bluuebunny/crossref_metadata_2025 huggingface dataset:
Limestone Provenance in Roman Lime‐Volcanic Ash Mortars from the Villa dei Quintili, Rome
Authors: Fichera Giusj Valentina , Belfiore Cristina Maria , La Russa Mauro Francesco , Ruffolo Silvestro Antonio , Barca Donatella , Frontoni Riccardo , Galli Giuliana , Pezzino Antonino
Published: February 2015

Roman mortars were collected from the Villa dei Quintili in Rome, an archaeological site consisting of numerous edifices from nine construction phases dating from the 2nd century A.D. to modern times. A multianalytical approach was used on 34 mortar samples to infer the evolution of production techniques over time and to identify the source area of calcareous raw materials used in the preparation of the lime. Optical microscopy, scanning electron microscopy coupled with an energy‐dispersive system, and laser ablation inductively coupled plasma mass spectrometry were used to study the samples. The major and trace element data were compared with the compositions of two types of limestone samples (Calcare Massiccio and Calcare Maiolica) collected from the Cornicolani Mountains. The results suggest that the technological practices and the calcareous raw materials used for lime production remained unchanged over the time period considered (2nd century A.D. to 3rd century A.D.). The compositions of lime‐related particles in the mortars match those of Calcare Maiolica, which suggests its use as raw material for lime production. On the whole, the results are in agreement with data from existing literature regarding both the use by Roman builders of specific raw materials for the mortars’ production and the relative supply area.
Mild cognitive impairment in Parkinson's disease and its progression onto dementia: a 16‐year outcome evaluation of the Denbighshire cohort
Authors: Hobson Peter , Meara Jolyon
Published: February 2015

Objective

Mild cognitive impairment in Parkinson's disease (PD‐MCI) has been suggested to be a predictor for the development of PD dementia (PDD). This study explored the incidence and possible neuropsychological domain differences between PD patients with PD‐MCI and without cognitive impairment (normal cognitive function with PD), on the basis of the Movement Disorders Task Force Guidelines for PD‐MCI.

Methods

At baseline (T1), 4 years (T2) and 6 years (T3), 166 patients with PD were administered global neuropsychological assessments. At 16 years, case note and neuropsychological assessment review was employed to calculate the number of patients who had progressed to PDD.

Results

At baseline, 68 patients were classified as normal cognitive function with PD, 18 with PD‐MCI and 80 with PDD. At T2, 12 of the PD‐MCI cohort at T1 had progressed to PDD, and there were 15 incident cases of PD‐MCI. At T3, nine PD‐MCI cases at T2 had progressed to PDD. There were 10 incident cases of PD‐MCI at T3. The incidence of progression from PD‐MCI to PDD was 98.0 per 1000 person‐years, with an annual conversion rate to PDD of 11%. Neuropsychological predictors for conversion from PD‐MCI to PDD were semantic language, praxis (figure drawing/copying) and visuospatial deficits. At 16 years, 91% of the PD‐MCI cohort had progressed to PDD.

Conclusions

Mild cognitive impairment in Parkinson's disease is an important predictor for the progression to PDD. This investigation also confirmed that if PD patients live long enough, they will develop cognitive impairment or dementia. Early detection of cognitive impairment in these individuals is possible with existing standardised global cognitive assessments, which include semantic language assessment. Copyright © 2015 John Wiley & Sons, Ltd.
Phenolic Derivatives from the Root Bark of Oplopanax horridus
Authors: Huang Wei‐Hua , Zhang Qing‐Wen , Wang Chong‐Zhi , Yuan Chun‐Su , Li Shao‐Ping
Published: February 2015

Four new phenolic derivatives, including two phenylpropanoid glycosides, one benzoate glycoside, and one lignan glycoside, together with one known glyceride, were isolated from the root bark of Oplopanax horridus. The structures of the new compounds were elucidated as 3‐{4‐[(6‐O‐acetyl‐β‐D‐glucopyranosyl)oxy]‐3,5‐dimethoxyphenyl}propanoic acid (1), (+)‐[5,6,7,8‐tetrahydro‐7‐(hydroxymethyl)‐10,11‐dimehoxydibenzo[a,c][8]annulen‐6‐yl]methyl β‐D‐glucopyranoside (2), (+)‐methyl 4‐[6‐O‐{3‐hydroxy‐3‐methyl‐5‐(1‐methylpropyl)oxy]‐5‐oxopentanoyl}‐4‐O‐(β‐D‐glucopyranosyl)‐β‐D‐glucopyranosyl)oxy]‐3‐methoxybenzoate (3), and 2‐methoxy‐4‐[(1E)‐3‐methoxy‐3‐oxoprop‐1‐en‐1‐yl]phenyl 6‐O‐{3‐hydroxy‐3‐methyl‐5‐[(1‐methylpropyl)oxy]‐5‐oxopentanoyl‐4‐O‐β‐d‐glucopyranosyl‐β‐d‐glucopyranoside (4) on the basis of spectroscopic techniques including NMR and MS analyses. The known compound was identified as glycer‐2‐yl ferulate (5) by comparing its physical and spectral data with those reported in the literature.
New Furostanol Glycosides from the Roots of Digitalis ciliataTrautv.
Authors: Kemertelidze Ether , Skhirtladze Alexander , Ganzera Markus
Published: February 2015

