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Annual Report For The Town Of Hebron, New Hampshire For The Fiscal Year Ending December 31, 2014., Hebron Town Representatives

Hebron, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Annual Reports Of The Town Officers Of Hancock, New Hampshire For The Year Ending December 31, 2014., Hancock Town Representatives

Hancock, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Durham, New Hampshire 2014 Annual Report For The Fiscal Year Ended December 31, 2014., Durham Town Representatives

Durham, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

"Softness" In International Instruments: The Case Of Transnational Corporations, Harri Kalimo, Tim Staal

Syracuse Journal of International Law and Commerce

No abstract provided.

Governance And Uncertainty, Justin R. Pidot

Sturm College of Law: Faculty Scholarship

Government actors create law against a backdrop of uncertainty. Limited information, unpredictable events, and lack of understanding interfere with accurately predicting a legal regime’s costs, benefits, and effects on other legal and social programs and institutions. Does the availability of no-fault divorce increase the number of terminated marriages? Will bulk-collection of telecommunications information about American citizens reveal terrorist plots? Can a sensitive species breed in the presence of oil and gas wells? The answers to these questions are far from clear, but lawmakers must act nonetheless.

The problems posed by uncertainty cut across legal fields. Scholars and regulators in a …

Ontogenic Expression Of Human Carboxylesterase-2 And Cytochrome P450 3a4 In Liver And Duodenum: Postnatal Surge And Organ-Dependent Regulation, Yi-Tzai Chen, Lynnie Trzoss, Dongfang Yang, Bingfang Yan

Biomedical and Pharmaceutical Sciences Faculty Publications

Human carboxylesterase-2 (CES2) and cytochrome P450 3A4 (CYP3A4) are two major drug metabolizing enzymes that play critical roles in hydrolytic and oxidative biotransformation, respectively. They share substrates but may have opposite effect on therapeutic potential such as the metabolism of the anticancer prodrug irinotecan. Both CES2 and CYP3A4 are expressed in the liver and the gastrointestinal tract. This study was conducted to determine whether CES2 and CYP3A4 are expressed under developmental regulation and whether the regulation occurs differentially between the liver and duodenum. A large number of tissues (112) were collected with majority of them from donors at 1–198 days …

Deadline: Ethics And The Ethnographic Divorce, Lisa M. Tillmann Ph.D.

Faculty Publications

In the summer of 2009, the author receives a call from a New York Times reporter about her book Between Gay and Straight. The book portrays her (now-ex) husband’s and her integration into a network of gay male friends. “Deadline” explores tensions between private and public as the private turmoil of divorce clashes with the public construction of the author’s marriage and with her determination to continue the social justice work of Between Gay and Straight.

Novel Mechanisms Of Herbal Therapies For Inhibiting Hmgb1 Secretion Or Action, A. H. Wu, L. He, W. Long, Q. Zhou, S. Zhu, P. Wang, S. Fan, H. Wang

Journal Articles

High mobility group box 1 (HMGB1) is an evolutionarily conserved protein and is constitutively expressed in virtually all types of cells. In response to microbial infections, HMGB1 is secreted from activated immune cells to orchestrate rigorous inflammatory responses. Here we review the distinct mechanisms by which several herbal components inhibit HMGB1 action or secretion, such as by modulating inflammasome activation, autophagic degradation, or endocytic uptake. In light of the reciprocal interactions between these cellular processes, it is possible to develop more effective combinational herbal therapies for the clinical management of inflammatory diseases.

Comorbid Profile Rather Than Age Determines Hip Fracture Mortality In A Nonagenarian Population, A. Graver, S. Merwin, L. Collins, N. Kohn, A. Goldman

Journal Articles

BACKGROUND: In light of poor outcomes with nonoperative management of hip fractures, orthopedic surgeons are faced with difficult decisions about which patients are too ill or too old for surgical treatment. QUESTIONS/PURPOSES: This study sought to investigate if patients over 90 years had different preoperative laboratory, clinical, and injury characteristics than younger patients with the same injury. We compared our cohort with previously published data. We wished to identify if there were pre-injury risk factors associated with 30-day mortality, which could be modified to enhance postoperative outcomes. METHODS: This is a retrospective review of 198 operatively managed hip fractures in …

