bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term efficacy and safety of arsenic trioxide for first‐line treatment of elderly patients with newly diagnosed acute promyelocytic leukemia
Authors: Zhang Yingmei , Zhang Zhuo , Li Jinmei , Li Limin , Han Xueying , Han Lina , Hu Longhu , Wang Shuye , Zhao Yanhong , Li Xiaoxia , Zhang Ying , Fan Shengjin , Lv Chengfang , Li Yinghua , Su Yanhua , Zhao Hui , Zhang Xin , Zhou Jin
Published: August 2012

BACKGROUND:

The prognosis of acute promyelocytic leukemia (APL) in the elderly is poorer than that of younger patients after treatment with all‐trans retinoic acid plus chemotherapy, which is the current standard therapy for APL. A significantly higher mortality during consolidation therapy was found, which is mainly due to deaths from sepsis following chemotherapy‐induced myelosuppression.

METHODS:

A total of 33 patients aged 60 years or older with de novo APL were treated with single‐agent arsenic trioxide (ATO) for remission induction and postremission therapy. The postremission therapy continued for up to 4 years.

RESULTS:

Twenty‐nine patients (87.9%) achieved a hematologic complete remission, and the most common adverse event during remission induction was leukocytosis (63.6%). Definite differentiation syndrome was observed in 5 patients. Nonhematologic adverse events were all manageable and reversible. Twenty‐eight patients proceeded to postremission therapy. Adverse effects during postremission therapy were mild, transient, and no treatment was required. No patients died from ATO‐related toxicities. With a median follow‐up of 99 months, the 10‐year cumulative incidence of relapse, overall survival, disease‐free survival, and cause‐specific survival were 10.3%, 69.3%, 64.8%, and 84.8%, respectively, which are comparable with those in the younger APL partners. No significant risks for development of chronic arsenicosis or second malignancy were observed during the follow‐up period.

CONCLUSIONS:

The results indicate that the single‐agent ATO regimen is safe and effective with long‐term durable remission, and could be used as first‐line treatment for elderly patients with de novo APL. Cancer 2013. © 2012 American Cancer Society.
Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women
Authors: Schwartz Theresa , Stark Azadeh , Pang Judy , Awuah Baffour , Kleer Celina G. , Quayson Solomon , Kingman Stephanie , Aitpillah Francis , Abantanga Francis , Jiagge Evelyn , Oppong Joseph K. , Osei‐Bonsu Ernest , Martin Iman , Yan Xiaowei , Toy Kathy , Adjei Ernest , Wicha Max , Newman Lisa A.
Published: August 2012

BACKGROUND:

Breast cancers that are negative for the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 (human epidermal growth factor receptor 2) marker are more prevalent among African women, and the biologically aggressive nature of these triple‐negative breast cancers (TNBCs) may be attributed to their mammary stem cell features. Little is known about expression of the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) in African women. Novel data are reported regarding ALDH1 expression in benign and cancerous breast tissue of Ghanaian women.

METHODS:

Formalin‐fixed, paraffin‐embedded specimens were transported from the Komfo Anoyke Teaching Hospital in Kumasi, Ghana to the University of Michigan for centralized histopathology study. Expression of ER, PR, HER2, and ALDH1 was assessed by immunohistochemistry. ALDH1 staining was further characterized by its presence in stromal versus epithelial and/or tumor components of tissue.

RESULTS:

A total of 173 women contributed to this study: 69 with benign breast conditions, mean age 24 years, and 104 with breast cancer, mean age 49 years. The proportion of benign breast conditions expressing stromal ALDH1 (n = 40, 58%) was significantly higher than those with cancer (n = 44, 42.3%) (P = .043). Among the cancers, TNBC had the highest prevalence of ALDH1 expression, either in stroma or in epithelial cells. More than 2‐fold higher likelihood of ALDH1 expression was observed in TNBC cases compared with other breast cancer subtypes (odds ratio = 2.38, 95% confidence interval 1.03‐5.52, P = .042).

CONCLUSIONS:

ALDH1 expression was higher in stromal components of benign compared with cancerous lesions. Of the ER‐, PR‐, and HER2‐defined subtypes of breast cancer, expression of ALDH1 was highest in TNBC. Cancer 2013. © 2012 American Cancer Society.
Recommendations for including multiple symptoms as endpoints in cancer clinical trials
Authors: Cleeland Charles S. , Sloan Jeff A. , Cella David , Chen Connie , Dueck Amylou C. , Janjan Nora A. , Liepa Astra M. , Mallick Rajiv , O'Mara Ann , Pearson Jay D. , Torigoe Yasuhiro , Wang Xin Shelley , Williams Loretta A. , Woodruff Jeanie F.
Published: August 2012

