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In the current study, we determined the effects of chronic alcohol consumption on the mortality of young and old mice and immune responses during Mycobacterium tuberculosis (Mtb) infection. Eighty percent of Mtb H37Rv infected alcohol-fed young mice died in five months compared to twenty-five percent in Mtb infected alcohol-fed old mice. There is no significant difference in lung bacterial burden of control and alcohol diet fed young and old mice. IFN-α levels were significantly higher in the lungs of Mtb infected alcohol-fed young mice and treatment with anti-IFNAR-1 antibody enhanced their survival. There are significantly higher numbers of CD11b+Ly6G+ neutrophils in the lungs of Mtb infected alcoholic young mice compared to Mtb infected alcohol-fed old mice and Mtb infected control diet-fed young mice. CD11b+Ly6G+ neutrophils are the major source of IFN-α in Mtb-infected alcohol-fed young mice and IFN-α enhanced the expression of RIP-1 and RIP-3 molecules, which are known to be involved in necroptosis. Alcohol-fed old Mtb infected mice and Mtb infected control diet-fed old and young mice expressed low level of IFN-α and RIP-1 and RIP-3 in their lungs. In response to Mtb stimulation, peripheral blood mononuclear cells (PBMC) from young healthy alcoholic individuals with latent tuberculosis infection (LTBI) produced significantly higher amounts of IFN-α compared to non-alcoholic young, alcoholic and non-alcoholic old healthy LTBI+ individuals. Our findings demonstrate that in Mtb infected young mice, alcohol enhances CD11b+Ly6G+ neutrophil infiltration in lungs and excess IFN-α production by neutrophils causes lung macrophage necroptosis and enhanced mortality.

Resonant excitation of terahertz (THz) radiation by non-linear mixing of two lasers in the presence of an electrostatic wave is investigated. The electrostatic wave assists in k matching and contributes to non-linear coupling. In this plasma channel, the electron plasma frequency becomes minimum on the axis. The beat frequency ponderomotive force imparts an oscillating velocity to the electrons. In the presence of an ion-acoustic wave, density perturbation due to the ion-acoustic wave couples with the oscillating velocity of the electrons and give rise to non-linear current that gives rise to an ion-acoustic wave frequency assisted THz radiation field. The normalized field amplitude of ion acoustic wave assisted THz varies inversely for ω/ωp. The field amplitude of ion acoustic wave assisted THz decreases as ω/ωp increases.

Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth.

Objective: Inflammatory back pain (IBP) in Ankylosing Spondylitis (AS) and Undifferentiated Spondyloarthritis (UspA) adversely affects the quality of life. Herein combination DMARD vs. sulfasalazine (SSZ) monotherapy was evaluated in treatment of axial symptoms of AS and UspA. Methods: Patients with AS/UspA with disease duration ≤ 8 years, IBP of atleast 6 months duration, and BASDAI ≥ 4 or early morning stiffness ≥ 1 hour despite NSAID therapy for 6 weeks were included. Patients were initiated on SSZ with either combination DMARD [MTX (10 mg escalated by 2.5 mg every week up to 20 mg/week) and HCQS 200 mg/day] or SSZ Monotherapy group [placebo MTX and placebo HCQS]. ASAS20 response was assessed at baseline and at the end of 6 months. Results: Of thirty three patients (31 males) with mean disease duration 39 months and mean BASDAI of 6 at baseline, 27 completed the study (16 in Combination DMARD and 11 in SSZ monotherapy group). ASAS 20 response, was achieved in 68.4% (13/19) and 50% (7/14) in the Combination DMARD and SSZ monotherapy groups (p=0.47), respectively. BASDAI scores decreased significantly in both the groups after therapy. A significant improvement in BASFI, patient pain VAS, patient global disease VAS, HAQ, and MCS of SF-36 was observed in both the groups. In the combination DMARD group, significant improvement in BASMI, FACIT and PCS of SF-36 and decrease in the serum MMP-3 levels was observed following therapy. Conclusion: SSZ monotherapy is equally efficacious as combination DMARD group in a significant proportion of patients with NSAID refractory IBP associated with AS/ USpA.