Three new furostanol glycosides, named ciliatasides A, B, and C (1–3, resp.), have been isolated from the roots of Digitalis ciliata, along with two known furostanol glycosides. The structures of the new compounds were identified as (2α,3β,5α,14β,25R)‐26‐(β‐D‐glucopyranosyloxy)‐2‐hydroxyfurost‐20(22)‐en‐3‐yl β‐D‐glucopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐galactopyranoside (1), (2α,3β,5α,14β,22R)‐26‐(β‐D‐glucopyranosyloxy)‐2‐hydroxy‐22‐methoxyfurost‐25(27)‐en‐3‐yl β‐D‐galactopyranosyl‐(1→2)‐[β‐D‐xylopyranosyl‐(1→3)]‐β‐D‐glucopyranosyl‐(1→4)‐β‐D‐galactopyranoside (2), and (2α,3β,5α,14β,22R,25R)‐26‐(β‐D‐glucopyranosyloxy)‐2,22‐dihydroxyfurostan‐3‐yl β‐D‐glucopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐galactopyranoside (3).
Nordammarane Triterpenoids from Sanguisorba officinalis
Authors: Hu Jiang , Li Hui , Yang Ben‐Shou , Mao Xia , Shi Xiao‐Dong
Published: February 2015

Three new nordammarane triterpenoids, 12β‐O‐acetyl‐3β,22‐dihydroxy‐23,24,25,26,27‐pentanordammarane (1), 12β,22‐dihydroxy‐3‐oxo‐23,24,25,26,27‐pentanordammarane (2), and 3β,12β‐dihydroxy‐23,24,25,26,27‐pentanordammarane‐22‐carbaldehyde (3), were isolated from the EtOH extract of the roots of Sanguisorba officinalis. Structural elucidation of these new triterpenoids on the basis of spectroscopic analyses, including including 1D‐ and 2D‐NMR, and HR‐ESI‐MS, is reported
One‐Pot Synthesis of 3‐Acetyl‐2‐aryl‐3,4‐dihydroquinazolines from N‐[2‐(Azidomethyl)phenyl]benzamides Utilizing Intramolecular Aza‐Wittig Reaction
Authors: Kobayashi Kazuhiro , Matsumoto Naoki , Nagashima Mika , Inouchi Hiroki
Published: February 2015

A new and convenient method for the preparation of 3,4‐dihydroquinazolines 5 with aryl and Ac groups at C(2) and N(3), respectively, has been developed. The key sequence is the formation of aza‐phosphorane intermediates by the reaction of N‐[2‐(azidomethyl)phenyl]benzamides 1 with Ph3P, followed by intramolecular aza‐Wittig reaction and 3‐acetylation, which can be conducted in one‐pot.
1,3‐Dipolar Cycloadditions of α‐Diazo Ketones Derived from N‐Protected (S)‐Proline with Aromatic and Cycloaliphatic Thioketones
Authors: Mlostoń Grzegorz , Pipiak Paulina , Linden Anthony , Heimgartner Heinz
Published: February 2015

Enantiomerically pure α‐oxo diazo compounds derived from (S)‐proline were used for 1,3‐dipolar cycloaddition with aryl and hetaryl thioketones, as well as with cycloalkanethiones. Whereas the reactions with hetaryl thioketones in boiling THF yield α,β‐unsaturated ketones via a cascade of cycloaddition, 1,3‐dipolar electrocyclization, and desulfurization, the analogous reactions with thiobenzophenone and cycloalkanethiones result in the formation of 1,3‐oxathiole derivatives. In the latter case, the 1,5‐dipolar electrocyclization of the intermediate thiocarbonyl ylide is the key step of the reaction sequence. In all cases, the isolated products are optically active, i.e., the multistep processes occur with retention of the stereogenic center incorporated via the use of (S)‐proline as the precursor of the diazo compounds.
Principles and Applications of Multilevel Modeling in Human Resource Management Research
Authors: Shen Jie
Published: February 2015

Multilevel modeling is important for human resource management (HRM) research in that it often analyzes and interprets hierarchal data residing at more than one level of analysis. However, HRM research in general lags behind other disciplines, such as education, health, marketing, and psychology in the use of a multilevel analytical strategy. This article integrates the most recent literature into the theoretical and applied basics of multilevel modeling applicable to HRM research. A range of multilevel modeling issues have been discussed and they include statistical logic underpinning multilevel modeling, level conceptualization of variables, data aggregation, hypothesis tests, reporting mediation paths, and cross‐level interactions. An empirical example concerning complex cross‐level mediated moderation is presented that will suffice to illustrate the principles and the procedures for implementing a multilevel analytical strategy in HRM research. © 2015 Wiley Periodicals, Inc.
Spatial and temporal variations of pCO2, dissolved inorganic carbon and stable isotopes along a temperate karstic watercourse
Authors: van Geldern Robert , Schulte Peter , Mader Michael , Baier Alfons , Barth Johannes A. C.
Published: February 2015

This study investigated CO2 degassing and related carbon isotope fractionation effects in the Wiesent River that drains a catchment in the karst terrain of the Franconian Alb, Southern Germany. The river was investigated by physico‐chemical and stable isotope analyses of water and dissolved inorganic carbon during all seasons along 65‐km long downstream transects between source and mouth. Calculated pCO2 values at the source were 21 400 ± 2400 µatm. The pCO2 rapidly decreased in the river water and dropped to an average of 1240 ± 330 µatm near the mouth. About 90% of this decrease occurred within the first 6 km of the river. The river was supersaturated with respect to CO2 over its entire course and must have acted as a continuous year‐round CO2 source to the atmosphere. The average CO2 flux from the karst river was estimated with 450 mmol m−2 day−1 with higher fluxes up to 5680 mmol m−2 day−1 at the source. At the source, δ13CDIC values showed no seasonal variations with an average of −14.2 ± 0.2‰. This indicated that groundwater retained high pCO2 mainly from soil CO2. The contribution of soil CO2 to dissolved inorganic carbon was estimated at 65% to 72%. The downstream CO2 loss caused a positive shift in δ13CDIC values of 2‰ between source and mouth because of the preferential loss of the 12C isotope during degassing. Considering the findings of this study and the fact that carbonate lithology covers a significant part of the earth's surface, CO2 evasion from karst regions might contribute notably to the annual carbon dioxide release from global freshwater systems. Copyright © 2015 John Wiley & Sons, Ltd.
A retrospective, cross‐sectional study reveals that women with CRSwNP have more severe disease than men
Authors: Stevens Whitney W. , Peters Anju T. , Suh Lydia , Norton James E. , Kern Robert C. , Conley David B. , Chandra Rakesh K. , Tan Bruce K. , Grammer Leslie C. , Harris Kathleen E. , Carter Roderick G. , Kato Atsushi , Urbanek Margrit , Schleimer Robert P. , Hulse Kathryn E.
Published: February 2015

