supports and barriers for high school completion. The current study examined internal measurement properties (factor structure and reliability) of the upper-elementary and high school versions of the SOS-Q in two samples of Grade 4 ( N = 615) and Grades 7 and 9 ( N = 1,356) students, as an important step in the process of scale development and validation. Exploratory and confirmatory factor analyses (EFAs and CFAs) converged on a stable and reliable measurement structure for both versions of the scale, with common factors related to safe and caring school, peer relationships, self-confidence, external and internal resilience, and for the high school version only—perceived utility of school and extracurricular activities. Results are discussed in terms of incorporating the SOS-Q into comprehensive school assessment systems that go beyond the academic achievement and behavioral data and that can have important policy and program implications.
Varieties of psychiatric criticism
Authors: Szasz Thomas
Published: August 2012

I present a brief overview of the history of psychiatric criticism, followed by a critique of modern objections to diverse psychiatric practices, focusing on the critics’ neglect of the core problematic issue – the psychiatrist’s role in depriving innocent persons of liberty.
ROCK1 functions as a critical regulator of stress erythropoiesis and survival by regulating p53
Authors: Vemula Sasidhar , Shi Jianjian , Mali Raghuveer Singh , Ma Peilin , Liu Yan , Hanneman Philip , Koehler Karl R. , Hashino Eri , Wei Lei , Kapur Reuben
Published: August 2012

Erythropoiesis is a dynamic, multistep process whereby hematopoietic stem cells differentiate toward a progressively committed erythroid lineage through intermediate progenitors. Although several downstream signaling molecules have been identified that regulate steady-state erythropoiesis, the major regulators under conditions of stress remain poorly defined. Rho kinases (ROCKs) belong to a family of serine/threonine kinases. Using gene-targeted ROCK1-deficient mice, we show that lack of ROCK1 in phenylhydrazine-induced oxidative stress model results in enhanced recovery from hemolytic anemia as well as enhanced splenic stress erythropoiesis compared with control mice. Deficiency of ROCK1 also results in enhanced survival, whereas wild-type mice die rapidly in response to stress. Enhanced survivability of ROCK1-deficient mice is associated with reduced level of reactive oxygen species. BM transplantation studies revealed that enhanced stress erythropoiesis in ROCK1-deficient mice is stem cell autonomous. We show that ROCK1 binds to p53 and regulates its stability and expression. In the absence of ROCK1, p53 phosphorylation and expression is significantly reduced. Our findings reveal that ROCK1 functions as a physiologic regulator of p53 under conditions of erythroid stress. These findings are expected to offer new perspectives on stress erythropoiesis and may provide a potential therapeutic target in human disease characterized by anemia.
The highly conserved 5' untranslated region as an effective target towards the inhibition of Enterovirus 71 replication by unmodified and appropriate 2'-modified siRNAs
Authors: Deng Jun-Xia , Nie Xiao-Jing , Lei Ying-Feng , Ma Chao-Feng , Xu Dong-Liang , Li Biao , Xu Zhi-Kai , Zhang Guo-Cheng
Published: August 2012

Background

Enterovirus 71 (EV71) is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. It is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. Currently, no effective vaccine or specific clinical therapy is available against EV71.

Methods

Unmodified 21 nucleotide small interfering RNAs (siRNAs) and classic 2′-modified (2′-O-methylation or 2′-fluoro modification) siRNAs were designed to target highly conserved 5′ untranslated region (UTR) of the EV71 genome and employed as anti-EV71 agents. Real-time TaqMan RT-PCR, western blot analysis and plaque assays were carried out to evaluate specific viral inhibition by the siRNAs.

Results

Transfection of rhabdomyosarcoma (RD) cells with siRNAs targeting the EV71 genomic 5′ UTR significantly delayed and alleviated the cytopathic effects of EV71 infection, increased cell viability in EV71-infected RD cells. The inhibitory effect on EV71 replication was sequence-specific and dosage-dependent, with significant corresponding decreases in viral RNA, VP1 protein and viral titer. Appropriate 2′-modified siRNAs exhibited similar RNA interference (RNAi) activity with dramatically increased serum stability in comparison with unmodified counterparts.

Conclusion

Sequences were identified within the highly conserved 5′ UTR that can be targeted to effectively inhibit EV71 replication through RNAi strategies. Appropriate 2′-modified siRNAs provide a promising approach to optimizing siRNAs to overcome barriers on RNAi-based antiviral therapies for broader administration.
Immune responses in the lungs of patients with tuberculous pleural effusion without pulmonary tuberculosis
Authors: Qama Diana , Choi Won-Il , Kwon Kun Young
Published: August 2012

Background

Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis. Because most studies of TPE focused on the pleural space, little information regarding lung parenchyma is available. We therefore aimed to investigate immune responses in the lung parenchyma of TPE patients without pulmonary tuberculosis.

Methods

Patients with any evidence of pulmonary tuberculosis, either from radiologic or bacteriologic evaluation, were excluded. Bronchoalveolar lavage fluid (BALF) was collected from 10 newly diagnosed, untreated, HIV-negative TPE patients and 10 healthy controls. We analyzed T-lymphocyte subpopulations and measured 10 cytokines in BALF. Cytokine levels in BALF were standardised using urea.

Results

The concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and the CD4+/CD8+ ratio of T-lymphocytes were significantly higher in TPE patients without pulmonary tuberculosis than in the controls. Of the cytokines measured in BALF, VEGF showed the highest concentration. No difference was observed in T-helper type 2 cytokines between the 2 groups.

Conclusion

There were significant immune responses and increases in IFN-γ, TNF-α, and VEGF in the lung parenchyma of TPE patients without pulmonary tuberculosis. This result suggests that TPE may induce a significant immune response in lung parenchyma.
Acid stress response and protein induction in Campylobacter jejuni isolates with different acid tolerance
Authors: Birk Tina , Wik Monica Takamiya , Lametsch René , Knøchel Susanne
Published: August 2012

Background

During the transmission route from poultry to the human host, the major foodborne pathogen C. jejuni may experience many types of stresses, including low pH caused by different acids. However, not all strains are equally sensitive to the stresses. The aim of this study was to investigate the response to acid stress of three sequenced C. jejuni strains with different acid tolerances using HCl and acetic acid.

Results

Two-dimensional gel electrophoresis was used for proteomic analysis and proteins were radioactively labelled with methionine to identify proteins only related to acid exposure. To allow added radioactive methionine to be incorporated into induced proteins, a modified chemically defined broth was developed with the minimal amount of methionine necessary for satisfactory growth of all strains. Protein spots were analyzed using image software and identification was done with MALDI-TOF-TOF. The most acid-sensitive isolate was C. jejuni 327, followed by NCTC 11168 and isolate 305 as the most tolerant. Overall, induction of five proteins was observed within the pI range investigated: 19 kDa periplasmic protein (p19), thioredoxin-disulfide (TrxB), a hypothetical protein Cj0706 (Cj0706), molybdenum cofactor biosynthesis protein (MogA), and bacterioferritin (Dps). Strain and acid type dependent differences in the level of response were observed. For strain NCTC 11168, the induced proteins and the regulator fur were analysed at the transcriptomic level using qRT-PCR. In this transcriptomic analysis, only up-regulation of trxB and p19 was observed.

Conclusions

A defined medium that supports the growth of a range of Campylobacter strains and suitable for proteomic analysis was developed. Mainly proteins normally involved in iron control and oxidative stress defence were induced during acid stress of C. jejuni. Both strain and acid type affected sensitivity and response.