Identification of residues involved in binding of IL5 to beta(com) using beta(IL3) and beta(com) chimeras

In mice there are two forms of the beta chain used in the IL3 receptor system, beta(com) and beta(IL3). beta(com) is used by the IL3, ILS and GM-CSF receptors whereas Pns is only used in the IL3 receptor. In this work an assay was developed to identify residues of beta(IL3) that restrict IL5 activity. It was found that such residues reside within the 2nd CRM of the molecule. Furthermore, when residues in the beta(IL3) B'-C' loop were replaced with beta(com) sequence a form of beta(IL3) was produced that was able to respond to IL5. This region is also responsible for IL3 binding to beta(IL3) in the absence of alpha chain. It is therefore an important structural motif of beta(com) and beta(IL3) responsible for both ligand interaction and specificity. (C) 1999 Federation of European Biochemical Societies.

Multidimensional quantum solitons with nondegenerate parametric interactions: Photonic and Bose-Einstein condensate environments

We consider the quantum theory of three fields interacting via parametric and repulsive quartic couplings. This can be applied to treat photonic chi((2)) and chi((3)) interactions, and interactions in atomic Bose-Einstein condensates or quantum Fermi gases, describing coherent molecule formation together with a-wave scattering. The simplest two-particle quantum solitons or bound-state solutions of the idealized Hamiltonian, without a momentum cutoff, are obtained exactly. They have a pointlike structure in two and three dimensions-even though the corresponding classical theory is nonsingular. We show that the solutions can be regularized with a momentum cutoff. The parametric quantum solitons have much more realistic length scales and binding energies than chi((3)) quantum solitons, and the resulting effects could potentially be experimentally tested in highly nonlinear optical parametric media or interacting matter-wave systems. N-particle quantum solitons and the ground state energy are analyzed using a variational approach. Applications to atomic/molecular Bose-Einstein condensates (BEC's) are given, where we predict the possibility of forming coupled BEC solitons in three space dimensions, and analyze superchemistry dynamics.

Dynamics of trapped Bose-Einstein condensates: Beyond the mean-field

Since dilute Bose gas condensates were first experimentally produced, the Gross-Pitaevskii equation has been successfully used as a descriptive tool. As a mean-field equation, it cannot by definition predict anything about the many-body quantum statistics of condensate. We show here that there are a class of dynamical systems where it cannot even make successful predictions about the mean-field behavior, starting with the process of evaporative cooling by which condensates are formed. Among others are parametric processes, such as photoassociation and dissociation of atomic and molecular condensates.

Estimating the potential refolding yield of recombinant proteins expressed as inclusion bodies

Recombinant protein production in bacteria is efficient except that insoluble inclusion bodies form when some gene sequences are expressed. Such proteins must undergo renaturation, which is an inefficient process due to protein aggregation on dilution from concentrated denaturant. In this study, the protein-protein interactions of eight distinct inclusion-body proteins are quantified, in different solution conditions, by measurement of protein second virial coefficients (SVCs). Protein solubility is shown to decrease as the SVC is reduced (i.e., as protein interactions become more attractive). Plots of SVC versus denaturant concentration demonstrate two clear groupings of proteins: a more aggregative group and a group having higher SVC and better solubility. A correlation of the measured SVC with protein molecular weight and hydropathicity, that is able to predict which group each of the eight proteins falls into, is presented. The inclusion of additives known to inhibit aggregation during renaturation improves solubility and increases the SVC of both protein groups. Furthermore, an estimate of maximum refolding yield (or solubility) using high-performance liquid chromatography was obtained for each protein tested, under different environmental conditions, enabling a relationship between yield and SVC to be demonstrated. Combined, the results enable an approximate estimation of the maximum refolding yield that is attainable for each of the eight proteins examined, under a selected chemical environment. Although the correlations must be tested with a far larger set of protein sequences, this work represents a significant move beyond empirical approaches for optimizing renaturation conditions. The approach moves toward the ideal of predicting maximum refolding yield using simple bioinformatic metrics that can be estimated from the gene sequence. Such a capability could potentially screen, in silico, those sequences suitable for expression in bacteria from those that must be expressed in more complex hosts. (C) 2004 Wiley Periodicals, Inc.

