bluuebunny/crossref_metadata_2025 huggingface dataset:
An in vivo RNA interference screen identifies gene networks controlling Drosophila melanogasterblood cell homeostasis
Authors: Avet-Rochex Amélie , Boyer Karène , Polesello Cédric , Gobert Vanessa , Osman Dani , Roch Fernando , Augé Benoit , Zanet Jennifer , Haenlin Marc , Waltzer Lucas
Published: June 2010

Background

In metazoans, the hematopoietic system plays a key role both in normal development and in defense of the organism. In Drosophila, the cellular immune response involves three types of blood cells: plasmatocytes, crystal cells and lamellocytes. This last cell type is barely present in healthy larvae, but its production is strongly induced upon wasp parasitization or in mutant contexts affecting larval blood cell homeostasis. Notably, several zygotic mutations leading to melanotic mass (or "tumor") formation in larvae have been associated to the deregulated differentiation of lamellocytes. To gain further insights into the gene regulatory network and the mechanisms controlling larval blood cell homeostasis, we conducted a tissue-specific loss of function screen using hemocyte-specific Gal4 drivers and UAS-dsRNA transgenic lines.

Results

By targeting around 10% of the Drosophila genes, this in vivo RNA interference screen allowed us to recover 59 melanotic tumor suppressor genes. In line with previous studies, we show that melanotic tumor formation is associated with the precocious differentiation of stem-cell like blood progenitors in the larval hematopoietic organ (the lymph gland) and the spurious differentiation of lamellocytes. We also find that melanotic tumor formation can be elicited by defects either in the fat body, the embryo-derived hemocytes or the lymph gland. In addition, we provide a definitive confirmation that lymph gland is not the only source of lamellocytes as embryo-derived plasmatocytes can differentiate into lamellocytes either upon wasp infection or upon loss of function of the Friend of GATA cofactor U-shaped.

Conclusions

In this study, we identify 55 genes whose function had not been linked to blood cell development or function before in Drosophila. Moreover our analyses reveal an unanticipated plasticity of embryo-derived plasmatocytes, thereby shedding new light on blood cell lineage relationship, and pinpoint the Friend of GATA transcription cofactor U-shaped as a key regulator of the plasmatocyte to lamellocyte transformation.
Drawing the line between commensal and pathogenic Gardnerella vaginalis through genome analysis and virulence studies
Authors: Harwich Michael D , Alves Joao M , Buck Gregory A , Strauss Jerome F , Patterson Jennifer L , Oki Aminat T , Girerd Philippe H , Jefferson Kimberly K
Published: June 2010

Background

Worldwide, bacterial vaginosis (BV) is the most common vaginal disorder. It is associated with risk for preterm birth and HIV infection. The etiology of the condition has been debated for nearly half a century and the lack of knowledge about its cause and progression has stymied efforts to improve therapy and prevention. Gardnerella vaginalis was originally identified as the causative agent, but subsequent findings that it is commonly isolated from seemingly healthy women cast doubt on this claim. Recent studies shedding light on the virulence properties of G. vaginalis, however, have drawn the species back into the spotlight.

Results

In this study, we sequenced the genomes of a strain of G. vaginalis from a healthy woman, and one from a woman with bacterial vaginosis. Comparative analysis of the genomes revealed significant divergence and in vitro studies indicated disparities in the virulence potential of the two strains. The commensal isolate exhibited reduced cytotoxicity and yet the cytolysin proteins encoded by the two strains were nearly identical, differing at a single amino acid, and were transcribed at similar levels. The BV-associated strain encoded a different variant of a biofilm associated protein gene and demonstrated greater adherence, aggregation, and biofilm formation. Using filters with different pore sizes, we found that direct contact between the bacteria and epithelial cells is required for cytotoxicity.

Conclusions

The results indicated that contact is required for cytotoxicity and suggested that reduced cytotoxicity in the commensal isolate could be due to impaired adherence. This study outlines two distinct genotypic variants of G. vaginalis, one apparently commensal and one pathogenic, and presents evidence for disparate virulence potentials.
Prevalence and pattern of cognitive impairment in rural and urban populations from Northern Portugal
Authors: Nunes Belina , Silva Ricardo D , Cruz Vitor T , Roriz Jose M , Pais Joana , Silva Maria C
Published: June 2010

Background

Despite worldwide recognition of the burden of dementia, no epidemiological data is yet available in Portugal. The objective of this study is to estimate the prevalence and describe the pattern of cognitive impairment with dementia or no dementia (CIND) in rural and urban populations from Northern Portugal.

Methods

Two random samples of residents aged 55 to 79 years in rural and urban communities were drawn from the health centres registries to be screened for cognitive impairment. The screening criteria for dementia were an abnormal Mini-Mental State Examination (MMSE) score or a Blessed Dementia Scale score. After excluding those who tested positive for dementia, cut-off points for CIND were set at 1 standard deviation below the mean of the MMSE according to educational level. All those who screened positive either for dementia or CIND were examined by a neurologist for establishing a definitive diagnosis.

