bluuebunny/crossref_metadata_2025 huggingface dataset:
Influences of Desmin and Keratin 19 on Passive Biomechanical Properties of Mouse Skeletal Muscle
Authors: Shah Sameer B. , Love James M. , O'Neill Andrea , Lovering Richard M. , Bloch Robert J.
Published: January 2012

In skeletal muscle fibers, forces must be transmitted between the plasma membrane and the intracellular contractile lattice, and within this lattice between adjacent myofibrils. Based on their prevalence, biomechanical properties and localization, desmin and keratin intermediate filaments (IFs) are likely to participate in structural connectivity and force transmission. We examined the passive load-bearing response of single fibers from the extensor digitorum longus (EDL) muscles of young (3 months) and aged (10 months) wild-type, desmin-null, K19-null, and desmin/K19 double-null mice. Though fibers are more compliant in all mutant genotypes compared to wild-type, the structural response of each genotype is distinct, suggesting multiple mechanisms by which desmin and keratin influence the biomechanical properties of myofibers. This work provides additional insight into the influences of IFs on structure-function relationships in skeletal muscle. It may also have implications for understanding the progression of desminopathies and other IF-related myopathies.
Understanding the Determinants of Weight-Related Quality of Life among Bariatric Surgery Candidates
Authors: Tessier Annie , Zavorsky Gerald S. , Kim Do Jun , Carli Franco , Christou Nicolas , Mayo Nancy E.
Published: January 2012

Obesity and its relation to quality of life are multifaceted. The purpose of this paper was to contribute evidence to support a framework for understanding the impact of obesity on quality of life in 42 morbidly obese subjects considering a wide number of potential determinants. A model of weight-related quality of life (WRQL) was developed based on the Wilson-Cleary model, considering subjects' weight characteristics, arterial oxygen pressure (PaO2), walking capacity (6-minute walk test, 6MWT), health-related quality of life (HRQL; Physical and Mental Component Summaries of the SF-36 PCS/MCS), and WRQL. The model of WRQL was tested with linear regressions and a path analysis, which showed that as PaO2at rest increased 6MWT increased. 6MWT was positively associated with the PCS, which in turn was positively related to WRQL along with the MCS. The model showed good fit and explained 38% of the variance in WRQL.
Expression of Four Methionine Sulfoxide Reductases inStaphylococcus aureus
Authors: Singh Kuldeep , Singh Vineet K.
Published: January 2012

Staphylococcus aureuspossesses three MsrA enzymes (MsrA1, MsrA2, MsrA3) that reduce the S-epimer of methionine sulfoxide (MetO) and an MsrB enzyme that reduces R-MetO. The fourmsrgenes are expressed from three different promoters. ThemsrA1/msrBgenes are coexpressed. To determine the expression pattern ofmsrgenes, three independent reporter strains were constructed wheremsrpromoter was cloned in front of a promoterlesslacZand the resulting construct was integrated in the chromosome. Using these strains, it was determined that themsrA1/Bexpression is significantly higher inS. aureuscompared tomsrA2ormsrA3. Expression ofmsrA1/Bwas highest during stationary phase growth, but the expression ofmsrA2andmsrA3was highest during the early to midexponential growth phase. Expression ofmsrA1/Bwas induced by oxacillin and the expression ofmsrA3was upregulated by salt. Expression ofmsrA2remained unchanged under all tested conditions.
Estimation Algorithm of Machine Operational Intention by Bayes Filtering with Self-Organizing Map
Authors: Suzuki Satoshi , Harashima Fumio
Published: January 2012

We present an intention estimator algorithm that can deal with dynamic change of the environment in a man-machine system and will be able to be utilized for an autarkical human-assisting system. In the algorithm, state transition relation of intentions is formed using a self-organizing map (SOM) from the measured data of the operation and environmental variables with the reference intention sequence. The operational intention modes are identified by stochastic computation using a Bayesian particle filter with the trainedSOM. This method enables to omit the troublesome process to specify types of information which should be used to build the estimator. Applying the proposed method to the remote operation task, the estimator's behavior was analyzed, the pros and cons of the method were investigated, and ways for the improvement were discussed. As a result, it was confirmed that the estimator can identify the intention modes at 44–94 percent concordance ratios against normal intention modes whose periods can be found by about 70 percent of members of human analysts. On the other hand, it was found that human analysts' discrimination which was used as canonical data for validation differed depending on difference of intention modes. Specifically, an investigation of intentions pattern discriminated by eight analysts showed that the estimator could not identify the same modes that human analysts could not discriminate. And, in the analysis of the multiple different intentions, it was found that the estimator could identify the same type of intention modes to human-discriminated ones as well as 62–73 percent when the first and second dominant intention modes were considered.
Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice
Authors: Kawakami Tomoko , Puri Nitin , Sodhi Komal , Bellner Lars , Takahashi Toru , Morita Kiyoshi , Rezzani Rita , Oury Tim D. , Abraham Nader G.
Published: January 2012

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD(−/−)mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−)mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood pressure, impaired endothelial function, reduced p-eNOS, p-AKT and increased HO-1 expression; although, HO activity was significantly (P<0.05) attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P<0.05). CoPP, in EC-SOD(−/−)mice, enhanced HO activity (P<0.05) and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/−)mice.
Remarks on Confidence Intervals for Self‐Similarity Parameter of a Subfractional Brownian Motion
Authors: Liu Junfeng , Yan Litan , Peng Zhihang , Wang Deqing
Published: January 2012

