bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal Rectification Effects of Multiple Semiconductor Quantum Dot Junctions
Authors: Kuo David M.-T.
Published: October 2010

On the basis of the multiple-energy-level Anderson model, we theoretically study the thermoelectric effects of semiconductor quantum dots (QDs) in the nonlinear response regime. The charge and heat currents in the sequential tunneling process are calculated by Keldysh Green's function technique. The thermal rectification effect can be observed for such a multiple QD junction system, whereas the rectification efficiency is significantly affected by the tunneling rate, size fluctuation, and location distribution of QDs. We also find that the charge current rectification with respect to temperature bias can be observed.
Current–Voltage Characteristics in Nanoscale Tunnel Junctions Utilizing Thin-Film Edges
Authors: Kaiju Hideo , Kondo Kenji , Ishibashi Akira
Published: October 2010

We have derived a formula for current density–voltage (J–V) characteristics in nanoscale tunnel junctions, consisting of thin insulating barriers sandwiched between two thin metal films whose edges are crossing. As a result of the calculation ofJ–Vcharacteristics, the current density decreases with decreasing the metal thickness below 30–40 nm due to the quantization of the out-of-plane direction in the metal films. Moreover, as a result of the fabrication of Ni/NiO/Ni nanoscale tunnel junctions with a junction area of 24×24 nm2, we have found that experimentalJ–Vcharacteristics show a good fit to calculation results with a barrier height of 0.8 eV and a barrier thickness of 0.63 nm. These results indicate that the derived formula is useful for the evaluation of the barrier height and the barrier thickness and our fabrication method can be expected as a new technique for the creation of nanoscale tunnel junctions.
Low-Temperature Crystallization of Silicon Films Directly Deposited on Glass Substrates Covered with Yttria-Stabilized Zirconia Layers
Authors: Horita Susumu , Hana Sukreen
Published: October 2010

Si films were deposited at low temperatures on glass substrates covered with poly-yttria-stabilized zirconia (YSZ) layers. We investigated the dependences of crystallization on the Y content and cleaning solution for the YSZ layers. Transmission electron microscopy showed that some regions of the Si film deposited at 430 °C were directly crystallized on a YSZ layer without an amorphous region, where Si lattice fringes were tightly connected to YSZ lattice fringes. The crystallization of Si films on YSZ layers occurred at deposition temperatures lower than that on glass substrates by more than 100 °C. Zr, Y, and F concentrations in the Si film were negligible, except the Zr concentration near the interface. The discussion on the crystallization mechanism gave the following suggestions on the method of obtaining a high crystalline fraction. The YSZ layer should be chemically cleaned using a solution containing HF before Si film deposition, and the content ratio Y/(Zr+Y) of YSZ should be \gtrsim0.2.
Transient Phenomena in Plasma-Enhanced Chemical Vapor Deposition Processes of Thin-Film Silicon
Authors: Nunomura Shota , Yoshida Isao , Kondo Michio
Published: October 2010

The time-dependent gas phase kinetics in plasma-enhanced chemical vapor deposition (PECVD) processes has been studied. The temporal evolutions of the gas phase species, concentration and plasma parameters are measured in hydrogen-diluted silane plasmas, using plasma diagnostic techniques including mass spectrometry, optical emission spectroscopy, and probe and laser light scattering techniques. It is identified that gas phase kinetics such as electron collisions, chemical reactions, and particle transport play important roles in the transient phenomena of thin-film silicon PECVD processes. The characteristic times of the gas decomposition and depletion, diffusive transport, and nanoparticle growth and drift are discussed.
Investigation on Total Bremsstrahlung Radiation in High-Density Operation of Large Helical Device Based on Visible Bremsstrahlung Profile Measurement
Authors: Zhou Hangyu , Morita Shigeru , Goto Motoshi , Dong Chunfeng
Published: October 2010

Visible bremsstrahlung emission profiles have been studied over a wide range of electron densities in H2gas puff and solid-H2-pellet-fueled discharges of large helical device (LHD). Peaked profiles are observed in high-density discharges (ne≥1014cm-3) with pellet injection, whereas hollow profiles appeared in the normal discharges (ne≤1014cm-3) with gas puffing. The total bremsstrahlung radiation is analyzed from the visible bremsstrahlung profile by integrating the energy and plasma volume. It is found that the total bremsstrahlung radiation rapidly increases with the density in the pellet discharges, of which the increment is scaled by the square of density, while it is roughly constant against the density in the gas puff discharges. The total bremsstrahlung radiation becomes equal to the total radiation loss in the pellet discharges. The ratio of the total bremsstrahlung radiation to the total input power has only a range of 3–10% in the gas puff discharges. In contrast, the ratio increases with the density and reaches 30–40% in the pellet discharges. FlatZeffprofiles are observed not only in the gas puff discharges but also in the pellet discharges. This indicates that no impurity accumulation occurs in the high-density operation with H2pellet injection.
Development of Millimeter-Wave Planar Antennas Using Low-Loss Materials
Authors: Ito Naoki , Mase Atsushi , Kogi Yuichiro , Seko Noriaki , Tamada Masao , Shimazu Hiroshi , Sakata Eiji
Published: October 2010