Results

The prevalence of cognitive impairment was higher in rural than in urban populations, 16.8% (95% CI: 14.3-19.8%) vs. 12.0% (95%CI: 9.3-15.4%), with a rural/urban prevalence ratio (PR) of 2.16 (95% CI: 1.04-4.50) in the eldest and 2.19 (95% CI: 1.01-4.76) in persons with vascular risk factors. The prevalence of dementia was 2.7% (95% CI: 1.9-3.8%) with a rural/urban PR = 2.1 and the prevalence of CIND was 12.3% (95% CI: 10.4-14.4%) and PR = 1.3. The prevalence of dementia increases exponentially with age and in those with cerebrovascular disease or other comorbid conditions while the prevalence of CIND, besides these factors, is also higher in persons with low levels of education or vascular risk factors. Alzheimer's and vascular disease were equally likely aetiologies of dementia (38.7%), the later more common in men PR(F:M = 0.3) as opposed to the former PR(F:M = 2.0). Vascular CIND, associated either with cerebrovascular disease or vascular risk factors was more frequent (39.7%) then depression (18.4%) or any other aetiology.

Conclusions

The prevalence of cognitive impairment is higher in rural compared with urban populations. This is shown in the synergy between age and rurality, with the rural/urban prevalence ratio increasing with age. In this relatively young population from Northern Portugal, cerebrovascular disease as well as vascular risk factors account for 48% of overall cognitive impairment.
Centrosome clustering and cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors
Authors: del Rey Javier , Prat Esther , Ponsa Immaculada , Lloreta Josep , Gelabert Antoni , Algaba Ferran , Camps Jordi , Miró Rosa
Published: June 2010

Background

Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor.

Methods

Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed.

Results

Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes.

Conclusions

Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001).
Quercetin abrogates chemoresistance in melanoma cells by modulating ΔNp73
Authors: Thangasamy Thilakavathy , Sittadjody Sivanandane , Mitchell Geoffrey C , Mendoza Erin E , Radhakrishnan Vijayababu M , Limesand Kirsten H , Burd Randy
Published: June 2010

Background

The alkylating agent Dacarbazine (DTIC) has been used in the treatment of melanoma for decades, but when used as a monotherapy for cancer only moderate response rates are achieved. Recently, the clinical use of Temozolomide (TMZ) has become the more commonly used analog of DTIC-related oral agents because of its greater bioavailability and ability to cross the blood brain barrier. The response rates achieved by TMZ are also unsatisfactory, so there is great interest in identifying compounds that could be used in combination therapy. We have previously demonstrated that the bioflavonoid quercetin (Qct) promoted a p53-mediated response and sensitized melanoma to DTIC. Here we demonstrate that Qct also sensitizes cells to TMZ and propose a mechanism that involves the modulation of a truncated p53 family member, ΔNp73.

Methods

DB-1 melanoma (p53 wildtype), and SK Mel 28 (p53 mutant) cell lines were treated with TMZ (400 μM) for 48 hrs followed by Qct (75 μM) for 24 hrs. Cell death was determined by Annexin V-FITC staining and immunocytochemical analysis was carried out to determine protein translocation.

Results

After treatment with TMZ, DB-1 cells demonstrated increased phosphorylation of Ataxia telangiectasia mutated (ATM) and p53. However, the cells were resistant to TMZ-induced apoptosis and the resistance was associated with an increase in nuclear localization of ΔNp73. Qct treatment in combination with TMZ abolished drug insensitivity and caused a more than additive induction of apoptosis compared to either treatment alone. Treatment with Qct, caused redistribution of ΔNp73 into the cytoplasm and nucleus, which has been associated with increased p53 transcriptional activity. Knockdown of ΔNp73 restored PARP cleavage in the TMZ treated cells, confirming its anti-apoptotic role. The response to treatment was predominantly p53 mediated as the p53 mutant SK Mel 28 cells showed no significant enhancement of apoptosis.

Conclusion

This study demonstrates that Qct can sensitize cells to TMZ and that the mechanisms of sensitization involve modulation of p53 family members.
Candida glabrata endophthalmitis following penetrating keratoplasty in a patient with negative donor rim culture
Authors: Muzaliha Mohd Nor , Adil Hussein , Ibrahim Mohtar , Shatriah Ismail
Published: June 2010

Background

Candida glabrata endophthalmitis following keratoplasty is rare and almost always associated with positive donor rim culture.

Case presentation

A 63-year-old patient, diagnosed Fuch's endothelial dystrophy in both eyes underwent a penetrating keratoplasty in his right eye. He had multiple underlying medical problems, which included diabetes mellitus, hypertension, hypoadrenalism on oral dexamethasone and fatty liver secondary to hypertrigliseridemia. He developed multiple suture abscesses, corneal haziness, retrocorneal white plaques and a level of hypopyon two weeks after an uneventful penetrating keratoplasty in his right eye. Cultures of the donor button and the transport media culture were negative. Candida glabrata was isolated successfully from the aqueous and vitreous taps. He was treated with a combination of topical, intracameral, intravitreal and intravenous Amphotericin B. His final visual acuity remained poor due to the haziness of the corneal button.

