bluuebunny/crossref_metadata_2025 huggingface dataset:
Why a Large Amount of Rain Falls over the Sea in the Vicinity of Western Sumatra Island during Nighttime
Authors: Wu Peiming , Hara Masayuki , Hamada Jun-ichi , Yamanaka Manabu D. , Kimura Fujio
Published: February 2009

Precipitation measurements from the Tropical Rainfall Measuring Mission satellite indicate that annual rainfall over the sea in the vicinity of western Sumatra Island is among the highest on the earth, and most of this rainfall occurs during nighttime. Surface meteorological observations at Tabing on the western coast of the island show frequent occurrences of sudden offshore winds accompanied by an abrupt drop in surface temperatures in the late afternoon and evening. Model simulations for a 1-month period during the rainy season of the region successfully simulate the satellite-observed regional distribution and diurnal variation of rainfall. The simulation results show that convection develops across a wide area over the mountainous areas of the island at similar times in the afternoon with the development of thermally induced local circulations. At these times of the day, convection over the sea along the western coast of the island is suppressed by the thermally and topographically induced diurnal changes in the boundary layer flow. When convection over the mountains of the island dissipates in the late afternoon and evening, a zone of cold surface outflow along the western coast results from the mountain convection breaking out to the sea. Meanwhile, the convective inhibition offshore is reduced in the evening, and the offshore flow causes regular occurrences of convection over the sea near the coast. The triggered convective systems propagate offshore and westward in multicell cluster storms during nighttime, bringing heavy rainfall over the sea off the western coast of the island. Sensitivity experiments with a flat-topography model demonstrate that the frequent occurrence of offshore flow in the late afternoon and evening on the western coast is caused by the mountainous topography of the island and its induced afternoon convection. The mountains on the island and the resultant thermally and convectively induced local circulations can play an important role in the formation of nocturnal abundant rainfall over the sea west of Sumatra Island.
A Multiscale Ensemble Filtering System for Hydrologic Data Assimilation. Part I: Implementation and Synthetic Experiment
Authors: Pan Ming , Wood Eric F. , McLaughlin Dennis B. , Entekhabi Dara , Luo Lifeng
Published: February 2009

The multiscale autoregressive (MAR) framework was introduced in the last decade to process signals that exhibit multiscale features. It provides the method for identifying the multiscale structure in signals and a filtering procedure, and thus is an efficient way to solve the optimal estimation problem for many high-dimensional dynamic systems. Later, an ensemble version of this multiscale filtering procedure, the ensemble multiscale filter (EnMSF), was developed for estimation systems that rely on Monte Carlo samples, making this technique suitable for a range of applications in geosciences. Following the prototype study that introduced EnMSF, a strategy is devised here to implement the multiscale method in a hydrologic data assimilation system, which runs a land surface model. Assimilation experiments are carried out over the Arkansas–Red River basin, located in the central United States (∼645 000 km2), using the Variable Infiltration Capacity (VIC) model with a computing grid of 1062 pixels. A synthetic data assimilation experiment is performed, driven by meteorological forcing fields downscaled from the ensemble forecasts made by the NOAA/National Centers for Environmental Prediction (NCEP) Climate Forecast System (CFS). The classic full-rank ensemble Kalman filter is used as the benchmark to evaluate the multiscale filter performance, and comparisons are also made with a horizontally uncoupled filter. It is demonstrated that the multiscale filter is able to closely approximate the full-rank solution with a low computational cost (∼1/20 of the full-rank filter) in an experiment in which the top-layer soil moisture is assimilated, whereas the horizontally uncoupled filter fails to approximate the full-rank solution.
Access to Diabetes Self-management Education
Authors: Peyrot Mark , Rubin Richard R. , Funnell Martha M. , Siminerio Linda M.
Published: February 2009

Purpose To examine factors related to access to diabetes self-management education (DSME), including services delivered and sought; patient, physician, and program barriers to access; educator outreach and expansion efforts; and perceptions of alternative DSME delivery strategies.

Methods Internet surveys were completed by 1169 adults with diabetes (661 with prior DSME, 508 with no prior DSME) from a national community survey panel, 1871 educators who were AADE members, and 629 physicians (212 diabetes specialists, 417 primary care practitioners) from a national physician survey panel.

Results Physicians want patients to receive more self-management support, but some report that patients are told to do things with which the physician does not agree. Provider (physician and educator)—delivered DSME is more highly regarded among those who have received it than among those who have not received it. Physicians generally have positive perceptions of provider-delivered DSME, and educators see physicians as key to encouraging DSME use in patients. Some physicians are concerned about losing patients sent to DSME, and 11% of patients report changing physicians as a result of DSME. Most DSME programs have grown recently as a result of recruiting efforts and adding new programs/services; most programs plan more such efforts. Patients prefer traditional DSME sources/settings and are moderately accepting of media sources.