As the importance of advanced millimeter-wave diagnostics increases, the fabrication of high-performance devices and components becomes essential. In this paper, we describe the development of millimeter-wave planar antennas using low-loss fluorine substrates. The problems to be solved in this study are the low degree of adhesion between copper foil and the fluorine substrate and the accuracy of device pattern using conventional fabrication techniques. In order to solve these problems, a new surface treatment of fluorine films and a fabrication method using electro-fine-forming (EF2) are proposed. In order to confirm the performance of the treated films, microstrip lines (MSLs) and planar patch antennas with a low sidelobe level in the E-plane are designed and fabricated on conventional fluorine substrates and grafted poly(tetrafluoroethylene) (PTFE) films.
Elastic Properties of New Pressure-Transmitting Medium Daphne 7474 under High Pressure
Authors: Sasaki Shigeo , Kato Seiichi , Kume Tetsuji , Shimizu Hiroyasu , Okada Tahei , Aoyama Shoji , Kusuyama Fumihiko , Murata Keizo
Published: October 2010

High-pressure Brillouin measurements of a pressure-transmitting medium Daphne 7474 have been performed at pressures up to about 12 GPa. We have determined the acoustic phase velocity, refractive index, equation of state, and adiabatic bulk modulus for Daphne 7474 as a function of pressure, and have evaluated the performance of Daphne 7474 as a hydrostatic pressure-transmitting medium. The obtained elastic properties show that Daphne 7474 is an excellent pressure-transmitting medium for transport and optical experiments in comparison with the 4:1 methanol–ethanol mixture below the solidification pressure 3.7 GPa of Daphne 7474.
Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program
Authors: Andersson Ulrika , Henriksson Emma , Ström Kristoffer , Alenfall Jan , Göransson Olga , Holm Cecilia
Published: October 2010

The aim of this study was to investigate the metabolic effects of a dietary supplement of powdered rose hip to C57BL/6J mice fed a high-fat diet (HFD). Two different study protocols were used; rose hip was fed together with HFD to lean mice for 20 wk (prevention study) and to obese mice for 10 wk (intervention study). Parameters related to obesity and glucose tolerance were monitored, and livers were examined for lipids and expression of genes and proteins related to lipid metabolism and gluconeogenesis. A supplement of rose hip was capable of both preventing and reversing the increase in body weight and body fat mass imposed by a HFD in the C57BL/6J mouse. Oral and intravenous glucose tolerance tests together with lower basal levels of insulin and glucose showed improved glucose tolerance in mice fed a supplement of rose hip compared with control mice. Hepatic lipid accumulation was reduced in mice fed rose hip compared with control, and the expression of lipogenic proteins was downregulated, whereas AMP-activated protein kinase and other proteins involved in fatty acid oxidation were unaltered. Rose hip intake lowered total plasma cholesterol as well as the low-density lipoprotein-to-high-density lipoprotein ratio via a mechanism not involving altered gene expression of sterol regulatory element-binding protein 2 or 3-hydroxymethylglutaryl-CoA reductase. Taken together, these data show that a dietary supplement of rose hip prevents the development of a diabetic state in the C57BL/6J mouse and that downregulation of the hepatic lipogenic program appears to be at least one mechanism underlying the antidiabetic effect of rose hip.
Angiotensin-(1–7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats
Authors: Giani Jorge F. , Muñoz Marina C. , Pons Romina A. , Cao Gabriel , Toblli Jorge E. , Turyn Daniel , Dominici Fernando P.
Published: October 2010

Angiotensin (ANG)-(1–7) constitutes an important functional end-product of the renin-angiotensin-aldosterone system that acts to balance the physiological actions of ANG II. In the kidney, ANG-(1–7) exerts beneficial effects by inhibiting growth-promoting pathways and reducing proteinuria. We examined whether a 2-wk treatment with a daily dose of ANG-(1–7) (0.6 mg·kg−1·day−1) exerts renoprotective effects in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Body weight, glycemia, triglyceridemia, cholesterolemia, as well as plasma levels of Na+ and K+ were determined both at the beginning and at the end of the treatment. Also, the weekly evolution of arterial blood pressure, proteinuria, and creatinine clearance was evaluated. Renal fibrosis was determined by Masson's trichrome staining. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and nuclear factor-κB (NF-κB) levels were determined by immunohistochemistry and confirmed by Western blotting analysis. The levels of glomerular nephrin were assessed by immunofluorescence. Chronic administration of ANG-(1–7) normalized arterial pressure, reduced glycemia and triglyceridemia, improved proteinuria, and ameliorated structural alterations in the kidney of SHRSP as shown by a restoration of glomerular nephrin levels as detected by immunofluorescence. These results were accompanied with a decrease in both the immunostaining and abundance of IL-6, TNF-α, and NF-κB. In this context, the current study provides strong evidence for a protective role of ANG-(1–7) in the kidney.
Distinct genetic regions modify specific muscle groups in muscular dystrophy
Authors: Swaggart Kayleigh A. , Heydemann Ahlke , Palmer Abraham A. , McNally Elizabeth M.
Published: October 2010

Phenotypic expression in the muscular dystrophies is variable, even with the identical mutation, providing strong evidence that genetic modifiers influence outcome. To identify genetic modifier loci, we used quantitative trait locus mapping in two differentially affected mouse strains with muscular dystrophy. Using the Sgcg model of limb girdle muscular dystrophy that lacks the dystrophin-associated protein γ-sarcoglycan, we evaluated chromosomal regions that segregated with two distinct quantifiable characteristics of muscular dystrophy, membrane permeability and fibrosis. We previously identified a single major locus on murine chromosome 7 that influences both traits of membrane permeability and fibrosis in the quadriceps muscle. Using a larger cohort, we now found that this same interval strongly associated with both traits in all limb skeletal muscle groups studied, including the gastrocnemius/soleus, gluteus/hamstring, and triceps muscles. In contrast, the muscles of the trunk were modified by distinct genetic loci, possibly reflecting the embryological origins and physiological stressors unique to these muscle groups. A locus on chromosome 18 was identified that modified membrane permeability of the abdominal muscles, and a locus on chromosome 3 was found that regulated diaphragm and abdominal muscle fibrosis. Fibrosis in the heart associated with a region on chromosome 9 and likely reflects differential function between cardiac and skeletal muscle. These data underscore the complexity of inheritance and penetrance of single-gene disorders.
Successful Treatment of Early Endometrial Carcinoma by Local Delivery of Levonorgestrel: A Case Report
Authors: Wildemeersch D. , Anderson E. , Lambein K. , Pauwels P. , Dhont M.
Published: October 2010

