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We study laser-driven isomerization reactions through an excited electronic state using the recently developed Geometrical Optimization procedure. Our goal is to analyze whether an initial wave packet in the ground state, with optimized amplitudes and phases, can be used to enhance the yield of the reaction at faster rates, driven by a single picosecond pulse or a pair of femtosecond pulses resonant with the electronic transition. We show that the symmetry of the system imposes limitations in the optimization procedure, such that the method rediscovers the pump-dump mechanism.

Background: Bursa of Fabricius plays the vital functions on B cell development and antibody production in poultry. The bursal-derived peptide plays the essential roles on avian immature B cell development. Objectives: Here we explored the functions of the recently reported bursal nonapeptide (BP9) on the antibody production and the molecular basis of BP9 on avian immature B cell. Methods: Chicken were twice immunized with Avian Influenza Virus (AIV) inactivated vaccine plus with BP9 at three dosages, respectively. On two weeks after the second immunization, sera samples were collected from all experimental groups to measure AIV-specific Agglutination Inhibition (HI) antibody titers. Also, on 7th day after the second immunization, spleen lymphocytes were isolated from the immunized chicken to detect the lymphocyte viabilities. DT40 cells were treated with BP9 from 0.02 to 2 μg/mL for 4 and 20h to detect sIgM mRNA levels, and total RNAs from BP9-treated DT40 cells were collected to investigate the gene expression profiles of DT40 cells, and to analyze the enriched pathways and functional biological processes. Finally, nine gene expressions were validated with quantitative PCR (qPCR). Results: Our investigation proved the strong regulatory roles of BP9 on AIV-specific HI antibody titers and lymphocyte viabilities. BP9 promoted sIgM mRNA levels in DT40 cells, and upregulated 598 gene expressions and downregulated 395 gene expressions in DT40 cells with 0.2μg/mL BP9 treatment. Moreover, our findings verified the significantly enriched six pathways and various the biological functional processes of BP9 on avian immature B cell. Also, we found eight signaling pathways in the enriched biological processes of BP9-treated DT40 cells, and the expressions of nine selected genes with qPCR were identical to that of microarray data. Conclusion: BP9 promoted the antibody production in the 21-old-day chicken immunization, and stimulated the sIgM expression in DT40 cells. Furthermore, we analyzed the gene expression profile and immune-related biological processes of DT40 cells treated with BP9, which provided some new insights into the mechanism on immature B cell development, and provided important references for adjuvant development on vaccine improvement and clinical application.

The two-dimensional electron–nuclear Schrödinger equation using soft-core Coulomb potentials has been a cornerstone for modeling and predicting the behavior of one-active-electron diatomic molecules, particularly for processes where both bound and continuum states are important. The model, however, is computationally expensive to extend to more electron or nuclear coordinates. Here we propose use of the Ehrenfest approach to treat the nuclear motion, while the electronic motion is still solved by quantum propagation on a grid. In this work, we present results for a one-dimensional treatment of H2+, where the quantum and semiclassical dynamics can be directly compared, showing remarkably good agreement for a variety of situations. The advantage of the Ehrenfest approach is that it can be easily extended to treat as many nuclear degrees of freedom as needed.

A synergy between β-amyloid (Aβ) and tau appears to occur in Alzheimer disease (AD), but the mechanisms of interaction, and potential locations, are little understood. This study investigates the possibility of such interactions within the cortical synaptic compartments of APP/PS1 mice. We used label-free quantitative mass spectrometry to study the phosphoproteome of synaptosomes, covering 2400 phosphopeptides and providing an unbiased survey of phosphorylation changes associated with amyloid pathology. Hyperphosphorylation was detected on 36 synaptic proteins, many of which are associated with the cytoskeleton. Importantly, tau is one of the most hyperphosphorylated proteins at the synapse, upregulated at both proline-directed kinase (PDK) sites (S199/S202, S396/S404) and nonPDK sites (S400). These PDK sites correspond to well-known pathological tau epitopes in AD patients, recognized by AT8 and PHF-1 antibodies, respectively. Hyperphosphorylation at S199/S202, a rarely examined combination, was further validated in patient-derived human synaptosomes by immunoblotting. Global surveys of upregulated phosphosites revealed 2 potential kinase motifs, which resemble those of cyclin-dependent kinase 5 (CDK5, a PDK) and casein kinase II (CK2, a nonPDK). Our data demonstrate that, within synaptic compartments, amyloid pathology is associated with tau hyperphosphorylation at disease-relevant epitopes. This provides a plausible mechanism by which Aβ promotes the spreading of tauopathy.

