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  • 51.
    Wyon, Yvonne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Synnerstad, Ingrid
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Fredrikson, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Spectrophotometric analysis of melanocytic naevi during pregnancy2007In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 87, no 3, p. 231-237Article in journal (Refereed)
    Abstract [en]

    Malignant melanoma is the most common cancer during pregnancy, but it is unknown whether melanocytic naevi in general are activated. A total of 381 melanocytic naevi in 34 Caucasian primigravidae were examined using spectrophotometric intracutaneous analysis (SIAscopy) technology in early pregnancy and prior to delivery. The Siagraphs of each naevus were then compared in order to evaluate changes over time. A total of 163 melanocytic naevi in 21 nulliparous women served as an additional control group. At the first visit none of the Siagraphs examined for the case or control groups aroused suspicion of dysplastic naevus or melanoma and no significant structural changes were noted during the observation period. However, 2.1% of the melanocytic naevi in the pregnant group increased and 1.3% decreased in size. Corresponding figures in the non-pregnant group were 1.8% and 0%, respectively. Only one naevus in a pregnant woman increased slightly in epidermal pigmentation, and a decrease in pigmentation was noted in 3.7% of the melanocytic naevi in the cases and 1.8% in the controls. None of the differences within or between the groups was statistically significant. We conclude that pregnancy does not influence the appearance of pigmented naevi. A changing naevus during pregnancy should be examined carefully and considered for excision and histopathology. © 2007 Acta Dermato-Venereologica.

  • 52.
    Wårdell, Karin
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Andersson, T
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Analysis of laser Doppler perfusion images of experimental irritant skin reacsions1996In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 2, p. 149-157Article in journal (Refereed)
  • 53.
    Wårdell, Karin
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Ilias, Michail
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Falk, Magnus
    Division of Dermatology Universitetssjukhuset i Linköping.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Skin phototest using a divergent UVB-beam2002In: Nordic Baltic Conference on Biomedical Engineering and Medical Physics,2002, IFMBE , 2002, p. 39-Conference paper (Refereed)
  • 54.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    p53 plays a central role in UVA and UVB induced cell damage and apoptosis in melanoma cells2006In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 244, no 2, p. 229-238Article in journal (Refereed)
    Abstract [en]

    We investigated whether p53 plays a role in UV induced apoptosis in melanoma. UVA and UVB induced apoptosis in dose dependent and wild type p53 melanoma cells were much more vulnerable than the mutant cells, indicating that p53 played a role in UV-induced apoptosis in melanoma. No difference in p53 expression pattern between the primary and matched metastatic melanomas was noticed in tumour tissue or cell lines from the same patients. Our findings indicate that expression of p53 plays a role in UV-induced apoptosis in melanoma cells, but not important in melanoma progression from primary to metastasis. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 55.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Survivin protein in UVB induced apoptosis of melanoma cells and in melanoma progression.2005In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 13, no 6, p. 1121-1126Article in journal (Refereed)
    Abstract [en]

    A model system of cultivated melanoma cells and melanomas from patients were used in this study to clarify whether survivin protein was involved in UVB induced cell damage and in melanoma progression. The melanoma cells in culture were exposed to different doses of UVB and post-cultivated for various periods of time. Cell viability, apoptotic index and expression of survivin proteins were estimated. Expression of the survivin in normal tissue, nevi, primary and metastatic melanomas from the patients were also examined by immunohistochemistry. Results showed that UVB induced cell damage and apoptosis in melanoma cells. Primary and wt p53 cells were more sensitive than metastatic and mutant p53 melanoma cells. Expression of survivin protein was markedly decreased in the primary melanoma cells after exposure to UVB compared to the metastasis. The expression was markedly decreased in wt p53 melanoma cells, but not in the mutant p53 melanoma cells. Survivin protein was expressed in nevi, primary and metastatic melanomas. However, the normal tissues were not expressed in the survivin protein. Survivin plays an important role in UVB-induced apoptosis. Overexpression of survivin might be a biomarker for early diagnosis for melanoma.

  • 56.
    Zhang, Hong
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Dufmats, Monika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa.1998In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 34, no 13, p. 2053-2057Article in journal (Refereed)
    Abstract [en]

    The K-ras gene in codons 12 and 13 was investigated using allele-specific polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas. K-ras mutations in codon 12 were detected in 41/149 (28%) of tumours and 4/69 (6%) of transitional mucosa samples, but not in the normal mucosa. Further, mutation rates were increased in younger patients (P = 0.001) and in mucinous carcinomas (50%) compared with well differentiated (17%), moderately differentiated (26%) or poorly differentiated (24%) tumours. Our findings indicate that mucinous carcinoma may represent a distinct genetic entity.