Conclusions Additional efforts are required to guarantee that all people with diabetes receive the DSME they need. This will require increased referral by physicians, increased follow-through by patients, and increased availability of DSME in forms that make it appealing to patients and physicians.
The Roots of Resistance to Women's Self-Defense
Authors: Hollander Jocelyn A.
Published: February 2009

Those who teach or research women's self-defense often encounter significant resistance from others. In this article, the author discusses three major types of resistance to women's self-defense (and to women's resistance to violence more generally): the belief that women's resistance is impossible, that it is too dangerous, and that it risks blaming the victim. The author argues that one source of these reactions is people's taken-for-granted beliefs about gender, which limit their ability to understand the research on women's resistance and self-defense—and, indeed, prevent them from being able to conceptualize women as strong and competent social actors.
“What's the Problem?”
Authors: Murray Suellen , Powell Anastasia
Published: February 2009

The campaign of feminists to have domestic violence formally acknowledged as a key issue affecting Australian women succeeded in the early 1980s when governments began developing policy seeking to address the problem. Far from simply adopting feminist gendered understandings of domestic violence, however, the development of contemporary policy responses to this issue has been influenced by a number of competing discourses about the problem, its causes, and possible solutions. Drawing on Bacchi's policy analysis approach, the authors compare the discursive constructions of domestic violence inherent in how the issue is named, framed, and defined across contemporary Australian policy documents.
Twenty Years of Service Guarantee Research
Authors: Hogreve Jens , Gremler Dwayne D.
Published: February 2009

During the past two decades, service guarantees have received increased attention as a means for service firms to attract and retain customers and gain a competitive edge in the marketplace. Although many academic studies, referring to diverse service guarantee aspects, have appeared during this time, a synthesis of research is needed to clarify what researchers have learned about service guarantees and what remains unknown. To evaluate the state of published research on service guarantees, 109 articles published from 1985 to 2008 are collected and analyzed. The resultant review reveals a significant change in the type of research being performed, including a shift toward greater interest in the impact of service guarantees on consumer behavior and service firms. However, a significant shortfall marks empirical work directed toward the internal and operational effects of service guarantees. The effects of service guarantees on service performance, service recovery, and return on service guarantee investments are topics in need of further research.
MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1
Authors: Garzon Ramiro , Liu Shujun , Fabbri Muller , Liu Zhongfa , Heaphy Catherine E.A. , Callegari Elisa , Schwind Sebastian , Pang Jiuxia , Yu Jianhua , Muthusamy Natarajan , Havelange Violaine , Volinia Stefano , Blum William , Rush Laura J. , Perrotti Danilo , Andreeff Michael , Bloomfield Clara D. , Byrd John C. , Chan Kenneth , Wu Lai-Chu , Croce Carlo M. , Marcucci Guido
Published: February 2009

Aberrant DNA hypermethylation contributes to myeloid leukemogenesis by silencing structurally normal genes involved in hematopoiesis. MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs. Recently, miRNAs have been shown to play a role as both targets and effectors in gene hypermethylation and silencing in malignant cells. In the current study, we showed that enforced expression of miR-29b in acute myeloid leukemia cells resulted in marked reduction of the expression of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B at both RNA and protein levels. This in turn led to decrease in global DNA methylation and reexpression of p15INK4b and ESR1 via promoter DNA hypomethylation. Although down-regulation of DNMT3A and DNMT3B was the result of a direct interaction of miR-29b with the 3′ untranslated regions of these genes, no predicted miR-29b interaction sites were found in the DNMT1 3′ untranslated regions. Further experiments revealed that miR-29b down-regulates DNMT1 indirectly by targeting Sp1, a transactivator of the DNMT1 gene. Altogether, these data provide novel functional links between miRNAs and aberrant DNA hypermethylation in acute myeloid leukemia and suggest a potentially therapeutic use of synthetic miR-29b oligonucleotides as effective hypomethylating compounds.
Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1
Authors: Woodfin Abigail , Voisin Mathieu-Benoit , Imhof Beat A. , Dejana Elisabetta , Engelhardt Britta , Nourshargh Sussan
Published: February 2009