Reproductive Biology of the Freshwater Shrimp Atya scabra (Leach, 1815) (Crustacea: Atyidae) in Ilheus, Bahia, Brazil

Alexandre Oliveira Almeida, Emerson Contreira Mossolin, and Joaldo Rocha Luz (2010) Reproductive biology of the freshwater shrimp Atya scabra (Leach, 1815) (Crustacea: Atyidae) in Ilheus, Bahia, Brazil. Zoological Studies 49(2): 243-252. Reproduction and population aspects of the freshwater shrimp Atya scabra in the Santana River, city of Ilheus, state of Bahia, Brazil, were studied from Apr. 2004 to May 2005. During these 14 mo, 3752 individuals were captured, with a sex ratio of 1.01 males for each female. The total number of individuals caught per month ranged 80-532. Males were generally larger than females. The smallest female found (5.40 mm in carapace length and 29.03 mm in total length) was ovigerous, which indicates that only adult individuals were caught. Ovigerous females were found every month, which indicates continuous reproduction and a high index of reproductive activity during the year. The highest reproduction indices were observed in May (94.3%) and Oct. (98.6%) 2004, and Mar. (93.7%) 2005. Fecundity ranged 870-8907 eggs, with a mean of 3811 (+/- 1992.87) eggs per female. The size of the females and their fecundity were positively correlated. The distribution of individuals in length classes by month showed that representatives of smaller classes occurred throughout almost the entire study period. This indicates a constant input of individuals into the population, which corroborates the characterization of the reproductive period as being continuous, and explains the large numbers of ovigerous females found each month. The 2nd abdominal segment is proportionally larger in females than in males, in width, height, and pleural length: these female secondary characteristics are related to an increased incubation area for eggs. http://zoolstud.sinica.edu.tw/Journals/49.2/243.pdf

Bradycardia in the Early Postoperative Period of Liver Transplantation in Children

The aim of this investigation was to describe the occurrence of bradycardia during the early postoperative period of liver transplantation in children. We retrospectively analyzed a cohort of 79 children with end-stage liver diseases who underwent liver transplantation. All children experienced >= 1 episode of a cardiac rate below the 2nd percentile of a 1-hour minimum duration, which was considered to be bradycardia. Patients <24 months were compared with older ones. The overall incidence of bradycardia was 37% (n = 31), including 25 patients who displayed bradycardia until postoperative day 3. In all cases, the electrocardiogram was normal, showing sinus rhythm. A comparison of the groups demonstrated an increased incidence of bradycardia among patients <24 months of age (P = .03). In all patients, there were no hemodynamic consequences; the cardiac rate returned to normal uneventfully. The explanations for bradycardia could not be applied to these patients because none of them had any volume change or electrolyte disturbances; liver function tests were not seriously altered. The mechanisms of this postoperative complications are unclear.

Local inflammation is crucial for T cell mediated rejection of skin graft expressing foreign antigen

Most of the skin grafts from (K14hGH.FVB C57BL/6) F1 mice, which express foreign antigen (human growth hormone, hGH) in skin keratinocytes driven by keratin 14 promoter, were spontaneously rejected by syngeneic wild type F1 recipients and hGH-specific immune responses such as antibody and hGHspecific T cells were generated in these recipients. Interestingly, a 2nd F1 hGH-expressing skin graft was rejected by graft primed recipients, but was not rejected from such recipients if CD4+ or CD8+ T cells were depleted prior to the placement of the 2nd graft. Surprisingly, this 2nd graft retained healthy even after CD4+ or CD8+ T cells were allowed to recover so that the animal could reject a freshly placed 3rd F1 hGH-expressing graft. Furthermore, inflammatory response induced by topical treatment with imiquimod could lead to the rejection of some well-healed 2nd grafts. This result indicates that both CD4+ and CD8+ T cells are required for the rejection and the ability of effector T cells to reject a graft is determined by local factors in the graft which are presumably determined by inflammation induced by surgery or imiquimod treatment. Taken together, our results suggest that in addition to CD4+ and CD8+ T cells, local environmental factors induced by inflammation are also crucial for effector T cell functions leading to graft destruction. The understanding of these local factors will lead to more effective immunotherapy for established, epithelial cancer in the future.