  • 57.
    Zhang, Hong
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Bcl-xL and bcl-2 proteins in melanoma progression and UVB-induced apoptosis.2006In: International Journal of Oncology, ISSN 1019-6439, Vol. 28, no 3, p. 661-666Article in journal (Refereed)
    Abstract [en]

    Whether bcl-xL and bcl-2 play an essential role in melanoma progression and UVB-induced apoptosis is not completely understood. We investigated the expression of bcl-xL and bcl-2 in matched primary and metastatic melanoma tumors and melanoma cell lines from the same melanoma patients to clarify the importance of bcl-xL and bcl-2 in melanoma progression and in UVB-induced apoptosis. The expression of bcl-xL and bcl-2 proteins was examined by immunohisto(cyto)chemistry and Western blot in melanoma tumors and melanoma cells. Cellular viability and apoptosis were estimated after the melanoma cells were exposed to 30, 60 and 180 mJ/cm2 UVB. Both primary melanoma tumors and melanoma cells showed lower expression of bcl-xL and bcl-2 proteins estimated as frequency of positive cells than their matched metastatic tumors and cells in vitro. After exposure to UVB, the cell viability decreased and the number of apoptotic cells increased in both primary and metastatic melanoma cell lines. These changes were more pronounced in the primary melanoma cells than in the matched metastatic cells. After UVB exposure, the expression of bcl-xL protein decreased in primary melanoma cells in a dose- and time-dependent manner, but the expression of bcl-2 was not influenced. The expression of bcl-xL and bcl-2 proteins was increased during melanoma progression from primary to metastatic melanoma. Reduction of bcl-xL, but not bcl-2 expression was involved in UVB-induced apoptosis in primary melanoma cells.

  • 58.
    Zhang, Hong
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Deletion in p16INK4a and loss of p16 expression in human skin primary and metastatic melanoma cells.2004In: International Journal of Oncology, ISSN 1019-6439, Vol. 24, no 2, p. 331-335Article in journal (Refereed)
    Abstract [en]

    p16INK4a gene mapped at chromosome 9p21 region encodes a tumor suppressor protein p16 which is frequently inactivated in human cancers, including skin melanoma. In order to clarify the importance of p16 alterations in melanoma, we examined the deletions of p16INK4a and expression of p16 protein in eight unselected primary and metastatic melanoma cell lines from human skin melanomas. Normal skin melanocytes were used as controls. Deletions of entire exons in the p16INK4a gene were detected by PCR technique and expression of the p16 protein was examined by Western blotting and immunocytochemistry. Results showed that the fragments from exons 2A, 2C and 3 in p16INK4a gene were totally deleted in the metastatic melanoma cell line, FM28.7 and the fragment from exon 3 was deleted in the metastatic melanoma cell line, FM55M2. P16 protein was strongly expressed in two of the primary melanomas cell lines (FM55P and RaH3). The p16 protein was weakly expressed in one of the metastatic melanoma cell lines (FM55M1) and negative in the other metastasis (FM55M2) as compared to their matched primary melanoma cells (FM55P). The p16 protein was strongly expressed in normal skin melanocytes. Immunocytochemistry showed that p16 protein was mainly localized in the nuclei of the melanoma cells and normal melanocytes, if it was expressed. Deletions of p16INK4a gene was uncommon and loss of p16 protein expression was common event in melanoma, especially in the later stages of melanoma.

  • 59.
    Zhang, Hong
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Expression of p27 and MAPK proteins involved in all-trans retinoic acid-induced apoptosis and cell cycle arrest in matched primary and metastatic melanoma cells.2004In: International Journal of Oncology, ISSN 1019-6439, Vol. 25, no 5, p. 1241-1248Article in journal (Refereed)
    Abstract [en]

    We investigated whether p27 and mitogen-activated protein kinase (MAPK) proteins were involved in all-trans retinoic acid (atRA)-induced apoptosis and cell cycle arrest. Matched primary and metastatic melanoma cells were exposed to atRA. Apoptosis and cell cycle were detected by flow cytometry. Expression of p27, Ras, B-raf, Mek and Erk proteins was examined. Results showed that atRA induced apoptosis and cell cycle arrest in both primary and metastatic melanoma cells. The primary melanoma cells were more vulnerable than their matched metastatic cells. Expression of p27 was increased, while MAPK proteins were decreased, this response was dose- and time-dependent. Alterations of these proteins were more pronounced in primary melanoma cells than in the matched metastases. These data indicate that up-regulation of p27 and down-regulation of MAPK proteins were involved in atRA-induced apoptosis and cell cycle arrest in melanoma.

