DYNAMIC NUCLEAR POLARIZATION [D.N.P.]: ELEMENTARY EXPOSURE TO THE PHENOMENON OF DNP

Within a single experimental specimen there could be several spin species ensembles present. In a strong externally (external to the specimen) applied magnetic field, every one of the spin ensemble would be in equilibrium with the lattice (non-spin quantized levels of various degrees of freedom) and attain thermal equilibrium populations governed by the Boltzmann distribution for the corresponding quantization of energy level differences. In a Nuclear Magnetic Resonance, of the several nuclear species, one of the species is selected to apply the RF radiation at frequency corresponding to energy level difference of one of the species namely electron, proton, carbon, nitrogen, phosphorus etc. As a variation, it is possible to saturate the levels of one spin species. That is, by a high power RF radiation the RF induced transition rates can be increased so that the populations almost equalize. This would be a non-thermal population difference. Since this is part of the lattice of some other spin species, its population distribution can be affected. Presence of such a non thermal population difference can cause non-thermal equilibrium in another spin ensemble in the specimen. When such non-thermal equilibriums attain a steady ate, then what is called Dynamic Spin Population exists. In general when it pertains to nuclear ensembles it is referred to as Dynamic Nuclear Polarization. The description of such Dynamic Nuclear Polarization, and the enumeration of a variety of experiments involving Dynamically Polarized nuclear states are the subject matter to be included in this contribution.

A REVIEW OF THE ELEMENTS OF NUCLEAR MAGNETIC RESONANCE INSTRUMENTATION

The early efforts to detect nuclear magnetic resonance (NMR) when reviewed, carries a valuable message on how to go about making discoveries of phenomena on the basis of what is known already. Particularly the instrumentation is an effort which has an outlook on enterprises that provide various laboratory equipments and assembling these units in a way that brings out precisely what is being looked for is a creative preoccupation in scientific research. The kind of home-built spectrometers which have been used by every researcher for the achievements in the NMR spectroscopic technique  is an example of the material manipulation to improve stage by stage thoughtfully knowing what went on before. Thus the review would have educative value while revealing the lessons on scientific matter studied. NMR of the current days is aplenty with commercial spectrometers which have unimaginable features built in and produce high quality spectra automatically without the user having to know much about the settings. Essentially black-box approach to the use of the spectrometers makes possible strides in leaps and jumps in a wide variety of disciplines of study. On the other hand the early efforts have been more educative on the equipments and instrumentation aspects. The researchers themselves had a hand on laboratory exercise to make the equipment for what they have to research on. In this contrasting situation a review of the early days NMR instrumentation is provided in this article for the benefit of student community to find an occupation while innovating their learning methods. Descriptions in this article are oriented towards school and college standards so as  to inspire the readers to look for more on instrumental methods and grasp the recent advances quickly and confidently in these days of conveniently automated and much simplified ‘black-box’ approach to use of  instruments. An important point to mention is that the circuit diagrams given in this articles are the author’s original version of block diagrams or schemes similar to concept diagrams (pedagogically speaking) to introduce  newly certain topics. Hence the students should not expect to plug in working circuits to see the functions. Note carefully that no specific component value is given nor any model numbers to commercially available components – even the circuit elements are not copied ones but drawn by the author with MS WORD drawing tools

Magnetic Properties of Ni-Fe Nanowire Arrays: Effect of Template Material and Deposition Conditions

The objective of this work is to study the magnetic properties of arrays of Ni-Fe nanowires electrodeposited in different template materials such as porous silicon, polycarbonate and alumina. Magnetic properties were studied as a function of template material, applied magnetic field (parallel and perpendicular) during deposition, wire length, as well as magnetic field orientation during measurement. The results show that application of magnetic field during deposition strongly influences the c-axis preferred orientation growth of Ni-Fe nanowires. The samples with magnetic field perpendicular to template plane during deposition exhibits strong perpendicular anisotropy with greatly enhanced coercivity and squareness ratio, particularly in Ni-Fe nanowires deposited in polycarbonate templates. In case of polycarbonate template, as magnetic field during deposition increases, both coercivity and squareness ratio also increase. The wire length dependence was also measured for polycarbonate templates. As wire length increases, coercivity and squareness ratio decrease, but saturation field increases. Such magnetic behavior (dependence on template material, magnetic field, wire length) can be qualitatively explained by preferential growth phenomena, dipolar interactioComment: 26 pages, 7 figures, 5 Tables Submitted to Physical Review

Activation and degranulation of CAR-T cells using engineered antigen-presenting cell surfaces

