bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Increased Activation of Persistent Inward Currents in Individuals With Chronic Hemiparetic Stroke
Authors: McPherson Jacob G. , Ellis Michael D. , Heckman C. J. , Dewald Julius P. A.
Published: October 2008

Despite the prevalence of hyperactive stretch reflexes in the paretic limbs of individuals with chronic hemiparetic stroke, the fundamental pathophysiological mechanisms responsible for their expression remain poorly understood. This study tests whether the manifestation of hyperactive stretch reflexes following stroke is related to the development of persistent inward currents (PICs) leading to hyperexcitability of motoneurons innervating the paretic limbs. Because repetitive volleys of 1a afferent feedback can elicit PICs, this investigation assessed motoneuronal excitability by evoking the tonic vibration reflex (TVR) of the biceps muscle in 10 awake individuals with chronic hemiparetic stroke and measuring the joint torque and electromyographic (EMG) responses of the upper limbs. Elbow joint torque and the EMG activity of biceps, brachioradialis, and the long and lateral heads of triceps brachii were recorded during 8 s of 112-Hz biceps vibration (evoking the TVR) and for 5 s after cessation of stimulation. Repeated-measures ANOVA tests revealed significantly ( P ≤ 0.05) greater increases in elbow flexion torque and EMG activity in the paretic as compared with the nonparetic limbs, both during and up to 5 s following biceps vibration. The finding of these augmentations exclusively in the paretic limb suggests that contralesional motoneurons may become hyperexcitable and readily invoke PICs following stroke. An enhanced tendency to evoke PICs may be due to an increased subthreshold depolarization of motoneurons, an increased monoaminergic input from the brain stem, or both.
Lapatinib (Tykerb, GW572016) Reverses Multidrug Resistance in Cancer Cells by Inhibiting the Activity of ATP-Binding Cassette Subfamily B Member 1 and G Member 2
Authors: Dai Chun-ling , Tiwari Amit K. , Wu Chung-Pu , Su Xiao-dong , Wang Si-Rong , Liu Dong-geng , Ashby Charles R. , Huang Yan , Robey Robert W. , Liang Yong-ju , Chen Li-ming , Shi Cheng-Jun , Ambudkar Suresh V. , Chen Zhe-Sheng , Fu Li-wu
Published: October 2008

Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells expressing these transporters, although a small synergetic effect was observed in combining lapatinib and conventional chemotherapeutic agents in parental sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and resistant cells. Additionally, lapatinib significantly increased the accumulation of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and inhibited the transport of methotrexate and E217βG by ABCG2. Furthermore, lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner. However, lapatinib did not affect the expression of these transporters at mRNA or protein levels. Importantly, lapatinib also strongly enhanced the effect of paclitaxel on the inhibition of growth of the ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic. [Cancer Res 2008;68(19):7905–14]
Endothelial p70 S6 Kinase 1 in Regulating Tumor Angiogenesis
Authors: Liu Ling-Zhi , Zheng Jenny Z. , Wang Xin-Ru , Jiang Bing-Hua
Published: October 2008

The p70 S6 kinase 1 (p70S6K1) exerts its function in regulating protein synthesis, cell proliferation, cell cycle progression, and cell survival in response to growth factors and other cellular signals. But the direct effect of p70S6K1 in regulating tumor growth and angiogenesis remains to be elucidated. Here, we investigated the effect of p70S6K1 expressed in human dermal microvascular endothelial cells (HDMEC) in regulating cancer cell–inducing tumor growth and angiogenesis and found that HDMECs enhance cancer cell–induced tumor growth and angiogenesis. Constitutive activation of p70S6K1 in HDMECs is sufficient to enhance tumor growth and angiogenesis. Inhibition of p70S6K1 by its dominant-negative mutant in HDMECs interferes with tumor growth and angiogenesis, indicating that p70S6K1 activity in endothelial cells is required for regulating tumor angiogenesis. We found that p70S6K1 regulates hypoxia-inducible factor-1α (HIF-1α) expression in the human endothelial cells. Knockdown of HIF-1α in the endothelial cells decreases tumor growth and angiogenesis. These results show that p70S6K1 and HIF-1 play an important role in regulating the endothelial functions for inducing tumor growth and angiogenesis. This study helps to understand the role and molecular mechanism of p70S6K1 in regulating angiogenesis and tumor growth, and the role of endothelial p70S6K1/HIF-1 signaling in the regulation of tumor microenvironment and angiogenesis. [Cancer Res 2008;68(19):8183–8]
Presentation of Telomerase Reverse Transcriptase, a Self-Tumor Antigen, is Down-regulated by Histone Deacetylase Inhibition
Authors: Pellicciotta Ilenia , Cortez-Gonzalez Xochitl , Sasik Roman , Reiter Yoram , Hardiman Gary , Langlade-Demoyen Pierre , Zanetti Maurizio
Published: October 2008

