bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent and Emergent Models in Affective Computing
Authors: Calvo Rafael A.
Published: July 2010

New research on affective computing aiming to develop computer systems that recognize and respond to affective states can also contribute to the issues raised by Coan. Research on how humans interact with computers, and computer models that automatically recognize affective states from features in our physiology, behaviour, and language, may provide insights on how emotions that are experienced and expressed come to be. For example, there is empirical evidence that affect recognition techniques using several modalities are more accurate than those using a single modality, but it is not clear if these improvements are caused by superadditivity (i.e., emergence) or redundancy.
The role of pharmacists in training doctors about infections and antimicrobial prescribing
Authors: Budwall B.
Published: July 2010

This paper highlights the role of clinical pharmacists in training doctors about infections and optimal antibiotic prescribing. Although these principles can be equally applied to both primary and secondary care, this paper will focus on such activity in secondary care alone. Most NHS trusts in the United Kingdom now have a specialist antimicrobial pharmacist taking the lead, but all pharmacists can take effective measures to educate prescribers and nurses about the prudent use of antimicrobials and improve the management of infections. Such quality efforts need to be maintained to ensure a sustained approach in the ever-changing field of infection.
Treatment strategies for osteoarthritis patients with pain and hypertension
Authors: Verdecchia Paolo , Angeli Fabio , Mazzotta Giovanni , Martire Paola , Garofoli Marta , Gentile Giorgio , Reboldi Gianpaolo
Published: July 2010

Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP), which is more marked in patients with established hypertension. NSAIDs and COX-2 inhibitors attenuate the antihypertensive effect of several antihypertensive agents. Frequent BP controls are needed in treated hypertensive patients who are concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase in BP may be associated with an important rise in the risk of major cardiovascular complications. In meta-analyses, an increase in systolic BP of 5 mmHg was associated with a 25% higher risk of cardiovascular events. These data have been confirmed in randomized studies with rofecoxib and celecoxib, where a modest increase in BP was associated with a significantly higher risk of cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric oxide donator (CINOD) class is promising in the treatment of patients with OA. Naproxcinod, the first CINOD investigated in clinical trials, is composed of the traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise in normotensive and hypertensive patients observed with naproxen. The BP benefit of naproxcinod over naproxen was greater in patients concomitantly receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. These investigational data suggest that naproxcinod is a valuable alternative to NSAIDs and COX-2 inhibitors for treatment of OA patients.
TAT-mediated transduction of NF-Ya peptide induces the ex vivo proliferation and engraftment potential of human hematopoietic progenitor cells
Authors: Domashenko Alevtina D. , Danet-Desnoyers Gwenn , Aron Alissa , Carroll Martin P. , Emerson Stephen G.
Published: July 2010

Retroviral overexpression of NF-Ya, the regulatory subunit of the transcription factor NF-Y, activates the transcription of multiple genes implicated in hematopoietic stem cell (HSC) self-renewal and differentiation and directs HSCs toward self-renewal. We asked whether TAT-NF-Ya fusion protein could be used to transduce human CD34+ cells as a safer, more regulated alternative approach to gene therapy. Here we show that externally added recombinant protein was able to enter the cell nucleus and activate HOXB4, a target gene of NF-Ya, using real-time polymerase chain reaction RNA and luciferase-based protein assays. After TAT-NF-Ya transduction, the proliferation of human CD34+ cells in the presence of myeloid cytokines was increased 4-fold. Moreover, TAT-NF-Ya-treated human primary bone marrow cells showed a 4-fold increase in the percentage of huCD45+ cells recovered from the bone marrow of sublethally irradiated, transplanted NOD-Scid IL2Rγnull mice. These data demonstrate that TAT-peptide therapies are an alternative approach to retroviral stem cell therapies and suggest that NF-Ya peptide delivery should be further evaluated as a tool for HSC/progenitors ex vivo expansion and therapy.
Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study
Authors: Kristinsson Sigurdur Y. , Tang Min , Pfeiffer Ruth M. , Björkholm Magnus , Blimark Cecilie , Mellqvist Ulf-Henrik , Wahlin Anders , Turesson Ingemar , Landgren Ola
Published: July 2010

Patients with multiple myeloma (MM) have an increased risk of fractures. On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk. Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls. MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years. The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001). On the basis of 10 years of follow-up, there was an increased risk of vertebral/pelvic (HR = 2.37; 95% CI, 2.02-2.78), sternal/costae (HR = 1.93; 95% CI, 1.5-2.48), arm (HR = 1.23; 95% CI, 1.06-1.43), leg (HR = 1.40; 95% CI, 1.26-1.56), and other/multiple fractures (HR = 4.25; 95% CI, 3.29-5.51). Risks for fractures did not differ by isotype or M protein concentration at diagnosis. MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia. Our results suggest that bone alterations are present in early myelomagenesis. Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.
Recipient T lymphocytes modulate the severity of antibody-mediated transfusion-related acute lung injury
Authors: Fung Yoke Lin , Kim Michael , Tabuchi Arata , Aslam Rukhsana , Speck Edwin R. , Chow Leola , Kuebler Wolfgang M. , Freedman John , Semple John W.
Published: July 2010

Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and has been ranked as one of the leading causes of transfusion-related fatalities. Nonetheless, many details of the immunopathogenesis of TRALI, particularly with respect to recipient factors are unknown. We used a murine model of antibody-mediated TRALI in an attempt to understand the role that recipient lymphocytes might play in TRALI reactions. Intravenous injection of an IgG2a antimurine major histocompatibility complex class I antibody (34-1-2s) into BALB/c mice induced moderate hypothermia and pulmonary granulocyte accumulation but no pulmonary edema nor mortality. In contrast, 34-1-2s injections into mice with severe combined immunodeficiency caused severe hypothermia, severe pulmonary edema, and approximately 40% mortality indicating a critical role for T and B lymphocytes in suppressing TRALI reactions. Adoptive transfer of purified CD8+ T lymphocytes or CD4+ T cells but not CD19+ B cells into the severe combined immunodeficiency mice alleviated the antibody-induced hypothermia, lung damage, and mortality, suggesting that T lymphocytes were responsible for the protective effect. Taken together, these results suggest that recipient T lymphocytes play a significant role in suppressing antibody-mediated TRALI reactions. They identify a potentially new recipient mechanism that controls the severity of TRALI reactions.
Comparative analysis of secreted protein evolution using expressed sequence tags from four poplar leaf rusts (Melampsora spp.)
Authors: Joly David L , Feau Nicolas , Tanguay Philippe , Hamelin Richard C
Published: July 2010

Background

Obligate biotrophs such as rust fungi are believed to establish long-term relationships by modulating plant defenses through a plethora of effector proteins, whose most recognizable feature is the presence of a signal peptide for secretion. Since the phenotypes of these effectors extend to host cells, their genes are expected to be under accelerated evolution stimulated by host-pathogen coevolutionary arms races. Recently, whole genome sequence data has allowed the prediction of secretomes, facilitating the identification of putative effectors.

Results

We generated cDNA libraries from four poplar leaf rust pathogens (Melampsoraspp.) and used computational approaches to identify and annotate putative secreted proteins with the aim of uncovering new knowledge about the nature and evolution of the rust secretome. While more than half of the predicted secretome members encoded lineage-specific proteins, similarities with experimentally characterized fungal effectors were also identified. A SAGE analysis indicated a strong stage-specific regulation of transcripts encoding secreted proteins. The average sequence identity of putative secreted proteins to their closest orthologs in the wheat stem rustPuccinia graminisf. sp.triticiwas dramatically reduced compared with non-secreted ones. A comparative genomics approach based on homologous gene groups unravelled positive selection in putative members of the secretome.

Conclusion

We uncovered robust evidence that different evolutionary constraints are acting on the rust secretome when compared to the rest of the genome. These results are consistent with the view that these genes are more likely to exhibit an effector activity and be involved in coevolutionary arms races with host factors.
Prevalence of Plasmodium vivax VK210 and VK247 subtype in Myanmar
Authors: Kim Tong-Soo , Kim Hyung-Hwan , Lee Sun-Sim , Na Byoung-Kuk , Lin Khin , Cho Shin-Hyeong , Kang Yoon-Joong , Kim Do-Kyung , Sohn Youngjoo , Kim Hyuck , Lee Hyeong-Woo
Published: July 2010

Background

Plasmodium vivax is divided into two subtypes, a dominant form, VK210 and a variant form, VK247. This division is dependent on the amino acid composition of the circumsporozoite (CS) protein. In this study, the prevalence of the VK247 variant form of P. vivax was investigated in Myanmar.

Methods

The existence of malaria parasites in blood samples was determined by microscopic examination, polymerase chain reaction (PCR) and DNA hybridization assays. To test for antibodies against P. vivax and Plasmodium falciparum in blood samples, an indirect immunofluorescence antibody test (IFAT) was performed using asexual blood antigens. An enzyme-linked immunosorbent assay with synthetic VK210 and VK247 antigens was carried out to discriminate between the P. vivax subtypes.

Results

By thick smear examination, 73 (n = 100) patients were single infected with P. vivax, one with P. falciparum and 13 with both species. By thin smear, 53 patients were single infected with P. vivax, eight with only P. falciparum and 16 with both. Most of the collected blood samples were shown to be P. vivax positive (n = 95) by PCR. All cases that were positive for P. falciparum by PCR (n = 43) were also positive for P. vivax. However, 52 cases were single infected with P. vivax. IFAT showed antibody titres from 1:32 to 1:4,096. Additionally, using specific antibodies for VK210 and VK247, ELISA showed that 12 patients had antibodies for only the VK210 subtype, 4 patients had only VK247 subtype antibodies and 21 patients had antibodies for both subtypes. Using a DNA hybridization test, 47 patients were infected with the VK210 type, one patient was infected with VK247 and 23 patients were infected with both subtypes.