We lay out the foundations of a general method of quantum control via geometrical optimization. We apply the method to state-selective population transfer using ultrashort transform-limited pulses between manifolds of levels that may represent, e.g., state-selective transitions in molecules. Assuming that certain states can be prepared, we develop three implementations: (i) preoptimization, which implies engineering the initial state within the ground manifold or electronic state before the pulse is applied; (ii) postoptimization, which implies engineering the final state within the excited manifold or target electronic state, after the pulse; and (iii) double-time optimization, which uses both types of time-ordered manipulations. We apply the schemes to two important dynamical problems: To prepare arbitrary vibrational superposition states on the target electronic state and to select weakly coupled vibrational states. Whereas full population inversion between the electronic states only requires control at initial time in all of the ground vibrational levels, only very specific superposition states can be prepared with high fidelity by either pre- or postoptimization mechanisms. Full state-selective population inversion requires manipulating the vibrational coherences in the ground electronic state before the optical pulse is applied and in the excited electronic state afterward, but not during all times.

Mucosa-associated lymphoid tissue (MALT) lymphoma is very rare in children. We report the first case of pediatric thymic MALT lymphoma in an adolescent Asian girl. She presented with chest pain, dyspnea, and low-grade fever. A large anterior mediastinal mass was biopsied that confirmed the diagnosis of MALT lymphoma with trisomy 18. The patient had secondary immunodeficiency with low NK cell count and high IgA and IgG levels. Because of the advanced stage and the presence of trisomy 18, she was treated with cyclophosphamide, vincristine, prednisone, and rituximab, followed by involved-field radiotherapy. She is currently undergoing maintenance therapy with rituximab and remains in complete remission at 13 months from diagnosis. Thymic MALT lymphoma should be suspected in any Asian child with a cystic thymic mass and autoimmune disease or hyperglobinemia. Because of the slow proliferation rate of this type of lymphoma, a long-term follow-up is needed.

De novo autoimmune hepatitis (AIH) recently was recognized as an important cause of late graft dysfunction after pediatric liver transplantation (LT). However, the significance of isolated elevation of autoantibodies in children after LT without history of prior autoimmune liver disease scarcely has been studied. The aim of the present study was to determine the prevalence and risk factors for autoantibodies production in pediatric LT recipients and to assess the impact of isolated elevation of autoantibodies over time on graft function.

De novo autoimmune hepatitis (AIH) recently was recognized as an important cause of late graft dysfunction after pediatric liver transplantation (LT). However, the significance of isolated elevation of autoantibodies in children after LT without history of prior autoimmune liver disease scarcely has been studied. The aim of the present study was to determine the prevalence and risk factors for autoantibodies production in pediatric LT recipients and to assess the impact of isolated elevation of autoantibodies over time on graft function. Sixty-eight children without history of autoimmune disease were recruited over the course of 1 year into this cross-sectional study. A single blood specimen was drawn at study entry to determine titers of autoantibodies. Clinical and laboratory assessment and medical history were obtained at study entry as well. Patients were then divided into positive and negative autoantibodies groups, and prospectively followed for 18 months for evidence of abnormal liver function tests. One or more autoantibodies were detected in 18 (26%) patients. Anti-smooth muscle was the most common (n = 13) antibody. Time since transplant (>4 years) was the only risk factor identified for the presence of autoantibodies (univariate risk ratio, 3.3; 95% confidence interval, 1.2–9). During the follow-up period, 5 patients with positive autoantibody screen developed de novo AIH (n = 3) or chronic rejection (n = 2), compared with 0 in the negative autoantibody group. Children with positive autoantibody screen were at higher risk for development of de novo AIH or chronic rejection (univariate risk ratio 13.9; 95% confidence interval, 1.7–111; P= 0.004). Positive autoantibodies are common in children after LT and their presence may denote a higher risk for the development of de novo AIH or chronic rejection over time.