Histone deacetylases (HDAC) modify the architecture of chromatin, leading to decreased gene expression, an effect that is reversed by HDAC inhibition. The balance between deacetylation and acetylation is central to many biological events including the regulation of cell proliferation and cancer but also the differentiation of immune T cells. The effects of HDAC inhibition on the interaction between antitumor effector T cells and tumor cells are not known. Here, we studied presentation of a universal self-tumor antigen, telomerase reverse transcriptase, in human tumor cells during HDAC inhibition. We found that HDAC inhibition with trichostatin A was associated with a decreased presentation and diminished killing of tumor cells by CTLs. Using gene array analysis, we found that HDAC inhibition resulted in a decrease of genes coding for proteasome catalytic proteins and for tapasin, an endoplasmic reticulum resident protein involved in the MHC class I pathway of endogenous antigen presentation. Our findings indicate that epigenetic changes in tumor cells decrease self-tumor antigen presentation and contribute to reduced recognition and killing of tumor cells by cytotoxic T lymphocytes. This mechanism could contribute to tumor escape from immune surveillance. [Cancer Res 2008;68(19):8085–93]
Brn-2 Represses Microphthalmia-Associated Transcription Factor Expression and Marks a Distinct Subpopulation of Microphthalmia-Associated Transcription Factor–Negative Melanoma Cells
Authors: Goodall Jane , Carreira Suzanne , Denat Laurence , Kobi Dominique , Davidson Irwin , Nuciforo Paolo , Sturm Richard A. , Larue Lionel , Goding Colin R.
Published: October 2008

The origin of tumor heterogeneity is poorly understood, yet it represents a major barrier to effective therapy. In melanoma and in melanocyte development, the microphthalmia-associated transcription factor (Mitf) controls survival, differentiation, proliferation, and migration/metastasis. The Brn-2 (N-Oct-3, POU3F2) transcription factor also regulates melanoma proliferation and is up-regulated by BRAF and β-catenin, two key melanoma-associated signaling molecules. Here, we show that Brn-2 also regulates invasiveness and directly represses Mitf expression. Remarkably, in melanoma biopsies, Mitf and Brn-2 each mark a distinct subpopulation of melanoma cells, providing a striking illustration of melanoma tumor heterogeneity with implications for melanoma therapy. [Cancer Res 2008;68(19):7788–94]
Addiction to Elevated Insulin-like Growth Factor I Receptor and Initial Modulation of the AKT Pathway Define the Responsiveness of Rhabdomyosarcoma to the Targeting Antibody
Authors: Cao Liang , Yu Yunkai , Darko Isaac , Currier Duane , Mayeenuddin Linnia H. , Wan Xiaolin , Khanna Chand , Helman Lee J.
Published: October 2008

Insulin-like growth factor I receptor (IGF-IR) and its ligands are overexpressed by tumors, mediating proliferation and protecting against stress-induced apoptosis. Accordingly, there has been a considerable amount of interest in developing therapeutic agents against IGF-IR. IGF-IR is believed to be ubiquitously expressed without detectable mutation or amplification in cancer. We explored the determinants of cellular response to a humanized anti–IGF-IR antibody. Our results showed a large variation in IGF-IR levels in rhabdomyosarcoma tumor specimens that were comparable with those in rhabdomyosarcoma cell lines. In vitro analysis revealed a direct and very significant correlation between elevated IGF-IR levels and antiproliferative effects of the antibody and defined a receptor number that would predict sensitivity. Our data further suggested a strong dependence on IGF-IR for AKT signaling in cells with elevated IGF-IR. The sensitivity of the high IGF-IR–expressing cells was blocked with a constitutively active AKT. The extracellular signal-regulated kinase pathway was not affected by the antibody. In vivo studies showed that anti–IGF-IR had single-agent antitumor activity; furthermore, predictions of responses based on IGF-IR levels were accurate. In vivo biomarker analysis suggested that h7C10 down-regulated both IGF-IR and p-AKT initially, concordant with antitumor activity. Subsequent progression of tumors was associated with reactivation of p-AKT despite sustained suppression of IGF-IR. These results identified the first predictive biomarker for anti–IGF-IR therapies in cancer. [Cancer Res 2008;68(19):8039–48]
The History of Tumor Virology
Authors: Javier Ronald T. , Butel Janet S.
Published: October 2008

In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. Later identification of mammalian tumor viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by Ludwik Gross, sparked the first intense interest in tumor virology by suggesting the possibility of a similar causal role for viruses in human cancers. This change in attitude opened the door in the 1960s and 1970s for the discovery of the first human tumor viruses—EBV, hepatitis B virus, and the papillomaviruses. Such knowledge proved instrumental to the development of the first cancer vaccines against cancers having an infectious etiology. Tumor virologists additionally recognized that viruses could serve as powerful discovery tools, leading to revolutionary breakthroughs in the 1970s and 1980s that included the concept of the oncogene, the identification of the p53 tumor suppressor, and the function of the retinoblastoma tumor suppressor. The subsequent availability of more advanced molecular technologies paved the way in the 1980s and 1990s for the identification of additional human tumor viruses—human T-cell leukemia virus type 1, hepatitis C virus, and Kaposi's sarcoma virus. In fact, current estimates suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus, viruses not only have been shown to represent etiologic agents for many human cancers but have also served as tools to reveal mechanisms that are involved in all human malignancies. This rich history promises that tumor virology will continue to contribute to our understanding of cancer and to the development of new therapeutic and preventive measures for this disease in the 21st century. [Cancer Res 2008;68(19):7693–706]
Therapeutic IMC-C225 Antibody Inhibits Breast Cancer Cell Invasiveness via Vav2-Dependent Activation of RhoA GTPase
Authors: Molli Poonam R. , Adam Liana , Kumar Rakesh
Published: October 2008

