Biomaterials selectively modulate interactions between human blood-derived polymorphonuclear leukocytes and monocytes

Implantation of a biomaterial into the body elicits a host foreign body response, during which polymorphonuclear leukocytes (PMNs) and then monocytes (MCs) are recruited to the site of implantation. MCs and MC-derived macrophages are central players in this response because they secrete proinflammatory and/or pro-wound-healing cytokines and growth factors that influence subsequent healing events. Although mechanisms of MC response to biomaterials are often studied in in vitro monoculture models, few studies have investigated how biomaterials modulate PMN-MC paracrine and juxtacrine interactions. To address this, we cultured human blood-derived MCs alone or in the presence of autologous PMN-conditioned medium (PCM) on poly(ethylene glycol) hydrogels, poly(dimethyl siloxane), and tissue culture polystyrene. We also directly co-cultured autologous PMNs and MCs on these biomaterials. PCM increased MC adhesion/viability and expression of IL-1β and tumor necrosis factor-α in a biomaterial- and time-dependent manner when compared with MCs that were not cultured in PCM. There were also biomaterial- and time-dependent differences in cell adhesion/viability, apoptosis, and expression of IL-6 and IL-8 in the PMN-MC direct co-cultures when compared with the sums of these activities in PMN and MC monocultures. In conclusion, these data suggest that biomaterials selectively modulate PMN-MC paracrine and juxtacrine interactions to influence MC and/or PMN adhesion/viability, apoptosis, and cytokine expression. Copyright © 2013 American Society for Investigative Pathology.Link_to_subscribed_fulltex

Multiple light scattering in nematic liquid crystals

We present a rigorous treatment of the diffusion approximation for multiple light scattering in anisotropic random media, and apply it to director fluctuations in a nematic liquid crystal. For a typical nematic material, 5CB, we give numerical values of the diffusion constants $D_{\|}$ and $D_{\perp}$. We also calculate the temporal autocorrelation function measured in Diffusing Wave Spectroscopy.Comment: 5 pages RevTeX, 1 postscript figure, to be published in Phys. Rev. E (Rapid Communication

The new (challenging) role of academia in biomaterial translational research and medical device development

With the ever-changing landscape of translational research, the medical device and pharmaceutical industries increasingly license technologies with the added value of clinical and/or pre-clinical data rather than those in earlier stages of development. Universities have the potential to fill the gap in product development from academic laboratories through enhanced student training and increased implementation of some development and manufacturing activities that are traditionally found only in the private sector. A development roadmap is described from initial product feasibility through commercialization in the context of efficient development practices. The specific challenges in the design and development of biomaterialbased medical devices are described in the context of this development path with an emphasis on unique challenges for academic laboratories. © The Author(s) 2012.Link_to_subscribed_fulltex

Supplementary Prognostic Variables for Pleural Mesothelioma A Report from the IASLC Staging Committee

Introduction: The staging system for malignant pleural mesothelioma is controversial. To revise this system, the International Association for the Study of Lung Cancer Staging Committee developed an international database. This report analyzes prognostic variables in a surgical population, which are supplementary to previously published CORE variables (stage, histology, sex, age, and type of procedure). Methods: Supplementary prognostic variables were studied in three scenarios: (1) all data available, that is, patient pathologically staged and other CORE variables available (2) only clinical staging available along with CORE variables, and (3) only age, sex, histology, and laboratory parameters are known. Survival was analyzed by Kaplan– Meier, prognostic factors by log rank and stepwise Cox regression modeling after elimination of nonsignificant variables. p value less than 0.05 was significant. Results: A total of 2141 patients with best tumor, node, metastasis (TNM) stages (pathologic with/without clinical staging) had nonmissing age, sex, histology, and type of surgical procedure. Three prognostic models were defined. Scenario A (all parameters): best pathologic stage, histology, sex, age, type of surgery, adjuvant treatment, white blood cell count (WBC) (≥15.5 or not), and platelets (≥400 k or not) (n = 550). Scenario B (no surgical staging): clinical stage, histology, sex, age, type of surgery, adjuvant treatment, WBC, hemoglobin (<14.6 or not), and platelets (n = 627). Scenario C (limited data): histology, sex, age, WBC, hemoglobin, and platelets (n = 906). Conclusion: Refinement of these models could define not only the appropriate patient preoperatively for best outcomes after cytoreductive surgery but also stratify surgically treated patients after clinical and pathologic staging who do or do not receive adjuvant therapy

A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies.

