FANCM regulates DNA chain elongation and is stabilized by S-phase checkpoint signalling.

FANCM binds and remodels replication fork structures in vitro. We report that in vivo, FANCM controls DNA chain elongation in an ATPase-dependent manner. In the presence of replication inhibitors that do not damage DNA, FANCM counteracts fork movement, possibly by remodelling fork structures. Conversely, through damaged DNA, FANCM promotes replication and recovers stalled forks. Hence, the impact of FANCM on fork progression depends on the underlying hindrance. We further report that signalling through the checkpoint effector kinase Chk1 prevents FANCM from degradation by the proteasome after exposure to DNA damage. FANCM also acts in a feedback loop to stabilize Chk1. We propose that FANCM is a ringmaster in the response to replication stress by physically altering replication fork structures and by providing a tight link to S-phase checkpoint signalling.

A Case Study of China’s Commercial Pork Value Chain, August 2005

In China, with the cost of improved technology rising, surplus labor shrinking, and demand for food quality and safety increasing, it will be just a matter of time before the country’s hog production sector will be commercialized like that of developed countries. However, even if China’s cost of production converges to international levels, as shown in this case study, China may continue to retain some competitive advantage because of the labor-intensive nature of the marketing services involved in hog processing and meat distribution. The supply of variety meats offers the most promising market opportunity for foreign suppliers in China. The market may open further if the tariff rate for variety meats is reduced from 20% and harmonized with the pork muscle meat rate of 12%, and if the value-added tax of 13% is applied equally to both imported and domestic products. The fast-growing Western-style family restaurant and higher-end dining sector is another market opportunity for high-quality imported pork.

Synthesis and anticancer activity of long-chain isonicotinic ester ligand-containing arene ruthenium complexes and nanoparticles

Arene ruthenium complexes containing long-chain N-ligands L1 = NC5H4-4-COO-C6H4-4-O-(CH2)9-CH3 or L2 = NC5H4-4-COO-(CH2)10-O-C6H4-4-COO-C6H4-4-C6H4-4-CN derived from isonicotinic acid, of the type [(arene)Ru(L)Cl2] (arene = C6H6, L = L1: 1; arene = p-MeC6H4Pr i , L = L1: 2; arene = C6Me6, L = L1: 3; arene = C6H6, L = L2: 4; arene = p-MeC6H4Pr i , L = L2: 5; arene = C6Me6, L = L2: 6) have been synthesized from the corresponding [(arene)RuCl2]2 precursor with the long-chain N-ligand L in dichloromethane. Ruthenium nanoparticles stabilized by L1 have been prepared by the solvent-free reduction of 1 with hydrogen or by reducing [(arene)Ru(H2O)3]SO4 in ethanol in the presence of L1 with hydrogen. These complexes and nanoparticles show a high anticancer activity towards human ovarian cell lines, the highest cytotoxicity being obtained for complex 2 (IC50 = 2 μM for A2780 and 7 μM for A2780cisR)

Reverse transcription quantitative real-time polymerase chain reaction reference genes in the spared nerve injury model of neuropathic pain: validation and literature search.