Leukocyte transmigration is mediated by endothelial cell (EC) junctional molecules, but the associated mechanisms remain unclear. Here we investigate how intercellular adhesion molecule-2 (ICAM-2), junctional adhesion molecule-A (JAM-A), and platelet endothelial cell adhesion molecule (PECAM-1) mediate neutrophil transmigration in a stimulus-dependent manner (eg, as induced by interleukin-1β [IL-1β] but not tumor necrosis factor-α [TNF-α]), and demonstrate their ability to act in sequence. Using a cell-transfer technique, transmigration responses of wild-type and TNF-α p55/p75 receptor-deficient leukocytes (TNFR−/−) through mouse cremasteric venules were quantified by fluorescence intravital microscopy. Whereas wild-type leukocytes showed a normal transmigration response to TNF-α in ICAM-2−/−, JAM-A−/−, and PECAM-1−/− recipient mice, TNFR−/− leukocytes exhibited a reduced transmigration response. Hence, when the ability of TNF-α to directly stimulate neutrophils is blocked, TNF-α–induced neutrophil transmigration is rendered dependent on ICAM-2, JAM-A, and PECAM-1, suggesting that the stimulus-dependent role of these molecules is governed by the target cell being activated. Furthermore, analysis of the site of arrest of neutrophils in inflamed tissues from ICAM-2−/−, JAM-A−/−, and PECAM-1−/− mice demonstrated that these molecules act sequentially to mediate transmigration. Collectively, the findings provide novel insights into the mechanisms of action of key molecules implicated in leukocyte transmigration.
The Trypanosoma cruzi nucleic acid binding protein Tc38 presents changes in the intramitochondrial distribution during the cell cycle
Authors: Duhagon María A , Pastro Lucía , Sotelo-Silveira José R , Pérez-Díaz Leticia , Maugeri Dante , Nardelli Sheila C , Schenkman Sergio , Williams Noreen , Dallagiovanna Bruno , Garat Beatriz
Published: February 2009

Background

Tc38 of Trypanosoma cruzi has been isolated as a single stranded DNA binding protein with high specificity for the poly [dT-dG] sequence. It is present only in Kinetoplastidae protozoa and its sequence lacks homology to known functional domains. Tc38 orthologues present in Trypanosoma brucei and Leishmania were proposed to participate in quite different cellular processes. To further understand the function of this protein in Trypanosoma cruzi, we examined its in vitro binding to biologically relevant [dT-dG] enriched sequences, its expression and subcellular localization during the cell cycle and through the parasite life stages.

Results

By using specific antibodies, we found that Tc38 protein from epimastigote extracts participates in complexes with the poly [dT-dG] probe as well as with the universal minicircle sequence (UMS), a related repeated sequence found in maxicircle DNA, and the telomeric repeat. However, we found that Tc38 predominantly localizes into the mitochondrion. Though Tc38 is constitutively expressed through non-replicating and replicating life stages of T. cruzi, its subcellular localization in the unique parasite mitochondrion changes according to the cell cycle stage. In epimastigotes, Tc38 is found only in association with kDNA in G1 phase. From the S to G2 phase the protein localizes in two defined and connected spots flanking the kDNA. These spots disappear in late G2 turning into a diffuse dotted signal which extends beyond the kinetoplast. This later pattern is more evident in mitosis and cytokinesis. Finally, late in cytokinesis Tc38 reacquires its association with the kinetoplast. In non-replicating parasite stages such as trypomastigotes, the protein is found only surrounding the entire kinetoplast structure.

Conclusions

The dynamics of Tc38 subcellular localization observed during the cell cycle and life stages support a major role for Tc38 related to kDNA replication and maintenance.
Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status
Authors: Ha Seon-Ah , Lee Youn Soo , Shin Seung Min , Kim Hyun Kee , Kim Sanghee , Namkoong Hong , Kim Hae Joo , Jung Sang Min , Lee Yu Sun , Chung Yeun Jun , Jung Sang Seol , Kim Jin Woo
Published: February 2009

Background

Oncoprotein HCCR-1 functions as a negative regulator of the p53 and contributes breast tumorigenesis. The serum HCCR-1 assay is useful in diagnosing breast cancer and mice transgenic for HCCR developed breast cancers. But it is unknown how HCCR-1 contributes to human breast tumorigenesis.

Methods

Oncogene HCCR-1 expression levels were determined in normal breast tissues, breast cancer tissues and cancer cell lines. We examined whether HCCR-1 protein expression in breast cancer is related to different biological characteristics, including ER, PR, p53 genotype, and HER2 status in 104 primary breast cancer tissues using immunohistochemical analyses.

Results

HCCR-1 was upregulated in breast cancer cells and tissues compared with normal breast tissues. In this study, overexpression of HCCR-1 was well correlated with known breast cancer prognostic markers including the presence of steroid receptors (ER and PR), p53 mutation and high HER2 overexpression. HCCR-1 was not detected in the ER-negative, PR-negative, p53 negative and low HER2 breast cancer tissues. These data indicate that the level of HCCR-1 in breast cancer tissues is relatively well correlated with known breast cancer factors, including the HER2 overexpression, p53 mutation, and ER/PR status.