We first present two convergence results about the second‐order
quadratic variations of the subfractional Brownian motion: the first is a deterministic
asymptotic expansion; the second is a central limit theorem. Next we combine these
results and concentration inequalities to build confidence intervals for the self‐similarity
parameter associated with one‐dimensional subfractional Brownian motion.
Determination of PV GeneratorI-V/P-VCharacteristic Curves Using a DC-DC Converter Controlled by a Virtual Instrument
Authors: Durán E. , Andújar J. M. , Enrique J. M. , Pérez-Oria J. M.
Published: January 2012

A versatile measurement system for systematic testing and measurement of the evolution of theI-Vcharacteristic curves of photovoltaic panels or arrays (PV generators) is proposed in this paper. The measurement system uses a circuit solution based on DC-DC converters that involves several advantages relative to traditional methods: simple structure, scalability, fast response, and low cost. The measurement of the desired characteristics of PV generators includes high speed of response and high fidelity. The prototype system built is governed by a microcontroller, and experimental results prove the proposed measurement system useful. A virtual instrument (VI) was developed for full system control from a computer. The developed system enables monitoring the suitable operation of a PV generator in real time, since it allows comparing its actual curves with those provided by the manufacturer.
Evaluation of the Mineral Status of Two Ecosystems for Sustainable Goat Rearing in the Iberian Peninsula
Authors: Vilallonga David , Jiménez Antonio , Sánchez Joaquín , Andrés Santiago
Published: January 2012

The mineral status in two ecosystems typical of the Iberian Peninsula was evaluated. Ecosystem I was formed by forests and ecosystem II by hilly areas. The levels of calcium, phosphorus, magnesium, iron, copper, zinc and selenium in soils, rations and serum were measured. The concentratons of iron, copper, zinc and selenium were also checked in liver. Ecosystem I showed higher values of every mineral, except for phosphorus. Seasonal differences were recorded for rations and serum, with higher values in spring. The rations produced by both ecosystems met the mineral requirements of goats in lactation. Thus, both ecosystems are suitable for the development of an ecological goat farming system. However, extra supply of minerals, particularly calcium, may be needed in the maximum productions periods.
The Need of Slanted Side Holes for Venous Cannulae
Authors: Park Joong Yull
Published: January 2012

Well-designed cannulae must allow good flow rate and minimize nonphysiologic load. Venous cannulae generally have side holes to prevent the rupture of blood vessel during perfusion. Optimizing side hole angle will yield more efficient and safe venous cannulae. A numerical modeling was used to study the effect of the angle (0°–45°) and number (0–12) of side holes on the performance of cannulae. By only slanting the side holes, it increases the flow rate up to 6% (in our models). In addition, it was found that increasing the number of side holes reduces the shear rate up to 12% (in our models). A new parameter called “penetration depth” was introduced to describe the interfering effect of stream jets from side holes, and the result showed that the 45°-slanted side holes caused minimum interfering for the flow in cannula. Our quantitative hemodynamic analysis study provides important guidelines for venous cannulae design.
Honeybee Venom Immunotherapy: A Comparative Study Using Purified and Nonpurified Aqueous Extracts in Patients with Normal Basal Serum Tryptase Concentrations
Authors: Bilò M. Beatrice , Cinti Barbara , Brianzoni M. Feliciana , Braschi M. Chiara , Bonifazi Martina , Antonicelli Leonardo
Published: January 2012

In this study, we compared a purified aqueous extract and the corresponding nonpurified aqueous preparation under the same build-up protocol in bee venom allergic patients with a normal baseline mast cell tryptase concentration.
Eighty patients with a history of a systemic reaction were enrolled for immunotherapy using a 5-day rush protocol. Patients treated with the purified extract and those treated with the non purified aqueous extract who developed a systemic reaction underwent maintenance therapy with the purified aluminium hydroxide adsorbed preparations. Patients treated with the nonpurified aqueous extract who did not experience a systemic reaction during the rush phase underwent the maintenance phase with that extract. Systemic reactions during the build-up phase occurred significantly more often in patients treated with nonpurified aqueous extract than in those treated with the corresponding purified aqueous preparations. During the one-year maintenance phase, no systemic reactions occurred in either of the groups. Neither age nor baseline mast cell tryptase concentration presented a significant correlation with the occurrence of a systemic reaction during the treatment, while the type of extract did. In conclusion, nonpurified aqueous extracts induced more frequent systemic reactions than the purified aqueous preparations, during the same rush protocol. The efficacy seemed to be comparable.
Leptin Promotes Glioblastoma
Authors: Lawrence Johnathan E. , Cook Nicholas J. , Rovin Richard A. , Winn Robert J.
Published: January 2012