  • 60.
    Zhang, Hong
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Expression profiles of Id1 and p16 proteins in all-trans-retinoic acid-induced apoptosis and cell cycle re-distribution in melanoma2005In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 217, no 1, p. 33-41Article in journal (Refereed)
    Abstract [en]

    All-trans-retinoic acid (atRA) exerts its effects via apoptosis and cell cycle re-distribution. However, the mechanisms behind the effects have not been fully understood. In this study, we used a model system of matched primary and metastatic melanoma cells to investigate whether expression of Id1 and p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution. Melanoma cells were exposed to 0.1 or 10 μM atRA for 1-96 h. Apoptosis and cell cycle were measured by flow cytometry. Expression of Id1 and p16 proteins was examined by Western blotting and immunocytochemistry. After exposure to atRA we found a marked increase in apoptosis and cell cycle re-distribution in both primary and metastatic melanoma cells. Expression level of Id1 protein was decreased and the p16 was increased in a dose- and time-dependent (P<0.05) manner after treatment with atRA. Alterations of these proteins were more pronounced in the primary melanoma cells than the matched metastases (P<0.05). These data suggested that the alterations of Id1 and/or p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution in melanoma. These expression profiles of Id1 and p16 proteins may provide molecular evidence for better chemotherapy primarily for early stages of melanoma.

  • 61.
    Zhang, Hong
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Expression profiles of p53, p21, bax and bcl-2 proteins in all-trans-retinoic acid treated primary and metastatic melanoma cells.2004In: International Journal of Oncology, ISSN 1019-6439, Vol. 25, no 2, p. 303-308Article in journal (Refereed)
    Abstract [en]

    We have previously shown that all-trans-retinoic acid (atRA) induces apoptosis in melanoma cells and primary melanoma cells are more sensitive to the exposure of atRA than the matched metastases. However, mechanisms behind the atRA-induced apoptosis have not been studied. In this study, we used a similar cell culture model system of matched primary and metastatic melanoma cells from the same patient to investigate whether p53 and bcl-2 family proteins were involved in atRA-induced apoptosis. The primary and metastatic melanoma cells were exposed to 0.1 and 10 micro M atRA in serum-free RPMI 1640 cell culture medium in the dark for up to 96 h. The protein expression of p53, p21, bax and bcl-2 were examined by Western blotting and immunocytochemistry. Expression of p53, p21 and bax was increased, and bcl-2 was decreased in melanoma cells after exposure to atRA at different concentrations for various periods of time. The changes of p53, p21, bax, and bcl-2 protein levels were dose- and time-dependent. The primary melanoma cells were more sensitive to the atRA treatments than cells from matched metastatic melanoma. These data indicate that p53, p21, bax and bcl-2 proteins were involved in atRA-induced apoptosis in melanoma cells. Modification of these protein levels in the tumour cells might be beneficial for early treatment of melanoma.

  • 62.
    Zhang, Hong
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Synnerstad, Ingrid
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Importance of FAS-1377, FAS-670, and FASL-844 polymorphisms in tumor onset, progression, and pigment phenotypes of Swedish patients with melanoma: a case-control analysis.2007In: Cancer Journal, ISSN 0765-7846, E-ISSN 1292-8658, Vol. 13, no 4, p. 233-237Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Human skin melanoma at later stages usually has an extremely poor prognosis. It is of importance to search for biologic markers to identify and monitor individuals at risk for melanoma for early diagnosis and to avoid tumor progression. The FAS gene and its natural ligand (FASL) gene initiate the death signal cascade, playing a central role in the apoptotic signaling pathway and tumor growth and metastasis. PATIENTS AND METHODS: In this study, we analyzed polymorphisms in 229 patients with melanoma and 351 age- and gender-matched tumor-free individuals. Genomic DNAs were isolated from mononuclear cells in peripheral vein blood, and the polymorphisms were examined with polymerase chain reaction-restriction fragment length polymorphism techniques. Frequency in distribution of the polymorphisms was compared between the patients with melanoma and the healthy control subjects, and associations with patients' pigment phenotypes, age at diagnosis, and melanoma characteristics were analyzed. RESULTS AND CONCLUSIONS: The FAS-1377, FAS-670, and FASL-844 polymorphisms were not found to be markers of melanoma risk (P > 0.05). In patients with melanoma, frequencies of the FAS-1377, FAS-670, and FASL-844 polymorphisms were different between the patients aged <50 and > or =50 years (P < or = 0.025, P < or = 0.025, and P < or = 0.01). Moreover, the FAS-670 polymorphism correlated with tumor Breslow thickness (P < or = 0.01) and Clark level (P < or = 0.001) and was associated with tumors developing in sun-exposed locations (P < or = 0.001). FAS and FASL were not markers for melanoma risk but might be important in the development and progression of sun-induced melanoma independently of skin type.

