bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantioselective Synthesis, Configurational Stability, and Reactivity of Lithium α‐tert‐Butylsulfonyl Carbanion Salts
Authors: Scholz Roland , Hellmann Gunther , Rohs Susanne , Özdemir Diana , Raabe Gerhard , Vermeeren Cornelia , Gais Hans‐Joachim
Published: July 2010

The reactions of enantiopure S‐tert‐butyl sulfones of the type R1CH(R2)SO2tBu (≥99 % ee) with lithiumorganyl compounds gave the corresponding chiral α‐sulfonyl carbanion salts [R1C(R2)SO2tBu]Li with ≥94 % ee. The enantioselectivity of the deprotonation of the phenyl‐ but not dialkyl‐substituted sulfones is strongly dependent on the nature of the lithiumorganyl. Because of this observation and the strong decrease in enantioselectivity in the presence of TMEDA and HMPA, we propose an intramolecular proton transfer following complexation of the sulfone by RLi. Racemization of [R1C(R2)SO2tBu]Li follows first‐order kinetics and seems to be mainly an enthalpic process with a small negative activation entropy, as revealed by polarimetric measurements at low temperatures. This is in accordance with Cα–S bond rotation as the rate‐determining step. The salts [R1C(R2)SO2tBu]Li have half‐lives of racemization in the order of several hours at –105 °C. The deuteriation of the salts at –105 °C with CF3CO2D proceeded with enantioselectivities of ≥94 % ee, the magnitude of which was not significantly affected by the presence of TMEDA and HMPA. The salts also reacted with carbon‐based electrophiles at low temperatures with high enantioselectivity. The conversion of R1CH(R2)SO2tBu via [R1C(R2)SO2tBu]Li to R1C(R2,E)SO2tBu, which involves the loss of stereogenicity at the α‐stereogenic center and its re‐establishment upon reaction of the chiral carbanion with electrophiles, occurred with high overall enantioselectivity. Electrophiles attack the anionic C atom of [R1C(R2)SO2tBu]Li with high selectivity on the side syn to the O atoms and anti to the tert‐butyl group. The reactivity of the dialkyl‐substituted salts [R1C(R2)SO2tBu]Li (R1, R2 = alkyl) is significantly higher than that of the benzylic salts [RC(Ph)SO2tBu]Li (R = alkyl) and the HMPA‐coordinated SIPs of [MeC(Ph)SO2tBu]Li are significantly more reactive towards EtI than the corresponding O–Li contact ion pairs.
Recent Progress in the Chemically Catalyzed Enantioselective Synthesis of Cyanohydrins
Authors: Wang Wentao , Liu Xiaohua , Lin Lili , Feng Xiaoming
Published: July 2010

The catalytic enantioselective cyanation of aldehydes and ketones has received growing attention because the resulting enantiomerically pure cyanohydrins are versatile building blocks for many biologically active compounds. To date, both metal‐based and organic catalysts have been successfully developed to promote these reactions enantioselectively. Great advances have been made in the catalytic enantioselective addition of various cyanide sources to carbonyl compounds. In this microreview, recent progress, including substrate scope and limitations, and probable reaction mechanisms are discussed. In addition, the application of this methodology to the synthesis of natural products is also presented briefly where appropriate.
Multicomponent Reactions of Furan‐2,3‐diones: Synthesis and Characterizations of Furo[3,2‐c]pyran‐4‐ones
Authors: Koca İrfan , Yıldırım İsmail , Şahin Ertan
Published: July 2010

Furo[3,2‐c]pyran‐4‐ones, which possess a natural‐product skeleton, are synthesizedviaa simple, one‐pot, three‐component reaction of furan‐2,3‐diones with dialkyl acetylenedicarboxylates and Ph3P.
One‐Pot, Pseudo‐Five‐Component Synthesis of Bis[2‐(arylimino)‐1,3‐thiazolidin‐4‐ones]
Authors: Alizadeh Abdolali , Noaparast Zohreh , Sabahno Hamideh , Zohreh Nasrin
Published: July 2010

Synthesis and characterization of bis[2‐(arylimino)‐1,3‐thiazolidin‐4‐ones] are described. The one‐pot, pseudo‐five‐component reaction of an aliphatic diamine, isothiocyanatobenzene, and dialkyl but‐2‐ynedioate at room temperature in anhydrous CH2Cl2 gives the title compound in relatively high yield. Under the same conditions, aromatic 1,2‐diamines yield 2‐(arylimino)‐N‐(enaminoaryl)‐1,3‐thiazolidin‐4‐ones in a pseudo‐four‐component reaction. Their structures were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme 3).
Total Synthesis of Nonenolide
Authors: Meshram Harshadas Mitaram , Kumar Dachepally Aravind , Ramesh Palakuri
Published: July 2010

A novel synthetic route has been reported for the synthesis of nonenolide. The syntheses of fragments were initiated from commercially available and inexpensive starting materials. The synthesis involves key steps like Sharpless epoxidation, Jacobsen's resolution, lactonization, and cross‐metathesis.
In‐ and Out‐of‐Cavity Interactions by Modulating the Size of Ruthenium Metallarectangles
Authors: Barry Nicolas P. E. , Furrer Julien , Therrien Bruno
Published: July 2010

