STUDIES ON THE CONFORMATIONAL STABILITY, DYNAMICS AND VISCOSITY OF IMMUNOGLOBULINS

Proteins, such as immunoglobulins, are inherently dynamic molecules with unique biological functions. The intra- and intermolecular interactions that govern the dynamic nature and function of immunoglobulins may also influence their stability. A molecular understanding of interrelationship between dynamics, function and conformational stability of immunoglobulins, both in solution and in presence of co-solutes, can be important for their pharmaceutical development. In addition, it is important to understand the differences in any such correlations between closely related immunoglobulins. Furthermore, molecular interactions in immunoglobulins can be unique at low and high concentrations, which necessitate newer complementary approaches to investigate such complex systems. Therefore, a better understanding of interactions that govern protein structure, dynamics and conformational stability at low and high concentrations and in presence of excipients should aid in designing, optimizing and developing rational formulation conditions for protein based therapeutics. A variety of experimental methods sensitive to structure, dynamics and conformational stability of proteins in solution were employed in these studies. External perturbations such a change in pH, ionic strength and temperature were used to probe the response of proteins, both at low and high concentrations. Different monoclonal antibodies within IgG1 isotype were used to investigate interrelationships between protein dynamics and conformational stability in absence and presence of co-solutes. In addition, an ultraviolet spectroscopy based approach was developed to understand interactions modulating solution viscosity in high concentration immunoglobulin solutions. These studies provide evidence that immunoglobulins belonging to the same IgG1 subtype can have notable differences in their conformational stability, dynamics, aggregation propensity, hydration properties and their response to co-solutes. In addition, alterations in protein dynamics (at a global protein level and in local regions with differences in solvent exposures) by stabilizing or destabilizing excipients were found to modulate the conformational stability of a monoclonal antibody. Furthermore, it was determined that potential interactions and factors modulating solution viscosity at high protein concentrations may also result in changes in their extinction coefficients. The work presented in this dissertation provides evidence that factors modulating protein dynamics and those governing intra- and intermolecular interactions can influence the conformational stability, aggregation and viscosity of proteins in solution

3D Printed Zeolite Monoliths for CO₂ Removal

Carbon dioxide (CO2) capture materials comprising one or more 3D-printed zeolite monoliths for the capture and or removal of CO2 from air or gases in enclosed compartments, including gases or mixtures of gases having less than about 5% CO2. Methods for preparing 3D-printed zeolite monoliths useful as CO2 capture materials and filters, as well as methods of removing CO2 from a gas or mixture of gases in an enclosed compartment using 3D-printed zeolite monoliths are provided

Comparative Evaluation of flank wear of uncoated, AlTiN and TiSiN Coated Cermet Insert by Machining of D2 Tool Steel

The life of a cutting tool is one of the major parameters which affects the cost and quality of machining. Hence manufacturing industries putting lots of effort and resources to increase tool life and productivity. This research focuses on increasing the life of cutting tool insert by suggesting new coating material for turning harden metals. An experimentation analysis is carried out on uncoated, conventional coated (AlTiN) and newly suggested coating (TiSiN) cermet insert. Experiments were carried out by selecting 90, 183, and 245 m/min as cutting speed, 0.2 mm/rev as feed, and 0.25 mm depth of cut. The result shows all three inserts give good performance at 90 m/min cutting speed. Tool life of AlTiN coated insert shows 20 min and TiSiN coated insert shows 22.21 min at 183 m/min cutting speed. At cutting speed 245 m/min all three types of cutting insert break even after 1 min of machining

Complications as indicators of quality assurance after 401 consecutive colorectal cancer resections: the importance of surgeon volume in developing colorectal cancer units in India

<p>Abstract</p> <p>Background</p> <p>The low incidence of colorectal cancer in India, coupled with absence of specialized units, contribute to lack of relevant data arising from the subcontinent. We evaluated the data of the senior author to better define the requirements that would enable development of specialized units in a country where colorectal cancer burden is increasing.</p> <p>Methods</p> <p>We retrospectively analyzed data of 401 consecutive colorectal resections from a prospective database of the senior author. In addition to patient demographics and types of resections, perioperative data like intraoperative blood loss, duration of surgery, complications, re-operation rates and hospital stay were recorded and analyzed.</p> <p>Results</p> <p>The median age was 52 years (10-86 years). 279 were males and 122 were females. The average duration of surgery was 220.32 minutes (range 50 - 480 min). The overall complication rate was 12.2% (49/401) with a 1.2% (5/401) mortality rate. The patients having complications had an increase in their median hospital stay (from 10.5 days to 23.4 days) and the re-operation rate in them was 51%. The major complications were anastomotic leaks (2.5%) and stoma related complications (2.7%).</p> <p>Conclusions</p> <p>This largest ever series from India compares favorably with global standards. In a nation where colorectal cancer is on the rise, it is imperative that high volume centers develop specialized units to train future specialist colorectal surgeons. This would ensure improved quality assurance and delivery of health care even to outreach, low volume centers.</p