The hormone leptin has a variety of functions. Originally known for its role in satiety and weight loss, leptin more recently has been shown to augment tumor growth in a variety of cancers. Within gliomas, there is a correlation between tumor grade and tumor expression of leptin and its receptor. This suggests that autocrine signaling within the tumor microenvironment may promote the growth of high-grade gliomas. Leptin does this through stimulation of cellular pathways that are also advantageous for tumor growth and recurrence: antiapoptosis, proliferation, angiogenesis, and migration. Conversely, a loss of leptin expression attenuates tumor growth. In animal models of colon cancer and melanoma, a decline in the expression and secretion of leptin resulted in a reduction of tumor growth. In these models, positive mental stimulation through environmental enrichment decreased leptin secretion and improved tumor outcome. This review explores the link between leptin and glioblastoma.
In-Fiber Subpicosecond Pulse Shaping for Nonlinear Optical Telecommunication Data Processing at 640 Gbit/s
Authors: Azaña J. , Oxenløwe L. K. , Palushani E. , Slavík R. , Galili M. , Mulvad H. C. H. , Hu H. , Park Y. , Clausen A. T. , Jeppesen P.
Published: January 2012

We review recent work on all-fiber (long-period fiber grating) devices for optical pulse shaping, particularly flat-top pulse generation, down to the subpicosecond range and their application for nonlinear switching (demultiplexing) of optical time-division multiplexed (OTDM) data signals in fiber-optic telecommunication links operating up to 640 Gbit/s. Experiments are presented demonstrating error-free 640-to-10 Gbit/s demultiplexing of the 64 tributary channels using the generated flat-top pulses for temporal gating in a Kerr-effect-based nonlinear optical loop mirror. The use of flat-top pulses has critical benefits in the demultiplexing process, including a significantly increased timing-jitter tolerance (up to ~500 fs, i.e., 30% of the bit period) and the associated improvement in the bit-error-rate performance (e.g., with a sensitivity increase of up to ~13 dB as compared with the use of Gaussian-like gating pulses). Long-period fiber grating pulse shapers with reduced polarization dependence are fabricated and successfully used for polarization-independent 640-to-10 Gbit/s demultiplexing experiments.
Vascular Disrupting Agent Arsenic Trioxide Enhances Thermoradiotherapy of Solid Tumors
Authors: Griffin Robert J. , Williams Brent W. , Koonce Nathan A. , Bischof John C. , Song Chang W. , Asur Rajalakshmi , Upreti Meenakshi
Published: January 2012

Our previous studies demonstrated arsenic trioxide- (ATO-) induced selective tumor vascular disruption and augmentation of thermal or radiotherapy effect against solid tumors. These results suggested that a trimodality approach of radiation, ATO, and local hyperthermia may have potent therapeutic efficacy against solid tumors. Here, we report the antitumor effect of hypofractionated radiation followed by ATO administration and local 42.5 °C hyperthermia and the effects of cisplatin and thermoradiotherapy. We found that the therapeutic efficacy of ATO-based thermoradiotherapy was equal or greater than that of cisplatin-based thermoradiotherapy, and marked evidence ofin vivoapoptosis and tumor necrosis were observed in ATO-treated tumors. We conclude that ATO-based thermoradiotherapy is a powerful means to control tumor growth by using vascular disruption to augment the effects of thermal and radiation therapy.
Evidence for AGN Feedback in Galaxy Clusters and Groups
Authors: Gitti Myriam , Brighenti Fabrizio , McNamara Brian R.
Published: January 2012

The current generation of flagship X-ray missions,ChandraandXMM-Newton, has changed our understanding of the so-called “cool-core” galaxy clusters and groups. Instead of the initial idea that the thermal gas is cooling and flowing toward the center, the new picture envisages a complex dynamical evolution of the intracluster medium (ICM) regulated by the radiative cooling and the nongravitational heating from the active galactic nucleus (AGN). Understanding the physics of the hot gas and its interplay with the relativistic plasma ejected by the AGN is key for understanding the growth and evolution of galaxies and their central black holes, the history of star formation, and the formation of large-scale structures. It has thus become clear that the feedback from the central black hole must be taken into account in any model of galaxy evolution. In this paper, we draw a qualitative picture of the current knowledge of the effects of the AGN feedback on the ICM by summarizing the recent results in this field.
Intermittent Fasting Modulation of the Diabetic Syndrome in Streptozotocin-Injected Rats
Authors: Belkacemi Louiza , Selselet-Attou Ghalem , Hupkens Emeline , Nguidjoe Evrard , Louchami Karim , Sener Abdullah , Malaisse Willy J.
Published: January 2012

This study investigates the effects of intermittent overnight fasting in streptozotocin-induced diabetic rats (STZ rats). Over 30 days, groups of 5-6 control or STZ rats were allowed free food access, starved overnight, or exposed to a restricted food supply comparable to that ingested by the intermittently fasting animals. Intermittent fasting improved glucose tolerance, increased plasma insulin, and lowered Homeostatis Model Assessment index. Caloric restriction failed to cause such beneficial effects. Theβ-cell mass, as well as individualβ-cell and islet area, was higher in intermittently fasting than in nonfasting STZ rats, whilst the percentage of apoptoticβ-cells appeared lower in the former than latter STZ rats. In the calorie-restricted STZ rats, comparable findings were restricted to individual islet area and percentage of apoptotic cells. Hence, it is proposed that intermittent fasting could represent a possible approach to prevent or minimize disturbances of glucose homeostasis in human subjects.
Inter- and Intraspecific Variation inDrosophilaGenes with Sex-Biased Expression
Authors: Müller Lena , Grath Sonja , von Heckel Korbinian , Parsch John
Published: January 2012