Purpose: Abnormalities in the expression and signaling pathways downstream of epidermal growth factor receptor (EGFR) contribute to progression, invasion, and maintenance of the malignant phenotype in human cancers. Accordingly, biological agents, such as the EGFR-blocking antibody IMC-C225 have promising anticancer potential and are currently in various stages of clinical development. Because use of IMC-C225 is limited, at present, only for treatment of cancer with high EGFR expression, the goal of the present study was to determine the effect of IMC-C225 on the invasiveness of breast cancer cells with high and low levels of EGFR expression.

Experimental Design: The effect of IMC-C225 on invasion was studied using breast cancer cell lines with high and low levels of EGFR expression.

Results: The addition of EGF led to progressive stress fiber dissolution. In contrast, cells treated with IMC-C225 showed reduced invasiveness and increased stress-fiber formation. Interestingly, IMC-C225 pretreatment was accompanied by EGFR phosphorylation, as detected using an anti–phosphorylated tyrosine antibody (PY99), which correlated with phosphorylation of Vav2 guanine nucleotide exchange factor and activation of RhoA GTPase irrespective of EGFR level, and Vav2 interacted with EGFR only in IMC-C225–treated cells. The underlying mechanism involved an enhanced interaction between β1 integrins and EGFR upon IMC-C225 treatment.

Conclusion: Here, we defined a new mechanism for IMC-C225 that cross-links integrins with EGFR, leading to activation of RhoA and inhibition of breast cancer cell invasion irrespective of the level of EGFR in the cells, thus providing a rationale for using IMC-C225 in the metastatic setting independent of the levels of EGFR.
A Phase I-II Study of Combined Blockade of the ErbB Receptor Network with Trastuzumab and Gefitinib in Patients with HER2 (ErbB2)-Overexpressing Metastatic Breast Cancer
Authors: Arteaga Carlos L. , O'Neill Anne , Moulder Stacy L. , Pins Michael , Sparano Joseph A. , Sledge George W. , Davidson Nancy E.
Published: October 2008

Purpose: To determine the safety, and efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in combination with trastuzumab in patients with metastatic HER2-positive metastatic breast cancer.

Experimental Design: Patients with HER2-overexpressing breast cancer were treated with trastuzumab 2 mg/kg/week and gefitinib 250 to 500 mg/day. The primary end point of the study was to increase the proportion progression-free from 50% to 65% at 6 months in chemotherapy-naive patients and from 50% to 70% at 3 months in patients previously treated with chemotherapy in the metastatic setting.

Results: In the phase I study, all patients treated with gefitinib 500 mg/day developed grade 3 diarrhea. The phase II study was conducted using trastuzumab and gefitinib 250 mg/day. One patient achieved a complete response, 2 had a partial response, and 6 had stable disease for an overall response rate of 9% and a clinical benefit rate of 28% (9 of 32). Median time to progression (TTP) was 3 months (95% confidence interval, 2.3-4.1) in patients with no prior systemic therapy in the metastatic setting (n = 23). In patients treated with prior systemic therapy (n = 9), the median TTP of 5.3 months (95% confidence interval, 2.8-8.1). Overall median survival was 27 months. TTP was similar in EGFR-positive compared with EGFR-negative patients.

Conclusions: Gefitinib 250 mg/day was the maximal dose that can be safely administered with weekly trastuzumab. Interim analysis of the efficacy suggested that the combination was unlikely to result in clinical benefit compared with trastuzumab alone. These results do not support the use of this combination in patients with HER2-positive breast cancer.
Single Nucleotide Polymorphisms, Apoptosis, and the Development of Severe Late Adverse Effects After Radiotherapy
Authors: Azria David , Ozsahin Mahmut , Kramar Andrew , Peters Sheila , Atencio David P. , Crompton Nigel E.A. , Mornex Françoise , Pèlegrin André , Dubois Jean-Bernard , Mirimanoff René-Olivier , Rosenstein Barry S.
Published: October 2008

Purpose: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, ≥3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation.

Experimental Design: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18).

Results: Overall, 13 and 21 patients were found to possess a total of <4 and ≥4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had ≥4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had ≥4 SNPs (P < 0.001).

Conclusions: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.
BKM1740, an Acyl-Tyrosine Bisphosphonate Amide Derivative, Inhibits the Bone Metastatic Growth of Human Prostate Cancer Cells by Inducing Apoptosis
Authors: Seo Seong Il , Gera Lajos , Zhau Haiyen E. , Qian Wei Ping , Iqbal Shareen , Johnson Nicole A. , Zhang Shumin , Zayzafoon Majd , Stewart John , Wang Ruoxiang , Chung Leland W.K. , Wu Daqing
Published: October 2008

Purpose: Survivin overexpression has been associated with an unfavorable outcome in human PCa; however, its role in metastasis remains elusive. We aim to (a) evaluate the clinical implications of survivin expression in PCa bone metastasis; (b) determine in vivo efficacy of BKM1740, a small-molecule compound, against PCa skeletal growth and survival; and (c) investigate molecular mechanism by which BKM1740 augments apoptosis in bone metastatic PCa cells.

