bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of combined maximum and minimum intensity projections to determine internal target volume in 4-dimensional CT scans for hepatic malignancies
Authors: Liu Jin , Wang Jia-Zhou , Zhao Jian-Dong , Xu Zhi-Yong , Jiang Guo-Liang
Published: January 2012

Background

To evaluate the accuracy of the combined maximum and minimum intensity projection-based internal target volume (ITV) delineation in 4-dimensional (4D) CT scans for liver malignancies.

Methods

4D CT with synchronized IV contrast data were acquired from 15 liver cancer patients (4 hepatocellular carcinomas; 11 hepatic metastases). We used five approaches to determine ITVs: (1). ITVAllPhases: contouring gross tumor volume (GTV) on each of 10 respiratory phases of 4D CT data set and combining these GTVs; (2). ITV2Phase: contouring GTV on CT of the peak inhale phase (0% phase) and the peak exhale phase (50%) and then combining the two; (3). ITVMIP: contouring GTV on MIP with modifications based on physician's visual verification of contours in each respiratory phase; (4). ITVMinIP: contouring GTV on MinIP with modification by physician; (5). ITV2M: combining ITVMIP and ITVMinIP. ITVAllPhases was taken as the reference ITV, and the metrics used for comparison were: matching index (MI), under- and over-estimated volume (Vunder and Vover).

Results

4D CT images were successfully acquired from 15 patients and tumor margins were clearly discernable in all patients. There were 9 cases of low density and 6, mixed on CT images. After comparisons of metrics, the tool of ITV2M was the most appropriate to contour ITV for liver malignancies with the highest MI of 0.93 ± 0.04 and the lowest proportion of Vunder (0.07 ± 0.04). Moreover, tumor volume, target motion three-dimensionally and ratio of tumor vertical diameter over tumor motion magnitude in cranio-caudal direction did not significantly influence the values of MI and proportion of Vunder.

Conclusion

The tool of ITV2M is recommended as a reliable method for generating ITVs from 4D CT data sets in liver cancer.
Bilateral enucleation alters gene expression and intraneocortical connections in the mouse
Authors: Dye Catherine A , Abbott Charles W , Huffman Kelly J
Published: January 2012

Background

Anatomically and functionally distinct sensory and motor neocortical areas form during mammalian development through a process called arealization. This process is believed to be reliant on both activity-dependent and activity-independent mechanisms. Although both mechanisms are thought to function concurrently during arealization, the nature of their interaction is not understood. To examine the potential interplay of extrinsic activity-dependent mechanisms, such as sensory input, and intrinsic activity-independent mechanisms, including gene expression in mouse neocortical development, we performed bilateral enucleations in newborn mice and conducted anatomical and molecular analyses 10 days later. In this study, by surgically removing the eyes of the newborn mouse, we examined whether early enucleation would impact normal gene expression and the development of basic anatomical features such as intraneocortical connections and cortical area boundaries in the first 10 days of life, before natural eye opening. We examined the acute effects of bilateral enucleation on the lateral geniculate nucleus of the thalamus and the neocortical somatosensory-visual area boundary through detailed analyses of intraneocortical connections and gene expression of six developmentally regulated genes at postnatal day 10.

Results

Our results demonstrate short-term plasticity on postnatal day 10 resulting from the removal of the eyes at birth, with changes in nuclear size and gene expression within the lateral geniculate nucleus as well as a shift in intraneocortical connections and ephrin A5 expression at the somatosensory-visual boundary. In this report, we highlight the correlation between positional shifts in ephrin A5 expression and improper refinement of intraneocortical connections observed at the somatosensory-visual boundary in enucleates on postnatal day 10.

Conclusions

Bilateral enucleation induces a positional shift of both ephrin A5 expression and intraneocortical projections at the somatosensory-visual border in only 10 days. These changes occur prior to natural eye opening, suggesting a possible role of spontaneous retinal activity in area border formation within the neocortex. Through these analyses, we gain a deeper understanding of how extrinsic activity-dependent mechanisms, particularly input from sensory organs, are integrated with intrinsic activity-independent mechanisms to regulate neocortical arealization and plasticity.
Predicting outcomes of steady-state 13C isotope tracing experiments using Monte Carlo sampling
Authors: Schellenberger Jan , Zielinski Daniel C , Choi Wing , Madireddi Sunthosh , Portnoy Vasiliy , Scott David A , Reed Jennifer L , Osterman Andrei L , Palsson Bernhard ∅
Published: January 2012

Background

Carbon-13 (13C) analysis is a commonly used method for estimating reaction rates in biochemical networks. The choice of carbon labeling pattern is an important consideration when designing these experiments. We present a novel Monte Carlo algorithm for finding the optimal substrate input label for a particular experimental objective (flux or flux ratio). Unlike previous work, this method does not require assumption of the flux distribution beforehand.