Age Influences Inflammatory Responses, Hemodynamics, And Cardiac Proteasome Activation During Acute Lung Injury, H. M. Linge, J. Y. Lee, K. Ochani, K. Koga, N. Kohn, K. Ojamaa, S. R. Powell, E. J. Miller

Journal Articles

Background: Acute lung injury (ALI) is a significant source of morbidity and mortality in critically ill patients. Age is a major determinant of clinical outcome in ALI. The increased ALI-associated mortality in the older population suggests that there are age-dependent alterations in the responses to pulmonary challenge. The objective of this observational study was to evaluate age-dependent differences in the acute (within 6 hours) immunological and physiological responses of the heart and lung, to pulmonary challenge, that could result in increased severity. Methods: Male C57Bl/6 mice (young: 2-3 months, old: 18-20 months) were challenged intratracheally with cell wall components from …

Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response, K. J. Tracey

Journal Articles

Mammalian immunity evolved by the process of natural selection that produced differential survival and reproduction advantages through combinations of hereditary traits underlying the response to pathogens. Primitive animals sense the presence of microbial pathogens through recognition of pathogen-derived molecules in their rudimentary immune and nervous systems. No molecular biological mechanism assigns primacy of pathogen sensing mechanisms to immune cells over neurons. Rather, in animals as diverse as Caenorhabditis elegans to mammals, neural reflexes are activated by the presence of pathogens and transduce neural mechanisms that control the development of immunity. A coming revolution in immunological thinking will require immunologists to …

Tlr7 Influences Germinal Center Selection In Murine Sle, A. Boneparth, W. Huang, R. Bethunaickan, M. Woods, R. Sahu, S. Arora, M. Akerman, M. Lesser, A. Davidson

Journal Articles

TLR7 enhances germinal center maturation and migration of B cells to the dark zone where proliferation and somatic hypermutation occur. Our goal was to determine how Tlr7 dose influences selection of the autoreactive B cell repertoire in NZW/BXSB. Yaa mice bearing the site-directed heavy chain transgene 3H9 that encodes for the TLR7 regulated anti-CL response. To create a physiologic setting in which autoreactive B cells compete for survival with non-autoreactive B cells, we generated bone marrow chimeras in which disease onset occurred with similar kinetics and the transferred 3H9+ female non-Yaa, male Yaa or male TLR7(-/Yaa) cells could be easily …

Weight Trends In United States Living Kidney Donors: Analysis Of The Unos Database, M. Sachdeva, L. M. Rosen, J. Varghese, S. Fishbane, E. P. Molmenti

Journal Articles

AIM: To analyze the national trends associated with body mass index (BMI) and living kidney donation. METHODS: Forty-seven thousand seven hundred and five adult living kidney donors as reported to the Organ Procurement and Transplantation Network from 1999 to 2011 were analyzed using their pre-donation BMI. Predictor variables of interest included age, gender, ethnicity, relationship, education status, and transplant region. RESULTS: Sixteen thousand nine hundred and seventy-one of the living kidney donors were normal weight (35.6%); 19337 were overweight (40.5%); 9007 were mildly obese (18.9%); 1992 were moderate to morbidly obese (4.2%). Overweight and mildly obese kidney donors have increased …

The Role Of B-1 Cells In Inflammation, M. Aziz, N. E. Holodick, T. L. Rothstein, P. Wang

Journal Articles

B-1 lymphocytes exhibit unique phenotypic, ontogenic, and functional characteristics that differ from the conventional B-2 cells. B-1 cells spontaneously secrete germline-like, repertoire-skewed polyreactive natural antibody, which acts as a first line of defense by neutralizing a wide range of pathogens before launching of the adaptive immune response. Immunomodulatory molecules such as interleukin-10, adenosine, granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-35 are also produced by B-1 cells in the presence or absence of stimulation, which regulate acute and chronic inflammatory diseases. Considerable progress has been made during the past three decades since the discovery of B-1 cells, which has improved not only …