Experimental Design: Survivin expression was analyzed in PCa specimens and experimental models. Bone metastatic C4-2 and ARCaPM cell lines were used to evaluate the in vitro effects of BKM1740 and molecular mechanism for the induction of apoptosis. C4-2 cells were grown intratibially in athymic nude mice to evaluate the in vivo efficacy of BKM1740. Tumor growth in mouse bone was assessed by serum prostate-specific antigen and radiography and confirmed by immunohistochemical analyses.

Results: Survivin expression is positively associated with clinical PCa bone metastasis. BKM1740 induced apoptosis in PCa cells by repressing survivin. Mice with established C4-2 tumors in tibia showed a marked decrease in serum prostate-specific antigen and much improved bone architecture radiographically after treatment with BKM1740. Immunohistochemical assays of mouse tumor samples confirmed that the in vivo effects were mediated by inhibition of survivin and induction of apoptosis.

Conclusions: Survivin expression is associated with PCa bone metastasis. BKM1740 treatment specifically inhibited survivin and induced apoptosis in vitro and was efficacious in retarding PCa skeletal growth in a mouse model. BKM1740 is a promising small-molecule compound that could be used to treat PCa bone metastasis.
Dedifferentiated Liposarcoma in the Retroperitoneum in an Atomic Bomb Survivor: Report of a Case
Authors: Nakamura Yukio , Yumiba Takeyoshi , Yamasaki Yoshio , Momiyama Takuya , Ito Akira , Akamaru Yusuke , Kasugai Tsutomu
Published: October 2008

A 76-year-old Japanese man was admitted to Kosei-Nenkin Hospital (Osaka, Japan) in November 2006; his chief complaint was a 10-kg loss in body weight over 3 months prior to admission. Abdominal computed tomography (CT) and dynamic magnetic resonance imaging (MRI) showed three masses in the retroperitoneum. The patient subsequently underwent surgery. The final histopathological diagnosis of tumors 1 and 2 was malignant fibrous histiocytoma of the retroperitoneum, and tumor 3 was a well-differentiated liposarcoma. By the presence of the liposarcoma, tumor 1 and 2 were thought to be the dedifferentiated areas of liposarcomas. At the age of 16, the patient had been exposed to radiation from the atomic bomb at Hiroshima towards the end of the Second World War. We postulate that in this case, radiation from the atomic bomb may have played an important role in the development of the sarcomas.
Estimation of Daytime Net Radiation from Shortwave Radiation Measurements and Meteorological Observations
Authors: Wang Kaicun , Liang Shunlin
Published: October 2008

Changes in surface net radiation Rn control the earth’s climate, the hydrological cycle, and plant photosynthesis. However, Rn is not readily available. This study develops a method to estimate surface daytime Rn from solar shortwave radiation measurements as well as conventional meteorological observations (or satellite retrievals) including daily minimum temperature, daily temperature range, and relative humidity, and vegetation indices from satellite data. Measurements collected at 22 U.S. and 2 Tibetan Plateau, China, sites from 2000 to 2006 are used to develop and validate the method. Land cover types include desert, semidesert, croplands, grasslands, and forest. Site elevations range from 98 to 4700 m. The results show that the method estimates Rn under clear and cloudy conditions accurately over a range of land cover types, elevations, and climates without requiring local calibration. The results show that the method estimates Rn accurately. The bias varies from −7.8 to 9.7 W m−2 (±3% in relative value) for different sites, and the root-mean-square error ranges from 12.8 to 21 W m−2 (from +5% to +9% in relative value) for different sites, with an average of 16.9 W m−2 (+6% relative) for all sites. The correlation coefficient for all sites is about 0.99. The correlation coefficient between the measured and predicted annual anomaly (year average subtracted from multiyear average) in daytime Rn is as high as 0.91, demonstrating that the method accurately estimates long-term variation in Rn.
Theoretical Studies of Convectively Forced Mesoscale Flows in Three Dimensions. Part I: Uniform Basic-State Flow
Authors: Han Ji-Young , Baik Jong-Jin
Published: October 2008

Convectively forced mesoscale flows in three dimensions are theoretically investigated by examining the transient response of a stably stratified atmosphere to convective heating. Solutions for the equations governing small-amplitude perturbations in a uniform basic-state wind with specified convective heating are analytically obtained using the Green function method. In the surface pulse heating case, it is explicitly shown that the vertical displacement at the center of the 3D steady heating decreases as fast as t−1 for large t. Hence, unlike in two dimensions, the steady state is approached in three dimensions. In the finite-depth steady heating case, the perturbation vertical velocity field in the stationary mode shows a main updraft region extending over the heating layer and V-shaped upward and downward motions above and below the heating layer. Including the third dimension results in a stronger updraft at an early stage, a weaker compensating downward motion, and a weaker stationary gravity wave field in a quasi-steady state than in the case of two dimensions. An examination of flow response fields for various vertical structures of convective heating indicates that stationary gravity waves above the main updraft region become strong in intensity as the height of the maximum convective heating increases. In response to the transient heating, a main updraft region extending over the heating layer no longer appears at a dissipation stage of deep convection. Instead, alternating regions of upward and downward motion with an upstream phase tilt appear.
Sea Ice in the Canadian Arctic Archipelago: Modeling the Past (1950–2004) and the Future (2041–60)
Authors: Sou Tessa , Flato Gregory
Published: October 2008