Conclusions

The proportion of the VK247 subtype in Myanmar was 43.1% (n = 25) among 58 positive cases by serodiagnosis and 25.6% (n = 24) among 94 positive cases by genetic diagnosis. In both diagnostic methods, the infection status of malaria patients is highly diverse with respect to malaria species, and multiple clonal infections are prevalent in Myanmar. Therefore, the complexity of the infection should be considered carefully when diagnosing malaria in Myanmar.
Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis
Authors: Barros Karina V , Xavier Roberta AN , Abreu Gilclay G , Martinez Carlos AR , Ribeiro Marcelo L , Gambero Alessandra , Carvalho Patrícia O , Nascimento Claudia MO , Silveira Vera LF
Published: July 2010

It was investigated whether dietary polyunsaturated fatty acids (PUFA) could influence colonic injury, tissue DNA damage, cytokines and myeloperoxidase activity (MPO) and plasma corticosterone in DSS-induced colitis rats. Male weaning Wistar rats were fed for 47 days with an AIN-93 diet with control (C), fish (F) or a mixture of fish and soybean oil (SF). The colitis was induced from day 36 until day 42 by 3% DSS in drinking water. On day 48, blood samples were collected for corticosterone determination. The distal colon was excised for histological analysis and to quantify the cytokine (IL-4, IL-10 and INF-γ), MPO and DNA damage. The disease activity index (DAI) was recorded daily during colitis induction. The DAI, MPO, histological analyses showed decreases only in the SF group compared with the C group. IL-10 was increased and DNA damage was reduced in the groups F and SF, and an inverse correlation between these variables was found. There were no differences in corticosterone, IFN-γ and IL-4 levels. Soybean and fish oil mixture may be effective in improving colonic injury and DNA damage, and it could be an important complementary therapy in UC to reduce the use of anti-inflammatory drugs and prevent colorectal cancer.
Modulation of collagen-induced arthritis by adenovirus-mediated intra-articular expression of modified collagen type II
Authors: Tang Bo , Cullins David L , Zhou Jing , Zawaski Janice A , Park Hyelee , Brand David D , Hasty Karen A , Gaber M Waleed , Stuart John M , Kang Andrew H , Myers Linda K
Published: July 2010

Introduction

Rheumatoid arthritis (RA) is a systemic disease manifested by chronic inflammation in multiple articular joints, including the knees and small joints of the hands and feet. We have developed a unique modification to a clinically accepted method for delivering therapies directly to the synovium. Our therapy is based on our previous discovery of an analog peptide (A9) with amino acid substitutions made at positions 260 (I to A), 261 (A to B), and 263 (F to N) that could profoundly suppress immunity to type II collagen (CII) and arthritis in the collagen-induced arthritis model (CIA).

Methods

We engineered an adenoviral vector to contain the CB11 portion of recombinant type II collagen and used PCR to introduce point mutations at three sites within (CII124-402, 260A, 261B, 263D), (rCB11-A9) so that the resulting molecule contained the A9 sequence at the exact site of the wild-type sequence.

Results

We used this construct to target intra-articular tissues of mice and utilized the collagen-induced arthritis model to show that this treatment strategy provided a sustained, local therapy for individual arthritic joints, effective whether given to prevent arthritis or as a treatment. We also developed a novel system for in vivo bioimaging, using the firefly luciferase reporter gene to allow serial bioluminescence imaging to show that luciferase can be detected as late as 18 days post injection into the joint.

Conclusions

Our therapy is unique in that we target synovial cells to ultimately shut down T cell-mediated inflammation. Its effectiveness is based on its ability to transform potential inflammatory T cells and/or bystander T cells into therapeutic (regulatory-like) T cells which secrete interleukin (IL)-4. We believe this approach has potential to effectively suppress RA with minimal side effects.
A prospective observational study of the relationship of critical illness associated hyperglycaemia in medical ICU patients and subsequent development of type 2 diabetes
Authors: Gornik Ivan , Vujaklija-Brajković Ana , Renar Ivana Pavlić , Gašparović Vladimir
Published: July 2010

Introduction

Critical illness is commonly complicated by hyperglycaemia caused by mediators of stress and inflammation. Severity of disease is the main risk factor for development of hyperglycaemia, but not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesised that acute disease only exposes a latent disturbance of glucose metabolism which puts those patients at higher risk for developing diabetes.

Methods

Medical patients with no history of impaired glucose metabolism or other endocrine disorder admitted to an intensive care unit between July 1998 and June 2004 were considered for inclusion. Glucose was measured at least two times a day, and patients were divided into the hyperglycaemia group (glucose ≥7.8 mmol/l) and normoglycaemia group. An oral glucose tolerance test was performed within six weeks after discharge to disclose patients with unknown diabetes or pre-diabetes who were excluded. Patients treated with corticosteroids and those terminally ill were also excluded from the follow-up which lasted for a minimum of five years with annual oral glucose tolerance tests.

Results

A five-year follow-up was completed for 398 patients in the normoglycaemia group, of which 14 (3.5%) developed type 2 diabetes. In the hyperglycaemia group 193 patients finished follow-up and 33 (17.1%) developed type 2 diabetes. The relative risk for type 2 diabetes during five years after the acute illness was 5.6 (95% confidence interval (CI) 3.1 to 10.2).