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

Friends of Hot Jupiters. I. A Radial Velocity Search for Massive, Long-Period Companions to Close-In Gas Giant Planets

In this paper we search for distant massive companions to known transiting hot Jupiters that may have influenced the dynamical evolution of these systems. We present new radial velocity observations for a sample of 51 hot Jupiters obtained using the Keck HIRES instrument, and use these observations to search for long-term radial velocity accelerations. We find new, statistically significant accelerations in seven systems, including: HAT-P-10, HAT-P-20, HAT-P-22, HAT-P-29, HAT-P-32, WASP-10, and XO-2. We combine our radial velocity fits with Keck NIRC2 AO imaging data to place constraints on the allowed masses and orbital periods of the companions. The estimated masses of the companions range between 1-500 M_(Jup), with orbital semi-major axes typically between 1-75 AU. A significant majority of the companions detected by our survey are constrained to have minimum masses comparable to or larger than those of the short-period hot Jupiters in these systems, making them candidates for influencing the orbital evolution of the inner hot Jupiters. They also appear to occur preferentially in systems with more metal-rich host stars, and with typical orbital separations that are larger than those of multi-planet systems without hot Jupiters. We estimate a total occurrence rate of 55% +11% / -10% for companions with masses between 1-13 M_(Jup) and orbital semi-major axes between 1-20 AU in our sample. We find no statistically significant difference between the frequency of companions in hot Jupiter systems with misaligned or eccentric orbits and those with well-aligned, circular orbits. We combine our expanded sample of radial velocity measurements with constraints from transit and secondary eclipse observations to provide improved measurements of the physical and orbital characteristics of all of the hot Jupiters included in our survey

A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers

Collagen structure has been shown to influence tumor cell invasion, metastasis and clinical outcome in breast cancer. However, it remains unclear how it affects other solid cancers. Here we utilized multi-photon laser scanning microscopy and Second Harmonic Generation to identify alterations to collagen fiber structure within the tumor stroma of head &amp; neck, esophageal and colorectal cancers. Image segmentation algorithms were then applied to quantitatively characterize these morphological changes, showing that elongated collagen fibers significantly correlated with poor clinical outcome (Log Rank p &lt; 0.05). We used TGF-? treatment to model fibroblast conversion to smooth muscle actin SMA-positive cancer associated fibroblasts (CAFs) and found that these cells induce the formation of elongated collagen fibers in vivo. However, proteomic/transcriptomic analysis of SMA-positive CAFs cultured ex-vivo showed significant heterogeneity in the expression of genes with collagen fibril organizing gene ontology. Notably, stratifying patients according to stromal SMA-positivity and collagen fiber elongation was found to provide a highly significant correlation with poor survival in all 3 cancer types (Log Rank p ? 0.003). In summary, we show that increased collagen fiber length correlates with poor patient survival in multiple tumor types and that only a sub-set of SMA-positive CAFs can mediate the formation of this collagen structure

A public health response to the methamphetamine epidemic: the implementation of contingency management to treat methamphetamine dependence