Adoptive cell transfer of Chimeric Antigen Receptor (CAR)-T cells showed promising results in patients with B cell malignancies. However, the detailed mechanism of CAR-T cell interaction with the target tumor cells is still not well understood. This work provides a systematic method for analyzing the activation and degranulation of second-generation CAR-T cells utilizing antigen-presenting cell surfaces. Antigen-presenting cell surfaces composed of circular micropatterns of CAR-specific anti-idiotype antibodies have been developed to mimic the interaction of CAR-T cells with target tumor cells using micro-contact printing. The levels of activation and degranulation of fixed non-transduced T cells (NT), CD19.CAR-T cells, and GD2.CAR-T cells on the antigen-presenting cell surfaces were quantified and compared by measuring the intensity of the CD3ζ chain phosphorylation and the Lysosome-Associated Membrane Protein 1 (LAMP-1), respectively. The size and morphology of the cells were also measured. The intracellular Ca2+ flux of NT and CAR-T cells upon engagement with the antigen-presenting cell surface was reported. Results suggest that NT and CD19.CART cells have comparable activation levels, while NT have higher degranulation levels than CD19.CAR-T cells and GD2.CAR-T cells. The findings show that antigen-presenting cell surfaces allow a quantitative analysis of the molecules involved in synapse formation in different CAR-T cells in a systematic, reproducible manner

Reovirus-Induced Apoptosis in the Intestine Limits Establishment of Enteric Infection

Several viruses induce intestinal epithelial cell death during enteric infection. However, it is unclear whether proapoptotic capacity promotes or inhibits replication in this tissue. We infected mice with two reovirus strains that infect the intestine but differ in the capacity to alter immunological tolerance to new food antigen. Infection with reovirus strain T1L, which induces an inflammatory immune response to fed antigen, is prolonged in the intestine, whereas T3D-RV, which does not induce this response, is rapidly cleared from the intestine. Compared with T1L, T3D-RV infection triggered apoptosis of intestinal epithelial cells and subsequent sloughing of dead cells into the intestinal lumen. We conclude that the infection advantage of T1L derives from its capacity to subvert host restriction by epithelial cell apoptosis, providing a possible mechanism by which T1L enhances inflammatory signals during antigen feeding. Using a panel of T1L × T3D-RV reassortant viruses, we identified the viral M1 and M2 gene segments as determinants of reovirus-induced apoptosis in the intestine. Expression of the T1L M1 and M2 genes in a T3D-RV background was sufficient to limit epithelial cell apoptosis and enhance viral infection to levels displayed by T1L. These findings define additional reovirus gene segments required for enteric infection of mice and illuminate the antiviral effect of intestinal epithelial cell apoptosis in limiting enteric viral infection. Viral strain-specific differences in the capacity to infect the intestine may be useful in identifying viruses capable of ameliorating tolerance to fed antigen in autoimmune conditions like celiac disease

Developing a Standard Set of Patient-centred Outcomes for Adult Oral Health - An International, Cross-disciplinary Consensus.

OBJECTIVE: To develop a minimum Adult Oral Health Standard Set (AOHSS) for use in clinical practice, research, advocacy and population health. MATERIALS AND METHODS: An international oral health working group (OHWG) was established, of patient advocates, researchers, clinicians and public health experts to develop an AOHSS. PubMed was searched for oral health clinical and patient-reported measures and case-mix variables related to caries and periodontal disease. The selected patient-reported outcome measures focused on general oral health, and oral health-related quality of life tools. A consensus was reached via Delphi with parallel consultation of subject matter content experts. Finally, comments and input were elicited from oral health stakeholders globally, including patients/consumers. RESULTS: The literature search yielded 1,453 results. After inclusion/exclusion criteria, 959 abstracts generated potential outcomes and case-mix variables. Delphi rounds resulted in a consensus-based selection of 80 individual items capturing 31 outcome and case-mix concepts. Global reviews generated 347 responses from 87 countries, and the patient/consumer validation survey elicited 129 responses. This AOHSS includes 25 items directed towards patients (including demographics, the impact of their oral health on oral function, a record of pain and oral hygiene practices, and financial implications of care) and items for clinicians to complete, including medical history, a record of caries and periodontal disease activity, and types of dental treatment delivered. CONCLUSION: In conclusion, utilising a robust methodology, a standardised core set of oral health outcome measures for adults, with a particular emphasis on caries and periodontal disease, was developed