Total Quality Management (TQM) and Total Productive Maintenance (TPM) have gained considerable acceptance in Indian manufacturing industry to take on the challenge of transition from protected economy to global competition. These two improvement drives are being adopted and adapted for raising performance standards of Indian companies to world class level. TQM and TPM are considered complementary to each other and thereby being implemented simultaneously by many companies to achieve synergy. This paper aims to provide empirical evidences on the comparative contributions of two drives to improve business performance in the context of Indian manufacturing industry. It also tries to establish a synergetic effect of TQM and TPM, when implemented in tandem. The paper highlights that a combined application brings out significantly higher improvements than individual drives. The study is based on data collected through a questionnaire as a research instrument and statistical analysis using Microsoft EXC...

Purpose – To study the strategic implications of TQM and TPM in an Indian manufacturing set‐up and to detail literature reviews to highlight gap areas. To examine the relationship between factors influencing the implementation of TQM and TPM and business performance for the following three approaches in an Indian context: TQM alone; TPM alone; both TQM and TPM together. This is done to extract significant factors for the above three approaches.Design/methodology/approach – Empirical survey‐based research on a sample size of 108 manufacturing companies. Uses bivariate correlation and multiple regression analysis techniques to extract significant factors using SPSS.Findings – The research identifies two sets of factors which are critical for the effectiveness of TQM and TPM: universally significant factors for all the three approaches like leadership, process management and strategic planning; and approach‐specific factors like equipment management and focus on customer satisfaction. The study also highligh...

PurposeTo examine the impact of experience in terms of time period on TQM's effectiveness in improving performance of Indian manufacturing companies. To establish the impact of TPM support on TQM's effectiveness.Design/methodology/approachThis is an empirical research with testing of hypotheses using t tests. The data are collected with the help of a questionnaire on six performance parameters, which are measured on a five‐point scale. The study considers three time periods (phases) of implementation and two improvement strategies, i.e. TQM alone and TQM supported by TPM (combined strategy), for the purpose of analysis. The analysis is based on valid responses from 111 manufacturing companies.FindingsThe performance improvements contributed by TQM in the transition phase have been marginal due to initial investments and efforts required as well as to country‐specific factors. The effectiveness of TQM in the stability and maturity phases is established in an Indian context. The synergetic effect of TPM support on TQM's performance is also established in an Indian context.Practical implicationsThe paper establishes the long‐term effects of TQM on companies' performance in an Indian context. It also highlights various country‐specific factors, which led to marginal improvement during the transition phase. The paper also establishes that TQM with TPM support can be an effective strategy to improve competitiveness of Indian manufacturing companies.Originality/valueThis paper studies the two important factors which influence TQM's effectiveness. Although the study has been carried out in an Indian context, it is equally significant in a global scenario. This paper addresses a pertinent issue of simultaneous implementation of TQM and TPM, which is commonly found in industry but not adequately researched.

Background: Diabetes mellitus and Metabolic syndrome, both are established risk factors for CAD. In our study, we tried to compare the effects of these two diseases individually as well as their combined effect.Methods: we performed an Observational, cross-sectional, hospital-based, single center study on 240 patients presenting at our hospital with chest pain. we assessed the severity of CAD with Syntax score and divided the study population into three groups with SS of =33.Results: statistically significant difference was found in each of the first three groups of combined MS plus DM, only MS without DM, only DM without MS when compared with the fourth group of nondiabetics nonmetabolic syndrome patients. Strongest difference was found between patients with combined diabetes and metabolic syndrome with those who had none of these (

Background: Reperfusion therapy of affected myocardium is among the most successful method for infarct size reduction and achieving the better outcome in patients with ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (pPCI) is among best procedures for successful reperfusion therapy which has effect in reduction of size of infarct, maintaining ventricular function for better outcome. In this study, authors were aimed to assess whether remote ischemic post-conditioning (RIPC) of lower limb could reduce enzymatic infarct size in patients with acute STEMI undergoing pPCI. Methods: A case control, cross sectional, hospital based randomized study was carried out in Institute of Cardiovascular Sciences, IPGMER, Kolkata, from February 2014 to October 2015. Total 40 patients (20 cases and 20 controls) who were undergoing primary PCI for acute myocardial infarction were taken for study. In the active treatment group, the protocol was started with thrombectomy. The lower limb was exposed to 3 cycles of ischemia/reperfusion, each obtained by 5 min cuff inflation at 200mmHg, followed by 5 min complete deflation. End point of the study will be enzymatic infarct size assessed by the area under the curve of creatine kinase-myocardial band (CK-MB) release. Results: The AUC of serum CK release during the first 72 hours of reperfusion was significantly reduced (p=0.0341) in the post-conditioned group compared with the control group, averaging 9632 units in postconditioned compared with 13493 units in control group which represented 26% of reduction of infarct size. Conclusions: Remote ischemic post conditioning of lower limb significantly improves blush grading and enzymatic infarct size reduction with a trend towards significant reduction of mean ST segment deviation.