We describe a case of a 67‐year‐old Caucasian woman with an early, moderately‐differentiated adenocarcinoma of the endometrium. A levonorgestrel‐releasing intrauterine system was inserted, which she tolerated well. A full D&C, following removal of the device, was performed after 9 months, confirming absence of tumoral tissue. Examination after 24 months showed a very thin endometrium, indicating complete remission.
New Technique to Estimate the Asymmetric Trimming Mean
Authors: Alkhazaleh A. M. H. , Razali A. M.
Published: October 2010

A trimming mean eliminates the extreme observations by removing observations from each end of the ordered sample. In this paper, we adopted the Hogg′s and Brys′s tail weight measures. In addition, a new algorithm was proposed as a linear estimator based on the quartile; we used a quartile to divide the data into three and four groups. Then two new estimators were proposed. These classes of linear estimators were examined via simulation method over a variety of asymmetric distributions. Sample sizes 50, 100, 150, and 200 were generated using R program. The results of 50 were tabulated, since we have similar results for the other sizes. These results were tabulated for 7 asymmetric distributions with total trimmed proportions 0.10 and 0.20 on both sides, respectively. The results for these estimators were ordered based on their relative efficiency.
Dynamic Probing of Nanoparticle StabilityIn Vivo: A Liposomal Model Assessed UsingIn SituMicrodialysis and Optical Imaging
Authors: Jeng Chien-Chung , Cheng Shih-Hsun , Ho Ja-an Annie , Huang Sam Hong-Yi , Chang Jerry C. , Tsai Pi-Ju , Yang Chung-Shi , Lo Leu-Wei
Published: October 2010

Nanoparticle-mediated drug delivery and controlled release has been a vigorous research area in contemporary nanomedicine. Thein vivostability of nanoparticle delivered on site is a prerequisite for the design of drug-controlled release by any means. In this study, the first methodology comprised of microdialysis and optical imaging to assess the liposome stabilityin vivois reported. Macroscopically, we demonstrated the DPPG liposomes with negative surface charge fast accumulated in the rat liver upon their i.v. administration using optical imaging. Microscopically, the concurrent analysis of fluorescent molecules leaching from the liposomes,in situsampled using microdialysis probe, provides the dynamic information of stability of DPPG liposomeslocus in quo. The current combination ofin situmicrodialysis and optical imaging possesses a great potential for use as a platform technology to evaluate the nanoparticle stability and the bioavailability of drug payload released on targeted sitein vivo.
Danger Signaling Protein HMGB1 Induces a Distinct Form of Cell Death Accompanied by Formation of Giant Mitochondria
Authors: Gdynia Georg , Keith Martina , Kopitz Jürgen , Bergmann Marion , Fassl Anne , Weber Alexander N.R. , George Julie , Kees Tim , Zentgraf Hans-Walter , Wiestler Otmar D. , Schirmacher Peter , Roth Wilfried
Published: October 2010

Cells dying by necrosis release the high-mobility group box 1 (HMGB1) protein, which has immunostimulatory effects. However, little is known about the direct actions of extracellular HMGB1 protein on cancer cells. Here, we show that recombinant human HMGB1 (rhHMGB1) exerts strong cytotoxic effects on malignant tumor cells. The rhHMGB1-induced cytotoxicity depends on the presence of mitochondria and leads to fast depletion of mitochondrial DNA, severe damage of the mitochondrial proteome by toxic malondialdehyde adducts, and formation of giant mitochondria. The formation of giant mitochondria is independent of direct nuclear signaling events, because giant mitochondria are also observed in cytoplasts lacking nuclei. Further, the reactive oxygen species scavenger N-acetylcysteine as well as c-Jun NH2-terminal kinase blockade inhibited the cytotoxic effect of rhHMGB1. Importantly, glioblastoma cells, but not normal astrocytes, were highly susceptible to rhHMGB1-induced cell death. Systemic treatment with rhHMGB1 results in significant growth inhibition of xenografted tumors in vivo. In summary, rhHMGB1 induces a distinct form of cell death in cancer cells, which differs from the known forms of apoptosis, autophagy, and senescence, possibly representing an important novel mechanism of specialized necrosis. Further, our findings suggest that rhHMGB1 may offer therapeutic applications in treatment of patients with malignant brain tumors. Cancer Res; 70(21); 8558–68. ©2010 AACR.
Zoledronic Acid Reduces Bone Loss and Tumor Growth in an Orthotopic Xenograft Model of Osteolytic Oral Squamous Cell Carcinoma
Authors: Martin Chelsea K. , Werbeck Jillian L. , Thudi Nanda K. , Lanigan Lisa G. , Wolfe Tobie D. , Toribio Ramiro E. , Rosol Thomas J.
Published: October 2010

