Motility of small nematodes in disordered wet granular media

The motility of the worm nematode \textit{Caenorhabditis elegans} is investigated in shallow, wet granular media as a function of particle size dispersity and area density ($\phi$). Surprisingly, we find that the nematode's propulsion speed is enhanced by the presence of particles in a fluid and is nearly independent of area density. The undulation speed, often used to differentiate locomotion gaits, is significantly affected by the bulk material properties of wet mono- and polydisperse granular media for $\phi \geq 0.55$. This difference is characterized by a change in the nematode's waveform from swimming to crawling in dense polydisperse media \textit{only}. This change highlights the organism's adaptability to subtle differences in local structure and response between monodisperse and polydisperse media

Performance tests on Screw Feeder Conveyor for Nodule Transfer Deep Sea Applications

A screw conveyor is a versatile conveyor used in many process plants for the transfer of bulk solids and powders. The following article has written to understand screw conveyor design and selection of the right screw conveyor for underwater applications to convey crushed manganese nodules to the pump system for nodule transfer. The nodules from the sea bed will be collected by a pickup device and crushed into less than 30mm pieces by using a crusher and pumped by a positive displacement pump to the mother vessel. Screw feeder is used to transfer curshed Polymetallic Nodules from hopper to pump system with controlled feed rate. A land based screw feeder is modified to suit the under water applications. Studies on screw conveyors were conducted to examine performance in land as well as underwater. Most of these studies were experimental in nature. This paper presents a critical review on the design and validation of a screw conveyor

A nonhuman primate model of inherited retinal disease.

Inherited retinal degenerations are a common cause of untreatable blindness worldwide, with retinitis pigmentosa and cone dystrophy affecting approximately 1 in 3500 and 1 in 10,000 individuals, respectively. A major limitation to the development of effective therapies is the lack of availability of animal models that fully replicate the human condition. Particularly for cone disorders, rodent, canine, and feline models with no true macula have substantive limitations. By contrast, the cone-rich macula of a nonhuman primate (NHP) closely mirrors that of the human retina. Consequently, well-defined NHP models of heritable retinal diseases, particularly cone disorders that are predictive of human conditions, are necessary to more efficiently advance new therapies for patients. We have identified 4 related NHPs at the California National Primate Research Center with visual impairment and findings from clinical ophthalmic examination, advanced retinal imaging, and electrophysiology consistent with achromatopsia. Genetic sequencing confirmed a homozygous R565Q missense mutation in the catalytic domain of PDE6C, a cone-specific phototransduction enzyme associated with achromatopsia in humans. Biochemical studies demonstrate that the mutant mRNA is translated into a stable protein that displays normal cellular localization but is unable to hydrolyze cyclic GMP (cGMP). This NHP model of a cone disorder will not only serve as a therapeutic testing ground for achromatopsia gene replacement, but also for optimization of gene editing in the macula and of cone cell replacement in general

Financial correlations at ultra-high frequency: theoretical models and empirical estimation

A detailed analysis of correlation between stock returns at high frequency is compared with simple models of random walks. We focus in particular on the dependence of correlations on time scales - the so-called Epps effect. This provides a characterization of stochastic models of stock price returns which is appropriate at very high frequency.Comment: 22 pages, 8 figures, 1 table, version to appear in EPJ

IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

A Study of Fracture in a Rotating Disc

This investigation deals with the fracture produced in a disc by simple rotation cycles as well as rotation cycles under an imposed hydrostatic pressure. In both the cases, relations are obtained between the critical angular speed omega and the number of cycles N, required to cause fracture

Measurement of Pion Enhancement at Low Transverse Momentum and of the Delta-Resonance Abundance in Si-Nucleus Collisions at AGS Energy

We present measurements of the pion transverse momentum (p_t) spectra in central Si-nucleus collisions in the rapidity range 2.0<y<5.0 for p_t down to and including p_t=0. The data exhibit an enhanced pion yield at low p_t compared to what is expected for a purely thermal spectral shape. This enhancement is used to determine the Delta-resonance abundance at freeze-out. The results are consistent with a direct measurement of the Delta-resonance yield by reconstruction of proton-pion pairs and imply a temperature of the system at freeze-out close to 140 MeV.Comment: 12 pages + 4 figures (uuencoded at end-of-file