Background: The role of uric acid as a risk factor in cases of acute ischaemic stroke is controversial. The present study was conducted with the aim to study the clinical profile and the incidence of stroke in patients with normal and elevated uric acid and its correlation with other risk factors.Methods: This study was conducted in 100 patients with acute ischaemic stroke who were admitted in NSCB Hospital Jabalpur from August 2009 to July 2010.Clinical records of patients and their serum uric acid level was investigated. The severity of neurological deficit was recorded according to the scandinavian stroke scale (SSS). Patients were followed up during hospital stay and outcome was graded by using modified Rankin’s scale (mRS). Finally, collected data were analyzed using Chi square and student t test wherever appropriate. P value 0.05). Significant, positive correlation p0.05). Majority (83%) of patients were having infarct in MCA artery territory. Majority of patients 20 (69%) with elevated serum uric acid were having SSS score >30. Statistically insignificant (p>0.05) association was observed between mean mRS score in patients with normal serum uric acid Vs patients with hyperuricemia.Conclusions: The prevalence of hyperuricemia in acute ischaemic stroke patients was lower than in normal population. Age, hypertension and alcoholism amongst males showed statistically significant positive correlation with hyperuricemia in patient with acute ischaemic stroke and hence they are considered to be the significant risk factors.

Background: Insulin resistance is the essential defect in the development of type 2 diabetes mellitus, hypertension and cardiovascular diseases. The aim of the present study was to evaluate the correlation between insulin resistance, metabolic syndrome and their associated factors in hypertensive patients.Methods: This comparative study was conducted on 100 patients who attended to the Department of Medicine, NSCB Medical College, Jabalpur, Madhya Pradesh, India. 50 patients of both sexes having essential hypertension were participated in the study and considered as hypertensive group. Other healthy 50 patients of similar sex and age group were studied as control group (normotensive) for comparison. Insulin resistance was estimated by using homeostasis model assessment (HOMA-IR) method.Results: Mean age of the patients of hypertensive group was 49.79±17.04 years and mean age of normotensive group was 51.94±16.64 years. Male preponderance was observed in both the groups. Out of 50 from each group, 19 (38%) of hypertensive patients and 7 (14%) of normotensive patients had insulin resistance. Metabolic syndrome was noted in 23 (46%) and 10 (20%) cases of hypertensive and normotensive groups respectively and this difference was found to be statistically significant (p=0.01). The mean fasting and post prandial blood sugar levels were almost similar in both groups (p=0.03). Mean total cholesterol levels were significantly lower in hypertensive groups than that of normotensive group (p=0.03). The mean serum insulin levels were high in hypertensive groups than that of normotensive group which was statistically significant (p=0.00). Mean HOMA-IR, waist size and waist hip ratio (WHR) was significantly (p=0.02) higher in hypertensive group than that of control group.Conclusions: The results of the present study support the strong correlation between insulin resistance and essential hypertension and also confirmed that insulin resistance was the major risk factor of metabolic syndrome.