Genes with sexually dimorphic expression (sex-biased genes) often evolve rapidly and are thought to make an important contribution to reproductive isolation between species. We examined the molecular evolution of sex-biased genes inDrosophila melanogasterandD. ananassae, which represent two independent lineages within themelanogastergroup. We find that strong purifying selection limits protein sequence variation within species, but that a considerable fraction of divergence between species can be attributed to positive selection. InD. melanogaster, the proportion of adaptive substitutions between species is greatest for male-biased genes and is especially high for those on the X chromosome. In contrast, male-biased genes do not show unusually high variation within or between populations. A similar pattern is seen at the level of gene expression, where sex-biased genes show high expression divergence between species, but low divergence between populations. InD. ananassae, there is no increased rate of adaptation of male-biased genes, suggesting that the type or strength of selection acting on sex-biased genes differs between lineages.
RNAi-Mediated Targeting of Noncoding and Coding Sequences in DNA Repair Gene Messages Efficiently Radiosensitizes Human Tumor Cells
Authors: Zheng Zhiming , Ng Wooi Loon , Zhang Xiangming , Olson Jeffrey J. , Hao Chunhai , Curran Walter J. , Wang Ya
Published: January 2012

Human tumor cell death during radiotherapy is caused mainly by ionizing radiation (IR)–induced DNA double-strand breaks (DSB), which are repaired by either homologous recombination repair (HRR) or nonhomologous end-joining (NHEJ). Although siRNA-mediated knockdown of DNA DSB repair genes can sensitize tumor cells to IR, this approach is limited by inefficiencies of gene silencing. In this study, we show that combining an artificial miRNA (amiR) engineered to target 3′-untranslated regions of XRCC2 (an HRR factor) or XRCC4 (an NHEJ factor) along with an siRNA to target the gene coding region can improve silencing efficiencies to achieve more robust radiosensitization than a single approach alone. Mechanistically, the combinatorial knockdown decreased targeted gene expression through both a reduction in mRNA stability and a blockade to mRNA translation. Together, our findings establish a general method of gene silencing that is more efficient and particularly suited for suppressing genes that are difficult to downregulate by amiR- or siRNA-based methods alone. Cancer Res; 72(5); 1221–8. ©2012 AACR.
Antigen-Specific CD4+ T Cells Regulate Function of Myeloid-Derived Suppressor Cells in Cancer via Retrograde MHC Class II Signaling
Authors: Nagaraj Srinivas , Nelson Allison , Youn Je-in , Cheng Pingyan , Quiceno David , Gabrilovich Dmitry I.
Published: January 2012

Myeloid-derived suppressor cells (MDSC) play a major role in cancer-related immune suppression, yet the nature of this suppression remains controversial. In this study, we evaluated the ability of MDSCs to elicit CD4+ T-cell tolerance in different mouse tumor models. In contrast to CD8+ T-cell tolerance, which could be induced by MDSCs in all the tumor models tested, CD4+ T-cell tolerance could be elicited in only one of the models (MC38) in which a substantial level of MHC class II was expressed on MDSCs compared with control myeloid cells. Mechanistic investigations revealed that MDSCs deficient in MHC class II could induce tolerance to CD8+ T cells but not to CD4+ T cells. Unexpectedly, antigen-specific CD4+ T cells (but not CD8+ T cells) could dramatically enhance the immune suppressive activity of MDSCs by converting them into powerful nonspecific suppressor cells. This striking effect was mediated by direct cell–cell contact through cross-linking of MHC class II on MDSCs. We also implicated an Ets-1 transcription factor–regulated increase in expression of Cox-2 and prostaglandin E2 in MDSCs in mediating this effect. Together, our findings suggest that activated CD4+ T cells that are antigen specific may enhance the immune suppressive activity of MDSCs, a mechanism that might serve normally as a negative feedback loop to control immune responses that becomes dysregulated in cancer. Cancer Res; 72(4); 928–38. ©2012 AACR.
Twenty-Third Annual Pezcoller Symposium: Engineering Influences in Cancer Research
Authors: Friedl Peter , Hubbell Jeff , Livingston David , Mihich Enrico
Published: January 2012

The cross-disciplinary focus of the meeting highlighted recent progress in physical and genetic analysis and engineering of cancer disease models. As the central theme, mechanical forces affecting cell signaling, growth, differentiation, and metastasis were discussed with emphasis on the tumor microenvironment and cellular immunity, taking into account novel nanotechnology, biosensing, and intravital microscopy tools to monitor animal cancer models and human cancer. Emerging themes were the role of extracellular matrix imposing mechanical mechanisms on tumor cell function, including microenvironmental cues controlling the movement of tumor and immune cells, advanced genetic animal models for cancer that better recapitulate human disease, and preclinical and clinical molecular imaging of tumor architecture and stiffness, as well as novel nanotechnologies for anticancer drug delivery. Cancer Res; 72(4); 841–4. ©2012 AACR.
Ponatinib (AP24534), a Multitargeted Pan-FGFR Inhibitor with Activity in Multiple FGFR-Amplified or Mutated Cancer Models
Authors: Gozgit Joseph M. , Wong Matthew J. , Moran Lauren , Wardwell Scott , Mohemmad Qurish K. , Narasimhan Narayana I. , Shakespeare William C. , Wang Frank , Clackson Tim , Rivera Victor M.
Published: January 2012

