Wai Lin - Academia.edu (original) (raw)

Papers by Wai Lin

The Journal of Immunology

TRAF3 is a negative regulator in B lymphocytes of CD40 and BAFF-R mediated signaling events, as w... more TRAF3 is a negative regulator in B lymphocytes of CD40 and BAFF-R mediated signaling events, as well as basal B cell survival and homeostasis. Loss of function mutants of TRAF3 are associated with multiple myeloma (MM) and B-cell lymphoma, and TRAF3-/- B cells in mice show greatly enhanced survival, as well as constitutive activation of the alternative NF-κB2 pathway. Current dogma is that TRAF3 promotes degradation of the kinase NIK to control activation of the NF-κB2 pathway, and stimulation through CD40 or BAFF-R induces TRAF3 degradation, allowing NIK to activate NF-κB2, which promotes survival. However, our recent findings indicate a more complex regulatory mechanism. The A/WySnJ mouse expresses a mutant BAFF-R in which the C terminal 8 amino acids are replaced by a proviral sequence. BAFF ligation of this mutant receptor does not activate NF-κB2, but induces TRAF3 degradation comparable to Wt BAFF-R. Additionally, we analyzed a human MM-derived TRAF3 mutant and found that its ...

The Journal of Immunology

BAFF receptor (BAFFR), a member of the TNFR superfamily, binds to the pro-survival cytokine BAFF ... more BAFF receptor (BAFFR), a member of the TNFR superfamily, binds to the pro-survival cytokine BAFF to promote B cell development and survival, and deficiencies of either BAFFR or BAFF result in inhibition of B cell development. BAFF-R engagement recruits TRAFs 2, 3 and 6 and activates the non-canonical NF-κB2 pathway. Current models propose that TRAF3 mediates degradation of the NF-κB activating kinase NIK, concluding that BAFFR-mediated TRAF3 degradation is necessary and sufficient for NF-κB2 activation. However, our recent studies of a mutant BAFFR indicate that this model is inadequate to fully explain how BAFFR activates the NF-κB2 pathway. The A/WySnJ mouse harbors a spontaneous mutation of BAFFR in which 8 residues of the cytoplasmic tail are replaced by 22 amino acids from a viral genome. Engagement of this mutant BAFF-R fails to activate the NF-κB2 pathway, and A/WySnJ mice have a substantial B cell deficiency. However, the mutant BAFF-R shows no decrease in recruitment or rec...

The Journal of Immunology

The pathogenesis and progression of B-cell lymphomas is a dynamic process involving reciprocal in... more The pathogenesis and progression of B-cell lymphomas is a dynamic process involving reciprocal interactions between malignant cells and surrounding components in the tumor microenvironment. Neoplastic B cells migrate to lymphoid sites and prompt the immune cell infiltration. The infiltrated cytotoxic lymphocytes potentially contribute to tumor cell killing and good prognosis. However, most immune cell types in the tumor niche often become unresponsive or end up promoting tumor growth. In this study we present a sorting strategy using the BD FACSymphony™ S6 Cell Sorter that enables concurrent isolation of six cell populations from a tumor niche in a murine B-cell lymphoma model. Single-cell sequencing was used downstream to unravel the respective roles of each cell subset for the tumor’s progression and/or evasion. The six cell subsets were isolated from mice that had been inoculated with an OVA-expressing B-cell lymphoma cell line and subsequently with either wild-type or BTLA-defic...

Journal of Immunology, May 1, 2013

Biophotonics Congress: Biomedical Optics 2020 (Translational, Microscopy, OCT, OTS, BRAIN), 2020

The time has now come to expand the use of optical coherence tomography and apply it in botany wh... more The time has now come to expand the use of optical coherence tomography and apply it in botany where the technology’s key advantages enable visualization of plant’s communication as it was never done before.

