bluuebunny/crossref_metadata_2025 huggingface dataset:
Athens: New capital of traditional Greek music: Testimonies on musical life at the beginning of the twentieth century
Authors: Peno Vesna
Published: February 2010

During its long Byzantine and Post-Byzantine history Constantinople was the center for church art in general, but especially for music. This old city on the Bosporus maintained its prime position until the beginning of the 20th century when, because of new political and social conditions, the Greek people started to acquire their independence and freedom, and Athens became the new capital in the cultural as well as the political sense. During the first decades of the 20th century the Athenian music scene was marked by an intensive dispute between those musicians who leaned towards the European musical heritage and its methods in musical pedagogy, and those who called themselves traditionalists and were engaged in the preservation of traditional values of church and folk music. The best insight into the circumstances in which Greek musical life was getting a new direction are offered by the numerous musical journals published in Athens before the First World War. Among them, The Formigs is of the special interest, firstly because of the long period during which it was published (1901-1912), and secondly because of its main orientation. The editor Ioannes Tsoklis, a church chanter, and his main collaborator, the famous Constantinopolitan musician and theorist and later Principal of the Department for Byzantine music at Athens musical school Konstantinos Psahos, with other associates firmly represented the traditional position. That is why most of the published articles and the orientation of the journal generally were dedicated to the controversial problems and current musical events that were attracting public attention. The editorial board believed that there was a connection between the preservation of musical traditions and their development on one side, and foreign musical influences that were evident in the promotion of polyphonic church music, which had been totally foreign to the Greek Orthodox church until the end of the 19th century, on the other. Tsoklis and Psahos were resolved to provide enough reliable documented articles and theoretical and historical studies on church and folk music to pull up the church chanters and in such a way contribute to their better musical education. They assured that this would be the best way to attract and recruit church chanters struggling to maintain their own musical heredity. The Formigs thus served primarily in the so-called Greek music question, actuated with the aim of eliminating polyphonic music from liturgical practice. However, it also assisted in national endeavors to ensure that church and folk music would obtain separate status in official Greek musical education, which had been significantly changed by non-traditional, European methodology.
Multi-temperature mixture of fluids
Authors: Ruggeri Tommaso
Published: February 2010

We present a survey on some recent results concerning the different models of a mixture of compressible fluids. In particular we discuss the most realistic case of a mixture when each constituent has its own temperature (MT) and we first compare the solutions of this model with the one with a unique common temperature (ST ). In the case of Eulerian fluids it will be shown that the corresponding (ST ) differential system is a principal subsystem of the (MT) one. Global behavior of smooth solutions for large time for both systems will also be discussed through the application of the Shizuta-Kawashima condition. Then we introduce the concept of the average temperature of mixture based upon the consideration that the internal energy of the mixture is the same as in the case of a single-temperature mixture. As a consequence, it is shown that the entropy of the mixture reaches a local maximum in equilibrium. Through the procedure of Maxwellian iteration a new constitutive equation for non-equilibrium temperatures of constituents is obtained in a classical limit, together with the Fick's law for the diffusion flux. Finally, to justify the Maxwellian iteration, we present for dissipative fluids a possible approach of a classical theory of mixture with multi-temperature and we prove that the differences of temperatures between the constituents imply the existence of a new dynamical pressure even if the fluids have a zero bulk viscosity.
Criminal acts related to the exploitation of child pornography through abuse of computer systems and networks: International and domestic criminal legislation framework
Authors: Stevanovic Ivana
Published: February 2010

The paper points out the importance of newly adopted international norms and standards that State Parties should undertake to aim a more adequate protection of children from sexual exploitation especially a pornography exploitation. A specific section of this paper is dedicated to the overview of the domestic criminal legislation framework regarding the protection of children victims of crimes related to their exploitation in pornography through abuse of computer systems and networks, and considering the recent changes in the criminal legislation in the Republic of Serbia. In this paper the author particularly analyses the compliance of certain provisions of the Criminal Code with the assumed international obligations.
Do Complexity, Governance, and Auditor Independence Influence whether Firms Retain Their Auditors for Tax Services?
Authors: Lassila Dennis R. , Omer Thomas C. , Shelley Marjorie K. , Smith L. Murphy
Published: February 2010

ABSTRACT: This study examines factors that influenced public companies to retain or dismiss their audit firms as tax service providers during the years immediately surrounding the passage of the Sarbanes-Oxley Act (SOX) in 2002. We find a positive relation between a company’s tax and operating complexity and the probability that it retained its auditor-provided tax services, suggesting that complexity increases the potential benefits from knowledge spillover relative to the costs from perceived auditor independence impairment. We find a positive relation between the strength of a company’s corporate governance and the probability that it retained auditor-provided tax services, suggesting that companies with strong governance expected benefits from knowledge spillover to exceed costs from perceived auditor independence impairment. Although we find no direct relation between auditor tenure and the decision to retain auditor-provided tax services, we do find a significant negative association between auditor retention and high nontax, nonaudit services (NAS) fees, and between auditor retention and the joint effect of long auditor tenure and high nontax NAS fees. Thus, firms with low auditor independence and long audit tenure are less likely to retain their auditor for tax services than are firms with high nontax NAS fees alone.
Near infrared imaging of micro-structured polymer-metal surface pattern
Authors: Han J. , Lee J. , Lee T. , Kang J.
Published: February 2010