Cationic (arene)ruthenium‐based tetranuclear complexes of the general formula [Ru4(η6‐p‐cymene)4(μ‐N∩N)2(μ‐OO∩OO)2]4+ were obtained from the dinuclear (arene)ruthenium complexes [Ru2(η6‐p‐cymene)2(μ‐OO∩OO)2Cl2] (p‐cymene=1‐methyl‐4‐(1‐methylethyl)benzene, OO∩OO=5,8‐dihydroxy‐1,4‐naphthoquinonato(2−), 9,10‐dihydroxy‐1,4‐anthraquinonato(2−), or 6,11‐dihydroxynaphthacene‐5,12‐dionato(2−)) by reaction with pyrazine or bipyridine linkers (N∩N=pyrazine, 4,4′‐bipyridine, 4,4′‐[(1E)‐ethene‐1,2‐diyl]bis[pyridine]) in the presence of silver trifluoromethanesulfonate (CF3SO3Ag) (Scheme). All complexes 4–12 were isolated in good yield as CF3SO$\rm{{_{3}^{-}}}$ salts, and characterized by NMR and IR spectroscopy. The host–guest properties of the metallarectangles incorporating 4,4′‐bipyridine and (4,4′‐[(1E)‐ethene‐1,2‐diyl]bis[pyridine] linkers were studied in solution by means of multiple NMR experiments (1D, ROESY, and DOSY). The largest metallarectangles 10–12 incorporating (4,4′‐[(1E)‐ethene‐1,2‐diyl]bis[pyridine] linkers are able to host an anthracene, pyrene, perylene, or coronene molecule in their cavity, while the medium‐size metallarectangles 7–9 incorporating 4,4′‐bipyridine linkers are only able to encapsulate anthracene. However, out‐of‐cavity interactions are observed between these 4,4′‐bipyridine‐containing rectangles and pyrene, perylene, or coronene. In contrast, the small pyrazine‐containing metallarectangles 4–6 show no interaction in solution with this series of planar aromatic molecules.
LACE‐conditioned autologous stem cell transplantation for relapsed or refractory diffuse large B‐cell lymphoma: treatment outcome and risk factor analysis from a single centre
Authors: Pavlů Jiří , Auner Holger W. , Ellis Sarah , Szydlo Richard M. , Giles Chrissy , Contento Alejandro , Rahemtulla Amin , Apperley Jane F. , Naresh Kikkeri , MacDonald Donald H. , Kanfer Edward J.
Published: July 2010

High‐dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed diffuse large B‐cell lymphoma. We have analysed 51 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara‐C), cyclophosphamide, etoposide) conditioning for relapsed (n = 34, 67%) or primary refractory (n = 17, 33%) diffuse large B‐cell lymphoma. With a median follow‐up of 60 months (range 2–216) the probabilities of overall survival (OS) and progression‐free survival (PFS) at 5 years were 47 and 42%, respectively. The cumulative treatment‐related mortality was 10% (n = 5). Probabilities for OS and PFS at 5 years were 56 and 50% for patients with chemosensitive and 29 and 27% for patients with chemorefractory disease. In multivariate analysis abnormal pre‐ASCT levels of C‐reactive protein (>5 mg/L) were identified as a risk factor for worse OS, whereas abnormal pre‐ASCT levels of C‐reactive protein and chemoresistance predicted inferior PFS. LACE followed by ASCT is an effective treatment for approximately half of patients with chemosensitive relapsed diffuse large B‐cell lymphoma, and a proportion of chemorefractory patients also benefit. Copyright © 2010 John Wiley & Sons, Ltd.
A novel mucosal orthotopic murine model of human papillomavirus‐associated genital cancers
Authors: Decrausaz Loane , Gonçalves Ana‐Rita , Domingos‐Pereira Sonia , Pythoud Christelle , Stehle Jean‐Christophe , Schiller John , Jichlinski Patrice , Nardelli‐Haefliger Denise
Published: July 2010

Cervical cancer results from infection with high‐risk type human papillomaviruses (HPV). Therapeutic vaccines aiming at controlling existing genital HPV infections and associated lesions are usually tested in mice with HPV‐expressing tumor cells subcutaneously implanted into their flank. However, effective vaccine‐induced regression of these ectopic tumors strongly contrasts with the poor clinical results of these vaccines produced in patients with HPV‐associated genital neoplasia. To assess HPV therapeutic vaccines in a more relevant setting, we have, here, established an orthotopic mouse model where tumors in the genital mucosa (GM) develop after an intravaginal instillation of HPV16 E6/E7‐expressing tumor cells transduced with a luciferase‐encoding lentiviral vector for in vivo imaging of tumor growth. Tumor take was 80–90% after nonoxynol‐9 induced damage of the epithelium. Tumors remained localized in the genital tract, and histological analysis showed that most tumors grew within the squamous epithelium of the vaginal wall. Those tumors induced (i) E7‐specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non‐regressing HPV lesions. This novel genital HPV‐tumor model by requiring GM homing of vaccine‐induced immune responses able to overcome local immuno‐suppression may be more representative of the situation occurring in patients upon therapeutic vaccination.
The development and application of the chemical mixture methodology in analysis of potential health impacts from airborne release in emergencies
Authors: Yu Xiao‐Ying , Petrocchi Achille J. , Craig Douglas K. , Glantz Clifford S. , Trott Donna M. , Ciolek John , Lu Po‐Yung , Bond Jayne‐Anne , Tuccinardi Thomas E. , Bouslaugh Philip
Published: July 2010