Squamous cell carcinoma (SCC) is the most common form of oral cancer. Destruction and invasion of mandibular and maxillary bone frequently occurs and contributes to morbidity and mortality. We hypothesized that the bisphosphonate drug zoledronic acid (ZOL) would inhibit tumor-induced osteolysis and reduce tumor growth and invasion in a murine xenograft model of bone-invasive oral SCC (OSCC) derived from an osteolytic feline OSCC. Luciferase-expressing OSCC cells (SCCF2Luc) were injected into the perimaxillary subgingiva of nude mice, which were then treated with 100 μg/kg ZOL or vehicle. ZOL treatment reduced tumor growth and prevented loss of bone volume and surface area but had no effect on tumor invasion. Effects on bone were associated with reduced osteolysis and increased periosteal new bone formation. ZOL-mediated inhibition of tumor-induced osteolysis was characterized by reduced numbers of tartrate-resistant acid phosphatase–positive osteoclasts at the tumor-bone interface, where it was associated with osteoclast vacuolar degeneration. The ratio of eroded to total bone surface was not affected by treatment, arguing that ZOL-mediated inhibition of osteolysis was independent of effects on osteoclast activation or initiation of bone resorption. In summary, our results establish that ZOL can reduce OSCC-induced osteolysis and may be valuable as an adjuvant therapy in OSCC to preserve mandibular and maxillary bone volume and function. Cancer Res; 70(21); 8607–16. ©2010 AACR.
Hierarchical Clustering of Human Papilloma Virus Genotype Patterns in the ASCUS-LSIL Triage Study
Authors: Wentzensen Nicolas , Wilson Lauren E. , Wheeler Cosette M. , Carreon Joseph D. , Gravitt Patti E. , Schiffman Mark , Castle Philip E.
Published: October 2010

Anogenital cancers are associated with ∼13 carcinogenic human papilloma virus (HPV) types in a broader group that cause cervical intraepithelial neoplasia (CIN). Multiple concurrent cervical HPV infections are common, which complicates the attribution of HPV types to different grades of CIN. Here we report the analysis of HPV genotype patterns in the atypical squamous cells of undetermined significance–low-grade squamous intraepithelial lesion triage study with the use of unsupervised hierarchical clustering. Women who underwent colposcopy at baseline (n = 2,780) were grouped into 20 disease categories based on histology and cytology. Disease groups and HPV genotypes were clustered with the use of complete linkage. Risk of 2-year cumulative CIN3+, viral load, colposcopic impression, and age were compared between disease groups and major clusters. Hierarchical clustering yielded four major disease clusters: cluster 1 included all CIN3 histology with abnormal cytology; cluster 2 included CIN3 histology with normal cytology and combinations with either CIN2 or high-grade squamous intraepithelial lesion cytology; cluster 3 included older women with normal or low-grade histology/cytology and low viral load; and cluster 4 included younger women with low-grade histology/cytology, multiple infections, and the highest viral load. Three major groups of HPV genotypes were identified: group 1 included only HPV16; group 2 included nine carcinogenic types, plus noncarcinogenic HPV53 and HPV66; and group 3 included noncarcinogenic types, plus carcinogenic HPV33 and HPV45. Clustering results suggested that colposcopy missed a prevalent precancer in many women with no biopsy/normal histology and high-grade squamous intraepithelial lesion. This result was confirmed by an elevated 2-year risk of CIN3+ in these groups. Our novel approach to study multiple genotype infections in cervical disease with the use of unsupervised hierarchical clustering can address complex genotype distributions on a population level. Cancer Res; 70(21); 8578–86. ©2010 AACR.
IQGAP1 Plays an Important Role in the Invasiveness of Thyroid Cancer
Authors: Liu Zhi , Liu Dingxie , Bojdani Ermal , El-Naggar Adel K. , Vasko Vasily , Xing Mingzhao
Published: October 2010

Purpose: This study was designed to explore the role of IQGAP1 in the invasiveness of thyroid cancer and its potential as a novel prognostic marker and therapeutic target in this cancer.

Experimental Design: We examined IQGAP1 copy gain and its relationship with clinicopathologic outcomes of thyroid cancer and investigated its role in cell invasion and molecules involved in the process.

Results: We found IQGAP1 copy number (CN) gain ≥3 in 1 of 30 (3%), 24 of 74 (32%), 44 of 107 (41%), 8 of 16 (50%), and 27 of 41 (66%) of benign thyroid tumor, follicular variant papillary thyroid cancer (FVPTC), follicular thyroid cancer (FTC), tall cell papillary thyroid cancer (PTC), and anaplastic thyroid cancer, respectively, in the increasing order of invasiveness of these tumors. A similar tumor distribution trend of CN ≥4 was also seen. IQGAP1 copy gain was positively correlated with IQGAP1 protein expression. It was significantly associated with extrathyroidal and vascular invasion of FVPTC and FTC and, remarkably, a 50%–60% rate of multifocality and recurrence of BRAF mutation–positive PTC (P = 0.01 and 0.02, respectively). The siRNA knockdown of IQGAP1 dramatically inhibited thyroid cancer cell invasion and colony formation. Coimmunoprecipitation assay showed direct interaction of IQGAP1 with E-cadherin, a known invasion-suppressing molecule, which was upregulated when IQGAP1 was knocked down. This provided a mechanism for the invasive role of IQGAP1 in thyroid cancer. In contrast, IQGAP3 lacked all these functions.

