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This study analyses the role of the caste of firms in getting finance or credit from different financial sources in Jharkhand. We find that establishments belonging to Scheduled Tribe (ST) and Scheduled Caste (SC) owners have a lower probability of getting credit from different financial sources like the government, financial institutions, non-financial institutions, or money lenders.

PDF file - 115K

Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence.Patients and Methods: Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival, and progression-free survival. Immunologic factors associated with response were also evaluated.Results: Best overall response for the entire cohort was 42%; 47% in 43 checkpoint-naïve patients, 38% when patients were exposed to anti-CTLA4 alone (21 patients) and 33% if also exposed to anti-PD1 (9 patients) prior to TIL ACT. Median overall survival was 17.3 months; 24.6 months in CTLA4-naïve patients and 8.6 months in patients with prior CTLA4 blockade. The latter patients were infused with fewer TIL and experienced a shorter duration of response. Infusion of higher numbers of TIL with CD8 predominance and expression of BTLA correlated with improved response in anti-CTLA4 naïve patients, but not in anti-CTLA4 refractory patients. Baseline serum levels of IL9 predicted response to TIL ACT, while TIL persistence, tumor recognition, and mutation burden did not correlate with outcome.Conclusions: This study demonstrates the deleterious effects of prior exposure to anti-CTLA4 on TIL ACT response and shows that baseline IL9 levels can potentially serve as a predictive tool to select the appropriate sequence of immunotherapies. Clin Cancer Res; 24(18); 4416–28. ©2018 AACR.

PDF file - 77K, Long term changes in the persistence of TCR Vβ clonotypes in the blood following TIL adoptive transfer in representative responding patients

PDF file - 58K, Demographics and clinical characteristics of enrolled patients

PDF file - 1856K, Fig. S1. Schema of TIL adoptive cell therapy clinical trial; Fig. S2. Recovery of total white blood cell counts (WBC), absolute lymphocyte counts (ALC), and absolute neutrophil counts (ANC) during adoptive transfer TIL therapy in 31 treated patients; Fig. S3. Durable partial response of an intrathoracic melanoma mass near the aorta and heart in one patient at 6 weeks and 18 months after TIL infusion; Figure S4. Kaplan-Meier curves of overall survival and progression-free survival for all 31 treated patients; Figure S5. Kaplan-Meier curves of landmark-based overall survival and progression-free survival for irRC responding and non-responding TIL-treated patients; Fig. S6. Change in tumor burden over the first 20-22 months following TIL transfer therapy in responders and non-responders; Fig. S7. Box and whisker plot showing that telomere length of infused TIL was not significantly different between responders and non-responders

Supplementary figures and tables

PDF file - 69K, Derivation of the irRC best overall score

PDF file - 76k, Table S3. Associations between categorical patient variables and clinical response; Table S4. Associations between continuous variables and clinical response

This study analyses the impact of co-location between formal and informal manufacturing sectors on plant-level productivity. We employ a unique data obtained by merging plant-level data from Annual Survey of Industries (ASI 2011–2012) and Survey of Unorganised Manufacturing and Repairing Enterprises provided by National Sample Survey Office (NSSO 67th round). We find that formal and informal manufacturing plants gain from localisation. Further, co-location with informal enterprises has a positive impact on productivity of formal sector plants; however, we observe insignificant impact of co-location on informal sector enterprises. Additionally, we find evidence that informal sector enterprises benefit from industrially diversified regions. JEL Codes: D24, R12, R3

This study analyses the impact of industrial agglomeration on the total factor productivity (TFP) of Indian manufacturing. We employ plant-level data from the Annual Survey of Industries (ASI) to measure TFP and industrial agglomeration. Our econometric analysis discerns a positive impact of industrial agglomeration on plant productivity. In addition, we find that the larger plants are the beneficiaries of productivity gains associated with agglomeration. Further, our findings are robust to alternate measures of TFP.

