Engineered islet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes

Pathak, Shiva,Regmi, Shobha,Gupta, Biki,Pham, Tung Thanh,Yong, Chul Soon,Kim, Jong Oh,Yook, Simmyung,Kim, Jae-Ryong,Park, Min Hui,Bae, Young Kyung,Jeong, Jee-Heon Federation of American Societies for Experimental 2017 The FASEB Journal Vol. No.

<P>An alternative route for pancreatic islet transplantation is the subcutaneous space; however, inadequate vascularization in the subcutaneous space limits the availability of oxygen and nutrients to the subcutaneously transplanted islets, which leads to the development of a necrotic core in the islets, thereby causing islet dysfunction. Thus, we aimed to prevent the early apoptosis of pancreatic islets after transplantation into subcutaneous space by preparing islet clusters of appropriate size. We prepared fully functional islet cell clusters (ICCs) by using the hanging-drop technique. We optimized the size of ICCs on the basis of viability and functionality after culture in an hypoxic environment. We transplanted ICCs into the subcutaneous space of diabetic mice and evaluated the viability of the islets at the transplantation site. In an hypoxic environment, ICCs exhibited improved viability and functionality compared with control islets. ICCs, upon transplantation into the hypoxic subcutaneous space of diabetic mice, showed better glycemic control compared with control islets. Live/dead imaging of the islets after retrieval fromthe transplanted area revealed significantly reduced apoptosis in ICCs. Transplantation of ICCsmay be an attractive strategy to prevent islet cell apoptosis that results from nonimmune-mediated physiologic stress at the transplantation site.-Pathak, S., Regmi, S., Gupta, B., Pham, T. T., Yong, C. S., Kim, J. O., Yook, S., Kim, J.-R., Park, M. H., Bae, Y. K., Jeong, J.-H. Engineeredislet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes.</P>

Feasibility of Bioleaching in Removing Metals (Al, Ni, V and Mo) from as Received Raw Petroleum Spent Refinery Catalyst: A Comparative Study on Leaching Yields, Risk Assessment Code and Reduced Partition Index

Pathak, Ashish,Srichandan, Haragobinda,Kim, Dong-Jin JAPAN INSTITUTE OF METALS 2015 MATERIALS TRANSACTIONS Vol.56 No.8

Fractionation Behavior of Metals (Al, Ni, V, and Mo) During Bioleaching and Chemical Leaching of Spent Petroleum Refinery Catalyst

Pathak, Ashish,Srichandan, Haragobinda,Kim, Dong-Jin Springer-Verlag 2014 Water, Air and Soil Pollution Vol.225 No.3

Fast Layout Generation of RF Embedded Passive Circuits Using Mathematical Programming

Pathak, M.,Sung Kyu Lim IEEE 2012 IEEE transactions on components, packaging, and ma Vol.2 No.1

<P>In this paper, we present a methodology for the automatic generation of layout for radio frequency (RF) designs using embedded passives. Our methodology is divided into three steps: 1) pre-layout optimization; 2) placement and routing; and 3) post-layout optimization. We show that our methodology generates layouts with small area and good performance response within a fraction of design time compared with fully manual design effort. We make use of circuit models to represent and optimize the physical layout of the resistance-inductance-capacitance (RLC) components as well as the entire RF circuit that uses them. We perform non-linear mathematical programming-based optimization at various stages of the methodology to achieve high quality layouts. Full wave electromagnetic simulations are kept completely out of the design loop, so our methodology significantly reduces design time. We have used our methodology to successfully generate layouts for large-scale filter circuits.</P>

Narrowband ultraviolet B emission from gadolinium activated Y₃Ga₅O₁₂ nano-garnets

Pathak, M.S.,Singh, N.,Singh, Vijay,Watanabe, S.,Rao, T.K.Gundu,Lee, Jung-Kul Elsevier 2018 Materials research bulletin Vol.97 No.-

<P><B>Abstract</B></P> <P>Gadolinium (Gd<SUP>3+</SUP>) doped Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB> nanocrystalline garnet was prepared by nitrate-fuel combustion technique that involves organic fuel glycine. Sample characterization was performed by powder X-ray diffraction and scanning electron microscope. Upon ultraviolet light excitation at 273nm, Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB>:Gd<SUP>3+</SUP> sample exhibits a sharp narrowband ultraviolet B emission at 311.9nm. The electron spin resonance spectrum of gadolinium doped Y<SUB>3</SUB>Ga<SUB>5</SUB>O<SUB>12</SUB> samples exhibit resonance signals with the effective g values at <I>g</I> ≈2.0, 2.2 and 5.8. These signals are attributed to Gd<SUP>3+</SUP> ion located in distorted surroundings experiencing a relatively strong crystal field.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A narrowband ultraviolet B emitting nano-garnet was synthesized. </LI> <LI> Narrow band centered at 311.9nm, good for phototherapy application. </LI> <LI> EPR results indicate the possible location of the Gd<SUP>3+</SUP> ion. </LI> <LI> Gd<SUP>3+</SUP> ion is likely to be located at the distorted dodecahedral site. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Delivery of Pancreatic Islets and Single Dose Local Immune Suppression Into Subcutaneous Space Using Injectable Hydrogel Provides Indefinite Survival of the Graft in Mouse Model of Diabetes

