Entry pathways of herpes simplex virus type 1 into human keratinocytes are dynamin- and cholesterol-dependent

Herpes simplex virus type 1 (HSV-1) can enter cells via endocytic pathways or direct fusion at the plasma membrane depending on the cell line and receptor(s). Most studies into virus entry have used cultured fibroblasts but since keratinocytes represent the primary entry site for HSV-1 infection in its human host, we initiated studies to characterize the entry pathway of HSV-1 into human keratinocytes. Electron microscopy studies visualized free capsids in the cytoplasm and enveloped virus particles in vesicles suggesting viral uptake both by direct fusion at the plasma membrane and by endocytic vesicles. The ratio of the two entry modes differed in primary human keratinocytes and in the keratinocyte cell line HaCaT. Inhibitor studies further support a role for endocytosis during HSV-1 entry. Infection was inhibited by the cholesterol-sequestering drug methyl-beta-cyclodextrin, which demonstrates the requirement for host cholesterol during virus entry. Since the dynamin-specific inhibitor dynasore and overexpression of a dominant-negative dynamin mutant blocked infection, we conclude that the entry pathways into keratinocytes are dynamin-mediated. Electron microscopy studies confirmed that virus uptake is completely blocked when the GTPase activity of dynamin is inhibited. Ex vivo infection of murine epidermis that was treated with dynasore further supports the essential role of dynamin during entry into the epithelium. Thus, we conclude that HSV-1 can enter human keratinocytes by alternative entry pathways that require dynamin and host cholesterol

The role of clustering and gridlike ordering in epidemic spreading

The spreading of an epidemic is determined by the connectiviy patterns which underlie the population. While it has been noted that a virus spreads more easily on a network in which global distances are small, it remains a great challenge to find approaches that unravel the precise role of local interconnectedness. Such topological properties enter very naturally in the framework of our two-timestep description, also providing a novel approach to tract a probabilistic system. The method is elaborated for SIS-type epidemic processes, leading to a quantitative interpretation of the role of loops up to length 4 in the onset of an epidemic.Comment: Submitted to Phys. Rev. E; 15 pages, 11 figures, 5 table

Condition numbers and scale free graphs

In this work we study the condition number of the least square matrix corresponding to scale free networks. We compute a theoretical lower bound of the condition number which proves that they are ill conditioned. Also, we analyze several matrices from networks generated with the linear preferential attachment model showing that it is very difficult to compute the power law exponent by the least square method due to the severe lost of accuracy expected from the corresponding condition numbers.Comment: Submitted to EP

Search for ultrahigh energy neutrinos in highly inclined events at the Pierre Auger Observatory

The Surface Detector of the Pierre Auger Observatory is sensitive to neutrinos of all flavors above 0.1 EeV. These interact through charged and neutral currents in the atmosphere giving rise to extensive air showers. When interacting deeply in the atmosphere at nearly horizontal incidence, neutrinos can be distinguished from regular hadronic cosmic rays by the broad time structure of their shower signals in the water-Cherenkov detectors. In this paper we present for the first time an analysis based on down-going neutrinos. We describe the search procedure, the possible sources of background, the method to compute the exposure and the associated systematic uncertainties. No candidate neutrinos have been found in data collected from 1 January 2004 to 31 May 2010. Assuming an E-2 differential energy spectrum the limit on the single-flavor neutrino is E2dN=dE-7GeVcm-2s-1sr-1 at 90% C.L. in the energy range 1 X 1017eV\u3c E 1020eV

Cinacalcet Treatment of Primary Hyperparathyroidism

Although parathyroidectomy remains the only curative approach to most primary hyperparathyroidism cases, medical treatment with cinacalcet HCl has been proven to be a reasonable alternative for several patient subgroups. Cinacalcet almost always controls hypercalcemia and hypophosphatemia sufficiently. PTH levels are lowered, and cognitive parameters improve. While an increase in bone mineral density DEXA scan scores was not demonstrated in cinacalcet trials, the same applies to more than half of patients after parathyroidectomy. Medical therapy should be first choice in patients with hyperplasia in all glands rather than an isolated adenoma (10–15%), patients with persisting HPT following unsuccessful surgery or inoperable cases due to comorbidities, and patients detected in lab screens for hypercalcemia before developing symptoms who should be treated early but are usually reluctant to undergo surgery. Nephrolithiasis was not found to occur more frequently in cinacalcet trial groups, but urine calcium excretion as one major risk factor of this complication of primary HPT may increase on cinacalcet. Patients carrying the rs1042636 polymorphism of the calcium-sensing receptor gene respond more sensitively to cinacalcet and have a higher risk of calcium stone formation. Cinacalcet is usually administered twice daily but three or four doses per day should be discussed to mimic the beneficial pulsatile PTH-pattern

End-colostomy diverticulitis with parastomal phlegmon: A case report.