Two-dimensional infrared scanning microscopy images of micro-structured surface patterns in an organic transistor device with metal electrode stripes on a polymer channel layer have been demonstrated. A compact single mode optical fiber scanning probe which has a micro dome-shape lens at the tip end was used for the scanning in which reflected beam intensities are coupled back to the optical fiber transceiver depending on the returned power of the sample material. Based on the experiment, the obtained structural dimensions of the micro structure specimen were well matched to the designed ones. These images were compared to the digital microscopy photos for a potential usage to conduct not only the in situ microscopic electrode pattern monitoring of the device but also to non-destructively investigate any surface reflecting material in micrometer scales.
Policies with Respect to Foreign Investors in the New Member States of the European Union and in the Developing Countries of Asia: A Comparative Aspects
Authors: Witkowska Janina
Published: February 2010

The purpose of this article is to provide a comparative analysis of policies aimed at foreign investors in the new member states of the European Union as well as in the developing countries of Asia. The policies demonstrate certain similarities in spite of the fact that the analyzed world economic regions are subject to different conditions. A common feature is the opening up of economies to foreign investors, coupled with the application of certain incentives intended to increase the attractiveness of the country to foreign investors. Countries strive to modernize their economies with the help of foreign capital. The developing countries of Asia, in contrast to the new member states of the European Union, are not restricted in their policies with respect to foreign investors by the requirements of regional economic integration.
In Search of a Strategy for Innovation Policy of Polish Economy
Authors: Kasperkiewicz Witold , Dworak Edyta
Published: February 2010

The paper considers the very important problem of innovativeness of Polish economy with particular attention given to its innovation policy. The purpose of the paper is to explain the character of innovation policy which has been implemented in Poland since the beginning of economic transformation. Additionally, the paper attempts to evaluate the level of innovativeness of Polish economy. The analysis is based on the set of indicators applied in the European Innovation Scoreboard and Statistical Survey presenting in Statistical Yearbook of Poland. Developing effective and consistent innovation policy requires choice of a particular strategy of innovation development which forms the basis for the policy. One can distinguish two such models in modern economy. In the first model, scientific and technical achievements of domestic R&D sector constitute the main factor indispensable for development of innovation. Investments in domestic scientific and development research determine invention and innovation supply. This model is applied in innovation policy of well-developed economies (Japan, the USA, Germany and Sweden). In contrast, the second model, referred to as adaptive, is based on import of new technologies. Poland should develop an adaptive model, however, its effectiveness will be dependent on the increase of the level of R&D investments, especially in the case of enterprises. The problem is that creative adaptation of imported technologies requires appropriate investments in financing domestic R&D institutions. The paper is divided into three parts. First deals with the characteristics of innovative potential and innovative activity of Polish economy. Second is devoted to the problem of innovation policy in Poland. Considerations presented in this part allow to come to a few conclusions concerning evaluation of innovation policy implemented in Poland. The last part discusses the issue of innovation strategy suitable for development of Polish economy in long run.
Economics of Non-Timber Forest Products and Services
Authors: Subedi Bhishma P
Published: February 2010

DOI: 10.3126/init.v1i0.2677The Initiation Vol.1 2007 p.32-35
Santi & Munia: Conservation for their Reunion
Authors: Thapa Kanchan
Published: February 2010

DOI: 10.3126/init.v1i0.2685The Initiation Vol.1 2007 p.77-78
Diversity, Uses and Management of Plant Resources in Leasehold Forests of Makwanpur District, Nepal
Authors: Kunwar Ripu M , Adhikar Nirmal
Published: February 2010

DOI: 10.3126/init.v1i0.2688The Initiation Vol.1 2007 p.88-92
Protected Mammals of Nepal
Authors: Gotame Bharat
Published: February 2010

DOI: 10.3126/init.v1i0.2693The Initiation Vol.1 2007 p.112-116
Writing with a purpose
Authors: Dhungana V
Published: February 2010

DOI: 10.3126/kumj.v7i2.2696Kathmandu University Medical Journal (2009) Vol.7, No.2 Issue 26, 91
Hospital based analytic study of peptic ulcer disease in patients with dyspeptic symptoms
Authors: Sharma SK , Maharjan DK , Thapa PB
Published: February 2010

Background: Peptic ulcer disease is one of the most common diseases prevalent in developing country like Nepal and with availability of endoscopy there have been increase in diagnosis and therapeutic use of endoscopy. Objective: The aim of this study is to investigate the prevalence of peptic ulcer disease in patient who came for upper gastrointestinal endoscopy in Kathmandu Medical College Teaching Hospital. Materials and methods: All patients who were referred to department of endoscopy from outpatient department (OPD) and inpatient department with symptoms like dyspepsia, upper GI bleeding were included from August 2004 to August 2008. Results: A total of 2761 patient were evaluated, with mean age group of 40.57 years (range 8- 95 years) and with sex distribution of male 1353 (49%) and female 1408 (51%) and racial difference into Aryan 2050 (74.2%) and Mongoloid 771 (25.8%). There were 983 patients (35.60%) with peptic disease which includes erosive gastritis, non erosive gastritis, duodenitis and gastroduodenitis without obvious ulcer. The prevalence of peptic disease with or without ulcer was more common in age group of 20- 49 years (n= 764, 27.67 %) with 70 patient with gastric ulcer (2.5%) and 50 patient with duodenal ulcer (1.8%). There was no significant racial difference among incidence of peptic ulcer (P value= 0.527). Conclusions: Peptic ulcer disease is a significant cause of morbidity in urban population of Nepal with more prevalent of erosive diseases in productive age group (20-49 years). However both male and female have equal incidence of peptic ulcer disease and there was no significant racial difference in its incidence. Key words: Peptic ulcer diseases; Oesophago-gastroduodenoscopy; H. pylori DOI: 10.3126/kumj.v7i2.2706 Kathmandu University Medical Journal (2009) Vol.7, No.2 Issue 26, 135-138
Evaluation of fine needle aspiration cytology of lymph nodes in Kathmandu Medical College, Teaching hospital
Authors: Hirachand S , Lakhey M , Akhter J , Thapa B
Published: February 2010