  • 63.
    Öhman, Hans
    Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Linköping University, Faculty of Health Sciences.
    Studies on the pH gradient in normal and ichthyotic human skin1998Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    In search for pathogenetic mechanisms underlying hyperkeratosis, we examined the pH gradient across the stratum corneum in normal and ichthyotic skin. Twenty students and employees, (12 men and 8 womenaged 25-69 years) served as controls. Patients with ichthyoses were recruited from the outpatient clinic (13 men aged 12-71 years). Diagnosis was made on the basis of clinical examination and serum lipid electrophoresis.

    For recording pH values, a flat glass electrode was repeatedly applied to the skin during tape stripping of volar forearm skin. Before stripping, surface pH (mean±SD) was higher in autosomal dominant ichthyosis vulgaris (IV) (5.2±0.3; n=7) than in x-linked recessive ichthyosis (XRI) (4.6±0.2; n=6) and healthy control skin (4.5±0.2; n=7). This comparision was made between men since a sex difference was observed when comparing men and women in the control group (4.5±0.2; n=7 for men and 5.3±0.5 for women).

    Removal of stratum corneum, which required 170-200 strippings in ichthyotic skin and 100-120 strippings in healthy control skin, dicsclosed markedly different pH variations in the two types of ichthyoses. The major abnormality in IV skin was that a neutral pH was attained already after half the total number of strippings through the hyperkeratotic stratum corneum, which may reflect a lack of acidickeratohyalin breakdown products in this condition.This in contrast to XRI where the pH gradient was less steep and eventually plateaued at pH 6.2-6.6 instead of at 6.7-7.0 as in normal skin. A likely explanation is the accumulation of cholesterol sulfate in lower stratum corneum which occurs in XRI.

    Our results suggest that the 'acid mantle' of normal skin, which penetrates deep into the stratum corneum, is the combined result of cornification-associated organic acids and back-diffusion of of acid material from the surface. Since comeocyte desquamation involves many pH dependent enzymes, abnormalities in the transcomeal pH gradient might play a role in the pathogenesis of ichthyoses.

  • 64.
    Öhman, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    The pH gradient in the epidermis evaluated by serial tape stripping2006In: Handbook of non-invasive methods and the skin / [ed] Gary L. Grove ,Gregor B.E. Jemec and Jorgen Serup, Boca Raton, Florida: Taylor & Francis , 2006, 2, p. 421-427Chapter in book (Other academic)
    Abstract [en]

    Inbunden

                Handbook of Non-Invasive Methods and the Skin       

    Engelska, 2006Firmly established as the leading international reference in this field, Non-Invasive Methods and the Skin broke new ground with its comprehensive coverage of methods used in both clinical and experimental dermatology. Completely revised and updated, containing more than twice as much information, the Second Edition continues the tradition. The authors' thorough research and clear organization make this book a baseline reference for those using noninvasive biophysical methods to study the skin.  Arranged by physical modality and structured to provide educational and practical information, the second edition, like its predecessor, will prove to be of value to young researchers and senior scientists alike. The coverage of major evaluation and measurement methods share a consistent format, including scope, sources of error, application, and validity. This edition incorporates 69 revised chapters with more than 90 new chapters covering topics such as computer technique, imaging techniques, skin friction, barrier functions, and more.New chapters provide coverage of: computers, computer techniques, and image analysis imaging techniques, including clinical photography legal situations and guidelines behind instrumental use skin friction barrier functions important new techniques such as in vitro confocal microscopy, OCT, and Raman spectroscopy veterinary/animal research use of methods  The truly interdisciplinary, international panel of contributors includes experts from the specialties of dermatology, bioengineering, pathology, manufacturing engineering, medical physics, pharmacology, microbiology, neurology, surgery, obstetrics and gynecology, cardiovascular research, and pharmacy from academic institutions and hospitals in countries such as Denmark, Germany, the United Kingdom, the United States, Japan, Israel, Taiwan, and Singapore. The revision is extensive and covers a broad spectrum of methods while providing the same caliber of authoritative information that made the previous edition so popular. Application oriented, practical, and instructive, this Second Edition will meet the needs of the researchers today, and in years to come.

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