Conclusion

Candida glabrata endophthalmitis following penetrating keratoplasty can occur in negative donor rim and transport media cultures. The growth of the organism is facilitated by the patient's immunocompromised status. Awareness by the ophthalmologists and appropriate choice of antibiotics are mandatory in this challenging condition.
Hydrocarbon phenotyping of algal species using pyrolysis-gas chromatography mass spectrometry
Authors: Barupal Dinesh K , Kind Tobias , Kothari Shankar L , Lee Do Yup , Fiehn Oliver
Published: June 2010

Background

Biofuels derived from algae biomass and algae lipids might reduce dependence on fossil fuels. Existing analytical techniques need to facilitate rapid characterization of algal species by phenotyping hydrocarbon-related constituents.

Results

In this study, we compared the hydrocarbon rich algaeBotryococcus brauniiagainst the photoautotrophic model algaeChlamydomonas reinhardtiiusing pyrolysis-gas chromatography quadrupole mass spectrometry (pyGC-MS). Sequences of up to 48 dried samples can be analyzed using pyGC-MS in an automated manner without any sample preparation. Chromatograms of 30-min run times are sufficient to profile pyrolysis products from C8 to C40 carbon chain length. The freely available software tools AMDIS and SpectConnect enables straightforward data processing. InBotryococcussamples, we identified fatty acids, vitamins, sterols and fatty acid esters and several long chain hydrocarbons. The algae speciesC. reinhardtii, B. brauniirace A andB. brauniirace B were readily discriminated using their hydrocarbon phenotypes. Substructure annotation and spectral clustering yielded network graphs of similar components for visual overviews of abundant and minor constituents.

Conclusion

Pyrolysis-GC-MS facilitates large scale screening of hydrocarbon phenotypes for comparisons of strain differences in algae or impact of altered growth and nutrient conditions.
Proton dynamics in cancer
Authors: Huber Veronica , De Milito Angelo , Harguindey Salvador , Reshkin Stephan J , Wahl Miriam L , Rauch Cyril , Chiesi Antonio , Pouysségur Jacques , Gatenby Robert A , Rivoltini Licia , Fais Stefano
Published: June 2010

Cancer remains a leading cause of death in the world today. Despite decades of research to identify novel therapeutic approaches, durable regressions of metastatic disease are still scanty and survival benefits often negligible. While the current strategy is mostly converging on target-therapies aimed at selectively affecting altered molecular pathways in tumor cells, evidences are in parallel pointing to cell metabolism as a potential Achilles' heel of cancer, to be disrupted for achieving therapeutic benefit. Critical differences in the metabolism of tumor versus normal cells, which include abnormal glycolysis, high lactic acid production, protons accumulation and reversed intra-extracellular pH gradients, make tumor site a hostile microenvironment where only cancer cells can proliferate and survive. Inhibiting these pathways by blocking proton pumps and transporters may deprive cancer cells of a key mechanism of detoxification and thus represent a novel strategy for a pleiotropic and multifaceted suppression of cancer cell growth.

Research groups scattered all over the world have recently started to investigate various aspects of proton dynamics in cancer cells with quite encouraging preliminary results. The intent of unifying investigators involved in this research line led to the formation of the "International Society for Proton Dynamics in Cancer" (ISPDC) in January 2010. This is the manifesto of the newly formed society where both basic and clinical investigators are called to foster translational research and stimulate interdisciplinary collaboration for the development of more specific and less toxic therapeutic strategies based on proton dynamics in tumor cell biology.
Tomato leaf curl Kerala virus (ToLCKeV) AC3 protein forms a higher order oligomer and enhances ATPase activity of replication initiator protein (Rep/AC1)
Authors: Pasumarthy Kalyan K , Choudhury Nirupam R , Mukherjee Sunil K
Published: June 2010

Background

Geminiviruses are emerging plant viruses that infect a wide variety of vegetable crops, ornamental plants and cereal crops. They undergo recombination during co-infections by different species of geminiviruses and give rise to more virulent species. Antiviral strategies targeting a broad range of viruses necessitate a detailed understanding of the basic biology of the viruses. ToLCKeV, a virus prevalent in the tomato crop of Kerala state of India and a member of genus Begomovirus has been used as a model system in this study.

Results

AC3 is a geminiviral protein conserved across all the begomoviral species and is postulated to enhance viral DNA replication. In this work we have successfully expressed and purified the AC3 fusion proteins from E. coli. We demonstrated the higher order oligomerization of AC3 using sucrose gradient ultra-centrifugation and gel-filtration experiments. In addition we also established that ToLCKeV AC3 protein interacted with cognate AC1 protein and enhanced the AC1-mediated ATPase activity in vitro.