BACKGROUND: The reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a widely used, highly sensitive laboratory technique to rapidly and easily detect, identify and quantify gene expression. Reliable RT-qPCR data necessitates accurate normalization with validated control genes (reference genes) whose expression is constant in all studied conditions. This stability has to be demonstrated.We performed a literature search for studies using quantitative or semi-quantitative PCR in the rat spared nerve injury (SNI) model of neuropathic pain to verify whether any reference genes had previously been validated. We then analyzed the stability over time of 7 commonly used reference genes in the nervous system - specifically in the spinal cord dorsal horn and the dorsal root ganglion (DRG). These were: Actin beta (Actb), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal proteins 18S (18S), L13a (RPL13a) and L29 (RPL29), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and hydroxymethylbilane synthase (HMBS). We compared the candidate genes and established a stability ranking using the geNorm algorithm. Finally, we assessed the number of reference genes necessary for accurate normalization in this neuropathic pain model. RESULTS: We found GAPDH, HMBS, Actb, HPRT1 and 18S cited as reference genes in literature on studies using the SNI model. Only HPRT1 and 18S had been once previously demonstrated as stable in RT-qPCR arrays. All the genes tested in this study, using the geNorm algorithm, presented gene stability values (M-value) acceptable enough for them to qualify as potential reference genes in both DRG and spinal cord. Using the coefficient of variation, 18S failed the 50% cut-off with a value of 61% in the DRG. The two most stable genes in the dorsal horn were RPL29 and RPL13a; in the DRG they were HPRT1 and Actb. Using a 0.15 cut-off for pairwise variations we found that any pair of stable reference gene was sufficient for the normalization process. CONCLUSIONS: In the rat SNI model, we validated and ranked Actb, RPL29, RPL13a, HMBS, GAPDH, HPRT1 and 18S as good reference genes in the spinal cord. In the DRG, 18S did not fulfill stability criteria. The combination of any two stable reference genes was sufficient to provide an accurate normalization.

Supply chain management implementation in the Spanish grocery sector: An exploratory study

This paper explores the integration process that firms follow to implementSupply Chain Management (SCM) and the main barriers and benefits relatedto this strategy. This study has been inspired in the SCM literature,especially in the logistics integration model by Stevens [1]. Due to theexploratory nature of this paper and the need to obtain an in depthknowledge of the SCM development in the Spanish grocery sector, we used thecase study methodology. A multiple case study analysis based on interviewswith leading manufacturers and retailers was conducted.The results of this analysis suggest that firms seem to follow the integration process proposed by Stevens, integrating internally first, andthen, extending this integration to other supply chain members. The casesalso show that Spanish manufacturers, in general, seem to have a higherlevel of SCM development than Spanish retailers. Regarding the benefitsthat SCM can bring, most of the companies identify the general objectivesof cost and stock reductions and service improvements. However, withrespect to the barriers found in its implementation, retailers andmanufacturers are not coincident: manufacturers seem to see more barrierswith respect to aspects related to the other party, such as distrust and alack of culture of sharing information, while retailers find as mainbarriers the need of a know-how , the company culture and the historyand habits.

Supply chain management: An opportunity for metaheuristics

In today s highly competitive and global marketplace the pressure onorganizations to find new ways to create and deliver value to customersgrows ever stronger. In the last two decades, logistics and supply chainhas moved to the center stage. There has been a growing recognition thatit is through an effective management of the logistics function and thesupply chain that the goal of cost reduction and service enhancement canbe achieved. The key to success in Supply Chain Management (SCM) requireheavy emphasis on integration of activities, cooperation, coordination andinformation sharing throughout the entire supply chain, from suppliers tocustomers. To be able to respond to the challenge of integration there isthe need of sophisticated decision support systems based on powerfulmathematical models and solution techniques, together with the advancesin information and communication technologies. The industry and the academiahave become increasingly interested in SCM to be able to respond to theproblems and issues posed by the changes in the logistics and supply chain.We present a brief discussion on the important issues in SCM. We then arguethat metaheuristics can play an important role in solving complex supplychain related problems derived by the importance of designing and managingthe entire supply chain as a single entity. We will focus specially on theIterated Local Search, Tabu Search and Scatter Search as the ones, but notlimited to, with great potential to be used on solving the SCM relatedproblems. We will present briefly some successful applications.

Natalizumab treatment alters the expression of T-cell trafficking marker LFA-1 α-chain (CD11a) in MS patients.