The Chemical Mixture Methodology (CMM) is used for emergency response and safety planning by the US Department of Energy, its contractors and other private and public sector organizations. The CMM estimates potential health impacts on individuals and their ability to take protective actions as a result of exposure to airborne chemical mixtures. It is based on the concentration of each chemical in the mixture at a designated receptor location, the protective action criteria (PAC) providing chemical‐specific exposure limit values and the health code numbers (HCNs) that identify the target organ groupings that may be impacted by exposure to each chemical in a mixture. The CMM has been significantly improved since its introduction more than 10 years ago. Major enhancements involve the expansion of the number of HCNs from 44 to 60 and inclusion of updated PAC values based on an improved development methodology and updates in the data used to derive the PAC values. Comparisons between the 1999 and 2009 versions of the CMM show potentially substantial changes in the assessment results for selected sets of chemical mixtures. In particular, the toxic mode hazard indices (HIs) and target organ HIs are based on more refined acute HCNs, thereby improving the quality of chemical consequence assessment, emergency planning and emergency response decision‐making. Seven hypothetical chemical storage and processing scenarios are used to demonstrate how the CMM is applied in emergency planning and hazard assessment. Copyright © 2010 John Wiley & Sons, Ltd.
Characterization of hematopoietic potential of mesenchymal stem cells
Authors: Freisinger Eva , Cramer Christopher , Xia Xiujin , Murthy Subramanyam N. , Slakey Douglas P. , Chiu Ernest , Newsome Edward R. , Alt Eckhard U. , Izadpanah Reza
Published: July 2010

Mesenchymal and hematopoietic tissues are important reservoirs of adult stem cells. The potential of tissue resident mesenchymal stem cells (MSCs) to differentiate into cells of mesodermal and ectodermal lineages has been reported previously. We examined the hypothesis that adherent adipose tissue resident mesenchymal stem cells (ASCs) are capable of generating cells with hematopoietic characteristics. When cultured in differentiation media, clonally isolated ASCs develop into cells with hematopoietic attributes. The hematopoietic differentiated cells (HD) express early hematopoietic (c‐kit, PROM1, CD4) as well as monocyte/macrophage markers (CCR5, CD68, MRC1, CD11b, CSF1R). Additionally, HD cells display functional characteristics of monocyte/macrophages such as phagocytosis and enzymatic activity of α‐Naphthyl Acetate Esterase. HD cells are also responsive to stimulation by IL‐4 and LPS as shown by increased CD14 and HLA‐DRB1 expressions and release of IL‐2, IL10, and TNF. Taken together, this study characterizes the potential of ASCs to generate functional macrophages in vitro, and therefore paves way for their possible use in cell therapy applications. J. Cell. Physiol. 225: 888–897, 2010. © 2010 Wiley‐Liss, Inc.
Bone resorption control of tooth eruption and root morphogenesis: Involvement of the receptor activator of NF‐κB (RANK)
Authors: Castaneda Beatriz , Simon Yohann , Jacques Jaime , Hess Estelle , Choi Yong‐Wong , Blin‐Wakkach Claudine , Mueller Christopher , Berdal Ariane , Lézot Frédéric
Published: July 2010

Activation of the receptor activator of NF‐κB (RANK) is a crucial step in osteoclastogenesis. Loss‐ and gain‐of‐function mutations in the Rank gene cause, respectively, osteopetrosis and several forms of extensive osteolysis. Tooth and alveolar bone alterations are associated with these pathologies but remain to be better characterized. The aim of the present study was to establish the tooth and alveolar bone phenotype of a transgenic mouse model of RANK over‐expression in osteoclast precursors. Early tooth eruption and accelerated tooth root elongation were observed subsequent to an increase in osteoclast numbers surrounding the tooth. The final root length appeared not to be affected by RANK over‐expression, but a significant reduction in root diameter occurred in both control and root‐morphogenesis‐defective Msx2 null mutant mice. These results indicate that root length is independent of the surrounding bone resorption activity. In contrast, root diameter is sensitive to the activity of alveolar bone osteoclasts. These data suggest that early eruption and thin root are phenotypic features that could be associated with extensive osteolytic pathologies. J. Cell. Physiol. 226: 74–85, 2010. © 2010 Wiley‐Liss, Inc.
Lentiviral airway gene transfer in lungs of mice and sheep: successes and challenges
Authors: Liu Chuanhe , Wong Edward , Miller Darren , Smith Greg , Anson Don , Parsons David
Published: July 2010

Background

Persistent airway gene expression can be achieved in mouse nasal airway using a vesicular stomatitis virus glycoprotein pseudotyped lentiviral (LV) gene vector in combination with lysophosphatidylcholine (LPC) pretreatment. We have now examined the acute in vivo effects of this combination single‐dose method for airway LV gene transfer in mouse and sheep lung.

Methods

Mouse and sheep lungs were exposed to LPC followed 1 h later with the LV vector. Lungs were processed 7 days later using X‐gal detection to measure β‐gal gene expression and identify transduced cell types.

Results

In mouse ciliated conducting airways, LPC pretreatment produced extensive gene transfer that extended from the tracheal dosing site into the bronchi and lower airways. Gene expression was present in both terminally differentiated surface cells and in basal cells. Without LPC pretreatment, transduction was limited to the dosing site. In sheep lung, small‐volume bronchoscopic instillation delivery produced localized and low‐level transduction near the dosing site. Gene expression was again present in surface and basal cells. Neither alterations in LPC dose parameters, nor larger vector volumes increased the level of transduction.

Conclusions

These findings are the first to confirm the applicability of LPC pretreatment in the production of extensive lentiviral gene transfer in mouse lung airways. However, improved methodologies to increase transduction efficiency are required for adult sheep lung. The results suggest that continued in vivo development of LPC‐enhanced lentiviral gene transfer is needed in the lungs of large animals to establish effective lentiviral gene transfer techniques suited to the treatment of airway disease. Copyright © 2010 John Wiley & Sons, Ltd.
Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter‐driven oncolytic adenovirus
Authors: Kubo Shuji , Kawasaki Yoshiko , Yamaoka Norie , Tagawa Masatoshi , Kasahara Noriyuki , Terada Nobuyuki , Okamura Haruki
Published: July 2010

Background

Malignant mesothelioma is a highly aggressive tumor with poor prognosis. We hypothesized that the tumor‐specific midkine (Mdk) promoter could confer transcriptional targeting to oncolytic adenoviruses for effective treatment of malignant mesothelioma.