The multiple symptoms arising from cancer and its treatment impose significant distress for patients. However, in clinical research, there is no agreed‐upon way of assessing and presenting the effects of treatment on multiple symptoms, as either individual scores or a composite score. The ASCPRO (Assessing the Symptoms of Cancer Using Patient‐Reported Outcomes) Multisymptom Task Force was established to make recommendations about measuring multiple symptoms as outcomes in cancer clinical trials. The Multisymptom Task Force addressed how to choose the symptoms to be assessed and how multiple individual symptom scores or composite scores of several symptoms might be used as clinical trial outcomes. Consensus was reached on a definition of a multisymptom outcome, the problem of source attribution, and the need for a hypothesis‐driven conceptual framework to measure multisymptom outcomes. Validated single‐item and multi‐item measures currently available or that can be easily generated for oncology use were deemed sufficient for measuring multiple symptoms. The relative value of a composite score versus a set of individual symptom scores was discussed, along with issues in developing and deploying such a composite measure. The results indicated that more research on combining scores of different symptoms is needed. Symptom data should be a required component of cancer clinical trials. Patient‐reported symptoms provide a unique patient perspective on treatment benefit and risk that goes beyond clinician‐reported adverse events. A representation of changes in multiple symptoms would clarify the impact of treatment and enhance the interpretation of cancer clinical trials for clinicians, patients, and those who make health care policy. Cancer 2013. © 2012 American Cancer Society.
Debye Sources and the Numerical Solution of the Time Harmonic Maxwell Equations II
Authors: Epstein Charles L. , Greengard Leslie , O'Neil Michael
Published: August 2012

In this paper, we develop a new integral representation for the solution of the time harmonic Maxwell equations in media with piecewise constant dielectric permittivity and magnetic permeability in
$\font\open=msbm10 at 10pt\def\R{\hbox{\open R}}\R^3$. This representation leads to a coupled system of Fredholm integral equations of the second kind for four scalar densities supported on the material interface. Like the classical Müller equation, it has no spurious resonances. Unlike the classical approach, however, the representation does not suffer from low‐frequency breakdown. We illustrate the performance of the method with numerical examples. © 2012 Wiley Periodicals, Inc.
Type 2 diabetes mellitus impairs the maturation of endothelial progenitor cells and increases the number of circulating endothelial cells in peripheral blood
Authors: Lombardo Marco F. , Iacopino Pasquale , Cuzzola Maria , Spiniello Elisa , Garreffa Cristina , Ferrelli Francesca , Coppola Andrea , Saccardi Riccardo , Piaggesi Alberto , Piro Rosanna , Mannino Domenico , Grossi Giovanni , Lauro Davide , Irrera Giuseppe
Published: August 2012

Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, which leads to vascular complications. Endothelial progenitor cells (EPCs) are thought to be a subset of cells derived from the bone marrow that play a crucial role in the neovascularization of ischemic tissue and in the maintenance of endothelial cell integrity. In contrast, circulating endothelial cells (CECs) are of endothelial origin and become detached from the intima of blood vessels in response to pathological stimuli. The study investigated the effects of T2DM on subpopulations of EPCs and CECs in peripheral blood, as compared with the effects on unacylated (UAG) and acylated (AG) ghrelin levels, which have been shown recently to play an important role in endothelial dysfunction associated with diabetes. Using the high‐performance flow cytometer FACSCanto, and UAG/AG ghrelin enzyme immunoassay kits, we analyzed whole peripheral blood samples from: (i) diabetic patients with a history of disease of less than 1 year and no clinical evidence of angiopathy, (ii) diabetic patients with long‐standing disease with vascular complications, and (iii) healthy donors. We found that T2DM did not affect bone‐marrow mobilization, but it altered the UAG/AG profile and decreased the number of highly differentiated EPCs (late EPCs) greatly. In addition, T2DM increased the number of CECs, together with the number of activated CECs. Our results suggest that: (i) the endothelial damage could be due mainly to altered maturation/commitment of EPCs, rather than a simple decrease in their production in the bone marrow; and (ii) EPC subpopulations and ghrelin levels could be useful markers to assess endothelial damage in diabetes. © 2012 International Society for Advancement of Cytometry
Multicolor flow cytometry analysis of the proliferations of T‐lymphocyte subsets in vitro by EdU incorporation
Authors: Sun Yanli , Sun Yu , Lin Guigao , Zhang Rui , Zhang Kuo , Xie Jiehong , Wang Lunan , Li Jinming
Published: August 2012

EdU (5‐ethynyl‐2′‐deoxyuridine) incorporation has proved advantageous in the studies of cell kinetics, DNA synthesis, and cellular proliferation in vitro and in vivo compared to [3H]thymidine incorporation and BrdU (5‐bromo‐2′‐deoxyuridine) incorporation. Here, we describe a method that combines EdU incorporation and immunostaining with flow cytometric analysis to detect the proliferations of T lymphocyte subsets in vitro and optimized the assay's conditions. We found that the number of EdU+ cells were associated with EdU concentration, incubation time, and the volume of Click reaction solution, the best EdU concentration 10–50 μM, the optimal incubation time 8–12 h and the proper volume of Click volume 100 μl for labeling 1 × 106 lymphocytes. Fixation was better to be performed before permeabilization, not together with. Furthermore, the permeabilization detergent reagent, PBS with 0.05% saponin was better than Tris buffer saline (TBS) with 0.1% Triton X‐100. In addition, sufficient wash with PBS with 0.05% saponin has no influence on the staining of EdU+ cells. Also, the lymphocytes incorporating EdU could be stored at 4°C, −80°C, and in liquid nitrogen up to 21 days. The present study will aid in optimization of flow cytometry assay to detect the proliferations of T cell subsets by EdU incorporation and the labeling of cell surface antigens. © 2012 International Society for Advancement of Cytometry
Estimating risk factors and perinatal outcomes for gestational diabetes and impaired glucose tolerance in teen mothers
Authors: Baker Arthur M. , Haeri Sina
Published: August 2012

Background

Our objective was to identify potentially modifiable risk factors and outcomes for gestational diabetes and impaired glucose tolerance in a contemporary American teen population.