Milk Fat Globule-Egf Factor Viii Attenuates Cns Injury By Promoting Neural Stem Cell Proliferation And Migration After Cerebral Ischemia, C. Cheyuo, M. Aziz, W. L. Yang, A. Jacob, M. Zhou, P. Wang

Journal Articles

The mediators in activating neural stem cells during the regenerative process of neurogenesis following stroke have not been fully identified. Milk fat globule-EGF Factor VIII (MFGE8), a secreted glycoprotein serves several cellular functions by binding to its receptor, alpha(v)beta(3)-integrin. However, its role in regulating neural stem cells after stroke has not been determined yet. We therefore, aim to reveal whether MFG-E8 promotes neural stem cell proliferation and migration during stroke. Stroke was induced in wild-type (Wt) and MFG-E8-deficinet (Mfge8(-/-)) mice by transient middle cerebral artery occlusion (tMCAO). Commercially available recombinant mouse MFG-E8 (rmMFG-E8) was used for mechanistic assays in neural …

Blocking Cold-Inducible Rna-Binding Protein Protects Liver From Ischemia-Reperfusion Injury, A. Godwin, W. L. Yang, A. Sharma, A. Khader, Z. Wang, F. Zhang, J. Nicastro, G.F. Coppa, P. Wang

Journal Articles

Cold-inducible RNA-binding protein (CIRP) is a nuclear protein that has been recently identified as a novel inflammatory mediator in hemorrhagic shock and sepsis. We hypothesized that CIRP acts as a potent inflammatory mediator in hepatic ischemia-reperfusion (I/R), and thus blocking CIRP protects against I/R-induced liver injury. Male C57BL/6 mice were subjected to 70% hepatic ischemia by microvascular clamping of the hilum of the left and median liver lobes for 60 min, followed by reperfusion. Anti-CIRP antibody (1 mg/kg body weight) or vehicle (normal saline) in 0.2 mL was injected via the internal jugular vein at the beginning of the reperfusion. …

Endoplasmic Reticulum Stress In Sepsis, M. M. Khan, W.L. Yang, P. Wang

Journal Articles

Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units. Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration, is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle, is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. …

Stimulation Of Wnt/Beta-Catenin Signaling Pathway With Wnt Agonist Reduces Organ Injury After Hemorrhagic Shock, M. Kuncewitch, W.L. Yang, A. Jacob, A. Khader, M. Giangola, Jeffrey Nicastro, G. Coppa, P. Wang

Journal Articles

BACKGROUND: Hemorrhagic shock is a leading cause of morbidity and mortality in surgery and trauma patients. Despite a large number of preclinical trials conducted to develop therapeutic strategies against hemorrhagic shock, there is still an unmet need for effective therapy for hemorrhage patients. Wnt/beta-catenin signaling controls developmental processes and cellular regeneration owing to its central role in cell survival and proliferation. We therefore hypothesized that the activation of Wnt signaling reduces systemic injury caused by hemorrhagic shock. METHODS: Adult male Sprague-Dawley rats underwent hemorrhagic shock by controlled bleeding of the femoral artery to maintain a mean arterial pressure of 30 …

Differential Alterations Of Tissue T-Cell Subsets After Sepsis, A. Sharma, W.L. Yang, S. Matsuo, P. Wang

Journal Articles

Among immune cells in responding to sepsis, macrophages and neutrophils have been extensively studied, while the contribution of T lymphocytes and natural killer T (NKT) cells is less well characterized. Here we monitored tissue specific changes of T cell subsets in male C57BL/6 mice subjected to sham operation or cecal ligation and puncture (CLP) to induce polymicrobial sepsis. Thymus, spleen, liver, lungs and blood were processed and analyzed 20h later. Total lymphocyte count showed a significant reduction in septic thymus, spleen and blood but not in lungs and liver. The septic thymi were hypocellular with severe reduction in cell numbers …

Combining Task-Evoked And Spontaneous Activity To Improve Pre-Operative Brain Mapping With Fmri, M. D. Fox, T. Qian, J. R. Madsen, D. Wang, M. Ge, H. C. Zuo, D. M. Groppe, A. D. Mehta, B. Hong, H. Liu, +1 Additional Author