Conclusions: IQGAP1, through genetic copy gain, plays an important role in the invasiveness of thyroid cancer and may represent a novel prognostic marker and therapeutic target for this cancer. Clin Cancer Res; 16(24); 6009–18. ©2010 AACR.
Diallyl Trisulfide Inhibits Activation of Signal Transducer and Activator of Transcription 3 in Prostate Cancer Cells in Culture and In vivo
Authors: Chandra-Kuntal Kumar , Singh Shivendra V.
Published: October 2010

Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor implicated in prostate carcinogenesis. The present study shows that diallyl trisulfide (DATS), a promising cancer-chemopreventive constituent of processed garlic, inhibits phosphorylation of STAT3 in prostate cancer cells in culture and in vivo. Exposure of DU145 and LNCaP human prostate cancer cells to growth-suppressive and pharmacologically relevant concentrations of DATS (20 and 40 μmol/L) resulted in suppression of constitutive (DU145) as well as interleukin-6 (IL-6)–induced (LNCaP) phosphorylation of STAT3 (Tyr705), which correlated with inhibition of Janus-activated kinase 2 phosphorylation. Constitutive and/or IL-6–induced nuclear translocation of pSTAT3 and STAT3 dimerization was also markedly inhibited on treatment with DATS in both cell lines. Inhibition of prostate cancer development in transgenic adenocarcinoma of mouse prostate mice by gavage of DATS correlated with a visible decrease in the levels of pSTAT3. Interestingly, the IL-6–mediated activation of STAT3 largely failed to confer protection against proapoptotic response to DATS in both cells. Likewise, DATS-mediated inhibition of cell migration was either not affected or minimally reversed by IL-6 treatment or ectopic expression of constitutively active STAT3. In conclusion, the present study indicates that DATS treatment suppresses STAT3 phosphorylation in prostate cancer cells in culture and in vivo, but activation of this oncogenic transcription factor is largely dispensable for cellular responses to DATS. Ability of DATS to overcome STAT3 activation is a therapeutic advantage for this chemopreventive agent. Cancer Prev Res; 3(11); 1473–83. ©2010 AACR.
Synthetic Triterpenoids Prolong Survival in a Transgenic Mouse Model of Pancreatic Cancer
Authors: Liby Karen T. , Royce Darlene B. , Risingsong Renee , Williams Charlotte R. , Maitra Anirban , Hruban Ralph H. , Sporn Michael B.
Published: October 2010

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and is nearly always fatal. Whereas early detection offers the most promising approach for reducing the mortality of this disease, there is still a need to develop effective drugs for the prevention and treatment of pancreatic cancer. We tested two promising classes of noncytotoxic drugs, synthetic oleanane triterpenoids and rexinoids, for the prevention of carcinogenesis in the highly relevant LSL-KrasG12D/+;LSL-Trp53R127H/+;Pdx-1-Cre (KPC) mouse model of pancreatic cancer. KPC transgenic mice closely recapitulate the genetic mutations, clinical symptoms, and histopathology found in human pancreatic cancer. Beginning at 4 weeks of age, mice were fed powdered control diet or a diet containing the triterpenoids CDDO-methyl ester (CDDO-Me) or CDDO-ethyl amide, the rexinoid LG100268 (LG268), or the combination, until the mice displayed overt symptoms of pancreatic cancer. CDDO-Me, LG268, the combination of CDDO-Me and LG268, and the combination of CDDO-ethyl amide and LG268, all significantly (P < 0.05) increased survival in the KPC mice by 3 to 4 weeks. Recent studies have shown that gemcitabine, the current standard of care for human pancreatic cancer, does not extend survival in KPC mice. In cell lines developed from the KPC mice, the triterpenoids directly interact with both signal transducer and activator of transcription 3 and IκB kinase (IKK) to decrease constitutive interleukin-6 secretion, inhibit constitutive signal transducer and activator of transcription 3 phosphorylation, and block the degradation of IκBα when challenged with tumor necrosis factor α. These results suggest that oleanane triterpenoids and rexinoids have the potential to prevent pancreatic cancer. Cancer Prev Res; 3(11); 1427–34. ©2010 AACR.
Development of a Rapid PCR Assay for Screening of Maternal Colonization by Group B Streptococcus and Neonatal Invasive Escherichia coli during Labor
Authors: Martínez de Tejada Begoña , Stan Catalin M. , Boulvain Michel , Renzi Gesuele , François Patrice , Irion Olivier , Schrenzel Jacques
Published: October 2010

Objective: Group B Streptococcus (GBS) and Escherichiacoli(E. coli) are the leading causes of early-onset neonatal disease (EOD). Intrapartum antibiotic prophylaxis of GBS-colonized women decreases vertical transmission and EOD due to GBS. Nevertheless, no intervention has been developed to reduce the risk of EOD related to E. coli. Timely and accurate identification of colonized mothers is necessary to implement preventive strategies against neonatal sepsis. To screen for colonization during labor, we developed a real-time PCR assay for the simultaneous detection of GBS and neonatal invasive strains of E. coli. Study Design: Specific DNA targets for GBS are publicly available. For neonatal invasive E. coli, we analyzed candidate DNA targets by DNA hybridization on microarrays of invasive strains isolated from neonatal E. coli sepsis or meningitis (K1 and not K1 ‘invasive’ serotypes). Specificity of DNA probes was tested against a panel of bacteria and by simulating clinical conditions (spiking vaginal samples from pregnant women). Then, the characteristics of the selected probes were evaluated in a pilot study including 200 women in labor. Results: Prevalence of rectovaginal GBS and of vaginal and cervical E. coliserotype K1 colonization were 16.0, 3.5 and 3.5% by culture and 27, 10 and 8.5% by PCR, respectively. The prevalence of other invasive E. coli in the vagina and in the cervix, detected by PCR, was around 10%. Compared to the culture, considered as the gold standard, the sensitivities of the PCRs for the GBS and E. coli K1 were 97 and 71%, respectively. Specificities were 86 and 92%, respectively. Specificity is difficult to interpret, as a false-positive PCR result may in fact be a false-negative result of the culture. The turnaround time needed for PCR analysis was 2.5 h, compared to a minimum of 48 h for the culture. Conclusion: Our rapid PCR is reliable in detecting GBS in women in labor. Optimization of the PCR for invasive E. coli is needed before its implementation in clinical practice. More efforts to fight against main causes of neonatal sepsis need to be undertaken to prevent this terrible medical complication.
Management of Recurrent Vulvo-Vaginal Candidosis as a Chronic Illness
Authors: Donders Gilbert G.G. , Bellen Gert , Mendling Werner
Published: October 2010

