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Animal models of human type 1 diabetes will be of a great importance for the evaluation of new combination therapies with curative potential. However, reliable predictive power for successful translation to patients with type 1 diabetes is crucial. This will be particularly important in the future when evaluating success of new combination therapies that show great promise for preservation and restoration of beta cell mass and thereby reverse the type 1 diabetic hyperglycaemia. But not all spontaneous animal models are equally well suited for this purpose. The advantages and disadvantages of the three spontaneous rat models (BioBreeding diabetes-prone [BB] rat, Komeda [KDP] rat, and LEW.1AR1-iddm [IDDM] rat) as well as the NOD mouse, compared with the characteristics of human type 1 diabetes, are considered in this review.

The arguments put forward by Phillips and McGlory do not take into consideration advances in the field over the past 5 years. These new discoveries have provided critical information on disuse atrophy in both human and rodent muscle. They also call into question key elements of our opponents’ reasoning. The assertion that disuse atrophy largely reflects a decline in protein synthesis is based solely on data from human vastus lateralis muscle. Recent studies demonstrate the limitations of this approach. For example, during cast immobilization, disuse atrophy occurs in a variety of leg muscles at least 2 weeks before significant atrophy is detectable in vastus lateralis (Psatha et al. 2012), suggesting the response of vastus lateralis is delayed relative to other muscles. New data also show that atrophy of vastus lateralis is non-uniform, affecting some regions more than others (Miokovic et al. 2012). Such confounding variables preclude the use of localized measurements in vastus lateralis, indeed any single muscle, as the sole source of information on disuse atrophy. Our opponents argue for limiting research to human vastus lateralis because ‘inherent species-specific differences’ exist between rodent and human muscles. Again, a plethora of recent research has debunked this misconception. As in rodent limb muscle, new data show that human type I fibres undergo greater atrophy than human type II fibres in soleus, gastrocnemius and vastus lateralis muscles after prolonged unloading (Fitts et al. 2010; Brocca et al. 2012). As in rodents, disuse atrophy of human muscle can be detected in as few as 4–5 days (Suetta et al. 2012; Wall et al. 2014), causes losses of up to 2.5–6% per day (Suetta et al. 2012; Grosu et al. 2012; Wall et al. 2014), and occurs at rates that differ widely among human muscles (Belavý et al. 2009; Miokovic et al. 2012; Psatha et al. 2012). Recent data also confirm that human muscle mimics rodent muscle by upregulating proteolytic gene products (Suetta et al. 2012). This consistency among species is fundamental, broad based, and compelling. It provides a solid scientific foundation for translational research in the field. Preclinical studies in rodents have been instrumental in defining the mechanisms of disuse atrophy, identifying atrophy-related pathways, and discovering genes that regulate the process. Rodent research has also demonstrated that proteolytic blockade can inhibit disuse atrophy (Jamart et al. 2011; Talbert et al. 2013), establishing a causal role for proteolysis. Modern evidence leads to the inexorable conclusion that proteolysis is not simply important for disuse atrophy. It is essential.

Purpose: Peri-implant osteogenesis is reported to be impaired in patients with diabetes. The current study tested the hypothesis that ultraviolet (UV) treatment of titanium, or photofunctionalization, is able to mitigate the impaired osseointegration associated with type 2 diabetes. Materials and Methods: Untreated and photofunctionalized titanium implants were placed into the femurs of genetically modified rats with a close phenotypic resemblance to human type 2 diabetes, as characterized by late-onset hyperglycemia and obesity. Implants were photofunctionalized with UV light for 15 minutes immediately before placement. The strength of osseointegration was evaluated using a biomechanical push-in test, and the tissue-implant interface was examined using scanning electron microscopy and energy-dispersive spectroscopy. Results: Photofunctionalization converted implants from hydrophobic to superhydrophilic. Photofunctionalizationinduced hemophilicity was also confirmed during surgery. The strength of osseointegration of photofunctionalized implants was significantly greater than that of untreated implants, by 1.8 and 3 times, at weeks 2 and 4 of healing, respectively. Osseointegration of photofunctionalized implants in diabetic animals was even stronger than that of untreated implants placed in normal animals throughout the healing period. Photofunctionalized implants placed in diabetic rats were extensively covered with calcium- and phosphorusrich tissue that masked the titanium signal. Conclusion: Photofunctionalization accelerated and enhanced levels of osseointegration and overcame impaired osseointegration in a rat model of type 2 diabetes. Further prospective studies are warranted to establish the clinical efficacy of photofunctionalization in patients with diabetes.

There are no drugs approved specifically to treat disseminated adenovirus (Ad) infections in humans. Cidofovir is active against Ad in cell culture, and it is used frequently in the clinic with disseminated infection in pediatric transplant patients; however, controlled clinical studies have not been conducted to prove the anti-Ad efficacy of cidofovir. Brincidofovir, a lipid-linked derivative of cidofovir, which has strong activity against Ad in cell culture and in animal models, is a promising new drug currently in clinical trials. Ribavirin, which has modest activity against some Ad types in cell culture, has been used in the clinic against disseminated Ad, but the efficacy of ribavirin is unknown. In the current study, we have examined the activity of cidofovir, brincidofovir, and ribavirin against disseminated Ad5 infection in the immunosuppressed Syrian hamster model. Hamsters are immunosuppressed by treatment with cyclophosphamide, then infected intravenously with Ad5, leading to disseminated Ad5 infection, especially in the liver. We found that cidofovir and brincidofovir have excellent activity against Ad5 pathology and replication in the liver, even when administered therapeutically starting at 3 days post-challenge with Ad5. Ribavirin did not have anti-Ad5 activity in our model. Our data support the use of cidofovir and brincidofovir in humans for the treatment of disseminated Ad infections in humans.

Type 1 diabetes is a multifactorial disease resulting from a complex interplay between host genetics, the immune system and the environment, that culminates in the destruction of insulin-producing beta cells. The incidence of type 1 diabetes is increasing at an alarming rate, especially in children under the age of 5 (Gepts in Diabetes 14(10):619-613, 1965; Foulis et al. in Lancet 29(5):267-274, 1986; Gamble, Taylor and Cumming in British Medical Journal 4(5887):260-262 1973). Genetic predisposition, although clearly important, cannot explain this rise, and so, it has been proposed that changes in the 'environment' and/or changes in 'how we respond to our environment' must contribute to this rising incidence. In order to gain an improved understanding of the factors influencing the disease process, it is important, firstly, to focus on the organ at the centre of the illness-the pancreas. This review summarises our knowledge of the pathology of the endocrine pancreas in human type 1 diabetes and, in particular, explores the progression of this understanding over the past 25 years.