Background: Fine Needle Aspiration Cytology (FNAC) is a simple and rapid diagnostic technique. Because of early availability of results, simplicity, minimal trauma and complications, the aspiration cytology is now considered a valuable diagnostic aid and is part and parcel of a pathologist's repertoire. Objectives: The aim of the study was to evaluate the results of fine needle aspiration cytology (FNAC) of lymph nodes in our institution in comparison to result of histopathology. Materials and methods: The present study on 130 patients of lymphadenopathy was conducted in the Department of Pathology Kathmandu Medical College Teaching hospital, Kathmandu from June 2006 to May 2008 (2 years). Results: In this series of FNAC cervical lymph nodes were 66 (50.76%), and axillary lymph nodes were 20 (15.38%). Male to female ratio of the patients was 1: 0.9. Th age of patients ranged from 3 to 85 years. FNAC diagnosis was found to be as follows : reactive hyperplasia 54( 41.55%), tubercular lymphadenitis 36 (28 %), metastatic carcinoma 16 (12.3%), granulomatous lymphadenitis 12 ( 9.2 % ), lymphoma 8 (6%) and suppurative lymphadenitis 4(3%). Out of 28 cases of FNAC 26 (92.85%) were consistent with histopathological diagnosis of tubercular lymphadenitis. In metastatic carcinoma to lymph nodes sensitivity and specificity of FNAC were 100% each. Conclusion: FNAC is useful and reliable in diagnosing neoplastic and non- neoplastic lesions of lymph nodes. It helps in planning surgery for malignant cases, where definitive operative intervention can be performed in one session. Key words: FNAC; lymphadenopathy. DOI: 10.3126/kumj.v7i2.2707 Kathmandu University Medical Journal (2009) Vol.7, No.2 Issue 26,139-142
Congenital cytomegalovirus virus infection
Authors: Rana PVS
Published: February 2010

A 14 months old male child with psychomotor retardation and hypotonia is reported, where computerized axial tomography revealed multiple calcification and ventriculomegaly secondary to cortical atrophy. Investigation suggested the diagnosis of cytomegalovirus infection. Importance of early diagnosis is emphasized as the potential long term sequelae can be prevented or reduced markedly with available therapeutic options. Key words: Congenital; Cytomegalovirus; Psychomotor retardation; Calcification; Ganciclovir; Hyper immune globulin DOI: 10.3126/kumj.v7i2.2709 Kathmandu University Medical Journal (2009) Vol.7, No.2 Issue 26, 145-148
Role of pharmacogenomics in the drug development
Authors: Suvarna BS
Published: February 2010

Individuals respond differently to drugs and sometimes the effects are unpredictable. Differences in DNA that alter the expression or function of proteins targeted by drugs can contribute significantly to the variation in the individuals responses. The use of pharmacogenomics is to identify genetic polymorphisms that predispose patients to adverse drug effects that, although they may occur in only a small subset of the people treated with a new medication, are sufficiently toxic to jeopardise further development of the drug for all patients. Given the potential value of knowing all the possible factors that influence the effects of new agents, it is likely that pharmacogenomics will have an increasingly important role in drug discovery and development. This article briefly reviews concepts that underlie the emerging fields of pharmacogenetics and pharmacogenomics, with an emphasis on the pharmacogenetics of drug metabolism. Although only a few examples will be provided to illustrate concepts and to demonstrate the potential contribution of pharmacogenetics to medical practice, it is now clear that virtually every pathway of drug metabolism will eventually be found to have genetic variation. Key words: Drug; genotype; pharmacogenetics; pharmacogenomics DOI: 10.3126/kumj.v7i2.2716 Kathmandu University Medical Journal (2009) Vol.7, No.2 Issue 26, 172-176
Nepal Medical Council: The past and the future
Authors: Dixit H
Published: February 2010

The Nepal Medical Council (NMC) has been technically in operation for forty six years though in reality it is much less. The initial years were spent in establishing it. It is only in the last fifteen years or so that there has been much interest in it's functioning. The objective of the NMC is to protect the public and also to oversee the medical education being conducted within the country. A brief account of the NMC from its date of establishment till the present is given here. Key words: NMC; NMA; Medical Education; Medical Colleges. DOI: 10.3126/kumj.v7i3.2723 Kathmandu University Medical Journal (2009) Vol.7, No.3 Issue 27, 196-203
The significance of lipid profile and positive troponin in predicting cardiac event
Authors: De Silva LDR , Kumar A , Sathian B
Published: February 2010