Conclusion

Determination of HCCR-1 levels as options for HER2 testing is promising although it needs further evaluation.
In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) copolymer
Authors: Gong Chang Yang , Shi Shuai , Dong Peng Wei , Zheng Xiu Ling , Fu Shao Zhi , Guo Gang , Yang Jing Liang , Wei Yu Quan , Qian Zhi Yong
Published: February 2009

Background

Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.

Results

A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 μg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.

Conclusion

The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.
Release of volatile organic compounds (VOCs) from the lung cancer cell line CALU-1 in vitro
Authors: Filipiak Wojciech , Sponring Andreas , Mikoviny Tomas , Ager Clemens , Schubert Jochen , Miekisch Wolfram , Amann Anton , Troppmair Jakob
Published: February 2009

Background

The aim of this work was to confirm the existence of volatile organic compounds (VOCs) specifically released or consumed by lung cancer cells.

Methods

50 million cells of the human non-small cell lung cancer (NSCLC) cell line CALU-1 were incubated in a sealed fermenter for 4 h or over night (18 hours). Then air samples from the headspace of the culture vessel were collected and preconcentrated by adsorption on solid sorbents with subsequent thermodesorption and analysis by means of gas chromatography mass spectrometry (GC-MS). Identification of altogether 60 compounds in GCMS measurement was done not only by spectral library match, but also by determination of retention times established with calibration mixtures of the respective pure compounds.

Results

The results showed a significant increase in the concentrations of 2,3,3-trimethylpentane, 2,3,5-trimethylhexane, 2,4-dimethylheptane and 4-methyloctane in the headspace of CALU-1 cell culture as compared to medium controls after 18 h. Decreased concentrations after 18 h of incubation were found for acetaldehyde, 3-methylbutanal, butyl acetate, acetonitrile, acrolein, methacrolein, 2-methylpropanal, 2-butanone, 2-methoxy-2-methylpropane, 2-ethoxy-2-methylpropane, and hexanal.

Conclusion

Our findings demonstrate that certain volatile compounds can be cancer-cell derived and thus indicative of the presence of a tumor, whereas other compounds are not released but seem to be consumed by CALU-1 cells.
Upregulation of prolylcarboxypeptidase (PRCP) in lipopolysaccharide (LPS) treated endothelium promotes inflammation
Authors: Ngo My-Linh , Mahdi Fakhri , Kolte Dhaval , Shariat-Madar Zia
Published: February 2009

Background

Prolylcarboxypeptidase (Prcp) gene, along with altered PRCP and kallikrein levels, have been implicated in inflammation pathogenesis. PRCP regulates angiotensin 1–7 (Ang 1–7) – and bradykinin (BK) – stimulated nitric oxide production in endothelial cells. The mechanism through which kallikrein expression is altered during infection is not fully understood. Investigations were performed to determine the association between PRCP and kallikrein levels as a function of the upregulation of PRCP expression and the link between PRCP and inflammation risk in lipopolysaccharide (LPS)-induced endothelium activation.

Methods

ThePrcptranscript expression in LPS-induced human umbilical vein endothelial cells (HUVEC) activation was determined by RT-PCR for mRNA. PRCP-dependent kallikrein pathway was determined either by Enzyme Linked ImmunoSorbent Assay (ELISA) or by biochemical assay.

Results

We report that PRCP is critical to the maintenance of the endothelial cells, and its upregulation contributes to the risk of developing inflammation. Significant elevation in kallikrein was seen on LPS-treated HUVECs. The conversion of PK to kallikrein was blocked by the inhibitor of PRCP, suggesting that PRCP might be a risk factor for inflammation.

Conclusion

The increased PRCP lead to a sustained production of bradykinin in endothelium following LPS treatment. This amplification may be an additional mechanism whereby PRCP promotes a sustained inflammatory response. A better appreciation of the role of PRCP in endothelium may contribute to a better understanding of inflammatory vascular disorders and to the development of a novel treatment.
Altered microRNA expression in patients with non-obstructive azoospermia
Authors: Lian Jie , Zhang Xiansheng , Tian Hui , Liang Ning , Wang Yong , Liang Chaozhao , Li Xin , Sun Fei
Published: February 2009

Background

MicroRNAs (miRNAs), a class of small non-coding RNA molecules, are indicated to play essential roles in spermatogenesis. However, little is known about the expression patterns or function of miRNAs in human testes involved in infertility.

Methods

In this study, the miRNA expression profiles of testes of patients with non-obstructive azoospermia (NOA) and normal controls were performed by using microarray technologies.

Results

Altered microRNA expression in NOA patients was found, with 154 differentially down-regulated and 19 up-regulated miRNAs. These findings have been confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) assays on select miRNAs, including miR-302a, miR-491-3p, miR-520d-3p and miR-383. Several down-regulated miRNA clusters in patients with NOA were identified, such as the oncogenic potential of the mir-17-92 cluster and mir-371,2,3 cluster.