Conclusions

Highly hydrophobic viral protein AC3 can be purified as a fusion protein with either MBP or GST. The purification method of AC3 protein improves scope for the biochemical characterization of the viral protein. The enhancement of AC1-mediated ATPase activity might lead to increased viral DNA replication.
Improved xylose and arabinose utilization by an industrial recombinant Saccharomyces cerevisiae strain using evolutionary engineering
Authors: Garcia Sanchez Rosa , Karhumaa Kaisa , Fonseca César , Sànchez Nogué Violeta , Almeida João RM , Larsson Christer U , Bengtsson Oskar , Bettiga Maurizio , Hahn-Hägerdal Bärbel , Gorwa-Grauslund Marie F
Published: June 2010

Background

Cost-effective fermentation of lignocellulosic hydrolysate to ethanol by Saccharomyces cerevisiae requires efficient mixed sugar utilization. Notably, the rate and yield of xylose and arabinose co-fermentation to ethanol must be enhanced.

Results

Evolutionary engineering was used to improve the simultaneous conversion of xylose and arabinose to ethanol in a recombinant industrial Saccharomyces cerevisiae strain carrying the heterologous genes for xylose and arabinose utilization pathways integrated in the genome. The evolved strain TMB3130 displayed an increased consumption rate of xylose and arabinose under aerobic and anaerobic conditions. Improved anaerobic ethanol production was achieved at the expense of xylitol and glycerol but arabinose was almost stoichiometrically converted to arabitol. Further characterization of the strain indicated that the selection pressure during prolonged continuous culture in xylose and arabinose medium resulted in the improved transport of xylose and arabinose as well as increased levels of the enzymes from the introduced fungal xylose pathway. No mutation was found in any of the genes from the pentose converting pathways.

Conclusion

To the best of our knowledge, this is the first report that characterizes the molecular mechanisms for improved mixed-pentose utilization obtained by evolutionary engineering of a recombinant S. cerevisiae strain. Increased transport of pentoses and increased activities of xylose converting enzymes contributed to the improved phenotype.
Characterization of the Taenia spp HDP2 sequence and development of a novel PCR-based assay for discrimination of Taenia saginata from Taenia asiatica
Authors: González Luis M , Bailo Begoña , Ferrer Elizabeth , García Maria D Fernandez , Harrison Leslie JS , Parkhouse Michael RE , McManus Donald P , Gárate Teresa
Published: June 2010

A previously described Taenia saginata HDP2 DNA sequence, a 4-kb polymorphic fragment, was previously used as the basis for developing PCR diagnostic protocols for the species-specific discrimination of T. saginata from T. solium and for the differentiation of T. saginata from T. asiatica. The latter was shown subsequently to lack the required specificity, so we undertook genetic studies of the HDP2 sequence from T. saginata and T. asiatica to determine why, and to develop a novel HDP2-PCR protocol for the simultaneous unambiguous identification of human taeniids. Sequencing and further analysis of the HDP2 DNA fragments of 19 Asiatic isolates of T. saginata and T. asiatica indicated that the HDP2 sequences of both species exhibited clear genomic variability, due to polymorphic variable fragments, that could correspond to the non-transcribed region of ribosomal DNA. This newly observed polymorphism allowed us to develop a novel, reproducible and reliable HDP2-PCR protocol which permitted the simultaneous discrimination of all T. saginata and T. asiatica isolates examined. This species-specific identification was based on, and facilitated by, the clear size difference in amplicon profiles generated: fragments of 1300 bp, 600 bp and 300 bp were produced for T. asiatica, amplicons of 1300 bp and 300 bp being obtained for T. saginata. Control T. solium samples produced one amplicon of 600 bp with the HDP2-PCR protocol. The assay has the potential to prove useful as a diagnostic tool in areas such as South East Asia where T. saginata, T. asiatica and T. solium coexist.
Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells
Authors: Wu Kong-Yan , Zhou Xiu-Ping , Luo Zhen-Ge
Published: June 2010

Background

During cerebellar development, Purkinje cells (PCs) form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT) is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs.

Results

We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML), the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA) inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor (BDNF) promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K+ was inhibited by inhibition or down-regulation of GGT.

Conclusion

Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis in vivo.
Looking through the ‘window of opportunity’: is there a new paradigm of podiatry care on the horizon in earlyrheumatoid arthritis?
Authors: Woodburn James , Hennessy Kym , Steultjens Martijn PM , McInnes Iain B , Turner Deborah E
Published: June 2010

Over the past decade there have been significant advances in the clinical understanding and care of rheumatoid arthritis (RA). Major paradigm changes include earlier disease detection and introduction of therapy, and ‘tight control’ of follow‐up driven by regular measurement of disease activity parameters. The advent of tumour necrosis factor (TNF) inhibitors and other biologic therapies have further revolutionised care. Low disease state and remission with prevention of joint damage and irreversible disability are achievable therapeutic goals. Consequently new opportunities exist for all health professionals to contribute towards these advances. For podiatrists relevant issues range from greater awareness of current concepts including early referral guidelines through to the application of specialist skills to manage localised, residual disease activity and associated functional impairments. Here we describe a new paradigm of podiatry care in early RA. This is driven by current evidence that indicates that even in low disease activity states destruction of foot joints may be progressive and associated with accumulating disability. The paradigm parallels the medical model comprising early detection, targeted therapy, a new concept of tight control of foot arthritis, and disease monitoring.