Conclusions

Patients with hyperglycaemia during acute illness who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes. They should, therefore, be followed-up, in order to be timely diagnosed and treated.
Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria
Authors: McCall Matthew B B , Sauerwein Robert W
Published: July 2010

Review underscores the ubiquitous contribution of IFN-δ to immune responses against malaria, evidence for its protective role and critical issues relating to its induction.

Immune responses against Plasmodium parasites, the causative organisms of malaria, are traditionally dichotomized into pre-erythrocytic and blood-stage components. Whereas the central role of cellular responses in pre-erythrocytic immunity is well established, protection against blood-stage parasites has generally been ascribed to humoral responses. A number of recent studies, however, have highlighted the existence of cellular immunity against blood-stage parasites, in particular, the prominence of IFN-γ production. Here, we have undertaken to chart the contribution of this prototypical cellular cytokine to immunity against pre-erythrocytic and blood-stage parasites. We summarize the various antiparasitic effector functions that IFN-γ serves to induce, review an array of data about its protective effects, and scrutinize evidence for any deleterious, immunopathological outcome in malaria patients. We discuss the activation and contribution of different cellular sources of IFN-γ production during malaria infection and its regulation in relation to exposure. We conclude that IFN-γ forms a central mediator of protective immune responses against pre-erythrocytic and blood-stage malaria parasites and identify a number of implications for rational malaria vaccine development.
Involvement of TLR2 and TLR4 in cell responses to Rickettsia akari
Authors: Quevedo-Diaz Marco A , Song Chang , Xiong Yanbao , Chen Haiyan , Wahl Larry M , Radulovic Suzana , Medvedev Andrei E
Published: July 2010

Differential mechanisms between live and heat-killed R. akari in engaging TLR2 and TLR4 to active NF-κB, p38 MAP kinase and induce cytokine expression.

A better understanding of the pathogenesis of rickettsial disease requires elucidation of mechanisms governing host defense during infection. TLRs are primary sensors of microbial pathogens that activate innate immune cells, as well as initiate and orchestrate adaptive immune responses. However, the role of TLRs in rickettsia recognition and cell activation remains poorly understood. In this study, we examined the involvement of TLR2 and TLR4 in recognition of Rickettsia akari, a causative agent of rickettsialpox. Transfection-based complementation of TLR2/4-negative HEK293T cells with human TLR2 or TLR4 coexpressed with CD14 and MD-2 enabled IκB-α degradation, NF-κB reporter activation, and IL-8 expression in response to heat-killed (HK) R. akari. The presence of the R753Q TLR2 or D299G TLR4 polymorphisms significantly impaired the capacities of the respective TLRs to signal HK R. akari-mediated NF-κB reporter activation in HEK293T transfectants. Blocking Ab against TLR2 or TLR4 markedly inhibited TNF-α release from human monocytes stimulated with HK R. akari, and TNF-α secretion elicited by infection with live R. akari was reduced significantly only upon blocking of TLR2 and TLR4. Live and HK R. akari exerted phosphorylation of IRAK1 and p38 MAPK in 293/TLR4/MD-2 or 293/TLR2 stable cell lines, whereas only live bacteria elicited responses in TLR2/4-negative HEK293T cells. These data demonstrate that HK R. akari triggers cell activation via TLR2 or TLR4 and suggest use of additional TLRs and/or NLRs by live R. akari.
Differential Effects of Insufflated, Subcutaneous, and Intravenous Growth Hormone on Bone Growth, Cognitive Function, and NMDA Receptor Subunit Expression
Authors: Park Sung Won , Shin Sooyoung , Kim Chi Hwa , Ko Ah-ra , Kwak Min Jung , Nam Mi Hyun , Park So Young , Kim Su Jin , Sohn Young Bae , Galinsky Raymond E. , Kim Hojoong , Yeo Yoon , Jin Dong-Kyu
Published: July 2010

The objective of this study was to characterize the effect of inhalable growth hormone (GH) delivered by an insufflator to the lungs of hypophysectomized Sprague Dawley rats. In the first cohort, the safety and efficacy of the insufflated GH were evaluated. Three experimental groups (n = 7 per group) were treated with GH for 15 d: One group received sc injection of GH daily at 200 μg/kg (SC200). Two other groups received GH by insufflation daily: 200 μg/kg (INS 200) and 600 μg/kg (INS 600). In the second set of experiments, GH was administered in three routes [SC200, INS200, intravenous (IV200)] (n=10) for 5 d, and escape latency and N-methyl D-aspartate (NMDA) receptor expression were evaluated. In the first cohort, INS200 showed similar bioactivity as SC200 in growth promotion, tibial growth, as well as escape latency on the 12th day of treatment. Insufflated GH was well tolerated without significant inflammatory responses. In the second cohort, expression of the NMDA receptor 1 and 2B in hippocampus measured after 3 or 6 d of daily treatments were significantly higher in INS200 as compared to IV200, consistent with the improvement of the escape latency. In summary, the inhalable form of GH delivered by intratracheal insufflation was safe, and its bioactivity was comparable to sc injection both in promotion of growth and acquisition of learning ability. If applied properly to human, inhalable GH would be effective for growth promotion and possibly for several disorders caused by underexpression of NMDA receptors.
Osteoclast Inhibitory Peptide-1 Binding to the FcγRIIB Inhibits Osteoclast Differentiation
Authors: Shanmugarajan Srinivasan , Beeson Craig C. , Reddy Sakamuri V.
Published: July 2010