Members of the fibroblast growth factor receptor family of kinases (FGFR1–4) are dysregulated in multiple cancers. Ponatinib (AP24534) is an oral multitargeted tyrosine kinase inhibitor being explored in a pivotal phase II trial in patients with chronic myelogenous leukemia due to its potent activity against BCR-ABL. Ponatinib has also been shown to inhibit the in vitro kinase activity of all four FGFRs, prompting us to examine its potential as an FGFR inhibitor. In Ba/F3 cells engineered to express activated FGFR1–4, ponatinib potently inhibited FGFR-mediated signaling and viability with IC50 values <40 nmol/L, with substantial selectivity over parental Ba/F3 cells. In a panel of 14 cell lines representing multiple tumor types (endometrial, bladder, gastric, breast, lung, and colon) and containing FGFRs dysregulated by a variety of mechanisms, ponatinib inhibited FGFR-mediated signaling with IC50 values <40 nmol/L and inhibited cell growth with GI50 (concentration needed to reduce the growth of treated cells to half that of untreated cells) values of 7 to 181 nmol/L. Daily oral dosing of ponatinib (10–30 mg/kg) to mice reduced tumor growth and inhibited signaling in all three tumor models examined. Importantly, the potency of ponatinib in these models is similar to that previously observed in BCR-ABL–driven models and plasma levels of ponatinib that exceed the IC50 values for FGFR1–4 inhibition can be sustained in patients. These results show that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers. Mol Cancer Ther; 11(3); 690–9. ©2012 AACR.
DLK1 as a Potential Target against Cancer Stem/Progenitor Cells of Hepatocellular Carcinoma
Authors: Xu Xiao , Liu Rui-Fang , Zhang Xin , Huang Li-Yu , Chen Fei , Fei Qian-Lan , Han Ze-Guang
Published: January 2012

Delta-like 1 homolog (DLK1; Drosophila) is a hepatic stem/progenitor cell marker in fetal livers that plays a vital role in oncogenesis of hepatocellular carcinoma (HCC). The aim of this study is to investigate whether DLK1 could serve as a potential therapeutic target against cancer stem/progenitor cells of HCC. DLK1+ and DLK1− cells were sorted by fluorescence-activated cell sorting and magnetic-activated cell sorting, respectively, and then were evaluated by flow cytometry. The biological behaviors of these isolated cells and those with DLK1 knockdown were assessed by growth curve, colony formation assay, spheroid colony formation, chemoresistance, and in vivo tumorigenicity. Adenovirus-mediated RNA interference was used to knockdown the endogenous DLK1. We found that DLK1+ population was less than 10% in almost all 17 HCC cell lines examined. DLK1+ HCC cells showed stronger ability of chemoresistance, colony formation, spheroid colony formation, and in vivo tumorigenicity compared with DLK1− cells. The DLK1+ HCC cells could generate the progeny without DLK1 expression. Furthermore, DLK1 knockdown could suppress the ability of proliferation, colony formation, spheroid colony formation, and in vivo tumorigenicity of Hep3B and Huh-7 HCC cells. Our data suggested that DLK1+ HCC cells have characteristics similar to those of cancer stem/progenitor cells. RNA interference against DLK1 can suppress the malignant behaviors of HCC cells, possibly through directly disrupting cancer stem/progenitor cells, which suggested that DLK1 could be a potential therapeutic target against the HCC stem/progenitor cells. Mol Cancer Ther; 11(3); 629–38. ©2012 AACR.
Dissecting “PI3Kness”: The Complexity of Personalized Therapy for Ovarian Cancer
Authors: Bast Robert C. , Mills Gordon B.
Published: January 2012

Epithelial ovarian cancers exhibit marked heterogeneity and can be divided into low-grade type I and more prevalent high-grade type II lesions that differ in stage at diagnosis, rate of growth, and susceptibility to platinum-based chemotherapy. Activation of the phosphatidylinositol 3′ kinase (PI3K) pathway occurs in a significant fraction of both types of ovarian cancer, driven predominantly by mutations in type I and amplification in type II. Available cell lines do not often reflect the genotype of type II ovarian cancers, but studies with cell lines driven by mutation suggest that blocking activated AKT is necessary, but not sufficient to inhibit cancer cell growth. Inhibition of multiple signaling pathways will likely be required to achieve effective personalized therapy for patients whose cancers exhibit “PI3Kness.” Cancer Discovery; 2(1); 16–8. ©2012 AACR.

Commentary on Hanrahan et al., p. 56.
International Reporting Scale of BCR-ABL1 Fusion Transcript in Chronic Myeloid Leukemia: First Report from India
Authors: Balasubramanian Poonkuzhali , Chendamarai Ezhilarasi , Markose Preetha , Fletcher Linda , Branford Susan , George Biju , Mathews Vikram , Chandy Mammen , Srivastava Alok
Published: January 2012