Background: Diagnosis of Acute cardiac event in the early stage of its onset is important in the treatment process. The development of highly sensitive and specific immunoassays for myocardial proteins such as cardiac Troponin I (cTnI) had made it possible. However Troponin indicates cardiac events only after its onset or after cardiac tissue necrosis. Traditionally such high risk subjects were identified using lipid profiles. The identification of subjects with high risk of developing cardiac event in the future is more significant as it will provide time to prevent such incidents. Objectives: In this study we proposed to study the usefulness of traditional lipid profile levels in screening subjects who had developed chest pain due to cardiac event as indicated by a positive Troponin I test. Materials and methods: In this retrospective study data of the 259 patients presented to the emergency department with symptoms of cardiac ischemia who underwent both Troponin and lipid profiles tests were compared with the lipid profiles of 105 normal healthy subjects (controls). The Trponin was detected qualitatively when a specimen contains Troponin I (cTnI) above the 99th percentile (TnI >0.5 ng/ml). The Total cholesterol (TC), High density lipoproteins cholesterol (HDL), Very low density lipoproteins (VLDL), and Triacyl glycerol levels (TG) were also analysed and low density lipoprotein level (LDL) was calculated using Friedelwald formula. Results: Subjects with chest pain and positive Troponin test (with confirmed cardiac event) were found to have significantly elevated levels of TC, TG , LDL and significantly reduced HDL levels when compared to the subjects who had only chest pain (Negative Troponin) and healthy controls. Conclusion: Traditional lipid profile levels still can be used in screening populations to identify the subjects with high risk of developing cardiac event which is identified by highly sensitive and specific positive Troponin test. Key words: Troponin; Chest pain; Cardiac event; lipid profile DOI: 10.3126/kumj.v7i3.2735 Kathmandu University Medical Journal (2009) Vol.7, No.3 Issue 27, 263-267
How to uphold standards of medical education in Nepal: Some recommendations
Authors: Baral P
Published: February 2010

DOI: 10.3126/kumj.v7i3.2747 Kathmandu University Medical Journal (2009) Vol.7, No.3 Issue 27, 328-329
Painting the CANVAS
Authors: Dhungana V , Sthapit B , Sigdel B
Published: February 2010

DOI: 10.3126/kumj.v7i3.2749 Kathmandu University Medical Journal (2009) Vol.7, No.3 Issue 27, 334-335
From Practice to Education: Perspectives From Three Nurse Leaders
Authors: Danna Denise , Schaubhut Rose M. , Jones John R.
Published: February 2010

Three nurse leaders recount their experiences transitioning from a practice career to an academic career. These nurse leaders discuss their experiences with role transition and gaining new competencies, comparing and contrasting the competencies of nurse educators and nurse leaders. Specific examples are presented addressing collaborative efforts between practice and education.

J Contin Educ Nurs
2010;41(2):83–87.
Using Reusable Learning Objects
Authors: Billings Diane M.
Published: February 2010

Reusable learning objects (RLOs) are predeveloped digital learning activities that can be integrated into lessons, modules, and courses. Several repositories have nursing-specific RLOs waiting to be used by nurse educators.

J Contin Educ Nurs
2010;41(2):54–55.
The Validity of Schizophrenia vs. Bipolar Disorder
Authors: Lake C. Ray
Published: February 2010

CME Educational Objectives

1.

Differentiate the consistencies of the historical concepts of bipolar disorder versus schizophrenia and distinguish that the diagnostic criteria for bipolar disorder are unique and disease-specific in contrast with those of schizophrenia.

2.

Compare the validities of schizophrenia versus bipolar disorder.

3.

Outline the signs and symptoms of bipolar disorder.
Molecular Genetics and the Kraepelinian Dichotomy: One Disorder, Two Disorders, or Do We Need to Start Thinking Afresh?
Authors: Craddock Nick , Owen Michael J.
Published: February 2010

CME Educational Objectives

1.

Cite genetic findings in mood and psychotic illness.

2.

Review implications of recent genetic findings for understanding the relationship between mood and psychotic illness.

3.

Discuss implications of recent findings for understanding the relationship between mood and psychotic illness and other psychiatric phenotypes, such as autism.
Accuracy and Reproducibility of Artemis Central Flap Thickness and Visual Outcomes of LASIK With the Carl Zeiss Meditec VisuMax Femtosecond Laser and MEL 80 Excimer Laser Platforms
Authors: Reinstein Dan Z. , Archer Timothy J. , Gobbe Marine , Johnson Neil
Published: February 2010

PURPOSE:

To quantify the accuracy and reproducibility of central flap thickness for flaps created with the VisuMax femtosecond laser system.

METHODS:

This was a prospective study of 24 eyes of 12 myopic LASIK patients. The VisuMax femtosecond laser was used to create flaps with an intended central flap thickness of 110
µ
m. Artemis 1 very high-frequency digital ultrasound scans were performed preoperatively and 3 months postoperatively. Central flap thickness was calculated as the addition of the preoperative epithelial thickness and the postoperative stromal component of the flap. Descriptive statistics (mean, standard deviation, minimum, maximum, and range) of central Reinstein Flap Thickness were calculated for all flaps. Central flap thickness accuracy was calculated as the difference between the mean and intended flap thickness. Reproducibility was evaluated as the flap thickness standard deviation between eyes.