In-house R&D, importing technology and R&D tax credit play different roles in different economies. The role even may change among firms of various technological intensities. Therefore, this study investigates the impact of in-house R&D, importing technology and R&D tax credits on India’s manufacturing firms’ productivity according to their technological intensity. Our results show that R&D and technology imports have a significant and positive impact on productivity in all technologically intense industries. We have further estimated a substitute relationship between R&D and Importing Technology in high-tech, medium–high-tech and medium–low-tech industries. However, the complementarity relationship between R&D and importing technology appears more pronounced in low-tech industries. Further, the R&D tax credit policy positively impacts firm productivity in medium–high-tech, medium–low-tech and low-tech industries. In order to boost productivity, there need to be policies that support R&D, including R&D tax incentives for companies in all technologically intensive industries. JEL Classifications: C23, D24, O31, 032

Implementation of a state of the art data acquisition and analysis program for variable low energy positron beam using LabVIEW based automation software is described. The program does the following functions: (a) controlling the remote programmable high voltage–power supply to bias the sample negatively (i.e., to vary the positron beam energy), (b) control of Windows based PCI MCA card, (c) calculating the S, W, R and ortho-positronium self-annihilation fraction (fPs) parameters, errors, and other relevant parameters, (d) saving the raw spectra, results and log data file and (e) dynamic display of raw spectrum and S, W, fPs versus energy for easy visualization of progress of the experiment. The USB based interfacing standard of this design provides easy connectivity to the personal computers.

The formation of hydrogen and helium associated defect complexes and their influence on the nucleation and growth of helium bubbles in Indian Reduced Activation Ferritic/Martensitic steel have been investigated using positron annihilation spectroscopy. Isochronal annealing study has been performed on the samples individually irradiated with H and He ions, and sequentially irradiated with both H and He ions. All the as-irradiated samples show higher S-parameter as compared to the unirradiated sample due to the presence of irradiation-induced vacancy-type defects. Among the single ion irradiated samples, hydrogen irradiated sample shows the presence of H-vacancy complexes having high hydrogen content in the as-irradiated state, an increase in S-parameter due to the release of hydrogen from these complexes at 373 K, and complete defect recovery after annealing at 673 K. The helium irradiated sample shows three distinct stages of annealing; a defect annealing stage with decrease in S-parameter from as-irradiated to 573 K, bubble nucleation stage with a stable S-parameter from 573 to 673 K and the bubble growth region characterized by an increase in S-parameter is observed from 673 to 973 K. Among the sequential irradiated samples, the sample irradiated with helium first and then with hydrogen shows a reduced S-parameter which is due to the saturation of helium-induced vacancies by hydrogen or the formation of H-He-vacancy complexes. Both the sequential irradiated samples show a reduced S-parameter from 573 to 673 K due to the formation of H-He-vacancy complexes under post-irradiation annealing. The nucleation and growth stage of helium bubbles observed under isochronal annealing is independent of the sequence of irradiation. Both the sequential irradiated samples show the bubble nucleation and growth stage similar to helium irradiated sample and further, the presence of hydrogen has no noticeable role in this stage.

In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8 TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8CD3 TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in

Indian reduced activation ferritic-martensitic steel was irradiated with 1.1 MeV Fe ions to various doses from 1 to100 dpa at room temperature. The depth profiling of irradiation-induced vacancy-ty...

Herein we present a new approach to develop nanocomposites based on plasticized poly (vinyl chloride)/multi-walled carbon nanotubes. The free volume is found to increase with increase in MWCNT content up to 1% CNT, but exceptional decrease was observed at higher loading. The increase in free volume is as a result of intercalation of carbon nanotubes between polymer chains, there by introducing slight disorder to nanocomposites. The decrease in free volume is as a result of bridging of polymer chains by carbon nanotubes, resulting in the decrease in free volume at the vicinity of carbon nanotubes. Structural studies via Raman spectra and Doppler Broadening reveals disorder and interfacial interactions in nanocomposites. A frequency up shift of G band is due to π electron transfer from MWCNT to chlorine in PPVC. Using Tao-Eldrup model, radius of free volume (R) and volume of free volume (Vf) are calculated for nanocomposites. Morphological studies via FESEM and TEM reveal uniform dispersion of MWCNT throughout the polymer matrix. Hence, nanocomposite with maximum MWCNT loading showed electrical conductivity of 4.2E-10 S/cm. Thus this is a new composite material for antistatic application.

High-temperature irradiation damage studies of Indian Reduced Activation Ferritic/Martensitic (INRAFM) steel have been carried out at doses relevant to fusion reactor first-wall irradiation conditions. The samples were irradiated up to 70 dpa with 1.1 MeV Fe ions at various temperatures viz., room temperature (RT), 473 K, 673 K and 773 K, with and without pre-injected helium. Depth-wise distribution of irradiation-induced defects and their thermal stability has been studied using positron beam based Doppler broadening spectroscopy. Samples without pre-injected helium show an overall reduction in S-parameter with respect to the irradiation temperature and no growth of voids has occurred, and complete defect recovery is observed at 673 K. In samples that were pre-injected with helium, a decrease in S-parameter due to annealing of vacancies and the formation of HemVn clusters is observed from RT to 673 K, and an increase in S-parameter associated with the growth of helium bubbles is observed at 773 K. Thus, helium is found to be necessary and crucial in stabilization and growth of the bubble cavities.