Achieving a major molecular response (MMR) is an important predictor of progression-free survival in chronic myeloid leukemia patients treated with imatinib. This requires accurate measurement of BCR-ABL1 transcripts normalized to a control gene, as well as defining a level (BCR-ABL1/control gene ratio) that will correlate with sustained clinical response. To make these measurements comparable between laboratories, an international scale (IS) is necessary. A BCR-ABL1/control gene ratio of 0.10% represents MMR in the IS. In collaboration with an international reference laboratory in Adelaide, S.A., Australia, we have established and validated a lab-specific conversion factor for expressing BCR-ABL1 transcript levels in the IS. In this report, we explain the process and steps involved in obtaining a valid lab-specific conversion factor for expressing BCR-ABL1 transcript levels in the IS.
Habitat Separation of Sympatric Microcebus spp. in the Dry Spiny Forest of South-Eastern Madagascar
Authors: Martins M.M. , Nascimento A.T.A. , Nali C. , Velastin G.O. , Mangini P.B. , Valladares-Padua C.B. , Galetti P.M.
Published: January 2012

We investigated whether or not habitat structure contributes to the separation of two sister species of lemurs and their hybrids. For this, we studiedMicrocebusmurinusandM. griseorufusalong a continuous vegetation gradient where populations of the two species occur in sympatry or in allopatry. In allopatry, the two species are generalists without any sign of microhabitat selectivity. In sympatry, both species differed significantly and discriminated against certain habitat structures:M. murinuswas found in microhabitats with larger trees than average whileM. griseorufusutilized microhabitats with smaller trees. Hybrids between the two species did not show any significant discrimination for or against microhabitat structure and did not differ in their habitat utilization from either parent species. Both species can go into torpor and hibernation.M. griseorufusis seen more frequently during the cool dry season thanM. murinus. We assume thatM. murinusgoes into extended torpor or hibernation more frequently thanM. griseorufus. We interpret the different occurrence of large-sized trees in microhabitats ofM. murinusas a prerequisite forM. murinusto be able to spend extended periods of time in tree holes that are isolated and allow hibernation at reduced temperature levels.
Elevated CD14
++
CD16
−
Monocytes Predict Cardiovascular Events
Authors: Berg Katarina E. , Ljungcrantz Irena , Andersson Linda , Bryngelsson Carl , Hedblad Bo , Fredrikson Gunilla N. , Nilsson Jan , Björkbacka Harry
Published: January 2012

Background—

Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies.

Methods and Results—

The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects experienced ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991 to 1994 were thawed and analyzed with flow cytometry to enumerate monocyte subsets, based on CD14 and CD16 expression. The percentage and number of classical CD14
++
CD16
−
monocytes were increased in the cardiovascular-event group compared with the event-free subjects (median, 69% [interquartile range, 62% to 76%] versus 67% [59% to 72%],
P
=0.017; 344 [251 to 419] cells/μL versus 297 [212 to 384] cells/μL,
P
=0.003). The hazard ratio was 1.66 for suffering a cardiovascular event in the highest tertile of the number of CD14
++
CD16
−
monocytes compared with the lowest tertile, even after adjustment for common risk factors (HR, 1.66; 95% CI: 1.02 to 2.72). CD14
++
CD16
−
monocytes did not, however, associate with the extent of atherosclerosis at baseline. In contrast, the percentage of monocytes expressing CD16 was negatively associated to the extent of carotid atherosclerosis measured as intima-media thickness at baseline. The chemokine receptors CCR2, CX3CR1, and CCR5 were not differentially expressed between cases and controls on any of the monocyte subsets, but CCR5 expression on CD14
+
CD16
++
monocytes was negatively associated to carotid intima-media thickness.

Conclusions—

This study shows that classical CD14
++
CD16
−
monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population.
General and Disease-Specific Psychosocial Adjustment in Patients With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy With Implantable Cardioverter Defibrillators: A Large Cohort Study
Authors: James Cynthia A. , Tichnell Crystal , Murray Brittney , Daly Amy , Sears Samuel F. , Calkins Hugh
Published: January 2012

Background—

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by frequent life-threatening ventricular arrhythmias, diagnosed on average in the teens to mid-50s and commonly treated by implantable cardioverter defibrillators (ICDs). As younger age and high frequency of ICD discharges are risk factors for difficulties in psychosocial adjustment, we developed a study to assess psychosocial adjustment among patients with ARVD/C and to determine risk factors for poor adjustment in this high-risk population.

Methods and Results—

Eighty-six adults enrolled in the Johns Hopkins ARVD Registry (38 male; mean age, 45.4±12.9 years), with an ICD in place for a median 3.2 years (range, 0.2 to 20.1 years), completed a set of questionnaires measuring ICD-specific anxiety (Florida Shock Anxiety Scale), device acceptance (Florida Patient Acceptance Survey), anxiety and depression (Hospital Anxiety and Depression Scale), and functional capacity (Duke Activity Status Index). Although overall device acceptance (Florida Patient Acceptance Survey mean, 76.7±15.3) was normative, patients with ARVD/C had substantially elevated body image concerns (Florida Patient Acceptance Survey subscale mean, 17.9±23.5) and device-related distress (subscale mean, 26.5±19.2), particularly among younger patients (
P
<0.01). Patients with ARVD/C had elevated ICD-specific (Florida Shock Anxiety Scale mean, 22.9±7.8) and general clinical anxiety (Hospital Anxiety and Depression Scale anxiety subscale mean, 6.2±3.9). Device-specific anxiety (Florida Shock Anxiety Scale) was predicted by younger age (
P
<0.0001), poorer functional capacity (
P
=0.016), having an ICD shock (
P
=0.003), and shorter time since ICD implant (
P
=0.007). Participants with poor device adjustment had an increased likelihood of clinically significant anxiety (
P
=0.006) and depression (
P
=0.008).