BACKGROUND: In response to increases in methamphatemine-associated sexually transmitted diseases, the San Francisco Department of Public Health implemented a contingency management (CM) field program called the Positive Reinforcement Opportunity Project (PROP). METHODS: Methamphetamine-using men who have sex with men (MSM) in San Francisco qualified for PROP following expressed interest in the program, provision of an observed urine sample that tested positive for methamphetamine metabolites and self-report of recent methamphetamine use. For 12 weeks, PROP participants provided observed urine samples on Mondays, Wednesdays and Fridays and received vouchers of increasing value for each consecutive sample that tested negative to metabolites of methamphetamine. Vouchers were exchanged for goods and services that promoted a healthy lifestyle. No cash was provided. Primary outcomes included acceptability (number of enrollments/time), impact (clinical response to treatment and cost-effectiveness as cost per patient treated). RESULTS: Enrollment in PROP was brisk indicating its acceptability. During the first 10 months of operation, 143 men sought treatment and of these 77.6% were HIV-infected. Of those screened, 111 began CM treatment and averaged 15 (42%) methamphetamine-free urine samples out of a possible 36 samples during the 12-week treatment period; 60% completed 4 weeks of treatment; 48% 8 weeks and 30% 12 weeks. Across all participants, an average of $159 (SD =$165) in vouchers or 35.1% of the maximum possible ($453) was provided for these participants. The average cost per participant of the 143 treated was$800. CONCLUSION: Clinical responses to CM in PROP were similar to CM delivered in drug treatment programs, supporting the adaptability and effectiveness of CM to non-traditional drug treatment settings. Costs were reasonable and less than or comparable to other methamphetamine outpatient treatment programs. Further expansion of programs like PROP could address the increasing need for acceptable, feasible and cost-effective methamphetamine treatment in this group with exceptionally high rates of HIV-infection

Orbital Phase Variations of the Eccentric Giant Planet HAT-P-2b

We present the first secondary eclipse and phase curve observations for the highly eccentric hot Jupiter HAT-P-2b in the 3.6, 4.5, 5.8, and 8.0 μm bands of the Spitzer Space Telescope. The 3.6 and 4.5 μm data sets span an entire orbital period of HAT-P-2b (P = 5.6334729 d), making them the longest continuous phase curve observations obtained to date and the first full-orbit observations of a planet with an eccentricity exceeding 0.2. We present an improved non-parametric method for removing the intrapixel sensitivity variations in Spitzer data at 3.6 and 4.5 μm that robustly maps position-dependent flux variations. We find that the peak in planetary flux occurs at 4.39 ± 0.28, 5.84 ± 0.39, and 4.68 ± 0.37 hr after periapse passage with corresponding maxima in the planet/star flux ratio of 0.1138% ± 0.0089%, 0.1162% ± 0.0080%, and 0.1888% ± 0.0072% in the 3.6, 4.5, and 8.0 μm bands, respectively. Our measured secondary eclipse depths of 0.0996% ± 0.0072%, 0.1031% ± 0.0061%, 0.071%^(+0.029%)_(-0.013%), and 0.1392% ± 0.0095% in the 3.6, 4.5, 5.8, and 8.0 μm bands, respectively, indicate that the planet cools significantly from its peak temperature before we measure the dayside flux during secondary eclipse. We compare our measured secondary eclipse depths to the predictions from a one-dimensional radiative transfer model, which suggests the possible presence of a transient day side inversion in HAT-P-2b's atmosphere near periapse. We also derive improved estimates for the system parameters, including its mass, radius, and orbital ephemeris. Our simultaneous fit to the transit, secondary eclipse, and radial velocity data allows us to determine the eccentricity (e = 0.50910 ± 0.00048) and argument of periapse (ω = 188°.09 ± 0°.39) of HAT-P-2b's orbit with a greater precision than has been achieved for any other eccentric extrasolar planet. We also find evidence for a long-term linear trend in the radial velocity data. This trend suggests the presence of another substellar companion in the HAT-P-2 system, which could have caused HAT-P-2b to migrate inward to its present-day orbit via the Kozai mechanism

Direct observation of active material concentration gradients and crystallinity breakdown in LiFePO4 electrodes during charge/discharge cycling of lithium batteries

The phase changes that occur during discharge of an electrode comprised of LiFePO4, carbon, and PTFE binder have been studied in lithium half cells by using X-ray diffraction measurements in reflection geometry. Differences in the state of charge between the front and the back of LiFePO4 electrodes have been visualized. By modifying the X-ray incident angle the depth of penetration of the X-ray beam into the electrode was altered, allowing for the examination of any concentration gradients that were present within the electrode. At high rates of discharge the electrode side facing the current collector underwent limited lithium insertion while the electrode as a whole underwent greater than 50% of discharge. This behavior is consistent with depletion at high rate of the lithium content of the electrolyte contained in the electrode pores. Increases in the diffraction peak widths indicated a breakdown of crystallinity within the active material during cycling even during the relatively short duration of these experiments, which can also be linked to cycling at high rate