Critical Care Medicine, 2019

Street foods vending offers economic benefits to vendors and nutritious foods for urban consumers... more Street foods vending offers economic benefits to vendors and nutritious foods for urban consumers, especially in developing countries. In Myanmar, the Yangon City Development Council (YCDC) is mainly responsible for controlling food stalls. The aims of this study were to investigate the authority’s controlling aspects of street foods towards safety, to investigate the vendors’ understanding of proper practices for safety and also to find out the constraints that prevent them from following proper food handling practices. Interviews were conducted with the authority from the health department of YCDC. A total of seventy two (n=72) street food vendors from the downtown area included. Demographic profiles of vendors, their food safety knowledge, constraints regarding proper handling practices etc. were assessed by using a semi-structured questionnaire. It found that the YCDC had already established five key components of food control system for controlling food stalls, however, street ...

Frontiers in Immunology, 2020

Neuronal regulation of diverse physiological functions requires complex molecular interactions in... more Neuronal regulation of diverse physiological functions requires complex molecular interactions in innervated tissues to maintain proper organ function. Here we show that loss of the neuronal cell surface adhesion/recognition molecule Contactin-1 (Cntn1) directly impairs intestinal function causing wasting that subsequently results in global immune defects. Loss of Cntn1 results in hematologic alterations and changes in blood metabolites associated with malnourishment. We found thymus and spleen of Cntn1-deficient animals atrophied with severe reductions in lymphocyte populations. Elevated thymic Gilz expression indicated ongoing glucocorticoid signaling in Cntn1-deficient animals, consistent with the malnourishment phenotype. Intestinal Contactin-1 was localized to neurons in the villi and the submucosal/myenteric plexus that innervates smooth muscle. Loss of Cntn1 was associated with reduced intestinal Bdnf and Adrb2, indicating reduced neuromuscular crosstalk. Additionally, loss of Cntn1 resulted in reduced recruitment of CD3 + T cells to villi within the small intestine. Together, these data illustrate the critical role of Contactin-1 function within the gut, and how this is required for normal systemic immune functions.

Key Engineering Materials, 2019

Most of the corrosion inhibitors that are used in industry contain chemicals that are harmful to ... more Most of the corrosion inhibitors that are used in industry contain chemicals that are harmful to health and environment. Corrosion inhibitors derived from green sources are, therefore, believed to be a good option for replacing the chemical corrosion inhibitors. In this work, a green oleochemical corrosion inhibitor derived from Jatropha Curcas is introduced. The paper discusses the methodology of deriving the corrosion inhibitor as well as the experimental test conducted for evaluating its corrosion inhibition efficiency. The new oleochemical corrosion inhibitor was derived via two reactions. Jatropha oil was firstly saponified with sodium hydroxide to yield gras acid and glycerol, which was then esterified with boron fluoride in presence of excess methanol to produce the oil methyl esters, which is used as oleo-chemical corrosion inhibitor. To evaluate the oleo-chemical corrosion inhibitor, the corrosion rate of mild steel in NaCl corrosive medium with CO2 is tested at static cond...

Cancer Research, 2020

As for most neoplasms, the pathogenesis and progression of B-cell malignancies is a dynamic proce... more As for most neoplasms, the pathogenesis and progression of B-cell malignancies is a dynamic process involving reciprocal interactions between malignant cells and surrounding components in the tumor microenvironment. In the case of certain B-cell lymphomas, neoplastic cells migrate to lymphoid sites and prompt the infiltration of non-malignant immune cells. The infiltration of cytotoxic lymphocytes correlates with tumor cell killing and good prognosis. However, most immune cell types in the tumor niche often become unresponsive or end up promoting tumor growth. In this study we present a sorting strategy using the BD FACSymphony™ S6 Cell Sorter that enables concurrent isolation of six cell populations from a tumor niche in a model of B-cell lymphoma. Downstream application of single-cell sequencing was used to unravel the respective roles of each cell subset for the tumor's progression and/or evasion. The six cell subsets were isolated from two groups of mice that had been inocul...