Conclusions—

Patients with ARVD/C are at elevated risk for anxiety, and young patients face challenges with device acceptance. Risk factors for poor device adjustment may be used clinically to identify patients at high-risk of psychological distress.
The Cycling of Acetyl-Coenzyme A Through Acetylcarnitine Buffers Cardiac Substrate Supply
Authors: Schroeder Marie A. , Atherton Helen J. , Dodd Michael S. , Lee Phillip , Cochlin Lowri E. , Radda George K. , Clarke Kieran , Tyler Damian J.
Published: January 2012

Background—

Carnitine acetyltransferase catalyzes the reversible conversion of acetyl-coenzyme A (CoA) into acetylcarnitine. The aim of this study was to use the metabolic tracer hyperpolarized [2-
13
C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase facilitates carbohydrate oxidation in the heart.

Methods and Results—

Ex vivo, following hyperpolarized [2-
13
C]pyruvate infusion, the [1-
13
C]acetylcarnitine resonance was saturated with a radiofrequency pulse, and the effect of this saturation on [1-
13
C]citrate and [5-
13
C]glutamate was observed. In vivo, [2-
13
C]pyruvate was infused into 3 groups of fed male Wistar rats: (1) controls, (2) rats in which dichloroacetate enhanced pyruvate dehydrogenase flux, and (3) rats in which dobutamine elevated cardiac workload. In the perfused heart, [1-
13
C]acetylcarnitine saturation reduced the [1-
13
C]citrate and [5-
13
C]glutamate resonances by 63% and 51%, respectively, indicating a rapid exchange between pyruvate-derived acetyl-CoA and the acetylcarnitine pool. In vivo, dichloroacetate increased the rate of [1-
13
C]acetylcarnitine production by 35% and increased the overall acetylcarnitine pool size by 33%. Dobutamine decreased the rate of [1-
13
C]acetylcarnitine production by 37% and decreased the acetylcarnitine pool size by 40%.

Conclusions—

Hyperpolarized
13
C magnetic resonance spectroscopy has revealed that acetylcarnitine provides a route of disposal for excess acetyl-CoA and a means to replenish acetyl-CoA when cardiac workload is increased. Cycling of acetyl-CoA through acetylcarnitine appears key to matching instantaneous acetyl-CoA supply with metabolic demand, thereby helping to balance myocardial substrate supply and contractile function.
Long-Term Propensity Score–Matched Comparison of Percutaneous Closure of Patent Foramen Ovale With Medical Treatment After Paradoxical Embolism
Authors: Wahl Andreas , Jüni Peter , Mono Marie-Luise , Kalesan Bindu , Praz Fabien , Geister Laura , Räber Lorenz , Nedeltchev Krassen , Mattle Heinrich P. , Windecker Stephan , Meier Bernhard
Published: January 2012

Background—

Patients with ischemic stroke or transient ischemic attack presumably related to patent foramen ovale (PFO) are at risk for recurrent cerebrovascular events. Differences in long-term clinical outcome were investigated among patients with percutaneous PFO closure and those who received medical treatment.

Methods and Results—

Between 1994 and 2000, 308 consecutive patients with cerebrovascular events presumably related to PFO underwent either percutaneous PFO closure (150 patients) or medical treatment (158 patients). Patients were followed up prospectively for up to 15 years. Seven patients were lost during follow-up. The primary outcome was a composite of stroke, transient ischemic attack, or peripheral embolism. We analyzed 103 propensity score–matched pairs of patients who underwent percutaneous PFO closure or medical treatment. At a median follow-up of 9 years, the primary composite outcome occurred in 11 patients slated to PFO closure (11%) and 22 patients slated to medical treatment (21%; hazard ratio=0.43; 95% confidence interval=0.20–0.94;
P
=0.033). The treatment effect was driven by a decrease in the risk of transient ischemic attack of 5% versus 14%, respectively (hazard ratio=0.31; 95% confidence interval=0.10–0.94;
P
=0.039). The risk of all-cause (6% in both groups) and cardiovascular (3% in both groups) mortality appeared to be identical.

Conclusion—

In this long-term observational, propensity score–matched study, percutaneous PFO closure was more effective than medical treatment for the secondary prevention of recurrent cerebrovascular events among patients with PFO-related transient ischemic attack or stroke.
Team Weak Crossover
Authors: Agüero-Bautista Calixto
Published: January 2012

It is generally assumed that the weak crossover (WCO) effect arises when an operator fails to bind a pronoun that stands in a particular syntactic configuration with the given operator. In this article, I introduce a new kind of crossover effect in which the binding dependencies of two different operators work in tandem to yield the given effect. The new effect is radically different from the traditional crossover cases, which involve the binding dependency of just one operator. I show that theories that define the WCO principle as a condition regulating the binding of pronouns cannot account for the new effect. I also show that to account for all the varieties of crossover effects, the WCO principle must be defined as a condition regulating the semantic relation of dependence and must make use of the notion of Spell-Out domain discussed by Chomsky ( 2001 , 2004 ).
Reconsidering Rightward Scrambling: Postverbal Constituents in Hindi-Urdu
Authors: Manetta Emily
Published: January 2012