Pathak, Shiva,Regmi, Shobha,Pham, Tung Thanh,Yong, Chul Soon,Kim, Jong Oh,Yook, Simmyung,Park, Min-Hui,Bae, Yong Kyung,Jeong, Jee-Heon Wolters Kluwer Health, Inc. All rights reserved. 2018 Transplantation Vol.102 No.7

INTRODUCTION: Pancreatic islet transplantation is a promising technique to treat type 1 diabetes. Long-term survival of the graft is required for a successful islet transplantation. Repeated use of immunosuppressive drugs after organ/cell transplantation often leads to severe adverse effects including nephrotoxicity, hepatotoxicity, and opportunistic infections. Thus, development of a local immunosuppression protocol is necessary to improve the islet graft survival in clinics. MATERIALS AND METHODS: Pancreatic islets from Sprague-Dawley rats were transplanted into the subcutaneous space of B6 mice using injectable hydrogel. Three major groups were prepared for transplantation. (1) Islets transplanted FK506-loaded poly(lactic-co-glycolic acid) microspheres (10 mg/kg), (2) Islets transplanted with clodronate liposomes (6.25 mg/kg), and (3) Islet transplanted with the combination of both immune suppressants. The suspension of islets and immune suppressants in Matrigel was then injected into the subcutaneous space over the flanks of streptozocin-induced diabetic mice. RESULTS: Islets transplanted without any immunosuppression were rejected within two weeks. In contrast, the islets transplanted with the single immunosuppressive regimen of FK506 or clodronate improved survival rate compared with that of the control mice. More interestingly, the graft transplanted using the combination of both immune suppressants survived indefinitely. Immunological studies revealed that the immunosuppressive cocktail inhibited the proliferation of immune cells residing at the peripheral lymph nodes. Interestingly, the systemic immune system of the transplanted mice remained unaffected. Furthermore, histochemical analysis revealed the intact morphology of the islets at the transplanted site when codelivered with the immunosuppressant. DISCUSSION: Antigen presenting cells and T-cells orchestrate the immune rejection cascade. Macrophage depletion by the liposomal clodronate and the inhibition of T-cell activation by FK506 completely blocked the immune rejection cascade in the immune competent mice. The inhibition of immune stimulation in the peripheral lymph nodes improved the islet grafted into the subcutaneous space. Thus, the use of local immune suppression is an effective approach to enhance the survival of the transplanted islets. CONCLUSION: We developed a protocol for the local codelivery of pancreatic islets and immune suppressive agents. Indefinite graft survival was obtained with the use of macrophage depleting agent and T-cell inhibitor. The single dose of local immune suppression during transplantation may avoid toxic effects associated with a long-term use of immune suppressive agents in clinics.National Research Foundation of Korea (NRF) Grant nos: 2015R1A5A2009124 and 2017R1D1A1B03027831. Korea Health Industry Development Institute (KHIDI) Grant no: HI16C1767.

Synthesis and investigations on correlation between EPR and optical properties of Fe doped Li₂SiO₃

Pathak, M.S.,Gopal, N.O.,Singh, N.,Mohapatra, M.,Rao, J.L.,Lee, Jung-Kul,Singh, Vijay Elsevier 2018 Journal of non-crystalline solids Vol.500 No.-

<P><B>Abstract</B></P> <P>Iron doped lithium metasilicate sample was synthesized using a combustion technique and characterized by XRD (X ray diffraction), SEM (scanning electron microscopy), FTIR (Fourier transform infrared spectroscopy), optical, and EPR (electron paramagnetic resonance) analyses. The phase purity of the combustion synthesized products was confirmed by XRD analysis. SEM data suggested the formation of a porous compound by virtue of the entrapment of the gases that evolved during the sample synthesis. FTIR data confirmed the formation of SiO bonds in the system. Optical data confirmed the existence of both divalent and trivalent iron in the system. Characteristic absorption bands in the region 215–270 nm and 535–620 nm were observed due to the presence of Fe<SUP>3+</SUP> in Oh and Td geometry respectively. On the other hand, the presence of bands at 967 and 1442 nm suggested the stabilisation of Fe<SUP>2+</SUP> also in both Oh and Td geometries, respectively. The divalent iron being a non-Kramer ion, could not be observed by EPR. However, strong temperature-dependent EPR signals were observed in the sample owing to Fe<SUP>3+</SUP>. By analyzing the EPR data, super-paramagnetic type of behaviour was observed in the system. Furthermore, the relaxation times along with other EPR spectroscopic parameters were estimated for the system.</P>