Background: Rheumatic heart disease remains a considerable cause of cardiovascular morbidity and mortality in developing countries such as India. The aim of the present study was to compare ventricular (LV and RV) function in patients with severe mitral stenosis (MS) undergoing balloon mitral Valvuloplasty (BMV) with those on medical management and also with healthy controls and to assess the burden of ventricular (LV and RV) systolic dysfunction, its determinants, and its reversibility with percutaneous balloon mitral Valvuloplasty using speckle tracking echocardiography in patients with severe MS.Methods: This prospective study was performed in a tertiary care center, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow in patients with severe MS, from September 2014 to September 2015. A total of 60 were divided into three groups. Cases (n=30), patients with severe MS undergoing BMV; case controls (n=20), patients with severe MS who did not give consent for BMV and chose medical management and healthy controls (n=10). Cases who underwent BMV were analyzed pre and post BMV and detailed echocardiographic and speckle-tracking echocardiography (STE) was done at baseline, 24-48 hours after BMV and at post one month after BMV. Appropriate statistical analysis was applied and different parameters were compared.Results: Most of the cases (56.7%) control (65%) and healthy controls (40%) were between 21-30 years of age. Female preponderance was observed in the study. A significant (p=0.01) decrease in the LA size, PASP (p=0.0001), MV PG area (p=0.0001) and significant (p=0.0001) increase in the LVEF, MVA area was observed from baseline to post 24-48 hours and at post one month after BMV among cases. Significant improvement was noticed in longitudinal strain and regional rotation in different LV segments as assessed by STE at post 24-48 hours and post one month after BMV (p value 0.001) among cases. No significant (p>0.05) difference in the 2D echo parameters was seen from baseline to follow-ups among the case controls. No significant improvement was observed in regional rotation, global rotation in different LV and RV segments after one month as assessed by STE among case controls whereas significant improvement was seen in cases.Conclusions: BMV results in marked improvement in LV and RV GLS immediately post BMV with improvement towards normalization at follow up after one month and the same can be easily assessed by Speckle tracking echocardiography.

CD4+CD25+FoxP3+ cells (Tregs) inhibit inflammatory immune responses to allografts. Here we found that co-transplantation of allogeneic pancreatic islets with Tregs that are defective in JNK1 signaling prolong the islet allograft survival in the liver parenchyma of the T1D mice. Deletion of the JNK1 in Tregs increased the expression of anti-apoptotic molecules Mcl-1, Bcl-Xl and anti-inflammatory cytokine IL-10 production. JNK1−/− Tregs persist for long period in the transplanted liver and prolong the islet allograft survival compared to WT Tregs. JNK1−/− Tregs demonstrated improved control of allo-inflammation compared to WT Tregs in the T1D liver upon co-transplantation. JNK1−/− Tregs specifically inhibit IL-17 and IL-21 medited alloimmune response. Inhibition of alloimmune response by JNK1−/− Tregs independently mediated through the LAG3 on its cell surface and the increased production of IL-10. Our study identifies a novel role of JNK1 signaling in the Tregs function and co-transplantation of JNK1 deficient Tregs enhances the islet allograft survival in the liver parenchyma of T1D mice.

A laser produced plasma, and an electrostatic wave, helps to generate a strong harmonic radiation. The electrostatic wave assists k matching and contributes to non-linear coupling. In the case of the Bernstein wave assisted second harmonic, the frequency of the second harmonic is shifted from the laser second harmonic by electron cyclotron frequency. The lower hybrid wave (LHW) assisted second harmonic has frequency slightly shifted from the laser second harmonic. The upper hybrid wave (UHW) assisted second harmonic has frequency shifted by an amount ω that lies between max( ω c , ω p) and ω U H. At a 0 = 0.1 and n ω , k → / n 0 0 = 0.1, the normalized amplitude value the of electrostatic wave assisted second harmonic is quite high near the upper hybrid resonance. The effect of increasing ω c / ω p increases the max value of normalized amplitude.

The past few decades have witnessed dramatic changes and advances in diagnostic imaging. In the field of arthritis, these changes have contributed to enhance the diagnostic accuracy and to conduct serial monitoring of synovial inflammation without synovial biopsy. Advanced imaging techniques employ target-specific probes to non-invasively assess molecular, cellular, and physiological abnormalities associated with the underlying pathology. Dynamic and diffusion magnetic resonance imaging (MRI) are being developed to evaluate the discrete aspects of specific inflammatory and destructive pathways of inflammatory arthritis. These newer imaging modalities provide an earlier and more reliable assessment of clinical outcome, disease activity, severity, location, and therapeutic response. These techniques will be incorporated soon in routine clinical practice, and their adoption may enable clinicians to measure the treatment response and tailor the therapeutic interventions accordingly. In this review, we have attempted to summarize the emerging non-invasive imaging techniques and their application in quantifying synovial inflammation.