Methods

We conducted a retrospective cohort analysis of all teenage deliveries (≤18 years old) at one institution over a 4‐year period with documented oral glucose tolerance testing. All cases of gestational diabetes and impaired glucose tolerance were identified using the Carpenter and Coustan diagnostic criteria and compared with teenage mothers with normal glucose tolerance testing.

Results

Of the 670 included teen deliveries, 668 were either African American or Hispanic/Latino; 31 (5%) were diagnosed with gestational diabetes (n = 5) or impaired glucose tolerance (n = 26). Higher maternal prepregnancy body mass index (34.3 ± 7.8 vs 30.3 ± 6.4, p = 0.001) and morbid obesity (body mass index ≥ 35 kg/m2, RR 2.0, 95% CI 1.1–3.6) were associated with gestational diabetes and impaired glucose tolerance. There was no association with weight gain above the Institute of Medicine recommended levels (RR 1.6, 95% CI 0.77–3.4). On postpregnancy follow up, three of the five (60%) teens with gestational diabetes and none of the 26 (0%) teens with impaired glucose tolerance were diagnosed with diabetes mellitus.

Conclusions

Higher prepregnancy body mass index, especially morbid obesity, places the gravid teen at higher risk for development of gestational diabetes and impaired glucose tolerance in pregnancy. The potentially modifiable nature of these risk factors coupled with the emerging teen obesity epidemic underscores the need for increased public health focus on this problem. Copyright © 2012 John Wiley & Sons, Ltd.
The relation among NGF, EGF and insulin is important for triggering pancreatic β cell apoptosis
Authors: Gezginci‐Oktayoglu S. , Karatug A. , Bolkent S.
Published: August 2012

Background

Nerve growth factor (NGF) is a well‐known mediator for maintaining the survival of neurons, while recent studies report that its absence induces apoptosis in cultured β cells of humans and rats. However, its relationship with other growth factors that have important roles in the survival and function of β cells such as epidermal growth factor (EGF) has not yet been elucidated. The aim of this study was to investigate the effects of NGF withdrawal on the synthesis and secretion of EGF, insulin with respect to β cell apoptosis in hyperglycemic rats.

Method

β cells were isolated from euglycemic and streptozotocin‐induced hyperglycemic rats and treated with NGF neutralizing antibody for withdrawal of NGF in culture medium. NGF, EGF and insulin levels in cell lysates and secretion samples were measured by enzyme‐linked immunosorbent assay, and their gene expressions were determined by real‐time reverse transcription polymerase chain reaction assay. Apoptosis was quantitatively determined by cytoplasmic histone‐associated DNA fragments.

Results

Nerve growth factor neutralization triggered β cell apoptosis. In addition decreased insulin, increased NGF and EGF were observed at gene expression and protein levels by NGF neutralization. Moreover, NGF withdrawal decreased secretion of these peptides from β cells. Although the alterations seemed to be similar under euglycemic and hyperglycemic conditions, NGF withdrawal more strongly affected β cells of hyperglycemic rats.

Conclusions

These important findings indicate that NGF is an important regulator for the synthesis and secretion of EGF and insulin from the β cells. Moreover, results suggested that NGF withdrawal causes apoptosis by decreasing EGF, NGF and insulin secretion from β cells of hyperglycemic rats. Copyright © 2012 John Wiley & Sons, Ltd.
Podocyte‐specific overexpression of metallothionein mitigates diabetic complications in the glomerular filtration barrier and glomerular histoarchitecture: a transmission electron microscopy stereometric analysis
Authors: Carlson Edward C. , Chhoun Jennifer M. , Laturnus Donna I. , Bikash KC , Berg Brittany , Zheng Shirong , Epstein Paul N.
Published: August 2012

Background

We previously demonstrated that cellular and extracellular components of the blood–urine barrier in renal glomeruli are susceptible to damage in OVE transgenic mice, a valuable model of human diabetic nephropathy that expresses profound albuminuria.

Methods

To test our hypothesis that glomerular filtration barrier damage in OVE mice may be the result of oxidative insult to podocytes, 150‐day‐old bi‐transgenic OVENmt diabetic mice that overexpress the antioxidant metallothionein specifically in podocytes were examined by enzyme‐linked immunosorbent assay for albuminuria mitigation and by unbiased transmission electron microscopy (TEM) stereometry for protection from chronic structural diabetic complications.

Results

Although blood glucose and HbA1c levels were indistinguishable in OVE and OVENmt animals, albuminuria was significantly reduced (average >7‐fold) in OVENmt mice through 8 months of age. Interestingly, the Nmt transgene provided significant glomerular protection against diabetic nephropathic complications outside of the podocyte. Glomerular filtration barrier damage was reduced in OVENmt mice, including significantly increased area occupied by endothelial luminal fenestrations (~13%), significantly reduced glomerular basement membrane (GBM) thickening (~17%) and significantly less podocyte effacement (~18%). In addition, OVENmt mice exhibited significantly reduced glomerular volume (~50%), fewer glomerular endothelial cells (~33%), fewer mesangial cells (~57%) and fewer total glomerular cells (~40%).