RESULTS:

At 3 months, mean central Reinstein Flap Thickness was 112.3±7.9
µ
m (range: 102.6 to 132.9
µ
m). The accuracy was +2.3
µ
m and reproducibility was 7.9
µ
m. On average, the flap diameter was 0.47±0.21 mm greater than the intended flap diameter.

CONCLUSIONS:

The VisuMax femtosecond laser system was found to create flaps accurate to the intended thickness in the center with a low standard deviation, which will help reduce the risk of obtaining an excessively thick flap. [
J Refract Surg
. 2010;26:107–119.]
Evaluation of a Risk Factor Scoring System for Corneal Ectasia After LASIK in Eyes With Normal Topography
Authors: Binder Perry S. , Trattler William B.
Published: February 2010

PURPOSE:

To assess a previously published risk score system for predicting postoperative LASIK ectasia in eyes with normal preoperative topography.

METHODS:

A retrospective review of one surgeon's LASIK database was performed for eyes with Randleman ectasia risk scores based on patient age <30 years, pre-operative central corneal thickness <510 µm, residual stromal bed thickness <300 µm, and/or a preoperative manifest refraction spherical equivalent >−8.00 diopters that had a minimum follow-up of 1 year.

RESULTS:

Of 1702 eyes with myopic errors and normal topographies, 35 (2.0%) eyes had a combined risk score between 5 and 9 points, 92 (5.4%) eyes had a combined risk score of 4 or higher, and 208 (12.2%) eyes had a combined score of 3 or higher. None of these eyes developed ectasia, whereas 3 eyes with preoperative topographic keratoconus with no other risk factors developed ectasia.

CONCLUSIONS:

The current risk score system would have eliminated 5.4% of eyes with 4 or more points from LASIK surgery, and would have also required the surgeon to advise an additional 6.8% of eyes with a score of 3 that they were at “moderate risk” and should “proceed with caution.” In eyes with normal preoperative topographies, the scoring system may not accurately predict whether patients are at increased risk for developing postoperative LASIK ectasia. [
J Refract Surg
. 2010;26:241–250.]
Factors Related to the Correction of Astigmatism by LASIK After Penetrating Keratoplasty
Authors: Lee Hyun Soo , Kim Man Soo
Published: February 2010

Purpose:

To analyze the preoperative factors related to successful correction of astigmatism by LASIK after penetrating keratoplasty (PKP).

Methods:

This retrospective chart review included 71 patients (75 eyes) undergoing LASIK after PKP. The full refractive cylindrical (thus near-spherical) errors were treated by laser ablation. Postoperative follow-up examinations included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest autorefraction, slit-lamp examination, topography, specular microscopy, and simple questionnaire regarding satisfaction with LASIK at 1 day, 1 week, and 1, 6, and 12 months.

Results:

Before surgery, no eye had UDVA of 20/60 or better and 42 (56%) eyes had CDVA of 20/40 or better. At 1 year, 45 (60%) eyes had UDVA of 20/60 or better and 57 (76%) eyes had CDVA of 20/40 or better. The mean astigmatism was 6.80±2.10 diopters (D) preoperatively. The mean reduction of astigmatism was 3.80±2.30 D (53.9±28.7%) at 12 months after LASIK and was relatively stable between 6 and 12 months. Although mean achieved correction showed a tendency toward undercorrection, CDVA and contact lens/spectacle tolerance were significantly increased. The younger the patient, the lesser magnitude of refractive cylinder, and greater endothelial cell density showed better astigmatism reduction in the multiple regression analysis.

Conclusions:

LASIK is a safe and effective procedure with stability for reducing astigmatism following PKP and increasing spectacle or contact lens tolerance. For optimal predictability and visual outcomes after LASIK, we recommend the full identification of astigmatism after PKP and preoperative analysis of the endothelial cell density.
Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy
Authors: Alam Kaiser , Ghousunnissa Sheikh , Nair Shiny , Valluri Vijaya Lakshmi , Mukhopadhyay Sangita
Published: February 2010

The glutathione-redox balance, expressed as the ratio of intracellular reduced glutathione (GSH) and oxidized glutathione, plays an important role in regulating cellular immune responses. In the current study, we demonstrate that alteration of glutathione-redox balance in macrophages by GSH donors like cell-permeable glutathione ethyl ester reduced or N-acetyl-l-cysteine (NAC) can differentially regulate production of IL-12 cytokine in macrophages. A low concentration of NAC increased IL-12 p40/p70 production, whereas at high concentration, IL-12 production was inhibited due to increased calmodulin expression that binds and sequesters c-rel in the cytoplasm. Although NAC treatment increased the IκBα phosphorylation, it failed to increase TNF-α levels due to enhanced expression of suppressor of cytokine signaling 1, which specifically prevented nuclear translocation of p65 NF-κB. We demonstrate that NAC at 3 mM concentration could increase bacillus Calmette-Guérin–induced IFN-γ production by PBMCs from patients with active tuberculosis and shifts the anti–bacillus Calmette-Guérin immune response toward the protective Th1 type. Our results indicate that redox balance of glutathione plays a critical role in regulating IL-12 induction in native macrophages, and NAC can be used in tailoring macrophages to induce enhanced Th1 response that may be helpful to control tuberculosis and other pathophysiological disorders.
Detailed Characterization of T Cell Responses to Herpes Simplex Virus-2 in Immune Seronegative Persons
Authors: Posavad Christine M. , Remington Michael , Mueller Dawn E. , Zhao Lin , Magaret Amalia S. , Wald Anna , Corey Lawrence
Published: February 2010