In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice., Author Summary In the current study, we employed an experimentally induced type 2 diabetes mellitus (T2DM) model in wild type C57BL/6 mice and investigated the immune response to Mycobacterium tuberculosis (Mtb) infection. We found that natural killer (NK) and CD11c+ cell interactions in Mtb-infected T2DM mice led to increased IL-6 production, which drives the pathological immune response and reduces survival of Mtb-infected T2DM mice. We also found that IL-6 increases inflammatory cytokine production in pulmonary tuberculosis patients with T2DM. The NK-CD11c+ axis and the IL-6 pathway may be promising new targets for host-directed therapies aimed at reducing the severity of immune pathology, which drives morbidity and mortality in those infected by tuberculosis (TB).The study demonstrates for the first time that NK-CD11c+ cell interactions increase IL-6-mediated inflammation and reduce survival in T2DM mice infected with Mtb. The NK-CD11c+ cell axis appears to be a promising new target for reducing inflammation and mortality in tuberculosis patients with type 2 diabetes.

The process of Bernstein wave aided resonant third harmonic generation of laser in a magnetized plasma is investigated. The extra-ordinary mode (X-mode) laser of frequency ω0 and wave number k→0, travelling across the magnetic field in a plasma, exerts a second harmonic ponderomotive force on the electrons imparting them an oscillatory velocity v→2ω0,2k→0. This velocity beats with the density perturbation due to the Bernstein wave to produce a density perturbation at cyclotron frequency shifted second harmonic. The density perturbation couples with the oscillatory velocity v→ω0,k→0 of X-mode of the laser to produce the cyclotron frequency shifted third harmonic current density leading to harmonic radiation. The phase matching condition for the up shifted frequency is satisfied when the Bernstein wave is nearly counter-propagating to the laser. As the transverse wave number of the Bernstein wave is large, it is effective in the phase matched third harmonic generation, when the laser frequency is not too fa...

Tubercular liver abscess is a rare extrapulmonary manifestation of tuberculosis. We are presenting a case of isolated tubercular liver abscess in a 70 year old diabetic male without any evidence of tuberculosis in the lungs or abdomen. Diagnosis was made on the basis of radiological findings along with PCR for Mycobacterium tuberculosis in pus aspirated from abscess under CT guidance. Systemic antitubercular drugs were given for 6 months. On follow up patient improved clinically with radiological evidence of resolution of abscess.

A new series of 1,3-biarylsulfanyl derivatives (homodibenzyl core motif) have been designed and synthesized as new estrogen receptor ligands by chopping benzothiophene core of raloxifene to engender seco-raloxifene scaffold. All the synthesized compounds were screened for anti-proliferative, anti-osteoporotic, and anti-implantation activity. Compounds (35, 36) having basic amino anti-estrogenic side chain were exhibiting potential anti-proliferative activity in MCF-7, MDA-MB-231 and ishikawa cell lines. Some of the synthesized compounds having homodibenzyl motif (5, 8, 10) have shown moderate anti-osteoporotic activity.

A mild, efficient, and green method with a reusable catalyst for the synthesis of the biologically active natural compounds (III) is developed.

Arylethanones of type (I) and (IV) are applied as Julia coupling partners for the reaction with aromatic aldehydes to give chalcones and flavanones, correspondingly.

Large scale firms have been adopting various management practices to remain competitive in today’s global economy. Lean manufacturing is one such initiative, which significantly improves performance in terms of cost, delivery, quality and flexibility. Although small and medium enterprises (SMEs) play a very significant role in overall manufacturing supply network, less is known about the extent to which lean is present in these firms. The present study investigates this issue by exploring the scenario of implementation of lean manufacturing in Indian SMEs. It also examines the constraints, which need to be addressed for real penetration of lean on a wider scale and the role information and communication technologies like pervasive computing play in successful implementation of this initiative. This aspect is considered important as no organization, whether big or small, can afford to neglect it in today’s business environment. The study reveals that although lean manufacturing is not implemented as a formal management initiative in SMEs, its elements could be traced with varying degrees in firms. However, a need is felt to improve upon various identified constraints, so that SMEs are able to implement it as formal system and reap maximum benefits. It is also experienced that IT solutions like pervasive computing help in improving lean manufacturing performance but Indian SMEs in general have not taken considerable initiatives in this direction.