Considering the recent losses observed in Arctic sea ice and the anticipated future warming due to anthropogenic greenhouse gas emissions, sea ice retreat in the Canadian Arctic Archipelago (CAA) is expected and indeed is already being observed. As most global climate models do not resolve the CAA region, a fine-resolution ice–ocean regional model is developed and used to make a projection of future changes in the CAA sea ice. Results from a historical run (1950–2004) are used to evaluate the model. The model does well in representing observed sea ice spatial and seasonal variability, but tends to underestimate summertime ice cover. The model results for the future (2041–60) show little change in wintertime ice concentrations from the past, but summertime ice concentrations decrease by 45%. The ice thickness is projected to decrease by 17% in the winter and by 36% in summer. Based on this study, a completely ice-free CAA is unlikely by the year 2050, but the simulated ice retreat suggests that the region could support some commercial shipping.
Mechanisms for the Interannual Variability of SST in the East Pacific Warm Pool
Authors: Karnauskas Kristopher B. , Busalacchi Antonio J.
Published: October 2008

In comparison with the western and equatorial Pacific Ocean, relatively little is known about the east Pacific warm pool (EPWP). Observations indicate that the interannual variability of sea surface temperature (SST) in the EPWP is highly correlated (0.95) with the El Niño–Southern Oscillation (ENSO). In this paper, an ocean general circulation model (OGCM) of the tropical Pacific Ocean and various atmospheric and oceanic observations are used to diagnose the physical processes governing the interannual variability of SST in the EPWP. Atmospheric forcings for the OGCM are derived purely from satellite observations between 1988 and 2004.

Shortwave heating is identified as playing a dominant role in the interannual SST tendency of the EPWP. The high correlation between SST in the EPWP and eastern equatorial Pacific is therefore explained not by ocean processes, but by an atmospheric link. ENSO-driven equatorial SST anomalies modify the distribution of the overlying atmospheric vertical motions and therefore cloud cover and ultimately shortwave heating. During an El Niño event, for example, the ITCZ is equatorward displaced from its normal position over the EPWP, resulting in anomalously large shortwave heating over the EPWP. Analysis of poleward ocean heat transport and coastal Kelvin waves confirms that oceanic processes are not sufficient to explain the interannual variability of the EPWP.
Improved Turbulent Air–Sea Flux Bulk Parameters for Controlling the Response of the Ocean Mixed Layer: A Sequential Data Assimilation Approach
Authors: Skachko Sergey , Brankart Jean-Michel , Castruccio Frédéric , Brasseur Pierre , Verron Jacques
Published: October 2008

Bulk formulations parameterizing turbulent air–sea fluxes remain among the main sources of error in present-day ocean models. The objective of this study is to investigate the possibility of estimating the turbulent bulk exchange coefficients using sequential data assimilation. It is expected that existing ocean assimilation systems can use this method to improve the air–sea fluxes and produce more realistic forecasts of the thermohaline characteristics of the mixed layer. The method involves augmenting the control vector of the assimilation scheme using the model parameters that are to be controlled. The focus of this research is on estimating two bulk coefficients that drive the sensible heat flux, the latent heat flux, and the evaporation flux of a global ocean model, by assimilating temperature and salinity profiles using horizontal and temporal samplings similar to those to be provided by the Argo float system. The results of twin experiments show that the method is able to correctly estimate the large-scale variations in the bulk parameters, leading to a significant improvement in the atmospheric forcing applied to the ocean model.
An Analysis of the Large-Scale Climate Anomalies Associated with the Snowstorms Affecting China in January 2008
Authors: Wen Min , Yang Song , Kumar Arun , Zhang Peiqun
Published: October 2008

Extraordinarily frequent and long-lasting snowstorms affected China in January 2008, causing above-normal precipitation, below-normal temperature, and severe icing conditions over central–southern China. These snowstorms were closely linked to the change in the Middle East jet stream (MEJS), which intensified and shifted southeastward. The change in MEJS was accompanied by southeastward shifts of the ridge and the trough over Europe and western Asia. The intensified MEJS also strengthened the trough embedded in the southern branch of the subtropical westerlies over the southern Tibetan Plateau, enhancing the water vapor transport from western Asia and the Bay of Bengal to China. In the meantime, the subtropical western Pacific high (SWPH) was stronger and its ridgeline was farther north than normal. The anomalous high slowed down the eastward propagation of weather systems to the Pacific and favored convergence of water vapor over central–southern China. The MEJS is usually strong when the Arctic Oscillation (AO) is positive and the SWPH is farther north than normal in La Niña winters. Compared to the SWPH and the Niño-3.4 sea surface temperature (SST), the MEJS and the AO exert stronger influences on the temperature and the precipitation over central–southern China, despite the fact that these possible impacting factors are not completely independent from each other. Although the La Niña event might contribute to the climate anomalies through its relation with the SWPH in January 2008, an analysis of historical events indicates that La Niña conditions alone can hardly cause severe and persistent snow conditions over central–southern China. In addition, compared to the Niño-3.4 SST and the SWPH, the conditions of December MEJS and AO exhibit stronger precursory signals of the variability of January temperature over central–southern China.
Thermal Management for Boron Nitride Filled Metal Core Printed Circuit Board
Authors: Yung K.C. , Wang J. , Yue T.M.
Published: October 2008