Bilateral Anterior Thalamic Nucleus Lesions Are Not Protective against Seizures in Chronic Pilocarpine Epileptic Rats

Aims: To investigate whether anterior thalamic nucleus (AN) lesions are protective against spontaneous recurrent seizures in the chronic phase of the pilocarpine model of epilepsy. Methods: Two groups of rats were treated with bilateral AN radiofrequency thalamotomies or sham surgery 2 weeks after pilocarpine-induced status epilepticus. After the lesions, animals were videotaped from the 2nd to the 8th week after status epilepticus (total 180 h). Results: During the 6 weeks of observation, no differences in the frequency of spontaneous seizures were found between animals that had bilateral AN lesions (n = 26; 3.1 +/- 0.6 seizures per animal) and controls (n = 25; 3.0 +/- 0.6 seizures per animal; p = 0.8). Conclusions: We conclude that AN thalamotomies were not effective in reducing the frequency of seizures during the chronic phase of the pilocarpine model of epilepsy. Copyright (C) 2009 S. Karger AG, Basel

A synergistic relationship of elevated low-density lipoprotein cholesterol levels and systolic blood pressure with coronary artery calcification

We sought to evaluate this ""response-to-injury"" hypothesis of atherosclerosis by studying the interaction between systolic blood pressure (SBP) and LDL-cholesterol (LDL-C) in predicting the presence of coronary artery calcification (CAC) in asymptomatic men. We Studied 526 men (46 +/- 7 years of age) referred for electron-beam tomography (EBT) exam. The prevalence of CAC was determined across LDL-C tertiles (low: <115 mg/dl; middle: 115-139 mg/dl high: >= 140 mg/dl) within tertiles of SBP (low: <121 mmHg; middle: 121-130 mmHg; high: >= 131 mmHg). CAC was found in 220 (42%) men. There was no linear trend in the presence of CAC across LDL-C tertiles in the low (p = 0.6 for trend) and middle (p = 0.3 for trend) SBP tertile groups, respectively. In contrast, there was a significant trend for increasing CAC with increasing LDL-C (1st: 44%; 2nd: 49%; 3rd: 83%; p < 0.0001 for trend) in the high SBP tertile group. In multivariate logistic analyses (adjusting for age, smoking, triglyceride levels, HDL-cholesterol levels, body mass index, and fasting glucose levels), the odds ratio for any CAC associated with increasing LDL-C was significantly higher in those with highest SBP levels, whereas no such relationship was observed among men with SBP in the lower two tertiles. An interaction term (LDL-C x SBP) incorporated in the multivariate analyses was statistically significant (p = 0.038). The finding of an interaction between SBP and LDL-C relation to CAC in asymptomatic men support the response-to-injury model of atherogenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Imaging and lung cancer

Lung cancer remains the most common cause of cancer-related mortality in Scotland, accounting for 28.9% of all cancer deaths in 2007. Current guidelines recommend assessment of patient fitness and operability by a multidisciplinary team when selecting management options. Two of the most important prognostic markers are the stage of disease and ECOG performance status. In 1996, the International Association for the Study of Lung Cancer (IASLC) launched a worldwide TNM staging project to create international databases that would be used to continue the excellent efforts of Dr. Cliff Mountain, who pioneered this approach to lung cancer staging in 1973. Successive iterations of tumor, nodule, metastasis (TNM) staging for lung cancer have addressed shortcomings identified by the oncology community. Similarly, the IASLC recognized that it is important that further revisions continue to be made to ensure that the international staging system for lung cancer remains fit for its purpose. The last work of the International Staging Committee (ISC) was the conduct of the study that informed the seventh edition of the international staging system for lung cancer, in 2010. This review of image and staging in non small cell lung cancer (NSCLC), includes a summary of the different noninvasive tests currently available for staging non small cell lung cancer.