Mevlânâ Celaleddin-i Rumî'nin Mesnevî-yi Manevî adlı eserine odaklanan bu tezde söz konusu manzumenin içinde yer alan insan tiplerinin belirli bir klasifikasyon çerçevesinde belirlenerek serimlenmesi amaçlanmıştır. Çalışmada Mesnevî'nin Farsça esas metni üzerinde, kelime bazında gerçekleştirilen tarama sonucunda insan tipi kapsamına girebilecek bütün ifadeler ayıklanmış, bu ifadelerin geçtiği beyitler tespit edilip ayrıştırılmıştır. Söz konusu ayrıştırma sonucu doğrudan insan isimleri, sıfatları ve insanî özellikler kapsamındaki insan tipleri elde edilmiştir. Ortaya çıkarılan tipler belirli bir sistematikle kategorize edilmiş ve sınıflandırılmıştır.Mesnevî'deki insan tiplerinin klasifikasyonu yapıldığında Mevlânâ'nın 'insan'ı çok boyutlu ve çok katmanlı bir yapıda kavradığı ve yansıttığı görülmüştür. Yaşamın her düzeyindeki insanı bütün gerçekliğiyle ve olduğu gibi ele alan Mevlânâ, gerek somut gerek soyut düzlemde insanî varoluşun tüm aşamalarını kuşatıcı bir biçimde teşhis ettiği sonucuna varılmıştır.Eserde insan tipolojisinin farklılıkları, zıtlıkları; denklikleri, eşitlikleri ve sair nitelikleriyle bütüncül bir tarzda ele alınmış olması, ona her daim güncel bir eser olma vasfını sağlayan unsurlardan biridir. Bu bağlamda çalışma kapsamında bulgulanan her bir insan kategorisini 'ideal insan nosyonu'nun yapı taşları olarak değerlendirmek mümkündür.Anahtar Kelimeler: Mevlânâ, Mesnevî, İnsan, İnsan Tipleri, Klasifikasyon. This dissertation aimed at portraying and classifying human characters in the Masnavi-i Ma'navi of Mavlana Jalaluddin-i Rumi. Having detected all expressions related to human characters through word-by-word review of the original Persian text of the Masnavi, couplets containing such expressions are selected. At the end of this selection process, human characters are determined according to names, titles and humane characteristics. Then the human characters are systematically categorized and classified.Having classified the human characters in the Masnavi, it is realized that Mavlana comprehends and illustrates 'human' in a multidimensional and multilayered nature. It concludes that Mavlana who addressed human with all authenticity and as it is in every aspect of life, comprehensively identified all stages of humane existence both in concrete and in abstract levels.The address of human characters with differences, contrasts, equivalence, evenness and other qualifications in the Masnavi is one of its features that made it always live. Hence, every human characters that are determined through the study could be viewed as fundamentals of 'ideal type of human.' Keywords: Mavlana, Rumi, Masnavi, Mathnawi, Human, Human Types, Classification. 281

Machine-to-machine wireless systems are being standardized to provide ubiquitous connectivity between machines without the need for human intervention. A natural concern of cellular operators and service providers is the impact that these machine type communications will have on current human type communications. Given the exponential growth of machine type communication traffic, it is of utmost importance to ensure that current voice and data traffic is not jeopardized. This article investigates the limits of machine type communication traffic coexisting with human communication traffic in LTE-A networks, such that human customer churn is minimized. We show that under proper design, the outage probability of human communication is marginally impacted whilst duty cycle and access delay of machine type communications are reasonably bounded to ensure viable M2M operations.

Prolyl-4-hydroxylase catalyzes the formation of 4-hydroxyproline in collagens. In contrast to deacetoxy/deacetylcephalosporin C synthase, p-hydroxyphenylpyruvate hydroxylase, lysyl hydroxylase and alpha-ketoisocaproate oxygenase, no incorporation of (18)O-labeled water into the hydroxylated product was found for the human type I prolyl-4-hydroxylase when N-Cbz-Gly-L-Phe-L-Pro-Gly-OEt was used as a substrate. This suggests that the ferryl intermediate for this enzyme is not solvent accessible. Copyright 2000 Academic Press.

There is probably only one idiomatic phrase in the proverb collection by Janos Baranyai Decsi that doubtless originates in contemporary everyday Hungarian language and the 16th century literary background of which can be clearly identified. The phrase " Nem jobb o is a deakne vasznanal " ( " Not a whit better than anybody else " ) has always been popular since the 16th century. The funny, sarcastic poem ( The cloth of the famous deakne, written before 1580) recounts the fatal marriage of a certain Mate deak - partly in the form of dialogue. This poem is one of the oldest Hungarian women mocking songs within the genre of wedding songs. It demonstrates all the characteristics of the old Hungarian trufa genre: it can be performed as a farce, the joke has its cream and it is based on mummery and pretence: it provides a parody of a well-known human type. It is possible that this trufa was a stock play of contemporary popular tricksters and jugglers. It mocked the wife of Mate deak who was " lazy to weave " .

La naissance de la photographie est contemporaine de l’apparition de l’anthropologie. En France, l’anthropologie issue d’une approche « physique » fut rapidement aux mains des medecins et biologistes qui pratiquaient une « armchair anthropology » dans leurs laboratoires. L’image photographique, percue comme une amelioration du dessin et un moyen de voyager « par procuration », entra au Museum d’histoire naturelle des les annees 1840. Rapidement, des projets de grande ampleur visant a mettre en evidence les « types humains » se mirent en place. Avec la creation de la Societe anthropologique de Paris en 1859, l’approche medicale devint dominante et s’orienta vers une demarche anthropometrique de plus en plus poussee, dictant ses principes a la prise de vue photographique. Mais progressivement, la photographie apparut incapable de satisfaire les exigences de cette anthropologie medicale, si bien que, vers la fin du XIXe siecle, elle fut delaissee par les anthropologues. Cependant, au meme moment, les methodes strictement medicales et anthropometriques etaient a leur tour abandonnees. Par son echec, l’image photographique aurait‑elle donc contribue a changer radicalement les methodes de comprehension de l’Autre ?