Vaccines based on live attenuated viruses often induce broad, multifaceted immune responses. Howe... more Vaccines based on live attenuated viruses often induce broad, multifaceted immune responses. However, they also usually sacrifice immunogenicity for attenuation. It is particularly difficult to elicit an effective vaccine for herpesviruses due to an armament of immune evasion genes and a latent phase. Here, to overcome the limitation of attenuation, we developed a rational herpesvirus vaccine in which viral immune evasion genes were deleted to enhance immunogenicity while also attaining safety. To test this vaccine strategy, we utilized murine gammaherpesvirus-68 (MHV-68) as a proof-of-concept model for the cancer-associated human γ-herpesviruses, Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus. We engineered a recombinant MHV-68 virus by targeted inactivation of viral antagonists of type I interferon (IFN-I) pathway and deletion of the latency locus responsible for persistent infection. This recombinant virus is highly attenuated with no measurable capacity for replica...

IOP Conference Series: Materials Science and Engineering, 2019

Nowadays, construction cost plays an essential role in various projects, which are buildings, roa... more Nowadays, construction cost plays an essential role in various projects, which are buildings, roads, railways, and bridges projects. Conceptual cost estimation in feasibility study is require high accuracy and less validation error especially in construction projects at early stages. The more improvement of estimation techniques, it would lead to the lesser problems of cost overrun, and extra expenses. This paper developed a cost estimation model for new constructed rural road projects. Considering the estimation methods for predicting the cost model, parametric method based on regression learner and NN method are applied. Previously, many researchers studied the cost applicable model by using various computer applications, so that this paper differed to compare these methods based on MATLAB. Accordingly, 44 road projects were compiled from DRR database, after that identifying the effective cost parameters referred on collected data. Subsequently, the data implementation process was...

Journal of the Endocrine Society, 2019

Abstract Introduction: mTBI is associated with anterior pituitary hormone dysfunction. The potent... more Abstract Introduction: mTBI is associated with anterior pituitary hormone dysfunction. The potential long-term effect of this injury on pituitary function in Veterans is not clear. Methods: We present an interim report of our 4-year longitudinal prospective pilot study of pituitary function in Veterans diagnosed with mTBI. Of the 34 mTBI Veterans enrolled, we have tested 28 of them (4 female, 24 male; mean±SD age and BMI, 31.1±7.0 years and 30.2±6.2, respectively) for baseline pituitary hormone levels and cortisol response to ACTH. In 22 subjects growth hormone response to glucagon stimulation (GST) was tested at baseline. The same baseline data were obtained for 15 age-, sex-, deployment- and BMI-matched control subjects without mTBI (2 female,13 male; mean±SD age and BMI 33.9±6.8 years and 32.7±7.2, respectively). Follow-up testing has been done for 18 mTBI subjects in Year 1, 13 subjects in Year 2, 8 subjects in Year 3 and 3 subjects in Year 4. GH cutoffs of <1ng/mL for patients with a BMI≥25, and ≤ 3 ng/mL for a BMI < 25 were used for the diagnosis of GHD. Results: GHD was present in 9% (2/22) at baseline, 22% (4/18) at Year 1, 8% (1/13) at Year 2, 22% (2/9) at Year 3, and 0% (0/3) at Year 4. GHD did not occur in the same subject in subsequent years, and it appeared to recover within a year. The peak GST GH level for all subjects at each year trended downward from baseline to Years 1, 2, 3, and 4: (ng/mL, mean±SD) 7.6±7.7; 7.5±13.0; 3.5±3.3; 4.4±4.3; 1.9±0.9, respectively. Secondary hypogonadism occurred in 11%, 6%, 8% of subjects at baseline, Year 1 and Year 2, respectively; none has been found in Years 3 and 4. There are no subjects identified with hypothyroidism or overt adrenal insufficiency at baseline or over 4 years. Unexpectedly, GHD was detected in 27% (4/15) of control subjects. The mean±SD BMI of 39.4±7.8 for these subjects was higher than the BMI values for GH sufficient (GHS) control subjects (30.2±5.2), mTBI patients with GHD (29.6±4.6) and GHS (30.9±6.2). Secondary hypogonadism was present in 14%, and there were no cases of hypothyroidism or adrenal insufficiency. Conclusions: GHD occurs in patients with mTBI at up to 3 years of observation using the stricter GH cutoff criterion with a BMI ≥25. Because each patient with GHD in a particular year was unique, the cumulative occurrence of GHD thus far is 41% (9/22) over 4 years. The highest prevalence was in Year 2. Each subject appeared to recover from GHD in one year. Attrition of subjects has decreased the later year numbers; a more complete review will be possible when the remaining subject testing is completed. The detection of GHD in the non-mTBI control group suggests there may be additional factors in deployment itself that can put military personnel at risk. BMI as a confounding factor with the GST or any GH testing cannot be excluded. Identification of GHD and hypogonadism in Veterans with mTBI will provide treatment opportunities to enhance their recovery.