Conclusions

These results provide evidence of oxidative damage to podocytes induces primary diabetic nephropathic features including severe and sustained albuminuria, specific glomerular filtration barrier damage and alterations in glomerular endothelial and mesangial cell number. Importantly, these diabetic complications are significantly mitigated by podocyte targeted metallothionein overexpression. Copyright © 2012 John Wiley & Sons, Ltd.
Protocadherin‐17 function in Zebrafish retinal development
Authors: Chen Yun , Londraville Richard , Brickner Sarah , El‐Shaar Lana , Fankhauser Kelsee , Dearth Cassandra , Fulton Leah , Sochacka Alicja , Bhattarai Sunil , Marrs James A. , Liu Qin
Published: August 2012

Cadherin cell adhesion molecules play crucial roles in vertebrate development including the development of the retina. Most studies have focused on examining functions of classic cadherins (e.g. N‐cadherin) in retinal development. There is little information on the function of protocadherins in the development of the vertebrate visual system. We previously showed that protocadherin‐17 mRNA was expressed in developing zebrafish retina during critical stages of the retinal development. To gain insight into protocadherin‐17 function in the formation of the retina, we analyzed eye development and differentiation of retinal cells in zebrafish embryos injected with protocadherin‐17 specific antisense morpholino oligonucleotides (MOs). Protocadherin‐17 knockdown embryos (pcdh17 morphants) had significantly reduced eyes due mainly to decreased cell proliferation. Differentiation of several retinal cell types (e.g. retinal ganglion cells) was also disrupted in the pcdh17 morphants. Phenotypic rescue was achieved by injection of protocadherin‐17 mRNA. Injection of a vivo‐protocadherin‐17 MO into one eye of embryonic zebrafish resulted in similar eye defects. Our results suggest that protocadherin‐17 plays an important role in the normal formation of the zebrafish retina. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013
Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos
Authors: Chen Yi‐Hui , Yu John
Published: August 2012

Background: Parthenogenetic mammalian embryos were reported to die in utero no later than the 25‐somite stage due to abnormal development of both embryonic and extraembryonic lineages. Interestingly, it has been shown that parthenogenetic ICM cells tend to differentiate more into primitive endoderm cells and less into epiblast and ES cells. Hence we are interested in studying the molecular mechanisms underlying lineage defects of parthenotes. Results: We found that parthenote inner cell masses (ICMs) contained decreased numbers of Sox2+/Nanog+ epiblast cells but increased numbers of Gata4+ primitive endoderm cells, indicating an unusual lineage segregation. We demonstrate for the first time that the increased Gata4 level in parthenotes may be explained by the strong up‐regulation of Fgf3 and Fgfr2 phosphorylation. Inhibition of Fgfr2 activation by SU5402 in parthenotes restored normal Nanog and Gata4 levels without affecting Fgf3, indicating that Fgf3 is upstream of Fgfr2 activation. In parthenote trophectoderm, we detected normal Cdx2 but ectopic Gata4 expression and reduced Elf5 and Tbr2(Eomes) levels. Conclusions: Taken together, our work provides for the first time the insight into the molecular mechanisms of the developmental defects of parthenogenetic embryos in both the trophectoderm and ICM. Developmental Dynamics 241:1651–1664, 2012. © 2012 Wiley Periodicals,Inc.
Comprehensive timeline of mesodermal development in the quail small intestine
Authors: Thomason Rebecca T. , Bader David M. , Winters Nichelle I.
Published: August 2012

Background: To generate the mature intestine, splanchnic mesoderm diversifies into six different tissue layers each with multiple cell types through concurrent and complex morphogenetic events. Hindering the progress of research in the field is the lack of a detailed description of the fundamental morphological changes that constitute development of the intestinal mesoderm. Results: We used immunofluorescence and morphometric analyses of wild‐type and Tg(tie1:H2B‐eYFP) quail embryos to establish a comprehensive timeline of mesodermal development in the avian intestine. The following landmark features were analyzed from appearance of the intestinal primordium through generation of the definitive structure: radial compartment formation, basement membrane dynamics, mesothelial differentiation, mesenchymal expansion and growth patterns, smooth muscle differentiation, and maturation of the vasculature. In this way, structural relationships between mesodermal components were identified over time. Conclusions: This integrated analysis presents a roadmap for investigators and clinicians to evaluate diverse experimental data obtained at individual stages of intestinal development within the longitudinal context of intestinal morphogenesis. Developmental Dynamics 241:1678–1694, 2012. © 2012 Wiley Periodicals,Inc.
Rainfall can explain adaptive phenotypic variation with high gene flow in the New Holland Honeyeater (Phylidonyris novaehollandiae)
Authors: Myers Steven A. , Donnellan Stephen , Kleindorfer Sonia
Published: August 2012