Conclusion

This is the first report that the expression of miRNAs is altered in testicular tissues of patients with NOA, suggesting a role of miRNAs in regulating spermatogenesis in human males.
Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases
Authors: Vivancos ValȲrie , Chen Ping , Spassky Nathalie , Qian Dong , Dabdoub Alain , Kelley Matthew , Studer Michȳle , Guthrie Sarah
Published: February 2009

Background

Wnt proteins play roles in many biological processes, including axon guidance and cell migration. In the mammalian hindbrain, facial branchiomotor (FBM) neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. In this study, we investigated a possible role of Wnts and the planar cell polarity (PCP) pathway in this process.

Results

Here we demonstrate a novel role for Wnt proteins in guiding FBM neurons during their rostral to caudal migration in the hindbrain. We found that Wnt5a is expressed in a caudalhigh to rostrallow gradient in the hindbrain. Wnt-coated beads chemoattracted FBM neurons to ectopic positions in an explant migration assay. The rostrocaudal FBM migration was moderately perturbed in Wnt5a mutant embryos and severely disrupted in Frizzled3 mutant mouse embryos, and was aberrant following inhibition of Wnt function by secreted Frizzled-related proteins. We also show the involvement of the Wnt/PCP pathway in mammalian FBM neuron migration. Thus, mutations in two PCP genes, Vangl2 and Scribble, caused severe defects in FBM migration. Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins.

Conclusion

These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process. Molecules of the PCP pathway and the JNK and ROCK kinases also play a role in the FBM migration and are likely mediators of Wnt signalling.
Spatial antialias filtering in the slowness-frequency domain
Authors: Dev Ashwani , McMechan George A.
Published: February 2009

A rigorous, explicit spatial antialias filter is designed and applied to spatially coarsely sampled seismic data by removing all energy above the first Nyquist wavenumber, and aliased energy that is folded back across the Nyquist, in the horizontal slowness-frequency domain. The spatial filtering in the slowness-frequency domain is explicit, free from any event linearity assumption, and does not require any interpolation. The spatially aliased energy is dispersive, and present at small and large slownesses. Comparison of the output data after antialias spatial filtering, with output data after conventional antialias frequency filtering, shows that the filter removes the spatially aliased frequencies selectively at each slowness; antialias low-pass frequency filtering under- or overcorrects for spatial aliasing at all slownesses. A seismic gather can be spatially dealiased only at the expense of wavelet spectral changes; dealiasing and preservation of amplitude variations with offset are not simultaneously possible.
Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins
Authors: Bialas Nathan J. , Inglis Peter N. , Li Chunmei , Robinson Jon F. , Parker Jeremy D. K. , Healey Michael P. , Davis Erica E. , Inglis Chrystal D. , Toivonen Tiina , Cottell David C. , Blacque Oliver E. , Quarmby Lynne M. , Katsanis Nicholas , Leroux Michel R.
Published: February 2009

Meckel syndrome (MKS) is a ciliopathy characterized by encephalocele, cystic renal disease, liver fibrosis and polydactyly. An identifying feature of MKS1, one of six MKS-associated proteins, is the presence of a B9 domain of unknown function. Using phylogenetic analyses, we show that this domain occurs exclusively within a family of three proteins distributed widely in ciliated organisms. Consistent with a ciliary role, all Caenorhabditis elegans B9-domain-containing proteins, MKS-1 and MKS-1-related proteins 1 and 2 (MKSR-1, MKSR-2), localize to transition zones/basal bodies of sensory cilia. Their subcellular localization is largely co-dependent, pointing to a functional relationship between the proteins. This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia. As reported for MKS1, disrupting human MKSR1 or MKSR2 causes ciliogenesis defects. By contrast, single, double and triple C. elegans mks/mksr mutants do not display overt defects in ciliary structure, intraflagellar transport or chemosensation. However, we find genetic interactions between all double mks/mksr mutant combinations, manifesting as an increased lifespan phenotype, which is due to abnormal insulin–IGF-I signaling. Our findings therefore demonstrate functional interactions between a novel family of proteins associated with basal bodies or cilia, providing new insights into the molecular etiology of a pleiotropic human disorder.
Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility
Authors: Papusheva Ekaterina , de Queiroz Fernanda Mello , Dalous Jeremie , Han Yunyun , Esposito Alessandro , Jares-Erijmanxa Elizabeth A. , Jovin Thomas M. , Bunt Gertrude
Published: February 2009