Up to 50% of patients with chronic rhinosinusitis (CRS) have comorbid asthma, and we have reported that a subset of CRS patients who have nasal polyps (CRSwNP) have elevated autoantigen‐specific antibodies within their nasal polyps (NP). While increases in the prevalence and/or severity of both asthma and autoimmunity in women are well characterized, it is not known whether CRSwNP is more severe or frequent in women than men. We sought to determine whether CRSwNP demonstrated sex‐specific differences in frequency and/or severity. Using a retrospectively collected database of tertiary care patients (n = 1393), we evaluated the distribution of sex in patients with CRSwNP with or without comorbid asthma or aspirin hypersensitivity. We further compared the severity of sinus disease between men and women with CRSwNP. Although women comprised 55% of CRS patients without NP (CRSsNP), a significantly smaller proportion of CRSwNP patients were female (38%, P < 0.001). Interestingly, women with CRSwNP were significantly more likely than men to have comorbid asthma (P < 0.001), and 61% of patients with the most severe form of disease (aspirin‐exacerbated respiratory disease (CRSwNP plus asthma plus aspirin sensitivity)) were women (P < 0.05). Women with CRSwNP were significantly more likely to have taken oral steroids, and were more likely to have a history of revision surgeries (P < 0.05) compared to men. These data suggest that women with CRSwNP have more severe disease than men in a tertiary care setting. Future studies are needed to elucidate the mechanisms that drive disease severity in men and women, paving the way for the development of personalized treatment strategies for CRSwNP based on sex.
Nasopharyngeal carcinoma in non‐chinese populations with special reference to South‐East Asia and Africa
Authors: Muir C. S.
Published: February 2015

Nasopharyngeal cancer (NPC) is very common in Chinese, the incidence rates (age‐adjusted to the “world” population distribution) per 100,000 per annum varying between 10 to 20 for males and 5 to 10 for females. In virtually all occidental countries, the rates are very low, generally well below 1.0 per 100,000 per annum.

The evidence suggesting intermediate levels of risk in certain non‐Chinese mongoloid populations in South‐East Asia, in the Sudan and the Maghreb, is examined. Although whenever possible incidence rates are quoted, most of the available data are based on relative frequency series, often with rather small numbers.

Rare in Japan and India, NPC is fairly common in non‐Chinese mongoloid groups in South‐East Asia. NPC incidence in Tunisia is raised, and the relative frequency is probably raised in the Sudan and Algeria.

NPC is probably not unduly common in Kenya or Uganda but there are differences between ethnic groups in these countries which may be related to environmental factors. NPC incidence in Hawaii is raised for all ethnic groups, the rate for male Hawaiians (7.8) approaching that for male Chinese (10.4). In Israel, the incidence in the non‐Jewish (Arab) population and in Jews born in Africa or Asia (many of whom were born in Morocco or Tunisia) is higher than in Israel‐born Jews or in Jews born in America or Europe.

The effect of intermarriage with Chinese is examined. There is a general trend suggesting that NPC is commoner in those South‐East Asian groups with admixture of Chinese blood, exemplified by NPC incidence in Singapore where the rates for male and female Chinese were 20.2 and 9.0 whereas those for the mongoloid Malays were 5.8 and 2.0 respectively. By contrast, the rates for the caucasoid Indians and Pakistanis were 0.2 and 0. It is highly unlikely that these differences are artefactual.

The demonstration of an intermediate NPC risk level in Tunisia and other parts of Africa should, when confirmed, permit examination of viral and other aetiological hypotheses in populations with little or no Chinese genetic material.
Studies of carcino‐fetal proteins. III. Development of a radioimmunoassay for α‐fetoprotein. Demonstration of α‐fetoprotein in serum of healthy human adults
Authors: Ruoslahti Erkki , Seppälä Markku
Published: February 2015

A radioimmunoassay (RIA) for human α‐fetoprotein (α‐FP) was developed. The sensitivity threshold of the method is 250 picograms per ml, which means that it is 20,000‐40,000 times more sensitive than immunodiffusion, and covers completely the thousandfold concentration gap between the α‐FP levels in normal human serum and the level detectable by immunodiffusion. Evidence for the presence of α‐FP in serum of healthy human individuals is as follows: (I) Normal serum in 1:5 dilution inhibited the binding of labelled α‐FP by antibody. (2) The activity inhibiting in RIA could be removed from serum by prior treatment with anti‐α‐FP immunoadsorbent. (3) At low pH α‐FP could be eluted from immunoadsorbent that had been previously treated with serum. (4) After fractionation of normal human serum by electrofocusing the activity inhibiting in RIA was present in a fraction whose isoelectric point was that previously shown for fetal α‐FP.