Osteoclast inhibitory peptide-1 (OIP) is an autocrine/paracrine inhibitor of osteoclast differentiation, and mice that overexpress OIP-1 in osteoclast lineage cells develop an osteopetrosis bone phenotype. In this study, we show that OIP-1 binding to the Fcγ receptor IIB (FcγRIIB) inhibits osteoclast differentiation. Confocal microscopy revealed colocalization of OIP-1 with FcγRIIB in osteoclasts, and we observed that OIP-1 carboxy-terminal GPI-linked peptide forms a 1:1 complex with recombinant FcγRIIB protein with an affinity binding of a dissociation constant of approximately 4 μm. Immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter proteins (FcRγ and DNAX-activating protein of molecular mass 12 kDa) are critical for osteoclast development, and OIP-1 transgenic mouse-derived preosteoclast cells demonstrated suppression (6-fold) of ITAM phosphorylation of FcRγ but not DNAX-activating protein of molecular mass 12 kDa. Interestingly, these preosteoclast cells demonstrated increased levels (4-fold) of immunoreceptor tyrosine-based inhibitory motif phosphorylation of FcγRIIB and Src homology 2-domain-containing proteins tyrosine phosphatase 1 activation. Further, OIP-1 mouse-derived preosteoclasts cells demonstrated inhibition of spleen tyrosine kinase activation (4.5-fold), compared with wild-type mice. These results suggest that cross-regulation of immunoreceptor tyrosine-based inhibitory motif and ITAM bearing Fc receptors may play a role in OIP-1 suppression of spleen tyrosine kinase activation and inhibition of osteoclast differentiation. Thus, OIP-1 is an important physiologic regulator of osteoclast development and may have therapeutic utility for bone diseases with high bone turnover.
Real-Time Monitoring of Somatostatin Receptor-cAMP Signaling in Live Pituitary
Authors: Jacobs Stefan , Calebiro Davide , Nikolaev Viacheslav O. , Lohse Martin J. , Schulz Stefan
Published: July 2010

Fluorescence resonance energy transfer using genetically encoded biosensors has proven to be a powerful technique to monitor the spatiotemporal dynamics of cAMP signals stimulated by Gs-coupled receptors in living cells. In contrast, real-time imaging of Gi-mediated cAMP signals under native conditions remains challenging. Here, we describe the use of transgenic mice for cAMP imaging in living pituitary slices and primary pituitary cells. This technique can be widely used to assess the contribution of various pituitary receptors, including individual Gi protein-coupled somatostatin receptors, to the regulation of cAMP levels under physiologically relevant settings.
Targeted Disruption of Mapk14 (p38MAPKα) in Granulosa Cells and Cumulus Cells Causes Cell-Specific Changes in Gene Expression Profiles that Rescue COC Expansion and Maintain Fertility
Authors: Liu Zhilin , Fan Heng-Yu , Wang Yibin , Richards JoAnne S.
Published: July 2010

MAPK14 (p38MAPKα) is critical for FSH and prostaglandin E (PGE)2 signaling cascades in granulosa cells (GCs) and cumulus cell-oocyte complexes (COCs) in culture, indicating that this kinase might impact follicular development and COC expansion in vivo. Because Mapk14 knockout mice are embryonic lethal, we generated GC specific Mapk14 knockout mice (Mapk14gc−/−) by mating Mapk14fl/fl and Cyp19-Cre mice. Unexpectedly, the Mapk14gc−/− female mice were fertile. Analyses of gene expression patterns showed that amphiregulin (Areg) and epiregulin (Ereg), two key regulators of ovulation and COC expansion, were up-regulated in the GCs but down-regulated in cumulus cells of the mutant mice in vivo. COCs from the mutant mice expanded and expressed matrix-related genes, if cultured with AREG, but not when cultured with forskolin or PGE2, the latter being a key factor regulating MAPK14 activity in cumulus cells. Conversely, when GCs from the Mapk14gc−/− mice were cultured with forskolin, they produced more Areg and Ereg mRNA than did wild-type GCs. These results indicate that disruption of Mapk14 selectively alters the expression of Areg and other genes in each cell type. Greater AREG and EREG produced by the GCs appears to by-pass and compensate for the critical need for MAPK14 signaling and induction of Areg/Ereg (and hence matrix genes) by PGE2 in cumulus cells of the mutant mice. In conclusion, although MAPK14 is not overtly essential for preovulatory follicle development or events associated with ovulation and luteinization in vivo, it does impact gene expression profiles.
Regulatory interactions specifying Kolmer-Agduhr interneurons
Authors: Yang Lixin , Rastegar Sepand , Strähle Uwe
Published: July 2010

