Dynamical Response of Nanomechanical Oscillators in Immiscible Viscous Fluid for in vitro Biomolecular Recognition

Dynamical response of nanomechanical cantilever structures immersed in a viscous fluid is important to in vitro single-molecule force spectroscopy, biomolecular recognition of disease-specific proteins, and the detection of microscopic dynamics of proteins. Here we study the stochastic response of biofunctionalized nanomechanical cantilevers beam in a viscous fluid. Using the fluctuation-dissipation theorem we derive an exact expression for the spectral density of the displacement and a linear approximation for the resonance frequency shift. We find that in a viscous solution the frequency shift of the nanoscale cantilever is determined by surface stress generated by biomolecular interaction with negligible contributions from mass loading.Comment: 4 pages, 2 figures, RevTex4. See http://nano.bu.edu/ for related paper

Defect structures in nematic liquid crystals around charged particles

We numerically study the orientation deformations in nematic liquid crystals around charged particles. We set up a Ginzburg-Landau theory with inhomogeneous electric field. If the dielectric anisotropy varepsilon_1 is positive, Saturn ring defects are formed around the particles. For varepsilon_1<0, novel "ansa" defects appear, which are disclination lines with their ends on the particle surface. We find unique defect structures around two charged particles. To lower the free energy, oppositely charged particle pairs tend to be aligned in the parallel direction for varepsilon_1>0 and in the perpendicular plane for varepsilon_1<0 with respect to the background director . For identically charged pairs the preferred directions for varepsilon_1>0 and varepsilon_1<0 are exchanged. We also examie competition between the charge-induced anchoring and the short-range anchoring. If the short-range anchoring is sufficiently strong, it can be effective in the vicinity of the surface, while the director orientation is governed by the long-range electrostatic interaction far from the surface.Comment: 10 papes, 12 figures, to appear in European Physical Journal

Attitudes towards medication non-adherence in elderly kidney transplant patients: A Q methodology study

Background. Non-adherence to the post-transplant regime is a common problem in kidney transplant patients and may lead to rejection or even graft failure. This study investigated attitudes towards the post-transplant regime of immunosuppressive medication among the ever growing population of elderly kidney recipients.Methods. Q methodology was used to explore attitude profiles. Participants (> 65 years) were asked to rank-order opinion statements on issues associated with (non-)adherence. The rankings were subject to by-person factor analysis, and the resulting factors were interpreted and described as attitudes.Results. Twenty-six elderly renal transplant recipients participated in the study. All passed the Mini-Mental

Antibody-induced erythrophagocyte reprogramming of Kupffer cells prevents anti-CD40 cancer immunotherapy-associated liver toxicity

BackgroundAgonistic anti-CD40 monoclonal antibodies (mAbs) have emerged as promising immunotherapeutic compounds with impressive antitumor effects in mouse models. However, preclinical and clinical studies faced dose-limiting toxicities mediated by necroinflammatory liver disease. An effective prophylactic treatment for liver immune-related adverse events that does not suppress specific antitumor immunity remains to be found.MethodsWe used different mouse models and time-resolved single-cell RNA-sequencing to characterize the pathogenesis of anti-CD40 mAb induced liver toxicity. Subsequently, we developed an antibody-based treatment protocol to selectively target red blood cells (RBCs) for erythrophagocytosis in the liver, inducing an anti-inflammatory liver macrophage reprogramming.ResultsWe discovered that CD40 signaling in Clec4f$^{+}$Kupffer cells is the non-redundant trigger of anti-CD40 mAb-induced liver toxicity. Taking advantage of the highly specific functionality of liver macrophages to clear antibody-tagged RBCs from the blood, we hypothesized that controlled erythrophagocytosis and the linked anti-inflammatory signaling by the endogenous metabolite heme could be exploited to reprogram liver macrophages selectively. Repeated low-dose administration of a recombinant murine Ter119 antibody directed RBCs for selective phagocytosis in the liver and skewed the phenotype of liver macrophages into a Hmox$^{high}$/Marco$^{high}$/MHCII$^{low}$anti-inflammatory phenotype. This unique mode of action prevented necroinflammatory liver disease following high-dose administration of anti-CD40 mAbs. In contrast, extrahepatic inflammation, antigen-specific immunity, and antitumor activity remained unaffected in Ter119 treated animals.ConclusionsOur study offers a targeted approach to uncouple CD40-augmented antitumor immunity in peripheral tissues from harmful inflammatoxicity in the liver