‘Podiatrists are experts on foot disorders: both patients and rheumatologists can profit from the involvement of a podiatrist’

‐ Korda and Balint, 2004 [1].
Progesterone reverses the mesenchymal phenotypes of basal phenotype breast cancer cells via a membrane progesterone receptor mediated pathway
Authors: Zuo Lian , Li Wei , You Shaojin
Published: June 2010

Introduction

Basal phenotype breast cancers (BPBC) are often associated with apparent epithelial to mesenchymal transition (EMT). The role of progesterone (P4) in regulating EMT of BPBC has not been reported.

Methods

The EMT relevant biology was investigatedin vitrousing human BPBC cell models (MDA-MB468 and MDA-MB231) with P4, PR agonist (RU486), and PR antagonist (R5020) treatments. The essential role of membrane progesterone receptor α (mPRα) in the P4-regulated EMT was demonstrated by knocking down the endogenous gene and/or stably transfecting exogenous mPRα gene in the BPBC cell models.

Results

The expression of snail and down-stream EMT proteins such as occludin, fibronectin, and E-cadherin was significantly regulated by P4 incubation, which was accompanied by cell morphological reversion from mesenchymal to epithelial phenotypes. In searching for the cell mediator of P4' action in the MDA-MB468 (MB468) cells, it was found that mPRα but not the nuclear PR has an essential role in the P4 mediated EMT inhibition. Knocking down the expression of mPRα with specific siRNA blocked the P4's effects on expression of the EMT proteins. In another BPBC cell line - MDA-MB231 (MB231), which is mPRα negative by Western blotting, P4 treatment did not alter cell proliferation and EMT protein expressions. Introduction of the exogenous mPRα cDNA into these cells caused cell proliferation, but not EMT, to become responsive to P4 treatment. In further studies, it was found that activation of the PI3K/Akt pathway is necessary for the P4-induced EMT reversion. To define the potential inter-mediate steps between mPRα and PI3K, we demonstrated that mPRα, caveolin-1 (Cav-1), and epidermal growth factor receptor (EGFR) are colocalized in the membrane of caveolar vesicle and the P4-repressed EMT in MB468 cells can be blocked by EGFR inhibitor (AG1478) and PI3K inhibitor (wortmannin).

Conclusions

Our data suggest that the signaling cascade of P4 induced mesenchymal repression is mediated through mPRα and other caveolae bound signaling molecules namely Cav-1, EGFR, and PI3K. This novel finding may have great impact on fully understanding the pathogenesis of BPBC and provide an essential clue for developing a targeted therapeutic strategy for treatment of BPBC.
Pulse-pressure variation and hemodynamic response in patients with elevated pulmonary artery pressure: a clinical study
Authors: Wyler von Ballmoos Moritz , Takala Jukka , Roeck Margareta , Porta Francesca , Tueller David , Ganter Christoph C , Schröder Ralph , Bracht Hendrik , Baenziger Bertram , Jakob Stephan M
Published: June 2010

Introduction

Pulse-pressure variation (PPV) due to increased right ventricular afterload and dysfunction may misleadingly suggest volume responsiveness. We aimed to assess prediction of volume responsiveness with PPV in patients with increased pulmonary artery pressure.

Methods

Fifteen cardiac surgery patients with a history of increased pulmonary artery pressure (mean pressure, 27 ± 5 mm Hg (mean ± SD) before fluid challenges) and seven septic shock patients (mean pulmonary artery pressure, 33 ± 10 mm Hg) were challenged with 200 ml hydroxyethyl starch boli ordered on clinical indication. PPV, right ventricular ejection fraction (EF) and end-diastolic volume (EDV), stroke volume (SV), and intravascular pressures were measured before and after volume challenges.

Results

Of 69 fluid challenges, 19 (28%) increased SV > 10%. PPV did not predict volume responsiveness (area under the receiver operating characteristic curve, 0.555; P = 0.485). PPV was ≥13% before 46 (67%) fluid challenges, and SV increased in 13 (28%). Right ventricular EF decreased in none of the fluid challenges, resulting in increased SV, and in 44% of those in which SV did not increase (P = 0.0003). EDV increased in 28% of fluid challenges, resulting in increased SV, and in 44% of those in which SV did not increase (P = 0.272).

Conclusions

Both early after cardiac surgery and in septic shock, patients with increased pulmonary artery pressure respond poorly to fluid administration. Under these conditions, PPV cannot be used to predict fluid responsiveness. The frequent reduction in right ventricular EF when SV did not increase suggests that right ventricular dysfunction contributed to the poor response to fluids.
IL-15 has innate anti-tumor activity independent of NK and CD8 T cells
Authors: Davies Elizabeth , Reid Sarah , Medina Maria Fe , Lichty Brian , Ashkar Ali A
Published: June 2010

IL-15 can have innate anti-tumor activity independent of NK and CD8+ T cells and the common gamma chain receptor.