Acute colonic diverticulitis is a well-known surgical emergency, which occurs in about 10 percent of patients known for diverticulosis. The case of a 77-year-old woman is reported, with past history of abdominoperineal resection with end-colostomy for low rectal adenocarcinoma, and who developed an acute colonic diverticulitis in a subcutaneous portion of colostomy with parastomal phlegmon. Initial computed tomography imaging demonstrated a significant submucosal parietal edema with local fat tissues infiltration in regard of 3 diverticula. A two-step treatment was decided: first a nonoperative treatment was initiated with 2 weeks antibiotics administration, followed by, 6 weeks after, a segmental resection of the terminal portion of the colon with redo of a new colostomy by direct open approach. Patient was discharged on the second postoperative day without complications. Follow-up at 2 weeks revealed centimetric dehiscence of the stoma, which was managed conservatively until sixth postoperative week by stomatherapists. Treatment of acute diverticulitis with parastomal phlegmon in a patient with end-colostomy could primary be nonoperative. Delayed surgical treatment with segmental colonic resection was proposed to avoid recurrence and potential associated complications

Suitability of Small and Large Size Dairy Cows in a Pasture-Based Production System

Pasture-based dairy production with greatly reduced supplemental feeding and block-calving in spring is increasingly applied in Switzerland. The prevalent cow type has been selected mainly for high individual production in a barn feeding system with balanced diet. This cow type has continuously increased in size over the last 30 years. The question arises whether this type is suitable for the new system, and particularly if cow size is a critical factor. Theoretically a large, heavy type of cow has a higher intake capacity, while the nutrient requirements for a small, light type are easier to satisfy

Renormalization : A number theoretical model

We analyse the Dirichlet convolution ring of arithmetic number theoretic functions. It turns out to fail to be a Hopf algebra on the diagonal, due to the lack of complete multiplicativity of the product and coproduct. A related Hopf algebra can be established, which however overcounts the diagonal. We argue that the mechanism of renormalization in quantum field theory is modelled after the same principle. Singularities hence arise as a (now continuously indexed) overcounting on the diagonals. Renormalization is given by the map from the auxiliary Hopf algebra to the weaker multiplicative structure, called Hopf gebra, rescaling the diagonals.Comment: 15 pages, extended version of talks delivered at SLC55 Bertinoro,Sep 2005, and the Bob Delbourgo QFT Fest in Hobart, Dec 200

Brain serotonin critically contributes to the biological effects of electroconvulsive seizures

Compounds targeting serotonin (5-HT) are widely used as antidepressants. However, the role of 5-HT in mediating the effects of electroconvulsive seizure (ECS) therapy remains undefined. Using Tph2(-/-) mice depleted of brain 5-HT, we studied the effects of ECS on behavior and neurobiology. ECS significantly prolonged the start latency in the elevated O-Maze test, an effect that was abolished in Tph2(-/-) mice. Furthermore, in the absence of 5-HT, the ECS-induced increase in adult neurogenesis and in brain-derived neurotrophic factor signaling in the hippocampus were significantly reduced. Our results indicate that brain 5-HT critically contributes to the neurobiological responses to ECS

Bias reduction in traceroute sampling: towards a more accurate map of the Internet

Traceroute sampling is an important technique in exploring the internet router graph and the autonomous system graph. Although it is one of the primary techniques used in calculating statistics about the internet, it can introduce bias that corrupts these estimates. This paper reports on a theoretical and experimental investigation of a new technique to reduce the bias of traceroute sampling when estimating the degree distribution. We develop a new estimator for the degree of a node in a traceroute-sampled graph; validate the estimator theoretically in Erdos-Renyi graphs and, through computer experiments, for a wider range of graphs; and apply it to produce a new picture of the degree distribution of the autonomous system graph.Comment: 12 pages, 3 figure