p130Cas is an essential transducer element in ErbB2 transformation

The ErbB2 oncogene is often overexpressed in breast tumors and associated with poor clinical outcome. p130Cas represents a nodal scaffold protein regulating cell survival, migration, and proliferation in normal and pathological cells. The functional role of p130Cas in ErbB2-dependent breast tumorigenesis was assessed by its silencing in breast cancer cells derived from mouse mammary tumors overexpressing ErbB2 (N202-1A cells), and by its reexpression in ErbB2-transformed p130Cas-null mouse embryonic fibroblasts. We demonstrate that p130Cas is necessary for ErbB2-dependent foci formation, anchorage-independent growth, and in vivo growth of orthotopic N202-1A tumors. Moreover, intranipple injection of p130Cas-stabilized siRNAs in the mammary gland of Balbc-NeuT mice decreases the growth of spontaneous tumors. In ErbB2-transformed cells, p130Cas is a crucial component of a functional molecular complex consisting of ErbB2, c-Src, and Fak. In human mammary cells, MCF10A.B2, the concomitant activation of ErbB2, and p130Cas overexpression sustain and strengthen signaling, leading to Rac1 activation and MMP9 secretion, thus providing invasive properties. Consistently, p130Cas drives N202-1A cell in vivo lung metastases colonization. These results demonstrate that p130Cas is an essential transducer in ErbB2 transformation and highlight its potential use as a novel therapeutic target in ErbB2 positive human breast cancers.-Cabodi, S., Tinnirello, A., Bisaro, B., Tornillo, G., Camacho-Leal, M. P., Forni, G., Cojoca, R., Iezzi, M., Amici, A., Montani, M., Eva, A., Di Stefano, P., Muthuswamy, S. K., Tarone, G., Turco, E., Defilippi, P. p130Cas is an essential transducer element in ErbB2 transformation

Combination of IFNα and poly-I: C reprograms bladder cancer microenvironment for enhanced CTL attraction

Background: BCG is a prototypal cancer immunotherapeutic factor currently approved of bladder cancer. In attempt to further enhance the effectiveness of immunotherapy of bladder cancer and, potentially, other malignancies, we evaluated the impact of BCG on local production of chemokines attracting the desirable effector CD8+ T cells (CTLs) and undesirable myeloid-derived suppressor cell (MDSCs) and regulatory T(reg) cells, and the ability of bladder cancer tissues to attract CTLs.Methods: Freshly resected bladder cancer tissues were either analyzed immediately or cultured ex vivo in the absence or presence of the tested factors. The expression of chemokine genes, secretion of chemokines and their local sources in freshly harvested and ex vivo-treated tumor explants were analyzed by quantitative PCR (Taqman), ELISAs and immunofluorescence/confocal microscopy. Migration of CTLs was evaluated ex vivo, using 24-transwell plates. Spearman correlation was used for correlative analysis, while paired Students T test or Wilcoxon was used for statistical analysis of the data.Results: Bladder cancer tissues spontaneously expressed high levels of the granulocyte/MDSC-attractant CXCL8 and Treg-attractant CCL22, but only marginal levels of the CTL-attracting chemokines: CCL5, CXCL9 and CXCL10. Baseline CXCL10 showed strong correlation with local expression of CTL markers. Unexpectedly, BCG selectively induced only the undesirable chemokines, CCL22 and CXCL8, but had only marginal impact on CXCL10 production. In sharp contrast, the combination of IFNα and a TLR3 ligand, poly-I:C (but not the combinations of BCG with IFNα or BCG with poly-I:C), induced high levels of intra-tumoral production of CXCL10 and promoted CTL attraction. The combination of BCG with IFNα + poly-I:C regimen did not show additional advantage.Conclusions: The current data indicate that suboptimal ability of BCG to reprogram cancer-associated chemokine environment may be a factor limiting its therapeutic activity. Our observations that the combination of BCG with (or replacement by) IFNα and poly-I:C allows to reprogram bladder cancer tissues for enhanced CTL entry may provide for new methods of improving the effectiveness of immunotherapy of bladder cancer, helping to extend BCG applications to its more advanced forms, and, potentially, other diseases

Promoting integrated care in prostate cancer through online prostate cancer-specific holistic needs assessment: a feasibility study in primary care

PURPOSE: This study assessed the feasibility of implementing a novel model of integrated prostate cancer care involving an online prostate cancer-specific holistic needs assessment (sHNA) and shared digital communication between patients and their healthcare professionals (HCPs). The sHNA produces a semi-automated care plan that is finalised in consultation between the patient and their practice nurse. METHODS: Men living with and beyond prostate cancer were invited to participate in a 9-month non-randomised cluster controlled feasibility study. The intervention group was asked to complete the sHNA on three occasions. Data were collected using Patient Reported Outcome Measures (PROMs) at baseline, 10 and 24 weeks, and 9 months. Outcomes included recruitment, retention, acceptability, and engagement with the sHNA and PROMs. RESULTS: Fourteen general practices (8 intervention and 6 control), and 41 men (29 intervention and 12 control) participated. Initial patient engagement with the sHNA was high, with all but one receiving practice nurse-led follow-up and an individualised care plan. The sHNA proved useful in identifying ‘red flag’ symptoms, and helping practice nurses decide when to seek further medical care for the patients. There was a high level of acceptability for patients and HCPs. However, integration of care did not occur as intended because of problems linking hospital and general practice IT systems. CONCLUSION: While the study demonstrated the feasibility of implementing the sHNA, it did not meet the a priori progression criteria; as such, undertaking a definitive randomised controlled trial is not appropriate until the identified methodological and technical issues have been addressed