This study analyses the spatial and sectoral distribution of Greenfield Foreign Direct Investment (GFDI) and its impact on industrial agglomeration in India for the time period 2006–2015. We employ a unique dataset obtained by merging GFDI data from FDI Markets and plant level data from Annual Survey of Industries (ASI). We find that the Indian manufacturing sector shows signs of industrial dispersion rather than agglomeration throughout the sample period. Likewise, the spatial distribution pattern of GFDI also shows a decline in regional concentration and, interestingly, GFDI also seems to target new destinations. We also find that the increased spatial spread of GFDI leads to an industrial dispersion in Indian manufacturing industries.

Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence. Patients and Methods: Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival, and progression-free survival. Immunologic factors associated with response were also evaluated. Results: Best overall response for the entire cohort was 42%; 47% in 43 checkpoint-naïve patients, 38% when patients were exposed to anti-CTLA4 alone (21 patients) and 33% if also exposed to anti-PD1 (9 patients) prior to TIL ACT. Median overall survival was 17.3 months; 24.6 months in CTLA4-naïve patients and 8.6 months in patients with prior CTLA4 blockade. The latter patients were infused with fewer TIL and experienced a shorter duration of response. Infusion of higher numbers of TIL with CD8 predominance and expression of BTLA correlated with improved response in anti-CTLA4 naïve patients, but not in anti-CTLA4 refractory patients. Baseline serum levels of IL9 predicted response to TIL ACT, while TIL persistence, tumor recognition, and mutation burden did not correlate with outcome. Conclusions: This study demonstrates the deleterious effects of prior exposure to anti-CTLA4 on TIL ACT response and shows that baseline IL9 levels can potentially serve as a predictive tool to select the appropriate sequence of immunotherapies. Clin Cancer Res; 24(18); 4416–28. ©2018 AACR.

The microstructure, mechanical strength, dielectric properties, Doppler broadening measurements and positron life time studies of the composites containing multi walled carbon nanotubes (MWCNTs) and natural rubber (NR) are investigated. The uniform distribution of MWCNTs in the elastomer medium is studied by Raman spectroscopy and the electron microscopy images show the composite’s internal microstructure. Free volume sizes and interstitial mesopore sizes of the nanocomposites are determined by positron annihilation lifetime spectroscopy (PALS). PALS investigates the influence of the nanotubes in regulating the interphase nanoscale character. Strong interfacial interaction causes an apparent reduction of the free-volume fraction of NR probably by depressing the formation of free-volume holes in the interfacial region. The mechanical percolation and percolation observed from the dielectric measurements are correlated with the life time values. It is established that the sub-nano level free volumes and nano level structure of the composites have significant roles in regulating the mechanical properties.

Following the clinical success achieved with the first generation of adoptive cell therapy (ACT) utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs), the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP) environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center.

The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8+ T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.

Single phase perovskite structured barium cerate (BaCeO3) doped with europium phosphors were prepared through solution combustion route followed by calcination in air atmosphere. The morphology of the phosphor was analyzed from scanning electron micrograph. Diffuse reflectance spectra were recorded to determine the band gap energy of both undoped and Eu-doped BaCeO3 using the Kubelka-Munk method. Eu3+ exhibited intense red emission with high color purity and varied with Eu-concentration. The asymmetry ratio of Eu3+ varied for different excitation wavelength and Eu-concentration. The environment around Eu3+ was found to be more symmetric at 77 K unlike at 300 K. PL lifetime decay measurements of Eu3+ luminescence revealed two different sites for it in this host. Time-resolved emission spectroscopy confirmed the presence of two different sites for Eu3+ occupancy, exhibiting two different emission profiles. Thermally stimulated luminescence indicated multiple trap sites, and the intensity was linear with γ-dose in the range of 0–1000 Gy suggesting the possibility of using this material as a dosimetry phosphor. Positron annihilation lifetime spectroscopic studies indicated the presence of oxygen and barium vacancy-related defects.