Methods

We analysed Mdk expression by quantitative reverse transcription‐polymerase chain reaction in six human mesothelioma cell lines, and tested Mdk promoter activity by luciferase reporter assay. On the basis of these data, we constructed a replication‐selective oncolytic adenovirus designated AdMdk‐E1‐iresTK. This virus contains a Mdk promoter‐driven adenoviral E1 gene and herpes simplex virus‐thymidine kinase (TK) suicide gene and cytomagalovirus promoter‐driven enhanced green fluorescent protein marker gene. Selectivity of viral replication and cytolysis were characterized in normal versus mesothelioma cells in vitro, and intratumoral spread and antitumor efficacy were investigated in vivo.

Results

Mdk promoter activity was restricted in normal cells, but highly activated in mesothelioma cell lines. AdMdk‐E1‐iresTK was seen to efficiently replicate, produce viral progeny and spread in multiple mesothelioma cell lines. Lytic spread of AdMdk‐E1‐iresTK mediated the efficient killing of these mesothelioma cells, and its in vitro cytocidal effect was significantly enhanced by treatment with the prodrug, ganciclovir. Intratumoral injection of AdMdk‐E1‐iresTK caused complete regression of MESO4 and MSTO human mesothelioma xenografts in athymic mice. In vivo fluorescence imaging demonstrated intratumoral spread of AdMdk‐E1‐iresTK‐derived signals, which vanished after tumor eradication.

Conclusions

These data indicate that transcriptional targeting of viral replication by the Mdk promoter represents a promising general strategy for oncolytic virotherapy of cancers with up‐regulated Mdk expression, including malignant mesothelioma. Copyright © 2010 John Wiley & Sons, Ltd.
High frequency of lamivudine resistance mutations in Brazilian patients co‐infected with HIV and hepatitis B
Authors: Mendes‐Correa M.C. , Pinho J.R.R. , Locarnini S. , Yuen L. , Sitnik R. , Santana R.A.F. , Gomes‐Gouvêa M.S. , Leite O.M. , Martins L.G. , Silva M.H. , Gianini R.J. , Uip D.E.
Published: July 2010

This study analyzed the genotype distribution and frequency of lamivudine (LAM) and tenofovir (TDF) resistance mutations in a group of patients co‐infected with HIV and hepatitis B virus (HBV). A cross‐sectional study of 847 patients with HIV was conducted. Patients provided blood samples for HBsAg detection. The load of HBV was determined using an “in‐house” real‐time polymerase chain reaction. HBV genotypes/subgenotypes, antiviral resistance, basal core promoter (BCP), and precore mutations were detected by DNA sequencing. Twenty‐eight patients with co‐infection were identified. The distribution of HBV genotypes among these patients was A (n = 9; 50%), D (n = 4; 22.2%), G (n = 3; 16.7%), and F (n = 2; 11.1%). Eighteen patients were treated with LAM and six patients were treated with LAM plus TDF. The length of exposure to LAM and TDF varied from 4 to 216 months. LAM resistance substitutions (rtL180M + rtM204V) were detected in 10 (50%) of the 20 patients with viremia. This pattern and an accompanying rtV173L mutation was found in four patients. Three patients with the triple polymerase substitution pattern (rtV173L + rtL180M + rtM204V) had associated changes in the envelope gene (sE164D + sI195M). Mutations in the BCP region (A1762T, G1764A) and in the precore region (G1896A, G1899A) were also found. No putative TDF resistance substitution was detected. The data suggest that prolonged LAM use is associated with the emergence of particular changes in the HBV genome, including substitutions that may elicit a vaccine escape phenotype. No putative TDF resistance change was detected after prolonged use of TDF. J. Med. Virol. 82:1481–1488, 2010. © 2010 Wiley‐Liss, Inc.
Occult hepatitis B in the genotype H‐infected Nahuas and Huichol native Mexican population
Authors: Roman Sonia , Tanaka Yasuhito , Khan Anis , Kurbanov Fuat , Kato Hideaki , Mizokami Masashi , Panduro Arturo
Published: July 2010

Mexico is considered to be a low endemic country for HBV infection. However, a high anti‐HBc against a low hepatitis B surface antigen (HBsAg) seroprevalence is the reported characteristic of native Mexicans. HBV diagnosis and genotype distribution was examined in native populations (Nahuas and Huichol, n = 306), and compared to a non‐native population (Mestizos, n = 17). Overall, 6% of the natives were positive for HBsAg and 33% had detectable anti‐HBc. HBsAg prevalence was lower in Nahuas compared to Huichols (1.4% vs. 9.4%,P < 0.002). Occult hepatitis B was detected in 14.2% (41/289) of natives, who either tested positive (5.88%, 17/289 HBsAg‐negative) or negative for anti‐HBc marker (8%, 24/289 HBsAg‐negative). Age‐adjusted anti‐HBc seroprevalence and HBsAg quantitation revealed a sub‐optimal sensitivity of conventional immunoassays. Nahuas had HBV/H and Huichol had HBV/A as the predominant genotypes followed by genotypes D, C, B, A, and D, G and H, respectively. A less variable HBV/H was characteristic in Mestizos, compared to a much variable HBV/H identified among the Nahuas. In conclusion, these findings indicate a high HBV endemicity among native Mexican groups where occult B infection is common. The different distribution of HBV genotypes among natives suggests multiple reservoirs of HBV from which these genotypes spread into the local communities. High anti‐HBc seroprevalence against a low HBsAg prevalence rate may be due to the limited sensitivity of the immunoassays for the detection of HBsAg that are available in Mexico and/or unknown immunogenetic characteristics of native Mexicans. J. Med. Virol. 82:1527–1536, 2010. © 2010 Wiley‐Liss, Inc.
Early and reliable detection of herpes simplex virus type 1 and varicella zoster virus DNAs in oral fluid of patients with idiopathic peripheral facial nerve palsy: Decision support regarding antiviral treatment?
Authors: Lackner Andreas , Kessler Harald H. , Walch Christian , Quasthoff Stefan , Raggam Reinhard B.
Published: July 2010