Study of ectopic pregnancy in a tertiary care centre

Background: Ectopic pregnancy is a life threatening emergency leading to maternal death. Incidence of ectopic pregnancies has been increasing in last two to three decades with reduction in mortality. The presenting symptoms include abdominal pain, amenorrhoea and/or irregular vaginal bleeding. The present study was undertaken to study the clinical features of ectopic pregnancies in a tertiary care hospital.Methods: The present study on ectopic pregnancies was carried out in Department of Pathology, Krishna Institute of Medical Sciences, Karad, Maharashtra, India from January 2010 to June 2014. All the cases of ectopic pregnancy managed surgically were included in the study.Results: Total 102 cases of ectopic pregnancy were studied. Proportion of ectopic pregnancy in the present study is 1 in 205 deliveries. Majority of the cases (37) (36.27%) were noted between 21 to 25 years of age group followed by the age group 26 to 30 years. Ectopic pregnancy was most commonly noted in nulliparous women (44/102) (43.14%). Majority of the cases (50/102) (49.02%) had no risk factors. Abortion was the most common risk factor identified, alone as well as in conjunction with other factors. Ampulla was the most common site for ectopic pregnancy. 55% of the cases were on the right side where as 45% on the left side. We had 2 cases of heterotropic pregnancy with tubal ectopic in both the cases. The typical triad of amenorrhoea, pain in abdomen and bleeding was observed in 21.57% cases.Conclusions: The incidence of ectopic pregnancies is on rise as evident in this study. In order to reduce the morbidity and mortality due to ectopic pregnancies, there is need for early diagnosis especially in high risk cases

Cotransplantation of Adipose Tissue-Derived Insulin-Secreting Mesenchymal Stem Cells and Hematopoietic Stem Cells: A Novel Therapy for Insulin-Dependent Diabetes Mellitus

Aims. Insulin dependent diabetes mellitus (IDDM) is believed to be an autoimmune disorder with disturbed glucose/insulin metabolism, requiring life-long insulin replacement therapy (IRT), 30% of patients develop end-organ failure. We present our experience of cotransplantation of adipose tissue derived insulin-secreting mesenchymal stem cells (IS-AD-MSC) and cultured bone marrow (CBM) as IRT for these patients. Methods. This was a prospective open-labeled clinical trial to test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM, approved by the institutional review board after informed consent in 11 (males : females: 7 : 4) patients with 1–24-year disease duration, in age group: 13–43 years, on mean values of exogenous insulin requirement of 1.14 units/kg BW/day, glycosylated hemoglobin (Hb1Ac): 8.47%, and c-peptide levels: 0.1 ng/mL. Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected to defined culture conditions and phenotypically differentiated to insulin-secreting cells, with mean quantum: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1 × 103/μL, CD45−/90+/73+:40/30.1%, C-Peptide level:1.8 ng/mL, and insulin level: 339.3  IU/mL with CBM mean quantum: 96.3 mL and cell counts: 28.1 × 103/μL, CD45−/34+:0.62%, was carried out. Results. All were successfully transplanted without any untoward effect. Over mean followup of 23 months, they had a decreased mean exogenous insulin requirement to 0.63 units/kgBW/day, Hb1Ac to 7.39%, raised serum c-peptide levels to 0.38 ng/mL, and became free of diabetic ketoacidosis events with mean 2.5 Kg weight gain on normal vegetarian diet and physical activities. Conclusion. This is the first report of treating IDDM with insulin-secreting-AD-MSC+CBM safely and effectively with relatively simple techniques

Giant prostatic hyperplasia: surgical treatment a rare case

We report a rare case of giant prostatic hyperplasia in an 80-year-old male patient. MRI revealed a markedly enlarged prostate measuring 814gm.We have performed suprapubic open prostatectomy (Transvesical). The adenoma was completely enucleated in one piece which was 11cm×16cm in size and weighed 504gm

Pseudospectral Calculation of the Wavefunction of Helium and the Negative Hydrogen Ion

We study the numerical solution of the non-relativistic Schr\"{o}dinger equation for two-electron atoms in ground and excited S-states using pseudospectral (PS) methods of calculation. The calculation achieves convergence rates for the energy, Cauchy error in the wavefunction, and variance in local energy that are exponentially fast for all practical purposes. The method requires three separate subdomains to handle the wavefunction's cusp-like behavior near the two-particle coalescences. The use of three subdomains is essential to maintaining exponential convergence. A comparison of several different treatments of the cusps and the semi-infinite domain suggest that the simplest prescription is sufficient. For many purposes it proves unnecessary to handle the logarithmic behavior near the three-particle coalescence in a special way. The PS method has many virtues: no explicit assumptions need be made about the asymptotic behavior of the wavefunction near cusps or at large distances, the local energy is exactly equal to the calculated global energy at all collocation points, local errors go down everywhere with increasing resolution, the effective basis using Chebyshev polynomials is complete and simple, and the method is easily extensible to other bound states. This study serves as a proof-of-principle of the method for more general two- and possibly three-electron applications.Comment: 23 pages, 20 figures, 2 tables, Final refereed version - Some references added, some stylistic changes, added paragraph to matrix methods section, added last sentence to abstract

Corrections to the Nonrelativistic Ground Energy of a Helium Atom

Considering the nuclear motion, the authors give out the nonrelativistic ground energy of a helium atom by using a simple but effective variational wave function with a flexible parameter $k$. Based on this result, the relativistic and radiative corrections to the nonrelativistic Hamiltonian are discussed. The high precision value of the helium ground energy is evaluated to be -2.90338 a.u., and the relative error is 0.00034%.Comment: 8 pages, no figures, 2 table