Journal Articles

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional …

Regulation Of Post-Translational Modifications Of Hmgb1 During Immune Responses, B. Lu, Y. Tang, X. Zhao, D. Antoine, X. Xiao, H. Wang, U. Andersson, T. Billiar, K. J. Tracey

Journal Articles

SIGNIFICANCE: High mobility group protein 1 (HMGB1) is an evolutionarily conserved and multi-functional protein. The biological function of HMGB1 depends on its cellular locations, binding partners, and redox states. Extracellular HMGB1 is a mediator of inflammation during infection or tissue injury. Immune cells actively release HMGB1 in response to infection, which in turn orchestrates both innate and adaptive immune responses. RECENT ADVANCES: Hyperacetylation of HMGB1 within its nuclear localization sequences mobilizes HMGB1 from the nucleus to the cytoplasm and subsequently promotes HMGB1 release. The redox states of the cysteines in position 23, 45 and 106 determine the biological activity of …

A Unifying Principle Underlying The Extracellular Field Potential Spectral Responses In The Human Cortex, E. Podvalny, N. Noy, M. Harel, S. Bickel, G. Chechik, C. E. Schroeder, A. D. Mehta, M. Tsodyks, R. Malach

Journal Articles

Electrophysiological mass potentials show complex spectral changes upon neuronal activation. However, it is unknown to what extent these complex band-limited changes are interrelated or, alternatively, reflect separate neuronal processes. To address this question, intracranial electrocorticograms (ECoG) responses were recorded in patients engaged in visuomotor tasks. We found that in the 10- to 100-Hz frequency range there was a significant reduction in the exponent chi of the 1/f(chi) component of the spectrum associated with neuronal activation. In a minority of electrodes showing particularly high activations the exponent reduction was associated with specific band-limited power modulations: emergence of a high gamma (80-100 …

Antibodies As Mediators Of Brain Pathology, L. Brimberg, S. Mader, Y. Fujieda, Y. Arinuma, C. Kowal, B. T. Volpe, B. Diamond

Journal Articles

No abstract provided.

Autoantibodies In Systemic Autoimmune Diseases: Specificity And Pathogenicity, J. Suurmond, B. Diamond

Journal Articles

In this Review we focus on the initiation of autoantibody production and autoantibody pathogenicity, with a special emphasis on the targeted antigens. Release of intracellular antigens due to excessive cell death or to ineffective clearance of apoptotic debris, modification of self-antigens during inflammatory responses, and molecular mimicry contribute to the initiation of autoantibody production. We hypothesize that those autoreactive B cells that survive and produce pathogenic autoantibodies have specificity for self-antigens that are TLR ligands. Such B cells experience both B cell receptor (BCR) activation and TLR engagement, leading to an escape from tolerance. Moreover, the autoantibodies they produce form …

The Brighter (And Evolutionarily Older) Face Of The Metabolic Syndrome: Evidence From Trypanosoma Cruzi Infection In Cd-1 Mice, W. Brima, D. J. Eden, S. F. Mehdi, M. Bravo, M. M. Wiese, J. Stein, V. Almonte, D. Zhao, J. Roth, F. Nagajyothi, +5 Additional Authors

Journal Articles

BACKGROUND: Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS: In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS: In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 …

Enrichment Of Genetic Variants For Rheumatoid Arthritis Within T-Cell And Nk-Cell Enhancer Regions, J. Freudenberg, P. Gregersen, W. Li