Idiopathic peripheral facial nerve palsy has been associated with the reactivation of herpes simplex virus type 1 (HSV‐1) or varicella zoster virus (VZV). In recent studies, detection rates were found to vary strongly which may be caused by the use of different oral fluid collection devices in combination with molecular assays lacking standardization. In this single‐center pilot study, liquid phase‐based and absorption‐based oral fluid collection was compared. Samples were collected with both systems from 10 patients with acute idiopathic peripheral facial nerve palsy, 10 with herpes labialis or with Ramsay Hunt syndrome, and 10 healthy controls. Commercially available IVD/CE‐labeled molecular assays based on fully automated DNA extraction and real‐time PCR were employed. With the liquid phase‐based oral fluid collection system, three patients with idiopathic peripheral facial nerve palsy tested positive for HSV‐1 DNA and another two tested positive for VZV DNA. All patients with herpes labialis tested positive for HSV‐1 DNA and all patients with Ramsay Hunt syndrome tested positive for VZV DNA. With the absorption‐based oral fluid collection system, detections rates and viral loads were found to be significantly lower when compared to those obtained with the liquid phase‐based collection system. Collection of oral fluid with a liquid phase‐based system and the use of automated and standardized molecular methods allow early and reliable detection of HSV‐1 and VZV DNAs in patients with acute idiopathic peripheral facial nerve palsy and may provide a valuable decision support regarding start of antiviral treatment at the first clinical visit. J. Med. Virol. 82:1582–1585, 2010. © 2010 Wiley‐Liss, Inc.
Association of NKG2D genetic polymorphism with susceptibility to chronic hepatitis B in a Han Chinese population
Authors: Ma Juan , Guo Xinhui , Wu Xiaopan , Li Junhong , Zhu Xilin , Li Zhuo , Li Jingyun , Pan Liping , Li Tianjie , Li Hui , Liu Ying
Published: July 2010

Natural killer (NK) cells are important antiviral effectors of innate immunity because of their contribution to virus elimination. NK cell‐mediated immunological reaction to hepatitis B virus (HBV) infection depends on a fine balance between inhibitory and activating receptors. The aim of the study was to investigate genetic polymorphisms in NK cell receptors (NKR)—KLRD1 (CD94), KLRK1 (NKG2D), KLRC4 (NKG2F), and KLRC1 (NKG2A)—to evaluate the association of NKR genetic polymorphisms with susceptibility to chronic hepatitis B in a Han Chinese population. Twelve single nucleotide polymorphisms (SNPs), including rs2302489 in CD94; rs2255336, rs2617160, rs7980470, rs 2734565, and rs17513986 in NKG2D; rs2617170, rs17549004, and rs3825295 in NKG2F; rs2734414, rs7301582, and rs2734440 in NKG2A, were selected in the present study. SNP genotyping was undertaken in 500 Han Chinese patients (285 patients with chronic hepatitis B and 215 patients who cleared HBV spontaneously) by a polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and by the TaqMan method. Single marker association analysis was conducted and the SNP rs2617160 with a TT genotype in NKG2D was associated significantly with an increased risk of chronic hepatitis B (P = 0.044; OR = 1.49; 95% CI = 1.01–2.19). Haplotype analysis with multiple loci indicated that there was no significant association between the haplotypes of the NKR genes and susceptibility to chronic hepatitis B. The SNP rs2617160 in NKG2D associated with susceptibility to chronic hepatitis B in a Han Chinese population. J. Med. Virol. 82:1501–1507, 2010. © 2010 Wiley‐Liss, Inc.
Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg‐negative patients
Authors: Lin L.Y. , Wong V.W.S. , Zhou H.J. , Chan H.Y. , Gui H.L. , Guo S.M. , Wang H. , Huang L. , Bao S.S. , Xie Q. , Chan H.L.Y.
Published: July 2010

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg‐negative chronic hepatitis B patients. Thirty‐three treatment‐naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/106 cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg‐negative chronic hepatitis B. J. Med. Virol. 82:1494–1500, 2010. © 2010 Wiley‐Liss, Inc.
Confirmation of Choclo virus as the cause of hantavirus cardiopulmonary syndrome and high serum antibody prevalence in Panama
Authors: Nelson Randin , Cañate Raul , Pascale Juan Miguel , Dragoo Jerry W. , Armien Blas , Armien Anibal G. , Koster Frederick
Published: July 2010

Choclo virus (CHOV) was described in sigmodontine rodents, Oligoryzomys fulvescens, and humans during an outbreak of hantavirus cardiopulmonary syndrome (HCPS) in 1999–2000 in western Panama. Although HCPS is rare, hantavirus‐specific serum antibody prevalence among the general population is high suggesting that CHOV may cause many mild or asymptomatic infections. The goals of this study were to confirm the role of CHOV in HCPS and in the frequently detected serum antibody and to establish the phylogenetic relationship with other New World hantaviruses. CHOV was cultured to facilitate the sequencing of the small (S) and medium (M) segments and to perform CHOV‐specific serum neutralization antibody assays. Sequences of the S and M segments found a close relationship to other Oligoryzomys‐borne hantaviruses in the Americas, highly conserved terminal nucleotides, and no evidence for recombination events. The maximum likelihood and maximum parsimony analyses of complete M segment nucleotide sequences indicate a close relationship to Maporal and Laguna Negra viruses, found at the base of the South American clade. In a focus neutralization assay acute and convalescent sera from six Panamanian HCPS patients neutralized CHOV in dilutions from 1:200 to 1:6,400. In a sample of antibody‐positive adults without a history of HCPS, 9 of 10 sera neutralized CHOV in dilutions ranging from 1:100 to 1:6,400. Although cross‐neutralization with other sympatric hantaviruses not yet associated with human disease is possible, CHOV appears to be the causal agent for most of the mild or asymptomatic hantavirus infections, as well as HCPS, in Panama. J. Med. Virol. 82:1586–1593, 2010. © 2010 Wiley‐Liss, Inc.
Diagnosis of occult hepatitis C without the need for a liver biopsy
Authors: Castillo Inmaculada , Bartolomé Javier , Quiroga Juan Antonio , Barril Guillermina , Carreño Vicente
Published: July 2010