For sporadic acute Candida vaginitis, any oral or local antifungal therapy can be used. For women with recurrent vulvo-vaginal candidosis (RVC), on the other hand, such simple approaches are insufficient, regardless of the product chosen. Instead, RVC should be managed as any other chronic disease and requires long-term, prophylactic, suppressive antifungal treatment. A regimen using individualized, decreasing doses of oral fluconazole (the ReCiDiF regimen) was proven to be highly efficient and offered great comfort to the patients. During this regimen, it is crucial that patients are carefully examined by anamnestic, clinical, microscopic and culture-proven absence of Candida. If a relapse occurs, the medication is adjusted and efforts are taken to find a possible triggering factor for the reactivation of the infection. Care has to be taken not to accumulate ‘don’t do’s’, unless the efficiency of a measure has been proven, by trying to eliminate one risk factor at a time for 2 months. Known possible triggers to be kept in mind are (1) antibiotic use, (2) use of specific contraceptives, especially combined contraceptive pills, (3) disturbed glucose metabolism, (4) the use of personal hygienic products, and (5) tight clothing or plastic panty liners. In therapy-resistant cases, non-albicans infection must be ruled out, and alternative therapies should be tried. Boric acid is proven to be efficient in most of these resistant cases, but other non-azoles like amphotericin B, flucytosine, gentian violet, and even caspofungin may have to be tried. As a final remark it has to be said that many patients feel poorly understood and inefficiently managed by many care-givers, increasing their feelings of guilt and sexual inferiority. Therefore, attention has to be given to take the disease seriously, follow strict treatment regimens, and advise precisely and based on individual evidence concerning any possible risk factors for recurrence. In case of therapy-resistant vulvo-vaginitis, reconsider your diagnosis and/or consider referral to specialized therapists.
Pregnancy Loss Ascribable to Parvovirus B19/Erythrovirus Is Associated with a High Prevalence of Trisomy
Authors: Carlsen Karen , Beck Bjarne L. , Bagger Peter V. , Christensen Laurids S. , Donders Gilbert G.G.
Published: October 2010

Introduction: In most cases of stillbirth, the cause is still unknown. Aim: The impact of parvovirus B19/erythrovirus infection and chromosomal abnormalities in stillborns and neonatal deaths. Material and Methods: 57 consecutive cases, 23 second-trimester abortions (from gestational weeks 16 to 22), 27 intrauterine fetal deaths (from gestational week 22 onwards) and 7 early neonatal deaths were examined for intrauterine parvovirus B19 infection with PCR, dot blot, Southern blot, in situ hybridization, specific IgM and IgG antibodies in maternal serum, fetal serum, placenta and fetal liver tissue. Chromosomal analysis and extensive histopathology were performed on all fetuses. Results: A sensitive PCR was developed and enabled detection of 9 (15.8%) parvovirus B19-infected fetuses. Parvovirus B19 IgM and IgG antibody tests were in good concordance with PCR findings. 5 of 9 infected fetuses had a concurrent abnormality that could have contributed to fetal death, 4 of which (44%) were trisomy karyotypes, compared to 0/48 in the non-B19-infected group (p = 0.0004). Conclusion: Combination of PCR and specific parvovirus B19 IgG/IgM tests enabled high detection rates of parvovirus B19 infection in this series of 57 consecutive pregnancies with adverse outcomes. The high mortality rate in the B19-infected fetuses was partly explained by a high occurrence of fetal trisomy, compared to non-B19-infected fetuses, suggesting a higher vulnerability of the former. After correction for this concomitant karyotype abnormality, the percentage of presumably lethal infection due to parvovirus B19 was 8.8%.
Factor V Is an Anticoagulant Cofactor for Activated Protein C during Inactivation of Factor Va
Authors: Cramer Thomas J. , Griffin John H. , Gale Andrew J.
Published: October 2010

Coagulation factor V (FV) promotes inactivation of activated factor VIII (FVIIIa) by activated protein C (APC) and protein S. Loss of this APC cofactor activity is proposed to be partially responsible for the APC resistance phenotype of FVLeiden. However, FVIIIa loses activity rapidly due to dissociation of the A2 domain, and this may be the primary mechanism of FVIIIa inactivation. APC/protein S also readily inactivates activated FV (FVa). We therefore hypothesized that FV can function as an anticoagulant cofactor for APC/protein S in the inactivation of FVa. FV was titrated into FV-deficient plasma, and the APC sensitivity ratio (APCsr; a measure of APC activity) was measured in a clotting assay that was not sensitive to FVIII. Our results showed an increase in APCsr as the FV concentration increased, suggesting an anticoagulant function for FV in this assay. FVLeiden showed APC resistance with an APCsr of 1.0. Therefore, under our experimental conditions, FV acted as an anticoagulant cofactor for APC in the inactivation of FVa.
Characterization of a Late Gene, ORF134, from Bombyx mori Nucleopolyhedrovirus
Authors: Lin Feng , Chen Keping , Xia Hengchuan , Yao Qin , Gao Lu , Chen Huiqing
Published: October 2010