The α‐FP present in cancer is currently believed to be a product of an activated fetal gene which is suppressed at the adult stage. Our results show that this suppression is not complete in all cells. Measurement of α‐FP at the radioimmunoassay level is considered to be a contribution to the early diagnosis of cancer.
Occurrence of alpha‐fetoprotein in acute viral hepatitis
Authors: Smith J. Bruce
Published: February 2015

Using a very sensitive double antibody electrophoretic technique, we have found alpha‐1 fetoprotein (AFP) to occur transiently in the serum of adults during the course of acute viral hepatitis associated with Australia antigen (Au(1)) but not with acute viral hepatitis unassociated with Au(1). Occurrence in adult serum of this protein, which is a normal embryonic serum alpha‐1 globulin, has heretofore been associated with the presence of either primary hepatic malignancy or certain germinal cell cancers of the testis and ovary. The possible significance of the reappearance of AFP relative to cellular retro‐differentiation in viral hepatitis and hepatic malignancy is discussed.
Immunofluorescent detection of murine and hamster C‐type virus species‐specific (gs‐1) determinants by monospecific guinea‐pig sera and interspecies‐specific (gs‐3) determinants by tumor‐bearing rat sera
Authors: Hampar Berge , Gilden Raymond V. , Kelloff Gary , Oroszlan Stephen , Simms Donald
Published: February 2015

The species‐specific (gs‐1) determinants of murine and hamster C‐type viruses were detected by direct immunofluorescence (FA) in fixed virus‐infected cells using monospecific guinea‐pig antisera. The interspecies‐specific (gs‐3) determinants were also detected by FA using broad spectrum sera from tumor‐bearing rats.

The FA staining of gs‐1 and gs‐3 determinants in fixed infected cells was localized in the cytoplasm as punctate foci at or near the cell membrane and as a diffuse mass at the perinuclear region. The FA staining of live infected cells was limited to antisera with envelope activity.

The percentage of FA positive cells in any one cell preparation was inversely related to the efficiency of complete virus synthesis. Blocking experiments support the contention that the gs‐1 and gs‐3 determinants reside on the same molecule with the former occupying a more accessible or dominant position.
High‐frequency establishment of human immunoglobulin‐producing lymphoblastoid lines from normal and malignant lymphoid tissue and peripheral blood
Authors: Nilsson Kenneth
Published: February 2015

Human hematopoietic tissue and lymphocytes separated from 10‐20 ml samples of peripheral blood have been grown in vitro in a lens‐paper and a gelatin foam (Spongostan) grid organ culture.

Lymphoblastoid cell lines were established from the lymph nodes, and in one case from the spleen, of 22/23 consecutive, unselected adult individuals without manifest malignancy or infectious mononucleosis. Biopsies from 5/8 patients with malignancy were successful. The blood tines were derived from 5/10 patients with and 4/10 donors without malignancy.

The very high frequency of success from normal tissue confirms the assumption made before that the spontaneous establishment of lymphoblastoid cell lines is unrelated to manifest malignancy of the donor. The results indicate that lymphoid cells with a potential for infinite proliferation (“lymphoblastoid transformation”) are present in almost all adult individuals. The Spongostan grid culture is a superior instrument to select and/or adapt these cells in vitro.

All lymphoblastoid lines produced immunoglobulins. The majority started with a “polyclonal” pattern of immunoglobulin production but changed towards stable “ monoclonality “ during the course of long‐term cultivation. It is suggested that lymphoblastoid lines have a polyclonal origin and that the reason for development of a monoclonal line is a selection of one cell clone either in the organ culture during establishment or in long‐term culture.
The establishment of lymphoblastoid lines from adult and fetal human lymphoid tissue and its dependence on EBV
Authors: Nilsson Kenneth , Klein George , Henle Werner , Henle Gertrude
Published: February 2015

Continuous human lymphoblastoid cell lines (LL), derived from lymphoid tissue or peripheral blood of 20 adults without histories of recent infectious mononucleosis at a frequency close to 100 %, were examined for the presence of Epstein‐Barr virus (EBV) using immunofluorescence methods for the detection of EBV‐dependent cell membrane and EB viral capsid antigens. All lines except one were found to be EBV carriers in the initial tests, but the antigens gradually disappeared in most during the course of an observation period of 4 months. Only eight lines maintained the initial percentage of antigen‐containing cells. The results of the two immunofluorescence tests, performed simultaneously on each cell pool, were concordant in all instances.

Sera were available from 16/20 donors. All cell donors, except one, possessed antibodies to EBV as an indication of prior EBV infections.

The growth‐promoting role of EBV in the establishment of LL was supported by studies with fetal lymphoid tissue cultured by the same grid method which yielded the high frequency of LL from adults. In sharp contrast to the results obtained with adult lymphoid tissue, no lines were established from 20 fetuses aged 13‐20 weeks. However, when such tissue was exposed to a cell‐free filtrate prepared from an EBV‐carrying LL lymphoblastoid cell, lines were established in some instances. Filtrate from an EBV‐negative line inoculated into parallel cultures failed to promote the establishment of LL.

The results indicate that EBV infection in vivo or in vitro may be a prerequisite for the indefinite growth of lymphoblastoid cells in vitro and that EBV infections, as a rule, are not vertically transmitted.
Metabolism of polycyclic hydrocarbons in mammalian cell cultures
Authors: Diamond Leila
Published: February 2015

Two extraction procedures were used to measure the metabolism of tritiated polycyclic hydrocarbons in cell cultures derived from several mammalian species. Metabolism of the hydrocarbons to “ alkali‐extractable derivatives” was measured by extraction of the labeled medium with acetone:hexane, followed by extraction of the resulting acetone‐hexane phase with NaOH (Nebert and Bausserman, 1970); metabolism to “ water‐soluble derivatives “ was measured by extraction of the medium with chloroform:methanol:water (Diamond et al., 1968b). The extent of metabolism was dependent on the concentration of hydrocarbon, the number of cells and the time of incubation. The kinetics of hydrocarbon metabolism suggest that there may be sequential conversion of the parent compound first to alkali‐extractable derivatives and then to water‐soluble derivatives. Each of the cell cultures which was sensitive to the growth‐inhibitory effects of 3,4‐benzpyrene or 7,12‐dimethylbenz (a) anthracene was able to metabolize the respective hydrocarbon to water‐soluble derivatives. In general, little or no ability to metabolize the hydrocarbons was detected in cells which were resistant to the cytotoxic effects. Two resistant cell lines were exceptional in that they did metabolize the hydrocarbons to water‐soluble derivatives; however, no alkali‐extractable derivatives could be recovered from the medium of these cultures.
Reduction by pituitary isograft of inhibitory effect of large dose of estrogen on incidence of mammary tumors induced by carcinogen in ovariectomized rats
Authors: Nagasawa Hiroshi , Yanai Reiko
Published: February 2015