mentorship and support for the past five years. Gail provided me with excellent guidance and enco... more mentorship and support for the past five years. Gail provided me with excellent guidance and encouragement throughout my graduate training. Her endless support has not only fostered me to become a better scientist but also to become a better writer, and speaker. Without her support and guidance, my thesis work would not have been accomplished. I would like to thank the Interdisciplinary Graduate Program in Immunology for providing an excellent learning and training environment, and Dr. Bishop and Dr. Varga for overseeing the program. Special thanks go to Paulette Villhauer, Joshua Lobb and Kathy Dautremont for keeping me in check with the paperwork and deadlines. I would especially like to thank my thesis committee members (Dr. Jon Houtman, Dr. John Colgan, Dr. Siegfried Janz, and Dr. Frederick Quelle) for their guidance and support for my thesis work. I also wish to thank the Biosciences Program for providing me with financial support during my initial year of graduate school.

Immunity, 2016

Cytokines related to tumor necrosis factor (TNF) provide a communication network essential for co... more Cytokines related to tumor necrosis factor (TNF) provide a communication network essential for coordinating multiple cell types into an effective host defense system against pathogens and malignant cells. The pathways controlled by the TNF superfamily differentiate both innate and adaptive immune cells and modulate stromal cells into microenvironments conducive to host defenses. Members of the TNF receptor superfamily activate diverse cellular functions from the production of type 1 interferons to the modulation of survival of antigen-activated T cells. Here, we focus attention on the subset of TNF superfamily receptors encoded in the immune response locus in chromosomal region 1p36. Recent studies have revealed that these receptors use diverse mechanisms to either co-stimulate or restrict immune responses. Translation of the fundamental mechanisms of TNF superfamily is leading to the design of therapeutics that can alter pathogenic processes in several autoimmune diseases or promote immunity to tumors.

Proceedings of the 2015 International Conference on Industrial Technology and Management Science, 2015

Reliability Centered Maintenance (RCM) is a well-known method in several industries. RCM is a str... more Reliability Centered Maintenance (RCM) is a well-known method in several industries. RCM is a structure decision process to cost-effective determines and optimum maintenance requirements. This paper proposes the application of the RCM concept to a petrochemical case study. The results indicate that preventive maintenance plans and available time of maintenance staff are improved significantly.

Immunological Reviews, 2015

SummaryThe signaling adapter protein tumor necrosis factor receptor (TNFR)‐associated factor 3 (T... more SummaryThe signaling adapter protein tumor necrosis factor receptor (TNFR)‐associated factor 3 (TRAF3) is both modified by and contributes to several types of ubiquitination events. TRAF3 plays a variety of context‐dependent regulatory roles in all types of immune cells. In B lymphocytes, TRAF3 contributes to regulation of signaling by members of both the TNFR superfamily and innate immune receptors. TRAF3 also plays a unique cell type‐specific and critical role in the restraint of B‐cell homeostatic survival, a role with important implications for both B‐cell differentiation and the pathogenesis of B‐cell malignancies. This review focuses upon the relationship between ubiquitin and TRAF3, and how this contributes to multiple functions of TRAF3 in the regulation of signal transduction, transcriptional activation, and effector functions of B lymphocytes.