Identifying environmentally driven changes in traits that serve an ecological function is essential for predicting evolutionary outcomes of climate change. We examined population genetic structure, sex‐specific dispersal patterns, and morphology in relation to rainfall patterns across an island and three peninsulas in South Australia. The study system was the New Holland Honeyeater (Phylidonyris novaehollandiae), a nectarivorous passerine that is a key pollinator species. We predicted that rainfall‐related mechanisms would be driving local adaptation of morphological traits, such that in areas of lower rainfall, where nectar is less available, more insectivorous traits – shorter, deeper bills, longer tarsi, and longer wings – would be favored. The study populations differed in phenotype across the Eyre, Yorke, and Fleurieu Peninsulas and Kangaroo Island despite high gene flow (single continuous population) and sex‐biased dispersal (males were philopatric and females dispersed). We tested the role of rainfall in shaping the observed phenotypic differences, and found strong support for our predicted relationships: birds in areas of higher rainfall had higher condition indices, as well as longer bill‐head length, deeper bills, and shorter tarsi. Bill depth in males in high‐rainfall sites showed signals of stabilizing selection, suggesting local adaptation. In addition to these local indications of selection, a global pattern of directional selection toward larger size for bill‐head length, bill‐nostril length, and wing length was also observed. We suggest this pattern may reflect an adaptive response to the relatively dry conditions that South Australia has experienced over the last decade. We conclude that rainfall has shaped aspects of phenology in P. novaehollandiae, both locally, with different patterns of stabilizing and directional selection, and globally, with evidence of adaptive divergence at a landscape scale.
NYVAC immunization induces polyfunctional HIV‐specific T‐cell responses in chronically‐infected, ART‐treated HIV patients
Authors: Harari Alexandre , Rozot Virginie , Cavassini Matthias , Enders Felicitas Bellutti , Vigano Selena , Tapia Gonzalo , Castro Erika , Burnet Séverine , Lange Joep , Moog Christiane , Garin Daniel , Costagliola Dominique , Autran Brigitte , Pantaleo Giuseppe , Bart Pierre‐Alexandre
Published: August 2012

We report the results of the Theravac‐01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus‐based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC‐B vaccine was injected intra‐muscularly into ten HIV‐infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV‐specific T‐cell responses following immunization were quantitatively analyzed using an IFN‐γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC‐B vaccine is safe and highly immunogenic, as indicated by increased HIV‐specific T‐cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T‐cell responses, and the appearance of newly detected HIV‐specific CD4+ and CD8+ T‐cell responses were observed. Furthermore, immunization mostly induced an increase in Gag‐specific T‐cell responses. In conclusion, NYVAC‐B immunization induces broad, vigorous, and polyfunctional HIV‐specific T‐cell responses, suggesting that poxvirus‐based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.
Post separation adjustment of pH to enable the analysis of aminoglycoside antibiotics by microchip electrophoresis with amperometric detection
Authors: Ding Yongsheng , Bai Liang , Suo Xingmei , Meng Xiangying
Published: August 2012

Five aminoglycoside antibiotics (AGs), namely spectinomycin, streptomycin, amikacin, paromomycin, and neomycin, were analyzed by microchip electrophoresis with amperometric detection. Although the electrophoretic separation of AGs was carried out under acidic conditions, the amperometric detection was performed under alkaline conditions with an electrode fabricated by electrodeposition of an alloy of Cu‐Sn‐Cr. To achieve this, an alkaline solution was introduced into the end of the separation channel through two auxiliary channels, allowing the use of different conditions for each analytical operation. Along with the proposed pH adjustment, the use of electrodes modified with Cu‐Sn‐Cr enabled extending the lifetime of the electrodes. The alloy was co‐electrodeposited on a 25‐μm diameter platinum wire, which was then integrated in the microchip and used as working electrode. Furthermore, the effects of the pH and composition of buffer, separation potential, injection time, and detention potential were investigated in an effort to optimize both the separation and detection of AGs. Under the optimum conditions, linear relationships between the signal and the concentration were obtained in the 4.9–316.8 μM range, with regression coefficients of at least 0.99 and LODs ranging from 2.1 μM for amikacin to 4.6 μM for spectinomycin. Applicability of the method was demonstrated by analyzing five aminoglycoside antibiotics in spiked milk samples. The results showed that this alternative method is rapid, sensitive, and portable and enables the analysis of aminoglycoside antibiotics in milk sample.
Easy sample treatment for the determination of enrofloxacin and ciprofloxacin residues in raw bovine milk by capillary electrophoresis
Authors: Piñero María‐Ysabel , Garrido‐Delgado Rocío , Bauza Roberto , Arce Lourdes , Valcárcel Miguel
Published: August 2012

An easy, selective, and sensitive method has been developed for the determination of enrofloxacin (ENR) and its main active metabolite, ciprofloxacin (CIP), in raw bovine milk using CE with UV detection at 268 nm. Milk samples were prepared by a clean‐up/extraction procedure based on protein precipitation with hydrochloride acid followed by being defatted by centrifugation and SPE using a hydrophilic‐lipophilic balance cartridge. Optimum separation was obtained using a 50 mM phosphoric acid at pH 8.4 and the total electrophoretic run time was 6 min. Sample preparation by this method yielded clean extracts with quantitative and consistent mean recoveries from 89 to 97% for CIP and from 93 to 98% for ENR. LODs obtained were lower to the maximum residue limits for these fluoroquinolones. The precision of the ensuing method is acceptable; thus, the RSD for peak area and migration time was less than 8.5 and 0.5% for CIP and 9.9 and 0.9% for ENR, respectively. The results showed that the proposed method was efficient showing good recoveries, sensitivity, and precision for the studied compounds and could be satisfactorily applied in routine analysis for the monitoring of ENR and CIP residues in milk, due to its ruggedness and feasibility demonstrated.
Improved assessment of aggregate size in Taxus plant cell suspension cultures using laser diffraction
Authors: Wucherpfennig Thomas , Schilling Jana , Sieblitz Dominik , Pump Matthias , Schütte Kai , Wittmann Christoph , Krull Rainer
Published: August 2012