Objective: ORF134 of Bombyx mori nucleopolyhedrovirus (BmNPV) is a homolog of Autographa californica multiple NPV ORF5, but its function is unknown so far. The aim of this study is to characterize BmNPV ORF134 (Bm134). Methods: Transcription, protein expression and subcellular localization of Bm134 in BmN cells and silkworm midguts were analyzed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence, respectively. Results: Both the transcription and protein expression of Bm134 were not detected until 24 h post-infection (p.i.) by RT-PCR and Western blot, indicating that Bm134 is a late gene. Western blot revealed that Bm134 encodes an expected 12.4-kDa structural protein that is associated with occlusion-derived virus (ODV), not with budded virus. Immunofluorescence analysis showed that the Bm134 was first detected in the cytoplasm 24 h p.i. and then transported to the nucleus during later infection. Transcripts of Bm134 and the corresponding protein were only detected 48–72 h p.i. in BmNPV-infected larvae of 306, a highly BmNPV-susceptible silkworm strain, but not in the NB strain that is resistant to BmNPV infection. Conclusion: Taken together, our data suggest that Bm134 is a late gene of BmNPV and may function as an ODV structural protein.
Effect of Nilvadipine on Central Visual Field in Retinitis Pigmentosa: A 30-Month Clinical Trial
Authors: Nakazawa Mitsuru , Ohguro Hiroshi , Takeuchi Kimio , Miyagawa Yasuhiro , Ito Tadashi , Metoki Tomomi
Published: October 2010

Purpose: To assess the effects of nilvadipine on the progression of central visual field defect in retinitis pigmentosa (RP). Design: Prospective, randomized, nonmasked, single-center trial. Methods: Patients with RP were randomly divided into a treated group receiving oral nilvadipine at 4 mg/day for ≧30 months and a control group receiving tocopherol nicotinate at 300 mg/day, helenien at 15 mg/day or no medication for the same periods. Progression of RP was evaluated using the 10-2 SITA Fast Program of the Humphrey Visual Field Analyzer, and regression coefficients calculated from the time courses of mean deviation (MD slope) were compared between groups. Results: Nineteen patients in the treated group and 14 patients in the control group completed the follow-up for ≧30 months. The mean (±standard deviation) duration of observation was 48.8 ± 11.8 months (median 48 months, range 30–66 months) for the treated group and 49.2 ± 18.1 months (median 48 months, range 30–90 months) for the control group (p = 0.94). Mean (±standard error of the mean, SEM) regression coefficients of the averaged MD values for the initial 30 months were –0.35 ± 0.17 dB/year in the treated group and –0.75 ± 0.06 dB/year in the control group (p < 0.01). Mean (±SEM) MD slopes for total observational periods were –0.49 ± 0.17 dB/year in the treated group and –0.89 ± 0.16 dB/year in the control group (mean ± SEM, p = 0.042). Conclusion: Nilvadipine at 4 mg/day significantly retarded progression of central visual field defects in RP in this small patient series.
Lack of Accuracy for the Proposed ‘Dubois Criteria’ in Alzheimer’s Disease: A Validation Study from the Swedish Brain Power Initiative
Authors: Oksengard A.R. , Cavallin L. , Axelsson R. , Andersson C. , Nägga K. , Winblad B. , Eriksdotter-Jönhagen M. , Wahlund L.O.
Published: October 2010

Background/Aims: Our purpose was to investigate whether the new research criteria for Alzheimer’s disease proposed in 2007 by Dubois et al. are valid in a naturalistic memory clinic sample. Method: Retrospective diagnostic analyses were carried out to compare the traditional diagnostic criteria for dementia with the new criteria suggested by Dubois et al. No patient had gone through all procedures postulated as additional features in the proposed new Dubois criteria. Material: Two independent experienced geriatricians re-examined 150 complete patients’ records. The study physicians were blinded to any of the results of the core and additional features suggested by Dubois et al. to avoid circular diagnostic bias. Results:Among our 96 patients with a clinical diagnosis of subjective cognitive impairment and/or mild cognitive impairment, 2 of the patients with subjective cognitive impairment and 5 patients with mild cognitive impairment would classify as pre-dementia Alzheimer’s disease according to the Dubois criteria. In our 23 Alzheimer patients diagnosed clinically, only 12 of the cases fulfilled the criteria for Alzheimer’s disease suggested by Dubois et al. Interpretation: The proposed new criteria for Alzheimer’s disease are valid in 55% of our patients clinically diagnosed as having full-blown Alzheimer dementia. Additionally, 7.3% ‘true’ Alzheimer cases will be identified in a group of 96 clinically non-demented patients. Our results show that there is a large heterogeneity in a clinical naturalistic sample of patients with an Alzheimer phenotype. Conclusion: There is a need to further validate the currently existing biomarkers in large unselected samples and avoid the pitfall of workup bias and circular diagnostic processes. Additionally, valid age-specific cut-off values for the diagnostic markers in question have to be defined.
Detection of Bet v1, Bet v2 and Bet v4 Specific IgE Antibodies in the Sera of Children and Adult Patients Allergic to Birch Pollen: Evaluation of Different IgE Reactivity Profiles Depending on Age and Local Sensitization
Authors: Sekerková A. , Poláčková M.
Published: October 2010