In this paper, a competitive neural network architecture is used as an intelligent fault diagnosis system to detect the fault sources in different subsystems or elements of a plant or any other device. The prioritized modification rule for connection weights is introduced and four different procedures are studied and compared from the viewpoint of their efficiency. It is shown that the fourth procedure is more convenient for human type decision-making. The output functions of different neurons are considered as the possibility of being fault sources for different units. The system starts from a vague initial state and the connection weights are modified during the learning procedures. The simulation results of different strategies are analyzed and compared. A typical CNC machine is considered as a case study.

As type IX collagen is a minor cartilage component, it is difficult to purify sufficient amounts of it from tissues or cultured cells to study its structure and function. Also, the conventional pepsin digestion used for fibrillar collagens cannot be utilized for purifying type IX collagen, because it contains several interruptions in its collagenous triple helix. A baculovirus expression system was used here to produce recombinant human type IX collagen by coinfecting insect cells with three viruses containing full-length cDNAs for the α1(IX), α2(IX), and α3(IX) collagen chains together with a double promoter virus for the α and β subunits of human prolyl 4-hydroxylase. Correctly folded recombinant type IX collagen was secreted, consisting of the three α chains in a 1:1:1 ratio and showing the expected biphasic thermal melting profile. When the individual α chains were expressed, disulfide-bonded homotrimers and homodimers of the α chains were observed. When the cells were coinfected with the viruses for all three α chains, heterotrimers of α1(IX), α2(IX), and α3(IX) were detected in cell culture medium, and the other possible combinations were less prominent. When any two of the α chains were co-expressed, in addition to the homodimers and homotrimers, only α1(IX) and α3(IX) chains were disulfide-bonded. The results thus suggest that the most favored molecular species is an α1(IX)α2(IX)α3(IX) heterotrimer, but the chains are also able to form disulfide-bonded heterotrimers of α1(IX) and α3(IX) chains and (α1(IX))3, (α2(IX))3, and (α3(IX))3 homotrimers.

We examined the effects of eight subtypes of human interferon-alpha (IFN-alpha) and human IFN-beta on primary human B cells. In costimulation with antibodies to IgM (but not to CD40), some of these induced the cells to proliferate (but not to differentiate). Individual IFN differed greatly in their relative proliferative effects. IFN-alpha8 at 0.1-0.5 ng/ml induced proliferation, whereas most other subtypes were active only at concentrations5 ng/ml, and IFN-alpha1 was inactive. These marked differences were not due to a selective overall increase in B cell response only to some IFN subtypes, as all those tested similarly induced the IFN-inducible genes 6-16 and HLA class I. Our results show that human B cells must respond to type I IFN via two distinct pathways. One is specific for IFN-alpha8 but can be activated by other IFN at relatively high concentrations. The other responds to them all and causes activation of IFN-inducible genes.

We have developed a cell-based 96-well microtiter plate, high throughput assay for measuring both type I and type II interferon (IFN) activity on human cells. This assay makes use of a previously described IFN-specific reporter stably expressed in human HT 1080 cells. The induction of the reporter by IFN is determined by measuring the IFN-dependent expression of CD2 on the cell surface. The cytokine-induced expression of CD2 occurs within 48 h and is measured using a time-resolved fluorometric immunoassay. The limit of detection for type I IFN is.0.4 IU/ml. Interassay and intraassay coefficients of variation were 1.1% and 1.3% for the medium control (31 IU IFNb1b/ml), respectively. The limit of detection for type II IFN is.8 IU/ml, and the assay coefficients of variation are similar to those determined for type I IFNs. The level of sensitivity for this assay is comparable to other assays commonly used to measure IFN activity on cells. The current assay has an advantage over antiviral and antiproliferative assays, in that there is no requirement for the use of pathogenic virus or for determining viable cell numbers. The current assay is ideally suited for increasing sample screening and high-capacity automation, making it an excellent tool for drug discovery.

A monoclonal antibody (mAb) directed against the extracellular domain of the IFNAR1 chain of the human interferon-alpha (IFN-alpha) receptor (IFN-alphaR), which inhibits activation of the Jak-Stat signal transduction pathway, administered together with a subeffective dose of cyclosporine induced prolonged survival of skin allografts in major histocompatibility complex (MHC) divergent cynomolgus monkeys. Skin biopsies from animals treated with anti-IFN-alphaR mAb and cyclosporine revealed very low levels of MHC class I and class II antigen expression and the absence of histologic signs of rejection. Monkey antibodies (IgG) to the mouse antihuman IFN-alphaR mAb were not detected in the serum of any of the animals treated with the anti-IFN-alphaR mAb either alone or together with cyclosporine. The anti-IFN-alphaR mAb abrogated activation of the Jak-Stat signal transduction pathway in IFN-treated cells. These results, which show that selective and long-lasting immunosuppression can be obtained by short-term administration of an IFN-alpha antagonist together with a subeffective dose of cyclosporine, may have important implications for the therapy of human allograft rejection.

An internal domain from the human type 1 neurofibromin has previously been expressed in Escherichia coli as a fusion with gluthathione S-transferase (GST). The expression level of this protein was lower than expected and so a gene was constructed using the distribution of codons found in highly expressed E. coli proteins. Codons were assigned using a Microsoft Visual Basic computer program to give a distribution similar to those found in genes which are highly expressed in E. coli. The optimized gene was then cloned back into the same GST fusion plasmid and it was found that the expression of soluble protein had increased threefold.

It has been demonstrated that hard metal dust, which consists of a mixture of cobalt and tungsten carbide, is more toxic toward mouse peritoneal and rat alveolar macrophages than pure cobalt (Co) or tungsten carbide (WC). The aim of this study was to investigate the toxic effects of Co and hard metal dust on alveolar epithelial type II cells (AT-II), and to compare these with alveolar macrophages. Freshly isolated rat and human AT-II and rat alveolar macrophages were exposed for 18 hr to particles of Co, WC or Co/WC. As an index for cell toxicity, release of lactate dehydrogenase was measured. For rat AT-II, TD50 values per 10(5) cells were 672 micrograms (95% C.I. = 264-1706 micrograms) for pure Co and 101 micrograms (95% C.I. = 59-172 micrograms) for Co in Co/WC mixture. For rat alveolar macrophages, TD50 values per 10(5) cells were 18 micrograms (95% C.I. = 15-24 micrograms) for pure Co and 5 micrograms (95% C.I. = 5-6 micrograms) for Co in Co/WC mixture. WC only caused an increase in lactate dehydrogenase at high concentrations. No toxicity was found in human AT-II for either Co, WC or Co/WC. These results indicate that 1) rat AT-II are less sensitive to Co than rat alveolar macrophages, 2) human AT are less sensitive to Co than rat AT-II, 3) the toxicity of Co is increased by the presence of WC.