Objective:Information on the excretion of dietary phytate in humans under different conditions is limited. The purpose of this study was to investigate fecal excretion of dietary phytate and phosphorus in a group of young and elderly women consuming high and low phytate diets.Methods:Fifteen young and fourteen elderly women were fed two experimental diets, high phytate and low phytate, for 10 days each with a washout period of 10 days between the two diet periods. Duplicate diet samples from two different menus and complete fecal samples were collected for 5 days during each diet period and analyzed for phytate and phosphorus contents. Mean daily excretions and percentages of dietary intakes of phytate and phosphorus were calculated.Results:Dietary phytate level does impact phytate excretion, but the effect was observed only in young subjects. Fecal phytate excretion of young subjects during the high phytate diet (313mg/d) was significantly higher than during the low phytate diet (176mg/d), however, that of elderly subjects did not vary with dietary phytate levels. Phosphorus excretion, net absorption, and apparent absorption rate were affected by dietary phytate level but not by the age of the subjects.Conclusions:Results of this study indicate that phytate degradation in the gastrointestinal tract is substantial and more variable in young women than in elderly women. The high capacity of phytate degradation in elderly subjects may be related to long-term phytate intake but needs further clarification. Both beneficial and adverse health effects of phytate need to be studied considering the long-term phytate intake and age of subjects as well as dietary phytate levels.

The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators, particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1), an antagonist that blocks the capsaicin-induced and pH-induced uptake of ⁴⁵Ca²⁺ in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 ± 5 and 150 ± 80 nM, respectively. In this report, we describe the synthesis and structure−activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (Foral = 39% and 17%, respectively).

Primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES) rarely occurs in the skin and subcutaneous tissues. We present a case of a 16-year-old girl with primary cutaneous and subcutaneous PNET/ES of the abdominal wall. Despite wide local excision and chemotherapy, she rapidly developed cranial bone and brain metastases, followed by lung and skeletal metastases, and died shortly thereafter. The recurrent tumor exhibited light microscopic features of a small, round, blue cell tumor with intracytoplasmic glycogen. Immunohistochemical analysis showed positivity for CD99, CD56, S100, and glial fibrillary acid protein, and ultrastructural features included cytoplasmic glycogen and focal complex interdigitating synaptic junction-like cytoplasmic folds. Cytogenetic analysis of the relapsed tumor showed a complex karyotype: 47,XX,i(1)(q10), der(4)t(4;19) (q33~q35;q13.1), + 8,t(15;17)(q24;p11.2~p12),der(19)t (19;20)(q13.1;p11.2),der(22)t(20;22)(q13;q13). Cytogenetic, interphase fluorescence in situ hybridization, and molecular genetic analyses failed to show t(11:22) (q24;q12) or abnormalities of chromosome region 22q12. The clinical behavior and atypical and complex cytogenetic abnormalities exhibited by the tumor in this patient are unusual and represent the most aggressive end of the clinical spectrum of cutaneous and subcutaneous PNET/ES.

To delineate the relationship between the pulsatile gonadotropin inputs in early follicular phase of the menstrual cycle and the P secretions by the corpus luteum in women.