Focal adhesion kinase (FAK) controls cellular adhesion and motility processes by its tight link to integrin- and extracellular-matrix-mediated signaling. To explore the dynamics of the regulation of FAK, we constructed a FRET-based probe that visualizes conformational rearrangements of the FERM domain of FAK in living cells. The sensor reports on an integrin-mediated conformational change in FAK following cellular adhesion. The perturbation is kinase-independent and involves the polybasic KAKTLR sequence in the FERM domain. It is manifested by an increased FRET signal and is expressed primarily in focal adhesions, and to a lesser extent in the cytoplasm. The conformational change in the FERM domain of FAK is observed in two consecutive phases during spreading – early and late – and is enriched in fully adhered motile cells at growing and sliding peripheral focal-adhesion sites, but not in stable or retracting focal adhesions. Inhibition of the actomyosin system indicates the involvement of tension signaling induced by Rho-associated kinase, rather than by myosin light-chain kinase, in the modulation of the FERM response. We conclude that the heterogeneous conformation of the FERM domain in focal adhesions of migrating cells reflects a complex regulatory mechanism for FAK that appears to be under the influence of cellular traction forces.
Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36
Authors: Endo Akinori , Matsumoto Masaki , Inada Toshifumi , Yamamoto Akitsugu , Nakayama Keiichi I. , Kitamura Naomi , Komada Masayuki
Published: February 2009

The nucleolus is a subnuclear compartment and the site of ribosome biogenesis. Previous studies have implicated protein ubiquitylation in nucleolar activity. Here we show that USP36, a deubiquitylating enzyme of unknown function, regulates nucleolar activity in mammalian cells. USP36 localized to nucleoli via the C-terminal region, which contains basic amino acid stretches. Dominant-negative inhibition of USP36 caused the accumulation of ubiquitin-protein conjugates in nucleoli, suggesting that nucleoli are the site of USP36 action. USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation. RNAi-mediated depletion of cellular USP36 resulted in reduced levels of rRNA transcription and processing, a less-developed nucleolar morphology and a slight reduction in the cytoplasmic ribosome level, which eventually led to a reduced rate of cell proliferation. We conclude that by deubiquitylating various nucleolar substrate proteins including nucleophosmin/B23 and fibrillarin, USP36 plays a crucial role in regulating the structure and function of nucleoli.
A comparison of the dynamic properties of transducer adapters for measurement of hand-transmitted vibration
Authors: Song C M , Jang H-K , Chai J
Published: February 2009

The dynamic characteristics of five types of widely used transducer adapters were compared in terms of vibration transmissibility between an accelerometer on the surface of the gripping area and another within each of the transducer adapters over a frequency range of 25–1250 Hz. Performance was also assessed from the ratio between two human vibration exposure levels, ahv, 1 and ahv, 2, measured using the two accelerometers over nine combinations of grip force and feed force. In this study, vibration transmissibility and ahv ratio of unity are considered. The vibration transmissibility and ahv ratio indicated that the flexible palm adapter provided the best estimate of vibration transmission to the hand. This transducer adapter exhibited the smallest deviation from unity for vibration transmissibility, which was <1.8 per cent over the frequency range, and ahv ratio, which was <4 per cent over nine combinations of grip and feed forces. From the investigation, the flexible palm adapter showed negligible distortion over the frequency range and high applicability, regardless of the gripping condition. The handle-type adapter provided the second-best estimate.
The interaction of radiation with opposing mixed convection within a differentially heated square enclosure
Authors: Mahapatra S K
Published: February 2009

The present study addresses the mathematical modelling aspects of transport phenomena in steady, two-dimensional, laminar flow accompanied by heat transfer in a differentially heated cavity with moving walls in the presence of radiatively absorbing, emitting, and scattering grey medium. The discrete-ordinate method has been used in modelling the radiative transport equation, and finite-difference method based on finite-volume approach is used as the discretization technique. Two cases of opposing mixed convection arising out of vertical isothermal wall movement and horizontal adiabatic wall movement and their interaction with radiation have been critically examined. Buoyancy-opposed mixed convection interacting with radiation has been given emphasis in the present study. The effect of Richardson's number (i.e. Ri from 0.1 to 10) on fluid flow and energy transfer has been studied. In the presence of radiation, flow reversal is found to be one of the revealing characteristic features.
The design of spherical multilobe-cam mechanisms
Authors: Bai S , Angeles J
Published: February 2009

Cam—roller mechanisms can be used in transmissions and robotic devices as an alternative to their bevel-gear counterparts. As bevel gears are used to couple shafts of intersecting axes, their cam-mechanism replacements are bound to have intersecting axes as well. This means that the contact surface of the cam must be conical, which leads to spherical cam mechanisms. Compared with gear transmissions, cam—roller mechanisms feature low friction, low backlash, and high strength. However, cam mechanisms may end up with a high pressure angle if negative action, a motion in which the cam is driven by mechanism rollers, occurs. This article reports the design of transmissions with spherical multilobe cams (MLCs), as a means to reduce the pressure angle. The kinematics of MLC, including profile generation, undercutting-avoidance, and transmission-quality evaluation, is studied here. A case study has been included, in which the synthesis of a spherical MLC transmission is undertaken as a means to improve the transmission quality of a spherical epicyclic gear train. This train was introduced with the purpose of producing a singularity-free, unlimited-workspace pitch—roll wrist.
Hydromagnetic stability of a thin electrically conducting fluid film flowing down the outside surface of a long vertically aligned column
Authors: Cheng P-J
Published: February 2009