Objectives: Evaluation of the performance of a radioimmunoassay kit for measuring serum concentrations of the aminoterminal extension peptide of human type I procollagen, S-PINP. Design and Methods: S-PINP concentrations in 229 healthy subjects, 140 females, aged 3.8–81 years, and 89 males, aged 0.9–71 years, were measured with the kit. Because PINP and PICP (the carboxy-terminal propeptide of type I procollagen) are formed in equimolar concentrations, we also calculated the PICP/PINP ratio and compared the S-PINP values to those of S-PICP, which have been shown to correlate with bone formation rate. Results: The sensitivity of the assay was 2.3 μg/L, the spiking recovery ranged from 95.5 to 100.3%, the dilution recovery from 79.3 to 103.1%. The intra-assay imprecision was 2.3 to 3.5% (CV), the interassay imprecision within one reagent lot 2.5–5.2% and, between several reagent lots, 2.7 to 6.1% (CV). S-PINP in females over 20 years old ranged from 12 to 90 μg/L (x = 39.7, SD = 14.7), in males over 25 years old, from 22 to 89 μg/L (x = 49.9, SD = 15.8); the PICP/PINP ratio ranged from 1.5 to 5.2 and from 1.8 to 4.9, respectively. In females under 20 years old, S-PINP ranged from 52 to 820 μg/L, in males aged 25 years or younger from 35 to 1404 μg/L; the PICP/PINP ratio was 0.44–2.3 and 0.38–2.8. In females under 20 years and males under 25 years, there was a significant negative correlation between S-PINP and age: r = −0.70, p < 0.001 for females, r = −0.52, p = 0.004 for males. In different groups of healthy subjects, the correlation of S-PINP and S-PICP was significant (r = 0.67–0.86, p < 0.001). Conclusion: The assay performance is good. The significant positive relationship between S-PINP and S-PICP suggests that S-PINP also reflects bone formation rate. Because the clearance of PINP is probably less sensitive to hormonal changes, PINP may prove to be superior to PICP as a marker of bone formation.

Type I collagen is the most abundant and ubiquitously distributed of the collagen family of proteins. It is a heterotrimer comprising two alpha1(I) chains and one alpha2(I) chain which are encoded by the unlinked loci COL1A1 and COL1A2 respectively. Mutations at these loci result primarily in the connective tissue disorders osteogenesis imperfecta and Ehlers-Danlos syndrome types VIIA and VIIB. Two instances of osteoporosis and a single instance of Marfan syndrome are also the result of mutations at these loci. The mutation data are accessible on the world wide web at http://www.le.ac.uk/depts/ge/collagen/collagen.html

The effects of catechins obtained from the hot water extract of green tea leaves on two human type-A influenza virus strains of Aichi/2/68 and PR/8/34 were studied. In this study, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), (-)-epigallocatechin gallate (EGCg), the crude catechins containing these catechins and (+)-catechin were used. Consequently it was observed that catechins used in this study had an inhibitory effect on the hemolytic activity to red blood cells induced by these two type-A virus strains under acidic conditions (pH 5.1 or 5.4) although they did not have an influence on the agglutination activity to red blood cells induced by the same virus strains. After incubation of (-)-ECg and (-)-EGCg with A/Aichi/2/68 virus, MDCK cells, virus-sensitive cells, were infected with the virus and the ability of virus proliferation was measured in terms of an index of the agglutination activity of the virus to red blood cells. The used two catechins, (-)-ECg and (-)-EGCg, inhibited the virus proliferation at concentrations of 100μg/ml and 50μg/ml, respectively. Furthermore, at a concentration of 2.0 mg/ml these two catechins were found to inhibit the activity of neuraminidase on the surface of the virus membrane by 71.3% and 60.8%, respectively. From the above-mentioned results, it is considered that among the catechins contained in green tea leaves, such two catechins as (-)-ECg and (-)-EGCg inhibit the activity of neuraminidase present on the surface of human influenza virus in order to block the invasion of the influenza virus into virus-sensitive cells.

It is demonstrated that a new pulse sequence element, Spin-State-SelectiveCoherence Transfer (S3CT), via an intermediate state ofheteronuclear IS zero- or double-quantum coherence can transfer the twosingle-quantum coherences on one of the spins exclusively to any one of thetwo single-quantum coherences on the other spin. This fact is used for editinginto two subspectra that are most suitable for extraction of homo- orheteronuclear J coupling constants when S3CT is combined withhomonuclear coherence transfer during a mixing period. Experimentalconfirmation is obtained using a 15N-labeled 58-residue protein,the C-terminal Kunitz domain from human type VI collagen. The J coupling con-stants determined include 3JHN-Hα and3JN-Hβ related to the φ andχ1 angles, respectively.