Journal Articles

To identify disease-causative variants, we intersected the published results of a metaanalysis of genome-wide association studies (GWAS) for rheumatoid arthritis (RA) with the set of enhancer regions for 71 primary cell types that was provided by the FANTOM consortium. We first retrieved all single nucleotide polymorphisms (SNPs) that are associated (P < 5 x 10(8)) with RA in the GWAS meta-analysis and that are located in any of these enhancer regions. After excluding the major histocompatibility complex (MHC) region, we identified 50 such RA-associated SNPs that are located in enhancer regions. Enhancer sets from different cell types were then compared with each other for their number of RA-associated SNPs by permutation analysis. This analysis showed that RA-associated SNPs are preferentially located in enhancers from several immunological cell types. In particular, we see a strong relative enrichment in enhancer regions that are active in T cells (P < 0.001) and NK cells (P < 0.001). Several loci display multiple RA-associated SNPs in tight linkage disequilibrium that are located within the same or neighboring enhancers. These haplotypes may have a greater likelihood to influence enhancer activity than any SNP on its own. Taken together, these results support the hypothesis that RA-causative variants often act through altering the activity of immune cell enhancers. The enrichment in T-cell and NK-cell enhancer regions indicates that expression changes in these cell types are particularly relevant for the pathogenesis of RA. The specific SNPs that account for this enrichment can be used as a basis for focused genotype-phenotype studies of these cell types.

Excessive Antigen Reactivity May Underlie The Clinical Aggressiveness Of Chronic Lymphocytic Leukemia Stereotyped Subset #8, M. Gounari, S. Ntoufa, B. Apollonio, N. Papakonstantinou, M. Ponzoni, C. C. Chu, D. Rossi, G. Gaidano, N. Chiorazzi, P. Ghia, +1 Additional Author

Journal Articles

Subset #8 is a distinctive subset of patients with chronic lymphocytic leukemia (CLL) defined by the expression of stereotyped IGHV4-39/IGKV1(D)-39 B-cell receptors. Subset #8 patients experience aggressive disease and exhibit the highest risk for Richter transformation among all CLL. In order to obtain biological insight into this behavior, we profiled the antigen reactivity and signaling capacity of subset #8 vs other clinically aggressive stereotyped subsets, namely subsets #1 and #2. Twenty-seven monoclonal antibodies (mAbs) from subsets #1, #2, and #8 CLL clones were prepared as recombinant human immunoglobulin G1 and used as primary antibodies in enzyme-linked immuno-sorbent assays against representatives …

Functional Loss Of I Kappa B Epsilon Leads To Nf-Kappa B Deregulation In Aggressive Chronic Lymphocytic Leukemia, L. Mansouri, L. A. Sutton, V. Ljungstrom, S. Bondza, L. Arngarden, S. Bhoi, X. J. Yan, N. Chiorazzi, R. Rosenquist, +25 Additional Authors

Journal Articles

NF-kappa B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-kappa B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I kappa B epsilon, a negative regulator of NF-kappa B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic …

Resident Endothelial Cells And Endothelial Progenitor Cells Restore Endothelial Barrier Function After Inflammatory Lung Injury, S. Z. Mao, X. B. Ye, G. Liu, D. M. Song, S. F. Liu

Journal Articles

Objective Disruption of endothelial barrier integrity is a characteristic of many inflammatory conditions. However, the origin and function of endothelial cells (ECs) restoring endothelial barrier function remain unknown. This study defined the roles of resident ECs (RECs) and bone marrow-derived endothelial progenitor cells (BMDEPCs) in endothelial barrier restoration after endotoxemic lung injury. Approach and Results We generated mice that enable to quantify proliferating RECs or BMDEPCs and also to study the causal link between REC or BMDEPC proliferation and endothelial barrier restoration. Using these mouse models, we showed that endothelial barrier restoration was associated with increased REC and BMDEPC proliferation. …

Lps Down-Regulates Specificity Protein 1 Activity By Activating Nf-Kappab Pathway In Endotoxemic Mice, X. Ye, H. Liu, Y. S. Gong, S. F. Liu

Journal Articles

BACKGROUND: Specificity protein (Sp) 1 mediates the transcription of a large number of constitutive genes encoding physiological mediators. NF-kappaB mediates the expression of hundreds of inducible genes encoding pathological mediators. Crosstalk between Sp1 and NF-kappaB pathways could be pathophysiologically significant, but has not been studied. This study examined the crosstalk between the two pathways and defined the role of NF-kappaB signaling in LPS-induced down-regulation of Sp1 activity. METHODS AND MAIN FINDINGS: Challenge of wild type mice with samonelia enteritidis LPS (10 mg/kg, i.p.) down-regulated Sp1 binding activity in lungs in a time-dependent manner, which was concomitantly associated with an increased …