In the current study we asked whether modified CD4+CD25+FoxP3+ regulatory T-cells (T-regs) can induce long term allograft tolerance. Pancreatic islets from BALB/c mice survived in a type 1 diabetic C57BL/6 mice (recipient mice) liver up to 18-21 days (n=5). Preloading islets with T-regs from WT (wild type) C57BL/6 mice, enhanced survival up to 37 days (N=5 and p = 0.003). Further preloading islets with T-regs from JNK1-/- mice (C57BL/6 background) enhanced survival up to 107 days (N=5 and p = 0.002). In contrast preloading islets with T-regs from FAS-/- (C57BL/6 background) did not enhance islet survival beyond 45 days. T-cell receptor stimulation of T-regs from JNK1-/- mice produced significant high amount of IL-10 (14.67 ± 2.784 vs 3.803 ± 0.8325, p = 0.009) and TGF-β (27.93 ± 7.563 vs 9.920 ± 1.212, p = 0.05) compared to T-regs from WT mice. Preloading islets with T-regs from JNK1-/- mice reduced IL-1β (30.91 ± 2.41 vs 16.13 ± 2.76; p = 0.003), TNF-α (3.802 ± 0.69 vs 1.888 ± 0.26; p = 0.03) IL-17 (24.82 ± 4.07 vs 4.708 ± 1.57; p = 0.0017). Studies are underway to determine the JNK1-/-T-regs mediated mechanisms involved in prolongation of allograft survival.

IL-21 is a Th17 cytokine and is known for its anti-tumor and anti-viral effects. In the current study using IL-21receptor (IL-21r-/-) and IL-21 knockout (IL-21-/-) mice, we determined the role of IL-21 and IL-21r in Mycobacterium tuberculosis (M. tb) infection. Around 50% of M. tb H37Rv infected IL-21r-/- mice died in six months compared to no deaths in infected control mice. M. tb infected IL-21r-/- mice have enhanced bacterial burden (7.3 ± 1.0 x 106 vs. 0.7 ± 0.08 x 106,p

In this study, to determine whether diabetic (DM) mice are susceptible to Mycobacterium tuberculosis (Mtb) infection, we developed experimentally induced diabetes in wild type C57BL/6 mice with streptozotocin & nicotinamide. We then infected non-DM and DM mice with Mtb H37Rv by aerosol. Around 50% of Mtb infected DM (p=0.05) and 25% of uninfected DM (p=0.07) mice died in 5 to 6 months compared to no deaths in infected control mice. Six months after Mtb infection, there was a statistically significant but marginal increase in bacterial burden in the lungs of Mtb infected DM mice compared to non-DM infected mice (3.1 ± 0.4 x106 vs 0.9 ± 0.1 x 106, p=0.001) suggesting increased mortality was not due to increased bacterial burden. Real time PCR analysis of Mtb infected DM lungs indicated significantly increased pro- and anti-inflammatory cytokine gene expression compared to uninfected DM and infected control mice, including increased levels of IL-6 mRNA. Anti-IL-6 antibody treatment of Mtb infected DM mice enhanced the survival (100% vs 60% survival in isotype control antibody treated, p=0.02) and reduced pro- and anti-inflammatory cytokine production. Dendritic cells (DC), but not other immune cells were the major source for IL-6 in Mtb infected DM mice. NK cells of Mtb infected DM mice further enhanced IL-6 production by autologous DCs. Our results suggest NK-DC interaction enhance IL-6 production which drives the immune pathology and mortality of Mtb infected diabetic mice