OBJECTIVE: To determine the long-term effect of natalizumab (NTZ) treatment on the expression of integrins and chemokine receptors involved in the migration of T cells towards the central nervous system (CNS). METHODS: We drew the blood of 23 patients just before starting NTZ therapy and every 12 months thereafter, for up to 48 months of treatment. We assessed the ex-vivo expression of phenotype markers (CCR7 and CD45RA), CNS-addressing integrins (CD11a, CD49d and CD29) and chemokine receptors (CXCR3 and CCR6) in CD4+ or CD8+ T-cell subsets by flow cytometry. RESULTS: As compared to the pre-NTZ values, there was a marked increase in central memory (CCR7+/CD45RA-) CD4+ T cells and in effector memory (CCR7-/CD45RA-) CD8+ T cells at 12 and 24 months. In addition to an expected downregulation of both VLA-4 subunits (CD49d/CD29), we also found decreased T-cell expression of CXCR3 at 12 months, and of CD11a (LFA-1 αL subunit) at 12 months, but mostly at 24 months of NTZ treatment. CONCLUSION: Our data show a nadir of CD11a expression at 2 years of NTZ treatment, at the peak of incidence of progressive multifocal leukoencephalopathy (PML), indirectly suggesting that a lack of these molecules may play a role in the onset of PML in NTZ-treated patients.

E-supply chain management: Review, implications and directions for future research

This paper analyses the interaction of two topics: Supply Chain Management (SCM) andInternet. Merging these two fields is a key area of concern for contemporary managers andresearchers. They have realized that Internet can enhance SCM by making real timeinformation available and enabling collaboration between trading partners. The aim of thispaper is to define e-SCM, analyze how research in this area has evolved during the period1995-2003 and identify some lines of further research. To do that a literature review inprestigious academic journals in Operations Management and Logistics has beenconducted.

Culex nigripalpus Theobald (Diptera, Culicidae) feeding habit at the Parque Ecológico do Tietê, São Paulo, Brazil

The blood feeding of a population of Cx. nigripalpus from Parque Ecológico do Tietê (PET) was investigated using an indirect ELISA protocol. Mosquitoes were captured outside houses. Five hundred sixteen engorged females collected in a reforested area and 25 in an open area were tested. Rodents and dogs were the most common blood sources, accounting for approximately 65.3% of blood meals. Human blood was detected in 10.9%, dog blood in 26.1%, chicken blood in 2.4%, and rodent blood in 39.2% of the 541 insects tested. ELISA failed in identifying the blood sources of 233 engorged females, indicating that the mosquitoes may have fed on a host which was not tested. One hundred six individuals were positive for more than one host. The unweighted human blood index was 0.14 and the rodent/human, human/chicken, and dog/rodent feeding index values were 2.70, 1.51, and 1.33, respectively. Furthermore, rodents are defensive hosts for this haematophagous insect which looks for another host to complete blood-feeding. Considering that rodents are potential reservoirs for Mucambo virus and Saint Louis encephalitis virus and that Cx. nigripalpus feed on the blood of those mammals, we hypothesize that mosquito population in PET could participate in the transmission cycle of those arboviruses. Additionally, this species might be involved in the transmission of Dirofilaria immitis to dogs at this area.

La chaîne des secours: le modèle vaudois [An efficient example of a Swiss pre-hospital chain of survival: the state of Vaud model].

The state of Vaud model of the pre-hospital chain of survival is an example of an efficient way to deal with pre-hospital emergencies. It revolves around a centrally located dispatch center managing emergencies according to specific key words, allowing dispatchers to send out resources among which we find general practitioners, ambulances, physician staffed fast response cars or physician staffed helicopters and specific equipment. The Vaud pre-hospital chain of survival has been tailored according to geographical, demographical and political necessities. It undergoes constant reassessment and needs continuous adaptations to the ever changing demographics and epidemiology of pre-hospital medicine.

Histoplasma capsulatum var. duboisii infection in a patient with AIDS: rapid diagnosis using polymerase chain reaction-sequencing.

We describe an original case of disseminated infection with Histoplasma capsulatum (Hc) var. duboisii in an African patient with AIDS who migrated to Switzerland. The diagnosis of histoplasmosis was suggested using direct examination of tissues and confirmed in 24 h with a panfungal polymerase chain reaction assay. The variety duboisii of Hc was established using DNA sequencing of the polymorphic genomic region OLE. Molecular tools allow diagnosis of histoplasmosis in 24 h, which is drastically shorter than culture procedures.