In suspended culture, most relevant for biotechnological application, plant cells form aggregates. This phenomenon is of importance as it is related to productivity, leads to local heterogeneities, and might be a reason for the considerable shear sensitivity of these cultures. The valid measurement of plant cell aggregates, however, is not trivial, due to a rather large size distribution and measurement artifacts implied by the measuring method. In this study, laser diffraction was used as a novel method for characterization of Taxus chinensis cells, a major source for the antitumor agent paclitaxel. Aggregate size measured in shaking flask cultivations over 10 days revealed an increase during the growth phase of a batch cycle and a decrease during the stationary phase. During growth, the increase in bio dry weight was proportional to aggregate size. Laser diffraction was found superior to microscopy and image analysis, which had a tendency to underestimate aggregate size up to 20%. This novel approach provides a practicable, rapid, robust, and reproducible way to analyze a 100‐fold more samples in considerably less time than image analysis and is therefore of especial value for quality control in industrial plant cell cultivation.
Use of biodiesel‐derived crude glycerol for vancomycin production by Amycolatopsis orientalis XMU‐VS01
Authors: Zeng Xianhai , Wang Sili , Jing Keju , Zhang Zhixiang , Lu Yinghua
Published: August 2012

Crude glycerol is a primary by‐product in the biodiesel industry. Microbial fermentation on crude glycerol for producing value‐added products provides opportunities to utilize a large quantity of this by‐product. This study investigates the potential of using the crude glycerol to produce vancomycin (glycopeptide antibiotics) through fermentation of Amycolatopsis orientalis XMU‐VS01. The results show that crude glycerol was the most effective carbon source for mycelium growth and vancomycin production, with 40–60 g/L glycerol concentration as optimal range. Among other culture medium components, potato protein (nitrogen source) and the phosphate concentration had significant effects (p<0.05) for vancomycin production. A Box‐Behnken design and response surface methodology were employed to formulate the optimal medium. Their optimal values were determined as 52.73 g/L of glycerol, 17.36 g/L of potato protein, and 0.1 g/L of dipotassium phosphate. A highest vancomycin yield of 7.61 g/L with biomass concentration of 15.8 g/L was obtained after 120 h flask fermentation. The yield of vancomycin was 3.5 times higher than with basic medium. The results suggest that biodiesel‐derived crude glycerol is a promising feedstock for production of vancomycin from A. orientalis culture.
A fuzzy linear programming model for allocation of oil and gas resources in iran with the aim of reducing the greenhouse gases
Authors: Kazemi Aliyeh , Shakouri G. Hamed , Mehregan M. Reza , Hosseinzadeh Mahnaz
Published: August 2012

Energy plays a key role in sustainable development. Formulation of an energy model will help in the proper allocation of available energy resources. The objective of this article is to allocate optimally to each end user a certain amount of energy to be supplied by a given resource in Iran to reduce greenhouse gases. For this purpose, energy demands of end users are forecasted, and the outcomes are used in a fuzzy linear programming model, which determines the best allocation of energy resources in Iran from 2012 to 2020. The result shows a large portion of crude oil and natural gas will be allocated for exports. Transportation sector will be the major consumer of the petroleum products. Higher amounts of natural gas compared with the petroleum products will be allocated to power plants. Moreover, a considerable portion of natural gas should be injected into the oil reservoirs. These analyses would provide scientific basis for the optimal allocation of energy resources in meeting the future energy demand in Iran. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 854–859, 2013
Power consumption model for macrocell and microcell base stations
Authors: Deruyck Margot , Joseph Wout , Martens Luc
Published: August 2012

In this paper, a power consumption model for both macrocell and microcell base stations is proposed. This model is validated by temporal power measurements on actual base stations, and an excellent agreement is obtained. Furthermore, the power consumption's evolution during the day is investigated by means of these measurements. The energy efficiency of three different wireless technologies is compared namely mobile Worldwide Interoperability for Microwave Access, Long Term Evolution and High Speed Packet Access. With the model proposed, the deployment tool Green Radio Access Network Design is implemented, which allows to design an energy‐efficient access network for a predefined area. In general and with the assumptions made, a macrocell base station consumes about 4.4 times more than a microcell base station. However, a microcell base station is less energy efficient than a macrocell base station because of its lower coverage range. Despite this, it is still useful to introduce them in the network as the same coverage can be obtained with a lower total power consumption than with a network where only macrocell base stations are used. Copyright © 2012 John Wiley & Sons, Ltd.
Main enablers for advanced interference mitigation
Authors: Zirwas Wolfgang , Mennerich Wolfgang , Khan Aneeq
Published: August 2012

The vision of an interference‐free or interference‐exploiting mobile cellular radio system has attracted lots of research groups. It led to several 3GPP long term evolution coordinated multipoint transmission studies and working items. So far, the results achieved are still far from theoretical performance as expected from network‐wide cooperation. In reality, small to moderate gains will be easily lost in case of realistic channel estimation and feedback assumptions. Therefore, the European Union founded project ARTIST4G had a three‐fold goal: leveraging considerable system level gains in combination with an effective channel estimation and a low rate feedback scheme. One main enabler is the so‐called partial coordinated multipoint plus cover shift concept of overlapping cooperation areas approaching user centric clustering. ‘Simple’ but powerful is a novel interference floor shaping technique based on cooperation area specific vertical antenna tilting and power allocation. An enhanced scheduling strategy turns signal to interference and noise into spectral efficiency and coverage gains. For overcoming channel state information outdating and simultaneously minimizing feedback overhead, a model‐based channel prediction concept is proposed reporting location instead of channel state information. Copyright © 2012 John Wiley & Sons, Ltd.
Resource sharing in LTE‐Advanced relay networks: uplink system performance analysis
Authors: Bulakci Ömer , Bou Saleh Abdallah , Redana Simone , Raaf Bernhard , Hämäläinen Jyri
Published: August 2012