This article considers the stability of a thin electrically conducting fluid film flowing down the outer surface of a long vertical cylinder in the presence of an applied magnetic field. Using the long-wave perturbation method to solve the generalized non-linear kinematic equations with free film interface, the normal mode approach is first used to compute the linear stability solution. The method of multiple scales is then used to obtain the weak non-linear dynamics. The results indicate that both subcritical instability and supercritical stability conditions are possible. The degree of instability in the film flow is intensified by the lateral curvature of the cylinder. The results also show that increasing the strength of the magnetic field tends to enhance the stability.
A novel vibration system based on instantaneous motion centre for high accuracy dynamic balancing measurement of outboard rotor
Authors: Peng Q , Ping C
Published: February 2009

To overcome the disadvantages of the traditional vibration system used in a horizontal dynamic balancing machine, based on the principle of the instantaneous motion centre in theoretical mechanics, a novel two-degree-of-freedom vibration system comprising two non-parallel four-bar linkages in series is designed to improve the plane separation effect and minimum achievable residual unbalance for dynamic balancing measurement of an outboard rotor. The structure characteristics and unbalancing response of this vibration system are analysed in depth. The plane separation equations are derived. Theoretical analyses show that this vibration system integrates the advantages of both the overhanging beam structure and simple-supported beam structure, and its vibration centre keeps at the instantaneous motion centres, with the result that the balancing efficiency and plane separation performances are improved. Moreover, to improve the sensitivity of the vibration system, the distance between measuring planes is increased by adjusting the angles of two four-bar linkages. The transducers are installed on the same measuring plane; thus, the performance difference in transducers caused by environment fluctuation is reduced and the force coupling effect is eliminated. The result for this vibration system in long-term operation is a more accurate measurement with a lower requirement for a second correction run. The final experimental results validate the superiority of this vibration system in plane separation performance, minimum achievable residual unbalance, and repeatability.
Understanding and modelling the torsional stiffness of harmonic drives through finite-element method
Authors: Rhéaume F-E , Champliaud H , Liu Z
Published: February 2009

Torsional stiffness or rigidity is a crucial characteristic in the design of transmission devices, including harmonic drives (HDs). Among the various design aspects constituting a reduction mechanism in robotic systems, torsional stiffness is an important factor for positioning accuracy and control issues. One of the major advantages of HDs is their capacity to present a high reduction ratio while maintaining a small hardware size. However, manufacturing these drives remains a complex and costly process due to the high precision of its machined components; as a result, the use of such drives is still limited only to high-end mechanical products and technologies. Given these costs, numerical analysis becomes an effective alternative for obtaining valuable data through simulations, without the need for prototypes. This article presents a finite-element model to reproduce the behaviour of the torsional stiffness of an HD. The numerical model allows an evaluation of the effects of various geometrical parameters on the torsional stiffness of the HD. The numerical model of the HD can be used for optimization purposes, i.e. to develop an HD with a high torque capacity combined with a high-rated lifespan.
The New Dutch Timetable: The OR Revolution
Authors: Kroon Leo , Huisman Dennis , Abbink Erwin , Fioole Pieter-Jan , Fischetti Matteo , Maróti Gábor , Schrijver Alexander , Steenbeek Adri , Ybema Roelof
Published: February 2009

In December 2006, Netherlands Railways introduced a completely new timetable. Its objective was to facilitate the growth of passenger and freight transport on a highly utilized railway network and improve the robustness of the timetable, thus resulting in fewer operational train delays. Modifications to the existing timetable, which was constructed in 1970, were not an option; additional growth would require significant investments in the rail infrastructure.

Constructing a railway timetable from scratch for about 5,500 daily trains was a complex problem. To support this process, we generated several timetables using sophisticated operations research techniques. Furthermore, because rolling-stock and crew costs are principal components of the costs of a passenger railway operator, we used innovative operations research tools to devise efficient schedules for these two resources.