Results

Using a large E. coli isotopomer model, different commercially available substrate labeling patterns were tested computationally for their ability to determine reaction fluxes. The choice of optimal labeled substrate was found to be dependent upon the desired experimental objective. Many commercially available labels are predicted to be outperformed by complex labeling patterns. Based on Monte Carlo Sampling, the dimensionality of experimental data was found to be considerably less than anticipated, suggesting that effectiveness of 13C experiments for determining reaction fluxes across a large-scale metabolic network is less than previously believed.

Conclusions

While 13C analysis is a useful tool in systems biology, high redundancy in measurements limits the information that can be obtained from each experiment. It is however possible to compute potential limitations before an experiment is run and predict whether, and to what degree, the rate of each reaction can be resolved.
Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples
Authors: de la Blétière Diane Raingeard , Blanchet Odile , Cornillet-Lefèbvre Pascale , Coutolleau Anne , Baranger Laurence , Geneviève Franck , Luquet Isabelle , Hunault-Berger Mathilde , Beucher Annaelle , Schmidt-Tanguy Aline , Zandecki Marc , Delneste Yves , Ifrah Norbert , Guardiola Philippe
Published: January 2012

Background

Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified.

Methods

Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n = 101) and/or poor quality control criteria (n = 10) (test set).

Results

With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load.

Conclusion

Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion.
In vivo antinociception of potent mu opioid agonist tetrapeptide analogues and comparison with a compact opioid agonist - neurokinin 1 receptor antagonist chimera
Authors: Guillemyn Karel , Kleczkowska Patrycja , Novoa Alexandre , Vandormael Bart , Van den Eynde Isabelle , Kosson Piotr , Asim Muhammad Faheem , Schiller Peter W , Spetea Mariana , Lipkowski Andrzej W , Tourwé Dirk , Ballet Steven
Published: January 2012

Background

An important limiting factor in the development of centrally acting pharmaceuticals is the blood-brain barrier (BBB). Transport of therapeutic peptides through this highly protective physiological barrier remains a challenge for peptide drug delivery into the central nervous system (CNS). Because the most common strategy to treat moderate to severe pain consists of the activation of opioid receptors in the brain, the development of active opioid peptide analogues as potential analgesics requires compounds with a high resistance to enzymatic degradation and an ability to cross the BBB.

Results

Herein we report that tetrapeptide analogues of the type H-Dmt1-Xxx2-Yyy3-Gly4-NH2 are transported into the brain after intravenous and subcutaneous administration and are able to activate the μ- and δ opioid receptors more efficiently and over longer periods of time than morphine. Using the hot water tail flick test as the animal model for antinociception, a comparison in potency is presented between a side chain conformationally constrained analogue containing the benzazepine ring (BVD03, Yyy3: Aba), and a "ring opened" analogue (BVD02, Yyy3: Phe). The results show that in addition to the increased lipophilicity through amide bond N-methylation, the conformational constraint introduced at the level of the Phe3 side chain causes a prolonged antinociception. Further replacement of NMe-D-Ala2 by D-Arg2 in the tetrapeptide sequence led to an improved potency as demonstrated by a higher and maintained antinociception for AN81 (Xxx2: D-Arg) vs. BVD03 (Xxx2: NMe-D-Ala). A daily injection of the studied opioid ligands over a time period of 5 days did however result in a substantial decrease in antinociception on the fifth day of the experiment. The compact opioid agonist - NK1 antagonist hybrid SBCHM01 could not circumvent opioid induced tolerance.