In the most recent account of rightward displacement in Hindi-Urdu, Bhatt and Dayal (2007) claim that all postverbal constituents are derived via rightward movement of a remnant VP. In this article, I argue that the remnant-VP approach does not allow us to make distinctions between the positioning requirements of DPs and CPs. I propose an account of rightward scrambling (following Mahajan 1988 ) that captures the correlation in Hindi-Urdu between scope and linear order, and I claim that finite complement CPs do not undergo scrambling, but are instead obligatorily aligned to the right edge of their containing clause at the level of PF.
Observations of Urban Heat Island Influence on Lake-Breeze Frontal Movement
Authors: Keeler Jason M. , Kristovich David A. R.
Published: January 2012

Predictions of lake and sea breezes are particularly important in large coastal population centers because of the circulations’ influence on heat-wave relief, energy use, precipitation, and dispersion of pollutants. While recent numerical modeling studies have suggested that sea or lake breezes should move more slowly through urban areas than in the surrounding suburbs because of urban heat island (UHI) circulations, there have been few quantitative observational studies to evaluate these results. This study utilizes high-resolution Weather Surveillance Radar-1988 Doppler (WSR-88D) observations to determine the effect of the UHI on lake-breeze frontal movement through Chicago, Illinois, and nearby suburban areas. A total of 44 lake-breeze cases from the April–September 2005 period were examined. The inland movement of the lake-breeze front (LBF) was calculated by tracking “fine lines” of radar reflectivity along several cross sections perpendicular to the Lake Michigan shoreline. The average inland propagation speed of the LBF was 5.0 km h−1; there was substantial spatial and temporal variability in LBF propagation, however. Chicago’s UHI magnitude on lake-breeze days exhibited an average nighttime maximum urban–rural temperature difference near 4.5°C and an afternoon minimum near 0°C. The observed daytime UHI magnitude did not have a significant relationship with lake-breeze frontal movement through Chicago. However, the maximum magnitude of the nighttime UHI preceding lake-breeze development was found to be strongly related to a decrease in speed of LBF movement through Chicago’s southwest (inland) suburbs. This relationship is consistent with previous studies of the diurnal evolution of UHI circulations and may represent a useful method for predicting lake-breeze inland movement.
High-Latitude Contribution to Global Variability of Air–Sea Sensible Heat Flux
Authors: Song Xiangzhou , Yu Lisan
Published: January 2012

The study examined global variability of air–sea sensible heat flux (SHF) from 1980 to 2009 and the large-scale atmospheric and ocean circulations that gave rise to this variability. The contribution of high-latitude wintertime SHF was identified, and the relative importance of the effect of the sea–air temperature difference versus the effect of wind on decadal SHF variability was analyzed using an empirical orthogonal function (EOF) approach. The study showed that global SHF anomalies are strongly modulated by SHF at high latitudes (poleward of 45°) during winter seasons. Decadal variability of global wintertime SHF can be reasonably represented by the sum of two leading EOF modes, namely, the boreal wintertime SHF in the northern oceans and the austral wintertime SHF in the southern oceans. The study also showed that global wintertime SHF is modulated by the prominent modes of the large-scale atmospheric circulation at high latitudes. The increase of global SHF in the 1990s is attributable to the strengthening of the Southern Hemisphere annular mode index, while the decrease of global SHF after 2000 is due primarily to the downward trend of the Arctic Oscillation index. This study identified the important effects of wind direction and speed on SHF variability. Changes in winds modify the sea–air temperature gradient by advecting cold and dry air from continents and by imposing changes in wind-driven oceanic processes that affect sea surface temperature (SST). The pattern of air temperature anomalies dominates over the pattern of SST anomalies and dictates the pattern of decadal SHF variability.
Upper-Tropospheric Forcing on Late July Monsoon Transition in East Asia and the Western North Pacific
Authors: Wu Chi-Hua , Chou Ming-Dah
Published: January 2012

By investigating the large-scale circulation in the upper troposphere, it is demonstrated that the rapid late July summer monsoon transition in the East Asia and western North Pacific (EA-WNP) is associated with a weakened westerly at the exit of the East Asian jet stream (EAJS). Even in a normally stable atmosphere under the influence of the North Pacific (NP) high in late July, convection rapidly develops over the midoceanic region of the western NP (15°–25°N, 150°–170°E). Prior to the rapid transition, the EAJS weakens and shifts northward, which induces a series of changes in downstream regions; the northeastern stretch of the Asian high weakens, upper-tropospheric divergence in the region southwest of the mid-NP trough increases, and convection is enhanced. At the monsoon transition, upper-level high potential vorticity intrudes southward and westward, convection expand from the mid NP westward to cover the entire subtropical western NP, the lower-tropospheric monsoon trough deepens, surface southwesterly flow strengthens, and the western stretch of the NP high shifts northward ~10° latitude to the south of Japan. This series of changes indicates that the EA-WNP late July monsoon transition is initiated from changes in the upper-tropospheric circulation via the weakening of the EAJS south of ~45°N. The weakening of the EAJS south of ~45°N is related to a reduced gradient of the geopotential height on the northern flank of the Asian high, which is related to the massive inland heating and weakening of the South Asian monsoon circulation. The exact timing of the monsoon onset might be tied to the hypothesized “Silk Road pattern” and/or a strong weakening of the South Asian monsoon circulation.