In the zebrafish spinal cord, two classes of neurons develop from the lateral floor plate: Kolmer-Agduhr′ (KA′) and V3 interneurons. We show here that the differentiation of the correct number of KA′ cells depends on the activity of the homeobox transcription factor Nkx2.9. This factor acts in concert with Nkx2.2a and Nkx2.2b. These factors are also required for the expression of the zinc-finger transcription factor Gata2 in the lateral floor plate. In turn, Gata2 is necessary for expression of the basic helix-loop-helix transcription factor Tal2 that acts upstream of the GABA-synthesizing enzyme glutamic acid decarboxylase 67 gene (gad67) in KA′ cells. Expression of the transcription factor Sim1, which marks the V3 interneurons in the lateral floor plate, depends also on the three Nkx2 factors. sim1 expression does not require, however, gata2 and tal2. KA′ cells of the lateral floor plate and the KA′ cells located more dorsally in the spinal cord share expression of transcription factors. The functional connections between the different regulatory genes, however, differ in the two GABAergic cell types: although gata2 and tal2 are expressed in KA′ cells, they are dispensable for gad67 expression in these cells. Instead, olig2 and gata3 are required for the differentiation of gad67-expressing KA′ cells. This suggests that the layout of regulatory networks is crucially dependent on the lineage that differs between KA′ and KA′ cells.
Cadherin 6B induces BMP signaling and de-epithelialization during the epithelial mesenchymal transition of the neural crest
Authors: Park Ki-Sook , Gumbiner Barry M.
Published: July 2010

The development of neural crest cells involves an epithelial-mesenchymal transition (EMT) associated with the restriction of cadherin 6B expression to the pre-migratory neural crest cells (PMNCCs), as well as a loss of N-cadherin expression. We find that cadherin 6B, which is highly expressed in PMNCCs, persists in early migrating neural crest cells and is required for their emigration from the neural tube. Cadherin 6B-expressing PMNCCs exhibit a general loss of epithelial junctional polarity and acquire motile properties before their delamination from the neuroepithelium. Cadherin 6B selectively induces the de-epithelialization of PMNCCs, which is mediated by stimulation of BMP signaling, whereas N-cadherin inhibits de-epithelialization and BMP signaling. As BMP signaling also induces cadherin 6B expression and represses N-cadherin, cadherin-regulated BMP signaling may create two opposing feedback loops. Thus, the overall EMT of neural crest cells occurs via two distinct steps: a cadherin 6B and BMP signaling-mediated de-epithelialization, and a subsequent delamination through the basement membrane.
Specificity of Notch pathway activation: Twist controls the transcriptional output in adult muscle progenitors
Authors: Bernard Fred , Krejci Alena , Housden Ben , Adryan Boris , Bray Sarah J.
Published: July 2010

Cell-cell signalling mediated by Notch regulates many different developmental and physiological processes and is involved in a variety of human diseases. Activation of Notch impinges directly on gene expression through the Suppressor of Hairless [Su(H)] DNA-binding protein. A major question that remains to be elucidated is how the same Notch signalling pathway can result in different transcriptional responses depending on the cellular context and environment. Here, we have investigated the factors required to confer this specific response in Drosophila adult myogenic progenitor-related cells. Our analysis identifies Twist (Twi) as a crucial co-operating factor. Enhancers from several direct Notch targets require a combination of Twi and Notch activities for expression in vivo; neither alone is sufficient. Twi is bound at target enhancers prior to Notch activation and enhances Su(H) binding to these regulatory regions. To determine the breadth of the combinatorial regulation we mapped Twi occupancy genome-wide in DmD8 myogenic progenitor-related cells by chromatin immunoprecipitation. Comparing the sites bound by Su(H) and by Twi in these cells revealed a strong association, identifying a large spectrum of co-regulated genes. We conclude that Twi is an essential Notch co-regulator in myogenic progenitor cells and has the potential to confer specificity on Notch signalling at over 170 genes, showing that a single factor can have a profound effect on the output of the pathway.
Review of the flowability measuring techniques for powder metallurgy industry
Authors: Kulkarni P A , Berry R J , Bradley M S A
Published: July 2010

The flowability of bulk solids can be treated as one of the fundamental properties that determine their behaviour through industrial processes. Developing a standard meaningful test for measuring flowability has always been a challenge and numerous methods exist, based on the correlation of a number of physical properties such as gravity flowrate, internal strength, bulk density change, etc., which are thought to represent the ability of a powder to flow in some sort of a conceptual situation.

Different industries have employed and standardized different techniques for flowability measurement, and the results these obtain may not correlate.

The article details an investigation into the ability of various flowability measuring methods to detect small changes in the powder flow properties.

Four flowability measuring methods, Hall flow, Hausner ratio, compressibility, and shear cell (manual and automated), were used to measure the flowability of four physically and chemically similar iron blends.