The Journal of Immunology

TRAF3 is a negative regulator in B lymphocytes of CD40 and BAFF-R mediated signaling events, as w... more TRAF3 is a negative regulator in B lymphocytes of CD40 and BAFF-R mediated signaling events, as well as basal B cell survival and homeostasis. Loss of function mutants of TRAF3 are associated with multiple myeloma (MM) and B-cell lymphoma, and TRAF3-/- B cells in mice show greatly enhanced survival, as well as constitutive activation of the alternative NF-κB2 pathway. Current dogma is that TRAF3 promotes degradation of the kinase NIK to control activation of the NF-κB2 pathway, and stimulation through CD40 or BAFF-R induces TRAF3 degradation, allowing NIK to activate NF-κB2, which promotes survival. However, our recent findings indicate a more complex regulatory mechanism. The A/WySnJ mouse expresses a mutant BAFF-R in which the C terminal 8 amino acids are replaced by a proviral sequence. BAFF ligation of this mutant receptor does not activate NF-κB2, but induces TRAF3 degradation comparable to Wt BAFF-R. Additionally, we analyzed a human MM-derived TRAF3 mutant and found that its ...

The Journal of Immunology

BAFF receptor (BAFFR), a member of the TNFR superfamily, binds to the pro-survival cytokine BAFF ... more BAFF receptor (BAFFR), a member of the TNFR superfamily, binds to the pro-survival cytokine BAFF to promote B cell development and survival, and deficiencies of either BAFFR or BAFF result in inhibition of B cell development. BAFF-R engagement recruits TRAFs 2, 3 and 6 and activates the non-canonical NF-κB2 pathway. Current models propose that TRAF3 mediates degradation of the NF-κB activating kinase NIK, concluding that BAFFR-mediated TRAF3 degradation is necessary and sufficient for NF-κB2 activation. However, our recent studies of a mutant BAFFR indicate that this model is inadequate to fully explain how BAFFR activates the NF-κB2 pathway. The A/WySnJ mouse harbors a spontaneous mutation of BAFFR in which 8 residues of the cytoplasmic tail are replaced by 22 amino acids from a viral genome. Engagement of this mutant BAFF-R fails to activate the NF-κB2 pathway, and A/WySnJ mice have a substantial B cell deficiency. However, the mutant BAFF-R shows no decrease in recruitment or rec...

The Journal of Immunology

The pathogenesis and progression of B-cell lymphomas is a dynamic process involving reciprocal in... more The pathogenesis and progression of B-cell lymphomas is a dynamic process involving reciprocal interactions between malignant cells and surrounding components in the tumor microenvironment. Neoplastic B cells migrate to lymphoid sites and prompt the immune cell infiltration. The infiltrated cytotoxic lymphocytes potentially contribute to tumor cell killing and good prognosis. However, most immune cell types in the tumor niche often become unresponsive or end up promoting tumor growth. In this study we present a sorting strategy using the BD FACSymphony™ S6 Cell Sorter that enables concurrent isolation of six cell populations from a tumor niche in a murine B-cell lymphoma model. Single-cell sequencing was used downstream to unravel the respective roles of each cell subset for the tumor’s progression and/or evasion. The six cell subsets were isolated from mice that had been inoculated with an OVA-expressing B-cell lymphoma cell line and subsequently with either wild-type or BTLA-defic...

Journal of Immunology, May 1, 2013

Biophotonics Congress: Biomedical Optics 2020 (Translational, Microscopy, OCT, OTS, BRAIN), 2020

The time has now come to expand the use of optical coherence tomography and apply it in botany wh... more The time has now come to expand the use of optical coherence tomography and apply it in botany where the technology’s key advantages enable visualization of plant’s communication as it was never done before.