Interaction of prolactin and estrogen on the incidence of mammary tumors induced by 7,12‐dimethylbenz (a) anthracene (DMBA) in female Sprague‐Dawley rats was studied. Rats were bilaterally ovariectomized at 45 days of age and then treated subcutaneously with 20μg of estradiol benzoate (EB) every 2 days beginning the next morning. They received single intravenous injections of 5mg DMBA at 52 days of age. Two months later they were divided into four groups: Group I received no pituitary grafting: group II was grafted with three isologous pituitaries under the right kidney capsule: groups III and IV received six pituitaries each. EB injections were continued throughout the experiment to every group except group IV. Serum prolactin levels were determined by radioimmunoassay just before pituitary grafting, 20 days, 2 and 3 months after grafting. At the end of 5 months after DMBA injection, the mammary tumor incidence and the number of palpable tumors per tumor‐bearing rat apparently increased, and the percentage of completely regressed tumors decreased in groups II and III as compared to group I. Serum prolactin level was significantly higher in groups II and III than in group I at 3 months after pituitary grafting. Only one rat had palpable mammary tumors in group IV and serum prolactin levels were always significantly lower in this group than in the others.

These results indicate that prolactin secreted by the grafted pituitaries overcomes the inhibitory action of a large dose of estrogen on the growth of DMBA‐induced mammary tumors of the rat and results in an increased incidence of the tumors.
Epstein‐barr virus (EBV)‐associated antibody patterns in malignant lymphoma and leukemia. II. Chronic lymphocytic leukemia and lymphocytic lymphoma
Authors: Johansson Bo , Klein George , Henle Werner , Henle Gertrude
Published: February 2015

Sera from Swedish patients with chronic lymphocytic leukemia (CLL) and lymphocytic lymphona (LL) were titrated for antibodies to viral capsid antigens (VCA) of the Epstein‐Barr virus (EBV) by the indirect immunofluorescence technique and to EBV‐determined cell membrane antigens by blocking of direct cell membrane immunofluorescence (BI). Previously tested sera from healthy Swedish donors served as controls. While 40% of the sera from CLL patients showed relatively high serological reactivities, the mean anti‐VCA and BI values did not differ significantly from the control group. The LL group of sera showed significantly higher reactivities than the controls. The most highly reactive sera were found in patients with poorly differentiated LL at frequencies and with mean values approaching those seen in Burkitt's lymphoma, nasopharyngeal carcinoma and Hodgkin's sarcoma.
Report of a symposium sponsored by the UICC on principles and practice in clinical trials
Authors: Healy M. J. R. , Saracci R.
Published: February 2015

Various points were discussed by the 22 participants in the Symposium (doctors, statisticians and pharmacologists) under the following main headings: choice of subjects for a clinical trial, choice of treatments, criteria of assessment, trial design and “optimum” number of subjects. Difficulties most frequently met in each of these areas, open problems and hints at solutions are briefly reviewed in the report, special attention being paid to the alternative (especially relevant and critical in such fields as cancer clinical experimentation) between the two attitudes which are possible in a clinical trial context: the “explanatory” attitude (aimed at gaining basic knowledge about treatments) and the “pragmatic” attitude (aimed at guiding the decision on how to treat particular patients).
Glycosylation Chemistry of 3‐Deoxy‐D‐manno‐Oct‐2‐ulosonic Acid (Kdo) Donors
Authors: Pradhan Tapan Kumar , Mong Kwok Kong Tony
Published: February 2015

3‐Deoxy‐D‐manno‐Oct‐2‐ulosonic acid (Kdo)‐containing oligosaccharides are a conserved carbohydrate component in lipopolysaccharides (LPSs) of the outer membrane of Gram‐negative bacteria, and they are also present in capsular polysaccharides (CPSs) of bacteria and plant cells. The association of the bacterial LPS with the pathophysiology of bacterial infection have long been recognized. Structurepathophysiology studies of bacterial infection need to use pure and homogeneous LPS fragments. Such a requirement can be fulfilled by the synthesis of Kdo glycosides and related Kdooligosaccharide conjugates. This article provides an overview of the glycosylation chemistries of the synthesis of Kdo α‐/β‐glycosides, oligosaccharides with Kdo units such as LPS core oligosaccharides, and lipid A derivatives.
Aberrant methylation of APC and RARβ2 genes in breast cancer patients
Authors: Swellam Menha , Abdelmaksoud Mohamed D.E. , Sayed Mahmoud Magda , Ramadan Amal , Abdel‐Moneem Walid , Hefny Mona M.
Published: February 2015

