A Modified Collagen Dressing Induces Transition of Inflammatory to Reparative Phenotype of Wound Macrophages

Collagen containing wound-care dressings are extensively used. However, the mechanism of action of these dressings remain unclear. Earlier studies utilizing a modified collagen gel (MCG) dressing demonstrated improved vascularization of ischemic wounds and better healing outcomes. Wound macrophages are pivotal in facilitating wound angiogenesis and timely healing. The current study was designed to investigate the effect of MCG on wound macrophage phenotype and function. MCG augmented recruitment of macrophage at the wound-site, attenuated pro-inflammatory and promoted anti-inflammatory macrophage polarization. Additionally, MCG increased anti-inflammatory IL-10, IL-4 and pro-angiogenic VEGF production, indicating a direct role of MCG in resolving wound inflammation and improving angiogenesis. At the wound-site, impairment in clearance of apoptotic cell bioburden enables chronic inflammation. Engulfment of apoptotic cells by macrophages (efferocytosis) resolves inflammation via a miR-21-PDCD4-IL-10 pathway. MCG-treated wound macrophages exhibited a significantly bolstered efferocytosis index. Such favorable outcome significantly induced miR-21 expression. MCG-mediated IL-10 production was dampened under conditions of miR-21 knockdown pointing towards miR-21 as a causative factor. Pharmacological inhibition of JNK attenuated IL-10 production by MCG, implicating miR-21-JNK pathway in MCG-mediated IL-10 production by macrophages. This work provides direct evidence demonstrating that a collagen-based wound-care dressing may influence wound macrophage function and therefore modify wound inflammation outcomes

Tuning thermoelectric properties of Sb2_2Te3_3-AgSbTe2_2 nanocomposite thin film -- synergy of band engineering and heat transport modulation

The present study demonstrates a large enhancement in the Seebeck coefficient and ultralow thermal conductivity (TE) in Sb$_2$Te$_3$-AgSbTe$_2$ nanocomposite thin film. The addition of Ag leads to the in-situ formation of AgSbTe$_2$ secondary phase nanoaggregates in the Sb$_2$Te$_3$ matrix during the growth resulting in a large Seebeck coefficient and reduction of the thermal conductivity. A series of samples with different amounts of minor AgSbTe$_2$ phases are prepared to optimize the TE performance of Sb$_2$Te$_3$ thin films. Based on the experimental and theoretical evidence, it is concluded that a small concentration of Ag promotes the band flattening and induces a sharp resonate-like state deep inside the valence band of Sb$_2$Te$_3$, concurrently modifying the density of states (DOS) of the composite sample. In addition, the electrical potential barrier introduced by the band offset between the host TE matrix and the secondary phases promotes strong energy-dependent carrier scattering in the composite sample, which is also responsible for enhanced TE performance. A contemporary approach based on scanning thermal microscopy is performed to experimentally obtain thermal conductivity values of both the in-plane and cross-plane directions, showing a reduced in-plane thermal conductivity value by ~ 58% upon incorporating the AgSbTe$_2$ phase in the Sb$_2$Te$_3$ matrix. Benefitting from the synergistic manipulation of electrical and thermal transport, a large ZT value of 2.2 is achieved at 375 K. The present study indicates the importance of a combined effect of band structure modification and energy-dependent charge carrier scattering along with reduced thermal conductivity for enhancing TE properties

Automatic leukocyte nucleus segmentation by intuitionistic fuzzy divergence based thresholding

The paper proposes a robust approach to automatic segmentation of leukocyte‟s nucleus from microscopic blood smear images under normal as well as noisy environment by employing a new exponential intuitionistic fuzzy divergence based thresholding technique. The algorithm minimizes the divergence between the actual image and the ideally thresholded image to search for the final threshold. A new divergence formula based on exponential intuitionistic fuzzy entropy has been proposed. Further, to increase its noise handling capacity, a neighborhood-based membership function for the image pixels has been designed. The proposed scheme has been applied on 110 normal and 54 leukemia (chronic myelogenous leukemia) affected blood samples. The nucleus segmentation results have been validated by three expert haematologists. The algorithm achieves an average segmentation accuracy of 98.52% in noise-free environment. It beats the competitor algorithms in terms of several other metrics. The proposed scheme with neighborhood based membership function outperforms the competitor algorithms in terms of segmentation accuracy under noisy environment. It achieves 93.90% and 94.93% accuracies for Speckle and Gaussian noises respectively. The average area under the ROC curves comes out to be 0.9514 in noisy conditions, which proves the robustness of the proposed algorithm

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen

Objective: The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing. Background: Staphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging. Thus, isogenic mutant stains of S. aureus with varying degree of biofilm formation ability was studied in an established preclinical porcine model of wound biofilm infection. Methods: Isogenic mutant strains of S. aureus with varying degree (ΔrexB > USA300 > ΔsarA) of biofilm-forming ability were used to infect full-thickness porcine cutaneous wounds. Results: Compared with that of ΔsarA infection, wound biofilm burden was significantly higher in response to ΔrexB or USA300 infection. Biofilm infection caused degradation of cutaneous collagen, specifically collagen 1 (Col1), with ΔrexB being most pathogenic in that regard. Biofilm infection of the wound repressed wound-edge miR-143 causing upregulation of its downstream target gene matrix metalloproteinase-2. Pathogenic rise of collagenolytic matrix metalloproteinase-2 in biofilm-infected wound-edge tissue sharply decreased collagen 1/collagen 3 ratio compromising the biomechanical properties of the repaired skin. Tensile strength of the biofilm infected skin was compromised supporting the notion that healed wounds with a history of biofilm infection are likely to recur. Conclusion: This study provides maiden evidence that chronic S. aureus biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound tissue biomechanics. Clinically, such compromise in tissue repair is likely to increase wound recidivism