Critical Care Medicine, 2019

Street foods vending offers economic benefits to vendors and nutritious foods for urban consumers... more Street foods vending offers economic benefits to vendors and nutritious foods for urban consumers, especially in developing countries. In Myanmar, the Yangon City Development Council (YCDC) is mainly responsible for controlling food stalls. The aims of this study were to investigate the authority’s controlling aspects of street foods towards safety, to investigate the vendors’ understanding of proper practices for safety and also to find out the constraints that prevent them from following proper food handling practices. Interviews were conducted with the authority from the health department of YCDC. A total of seventy two (n=72) street food vendors from the downtown area included. Demographic profiles of vendors, their food safety knowledge, constraints regarding proper handling practices etc. were assessed by using a semi-structured questionnaire. It found that the YCDC had already established five key components of food control system for controlling food stalls, however, street ...

Frontiers in Immunology, 2020

Neuronal regulation of diverse physiological functions requires complex molecular interactions in... more Neuronal regulation of diverse physiological functions requires complex molecular interactions in innervated tissues to maintain proper organ function. Here we show that loss of the neuronal cell surface adhesion/recognition molecule Contactin-1 (Cntn1) directly impairs intestinal function causing wasting that subsequently results in global immune defects. Loss of Cntn1 results in hematologic alterations and changes in blood metabolites associated with malnourishment. We found thymus and spleen of Cntn1-deficient animals atrophied with severe reductions in lymphocyte populations. Elevated thymic Gilz expression indicated ongoing glucocorticoid signaling in Cntn1-deficient animals, consistent with the malnourishment phenotype. Intestinal Contactin-1 was localized to neurons in the villi and the submucosal/myenteric plexus that innervates smooth muscle. Loss of Cntn1 was associated with reduced intestinal Bdnf and Adrb2, indicating reduced neuromuscular crosstalk. Additionally, loss of Cntn1 resulted in reduced recruitment of CD3 + T cells to villi within the small intestine. Together, these data illustrate the critical role of Contactin-1 function within the gut, and how this is required for normal systemic immune functions.

Key Engineering Materials, 2019

Most of the corrosion inhibitors that are used in industry contain chemicals that are harmful to ... more Most of the corrosion inhibitors that are used in industry contain chemicals that are harmful to health and environment. Corrosion inhibitors derived from green sources are, therefore, believed to be a good option for replacing the chemical corrosion inhibitors. In this work, a green oleochemical corrosion inhibitor derived from Jatropha Curcas is introduced. The paper discusses the methodology of deriving the corrosion inhibitor as well as the experimental test conducted for evaluating its corrosion inhibition efficiency. The new oleochemical corrosion inhibitor was derived via two reactions. Jatropha oil was firstly saponified with sodium hydroxide to yield gras acid and glycerol, which was then esterified with boron fluoride in presence of excess methanol to produce the oil methyl esters, which is used as oleo-chemical corrosion inhibitor. To evaluate the oleo-chemical corrosion inhibitor, the corrosion rate of mild steel in NaCl corrosive medium with CO2 is tested at static cond...

Cancer Research, 2020

As for most neoplasms, the pathogenesis and progression of B-cell malignancies is a dynamic proce... more As for most neoplasms, the pathogenesis and progression of B-cell malignancies is a dynamic process involving reciprocal interactions between malignant cells and surrounding components in the tumor microenvironment. In the case of certain B-cell lymphomas, neoplastic cells migrate to lymphoid sites and prompt the infiltration of non-malignant immune cells. The infiltration of cytotoxic lymphocytes correlates with tumor cell killing and good prognosis. However, most immune cell types in the tumor niche often become unresponsive or end up promoting tumor growth. In this study we present a sorting strategy using the BD FACSymphony™ S6 Cell Sorter that enables concurrent isolation of six cell populations from a tumor niche in a model of B-cell lymphoma. Downstream application of single-cell sequencing was used to unravel the respective roles of each cell subset for the tumor's progression and/or evasion. The six cell subsets were isolated from two groups of mice that had been inocul...