The new resource schedules and the increased number of passengers resulted in an additional annual profit of €40 million ($60 million); the additional revenues generated approximately €10 million of this profit. We expect this profit to increase to €70 million ($105 million) annually in the coming years. However, the benefits of the new timetable for the Dutch society as a whole are much greater: more trains are transporting more passengers on the same railway infrastructure, and these trains are arriving and departing on schedule more than they ever have in the past. In addition, the rail transport system will be able to handle future transportation demand growth and thus allow cities to remain accessible to more people. Therefore, we expect that many will switch from car transport to rail transport, thus reducing the emission of greenhouse gases.
Optimizing the Norwegian Natural Gas Production and Transport
Authors: Rømo Frode , Tomasgard Asgeir , Hellemo Lars , Fodstad Marte , Eidesen Bjørgulf Haukelidsæter , Pedersen Birger
Published: February 2009

The network for transport of natural gas on the Norwegian Continental Shelf, with 7,800 km of subsea pipelines, is the world's largest offshore pipeline network. The gas flowing through this network represents approximately 15 percent of European consumption, and the system has a capacity of 120 billion standard cubic meters (bcm) a year. In a network of interconnected pipelines, system effects are prevalent, and the network must be analyzed as a whole to determine the optimal operation. SINTEF has developed a decision support tool, GassOpt, which is based on a mixed-integer program, to optimize the network configuration and routing for the main Norwegian shipper of natural gas, StatoilHydro, and the independent network operator, Gassco. GassOpt allows users to graphically model their network and run optimizations to find the best solutions quickly. StatoilHydro and Gassco use it to evaluate the current network and possible network extensions. Both companies use operations research (OR) methods in the departments that are responsible for transport planning and security of supply. Several new OR projects have grown out from this cooperation. StatoilHydro estimates that its accumulated savings related to the use of GassOpt were approximately US$2 billion in the period 1995–2008.
Reducing Flight Delays Through Better Traffic Management
Authors: Sud Ved P. , Tanino Midori , Wetherly James , Brennan Michael , Lehky Miro , Howard Ken , Oiesen Rick
Published: February 2009

As air traffic in the United States has grown over the last several years, traffic demand has begun to outstrip capacity. As of 2005, the Federal Aviation Administration (FAA) had no effective approach for strategically managing a weather event that has been very disruptive to the national aviation system—large-scale thunderstorms that block the major flight routes in the northeastern United States. The operations research team that supports the FAA's efforts to provide innovations in air traffic management, led by researchers at Metron Aviation, Inc. and the Volpe Transportation Center, recognized the consequence of this operational deficiency and set out to resolve it. In this paper, we show how this team

(1) developed and applied system-simulation models to quantify the extent of the traffic flow management problem and convey its magnitude to the FAA and to the aviation industry;

(2) designed the Airspace Flow Program (AFP), a new approach to managing air traffic that could correct the problem within the limitations of a short development cycle and a change-resistant culture;

(3) designed and developed an interactive simulation system that could be and was used to refine and perfect this concept prior to deployment by developing policies on the use of a decision support system;

(4) engaged FAA and airline traffic management experts in a series of interactive exercises using the simulation system to develop the final software design, operational procedures, and decision rules for deployment and use; and

(5) provided a clear and convincing postdeployment benefits assessment for the new traffic management approach.

The deployment of this new capability was an enormous success that both the FAA and the airline community heralded widely. The postdeployment impact assessment showed benefits to the aircraft operators and the flying public of almost $190 million in 2006 and 2007, the first two years of use, compared to less than $5 million in design and development costs. Broader usage of AFPs and new applications for them show a projected 10-year benefit of approximately $2.8 billion.
Priority Assignment Under Imperfect Information on Customer Type Identities
Authors: Argon Nilay Tanık , Ziya Serhan
Published: February 2009

In many service systems, customers are not served in the order they arrive, but according to a priority scheme that ranks them with respect to their relative “importance.” However, it may not be an easy task to determine the importance level of customers, especially when decisions need to be made under limited information. A typical example is from health care: When triage nurses classify patients into different priority groups, they must promptly determine each patient's criticality levels with only partial information on their conditions.

We consider such a service system where customers are from one of two possible types. The service time and waiting cost for a customer depends on the customer's type. Customers' type identities are not directly available to the service provider; however, each customer provides a signal, which is an imperfect indicator of the customer's identity. The service provider uses these signals to determine priority levels for the customers with the objective of minimizing the long-run average waiting cost. In most of the paper, each customer's signal equals the probability that the customer belongs to the type that should have a higher priority and customers incur waiting costs that are linear in time. We first show that increasing the number of priority classes decreases costs, and the policy that gives the highest priority to the customer with the highest signal outperforms any finite class priority policy. We then focus on two-class priority policies and investigate how the optimal policy changes with the system load. We also investigate the properties of “good” signals and find that signals that are larger in convex ordering are more preferable. In a simulation study, we find that when the waiting cost functions are nondecreasing, quadratic, and convex, the policy that assigns the highest priority to the customer with the highest signal performs poorly while the two-class priority policy and an extension of the generalized cμ rule perform well.