This study aims at investigating novel thermal material based on filled epoxy for metal-core printed circuit boards (PCBs). The next generation PCB materials are expected to possess high heat dissipation capability in addition to low coefficient of thermal expansion (CTE) as the accumulated heat from high performance electronic devices should be removed for proper operation. In this study, boron nitride (BN) filler with different size (from micro to nano size) and content were employed to prepare thermally conductive polymer composites. Various percentage of coupling agent was used for the surface treatment of fillers in order to produce homogenous composites with lower CTE. The effect of filler and coupling agent to thermal conductivity of composite are discussed. It indicated that the experimental results fit well with the Bruggeman model with variety filler size. The use of 1% of couple agent was found to be more effective in increasing thermal conductivity of the composite. Despite the maximum content of the BN allowed to be added into the epoxy is about 30% due to the comparatively high viscosity of the varnish, as low as 13% of the micron-sized BN-filled dielectric is enough to fulfil the requirement of thermal conductivity larger than 1 W/m K and balance other critical properties used for PCB application. It is feasible to be a cost-effective advanced thermal material.
Study of the Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Cellulose Nanowhisker Composites Prepared by Solution Casting and Melt Processing
Authors: Long Jiang  , Morelius Erving , Jinwen Zhang  , Wolcott Michael , Holbery James
Published: October 2008

In this study cellulose nanowhiskers (CNW) were prepared by sulfuric acid hyrolysis from microcrystalline cellulose (MCC). The biopolymer composites of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/CNW, was fabricated by solution casting using N,N-dimethylformamide (DMF) as the solvent. Homogeneous dispersion of the whiskers was achieved and the composites exhibited improved tensile strength and modulus and increased glass transition temperature. The melt processing (extrusion and injection molding) of PHBV/CNW composites was also attempted. Despite using polyethylene glycol (PEG) as a compatibilizer, CNW agglomerates formed during freeze-drying could not be broken and well dispersed by the extrusion process due to the large surface area and the polar nature of CNW. As a result, the melt processed PHBV/CNW composites exhibited decreased strength and constant glass transition temperature, a typical trend of microparticle filled polymer systems. MCC was also treated by high-speed mechanical homogenizer to reduce its particle size down to nanoscale range. The homogenized MCC (HMCC) was blended with PHBV by melt processing with the same conditions. The obtained composites were found to have similar properties as the melt-processed PHBV/CNW composites due to poor HMCC dispersion. To the best of our knowledge, PHBV/ CNW system has not been studied so far. The treatment of MCC with high-speed homogenizer has also not been reported. This study augments the research on CNW nanocomposites.
Thermomechanical Effects on Aluminum Matrix Composites Reinforced with AlB2 Particles
Authors: Calderón Hermes E. , Suarez O. Marcelo , Barrios Ernesto
Published: October 2008

Aluminum matrix composites (AMCs) reinforced with aluminum diboride (AlB 2) particles are obtained through a casting process. A mixture design experiment combined with split-split plot experiment helped to assess the significance of the effects of cold work on precipitation hardening prior to aging. Both cold work and aging allowed higher microhardness of the composite matrix, which is further increased by higher levels of boron and copper. Microstructure analysis showed a good distribution of reinforcements and revealed a grain subdivision pattern due to cold work. Tensile tests helped corroborate the microhardness measurements. Fracture surface analysis showed a predominantly mixed brittle—ductile mode.
Pharmacokinetics and Pharmacodynamics of Vildagliptin in Healthy Chinese Volunteers
Authors: Hu Pei , Yin Qi , Deckert Fabienne , Jiang Ji , Liu Dongyang , Kjems Lise , Dole William P. , He Yan‐Ling
Published: October 2008