The diagnosis of occult hepatitis C virus (HCV) infection is based on the presence of HCV‐RNA in the liver. This study aimed to evaluate the use of combining non‐invasive assays to diagnose occult HCV. A total of 122 patients with occult HCV (HCV‐RNA in the liver without detectable anti‐HCV and serum HCV‐RNA) and 45 patients with cryptogenic chronic hepatitis (without HCV‐RNA in the liver and negative for anti‐HCV and serum HCV‐RNA) were included. HCV‐RNA was tested in peripheral blood mononuclear cells (PBMCs) and in 2 ml of ultracentrifuged serum. Anti‐core HCV was examined by a non‐commercial enzyme‐linked immunosorbent assay. All controls were negative for the three HCV markers studied. Among patients with occult HCV, 36% were anti‐core HCV positive, 57% had serum HCV‐RNA after ultracentrifugation, and 61% had HCV‐RNA in PBMCs. Combining the results of the assays, 91% of the patients were positive for at least one marker. Intrahepatic HCV‐RNA load was significantly higher in patients who were positive simultaneously for the three HCV markers than in patients who were negative for all markers (P = 0.006) and than in those with one or two HCV markers (P = 0.039). Replication of HCV in liver was detected more frequently in patients with three (93%, P = 0.002), two (82%, P = 0.001), and one HCV marker (73%, P = 0.011) than in those without markers (27%). In conclusion, testing for all these markers allows diagnosis of occult HCV without the need for a liver biopsy and these assays may help to elucidate the clinical significance of occult HCV infection. J. Med. Virol. 82:1554–1559, 2010. © 2010 Wiley‐Liss, Inc.
Evaluation of a new screening assay for HTLV‐1 and ‐2 antibodies for large‐scale use
Authors: Malm Kerstin , Kjerstadius Torbjörn , Andersson Sören
Published: July 2010

Laboratory testing for Human T‐lymphotropic Virus type 1 and 2 (HTLV‐1 and ‐2) infections has become routine in blood transfusion, tissue transplantation and clinical diagnoses in many countries worldwide. Screening is usually based on the detection of antibodies to HTLV‐1 and/ or ‐2. The number of commercially available assays is limited, and among them, ELISA tests based on microtiter format are most commonly used. Recently, the new rHTLV‐I/II assay (Abbott Laboratories, Abbott Park, IL) was released; this assay was developed for an automatic large‐scale screening platform. This assay was evaluated using pre‐characterized serum panels and routine samples from the clinical laboratory. The sensitivity was 100% for HTLV‐1 and ‐2 (99/99 and 42/42, respectively, including one sample that was dually reactive, HTLV‐1 + 2). To test assay specificity, panels of blood donor sera, specimens from patients with autoimmune diseases and some viral infections were used. False‐reactive samples from previous HTLV diagnoses were also included. With these panels, the specificity was 99.4% (619/623). However, the four false‐reactive samples all belonged to the group of samples that were previously considered as false‐reactive for HTLV‐antibodies. All other samples were negative by the rHTLV‐I/II assay, and thus 100% specificity was obtained. The 1,412 samples tested in the clinic by this assay in routine use were all negative (100% specificity). Taken together, the overall specificity was 99.8%. The assay was sensitive, specific and appropriate for the large‐scale screening of samples for HTLV‐1/2 antibodies. J. Med. Virol. 82:1606–1611, 2010. © 2010 Wiley‐Liss, Inc.
Pharmacokinetic/ Pharmacodynamic‐Driven Drug Development
Authors: Gallo James M.
Published: July 2010

The drug discovery and development enterprise, traditionally an industrial juggernaut, has spanned into the academic arena that is partially motivated by the National Institutes of Health Roadmap highlighting translational science and medicine. Because drug discovery and development represents a pipeline of basic to clinical investigations, it meshes well with the “bench to the bedside” prime directive of translational medicine. The renewed interest in drug discovery and development in academia provides an opportunity to rethink the hiearchary of studies with the hope of improving the staid approaches that have been criticized for lacking innovation. One area that has received limited attention concerns the use of pharmacokinetic and pharmacodynamic studies in the drug‐development process. Using anticancer drug development as a focus, this review will address past and current deficencies in how pharmacokinetic/pharmacodynamic studies are conducted and offer new strategies that might bridge the gap between preclinical and clinical trials. Mt Sinai J Med 77:381–388, 2010. © 2010 Mount Sinai School of Medicine
Pursuit of Personalized Anticancer Therapy: Leveraging Collaboration Between Academia and the Biotech/Pharmaceutical Industry
Authors: Buck Elizabeth , Mulvihill Mark , Iwata Kenneth K.
Published: July 2010