Single Mode Lasing from Hybrid Hemispherical Microresonators

Enormous attention has been paid to optical microresonators which hold a great promise for microlasers as well as fundamental studies in cavity quantum electrodynamics. Here we demonstrate a three-dimensional (3D) hybrid microresonator combining self-assembled hemispherical structure with a planar reflector. By incorporating dye molecules into the hemisphere, optically pumped lasing phenomenon is observed at room temperature. We have studied the lasing behaviors with different cavity sizes, and particularly single longitudinal mode lasing from hemispheres with diameter ∼15 μm is achieved. Detailed characterizations indicate that the lasing modes shift under varying pump densities, which can be well-explained by frequency shift and mode hopping. This work provides a versatile approach for 3D confined microresonators and opens an opportunity to realize tunable single mode microlasers

Recommended curriculum for subspecialty training in transplant infectious disease on behalf of the American Society of Transplantation Infectious Diseases Community of Practice Educational Initiatives Working Group

R. Avery, H. Clauss, L. Danziger-Isakov, J. Davis, K. Doucette, D. van Duin, J. Fishman, F. Gunseren, A. Humar, S. Husain, C. Isada, K. Julian, D. Kaul, D. Kumar, S. Martin, M. Michaels, M. Morris, F. Silveira, A. Subramanian. Recommended curriculum for subspecialty training in transplant infectious disease on behalf of the American Society of Transplantation Infectious Diseases Community of Practice Educational Initiatives Working Group. Transpl Infect Dis 2010: 12: 190–194. All rights reservedThe American Society of Transplantation Infectious Diseases (ID) Community of Practice has established an education workgroup to identify core components of a curriculum for training specialists in transplant ID. Clinical, laboratory, and research training form the triad of components on which an additional year of ID training, dedicated to the care of solid organ and hematopoietic stem cell transplant recipients, should be based. The recommended training environment would have access to adequate numbers of transplant patients, along with qualified faculty committed to teaching specialized fellows in this area. The learning objectives for both inpatient and outpatient clinical training are presented. The laboratory component requires trainees to attain expertize in utilizing and interpreting cutting-edge diagnostics used in transplant medicine. The research component may involve basic science, and translational or clinical research individualized to the trainee. Finally, suggestions for evaluation of both the fellows and the training program are provided.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79192/1/j.1399-3062.2010.00510.x.pd

Coherent Random Lasing Realized in Polymer Vesicles

We have demonstrated the realization of a coherent vesicle random lasing (VRL) from the dye doped azobenzene polymer vesicles self-assembled in the tetrahydrofuran-water system, which contains a double-walled structure: a hydrophilic and hydrophobic part. The effect of the dye and azobenzene polymer concentration on the threshold of random laser has been researched. The threshold of random laser decreases with an increase in the concentration of the pyrromethene 597 (PM597) laser and azobenzene polymer. Moreover, the scattering of small size group vesicles is attributed to providing a loop to boost the coherent random laser through the Fourier transform analysis. Due to the vesicles having the similar structure with the cell, the generation of coherent random lasers from vesicles expand random lasers to the biomedicine filed

Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study.

BACKGROUND: Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D(+)/R(-)) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. METHODS: We prospectively included D(+)/R(-) patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon-γ levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. RESULTS: Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P &lt; .001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI], .74-.98) and 0.27 (95% CI, .18-.37), respectively. CONCLUSIONS: This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis. CLINICAL TRIALS REGISTRATION: NCT00817908