The innate immune system is crucial for host defense and immunosurveillance against pathogens and tumor cells. IL-15 is a pleiotropic cytokine with important effects on cells of the innate and adaptive immune systems. The NK cell- and CD8+ T cell-mediated functions of IL-15 against tumor cells have been well documented. However, it has not been established whether IL-15 has innate anti-tumor functions independent of these cells. Here, we explored the innate anti-tumor potential of IL-15 using a B16F10 melanoma tumor model. IL-15tg mice exhibited significantly more resistance to tumor growth and metastasis compared to B6 mice, and to IL-15−/− mice, which exhibited increased susceptibility to B16F10 challenge. In vivo depletion of NK cells and CD8+ T cells abrogated the innate resistance to B16F10 cells in B6 but not in IL-15tg mice. In addition, lung macrophages from IL-15tg mice produced significantly higher levels of NO and IL-12 compared with macrophages from B6 or IL-15−/− mice. To examine whether IL-15 has innate anti-tumor activity independent of NK cells and CD8+ T cells, we developed Ad-Op-hIL-15; this resulted in significantly higher levels of biologically active hIL-15. Delivery of Ad-Op-hIL-15 into RAG-2−/−/γc−/− mice significantly suppressed tumor burden in the lungs compared with the control adenovirus vector. Our results show that IL-15 can have innate anti-tumor activity independent of NK cells and CD8+ T cells and the common γcR.
Oxygen limitation and thermal tolerance in two terrestrial arthropod species
Authors: Stevens Meagan M. , Jackson Sue , Bester Susan A. , Terblanche John S. , Chown Steven L.
Published: June 2010

Recent studies of marine invertebrates and fish have suggested that lower and upper critical temperatures (CTmin and CTmax) are coupled by a common mechanism: oxygen and capacity limitation of thermal tolerance (OCLT). Using thermolimit respirometry, we tested the predictions of this theory for terrestrial arthropods by measuring maxima and minima for both critical temperatures and metabolic rate in two arthropods, the isopod Porcellio scaber and the beetle Tenebrio molitor, at 40%, 21%, 10% and 2.5% ambient O2. Critical temperatures were identified as particular points on both activity and traces in four ways. In the first two instances, we identified the inflection points in regressions of absolute difference sum (ADS) residuals calculated for activity (aADS) and (VI), respectively. In the third, we visually identified the lowest point before the post-mortal peak in CO2 release (PMV). Finally, we pinpointed the sudden drop in at death, where fell outside the 95% confidence intervals of the 5 min period immediately preceding the drop-off (CI). Minimum and maximum metabolic rates were determined using CO2 traces, and the temperatures corresponding to these identified as TMetMin and TMetMax. For both species, ambient oxygen concentration did not influence CTmin, minimum metabolic rate, or TMetMin. By contrast, severe hypoxia (2.5% O2) caused a 6.9°C decline in activity-based CTmax for T. molitor and a 10.6°C decline for P. scaber, relative to normoxia (21% O2). The magnitude of this decrease differed between methods used to estimated critical thermal limits, highlighting the need for a standard method to determine these endpoints during thermolimit respirometry. Maximum metabolic rate also declined with decreasing ambient oxygen in both species. The combination of increasing metabolic rate and oxygen limitation affected upper thermal limits in these arthropods only in severe hypoxia (2.5% O2). In both species, CTmin and CTmax responded differently to oxygen limitation, suggesting that this is not a common mechanism coupling upper and lower limits in terrestrial arthropods.
Effect of laboratory acclimation on the variation of reproduction-related characters in Drosophila melanogaster
Authors: Houot Benjamin , Svetec Nicolas , Godoy-Herrera Raùl , Ferveur Jean-François
Published: June 2010

The natural variation of sex-specific characters between populations can favor their behavioral isolation, eventually leading to the formation of new species. Marked variations for male courtship, mating and the production of sex pheromones – three complex characters potentially inducing sexual isolation – were found between Drosophila melanogaster populations of various origins acclimated for many generations in research laboratories. However, the natural variation of these three characters between natural populations and their evolution after long-term acclimation in the laboratory remains unknown. We measured many traits involved in these characters in six stocks initiated with distinct populations sampled in a restricted geographic area. Several sex-specific traits varied between stocks freshly brought back to the laboratory. After 100 generations spent in the laboratory without any experimental selection, traits varied in a strain-dependent manner. This variation was not related to a reduction of their variance except for copulation duration. This indicates that reproduction-related characters can diverge between neighboring D. melanogaster populations, and differently adapt to stable laboratory conditions.
Hydrodynamic determination of the moving direction of an artificial fin by a harbour seal (Phoca vitulina)
Authors: Wieskotten S. , Dehnhardt G. , Mauck B. , Miersch L. , Hanke W.
Published: June 2010