Industry standard methods and the shear cell were not able to rank the blends with confidence. Influence of container wall friction is also investigated in the presented work.
The Influence of Coolant Temperature on a Single-Effect Lithium Bromide—Water Absorption Chiller when Energized from a Low-Temperature Source
Authors: Masheiti S , Agnew B
Published: July 2010

A simulation study of several schematic models of both water- and air-cooled single-effect LiBr—H2O absorption chillers energized by a high-potential, low-temperature (73 °C) geothermal source has been carried out using IPSEpro refrigeration software package. All the simulated models were validated against a lithium bromide—water pressure—temperature DÜhring chart. The results obtained show that when the coefficient of performance, heat input into the generator, and cooling mass flowrates are fixed, the cycle parameters are highly affected by variation of the coolant temperature. This information will be useful to designers of absorption refrigeration systems.
Handling parameter and model uncertainties by continuous gates in fault tree analyses
Authors: Brissaud F , Barros A , Bérenguer C
Published: July 2010

Fault tree analyses are widely used in probabilistic risk assessments (PRA) to model and evaluate safety system reliability. Coherent results can then be obtained by expressing probabilities according to input information. However, if uncertainties in parameters (e.g. failure rates) and models (e.g. relationships between events) lead to high uncertainty in results, the latter may not be robust enough to be helpful. It is therefore necessary to perform uncertainty analyses and, in order to handle both parameter and model uncertainties in a fault tree framework, a continuous gate denoted the ‘C-gate’ is proposed. By acting on ‘weights’, it is then allowed to continuously graduate model part structures between parallel and series. C-gates can also be translated into equivalent fault trees, using fictitious events, so that classical reliability tools are used to perform reliability evaluations with both parameter (failure rates) and model (through the weights) uncertainty analyses. An application on a new technology-based transmitter shows that results can be obtained with relatively low uncertainty and, in some cases, even with lower variances than any of the inputs. These properties are discussed and tend to demonstrate that the lack of knowledge on the structures of some parts of the model can be handled and partially compensated for by the proposed fault tree approach to perform PRA.
Private sector treatment centres are treating less complex patients than the NHS
Authors: Mason Anne , Street Andrew , Verzulli Rossella
Published: July 2010

Summary

Objectives

In England, patients can choose to have their NHS elective care delivered by private (or ‘independent sector’) providers or by the NHS. Providers are paid a fixed tariff for each type of procedure. Our objectives were to compare NHS providers with private treatment centres in terms of (a) the quality of data coding and (b) patient complexity.

Design

We compared elective patients aged 18 years and over treated in the NHS and private sectors using the Hospital Episode Statistics (HES) data for 2007–2008. The absence of diagnostic information was used as a measure of data quality. We analysed differences in complexity for each of the 30 Healthcare Resource Groups (HRGs) that together account for 78% of coded private treatment centre activity. Statistical significance was assessed at the 1% level.

Setting

Hospitals and treatment centres.

Main outcome measures

Patient complexity was assessed by four characteristics: age; number of diagnoses; number of procedures; and income deprivation of residential area.

Results

NHS providers treated almost 7 million adult elective patients in 2007–2008. Fewer than 100,000 patients were treated by private providers (1.3% of elective activity). Less than 1% of NHS patients lacked diagnostic information compared to 36% of patients treated by private providers. For the top 30 HRGs, NHS patients had significantly (p<0.01) higher levels of co-morbidity, underwent more procedures and were more likely to come from deprived areas compared with patients treated by private providers. Although patients treated in private settings tended to be younger, the difference was not statistically significant.

Conclusions

Some private companies provide poor quality data. In general, the NHS is treating more complex patients than private providers. If complexity drives costs, then a fair reimbursement system would require higher payments for NHS providers.
Retention of spliceosomal components along ligated exons ensures efficient removal of multiple introns
Authors: Crabb Tara L. , Lam Bianca J. , Hertel Klemens J.
Published: July 2010

The majority of mammalian pre-mRNAs contains multiple introns that are excised prior to export and translation. After intron excision, ligated exon intermediates participate in subsequent intron excisions. However, exon ligation generates an exon of increased size, a feature of pre-mRNA splicing that can interfere with downstream splicing events. These considerations raise the question of whether unique mechanisms exist that permit efficient removal of introns neighboring ligated exons. Kinetic analyses of multiple intron-containing pre-mRNAs revealed that splicing is more efficient following an initial intron removal event, suggesting that either the recruitment of the exon junction complex (EJC) to ligated exons increases the efficiency of multiple intron excisions or that the initial definition of splice sites is sufficient to permit efficient splicing of introns neighboring ligated exons. Knockdown experiments show that the deposition of the EJC does not affect subsequent splicing kinetics. Instead, spliceosomal components that are not involved in the initial splicing event remain associated with the pre-mRNA to ensure efficient removal of neighboring introns. Thus, ligated exons do not require redefinition, providing an additional kinetic advantage for exon defined splice sites.
The Dynamic Uncapacitated Hub Location Problem
Authors: Contreras Ivan , Cordeau Jean-François , Laporte Gilbert
Published: July 2010

This paper presents a dynamic (or multi-period) hub location problem. It proposes a branch-and-bound algorithm that uses a Lagrangian relaxation to obtain lower and upper bounds at the nodes of the tree. The Lagrangian function exploits the structure of the problem and can be decomposed into smaller subproblems that can be solved efficiently. In addition, some reduction procedures based on the Lagrangian bounds are implemented. These yield a considerable reduction of the size of the problem and thus help reduce the computational burden. Numerical results on a set of instances with up to 100 nodes and 10 time periods are reported.
Laparoscopic splenectomy: a personal series of 140 consecutive cases
Authors: Pattenden Clare J , Mann Christopher D , Metcalfe Matthew S , Dyer Martin , Lloyd David M
Published: July 2010

Laparoscopic splenectomy has emerged as a safe and effective treatment for a variety of haematological conditions. The objective was to review the results from a large personal series from the perspective of outcomes according to operative time, conversion to open operation, complications and mortality. The application of laparoscopic splenectomy to cases of splenomegaly without hand assistance is examined.