Vildagliptin is an orally effective, potent, and selective inhibitor of dipeptidyl peptidase IV (DPP‐4) that improves glycemic control in patients with type 2 diabetes. This was a randomized, double‐blind, placebo‐controlled, time‐lagged, parallel‐group study in a total of 60 healthy Chinese participants. Single‐ and multiple‐dose pharmacokinetics and pharmacodynamics, and safety and tolerability of vildagliptin were assessed following administration of 25, 50, 100, or 200 mg qd, or 50 mg bid. Vildagliptin was rapidly absorbed (tmax 1.5–2.0 hours) across the dose range of 25 to 200 mg and was quickly eliminated with a terminal elimination half‐life (t1/2) of approximately 2 hours. Consistent with the short t1/2, no accumulation of vildagliptin was observed following the administration of multiple doses (accumulation factors were 1.00–1.05 across the 25‐ to 200‐mg dose range). Vildagliptin AUC and Cmax values increased in an approximately dose‐proportional fashion (dose proportionality constant β1.00–1.16). Administration of vildagliptin 25 to 200 mg led to rapid and near‐complete (>95%) inhibition of DPP‐4 activity for at least 4 hours after dosing, which was associated with increases in plasma active glucagon‐like peptide‐1 of up to 2‐ to 3‐fold compared with placebo. The duration of DPP‐4 inhibition increased with dose. Glucose and insulin levels were not affected by vildagliptin in healthy participants, consistent with the fact that the glucose‐lowering effects of vildagliptin occur in a glucose‐dependent fashion. Vildagliptin was well tolerated at the highest tested dose of 200 mg qd. Vildagliptin 25 to 200 mg qd exhibits approximately dose‐proportional pharmacokinetics with no evidence of accumulation after multiple dosing in healthy Chinese participants. Vildagliptin demonstrates potent inhibition of DPP‐4 activity with excellent tolerability at doses of up to and including 200 mg qd.
The Other Side of We: When Outgroup Members Express Common Identity
Authors: Gómez Ángel , Dovidio John F. , Huici Carmen , Gaertner Samuel L. , Cuadrado Isabel
Published: October 2008

Previous research on the common ingroup identity model has focused on how one's representations of members of the ingroup and outgroup influence intergroup attitudes. Two studies reported here investigated how learning how others, ingroup or outgroup members, conceive of the groups within a superordinate category affects intergroup bias and willingness to engage in intergroup contact. Across both studies, high school students who learned that other ingroup members categorized students at both schools within the common identity of “students” showed less intergroup bias in evaluations and greater willingness for contact. However, consistent with the hypothesized effects of identity threat, when participants read that outgroup members saw the groups within the superordinate category, they exhibited a relatively negative orientation, except when ingroup members also endorsed a superordinate identity (Study 1). This result occurred even when the relative status of the groups was manipulated (Study 2).
The Good and Bad of Relationships: How Social Hindrance and Social Support Affect Relationship Feelings in Daily Life
Authors: Rafaeli Eshkol , Cranford James A. , Green Amie S. , Shrout Patrick E. , Bolger Niall
Published: October 2008

The authors examined the effects of social hindrance and support on negative and positive relationship-specific feelings in three daily diary studies. Study 1 showed that hindrance and support independently predicted positive relationship feelings, but only hindrance predicted negative feelings. Study 2 used new measures of hindrance and support and showed that hindrance and support independently predicted same-day relationship feelings but that the effects of hindrance were stronger in magnitude. Study 3 yielded similar findings using the new measures of hindrance and support and controlling for morning feeling. These asymmetrical crossover effects suggest that bad is only stronger than good when it comes to bad outcomes; they also support the distinction between aversive and appetitive relational processes.
The Dark Side of Creativity: Biological Vulnerability and Negative Emotions Lead to Greater Artistic Creativity
Authors: Akinola Modupe , Mendes Wendy Berry
Published: October 2008

Historical and empirical data have linked artistic creativity to depression and other affective disorders. This study examined how vulnerability to experiencing negative affect, measured with biological products, and intense negative emotions influenced artistic creativity. The authors assessed participants' baseline levels of an adrenal steroid (dehydroepiandrosterone-sulfate, or DHEAS), previously linked to depression, as a measure of affective vulnerability. They then manipulated emotional responses by randomly assigning participants to receive social rejection or social approval or to a nonsocial situation. Participants then completed artistic collages, which were later evaluated by artists. Results confirmed a person-by-situation interaction. Social rejection was associated with greater artistic creativity; however, the interaction between affective vulnerability (lower baseline DHEAS) and condition was significant, suggesting that situational triggers of negative affect were especially influential among those lower in DHEAS, which resulted in the most creative products. These data provide evidence of possible biological and social pathways to artistic creativity.
Feasibility of Self‐Propelling Nasojejunal Feeding Tube in Patients With Acute Pancreatitis
Authors: Joubert Corinne , Tiengou Laurent‐Eric , Hourmand‐Ollivier Isabelle , Dao Manh‐Thông , Piquet Marie‐Astrid
Published: October 2008

Background & Aims: To assess the success rate of a self‐propelling nasojejunal feeding tube in patients with acute pancreatitis. Methods: All patients admitted for acute pancreatitis were included. A self‐propelling nasojejunal feeding tube was introduced into the stomach, and gastrointestinal motility was stimulated using metoclopramide. If the tube failed to advance to the ligament of Treitz, a nasojejunal tube was placed endoscopically. Results: A total of 108 patients, 94 with necrotizing pancreatitis (Balthazar D/E) and 14 with nonnecrotizing pancreatitis (Balthazar B/C), were referred for artificial nutrition. In 11 cases, ileus persisted and parenteral nutrition was initiated. Among the remaining 97 patients, 5 refused tube placement. The self‐propelling feeding tube was inserted in 92 patients with successful migration to the ligament of Treitz in 61% (n = 56) and failure in 39% (n = 36). Of the 36 patients with an initial failed placement, endoscopic placement of a nasojejunal tube was successful 80% of the time (29 patients). The success rate of a nasojejunal self‐propelling feeding tube placement correlated directly with the severity of the acute pancreatitis (92% in B/C vs 61% in D vs 48% in E; P < .05). Conclusions: Use of a self‐propelling nasojejunal tube is a simple technique that can be successfully performed in the majority of patients with acute pancreatitis. The utility of this procedure in the most severe cases of acute pancreatitis continues to pose a challenge.
Trochlear Contact Pressures after Straight Anteriorization of the Tibial Tuberosity
Authors: Rue John-Paul H. , Colton Anne , Zare Stephanie M. , Shewman Elizabeth , Farr Jack , Bernard R. Bach , Cole Brian J.
Published: October 2008