Harbour seals can use their vibrissal system to detect and follow hydrodynamic trails left by moving objects. In this study we determined the maximum time after which a harbour seal could indicate the moving direction of an artificial fish tail and analysed the hydrodynamic parameters allowing the discrimination. Hydrodynamic trails were generated using a fin-like paddle moving from left to right or from right to left in the calm water of an experimental box. The blindfolded seal was able to recognise the direction of the paddle movement when the hydrodynamic trail was up to 35 s old. Particle Image Velocimetry (PIV) revealed that the seal might have perceived and used two different hydrodynamic parameters to determine the moving direction of the fin-like paddle. The structure and spatial arrangement of the vortices in the hydrodynamic trail and high water velocities between two counter-rotating vortices are characteristic of the movement direction and are within the sensory range of the seal.
The effects of turbulent eddies on the stability and critical swimming speed of creek chub (Semotilus atromaculatus)
Authors: Tritico H. M. , Cotel A. J.
Published: June 2010

The effect of turbulent eddy diameter, vorticity and orientation on the 2 min critical swimming speed and stability of creek chub (Semotilus atromaculatus) is reported. Turbulent eddies were visualized and their properties were quantified using particle image velocimetry (PIV). Flow fields with an increasing range in eddy diameter were created by inserting cylinder arrays upstream from the swimming test section. Eddy vorticity increased with increasing velocity. Two orientations of eddies, eddies spinning about a vertical axis and eddies spinning about a horizontal (wall-to-wall) axis, were investigated. Stability challenges were not observed until the largest (95th percentile) eddy diameters reached 76% of the fish body total length. Under these conditions fish were observed to spin in an orientation consistent with the rotational axis of the large eddies and translate downstream. These losses in postural control were termed ‘spills’. Spills were 230% more frequent and lasted 24% longer in turbulent flow fields dominated by horizontal eddies than by vertical eddies of the same diameter. The onset of spills coincided with a 10% and 22% reduction in critical swimming speed in turbulent flows dominated by large vertical and horizontal eddies, respectively. These observations confirm predictions by Pavlov et al., Cada and Odeh, Lupandin, and Liao that the eddy diameter, vorticity and orientation play an important role in the swimming capacity of fishes.
Teaching Note—Using the Maximum Clique Problem to Motivate Branch-and-Bound
Authors: Strickland Dawn M.
Published: June 2010

In the typical OR classroom, the method of branch-and-bound is most often introduced when solving integer programs. In this note, we discuss teaching a branch-and-bound procedure motivated by the maximum clique problem rather than by a more traditional integer program. This teaching method is beneficial not only because it provides an alternate perspective on branch-and-bound for students, but also because it requires no optimization software to illustrate. The method is particularly useful in early optimization courses where students have math and engineering backgrounds. There is much literature focused on optimization students with non-technical backgrounds; we present a teaching method specifically intended to enhance the learning process for the more technical students.
Teaching Nonzero Sum Games Using a Diagrammatic Determination of Equilibria
Authors: Magirou Evangelos F. , Vassilakis Dimitrios K. , Androutsopoulos Ion
Published: June 2010

We present a diagrammatic method that allows the determination of all Nash equilibria of 2 × M nonzero sum games, extending thus the well known diagrammatic techniques for 2 × M zero sum and 2 × 2 nonzero sum games. We show its appropriateness for teaching purposes by analyzing modified versions of the prisoners' dilemma, the battle of the sexes, as well as of the zero sum game of matching pennies. We then use the method to give simple proofs for the existence of Nash equilibria in all 2 × M games, for both the nonzero sum (Nash existence theorem) and the zero sum case (Minimax theorem). We also prove in the same spirit the remarkable general fact that in a nondegenerate 2 × M nonzero sum game there is an odd number of equilibria.
An Introduction to Electricity Market Auctions Using a Spreadsheet
Authors: Farr John , Felder Frank A.
Published: June 2010

This paper presents a spreadsheet model of an electricity market that can be used to simulate two types of auctions, a single price auction and a paid your bid auction. This model can be used in a variety of pedagogical applications. From the perspective of management science and operations research (MS/OR), this application emphasizes model use and integrates several important concepts. From a business perspective, users can explore various bidding strategies and their implications, depending on the auction rules. From a public policy perspective, students can learn how market design decisions may influence market outcomes and the exercise of market power.
A Baseball Decision Problem
Authors: Brimberg Jack , Hurley Bill
Published: June 2010

This paper presents a Kahneman-Tversky type probability example in a baseball context with a counter-intuitive best strategy. The problem is ideally suited for classroom discussion in an introductory course on probability or managerial decision-making.
Simulating NHL Games to Motivate Student Interest in OR/MS
Authors: Ingolfsson Armann
Published: June 2010

Monte Carlo simulation models of regular season and playoff games in the National Hockey League can be used to motivate students who are sports fans to study OR/MS models. I describe how such models can be implemented in a spreadsheet, how my colleagues and I have used them in our courses, and how students have reacted to them.
Comparing the Impact of Star Rookies Carmelo Anthony and Lebron James: An Example on Simulating Team Performances in the NBA League
Authors: Ammar Salwa , Wright Ronald
Published: June 2010