OBJECTIVE: Previous in vitro studies have demonstrated that transfection of an activated ras gene induces malignant transformation in epithelial cell lines infected with the human papillomavirus (HPV). The results of these studies support the hypothesis that HPV may co-operate with an activated ras gene in epithelial tumor carcinogenesis. To test this hypothesis in head and neck cancers, we screened 35 oral carcinomas for the presence of HPV DNA and for a mutated H-ras gene. DESIGN: The design of the study was a screening survey type. Twenty-seven oral squamous cell carcinomas and eight verrucous carcinomas were analyzed for the presence of HPV DNA using the polymerase chain reaction, followed by Southern blot and probe hybridization. The tumors were also screened for point mutations of the H-ras gene using the polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Six (22%) of the 27 oral squamous cell carcinomas demonstrated point mutation in the H-ras gene. In addition, six tumors (22%) were positive for HPV DNA, with three tumors (11%) demonstrating both HPV DNA and H-ras gene point mutation. While the rate of simultaneous HPV infection and ras gene activation by point mutation was 11% in oral squamous cell carcinomas, 25% of oral verrucous carcinomas contained both HPV DNA and mutation in the H-ras gene. CONCLUSIONS: These results suggest a stronger association between HPV infection and activation of the H-ras gene in oral verrucous carcinomas. These results continue to confirm the multihit hypothesis of tumorigenesis and suggest that in some cases of oral cancer at least two of these events are H-ras gene mutation and HPV infection.(Arch Otolaryngol Head Neck Surg. 1994;120:755-760)

Aerosol particles in the size range of several tens of nanometers are normally assumed to stick upon Brownian contact, although van der Waals' theory allows for repulsive interaction in three-component systems, provided that the optical constants of these components meet certain criteria. It was the goal of the study to verify experimentally the effect of coating layers on the sticking probability. In a system consisting of 40-nm particles generated by an incandescent tungsten wire and subsequently coated with diiodobutane, resulting in a total particle size of ≈45 nm, and diffusion batteries made from different optical glasses but mechanically identical otherwise, small but reproducible penetration differences were observed. These results provide the first experimental evidence that van der Waals forces in multicomponent systems may be strongly reduced and lead to a drastic reduction of sticking probability in aerosol systems. Copyright 1995, 1999 Academic Press

Diffuse large cell lymphomas are aggressive tumors of B-cell origin. In some cases they arise from low-grade follicular lymphomas carrying the t(14;18) translocation, an event that leads to the overexpression of the BCL-2gene product. More frequently, however, they lack the t(14;18) translocation. Rearrangements of the c-MYCproto-onco-gene and mutations of the p53 tumor suppressor gene have also been documented in these lymphomas. This study examines the extent to which alterations in the BCL-2, c-MYC, and p53 genes co-exist within individual lymphomas. Eight diffuse large cell lymphoma cell lines and 11 diffuse large cell lymphoma tumors were assessed for genetic alterations in these three genes. Our results indicate that there is a heterogeneity in the oncogene/suppres-sor gene profile among diffuse large cell lymphomas. Two cell lines and one tumor carried alterations in all three genes, one cell line carried alterations of c-MYCand p53, and one primary tumor and one cell line carried p53 mutations and the t(14; 18). Single alterations of BCL-2and p53 were also observed. Another cell line had no alterations in any of these genes. The heterogeneity indicates that varied mechanisms may be involved in the generation of diffuse large cell lymphomas.

In the design of fuselage structure, not only the longitudinal stability should be considered, but also the circumferential stability of fuselage structure is important because of its circumferential bearing of bending moment, shear force and axial force, as well as considering crash conditions. In this paper, the circumferential stability test researches of the fuselage structure were performed on the single-frame curved panel test specimens. The buckling and post-buckling characteristics of the single-frame curved panel under the negative bending condition were examined by four-point bending loading method. At the same time, the buckling mode, failure process and damage mechanism of single-frame curved panel were analysed through the load-strain curves of the skin and the different degree of damage of the three test specimens. The experimental results show that the buckling of skin is an important factor causing the debonding between the cap-stringers and the skin. The expansion of the debonding area greatly reduces the bearing capacity of the curved stiffened panel structure, which eventually leads to the breakage of the frame.

Les mutations inactivatrices de PRKAR1A (sous-unité régulatrice RIA de la PKA) sont associées au développement de tumeurs corticosurrénales bilatérales (PPNAD) sécrétant du cortisol. La comparaison des transcriptomes de PPNAD et de cellules corticosurrénaliennes H295R avec et sans inactivation de PRKAR1A a permis d’identifier un gène dont l’expression est diminuée suite à la perte d’expression de PRKAR1A : KCTD20 (potassium channel tetramerisation domain containing 20). Ce travail a pour but de comprendre le rôle de KCTD20 dans l’hyperactivité endocrine et le développement tumoral des PPNAD.

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