We determined the role of liver NK1.1 cells in allograft survival. Pancreatic islets from BALB/c mice survived in a type 1 diabetic C57BL/6 mice liver up to 15-21 days (n=5, p=0.001). Anti NK1.1 but not isotype control antibody treatment of type 1 diabetic C57BL/6 mice before and after pancreatic islet transfer rejected graft within 3 days (n=5, p=0.001). Anti-NK1.1 antibody treatment enhanced IL-1β (45.13 ± 5.9 vs 94.25 ± 5.5; p = 0.0003), TNF-α (4.746 ± 2.4 vs 11.92 ± 1.8; p = 0.047) and IFN-γ (2.714 ± 0.45 vs 4.344 ± 0.4; p = 0.036) and inhibited IL-22 (24.82 ± 4.07 vs 11.01 ± 2.186; p = 0.01) gene expression by liver lymphocytes of recipient mice. NK1.1 cells are major source of IL-22 in islets recipient mice liver and anti-IL-22 antibody treatment of recipient mice reduced allograft survival to 6-9 days compared to 18-21 days in isotype control antibody treated mice. Recombinant IL-22 but not IFN-γ enhanced insulin production by pancreatic islets of BALB/c mice (102.0 ± 22.65 vs 33.41 ± 12.07; p = 0.03) and enhanced expression of genes Reg2, Reg3a and Reg3g involved in islet survival. Further studies indicated that immunization and challenge of type 1 diabetic C57BL/6 mice with TLR9 agonist can enhance IL-22 production by NK1.1 cells and prolongs pancreatic allograft survival from 15 days to 45 days. The sum of our studies suggests that IL-22 produced by liver NK1.1 cells enhance allograft survival and TLR9 agonist can be used to prolong pancreatic allograft survival.

In this study, we found that a subpopulation of CD4+CD25+ (85% Foxp3+) cells from persons with latent tuberculosis infection (LTBI) inhibits growth of M. tuberculosis (M. tb) in human monocyte-derived macrophages (MDMs). A soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic CD4+CD25+ (85% Foxp3+) cells is responsible for this inhibition of M. tb growth in human macrophages and in mice. M. tb-expanded CD4+CD25+Foxp3+D4GDI+ cells do not produce IL-10, TGF-β and IFN-γ. D4GDI inhibited growth of M. tb in MDMs by enhancing production of IL-1β, TNF-α and ROS, and by increasing apoptosis of M. tb-infected MDMs. D4GDI was concentrated at the site of disease in tuberculosis patients, with higher levels detected in pleural fluid than in serum. However, in response to M. tb, PBMC from tuberculosis patients produced less D4GDI than PBMC from persons with LTBI. M. tb-expanded CD4+CD25+ (85% Foxp3+) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen. Our study provides the first evidence that a subpopulation of CD4+CD25+ (85% Foxp3+) cells enhances immunity to M. tb, and that production of D4GDI by this subpopulation inhibits M. tb growth., Author Summary Most people who are infected with Mycobacterium tuberculosis (M. tb) have latent tuberculosis infection (LTBI) with protective immunity. Patients with active tuberculosis have severe disease and ineffective immunity. Understanding how LTBI individuals control infection without developing disease provides important insight into the mechanisms of protective immunity against tuberculosis, and this information is essential for development of an effective vaccine. It is known that a lymphocyte population called T-cells contributes significantly to protective immunity against tuberculosis infection. In the current study, using human and murine models of M. tb infection, we found that a soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by a subpopulation of T-cells (CD4+CD25+Foxp3+) inhibits M. tb growth. We also found that D4GDI induces M. tb genes that are expressed during the non-replicative state. Our results suggest that D4GDI has a previously undescribed positive effect on immunity by enhancing host antimicrobial activity. These findings also may aid in understanding the factors that induce LTBI. Further, this information will facilitate development of improved vaccines and immunotherapeutic strategies to prevent and treat tuberculosis, respectively.

A relativistic electron beam propagating through a dielectric lined waveguide, with ripple on the dielectric surface, excites a free electron laser type instability where ripple acts as a wiggler. The spatial modulation of permittivity in the ripple region couples a terahertz radiation mode to a driven mode of lower phase velocity, where the beam is in Cerenkov resonance with the slow mode. Both the modes grow at the expanse of beam energy. The terahertz frequency increases as the beam velocity increases. The growth rate of the instability goes as one third power of beam density.