Ideal soliton environment using parametric band gaps

Simultaneous solitary wave solutions for laser propagation in nonlinear parametric media with up to (3 + 1) dimensions are proved to exist. The combination of the large dispersion of a Bragg grating and the strong nonlinearity of chi((2)) optical material results in stable behavior with short interaction distances and low power requirements. The solutions are obtained by using the effective mass approximation to reduce the coupled propagation equations to those describing a dispersive parametric nonlinear waveguide, and are verified by solving the complete set of coupled band-gap equations numerically.

Updated Clinical Classification of Pulmonary Hypertension

The aim of a clinical classification of pulmonary hypertension (PH) is to group together different manifestations of disease sharing similarities in pathophysiologic mechanisms, clinical presentation, and therapeutic approaches. In 2003, during the 3rd World Symposium on Pulmonary Hypertension, the clinical classification of PH initially adopted in 1998 during the 2nd World Symposium was slightly modified. During the 4th World Symposium held in 2008, it was decided to maintain the general architecture and philosophy of the previous clinical classifications. The modifications adopted during this meeting principally concern Group 1, pulmonary arterial hypertension (PAH). This subgroup includes patients with PAH with a family history or patients with idiopathic PAH with germline mutations (e. g., bone morphogenetic protein receptor-2, activin receptor-like kinase type 1, and endoglin). In the new classification, schistosomiasis and chronic hemolytic anemia appear as separate entities in the subgroup of PAH associated with identified diseases. Finally, it was decided to place pulmonary venoocclusive disease and pulmonary capillary hemangiomatosis in a separate group, distinct from but very close to Group 1 (now called Group 1`). Thus, Group 1 of PAH is now more homogeneous. (J Am Coll Cardiol 2009;54:S43-54) (C) 2009 by the American College of Cardiology Foundation

Pulsed quadrature-phase squeezing of solitary waves in chi((2)) parametric waveguides

It is shown that coherent quantum simultons (simultaneous solitary waves at two different frequencies) can undergo quadrature-phase squeezing as they propagate through a dispersive chi((2)) waveguide. This requires a treatment of the coupled quantized fields including a quantized depleted pump field. A technique involving nonlinear stochastic parabolic partial differential equations using a nondiagonal coherent state representation in combination with an exact Wigner representation on a reduced phase space is outlined. We explicitly demonstrate that group-velocity matched chi((2)) waveguides which exhibit collinear propagation can produce quadrature-phase squeezed simultons. Quasi-phase-matched KTP waveguides, even with their large group-velocity mismatch between fundamental and second harmonic at 425 nm, can produce 3 dB squeezed bright pulses at 850 nm in the large phase-mismatch regime. This can be improved to more than 6 dB by using group-velocity matched waveguides.

Spatiotemporal solitons in multidimensional optical media with a quadratic nonlinearity

We consider solutions to the second-harmonic generation equations in two-and three-dimensional dispersive media in the form of solitons localized in space and time. As is known, collapse does not take place in these models, which is why the solitons may be stable. The general solution is obtained in an approximate analytical form by means of a variational approach, which also allows the stability of the solutions to be predicted. Then, we directly simulate the two-dimensional case, taking the initial configuration as suggested by the variational approximation. We thus demonstrate that spatiotemporal solitons indeed exist and are stable. Furthermore, they are not, in the general case, equivalent to the previously known cylindrical spatial solitons. Direct simulations generate solitons with some internal oscillations. However, these oscillations neither grow nor do they exhibit any significant radiative damping. Numerical solutions of the stationary version of the equations produce the same solitons in their unperturbed form, i.e., without internal oscillations. Strictly stable solitons exist only if the system has anomalous dispersion at both the fundamental harmonic and second harmonic (SH), including the case of zero dispersion at SH. Quasistationary solitons, decaying extremely slowly into radiation, are found in the presence of weak normal dispersion at the second-harmonic frequency.