Vaccines based on live attenuated viruses often induce broad, multifaceted immune responses. Howe... more Vaccines based on live attenuated viruses often induce broad, multifaceted immune responses. However, they also usually sacrifice immunogenicity for attenuation. It is particularly difficult to elicit an effective vaccine for herpesviruses due to an armament of immune evasion genes and a latent phase. Here, to overcome the limitation of attenuation, we developed a rational herpesvirus vaccine in which viral immune evasion genes were deleted to enhance immunogenicity while also attaining safety. To test this vaccine strategy, we utilized murine gammaherpesvirus-68 (MHV-68) as a proof-of-concept model for the cancer-associated human γ-herpesviruses, Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus. We engineered a recombinant MHV-68 virus by targeted inactivation of viral antagonists of type I interferon (IFN-I) pathway and deletion of the latency locus responsible for persistent infection. This recombinant virus is highly attenuated with no measurable capacity for replica...

IOP Conference Series: Materials Science and Engineering, 2019

Nowadays, construction cost plays an essential role in various projects, which are buildings, roa... more Nowadays, construction cost plays an essential role in various projects, which are buildings, roads, railways, and bridges projects. Conceptual cost estimation in feasibility study is require high accuracy and less validation error especially in construction projects at early stages. The more improvement of estimation techniques, it would lead to the lesser problems of cost overrun, and extra expenses. This paper developed a cost estimation model for new constructed rural road projects. Considering the estimation methods for predicting the cost model, parametric method based on regression learner and NN method are applied. Previously, many researchers studied the cost applicable model by using various computer applications, so that this paper differed to compare these methods based on MATLAB. Accordingly, 44 road projects were compiled from DRR database, after that identifying the effective cost parameters referred on collected data. Subsequently, the data implementation process was...

Journal of the Endocrine Society, 2019

Abstract Introduction: mTBI is associated with anterior pituitary hormone dysfunction. The potent... more Abstract Introduction: mTBI is associated with anterior pituitary hormone dysfunction. The potential long-term effect of this injury on pituitary function in Veterans is not clear. Methods: We present an interim report of our 4-year longitudinal prospective pilot study of pituitary function in Veterans diagnosed with mTBI. Of the 34 mTBI Veterans enrolled, we have tested 28 of them (4 female, 24 male; mean±SD age and BMI, 31.1±7.0 years and 30.2±6.2, respectively) for baseline pituitary hormone levels and cortisol response to ACTH. In 22 subjects growth hormone response to glucagon stimulation (GST) was tested at baseline. The same baseline data were obtained for 15 age-, sex-, deployment- and BMI-matched control subjects without mTBI (2 female,13 male; mean±SD age and BMI 33.9±6.8 years and 32.7±7.2, respectively). Follow-up testing has been done for 18 mTBI subjects in Year 1, 13 subjects in Year 2, 8 subjects in Year 3 and 3 subjects in Year 4. GH cutoffs of <1ng/mL for patients with a BMI≥25, and ≤ 3 ng/mL for a BMI < 25 were used for the diagnosis of GHD. Results: GHD was present in 9% (2/22) at baseline, 22% (4/18) at Year 1, 8% (1/13) at Year 2, 22% (2/9) at Year 3, and 0% (0/3) at Year 4. GHD did not occur in the same subject in subsequent years, and it appeared to recover within a year. The peak GST GH level for all subjects at each year trended downward from baseline to Years 1, 2, 3, and 4: (ng/mL, mean±SD) 7.6±7.7; 7.5±13.0; 3.5±3.3; 4.4±4.3; 1.9±0.9, respectively. Secondary hypogonadism occurred in 11%, 6%, 8% of subjects at baseline, Year 1 and Year 2, respectively; none has been found in Years 3 and 4. There are no subjects identified with hypothyroidism or overt adrenal insufficiency at baseline or over 4 years. Unexpectedly, GHD was detected in 27% (4/15) of control subjects. The mean±SD BMI of 39.4±7.8 for these subjects was higher than the BMI values for GH sufficient (GHS) control subjects (30.2±5.2), mTBI patients with GHD (29.6±4.6) and GHS (30.9±6.2). Secondary hypogonadism was present in 14%, and there were no cases of hypothyroidism or adrenal insufficiency. Conclusions: GHD occurs in patients with mTBI at up to 3 years of observation using the stricter GH cutoff criterion with a BMI ≥25. Because each patient with GHD in a particular year was unique, the cumulative occurrence of GHD thus far is 41% (9/22) over 4 years. The highest prevalence was in Year 2. Each subject appeared to recover from GHD in one year. Attrition of subjects has decreased the later year numbers; a more complete review will be possible when the remaining subject testing is completed. The detection of GHD in the non-mTBI control group suggests there may be additional factors in deployment itself that can put military personnel at risk. BMI as a confounding factor with the GST or any GH testing cannot be excluded. Identification of GHD and hypogonadism in Veterans with mTBI will provide treatment opportunities to enhance their recovery.