Changes in the status of DNA methylation are one of the most common molecular alterations in human neoplasia. We aimed to identify epigenetic molecular markers in serum for early detection of breast cancer. Authors analyzed retrospectively the methylation status of RARβ2 and APC genes in serum samples from 121 breast cancer patients, 79 patients with benign breast diseases, and 66 healthy volunteers using methylation‐specific PCR. The methylated APC and RARβ2 were significantly higher in breast cancer patients (93.4%, 95.6%) than benign (7.8%, 14.5%) but not detected in healthy volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant difference among clinicopathological factors apart from triple negative breast cancer patients as all of them (χ2 = 7.4, P = 0.007) reported to be methylated RARβ2 genes. Both methylated genes were detected in all grades and stages. Both sensitivities and specificities of the methylated genes for breast cancer detection were superior to traditional tumor markers in detection of breast cancer, early stage, low grade tumors, and triple negative breast cancer patients. Thus methylated APC and RARβ2 genes might be valuable serum‐based molecular markers for early detection of breast cancer. © 2015 IUBMB Life, 67(1):61–68, 2015
Involvement of mitogen‐activated protein kinase and NF‐κB signaling pathways in perfluorooctane sulfonic acid‐induced inflammatory reaction in BV2 microglial cells
Authors: Zhu Jingying , Qian Wenyi , Wang Yixin , Gao Rong , Wang Jun , Xiao Hang
Published: February 2015

Microglial activation is closely related to the pathogenesis of neurodegenerative diseases by producing proinflammatory cytokines. Perfluorooctane sulfonic acid (PFOS), known as an emerging persistent organic pollutant, is reported to disturb human immune homeostasis; however, whether it affects cytokine production or the immune response in the central nervous system remains unclear. The present study was aimed to explore whether PFOS contributed to inflammatory action and to investigate the corresponding mechanisms in BV2 microglia. PFOS‐mediated morphologic changes, cytokine responses and signaling events were examined by light microscopy, real‐time polymerase chain reaction, enzyme‐linked immunosorbent assay and Western blot assays. Our results indicated that PFOS increased BV2 cells activation and simultaneously increased tumor necrosis factor alpha and interleukin‐6 expression. In addition, the c‐Jun N‐terminal protein kinase inhibitor (SP600125), as well as ERK1/2 blocker (PD98059), transcriptionally at least, displayed anti‐inflammatory properties on PFOS‐elicited cytokine responses. Moreover, the inflammatory transcription factor NF‐κB was specifically activated by PFOS as well. These results, taken together, suggested that PFOS exerts its functional effects on the response of microglial cell activation via, in part, the c‐Jun N‐terminal protein kinase, ERK and NF‐κB signaling pathways with its subsequent influence on proinflammatory action. Copyright © 2015 John Wiley & Sons, Ltd.
Sustained Modeling-Based Bone Formation During Adulthood in Cynomolgus Monkeys May Contribute to Continuous BMD Gains With Denosumab
Authors: Ominsky Michael S , Libanati Cesar , Niu Qing-Tian , Boyce Rogely W , Kostenuik Paul J , Wagman Rachel B , Baron Roland , Dempster David W
Published: February 2015

Denosumab (DMAb) administration to postmenopausal women with osteoporosis is associated with continued bone mineral density (BMD) increases and low fracture incidence through 8 years, despite persistently reduced bone turnover markers and limited fluorochrome labeling in iliac crest bone biopsies. BMD increases were hypothesized to result from additional accrual of bone matrix via modeling-based bone formation—a hypothesis that was tested by examining fluorochrome labeling patterns in sections from ovariectomized (OVX) cynomolgus monkeys (cynos) treated with DMAb for 16 months. Mature OVX or Sham cynos were treated monthly with vehicle for 16 months, whereas other OVX cynos received monthly 25 or 50 mg/kg DMAb. DMAb groups exhibited very low serum bone resorption and formation biomarkers and near-absent fluorochrome labeling in proximal femur cancellous bone. Despite these reductions, femoral neck dual-energy X-ray absorptiometry (DXA) BMD continued to rise in DMAb-treated cynos, from a 4.6% increase at month 6 to 9.8% above baseline at month 16. Further examination of cortical bone in the proximal femur demonstrated consistent and prominent labeling on the superior endocortex and the inferior periosteal surface, typically containing multiple superimposed labels from month 6 to 16 over smooth cement lines, consistent with continuous modeling-based bone formation. These findings were evident in all groups. Quantitative analysis at another modeling site, the ninth rib, demonstrated that DMAb did not alter the surface extent of modeling-based labels, or the cortical area bound by them, relative to OVX controls, while significantly reducing remodeling-based bone formation and eroded surface. This conservation of modeling-based formation occurred concomitantly with increased femoral neck strength and, when coupled with a reduction in remodeling-based bone loss, is likely to contribute to increases in bone mass with DMAb treatment. Thus, this study provides preclinical evidence for a potential mechanism that could contribute to the clinical observations of continued BMD increases and low fracture rates with long-term DMAb administration. © 2015 American Society for Bone and Mineral Research.
Flavonol Regulation in Tumor Cells
Authors: Lea Michael A.
Published: February 2015

Flavonols comprise a group of flavonoid molecules that are widely distributes in fruits and vegetables. There is epidemiological data to suggest that consumption of flavonols can be accompanied by decreased cancer incidence. The anti‐oxidant activity of flavonols may have an important role in preventing carcinogenesis. Therapeutic potential of flavonols is indicated by their growth inhibitory action accompanied by a decrease in several hallmarks of cancer such as resistance to apoptosis. Multiple mechanisms of action have been reported for the action of flavonols on cancer cells. Particular emphasis has been directed to inhibitory effects on several protein kinases and on the potential for prooxidant effects. The diversity of actions presents a problem in trying to elucidate primary and secondary effects but it may be a strength of the therapeutic potential of flavonols that it renders development of resistance more difficult for cancer cells. Cancer chemotherapy is usually characterized by the use of drug combinations. Some additive or synergistic combinations have been identified for flavonols and this is an area of ongoing investigation. As with other polyphenolic molecules there have been questions of cellular uptake and bioavailability. Several investigations have been and are being conducted to modify the structures of flavonols with the goal of increasing bioavailability. At present many investigators are sufficiently encouraged by past observations that they are responding to the challenge to optimize the dietary and therapeutic use of flavonols in cancer prevention and treatment. J. Cell. Biochem. 116: 1190–1194, 2015. © 2015 Wiley Periodicals, Inc.
A DFT study on Cu(I) coordination in Cu‐ZSM‐5: Effects of the functional choice and tuning of the ONIOM approach
Authors: Morpurgo Simone
Published: February 2015