This paper describes a simulation exercise designed for introductory quantitative method classes both at the MBA and undergraduate level. The exercise tracks the performances of teams in the National Basketball Association (NBA) during the season of 2004. It is designed as a spreadsheet model and is developed in stages throughout the academic semester. The example is a significant illustration of the use of sports as a vehicle for teaching OR topics, specifically simulation. It also incorporates many spreadsheet modeling skills such as the use of Excel functions and Data Tables. The model provided a good mix of the ingredients for an effective simulation example including a variety of answers, challenges and surprises.
Towards an AoA-Free Courseware for the Critical Path Method
Authors: Sniedovich Moshe
Published: June 2010

One of the mysteries of OR/MS teaching is no doubt the AoA vs AoN syndrome. It poses the following dilemma in connection with teaching the Critical path Method: should the popular and well established Activity on Arc (AoA) paradigm or the pedagogically and practically superior Activity on Node (AoN) paradigm be used? In this discussion we argue that it is time to eradicate this affliction and call upon OR/MS courseware developers to once and for all abandon the AoA paradigm in favour of AoN. A simple on line module is provided for experimentation with the Critical Path Method.
An Interactive VBA Tool for Teaching Statistical Process Control (SPC) and Process Management Issues
Authors: Balakrishnan Jaydeep , Oh Sherry L.
Published: June 2010

With a global emphasis on improved quality, Statistical Process Control (SPC) is an important process management tool with renewed significance. In order to address this issue, we have developed an interactive VBA Tool for teaching SPC and process management issues. Students can experiment with the tool to interactively examine the various issues that affect SPC and gain insight into the important issues in managing a process. The graphical nature of the interface should allow students to visually see the effect of changes in process parameters. A detailed Instructor's Manual and a Student Lab Manual accompany the software.
Addressing Industrial Problems Using Various Mathematical Models
Authors: Stecke Kathryn E.
Published: June 2010

Mathematics has been called the language of science. Mathematics is used to solve many real-world problems in industry, the physical sciences, economics, social and human sciences, engineering, and technology, for example. We overview the many industrial problems that have been solved using fuzzy logic technology, multiobjective metaheuristics, neural networks, tabu search, genetic algorithms, simulated annealing, decision analysis, Petri nets, and queueing models. This overview could be useful for Ph.D. students in Industrial Engineering, Operations Research, and Operations Management who are looking to solve some real problems. Future industrial applications are also be described.
Business Technology Management: A Case Study
Authors: Andriole Stephen J. , Nydick Robert
Published: June 2010

This paper describes how we integrated two courses and two disciplines into a single, required “hands-on” course for undergraduates studying management science (MS) and management information systems (MIS). The motivation for what was initially an experiment (and is now a permanent part of the curriculum) was to exploit the synergy between the analytical approaches to modeling, decision-making and project management that are the mainstay of MS with the increasingly rigorous discipline of business technology management and that field's models, methods, tools and techniques. We describe the previous two courses, the re-designed course and several examples of how management science methods, tools and techniques were used to solve real business technology management problems selected by Villanova University's Chief Information Officer (CIO) and Chief Technology Officer (CTO).
PERT Completion Times Revisited
Authors: Williams Fred E.
Published: June 2010

Two sources of PERT completion time bias are well documented in the literature: near critical paths turning critical during execution and misspecified activity time probability models. Although simulation is clearly the most appropriate method for assessing project duration, most introductory discussions touch on these issues and move quickly to standard approximations, implying that PERT offers useful, if only approximate, project duration estimates. This paper uses simulation to illustrate the nature and extent of PERT approximation errors in simple examples from two excellent texts. The examples raise serious questions about the utility of PERT project duration estimates and suggest opportunities for improvement in introductory PERT instruction.
Professional Decision Modeling: Details of a Short MBA Practice Course
Authors: Regan Peter J.
Published: June 2010

This article describes the week-to-week dynamics of a five-week decision science elective practice course in Dartmouth's MBA program. The course begins with a refresher assignment in simulation and optimization. Next come two intense weeks of spreadsheet modeling to value an industrial asset in the status quo and with capital investments. The course then focuses on negotiating with potential buyers. I urge students to craft effective arguments to persuade decision makers of the best course of action. In closing, I propose an effort by faculty from multiple business schools to develop jointly a suite of multi-week cases, to be taught concurrently, with modest prizes for the best student work.
Simulating the Spread of a Virus in a Computer Network
Authors: Estrada Jihad , Drezner Zvi
Published: June 2010

In this paper we propose a simulation problem that can be used as an exercise in a simulation class using an excel add-on simulation package. Suppose that N objects (computers, people, animals, plants) are interacting in pairs. Every time unit (for example, a second for a computer, a day or a week for people), each object randomly selects another object and contacts it. Suppose that one object is infected with a virus. How long will it take until all objects are infected? How many objects are infected after 5 time units? This process is a simplified model for the spread of AIDS among humans, computer viruses among computers, or any communicable disease among humans, animals, or plants.