Background

Anteromedialization of the tibial tuberosity has been shown to decrease mean total contact pressures of the lateral trochlea and to shift contact pressures to the medial trochlea.

Hypothesis

Modifying the anteromedialization osteotomy to a straight anteriorization osteotomy of the tibial tuberosity can decrease trochlear contact pressures without a resultant medial shift of forces to the medial trochlear contact area.

Study Design

Controlled laboratory study.

Methods

Ten cadavers were tested before and after straight anteriorization tibial tuberosity osteotomy by loading the extensor mechanism with 89.1 and 178.2 N at 0°, 30°, 60°, and 90° of flexion following a validated patellofemoral joint loading protocol. Contact pressures were measured with electroresistive pressure sensors placed directly on the trochlea.

Results

The mean trochlear contact pressures after osteotomy decreased significantly ( P < .05) for loads of 89.1 and 178.2 N at both 30° (23% and 20%, respectively) and 60° (18.7% and 31.9%, respectively) of knee flexion. The peak contact pressures decreased significantly ( P < .05) for loads of 89.1 and 178.2 N at 30° (24.3% and 27.0%, respectively) and 60° (31.9% and 24.5%, respectively) and for loads of 89.1 N at 90° (13.4%) of knee flexion.

Conclusion

The authors demonstrated significantly decreased trochlear contact forces after straight anteriorization osteotomy of the tibial tuberosity, without a significant resultant medial shift of the center of force.

Clinical Relevance

Straight anteriorization of the tibial tuberosity may be a useful adjunct for patients with medial articular defects of the patellar or trochlea in whom anteromedialization would be otherwise contraindicated.
Cyclical Loading of Coracoclavicular Ligament Reconstructions
Authors: Lee Steven J. , Keefer Eric P. , McHugh Malachy P. , Kremenic Ian J. , Orishimo Karl F. , Ben-Avi Simon , Nicholas Stephen J.
Published: October 2008

Background

Reconstruction for injuries to the acromioclavicular joint remains controversial.

Hypothesis

A coracoclavicular ligament reconstruction with a semitendinosus tendon would have superior performance to the classic coracoacromial ligament transfer with or without augmentation.

Study Design

Controlled laboratory study.

Methods

Five cadaveric shoulders were used to reconstruct the coracoclavicular ligaments with 3 methods: coracoacromial ligament transfer without augmentation, coracoacromial ligament transfer augmented with No. 5 Ethibond suture, and a semitendinosus tendon. Each reconstruction was cyclically loaded at 40 N to 80 N for 2500 cycles, then from 40 N to 210 N for 2500 cycles, followed by loading to failure. The number of cycles to 50% and 100% loss of acromioclavicular joint reduction were recorded.

Results

During the 40 N to 80 N-loading cycle, the coracoacromial transfer without augmentation failed (15 ± 16 cycles). The augmented coracoacromial ligament transfer and the semitendinosus reconstruction did not fail ( P = .008). During the 40 N to 210 N-loading cycle, the augmented coracoacromial ligament transfer failed (207 ± 399 cycles). The semitendinosus reconstruction survived through both loading cycles ( P < .01).

Conclusion

Coracoclavicular ligament reconstruction with a semitendinosus graft is a biomechanically superior construct in a cyclically loaded setting to a coracoacromial ligament transfer augmented with a No. 5 Ethibond suture.

Clinical Relevance

The semitendinosus graft is a strong, biologic option for reconstruction of the coracoclavicular ligaments.
Pathways to Assisted Living
Authors: Ball Mary M. , Perkins Molly M. , Hollingsworth Carole , Whittington Frank J. , King Sharon V.
Published: October 2008

This article examines how race and class influence decisions to move to assisted living facilities. Qualitative methods were used to study moving decisions of residents in 10 assisted living facilities varying in size and location, as well as race and socioeconomic status of residents. Data were derived from in-depth interviews with 60 residents, 43 family members and friends, and 12 administrators. Grounded theory analysis identified three types of residents based on their decision-making control: proactive, compliant, and passive/resistant. Only proactive residents (less than a quarter of residents) had primary control. Findings show that control of decision making for elders who are moving to assisted living is influenced by class, though not directly by race. The impact of class primarily related to assisted-living placement options and strategies available to forestall moves. Factors influencing the decision-making process were similar for Black and White elders of comparable socioeconomic status.