Relay‐enhanced networks are expected to fulfil the demanding coverage and capacity requirements in a cost‐efficient way. Type 1 inband relaying has been standardised as an integral part of the Third Generation Partnership Project (3GPP) Long‐Term Evolution Release 10 and beyond (LTE‐Advanced). This type of relay nodes (RNs) supports a relaying mode where the RN to donor evolved node B (donor eNB, DeNB) link (relay link, a.k.a. backhaul link) transmission is time‐division multiplexed with the RN‐served user equipments (RUEs) to RN link (access link) transmission, whereas macrocell‐served user equipments (MUEs) share the same resources with the RNs at DeNB. Hence, system performance depends strongly on the resource sharing strategy among and within the links. Further, the set of subframes assigned for the relay link transmission is semi‐statically configured and thus a dynamic reconfiguration to adapt to fast‐changing system conditions (e.g. RN cell load) is not viable. Besides, in order to fully exploit the benefits of relaying, the inter‐cell interference, which is increased because of the presence of RNs, should be limited via a proper power control (PC) scheme on each link. Therefore, an optimisation of both the resource sharing and PC strategy is required to enhance the overall performance of relay networks. In order to tackle these issues, we employ a statistic‐based over‐provisioned backhaul subframe allocation to be utilised for flexible co‐scheduling of RNs and MUEs at the DeNB. In addition, we propose a combination of RN scheduling based on the number of RUEs and user throughput throttling achieving max–min fairness. Performance analysis of various resource sharing techniques along with PC optimisation is then carried out within the LTE‐Advanced uplink framework in urban and suburban scenarios. Comprehensive results show that the proposed schemes achieve significant throughput gains and high system fairness with substantially increased flexibility in resource allocation. Copyright © 2012 John Wiley & Sons, Ltd.
Spatial accuracy and performance of a mixed‐order, explicit multi‐stage method for unsteady flows
Authors: Waltz Jacob
Published: August 2012

We assess the spatial accuracy and performance of a mixed‐order, explicit multi‐stage method in which an inexpensive low‐order scheme is used for the initial stages, and a more expensive high‐order scheme is used for the final stage only. Compared with the use of a high‐order scheme for all stages, we observe that the mixed‐order scheme achieves comparable accuracy and convergence while providing a speed‐up of a factor of two on mesh sizes of O(106 − 107) tetrahedron. For calculations with significant adaptive mesh refinement, a more modest speed‐up of 30% is obtained. Published 2012. This article is a US Government work and is in the public domain in the USA.
Astrocytes as a regulated source of retinoic acid for the brain
Authors: Shearer Kirsty D. , Fragoso Yara D. , Clagett‐Dame Margaret , McCaffery Peter J.
Published: August 2012

Retinaldehyde dehydrogenases (RALDH) catalyze the synthesis of the regulatory factor retinoic acid (RA). Cultured astrocytes express several of the RALDH enzyme family, and it has been assumed that this can be extrapolated to astrocytes in vivo. However, this study finds that few astrocytes in the rodent brain express detectable RALDH enzymes, and only when these cells are grown in culture are these enzymes upregulated. Factors controlling the expression of the RALDHs in cultured astrocytes were explored to determine possible reasons for differences between in vitro versus in vivo expression. Retinoids were found to feedback to suppress several of the RALDHs, and physiological levels of retinoids may be one route by which astrocytic RALDHs are maintained at low levels. In the case of RALDH2, in vivo reduction of vitamin A levels in rats resulted in an increase in astrocyte RALDH2 expression in the hippocampus. Other factors though are likely to control RALDH expression. A shift in astrocytic RALDH subcellular localization is a potential mechanism for regulating RA signaling. Under conditions of vitamin A deficiency, RALDH2 protein moved from the cytoplasm to the nucleus where it may synthesize RA at the site of the nuclear RA receptors. Similarly, in conditions of oxidative stress RALDH1 and RALDH2 moved from the cytoplasm to a predominantly nuclear position. Thus, the RALDHs have been revealed to be dynamic in their expression in astrocytes where they may maintain retinoid homeostasis in the brain. © 2012 Wiley Periodicals, Inc.
Hippocampal neurons inhibit meal onset
Authors: Henderson Yoko O. , Smith Gerard P. , Parent Marise B.
Published: August 2012