Charles Chany, who passed away this April, had a passion for biology and devoted most of his life to its study. While the beginning of his scientific career focused primarily on viral detection and identification, his interest later was in the analysis of virus pathogenicity and virus–host interactions. He was one of the pioneers in this field in France, since he started his studies before cell culture techniques and molecular approaches were fully developed. Charles was born in 1920 in Budapest, and after he received his baccalaureate, he wished to continue his studies in medicine. However, in Hungary in 1938, the admission of Jews to graduate schools was very limited, and thus he was unable to enter the faculty of medicine. Then came the Second World War, which was a very difficult time for young Charles. His mother disappeared to an unknown German labor camp, and Charles was deported to a labor camp in the copper mines in Bor, Yugoslavia. Near the end of the war, in 1944, Charles walked with the other prisoners (900 km) to the Buchenwald camp, and was one of few who survived this journey (Charles described all these events in a book titled From the Steps of Death to the Life Sciences). After the liberation of the camp by the American troops, in 1945, he was taken by the Red Cross to France, where he chose to stay for the rest of his life, and he became a proud Frenchman. Charles went to medical school in Paris, and after finishing his education, he chose to study viruses. He was a trainee at the Institut Pasteur in the laboratory of Professor Pierre Lepine, and at the same time, he was associated with the Department of Pediatrics in the hospital St. Vincent de Paul. This allowed him to create a fertile interface between research and clinic. He was the first person to isolate the adenovirus in France in 1955–1956. He then spent a year in the laboratory of Dr. Wallace Rowe (discover of the adenovirus) at the National Institute of Health (NIH) in Bethesda, Maryland. After his return to France, he started his own laboratory at the hospital St. Vincent de Paul, which first served as a diagnostic laboratory. Here, Charles isolated the first parainfluenza 3 virus in France (at about the same time as Dr. Chanock at NIH). He and his collaborators also described the first epidemics of syncytial respiratory virus and adenovirus in France. In his thesis of medicine, he described for the first time the pulmonary lesions caused by adenovirus infection. His studies on the auto interference of the parainfluenza 3 virus1 drew his attention to the possible role of interferon (IFN) in viral infection. Later, his work mainly focused on IFN. Together with Ion Gresser, Jacqueline and Edward de Maeyer, and Rebecca and Ernesto Falcoff, they were the leaders in the IFN field in France. Charles was very involved in the Interferon Society, which was formed at about this time. He organized a very successful IFN meeting in Portugal in 1973. He regularly attended the yearly meetings of the Interferon Society, always excited to present recent results from his laboratory. His research group was later changed to a research unit—Inserm—where he assembled a group of very gifted students, fellows, and investigators who focused on different aspects in the IFN field. Among other findings, they showed an inhibitory effect of IFN on the oncogenic properties of the polyomavirus2 and the IFN-induced phenotypical reversion of Moloney sarcoma virus (MSV) transformed cells. A significant contribution to the IFN field was the development and use of human–mouse hybrid cells.3 Using these hybrid cells, Charles together with J. de Grouchy located the human type I IFN genes to chromosome 9.4 Another interesting finding was the existence of spontaneous IFN production in the placenta during pregnancy.5 This observation was confirmed recently by the discovery of expression of IFN eta in mouse placenta. One of Charles' major goals was the possible clinical application of IFN. With the assistance of the Institut Pasteur in 1980, his group produced IFNs from leukocytes for therapeutic testing. Treatments for measles encephalitis SSPE, multiple sclerosis, and cancers were initiated. However, these treatments were short term; the levels of IFN used were low, and thus the IFN treatment did not show any significant effects in these studies. Charles did, however, make a significant clinical contribution outside the IFN field. Together with the team of Pierre Tiollais, who had cloned the genome of the hepatitis B virus (HBV), they express the S antigen of HBV in vitro.6 This work led to the development of the current HBV vaccine. After his retirement, Charles donated his royalties from the HBV vaccine patent to the University of Paris 5 and installed his laboratory there. Here, he and his wife Francoise Chany Fournier continued to study the natural inhibitors able to regulate the IFN action in vivo.7–9 Here, Charles was a leader in the field, since the inhibition of the detrimental effects of IFN in autoimmune disease and inflammation is presently a priority. Thus collectively, while Charles' initial work contributed to the development of medical virology, he later made seminal contributions to the IFN field. The laboratory that he created at the hospital St. Vincent de Paul continues to function now at the Cochin hospital. In addition to his hospital work and his research, Charles also conveyed his interest in the IFN field to several generations of medical students and the great number of graduate students he trained. His talks on IFN always raised many questions from the audience. I (P.L.) had the privilege of taking one of his lectures given within the framework of “the great” course series in the Pasteur Institute. His enthusiasm for research and his willingness to share his time with students encouraged me to work with him for more than 20 years. He leaves us with the memory of an impassioned researcher, kind teacher, and generous man.

In this issue, Woodley et al. report restoration of anchoring fibril formation and dermal–epidermal adherence in a murine model of recessive dystrophic epidermolysis bullosa (RDEB) by intravenous injection of recombinant human type VII collagen. This work follows a previous report by the same group of the surprising capability of intradermally injected type VII collagen protein to reverse RDEB, and it opens new therapeutic avenues.

Type V myosins constitute the main cargo-transporting class of myosin motors in higher eukaryotes. They are mainly defined by their C-terminal globular domain, which is required for cargo binding as well as for motor auto-inhibition in the absence of cargo. To date, high-resolution structures only exist for globular domains from yeast. Since the majority of cellular cargoes in yeast are very different from the cargoes in higher eukaryotes, structural insights into the domain organization of globular domains from human type V myosins are important. The globular domain of human Myo5a was cloned, expressed and crystallized and data sets were collected. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 75.04, b = 86.70, c = 131.41 Å, α = β = γ = 90°, and diffracted with data-collection quality to 2.5 Å resolution.

In the prologue to Nietzsche’s Thus Spoke Zarathustra (1883), Zarathustra stands before an uncomprehending crowd and presents to them the apotropaic image of ‘the last man’: a human type characterized by uncritical contentment, satiated desire, and utter absence of motivation to initiate change or strive towards a goal. The last men represent an end-state precisely because they are so readily satisfied with their lot: ‘“We invented happiness,” say the last men, and they blink.’ This stasis of self-satisfaction represents for Zarathustra a form of live mummification, a movement toward death barely energetic enough to reach that seemingly inevitable destination. Putting words into the last man’s mouth, Zarathustra says: ‘a bit of poison once in a while: that makes for pleasant dreams. And much poison at the end, for a pleasant death.’ This drawn-out process of death by gradual anaesthetization grants the last man extreme longevity. As Zarathustra says: ‘the last man lives longest.’1

International audience; In this article, I argue that the problematic of “race and medicine”, which has been the object of many recent debates, has a long history that it may be useful to understand better. I show more specifically that, from the very first uses of the concept of “race” in natural history during the XVIIIth century, medical concepts and analogies served as important models. These medical models were especially useful to analyze “races” as alterations from an original identity. Different analogies are studied here. 1. The analogy between races’ peculiar temperaments and morbid alterations of human constitution. 2. The analogy between the transmission of the alterations along generations and hereditary diseases. In this second analogy, I differentiate between two models: the degeneration of the human type and the transmission of a molecular alteration of one character.; Cet article propose de prendre un peu de distance vis-à-vis du retour actuel de la notion de « race » dans le champ biomédical, en examinant le lien intime qui existe entre pensée médicale et problématique de la race lors de l’émergence du concept naturaliste de « race » aux XVIIIe-XIXe siècles. Il montre comment l’analogie avec les pathologies a été mobilisée alors par les naturalistes pour penser la « race » comme altération d’une identité d’origine, à travers, d’une part, le modèle des tempéraments maladifs, d’autre part celui des maladies héréditaires.