Vascular dysfunction in aged mice contributes to persistent lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease thought to result from impaired lung repair following injury and is strongly associated with aging. While vascular alterations have been associated with IPF previously, the contribution of lung vasculature during injury resolution and fibrosis is not well understood. To compare the role of endothelial cells (ECs) in resolving and non‐resolving models of lung fibrosis, we applied bleomycin intratracheally to young and aged mice. We found that injury in aged mice elicited capillary rarefaction, while injury in young mice resulted in increased capillary density. ECs from the lungs of injured aged mice relative to young mice demonstrated elevated pro‐fibrotic and reduced vascular homeostasis gene expression. Among the latter, Nos3 (encoding the enzyme endothelial nitric oxide synthase, eNOS) was transiently upregulated in lung ECs from young but not aged mice following injury. Young mice deficient in eNOS recapitulated the non‐resolving lung fibrosis observed in aged animals following injury, suggesting that eNOS directly participates in lung fibrosis resolution. Activation of the NO receptor soluble guanylate cyclase in human lung fibroblasts reduced TGFβ‐induced pro‐fibrotic gene and protein expression. Additionally, loss of eNOS in human lung ECs reduced the suppression of TGFβ‐induced lung fibroblast activation in 2D and 3D co‐cultures. Altogether, our results demonstrate that persistent lung fibrosis in aged mice is accompanied by capillary rarefaction, loss of EC identity, and impaired eNOS expression. Targeting vascular function may thus be critical to promote lung repair and fibrosis resolution in aging and IPF.Bleomycin‐induced lung injury promotes transient fibrosis accompanied by increased capillary density in young mice. In contrast, persistent fibrosis, capillary rarefaction, loss of endothelial cell identity, and reduction of Nos3 are observed in aged mice. eNOS/NO signal is an important driver of fibroblast quiescence and fibrosis resolution, that is lost with aging. Lung vascular bed plays a critical role during lung repair and fibrosis resolution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156458/2/acel13196_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156458/1/acel13196.pd

Phosphoregulation of the Titin-cap Protein Telethonin in Cardiac Myocytes

Telethonin (also known as titin-cap or t-cap) is a muscle-specific protein whose mutation is associated with cardiac and skeletal myopathies through unknown mechanisms. Our previous work identified cardiac telethonin as an interaction partner for the protein kinase D catalytic domain. In this study, kinase assays used in conjunction with MS and site-directed mutagenesis confirmed telethonin as a substrate for protein kinase D and Ca(2+)/calmodulin-dependent kinase II in vitro and identified Ser-157 and Ser-161 as the phosphorylation sites. Phosphate affinity electrophoresis and MS revealed endogenous telethonin to exist in a constitutively bis-phosphorylated form in isolated adult rat ventricular myocytes and in mouse and rat ventricular myocardium. Following heterologous expression in myocytes by adenoviral gene transfer, wild-type telethonin became bis-phosphorylated, whereas S157A/S161A telethonin remained non-phosphorylated. Nevertheless, both proteins localized predominantly to the sarcomeric Z-disc, where they partially replaced endogenous telethonin. Such partial replacement with S157A/S161A telethonin disrupted transverse tubule organization and prolonged the time to peak of the intracellular Ca(2+) transient and increased its variance. These data reveal, for the first time, that cardiac telethonin is constitutively bis-phosphorylated and suggest that such phosphorylation is critical for normal telethonin function, which may include maintenance of transverse tubule organization and intracellular Ca(2+) transients

Reovirus-Induced Apoptosis in the Intestine Limits Establishment of Enteric Infection

Several viruses induce intestinal epithelial cell death during enteric infection. However, it is unclear whether proapoptotic capacity promotes or inhibits replication in this tissue. We infected mice with two reovirus strains that infect the intestine but differ in the capacity to alter immunological tolerance to new food antigen. Infection with reovirus strain T1L, which induces an inflammatory immune response to fed antigen, is prolonged in the intestine, whereas T3D-RV, which does not induce this response, is rapidly cleared from the intestine. Compared with T1L, T3D-RV infection triggered apoptosis of intestinal epithelial cells and subsequent sloughing of dead cells into the intestinal lumen. We conclude that the infection advantage of T1L derives from its capacity to subvert host restriction by epithelial cell apoptosis, providing a possible mechanism by which T1L enhances inflammatory signals during antigen feeding. Using a panel of T1L × T3D-RV reassortant viruses, we identified the viral M1 and M2 gene segments as determinants of reovirus-induced apoptosis in the intestine. Expression of the T1L M1 and M2 genes in a T3D-RV background was sufficient to limit epithelial cell apoptosis and enhance viral infection to levels displayed by T1L. These findings define additional reovirus gene segments required for enteric infection of mice and illuminate the antiviral effect of intestinal epithelial cell apoptosis in limiting enteric viral infection. Viral strain-specific differences in the capacity to infect the intestine may be useful in identifying viruses capable of ameliorating tolerance to fed antigen in autoimmune conditions like celiac disease