Over the past 2 decades, our increased understanding of tumor biology has resulted in the delivery of a new generation of molecularly targeted cancer drugs with greater efficacy and less toxicity. This understanding has also provided pharmaceutical and academic institutions with a greater appreciation for the complexities and challenges associated with discovering and developing molecularly targeted drugs. To deal with the complexities of tumor biology and the associated technologies needed to develop molecularly targeted drugs, there has been increased cooperation and collaboration between academic and pharmaceutical‐industry researchers in a broader number of aspects of the drug discovery and development continuum, including structural biology and translational research. This collaborative effort has played a role in molecularly targeted drugs such as cetuximab, trastuzumab, imatinib, and new promising drug candidates such as OSI‐906. Cooperative efforts by industry and academia have also provided important insights to optimize the use of such agents in the clinic. This review aims to emphasize the need for academic/industrial collaborations for success and efficiency through the drug discovery and development continuum, and will highlight several examples of collaborations between academic and industrial scientists that facilitated the development of molecularly targeted antitumor agents into the clinic. Mt Sinai J Med 77:358–365, 2010. © 2010 Mount Sinai School of Medicine
Role of Antibodies in Developing Drugs That Target G‐Protein‐Coupled Receptor Dimers
Authors: Hipser Chris , Bushlin Ittai , Gupta Achla , Gomes Ivone , Devi Lakshmi A.
Published: July 2010

G‐protein‐coupled receptors are important molecular targets in drug discovery. These receptors play a pivotal role in physiological signaling pathways and are targeted by nearly 50% of currently available drugs. Mounting evidence suggests that G‐protein‐coupled receptors form dimers, and various studies have shown that dimerization is necessary for receptor maturation, signaling, and trafficking. However, the physiological implications of dimerization in vivo have not been well explored because detection of GPCR dimers in endogenous systems has been a challenging task. One exciting new approach to this challenge is the generation of antibodies against specific G‐protein‐coupled receptor dimers. Such antibodies could be used as tools for characterization of heteromer‐specific function; as reagents for their purification, tissue localization, and regulation in vivo; and as probes for mapping their functional domains. In addition, such antibodies could serve as alternative ligands for G‐protein‐coupled receptor heteromers. Thus, heteromer‐specific antibodies represent novel tools for the exploration and manipulation of G‐protein‐coupled receptor‐dimer pharmacology. Mt Sinai J Med 77:374–380, 2010. © 2010 Mount Sinai School of Medicine
Chemidex Cybrary – Rohstoffe für die chemische Industrie
Authors: Schunk Axel
Published: July 2010

Cybrary ist ein datenbankbasiertes Informationssystem. Es enthält überwiegend Informationen zu Rohstoffen für die Chemische Industrie. Die Datenbank verweist auf Datenblätter sowie Bezugsmöglichkeiten und liefert auch Forschern wichtige Informationen zu Grundchemikalien.
NMR mobil: Wie altert Polyethylen?
Authors: Blümich Bernhard
Published: July 2010

Die NMR‐Mouse für die zerstörungsfreie NMR‐Analytik läuft mit einem Spektrometer von der Größe eines Notebooks. Sie untersucht Rohre und Benzintanks aus Kunststoff, Autoreifen und Schläuche, Gemälde alter Meister, lebende Haut und Mumien. Auch Tomogramme und NMR‐Spektren von Flüssigkeiten lassen sich in Auflagetechnik messen.
Dynamische Differenzkalorimetrie: zufällig temperaturmoduliert
Authors: Neff Dirk
Published: July 2010

Ein zufällig sich veränderndes Temperaturprogramm splittet das kalorimetrische Messsignal in einen fühlbaren und einen latenten Wärmestromanteil. Damit lässt sich beispielsweise bei Epoxidharzen die Glasumwandlung von einer überlagerten Nachhärtungsreaktion durch eine einzige Messung trennen.
Hybridmaterialien in der analytischen Chemie
Authors: Descalzo Ana B. , Hoffmann Katrin , Rurack Kurt , Martinez‐Manez Ramon , Sancenon Felix
Published: July 2010

Immer kompliziertere Wirtmoleküle sind keine Garanten für eine immer selektivere molekulare Erkennung. Für praktische Zwecke einfacher und erfolgversprechender ist es, anorganische Trägermaterialien, z. B. poröse Festkörper, mit Erkennungseinheiten zu funktionalisieren. Durch synergistische Effekte entstehen dabei Hybridmaterialien, die sich für die Entwicklung von Sensoren und Assays empfehlen.
Win‐win in Changchun
Authors: Karger Gerhard
Published: July 2010

“Ausbau und Intensivierung” der gemeinsamen Projekte lautet das Motto der zweiten Phase in der Kooperation zwischen Bayer und der Chinese Academy of Sciences. Zur Zwischenbilanz, zur Präsentation von Highlights und zum Networking trafen vergangenes Jahr Bayer‐Forscher und Wissenschaftler aus Top‐Instituten Chinas in Changchun zu einem Symposium zusammen.
Partner für Perspektiven: Moderne Chemieparkbetreiber
Authors: Schäfer Klaus
Published: July 2010

Gegenüber ihren Bestandskunden und beim Werben um neue Investitionen stehen die deutschen Chemieparks im nationalen wie im internationalen Wettbewerb – und der wird zunehmend härter. Dabei bieten sie im Leistungsvergleich durchaus Vorteile.
Grenzflächencharakterisierung mit dem Du‐Noüy‐Ring
Authors: Franck Aly
Published: July 2010

Ein Rheometer mit Magnetschwebelager ermittelt, wie Proteine an Grenzflächen adsorbieren und sich durch Denaturierung und Gelieren verändern.
Die intrinsische Viskosität: Für Polymere rollt die Kugel
Authors: Fuchshofer Emanuel
Published: July 2010