A retrospective review of 140 patients undergoing laparoscopic splenectomy at a single university hospital by one surgeon during 1994-2006. Case notes were reviewed and data collected on operative time, conversion to open procedure, morbidity and mortality. Particular reference was made towards the results of cases of splenomegaly.

In total 140 laparoscopic splenectomies were performed with a complication rate of 15% and no mortality. The median operative time was 100 min and conversion to open procedure was necessary in 2.1%. Conversion for cases of splenomegaly was only 5.7%. The median hospital stay was 3 days.

Laparoscopic splenectomy is a safe procedure with acceptable morbidity. A laparoscopic approach for splenomegaly is feasible.
Recurrent recurrent gallstone ileus
Authors: Hussain Z , Ahmed MS , Alexander DJ , Miller GV , Chintapatla S
Published: July 2010

We describe the second reported case of three consecutive episodes of gallstone ileus and ask the question whether recurrent gallstone ileus justifies definitive surgery to the fistula itself or can be safely managed by repeated enterotomies.
The squelching hip: a sign of life-threatening sepsis following haemorrhoidectomy
Authors: Berstock James Robert , Bunni John , Torrie Alexander Peter
Published: July 2010

We report a case of fulminating infection tracking from the left ischiorectal fossa to the popliteal fossa as a consequence of rectal perforation 11 days following traditional Milligan–Morgan haemorrhoidectomy. The case presented as a loud squelching noise coming from the hip on walking. Extensive cellulitis was evident over the posterior aspect of the thigh, with a deep fluctuant collection in the left buttock that communicated with the posterior compartment of the thigh. Per rectal examination revealed a defect in the rectal wall, with a foul-smelling discharge. Extensive thigh incision and drainage, defunctioning colostomy, multiple washouts, and split skin grafting procedures were performed. The patient has now recovered.
Case of a congenital urethral duplication being unmasked following circumcision for balanitis xerotica obliterans
Authors: Boyd Matthew , Woodward Mark , Lambert Anthony
Published: July 2010

We present the case of an 11-year-old boy diagnosed with an Effmann Type II A1 urethral duplication after routine circumcision for balanitis xerotica obliterans (BXO). We discuss the pathophysiology, investigation and management both of BXO and urethral duplication.
Look what’s eroding through the chest wall? Salmonella osteomyelitis of the ribs in an immunocompetent adult not associated with sickle cell disease
Authors: Scarci Marco , Attia Rizwan , Routledge Tom , Harrison-Phipps Karen
Published: July 2010

We describe a case of Salmonella typhimurium osteomyelitis in an immunocompetent adult male patient without sickle cell disease. We are not aware of a previous report of this combination.
Triple-point defective surfaces
Authors: Chiantini Luca , Markwig Thomas
Published: July 2010

In this paper we study the linear series |L – 3p| of hyperplane sections with a triple point p on a surface S embedded via a very ample line bundle L for a general point p. If this linear series does not have the expected dimension we call (S, L) triple-point defective. We show that on a triple-point defective surface through a general point every hyperplane section has either a triple component or the surface is rationally ruled and the hyperplane section contains twice a fibre of the ruling.
Three-dimensional modeling of the structure formation and consolidation of wood composites
Authors: Drolet François , Dai Chunping
Published: July 2010

A new three-dimensional (3D) computer simulation model is proposed to study structure development in wood composites, particularly strand or short fiber wood composites. The model takes into account the stochastic positioning and orientation of the strands within the mat. It also predicts the response of individual strands within the structure to the compressive and shear forces produced during mat consolidation. The model provides a complete description of mat structure in three dimensions, including spatial distribution of porosity, inter-strand contact, and density. Predictions for porosity obtained with the 3D model compare very well with those from an earlier two-dimensional analytical model. Mat structure is dictated by mat density in a two-step process: rapid removal of macrovoids before the mat density reaches the original wood density and asymptotic elimination of microvoids at higher mat densification. Other factors of importance include original wood density and strand dimensions, particularly strand thickness and width. Although known for its influence on mechanical properties, strand orientation seems to have little effect on mat porosity and strand contact.
On Congruence Conditions for Primality
Authors: Gong Sherry , Kominers Scott Duke
Published: July 2010

For any
Long Arithmetic Progressions in Small Sumsets
Authors: Bardaji Itziar , Grynkiewicz David J.
Published: July 2010

Let

- max

- gcd(

- |

Then
On the Least Common Multiple of Q-Binomial Coefficients
Authors: Guo Victor J. W.
Published: July 2010

We first prove the following identity

where