There is extensive research regarding the neural mechanisms involved in satiety and meal termination; in contrast, there is very limited understanding of how meal onset is regulated. On the basis of several converging lines of evidence, we hypothesized that hippocampal neurons form a memory of a meal and inhibit meal onset during the postprandial period. As a first step, we tested whether reversible inactivation of the hippocampus with muscimol infusions after the end of one meal would accelerate the onset of the next meal. To test this, adult male Sprague–Dawley rats (N = 23) were implanted with a cannula aimed at the right or left dorsal hippocampus and then trained to consume a 32% sucrose solution at a scheduled time daily. On the experimental day, hippocampal neuronal activity was temporarily disrupted during the postprandial period by infusing muscimol (0.5 μg/μl; 1 μl) 5 min after the rats stopped consuming the sucrose solution. Compared to vehicle infusions, muscimol infusions significantly decreased the latency to start the postinfusion meal and increased the size of the postinfusion meal. In addition, muscimol disrupted the relationship between the size of a meal and length of the following postprandial period. These effects of muscimol on meal onset were not due to an effect on the speed of consumption. Collectively, these findings are consistent with the hypothesis that hippocampal neurons suppress meal initiation during the postprandial period. Given that overeating can impair hippocampal function, these findings suggest that impaired hippocampal functioning is a cause and consequence of overeating and obesity. © 2012 Wiley Periodicals, Inc.
Data assimilation methods for estimating a heterogeneous conductivity field by assimilating transient solute transport data via ensemble Kalman filter
Authors: Tong Juxiu , Hu Bill X. , Yang Jinzhong
Published: August 2012

An ensemble Kalman filter (EnKF) is developed to identify a hydraulic conductivity distribution in a heterogeneous medium by assimilating solute concentration measurements of solute transport in the field with a steady‐state flow. A synthetic case with the mixed Neumann/Dirichlet boundary conditions is designed to investigate the capacity of the data assimilation methods to identify a conductivity distribution. The developed method is demonstrated in 2‐D transient solute transport with two different initial instant solute injection areas. The influences of the observation error and model error on the updated results are considered in this study. The study results indicate that the EnKF method will significantly improve the estimation of the hydraulic conductivity field by assimilating solute concentration measurements. The larger area of the initial distribution and the more observed data obtained, the better the calculation results. When the standard deviation of the observation error varies from 1% to 30% of the solute concentration measurements, the simulated results by the data assimilation method do not change much, which indicates that assimilation results are not very sensitive to the standard deviation of the observation error in this study. When the inflation factor is more than 1.0 to enlarge the model error by increasing the forecast error covariance matrix, the updated results of the hydraulic conductivity by the data assimilation method are not good at all. Copyright © 2012 John Wiley & Sons, Ltd.
An improved hemispherical photography model for stream surface shortwave radiation estimations in a central U.S. hardwood forest
Authors: Bulliner Edward , Hubbart Jason A.
Published: August 2012

Hemispherical photographs of forest canopies can be used to develop sophisticated models that predict incident below canopy shortwave radiation on the surface of interest (i.e. soil and water). Hemispherical photographs were collected on eight dates over the course of a growing season to estimate leaf area index and to quantify solar radiation incident on the surface of two stream reaches based on output from Gap Light Analyser and Hemisfer software. Stream reaches were shaded by a mixed‐deciduous Ozark border forested riparian canopy. Hemispherical photo model results were compared to observed solar radiation sensed at climate stations adjacent to each stream reach for the entire 2010 water year. Modeled stream‐incident shortwave radiation was validated with above‐stream pyranometers for the month of September. On average, the best hemispherical photo models underestimated daily averages of solar radiation by approximately 14% and 12% for E–W and N–S flowing stream reaches, respectively (44.7 W/m2measuredvs38.4 W/m2modeled E–W, 46.8 W/m2vs. 41.1 W/m2N–S). The best hemispherical photo models overestimated solar radiation relative to in–Stream pyranometers placed in the center of each stream reach by approximately 7% and 17% for E–W and N–S stream reaches respectively (31.3 W/m2measuredvs33.5 W/m2modeled E–W, 31.5 W/m2vs. 37.1 W/m2N–S). The model provides a geographically transferable means for quantifying changes in the solar radiation regime at a stream surface due to changes in canopy density through a growing season, thus providing a relatively simple method for estimating surface and water heating in canopy altered environments (e.g. forest harvest).

Copyright © 2012 John Wiley & Sons, Ltd.
Circulating microRNAs in plasma as early detection markers for breast cancer
Authors: Cuk Katarina , Zucknick Manuela , Heil Jörg , Madhavan Dharanija , Schott Sarah , Turchinovich Andrey , Arlt Dorit , Rath Michelle , Sohn Christof , Benner Axel , Junkermann Hans , Schneeweiss Andreas , Burwinkel Barbara
Published: August 2012

In recent years, circulating miRNAs have attracted a great deal of attention as promising novel markers for various diseases. Here, we investigated their potential to serve as minimally invasive, early detection markers for breast cancer in blood plasma. We profiled miRNAs extracted from the plasma of early stage breast cancer patients (taken at the time‐point of diagnosis) and healthy control individuals using TaqMan low‐density arrays (TLDA). Selected candidates identified in the initial screen were further validated in an extended study cohort of 207 individuals including 127 sporadic breast cancer cases and 80 healthy controls via RT‐qPCR. Four miRNAs (miR‐148b, miR‐376c, miR‐409‐3p and miR‐801) were shown to be significantly upregulated in the plasma of breast cancer patients. ROC curve analysis showed that the combination of only three miRNAs (miR‐148b, miR‐409‐3p and miR‐801) had an equal discriminatory power between breast cancer cases and healthy controls as all four miRNAs together (AUC = 0.69). In conclusion, the identified miRNAs might be of potential use in the development of a multimarker blood‐based test to complement and improve early detection of breast cancer. Such a multimarker blood test might for instance provide a prescreening tool, especially for younger women, to facilitate decisions about which individuals to recommend for further diagnostic tests.