The coordination of Cu+ at the T1 and T7 positions of the M7 ring of Cu‐ZSM‐5, and the interaction of NO with coordinated Cu+ were investigated by means of DFT/ONIOM calculations. The B3LYP, BLYP, PBE1PBE, PBE, M06, and M062X functionals with the def2‐TZVP (def2‐QZVP for Cu) basis set were used in the high‐level part of ONIOM calculations, with the HF/3‐21G, B3LYP/LANL2DZ, M06/LANL2DZ, and M062X/LANL2DZ methods in the low‐level part. The ability of suitable combinations of the above methods to reproduce (i) the crystallographic structure of purely siliceous ZSM‐5, (ii) the tendency of Cu+ to be twofold or fourfold coordinated by framework oxygen atoms of Cu‐ZSM‐5, and (iii) the interaction energy and the NO stretching frequency of adsorbed nitrogen oxide are discussed, showing that different results are obtained depending on the adopted computational approach. With reference to above properties, some considerations about the employment of the ONIOM approximations are also included. © 2015 Wiley Periodicals, Inc.
The Influencing Mechanism of Acidity on the Oxidation Peak Currents of Uric Acid and Ascorbic Acid at the PACPE by Cyclic Voltammetry
Authors: Jing Li , En‐bo Shangguan , Quan‐min Li
Published: February 2015

In this paper, a pre‐anodized carbon paste electrode (PACPE) is fabricated by a simple electrochemical pretreatment method, which can be used for the simultaneous determination of uric acid (UA) and ascorbic acid (AA). The influencing mechanism of the acidity on the size of oxidation peak current (ip,a) of UA and AA is discussed in detail. According to the results, in different pH conditions, the intensity of hydrogen bonding between UA, AA and the surface of PACPE, the degree of reduction reaction at the auxiliary electrode, and the structural configurations of UA and AA with different species in reaction system have evident influence on the size of oxidation peak current. In pH 7.00 phosphate buffer solution, the calibration curves for UA and AA are obtained in the range of 5.0 x 10‐7–5.0 x 10‐5 mol/L and 3.0 x 10‐5–5.0 x 10‐3 mol/L, respectively. The detection limits for UA and AA are found to be 2.0 x 10‐8 mol/L and 1.2 x 10‐6 mol/L, respectively. This proposed method has been successfully applied to determine UA and AA in human urine simultaneously with satisfactory results.
Synthesis, Spectra Characterization, Electrochemical Behavior of Silyl Derivatives of Ferrocene
Authors: Abri Abdolreza , Rafe Abdolrahim abbaszad
Published: February 2015

Ferrocenyl‐substituted silanes via the reaction between mono and dilithio‐ferrocene with trimethyl, trietheyl, vinyldimethyl or t‐butyldimethyl chlorosilanes is prepared. The electrochemical behaviors of these compounds were investigated by cyclic voltammetry. This work describes the electrochemical and electrocatalytic properties of carbon ceramic electrode (CCE) modified with ferrocene composites as a new electrocatalyst material.
Regioselective One‐pot Synthesis of New Unsymmetric Spiro Dihydrofurans in the Reaction of Mixed Two Different Cyclic β‐Dicarbonyl Compounds with BrCN and Aldehydes in the Presence of Et3N
Authors: Noroozi Pesyan Nader , Shokr Alireza , Gharib Ali , Tunç Tuncay , Sahin Ertan
Published: February 2015

Crossed one‐pot reaction of mixed cyclic β‐dicarbonyl with various aldehydes in the presence of cyano gen bromide and triethylamine leads to the selective and efficient formation of crossed new unsymmetri cal spiro dihydrofurans at room temperature. The products were obtained in good to excellent yields. Structure elucidation was carried out by 1H NMR, 13C NMR, FT‐IR spectroscopy, Mass analyses and X‐ray crystallography technique. A proposed mechanism was discussed for the formation of products.
Polybenzoin Based Sensor for Determination of 2thiouracil in Biological Fluids and Pharmaceutical Formulations
Authors: Pattar Vijay P. , Nandibewoor Sharanappa T.
Published: February 2015

A carbon paste electrode was modified by electropolymerisation of benzoin using voltammetric technique. A novel polybenzoin modified carbon paste electrode (PB‐CPE) was developed for use as a detector in cyclic voltammetry and differential pulse adsorptive stripping voltammetry for the sensitive determination of 2thiouracil (2TU). The atomic force microscopy was applied to characterize the surface morphology of PB‐CPE. The modified electrode showed excellent electrocatalytic activity for the oxidation of 2TU. The oxidation process was irreversible over the pH range studied and exhibited a diffusion controlled behavior. All experimental parameters have been optimized. The peak current for the stripping of 2TU was found to be linear over the concentration range of 0.2–1.2 µM, with a detection limit of 2.21 nM. The practical application of the PB‐CPE in the determination of 2TU in human biological fluids and pharmaceutical samples were demonstrated that it has high sensitivity and good selectivity.
Simultaneous plasma and genital pharmacokinetics and pharmacodynamics of atazanavir and efavirenz in HIV‐infected women starting therapy
Authors: Neely Michael , Louie Stan , Xu Jiaao , Anthony Patricia , Thuvamontolrat Kasalyn , Mordwinkin Nicholas , Kovacs Andrea
Published: February 2015