Die Molmasse von Makromolekülen in Lösung lässt sich aus der Viskosität errechnen. So sind auch Wechselwirkungen des Polymers mit dem Lösungsmittel zu erkennen.
Two‐grid mixed finite‐element methods for nonlinear Schrödinger equations
Authors: Wu Li
Published: July 2010

Two‐grid mixed finite element schemes are developed for solving both steady state and unsteady state nonlinear Schrödinger equations. The schemes use discretizations based on a mixed finite‐element method. The two‐grid approach yields iterative procedures for solving the nonlinear discrete equations. The idea is to relegate all of the Newton‐like iterations to grids much coarser than the final one, with no loss in order of accuracy. Numerical tests are performed. © 2010 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 28: 63‐73, 2012
The discrete (G′/G)‐expansion method applied to the differential‐difference Burgers equation and the relativistic Toda lattice system
Authors: Aslan İsmail
Published: July 2010

We introduce the discrete (G′/G)‐expansion method for solving nonlinear differential–difference equations (NDDEs). As illustrative examples, we consider the differential–difference Burgers equation and the relativistic Toda lattice system. Discrete solitary, periodic, and rational solutions are obtained in a concise manner. The method is also applicable to other types of NDDEs. © 2010 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 28: 127‐137, 2012
Thermal and dynamic mechanical properties of epoxy resin/poly(urethane‐imide)/polyhedral oligomeric silsesquioxane nanocomposites
Authors: Song Jiangxuan , Chen Guangxin , Wu Gang , Cai Chunhua , Liu Pinggui , Li Qifang
Published: July 2010

Linear isocyanate‐terminated poly(urethane‐imide) (PUI) with combination of the advantages of polyurethane and polyimide was directly synthesized by the reaction between polyurethane prepolymer and pyromellitic dianhydride (PMDA). Then octaaminophenyl polyhedral oligomeric silsesquioxane (OapPOSS) and PUI were incorporated into the epoxy resin (EP) to prepare a series of EP/PUI/POSS organic–inorganic nanocomposites for the purpose of simultaneously improving the heat resistance and toughness of the epoxy resin. Their thermal degradation behavior, dynamic mechanical properties, and morphology were studied with thermal gravimetric analysis (TGA), dynamic mechanical analysis (DMA), and transmission electron microscope (TEM). The results showed that the thermal stability and mechanical modulus was greatly improved with the addition of PUI and POSS. Moreover, the EP/PUI/POSS nanocomposites had lower glass transition temperatures. The TEM results revealed that POSS molecules could self assemble into strip domain which could switch to uniform dispersion with increasing the content of POSS. All the results could be ascribed to synergistic effect of PUI and POSS on the epoxy resin matrix. Copyright © 2010 John Wiley & Sons, Ltd.
Mechanically active scaffolds from radio‐opaque shape‐memory polymer‐based composites
Authors: Cui J. , Kratz K. , Heuchel M. , Hiebl B. , Lendlein A.
Published: July 2010

The formation of functional tissue is strongly dependent on biochemical as well as physical signals. A common approach in tissue engineering is the application of passive scaffold systems with fixed morphology and stiffness. In this paper, we explored whether mechanically active scaffolds, exhibiting self‐sufficient shape changes under physiological conditions, can be prepared from radio‐opaque shape‐memory polymer composites (SMPCs). The influence of different thermomechanical treatments on the kinetics of the shape change was studied. Radio‐opaque SMPCs were obtained by incorporation of barium sulfate (BaSO4) microparticles (up to 40 wt%) into an amorphous polyether urethane (PEU) via co‐extrusion technique. The shape‐memory properties of the composites were investigated by cyclic, thermomechanical tensile tests consisting of a specific shape‐memory creation procedure (SMCP), in which the programming temperature (Tprog) was varied, followed by recovery under stress‐free condition, enabling the determination of the switching temperature (Tsw). An almost complete recovery with shape recovery rate (Rr) values ranging from 88% to 98% was realized within a small temperature interval of ΔTrec ≈ 30°C for all composites, while Tsw was found to be close to the applied Tprog. The feasibility of actively moving scaffolds was demonstrated using model scaffolds, where originally square‐shaped pores were temporarily fixed in an expanded circular shape at different Tprog. We found that the kinetics of the shape change obtained under physiological conditions could be adjusted by variation of Tprog between 1 and 6 hr. Such radio‐opaque scaffolds could serve as model scaffolds for investigating the active mechanical stimulation of cells in vitro or in vivo. Copyright © 2010 John Wiley & Sons, Ltd.
Structure and properties of clay nano‐biocomposites based on poly(lactic acid) plasticized with polyadipates
Authors: Martino Verónica P. , Jiménez Alfonso , Ruseckaite Roxana A. , Avérous Luc
Published: July 2010

The use of nano‐biocomposites based on plasticized poly(lactic acid) (PLA) has been proposed as a way to improve the polymer ductility and to expand PLA applications window. Novative nano‐biocomposites were elaborated with PLA plasticized by polyadipates (15 wt%) with different molar masses (from 1500 to 2500 Da), with 2.1 wt% of an organo‐modified montmorillonite (O‐MMT). These materials showed enhanced ductility and barrier properties. The clay was swelled in liquid polyadipates prior to their blending with PLA to facilitate chains intercalation and nanofiller exfoliation during melt‐blending. In certain processing conditions, quite homogenous and exfoliated structures were obtained, as shown by X‐ray diffraction (XRD) and transmission electronic microscopy (TEM) results. Irrespective of the average molar mass of the polyadipate, the clay addition induced a reduction in around 25% in oxygen transmission rate (OTR) without an important detriment in tensile properties. Nano‐biocomposites prepared with higher molar masses polyadipates showed the highest thermal stability as well as the lowest OTR, resulting in very promising and novative materials for different applications such as soft packaging. Copyright © 2010 John Wiley & Sons, Ltd.