Narrowband ultraviolet B emitting Gd doped CaAl₂O₄ phosphors – An ESR and photoluminescence study

Pathak, M.S.,Singh, N.,Singh, Vijay,Watanabe, S.,Gundu Rao, T.K.,Seshadri, M.,Lee, Jung-Kul Elsevier 2018 Journal of luminescence Vol.204 No.-

<P><B>Abstract</B></P> <P>Phosphors with the composition Ca<SUB>1-x</SUB>Gd<SUB>x</SUB>Al<SUB>2</SUB>O<SUB>4</SUB> (x = 0.0025–0.09) were synthesized by a simple combustion route in a short time. The formation of the as-prepared combustion products was confirmed by the X-ray diffraction analysis, indicating the formation of a monoclinic phase. The PL spectroscopy assessment shows that with increasing Gd<SUP>3+</SUP> concentration, the ultraviolet emission from Gd<SUP>3+</SUP> at 314 nm (<SUP>6</SUP>P<SUB>7/2</SUB>→<SUP>8</SUP>S<SUB>7/2</SUB>) progressively enhanced. The Gd<SUP>3+</SUP>-doped CaAl<SUB>2</SUB>O<SUB>4</SUB> displays electron spin resonance signals with the effective g values at <I>g</I> ≈ 1.95, 2.9, and 3.7. Additional lines were also observed at the approximate g values of ~2.2 and 5.3. Gd<SUP>3+</SUP> ion located in the distorted surroundings and experiencing relatively strong crystal field, give rise to low field lines. Distorted surroundings in the present system may result from the nearness of the charge compensator oxygen vacancies.</P>

Coincidence and fixed points for multi-valued mappings and its application to nonconvex integral inclusions

Pathak, H.K.,Agarwal, R.P.,Cho, Y.J. Koninklijke Vlaamse Ingenieursvereniging ; Elsevie 2015 Journal of computational and applied mathematics Vol.283 No.-

In this paper, we consider some problems on coincidence point and fixed point theorems for multi-valued mappings. Applying the characterizations of P-functions, we establish some new existence theorems for coincidence point and fixed point distinct from Nadler's fixed point theorem, Berinde-Berinde's fixed point theorem, Mizoguchi-Takahashi's fixed point theorem and Du's fixed point theorem for nonlinear multi-valued contractive mappings in complete metric spaces. Our results compliment and extend the main results given by some authors in the literature. In the sequel, we consider a nonconvex integral inclusion and prove the Filippov type existence theorem by using an appropriate norm on the space of selection of a multi-function and a multi-valued contraction for set-valued mappings.

Comparative study on simultaneous leaching of nutrients during bioleaching of heavy metals from sewage sludge using indigenous iron and sulphur oxidising microorganisms

Pathak, A.,Singh, P.,Dhama, P.,Dastidar, M.G.,Kim, D.J.,Heyes, G. Maney Publishing 2014 Canadian metallurgical quarterly Vol.53 No.1

The present study investigated the changes in nutrient profile of sewage sludge during bioleaching in a batch mode of operation. The study identified the optimum bioleaching period at which maximum solubilisation of metals is achieved while maintaining the fertilising property of the bioleached sludge. The bioleaching experiments were performed using anaerobically digested sewage sludge by employing indigenous iron and sulphur oxidising microorganisms. The results showed that bioleaching using sulphur oxidising microorganisms is comparatively advantageous due to the higher solubilisation of heavy metals. However, despite its high potential in solubilisation of heavy metals from the sludge, the bioleaching process resulted in the undesirable dissolution/loss of sludge bound nutrients (nitrogen and phosphorus), thus making the sludge less attractive for land application as a fertiliser. After 16 days of bioleaching about 45% of the nitrogen and 34% of the phosphorus were leached from the sludge using indigenous iron oxidising microorganisms, whereas about 78% of the nitrogen and 56% of the phosphorus were leached using indigenous sulphur oxidising microorganisms. The findings indicated that the fertilising property of the sewage sludge can be maintained by conducting the process for a shorter duration of time (up to 10 days). The optimum bioleaching period was 10 days where about 85%Cu, 71%Ni, 91%Zn and 61%Cr were solubilised from the sludge while the loss of nitrogen and phosphorus was only 56 and 51% respectively, by using sulphur oxidising microorganisms. The heavy metals remaining in the bioleached sludge were mostly in the residual fraction ensuring the safe disposal of bioleached sludge for land application as a fertiliser.