Few studies have characterized longitudinal female plasma and genital antiretroviral pharmacokinetics and pharmacodynamics. Among 20 regimen‐naive HIV‐infected adult women initiating atazanavir‐based therapy (n = 9) or efavirenz‐based therapy (n = 11), we measured blood CD4+ T lymphocytes, and paired plasma and genital HIV RNA and atazanavir or efavirenz 2 days before starting therapy and 2, 4, 7, 10, 21, 28, 60, 120, and 180 days after. The mean (range) log10 baseline plasma viral load was 4.89 copies/mL (2.64–6.09 copies/mL), and genital was3.30 (1.60–5.00). In the atazanavir and efavirenz groups, mean (SD) days to a 50% decrease in plasma viral load was 8.2 (4.9) versus 9.3 (7.4), P = .7, and in the genital tract it was 7.3 (3.5) versus 9.3 (7.7), P = .5. The median (interquartile range) plasma:genital concentration ratio for atazanavir was 0.11 (0.001–0.46) versus 0.34 (0.05–1.30) for efavirenz, P = .5. Average plasma efavirenz or atazanavir concentrations over time did not affect virologic response. Blood CD4+ percentages increased by +2.3 (P = .06) and +3.0 (P = .003) for every 1 mg/L increase in average plasma and genital drug concentration, respectively. Plasma and genital viral pharmacodynamics were similar between the groups and independent of average concentrations, but blood CD4+ response was related in particular to genital extravascular drug concentrations.
Numerical simulation of NO2 absorption using sodium sulfite in a spray tower
Authors: Zhuang Zhuokai , Sun Chenglang , Zhao Nan , Wang Haiqiang , Wu Zhongbiao
Published: February 2015

BACKGROUND

Wet flue gas desulfurization combined with ozone is a promising technology which could remove NOx effectively. However, there are few reports focusing on simulations of the absorption process of NO2 in a spray tower. A computational fluid dynamics model including chemical absorption was developed to simulate the absorption process of NO2. Simulations of different cases were executed to explore the influences of operating conditions.

RESULTS

The errors between predicted and experimental values were less than 5% under different operating conditions and the model had depicted the tendency very well. For instance, an increase in L/G from 11 to 16 resulted in the growth of η from 90.9% to 96.3%. When the solution concentration raised from 0.025 mol L−1 to 0.0875 mol L−1 could result in an increase of η from 89.1% to 98.6%.

CONCLUSION

The model developed in the present work was effective in determining the operating parameters of the spray tower for NO2 absorption, which could be utilized for the design and optimization of industrial apparatus. Moreover, the model can also evaluate the best positions of the spraying nozzles, the distance between the spray levels and other parameters for industrial application. © 2015 Society of Chemical Industry
The effect of water quality on the immunoreactivity of stress‐response cells and gonadotropin‐secreting cells in the pituitary gland of Nile tilapia, Oreochromis niloticus
Authors: Mousa Mostafa A. , Ibrahim Amal A.E. , Hashem Amal M. , Khalil Noha A.
Published: February 2015

The present experiments investigated the effect of water quality characteristics on the condition factor, the ovarian activity, cortisol level, and the immunoreactivity of stress‐response cells (adrenocorticotropic hormone; ACTH‐ and melanin stimulating hormone; MSH‐ and somatolactin; SL‐ secreting cells) and gonadotropin (GTH)‐secreting cells in the pituitary gland of Nile tilapia, Oreochromis niloticus. After 3 months of exposure to mixtures of water from different sources (Tap and Lake Manzalah waters), with high levels of minerals and heavy metals, water quality affected the number, size, and immunostaining of stress‐response‐immunoreactive (ir) cells and GTH‐ir cells, which showed a dramatic decrease in their size. The integrated optical density (IOD) of immunoreactivity of MSH‐ and GTH‐ cells was significantly increased; however, it was significantly decreased for ACTH‐ and SL‐ cells. Also, high levels of cortisol were observed in females exposed to waters with high concentrations of minerals and heavy metals. In parallel, low values of gonadosomatic index (GSI%) and the ovarian histology revealed a decrease of maturing follicles concomitant with an increase of atretic follicles in females exposed to Lake Manzalah polluted water. Taken together, the increased activity of stress‐response‐ir pituitary cells, serum cortisol level and ovarian atretic follicles in response to elevated concentrations of minerals and heavy metals, supports the possible role of ACTH, MSH, and SL in the adaptive stress response of fish. Therefore, minerals and heavy metals must be considered when discussing tilapia aquaculture status. J. Exp. Zool. 323A: 146–159, 2015. © 2015 Wiley Periodicals, Inc.
Effects of a novel climate on stress response and immune function in painted turtles (Chrysemys picta)
Authors: Refsnider Jeanine M. , Palacios Maria G. , Reding Dawn M. , Bronikowski Anne M.
Published: February 2015

Climate change may subject animals to increasingly stressful environmental conditions, which could have negative physiological consequences if stress levels are elevated for long periods. We conducted a manipulative experiment to determine the effects of a novel climate on stress levels and immune function in a model reptile species, the painted turtle. We collected turtles from four populations across the species' geographic range and housed them in a common‐garden in one population's local climate. We measured levels of the stress hormone corticosterone and tested two aspects of innate immune function, bactericidal capacity and natural antibody agglutination, at the time of capture (baseline) and three additional time points over 1 year. The four populations did not differ in corticosterone levels over the course of 1 year, and corticosterone levels were also similar at each sampling period except that post‐hibernation corticosterone levels were significantly lower than the previous three time points. Furthermore, we found no evidence that elevated corticosterone depressed immune function in the painted turtle. Our study suggests that turtles exposed to novel climatic conditions did not display a detectable stress response, nor did the novel climate depress immune function in the transplanted populations. Therefore, in terms of innate immune function, turtles may be relatively resilient to at least small changes in climatic conditions. J. Exp. Zool. 323A: 160–168, 2015. © 2015 Wiley Periodicals, Inc.