In 2003, we described a small cohort of subjects (n = 6) who possessed no detectable serum Abs to HSV-1 or HSV-2 and no clinical or virological evidence of mucosal HSV infection yet possessed consistently detectable HSV-specific T cell responses measured primarily by lymphoproliferative (LP) and CTL assays to whole HSV-2 Ag. We termed these persons immune seronegative (IS). This report characterizes the T cell responses in 22 IS subjects largely recruited from studies of HSV-seronegative subjects in ongoing sexual relationships with HSV-2–seropositive (HSV-2+) partners using pools of overlapping peptides spanning 16 immuno-prevalent HSV-2 proteins. Overall, 77% of IS subjects had HSV-specific LP responses, 85% had IFN-γ ELISPOT responses to at least one HSV-2 peptide pool, and 55% had both LP and IFN-γ ELISPOT responses. In some cases, IFN-γ ELISPOT responses were in excess of 500 spot-forming cells per 106 PBMCs and persisted for over 5 y. Although HSV-2+ subjects (n = 40) had frequent responses to glycoproteins and tegument and immediate-early (IE) proteins of HSV-2, T cell responses in IS subjects were directed primarily at UL39 and the IE proteins ICP4 and ICP0. These data suggest that the antigenic repertoire of T cells in IS subjects is skewed compared with that of HSV-2+ subjects and that IS subjects had more frequent T cell responses to IE proteins and infrequent T cell responses to virion components. Understanding the mechanism(s) by which such responses are elicited may provide important insights in developing novel strategies for preventing acquisition of sexually acquired HSV-2.
Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver
Authors: Oo Ye H. , Weston Chris J. , Lalor Patricia F. , Curbishley Stuart M. , Withers David R. , Reynolds Gary M. , Shetty Shishir , Harki Jehan , Shaw Jean C. , Eksteen Bertus , Hubscher Stefan G. , Walker Lucy S. K. , Adams David H.
Published: February 2010

Regulatory T cells (Tregs) are found at sites of chronic inflammation where they mediate bystander and Ag-specific suppression of local immune responses. However, little is known about the molecular control of Treg recruitment into inflamed human tissues. We report that up to 18% of T cells in areas of inflammation in human liver disease are forkhead family transcriptional regulator box P3 (FoxP3)+ Tregs. We isolated CD4+CD25+CD127lowFoxP3+ Tregs from chronically inflamed human liver removed at transplantation; compared with blood-derived Tregs, liver-derived Tregs express high levels of the chemokine receptors CXCR3 and CCR4. In flow-based adhesion assays using human hepatic sinusoidal endothelium, Tregs used CXCR3 and α4β1 to bind and transmigrate, whereas CCR4 played no role. The CCR4 ligands CCL17 and CCL22 were absent from healthy liver, but they were detected in chronically inflamed liver where their expression was restricted to dendritic cells (DCs) within inflammatory infiltrates. These DCs were closely associated with CD8 T cells and CCR4+ Tregs in the parenchyma and septal areas. Ex vivo, liver-derived Tregs migrated to CCR4 ligands secreted by intrahepatic DCs. We propose that CXCR3 mediates the recruitment of Tregs via hepatic sinusoidal endothelium and that CCR4 ligands secreted by DCs recruit Tregs to sites of inflammation in patients with chronic hepatitis. Thus, different chemokine receptors play distinct roles in the recruitment and positioning of Tregs at sites of hepatitis in chronic liver disease.
Ischemic Injury Enhances Dendritic Cell Immunogenicity via TLR4 and NF-κB Activation
Authors: Jurewicz Mollie , Takakura Ayumi , Augello Andrea , Naini Said Movahedi , Ichimura Takaharu , Zandi-Nejad Kambiz , Abdi Reza
Published: February 2010

Ischemic (isc) injury during the course of transplantation enhances the immunogenicity of allografts and thus results in poorer graft outcome. Given the central role of dendritic cells (DCs) in mounting alloimmune responses, activation of donor DCs by ischemia may have a primary function in the increased immunogenicity of isc allografts. In this study, we sought to investigate the effect of ischemia on DC activity in vitro. Following induction of ischemia, bone marrow-derived DCs were shown to augment allogeneic T cell proliferation as well as the IFN-γ response. Isc DCs produced greater levels of IL-6, and isc insult was concurrent with NF-κB activation. TLR4 ligation was also shown to occur in isc DCs, most likely in response to the endogenous ligand heat shock protein 70, which was found to be elevated in DCs following isc injury, and lack of TLR4 abrogated the observed effects of isc DCs. As compared with control DCs, isc DCs injected into the footpads of mice demonstrated enhanced migration, which was concomitant with increased recipient T cell activity. Moreover, isc DCs underwent a greater degree of apoptosis in the lymph nodes of injected mice, which may further demonstrate enhanced immunogenicity of isc DCs. We thus show that isc injury of DCs enhances DC function, augments the allogeneic T cell response, and occurs via ligation of TLR4, followed by activation of NF-κB. These data may serve to identify novel therapeutic targets to attenuate graft immunogenicity following ischemia.
CD8 T Cell Cross-Reactivity Networks Mediate Heterologous Immunity in Human EBV and Murine Vaccinia Virus Infections
Authors: Cornberg Markus , Clute Shalyn C. , Watkin Levi B. , Saccoccio Frances M. , Kim Sung-Kwon , Naumov Yuri N. , Brehm Michael A. , Aslan Nuray , Welsh Raymond M. , Selin Liisa K.
Published: February 2010