mentorship and support for the past five years. Gail provided me with excellent guidance and enco... more mentorship and support for the past five years. Gail provided me with excellent guidance and encouragement throughout my graduate training. Her endless support has not only fostered me to become a better scientist but also to become a better writer, and speaker. Without her support and guidance, my thesis work would not have been accomplished. I would like to thank the Interdisciplinary Graduate Program in Immunology for providing an excellent learning and training environment, and Dr. Bishop and Dr. Varga for overseeing the program. Special thanks go to Paulette Villhauer, Joshua Lobb and Kathy Dautremont for keeping me in check with the paperwork and deadlines. I would especially like to thank my thesis committee members (Dr. Jon Houtman, Dr. John Colgan, Dr. Siegfried Janz, and Dr. Frederick Quelle) for their guidance and support for my thesis work. I also wish to thank the Biosciences Program for providing me with financial support during my initial year of graduate school.

Immunity, 2016

Cytokines related to tumor necrosis factor (TNF) provide a communication network essential for co... more Cytokines related to tumor necrosis factor (TNF) provide a communication network essential for coordinating multiple cell types into an effective host defense system against pathogens and malignant cells. The pathways controlled by the TNF superfamily differentiate both innate and adaptive immune cells and modulate stromal cells into microenvironments conducive to host defenses. Members of the TNF receptor superfamily activate diverse cellular functions from the production of type 1 interferons to the modulation of survival of antigen-activated T cells. Here, we focus attention on the subset of TNF superfamily receptors encoded in the immune response locus in chromosomal region 1p36. Recent studies have revealed that these receptors use diverse mechanisms to either co-stimulate or restrict immune responses. Translation of the fundamental mechanisms of TNF superfamily is leading to the design of therapeutics that can alter pathogenic processes in several autoimmune diseases or promote immunity to tumors.

Proceedings of the 2015 International Conference on Industrial Technology and Management Science, 2015

Reliability Centered Maintenance (RCM) is a well-known method in several industries. RCM is a str... more Reliability Centered Maintenance (RCM) is a well-known method in several industries. RCM is a structure decision process to cost-effective determines and optimum maintenance requirements. This paper proposes the application of the RCM concept to a petrochemical case study. The results indicate that preventive maintenance plans and available time of maintenance staff are improved significantly.

Immunological Reviews, 2015

SummaryThe signaling adapter protein tumor necrosis factor receptor (TNFR)‐associated factor 3 (T... more SummaryThe signaling adapter protein tumor necrosis factor receptor (TNFR)‐associated factor 3 (TRAF3) is both modified by and contributes to several types of ubiquitination events. TRAF3 plays a variety of context‐dependent regulatory roles in all types of immune cells. In B lymphocytes, TRAF3 contributes to regulation of signaling by members of both the TNFR superfamily and innate immune receptors. TRAF3 also plays a unique cell type‐specific and critical role in the restraint of B‐cell homeostatic survival, a role with important implications for both B‐cell differentiation and the pathogenesis of B‐cell malignancies. This review focuses upon the relationship between ubiquitin and TRAF3, and how this contributes to multiple functions of TRAF3 in the regulation of signal transduction, transcriptional activation, and effector functions of B lymphocytes.