XIX. yüzyıl, ünlü Rus yazarlarının en verimli oldukları dönemde hem Rus hem de dünya edebiyatına zengin eserler kazandırdıkları, Rus edebiyatının parlamaya başladığı ve `Altın Çağ`ını yaşadığı bir dönemdir. Tezimizin konusu XIX. yüzyıl Rus edebiyatında `gereksiz insan` tiplemesidir. XIX. yüzyılda A.S.Puşkin, A.S.Griboyedov, M.Y.Lermontov, A.İ.Herzen, İ.S.Turgenev, İ.A.Gonçarov ve A.P.Çehov gibi birçok ünlü yazar ?gereksiz insan? sorununu eserlerinde ele almıştır.`Gereksiz insan` sorunu Rus toplumunda XIX. yüzyılın ilk çeyreğinde oluşmaya başlarken, ortaya çıkışında siyasal, toplumsal, kültürel, sosyolojik, ekonomik ve psikolojik nedenler etkili olmuştur. Dönemin yazarlarının gerçekçilik akımına yönelmesiyle birlikte Rus toplumuna eğilmeleri sonucu farkına vardıkları bu sorun, XIX. yüzyıl Rus edebiyatı eserlerine de `gereksiz insan` tiplemesi olarak yansımıştır. Gereksiz insan`, sahip olduğu üstün yetenekleri hayata uyarlayamamış, düşünceleri ile ruhu arasında ikileme düşmüş, aklındaki planlarını günlük yaşamına dökememiş, amaçsız ve uğraşsız bir şekilde yaşam sürmüş, toplumda kendisine herhangi bir yer edinememiş ve bunun sonucunda derin bir manevi çöküntüye düşmüş insanı yansıtan bir tiplemedir. Bu tiplemeler arasında öne çıkan karakterler arasında `Yevgeniy Onegin` adlı eserdeki Onegin, `Akıldan Bela`daki Çatskiy, `Zamanımızın Kahramanı`ndaki Peçorin, `Suçlu Kim?` adlı eserdeki Beltov, `Gereksiz Bir Adamın Günlüğü`ndeki Çulkaturin, eserle aynı adı taşıyan başkarakter Rudin, `Bir Soylu Yuvası`ndaki Lavretskiy, yine eserle aynı adı taşıyan başkarakter Oblomov, `Uçurum` adlı eserdeki Rayskiy, `İlkbahar Selleri`ndeki Sanin, `Ham Toprak`taki Nejdanov ve `Düello`daki Layevskiy yer almaktadır. `Gereksiz insan` tiplemeleri ortak özelliklere sahip olmalarının yanı sıra, toplumsal değişim sürecine bağlı olarak dönüşüme uğramış ve benliklerinde farklı nitelikler ortaya çıkmıştır.`Gereksiz insan` tiplemesi, gözlem yeteneği güçlü usta yazarların Rus toplumunda sürekli karşılaştıkları insanları gerçekçilik akımının büyüsüyle birlikte eserlerine yansıtıp tipleştirme yoluna gitmelerinin sonucunda doğmuştur. XIX. yüzyıl Rus edebiyatında `gereksiz insan` tiplemesi, dönemin yazarlarının gerçek yaşama ışık tutmaya başlamasıyla çağ boyunca birçok eserde kimi zaman başkarakter kimi zaman da yan karakter olarak sıklıkla ele alındığı için büyük bir öneme sahiptir. XIXth century is a period as famous Russian writers are the most productive, to bring in generous pieces to Russian literature as well as the world literature, that the Russian literature shine through and live its `Gold period`. The topic of our thesis is `superfluous man` characters in the XIXth century Russian literature. In the XIXth century lots of famous Russian writers like A.S.Pushkin, A.S.Griboyedov, M.Y. Lermontov, A.I.Herzen, I.S.Turgenev, I.A.Goncharov ve A.P.Chekhov dealt with the issue of `superfluous man` in their masterpieces.While `superfluous man` issue starts to show up in the first quarter of the XIXth century, the politic, social, cultural, sociological, economic, psychological causes are effective. The issue is realized by the period writers who are interested in Russian society as they head towards the realism movement, and echoed in the XIXth century Russian literature as `superfluous man` characters.The `superfluous man` is a character that cannot adopt the superior abilities he has got into real life, falls into a dilemma between the thoughts and soul, doesn't accomplish his plans into real life, has a life without an aim or effort, doesn't have a place in the society and as a result of all those, who fall into spiritual breakdown. The typecasting which come forward among these characters are; Onegin in the masterpiece `Eugene Onegin`, Chatsky in `Woe from Wit`, Pechorin in `A Hero of Our Time`, Beltov in the masterpiece named `Who is to Blame?`, Chulkaturin in `The Diary of a Superfluous Man`, Rudin as the main character of the book with the same name, Lavretsky in `A Nest of Gentlefolk`, Oblomov the main character of the book with the same name, Raisky in `The Precipice`, Nejdanov in `Nov`, Sanin in `Spring Torrents` and Laevsky in `The Duel`. Alongside the `superfluous man` has common characteristics, he transformed by the social changing process and different features arise in his personality.The `superfluous man` characters arise by Russian writers who are great observers as a result of having the people characterized that they had encountered in Russian society with the charm of the realism movement and reflecting in their works. The `superfluous man` characters in the XIXth century Russian literature has a great importance as it handled frequently in many literature works as the main or sub character throughout the era by the writers of the period who started to shed light on real life. 197

Vertebrate type V myosins (MyoV) Myo5a, Myo5b, and Myo5c mediate transport of several different cargoes. All MyoV paralogs bind to cargo complexes mainly by their C-terminal globular domains. In absence of cargo, the globular domain of Myo5a inhibits its motor domain. Here, we report low-resolution SAXS models for the globular domains from human Myo5a, Myo5b, and Myo5c, which suggest very similar overall shapes of all three paralogs. We determined the crystal structures of globular domains from Myo5a and Myo5b, and provide a homology model for human Myo5c. When we docked the Myo5a crystal structure into a previously published electron microscopy density of the autoinhibited full-length Myo5a, only one domain orientation resulted in a good fit. This structural arrangement suggests the participation of additional region of the globular domain in autoinhibition. Quantification of the interaction of the Myo5a globular domain with its motor complex revealed a tight binding with dissociation half-life in the order of minutes, suggesting a rather slow transition between the active and inactive states.