In this study, we demonstrate complex networks of CD8 T cell cross-reactivities between influenza A virus and EBV in humans and between lymphocytic choriomeningitis virus and vaccinia virus in mice. We also show directly that cross-reactive T cells mediate protective heterologous immunity in mice. Subsets of T cell populations reactive with one epitope cross-reacted with either of several other epitopes encoded by the same or the heterologous virus. Human T cells specific to EBV-encoded BMLF1280–288 could be cross-reactive with two influenza A virus or two other EBV epitopes. Mouse T cells specific to the vaccinia virus-encoded a11r198–205 could be cross-reactive with three different lymphocytic choriomeningitis virus, one Pichinde virus, or one other vaccinia virus epitope. Patterns of cross-reactivity differed among individuals, reflecting the private specificities of the host’s immune repertoire and divergence in the abilities of T cell populations to mediate protective immunity. Defining such cross-reactive networks between commonly encountered human pathogens may facilitate the design of vaccines.
Different Bacterial Pathogens, Different Strategies, Yet the Aim Is the Same: Evasion of Intestinal Dendritic Cell Recognition
Authors: Bedoui Sammy , Kupz Andreas , Wijburg Odilia L. , Walduck Anna K. , Rescigno Maria , Strugnell Richard A.
Published: February 2010

Given the central role of intestinal dendritic cells (DCs) in the regulation of gut immune responses, it is not surprising that several bacterial pathogens have evolved strategies to prevent or bypass recognition by DCs. In this article, we will review recent findings on the interaction between intestinal DCs and prototypical bacterial pathogens, such as Salmonella, Yersinia, or Helicobacter. We will discuss the different approaches with which these pathogens seek to evade DC recognition and subsequent T cell activation. These diverse strategies span to include mounting irrelevant immune responses, inhibition of Ag presentation by DCs, and stretch as far as to manipulate the Th1/Th2 balance of CD4+ T cells in the bacteria’s favor.
Diversity of the CD8+ T Cell Repertoire Elicited against an Immunodominant Epitope Does Not Depend on the Context of Infection
Authors: Rudd Brian D. , Venturi Vanessa , Smithey Megan J. , Way Sing Sing , Davenport Miles P. , Nikolich-Žugich Janko
Published: February 2010

The diversity of the pathogen-specific T cell repertoire is believed to be important in allowing recognition of different pathogen epitopes and their variants and thereby reducing the opportunities for mutation-driven pathogen escape. However, the extent to which the TCR repertoire can be manipulated by different vaccine strategies so as to obtain broad diversity and optimal protection is incompletely understood. We have investigated the influence of the infectious/inflammatory context on the TCR diversity of the CD8+ T cell response specific for the immunodominant epitope in C57BL/6 mice, derived from glycoprotein B of HSV-1. To that effect, we compared TCR V segment utilization, CDR3 length, and sequence diversity of the response to natural HSV-1 infection with those elicited by either Listeria monocytogenes or vaccinia virus expressing the immunodominant epitope in C57BL/6 mice. We demonstrate that although the type of infection in which the epitope was encountered can influence the magnitude of the CD8+ T cell responses, TCR β-chain repertoires did not significantly differ among the three infections. These results suggest that widely different live vaccine vectors may have little impact upon the diversity of the induced CTL response, which has important implications for the design of live CTL vaccine strategies against acute and chronic infections.
Contribution of Myelin Autoantigen Citrullination to T Cell Autoaggression in the Central Nervous System
Authors: Carrillo-Vico Antonio , Leech Melanie D. , Anderton Stephen M.
Published: February 2010

Breakdown in immunological self tolerance, leading to autoimmune diseases such as multiple sclerosis, might arise from immune recognition of self proteins that have undergone heightened posttranslational modification under pathophysiological conditions. A posttranslational modification of particular interest is the deimination of Arg to citrulline, catalyzed by peptidylarginyl deiminase (PAD) enzymes. As a CD4+ T cell-driven model of multiple sclerosis, we used experimental autoimmune encephalomyelitis (EAE) induced with the immunodominant 35–55 peptide of myelin oligodendrocyte glycoprotein (pMOG) in C57BL/6 mice to test whether citrullination of a T cell epitope can contribute to disease etiopathology. Immunization with an altered peptide ligand (APL) of pMOG with an Arg→citrulline conversion at a TCR contact (residue 41) led to the activation of two populations of APL-responsive T cells that either did, or did not cross-react with the native pMOG peptide. This APL could induce EAE. However, this reflected the activation of T cells that cross-reacted with the native pMOG epitope, because prior tolerization of these T cells using pMOG prevented APL-induced EAE. Using a passive transfer model, we found that T cells that responded specifically to the citrullinated form of pMOG were neither necessary, nor sufficient to initiate the EAE lesion. Nevertheless, these cells could provoke exacerbation of pathology if transferred into mice with ongoing EAE. The PAD2 and PAD4 enzymes were markedly upregulated in the inflamed CNS. Therefore, once inflammation is established, citrullination of target autoantigens can allow an expanded repertoire of T cells to contribute to CNS pathology.
Ruminant Grazing of Cover Crops: Effects on Soil Properties and Agricultural Production
Authors: Poffenbarger Hanna
Published: February 2010