Background: Birch pollen belongs to the major allergen triggers in the spring season in Europe. Our rapidly expanding knowledge of the allergenic molecules enables us to better recognize the individual differences between the reactivity of specific IgE antibodies of individual patients and allergic populations living in various regions of the world. Method: In a group of birch pollen-allergic patients living in the Czech Republic (107 children, 71 adults) we detected the presence of Bet v1, Bet v2 and Bet v4 specific IgE antibodies. Results: Bet v1 specific IgE antibodies were identified in most patients without any significant differences between children and adults. Bet v2 positivity was found more frequently in the group of children than in adults (p = 0.02). In most adult patients Bet v1 monospecificity was more expressed as compared to the pediatric group. More allergic subjects reacted against minor birch allergens in the pediatric group (p = 0.02). Specific IgE antibodies against Bet v1 were not detected in 10% of the tested patients. In this group, 5% of birch pollen-allergic patients were found to not have specific IgE antibodies against any of the tested recombinant allergens. Conclusion: The investigation of specific IgE antibodies against Bet v1, Bet v2 and Bet v4 demonstrated that the specificity of allergen-induced IgE antibodies in birch pollen-allergic individuals is dependent not only on the region in which a patient lives but also on age. Especially in children, there is an increase in the number of allergic subjects who do not react exclusively against the major allergen. The question is whether some allergen-specific IgE antibodies will disappear depending on age or on the contrary whether their synthesis will be increased.
Isomaltitol Exacerbates Neutrophilia but Reduces Eosinophilia: New Insights into the Sephadex Model of Lung Inflammation
Authors: Evaldsson Chamilly , Rydén Ingvar , Uppugunduri Srinivas
Published: October 2010

Background: We have previously examined isomaltitol in an in vitro static adhesion assay and were interested in investigating whether the potentially anti-inflammatory effects observed there could be relevant in vivo. The Sephadex-induced lung inflammation model was considered a suitablemodel due to the significant changes in global inflammatory endpoints seen upon provocation with Sephadex. Methods: Male Sprague-Dawley rats were instilled intratracheally with Sephadex (5 mg/ml), vehicle (0.9% NaCl), isomaltitol (50 mg/ml) or a combination of isomaltitol and Sephadex. After 24 h, the lungs were weighed to measure edema and preserved for histology. Bronchoalveolar lavage fluid was used for analysis of tumor necrosis factor, cysteinyl leukotrienes, and differential and total leukocyte counts. Results: Differential counts showed that isomaltitol increased the neutrophil component while decreasing the eosinophilia, thus asserting a modulatory role on the usually eosinophil-dominated Sephadex-induced cell profile. Isomaltitol alone also increased edema and cysteinyl leukotrienes, and generally aggravated total inflammation in combination with Sephadex. The mechanisms were not investigated in this study, but effects could relate to a combination of isomaltitol’s osmotic and structure-specific properties. Conclusion: Our results show that isomaltitol can modulate the inflammatory response induced by Sephadex instillation in addition to having proinflammatory effects on its own, and may therefore provide new insights into the mechanisms of this widely used animal model. Sugar alcohols similar to isomaltitol have already been used to aid mucus clearance in cystic fibrosis patients, and it is possible that isomaltitol could also be used for this purpose.
Hebrew Brain vs. English Brain: Language Modulates the Way It Is Processed
Authors: Bick Atira S. , Goelman Gadi , Frost Ram
Published: October 2010

Is language processing universal? How do the specific properties of each language influence the way it is processed? In this study, we compare the neural correlates of morphological processing in Hebrew—a Semitic language with a rich and systematic morphology, to those revealed in English—an Indo-European language with a linear morphology. Using fMRI, we show that while in the bilingual brain both languages involve a common neural circuitry in processing morphological structure, this activation is significantly modulated by the different aspects of language. Whereas in Hebrew, morphological processing is independent of semantics, in English, morphological activation is clearly modulated by semantic overlap. These findings suggest that the processes involved in reading words are not universal, and therefore impose important constraints on current models of visual word recognition.
Selective Cortical Mapping of Biological Motion Processing in Young Infants
Authors: Lloyd-Fox Sarah , Blasi Anna , Everdell Nick , Elwell Clare E. , Johnson Mark H.
Published: October 2010

How specialized is the infant brain for perceiving the facial and manual movements displayed by others? Although there is evidence for a network of regions that process biological motion in adults—including individuated responses to the perception of differing facial and manual movements—how this cortical specialization develops remains unknown. We used functional near-infrared spectroscopy [Lloyd-Fox, S., Blasi, A., & Elwell, C. Illuminating the developing brain: The past, present and future of functional near-infrared spectroscopy. Neuroscience and Biobehavioral Reviews, 34, 269–284, 2010] to investigate the ability of 5-month-old infants to process differing biological movements. Infants watched videos of adult actors moving their hands, their mouth, or their eyes, all in contrast to nonbiological mechanical movements, while hemodynamic responses were recorded over the their frontal and temporal cortices. We observed different regions of the frontal and temporal cortex that responded to these biological movements and different patterns of cortical activation according to the type of movement watched. From an early age, our brains selectively respond to biologically relevant movements, and further, selective patterns of regional specification to different cues occur within what may correspond to a developing “social brain” network. These findings illuminate hitherto undocumented maps of selective cortical activation to biological motion processing in the early postnatal development of the human brain.