Two nonsteroids, ONO-3805 and LY191704, were evaluated as inhibitors of the human and rat 5α-reductases (5αR). ONO-3805 was prepared in a 12-step convergent synthesis. This compound is a potent inhibitor of the human and rat 5αRs, with more potent inhibition seen against the rat enzymes. The inhibition patterns of this compound were best fit to an uncompetitive model which suggests binding in a ternary complex with enzyme and NADP+. ApparentKivalues of 27, 31, 1, and 0.5 n$of5$M versus testosterone were obtained with human type 1, human type 2, rat type 1, and rat type 2 5αR, respectively. Multiple inhibition studies with ONO-3805 and NADP+support synergistic binding of these two inhibitors with all isozymes. LY191704 was also evaluated as an inhibitor of the human and rat 5αRs. This compound is a selective, competitive inhibitor of human type 1 5αR. Poor inhibition was observed with human type 2 and rat types 1 and 2 5αR.

Transgenic mice were produced that expressed different plasma levels (3-60 mg/dl) of human apolipoprotein (apo) E2(Arg158 --Cys), which is associated with the recessive form of human type III hyperlipoproteinemia (HLP). In transgenic mice fed a normal chow diet, low levels of apoE2 (10 mg/dl) did not significantly alter the lipid phenotype. Mice expressing intermediate levels of apoE2 (10-30 mg/dl) had a 50-60% decrease in total cholesterol compared with nontransgenic mice. The decrease was almost entirely due to a reduction in high density lipoprotein (HDL) cholesterol. These hypolipidemic apoE2 transgenic mice were cross-bred with human apoB transgenic mice, which have increased total cholesterol and low density lipoprotein (LDL) levels. The apoE2/apoB double transgenics revealed that expression of apoE2 on the background of human apoB overexpression resulted in a substantial decrease in LDL and HDL cholesterol and a corresponding accumulation of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL). Thus, the double transgenics had a lipid phenotype resembling human type III HLP. In contrast to the hypolipidemic mice, mice expressing high levels of apoE2 (50 mg/dl) were hyperlipidemic. The VLDL and IDL in these mice were significantly increased and cholesterol-enriched and had other characteristics of remnant lipoproteins. Upon agarose gel electrophoresis, the VLDL and IDL from both intermediate and high expressers migrated more slowly toward the beta position compared with the pre-beta-mobility of nontransgenic mouse VLDL and IDL. Thus, depending on plasma apoE2 levels, the expression of human apoE2 in the transgenic mice leads to either a hypolipidemic or hyperlipidemic phenotype. This animal model provides the opportunity to study the factors that cause hypolipidemia and those that precipitate the hyperlipidemia of type III HLP.

CryptoDB (http://CryptoDB.org) represents a collaborative effort to locate all genome data for the apicomplexan parasite Cryptosporidium parvum in a single user-friendly database. CryptoDB currently houses the genomic sequence data for both the human type 1 H strain and the bovine type 2 IOWA strain in addition to all other available EST and GSS sequences obtained from public repositories. All data are available for data mining via BLAST, keyword searches of pre-computed BLASTX results and user-defined or PROSITE motif pattern searches. Release 1.0 of CryptoDB contains approximately 19 million bases of genome sequence for the H and IOWA strains and an additional approximately 24 million bases of GSS and EST sequence obtained from other sources. Open reading frames greater than 50 and 100 amino acids have been generated for all sequences and all data are available for bulk download. This database, like other apicomplexan parasite databases, has been built utilizing the PlasmoDB model.

Order parameters for the backbone N-H and C alpha-H bond vectors have been calculated from a 150 ps molecular dynamics (MD) simulation of human type-alpha transforming growth factor in H2O solvent. Two kinds of 'crankshaft motions' of the polypeptide backbone are observed in this MD trajectory. The first involves small-amplitude rocking of the rigid peptide bond due to correlated changes in the backbone dihedral angles psi i-1 and phi i. These high-frequency 'librational crankshaft' motions are correlated with systematically smaller values of motional order parameters for backbone N-H bond vectors compared to C alpha-H bond vectors. In addition, infrequent 'crankshaft flips' of the peptide bond from one local minimum to another are observed for several amino acid residues. These MD simulations demonstrate that comparisons of N-H and C alpha-H order parameters provide a useful approach for identifying crankshaft librational motions in proteins.

Type IV P-type ATPases (P4-ATPases) are believed to translocate aminophospholipids from the exoplasmic to the cytoplasmic leaflets of cellular membranes. The yeast P4-ATPases, Drs2p and Dnf1p/Dnf2p, flip nitrobenzoxadiazole-labeled phosphatidylserine at the Golgi complex and nitrobenzoxadiazole-labeled phosphatidylcholine (PC) at the plasma membrane, respectively. However, the flippase activities and substrate specificities of mammalian P4-ATPases remain incompletely characterized. In this study, we established an assay for phospholipid flippase activities of plasma membrane-localized P4-ATPases using human cell lines stably expressing ATP8B1, ATP8B2, ATP11A, and ATP11C. We found that ATP11A and ATP11C have flippase activities toward phosphatidylserine and phosphatidylethanolamine but not PC or sphingomyelin. By contrast, ATPase-deficient mutants of ATP11A and ATP11C did not exhibit any flippase activity, indicating that these enzymes catalyze flipping in an ATPase-dependent manner. Furthermore, ATP8B1 and ATP8B2 exhibited preferential flippase activities toward PC. Some ATP8B1 mutants found in patients of progressive familial intrahepatic cholestasis type 1 (PFIC1), a severe liver disease caused by impaired bile flow, failed to translocate PC despite their delivery to the plasma membrane. Moreover, incorporation of PC mediated by ATP8B1 can be reversed by simultaneous expression of ABCB4, a PC floppase mutated in PFIC3 patients. Our findings elucidate the flippase activities and substrate specificities of plasma membrane-localized human P4-ATPases and suggest that phenotypes of some PFIC1 patients result from impairment of the PC flippase activity of ATP8B1.

Hypoadrenocorticism was diagnosed in four related leonbergers. Two of the four dogs also had low-resting serum thyroxine (T4) levels and signs consistent with hypothyroidism. The familial association of the affected dogs and the presence of coexisting thyroid dysfunction are similar to what is seen in human type II polyglandular autoimmune syndrome.