Indian Reduced Activation Ferritic Martensitic steel is irradiated with 1.1 MeV Fe ions to a dose of 0.1 dpa at room temperature. The positron annihilation study showed a decrease in S-parameter with annealing temperature due to vacancy annealing. A complete defect recovery is observed beyond 1073 K. The linear nature of (S, W) correlation plot shows that only one kind of defect is present throughout the annealing temperature.

57Fe Mossbauer studies have been carried out in an alloy of U and Fe with atomic percentage in the ratio of 68%:32% in order to understand the local structure and valence of Fe atoms associated with different phases that may get formed. The effect of changes in the hyperfine parameters such as isomer shift and quadrupole splitting at Fe sites due to additional alloying of Zr has been studied in an alloy of U, Fe and Zr in the ratio of 44%:33%:23% respectively with respect to that of the U-Fe alloy chosen in the present study. Possible effect of solute clustering in these systems has been addressed in an analogous alloy of uranium and zirconium using positron lifetime spectroscopy.

138 Background: Adoptive cell therapy (ACT) of autologous tumor-infiltrating lymphocytes (TIL) can produce long lasting treatment responses in patients (pts) with metastatic melanoma. In our initial report of 31 treated pts, we demonstrated overall response rate (ORR) of 48%. Due to the evolution of treatment options for metastatic melanoma with heavy reliance on immunomodulatory therapies, we sought to re-evaluate responses in the era of checkpoint blockade. Methods: Pts receive treatment consisting of 7 days of lymphodepleting chemotherapy consisting of cyclophosphamide and fludarabine. High dose interleukin-2 (720,000 IU/kg IV q 8 hrs up to 15 doses) was infused after TIL infusion. Responses were assessed by imaging per irRC. Results: A total of 74 pts have been treated in our initial TIL study with an updated ORR assessment of 43%. Stratification of pts according to their checkpoint blockade immune-modulator therapy prior to TIL ACT, demonstrated that prior Ipilimumab (Ipi) decreased ORR to 33% compared to 51% in checkpoint naïve pts and decreased overall survival (OS) post-TIL therapy (median 7.7 vs 24.6 months respectively). There were too few pts to assess the impact of anti-PD1 as a single agent. A multiparametric analysis revealed that LDH levels at the time of therapy mainly influences OS and ORR to TIL but still could not invalidate the impact of Ipi prior to TIL ACT. The durability of the response was also found to be different between the 2 groups (30% for Ipi prior and 50% No Ipi prior). This new reality also impacted previously reported parameters that correlated with ORR to TIL ACT such as the expression of B-and-T lymphocyte attenuator (BTLA) on CD8+ TIL. Interestingly, assessment of mutation load (ML) of the tumors prior to TIL ACT showed that the check point naïve group display a high ML ( > 100) within their tumor whereas some patients who had Ipi prior to TIL have a low ML ( < 100). Conclusions: Our preliminary analysis shows that pre-treatment with Ipi decreases ORR to TIL ACT. Understanding how prior ipi modifies TIL, the tumor and microenvironment will help to define the full extent of the impact and how to best treat Ipi refractory pts with TIL. Clinical trial information: NCT00338377.

The dielectric constant of fluorinated polymides, their blends, and composites is known to decrease with the increase in free volume due to a decrease in the number of polarizable groups per unit volume. Herein, we report an interesting finding on the origin of dielectric constant in a polymer blend prepared using a fluorine-containing polymer and a polyimide probed in terms of its available free volume, which is distinct from the generally observed behavior in fluorinated polyimides. For this study, a blend of poly(vinylidene fluoride-co-hexafluoro propylene) and poly(ether imide) was chosen and the interaction between them was studied using FTIR, XRD, TGA, and SEM. The blend was investigated by positron annihilation lifetime spectroscopy (PALS), Doppler broadening (DB), and dielectric analysis (DEA). With the increase in the free volume content in the blend, surprisingly, the dielectric constant also increases and is attributed to additional space available for the polarizable groups to orient themselves to the applied electric field. The results obtained would pave the way for more effective design of polymeric electrical charge storage devices.

Purpose: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy. The effects of patient clinical features and the phenotypes of the T cells infused on the clinical response were determined. Results: Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T cells in the infusion product, a more differentiated effector phenotype of the CD8+ population, and a higher frequency of CD8+ T cells coexpressing the negative costimulation molecule “B- and T-lymphocyte attenuator” (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified. Conclusion: These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8+ T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression. Clin Cancer Res; 18(24); 6758–70. ©2012 AACR.