Integrating livestock into a cropping system by allowing ruminant animals to graze cover crops may yield economic and environmental benefits. The effects of grazing on soil physical properties, soil organic matter, nitrogen cycling and agricultural production are presented in this literature review. The review found that grazing cover crops generally led to increased bulk density, especially in no‐till systems. On the other hand, the negative effects of grazing on penetration resistance and aggregate stability were more prominent under conventional tillage than no‐till. The deleterious effects of grazing on soil physical properties were most severe when grazing was implemented at high intensity and on wet soils. Microbial biomass C was higher under grazed conditions than ungrazed conditions. Nitrogen was found to be higher when cover crops were grazed than not grazed; however, this was only true for conventional tillage systems. Generally, grazing cover crops did not negatively affect primary crop yields. Cover crops provided nutritious forage for cattle and reduced feed costs by offsetting the use of hay or other pasture.
A strategy for tailored design of efficient and low‐pressure drop packed column chromatography
Authors: Li Ping , Yu Jianguo , Xiu Guohua , Rodrigues Alirio E.
Published: February 2010

Packed chromatographic column, with higher efficiency and lower pressure drop is designed by using inert core adsorbents as stationary phase. The analytical solutions for moments and height equivalent to a theoretical plate (HETP) are given under the conditions of linear adsorption kinetics by taking into account of the axial dispersion, film mass‐transfer resistance, intraparticle diffusion resistance, and the sorption rate for chromatographic column packed with inert core adsorbents. By minimizing HETP, a nonlinear algebraic equation was derived to predict the optimized value of the inert core radius. For a given adsorbent with the optimized inert core radius, a strategy was presented to tailor the design of new packed chromatographic column with higher efficiency and lower pressure drop. As an example for supercritical carbon dioxide chromatography, reduced equations in terms of dimensionless inert core radius were derived by “order of magnitude” analysis. The quantitative analysis shows that the major benefit of the inert core adsorbent is a shorter diffusion path compared to conventional fully porous particles. The shorter diffusion path reduces dispersion of solutes and minimizes peak broadening leading to lower pressure drop while maintaining high‐separation efficiency. © 2010 American Institute of Chemical Engineers AIChE J, 2010
Thiol‐En‐Klickchemie
Authors: Hoyle Charles E. , Bowman Christopher N.
Published: February 2010

Nach Sharpless’ visionärer Charakterisierung verschiedener idealisierter Reaktionen als Klick‐Reaktionen hat man innerhalb der Materialwissenschaften und Synthesechemie große Anstrengungen unternommen, um solche Reaktionen zu finden und zu implementieren. In diesem Aufsatz diskutieren wir die radikalvermittelte Thiol‐En‐Reaktion, die über all die Merkmale einer Klick‐Reaktion verfügt: hohe Effizienz, einfache Durchführung, keine Nebenprodukte, hohe Reaktionsgeschwindigkeiten, hohe Ausbeuten. Darüber hinaus besteht die Möglichkeit, die Thiol‐En‐Reaktion photoinitiiert auszuführen, was insbesondere für Photopolymerisationen zur Synthese extrem einheitlicher Polymernetzwerke genutzt wird. Der Reaktionsmechanismus wird nach dem aktuellen Kenntnisstand erläutert, und zentrale Anwendungen der Thiol‐En‐Reaktion in der Material‐ und Molekülsynthese, der Biofunktionalisierung, der Polymersynthese und der Oberflächen‐ und Polymermodifizierung werden zusammengefasst.
Introducing gross pathology to undergraduate medical students in the dissecting room
Authors: Wood Andrew , Struthers Kate , Whiten Susan , Jackson David , Herrington C. Simon
Published: February 2010

Pathology and anatomy are both sciences that contribute to the foundations of a successful medical career. In the past decade, medical education has undergone profound changes with the development of a core curriculum combined with student selected components. There has been a shift from discipline‐based teaching towards problem‐based learning. Both anatomy and pathology are perceived to have suffered from this educational shift. The challenge is to introduce methods of learning for these subjects into an integrated student‐centered curriculum. The purpose of this study was to determine the prevalence of pathology in 12 donor cadavers in the dissecting room of the Bute Medical School, University of St Andrews. All of the cadavers had multiple pathologies (between three to four conditions) ranging from common to rare disorders. A number of prostheses and surgical interventions were also noted. This small study confirms that cadaveric dissection provides an excellent opportunity for the integration of anatomy, pathology, and clinical medicine into the early clinical training of undergraduate medical students. The identification of disease in a cadaver provides an excellent introduction to the gross features of a disease process, but does not substitute for the detailed study of a process later in the curriculum. Anat Sci Educ 3: 97–100, 2010. © 2010 American Association of Anatomists.