A novel and facile approach is developed to synthesize a magnetic nanoparticle (iron oxide)-doped carbogenic nanocomposite (IO-CNC) for magnetic resonance (MR)/fluorescence imaging applications. IO-CNC is synthesized by thermal decomposition of organic precursors in the presence of Fe(3) O(4) nanoparticles with an average size of 6 nm. IO-CNC shows wavelength-tunable fluorescence properties with high quantum yield. Magnetic studies confirm the superparamagnetic nature of IO-CNC at room temperature. IO-CNC shows MR contrast behavior by affecting the proton relaxation phenomena. The measured longitudinal (r(1) ) and transverse (r(2) ) relaxivity values are 4.52 and 34.75 mM(-1) s(-1) , respectively. No apparent cytotoxicity is observed and the nanocomposite shows a biocompatible nature. In vivo MR studies show both T(1) and T(2) * contrast behavior of the nanocomposite. Fluorescence imaging indicates selective uptake of IO-CNC by macrophages in spleen.

An efficient new multicomponent protocol for the C-3 functionalization of indoles with dihydrocoumarin has been developed using an artificial sweetener (saccharin)-based functional ionic liquid (imidazolium saccharinate). The reaction consists of the Knoevenagel coupling of salicylaldehyde and Meldrum's acid followed by a Michael type reaction with indole, resulting in concomitant lactonization via decarboxylative elimination to yield indole-3-dihydro-coumarins in good to excellent yields at room temperature.

Laser beat wave excitation of terahertz radiation in a rippled density clustered plasma, in the presence of an azimuthal magnetic field, is investigated. The lasers exert a beat ponderomotive force on cluster electrons, imparting them an oscillatory velocity with a significant transverse component due to the azimuthal magnetic field. The oscillatory velocity beats with the cluster density ripple and produces a nonlinear current, driving terahertz radiation. The terahertz field turns out to have ring shaped distribution. Its amplitude is enhanced by the cluster plasma resonance when 4π3nc0rc03ne/(ω2-ωpe2/3)>n0/ω2.

The energy transfer between two crossed lasers (a high frequency high amplitude pump and a low frequency low amplitude probe beam) through the coupling with a difference frequency electrostatic mode/quasimode in a plasma is examined. The electrostatic mode in an unmagnetized plasma is a linearly damped acoustic mode, while in a magnetized plasma it is also taken to be a lower hybrid mode. It is driven by the ponderomotive force due to the pump and probe beams. The electron density perturbation associated with the electrostatic mode beats with the oscillatory velocities due to the lasers to produce nonlinear current densities facilitating the energy transfer from the high frequency laser to the probe beam. Efficient energy transfer occurs when the phase matching conditions are satisfied. Even when a finite mismatch between the lasers and the low frequency mode/quasimode exists, a significant energy transfer is possible. The theoretical results for the unmagnetized plasma are in compliance with the published experimental results. In a magnetized plasma lower hybrid wave appears to be a potential contender for facilitating energy exchange between lasers.

A model of relaxing ponderomotive nonlinearity is developed to study the nonstationary self-focusing of a Gaussian laser pulse in a plasma. The ponderomotive force acts on the electrons instantaneously but the plasma density redistribution via the process of ambipolar diffusion is taken to evolve on the time scale τR≅r0/cs, where r0 is the laser spot size and cs is the sound speed. The paraxial ray approximation is used to solve the wave equation. The focusing is stronger at the rear of the pulse than at the front, causing considerable distortion of the pulse when pulse duration is comparable to nonlinearity relaxation time. The saturation effect of nonlinearity leads to focusing of any portion of the pulse to a minimum spot size r0fmin at an optimum distance zop and then the spot size increases. fmin and zop depend on the intensity of the portion of the pulse.

The nonlinear interaction of amplitude-modulated two-dimensional and three-dimensional laser beams with a cylindrical plasma column and the generation of terahertz (THz) radiation are studied. The plasma column could be formed by a cylindrically symmetric laser pre-pulse impinging on a gas jet target. A two-dimensional Gaussian laser beam propagating through the plasma exerts a ponderomotive force on electrons, imparting on them a resonant transverse velocity at the modulation frequency, Ω, when , where ωp is the plasma frequency of the column. The current produces THz radiation. In the case of a cylindrically symmetric Gaussian laser beam, the electron response to ponderomotive force misses the resonance, yet the phase matching introduced by a density ripple could efficiently produce THz radiation. The power conversion efficiency of the order of the ratio of THz radiation frequency to laser frequency can be achieved at a laser intensity of ≈1015 W cm−2 at 1 μm wavelength.