This study was undertaken to evaluate freeze-dried cross-linked human type I collagen when used as a barrier membrane for guided tissue regeneration (GTR) in periodontal surgery. 14 patients with radiographic evidence of bone loss and residual pocketing of > 6 mm on bilaterally matched sites were given preliminary scaling, polishing and oral hygiene instruction before undergoing contralateral flap surgery. At the experimental sites, a collagen membrane was adapted to the root surfaces, extending from 2 mm apical to the bone crest to just subgingival, before replacing the flap and closing with sutures. The control sites underwent a similar procedure but without the placement of the collagen barrier. The experimental sites were selected at random. Plaque index (PLI), gingival index (GI), bleeding index (BI), probing pocket depth (PPD) and probing attachment level (PAL) were recorded at baseline, 6, 12 and 26 weeks post-operatively. The bony defects were classified and furcation involvement noted. The clinical parameters were recorded by an examiner, previously assessed for accurate reproducibility of measurement, who was not the surgeon and unaware of the experimental sites. PPD and PAL were measured using a constant pressure probe localised by a soft stent. There was significant improvement in the PLI, GI and BI at both test and control sites at 6, 12 and 26 weeks compared to baseline (P < 0.001 for PLI; P < 0.0001 for GI and BI) but not significant difference between these sites.(ABSTRACT TRUNCATED AT 250 WORDS)

In this article we examine the contribution to the analysis of the problem of internalization made by the Russian psychologist Gal’perin. The concept of internalization has been criticized recently for restricting researchers to an old paradigm of Cartesian dualism, with the suggestion made that clearer concepts such as mastery or appropriation be substituted. In our view, the concept of internalization has the advantage of pointing to a specifically human type of appropriation. We propose an alternative solution. Rather than replacing one term with another, the very notions of internal and external in the realm of mental activity should be reconceptualized. In the framework of Gal’perin’s ideas, the processes underlying the internalization concept can be construed without creating dualistic confusion. The result is a better understanding of the specificity of human mental development.

Summary Conversion of erythrocyte membrane B antigen to H antigen produces blood type O which is universally transfusable. If efficient large-scale production of enzymatically converted red blood cells is to be achieved, then optimal conditions for deantigenation must be determined. Cell suspension assays were used to study the blood group B activity of Glycine max (soybean) α-D-galactosidase on native human erythrocytes. The enzyme readily hydrolyzed the terminal α-D-galactosyl residue of the B antigen, converting it to H antigen. Optimal conditions for the enzymatic conversion of red cells with the Glycine enzyme are described. Normal cell morphology and function were maintained under optimal conditions.

It is a qualitative research aimed to analyze the opinion of health professionals at the Testing and Counseling Center/ Specialized Attention Service (TCC/ EAS) comparing to advise provided to people living with human T-lymphotropic human type I and II (HTLV I / II) and identify the facilities/difficulties in implementing such advice. It was held in Santo Antonio de Jesus/Bahia/Brazil, in the CTA/SAE, with eight health professionals as informants. The strategy for collecting information was a semi-structured interview guided by a script. The information from the interviews was analyzed using thematic content analysis as proposed by Minayo. Ethics permeated the entire research process, according to Resolution 196/96 of the National Health Results. The results showed that the completion of counseling is usually compromised by limited information about HTLV. It is necessary to create a training program for HTLV, thus allowing the creation of multipliers of information, encouraging the knowledge of serological status, promoting prevention and reducing the infection rate.

Diabetes mellitus is a common endocrinopathy in humans and in cats. The general prevalence of diabetes mellitus, and in particular of type 2 diabetes, has risen dramatically in recent years. This increase has often been linked to the rise in the obesity pandemic because obesity and the ensuing metabolic consequences constitute major risk factors for human type 2 and for feline diabetes. Feline diabetes shares many features of human type 2 diabetes in respect to its pathophysiology, underlying risk factors and treatment strategies. This review will briefly summarize major characteristics in the human and the feline disease and where available, point out the current knowledge on similarities and differences.

Human type 2 diabetes is associated with β-cell apoptosis, and human islets from diabetic donors are ∼80% deficient in PAK1 protein. Toward addressing linkage of PAK1 to β-cell survival, PAK1–siRNA targeted MIN6 pancreatic β-cells were found to exhibit increased caspase-3 cleavage, cytosolic cytochrome-C and the pro-apoptotic protein Bad. PAK1+/− heterozygous mouse islets recapitulated the upregulation of Bad protein expression, as did hyperglycemic treatment of human or mouse islets; Bad levels were exacerbated most in PAK1+/− islets subjected to hyperglycemic stress. These data implicate PAK1 in β-cell survival via quenching of Bad protein expression, and suggest PAK1 as potential molecular target to preserve β-cell mass., Highlights ▸ Bad expression in islets was increased by chronic exposure to hyperglycemic conditions. ▸ Depletion of PAK1 in the absence of glucose induced Bad expression. ▸ Bad expression increased most in PAK1+/− heterozygous islets subjected to hyperglycemia. ▸ PAK1 is required to protect against β-cell apoptosis under hyperglycemic conditions.

a Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA b Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA c Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA d Glycan Array Synthesis Core-D, Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Nonhuman primates provide the ideal animal model for discovering and examining further the mechanisms underlying human type 2 diabetes mellitus. In all aspects studied to date the nonhuman primate has been shown to develop the same disease with the same features that develop in overweight middle-aged humans. This includes the progressive development of the known complications of diabetes, all of which are extraordinarily like those identified in humans. In addition, for the development and evaluation of new therapeutic agents, the translation of findings from nonhuman primates to application in humans has been highly predictable. Both therapeutic efficacy and identification of potential adverse responses can be effectively examined in nonhuman primates due to their great similarity to humans at the molecular, biochemical, and physiological levels. This chapter provides guidance for the development and management of a colony of monkeys with naturally occurring type 2 diabetes mellitus.

Identification of peptides binding to human leukocyte antigen (HLA) class II molecules is critical for understanding the basis of immunity, and for the development of vaccines and immunotherapeutic for autoimmune disease. A variety of methods have been successfully introduced into this field. However, lacking data is their common obstacle inducing a poor performance of prediction of peptides binding to some HLA class II molecules. For improving present condition, a coarse-graining idea, integrating peptides interacting with HLA class II molecules associated rheumatoid arthritis (RA) as the RA-associated dataset, was proposed. Then a new approach a novel mixed approach, combining dynamic immune algorithm (DIA) with support vector machine regression (SVR), was employed to build a prediction model of RA-associated antigen peptides on the RA-associated dataset. The rationality and advantage of this proposal is seen from the promising results (Acc = 93.1%, MCC = 0.863, AUC=0.966), and from the actual application of the human type II collagen.