Conclusions

We demonstrated that the introduction of a conformational constraint has an important impact on opioid receptor activation and subsequent antinociception in vivo. Further amino acid substitution allowed to identify AN81 as an opioid ligand able to access the CNS and induce antinociception at very low doses (0.1 mg/kg) over a time period up to 7 hours. However, tolerance became apparent after repetitive i.v. administration of the investigated tetrapeptides. This side effect was also observed with the dual opioid agonist-NK1 receptor antagonist SBCHM01.
Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database
Authors: Lim Poh‐Lian , Zhou Jialun , Ditangco Rossana A , Law Matthew G , Sirisanthana Thira , Kumarasamy Nagalingeswaran , Chen Yi‐Ming A , Phanuphak Praphan , Lee Christopher KC , Saphonn Vonthanak , Oka Shinichi , Zhang Fujie , Choi Jun Y , Pujari Sanjay , Kamarulzaman Adeeba , Li Patrick CK , Merati Tuti P , Yunihastuti Evy , Messerschmidt Liesl , Sungkanuparph Somnuek ,   the TREAT Asia HIV Observational Database
Published: January 2012

Background

Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality.

Methods

TAHOD patients with prospective follow up had data extracted for prophylaxis using co‐trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random‐effect Poisson regression models.

Results

There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co‐trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person‐years) and 169 died from all causes (1.36/100 person‐years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person‐years.

Conclusions

Approximately two‐thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under‐diagnosed, these data suggest that prophylaxis is associated with important survival benefits.
Short‐term risk of anaemia following initiation of combination antiretroviral treatment in HIV‐infected patients in countries in sub‐Saharan Africa, Asia‐Pacific, and central and South America
Authors: Zhou Jialun , Jaquet Antoine , Bissagnene Emmanuel , Musick Beverly , Wools‐Kaloustian Kara , Maxwell Nicola , Boulle Andrew , Wehbe Firas , Masys Daniel , Iriondo‐Perez Jeniffer , Hemingway‐Foday Jay , Law Matthew ,   the western Africa, eastern Africa, southern Africa, Caribbean and central and South America, and Asia Pacific regions of the International Epidemiologic Databases to Evaluate AIDS (IeDEA)
Published: January 2012

Background

The objective was to examine the short‐term risk and predictors of anaemia following initiation of combination antiretroviral therapy (cART) in HIV‐infected patients from the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian‐Pacific, and Caribbean and Central and South America regions of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration.

Methods

Anaemia was defined as haemoglobin of < 10 g/dL. Patients were included if they started cART with three or more drugs, had prior haemoglobin of > = 10 g/dL, and had one or more follow‐up haemoglobin tests. Factors associated with anaemia up to 12 months were examined using Cox proportional hazards models and stratified by IeDEA region.

Results

Between 1998 and 2008, 19,947 patients initiated cART with baseline and follow‐up haemoglobin tests (7358, 7289, 2853, 471, 1550 and 426 in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian‐Pacific, and Caribbean and Central and South America regions, respectively). At initiation, anaemia was found in 45% of Western Africa patients, 29% of Eastern Africa patients, 21% of Southern Africa patients, 36% of Central Africa patients, 15% of patients in Asian‐Pacific and 14% of patients in Caribbean and Central and South America. Among patients with haemoglobin of > = 10 g/dL at baseline (13,445), the risks of anaemia were 18.2, 6.6, 9.7, 22.9, 11.8 and 19.5 per 100 person‐years in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian, and Caribbean and Central and South America regions, respectively. Factors associated with anaemia were female sex, low baseline haemoglobin level, low baseline CD4 count, more advanced disease stage, and initial cART containing zidovudine.

Conclusions

In data from 34 cohorts of HIV‐infected patients from sub‐Saharan Africa, Central and South America, and Asia, the risk of anaemia within 12 months of initiating cART was moderate. Routine haemoglobin monitoring was recommended in patients at risk of developing anaemia following cART initiation.
Periodontal status of HIV-infected patients undergoing antiretroviral therapy compared to HIV-therapy naive patients: a case control study
Authors: Fricke Ulrich , Geurtsen Werner , Staufenbiel Ingmar , Rahman Alexander
Published: January 2012

Background

Although severe oral opportunistic infections decreased with the implementation of highly active antiretroviral therapy, periodontitis is still a commonly described problem in patients infected with human immunodeficiency virus (HIV). The objective of the present investigation was to determine possible differences in periodontal parameters between antiretroviral treated and untreated patients.

Methods

The study population comprised 80 patients infected with HIV divided into two groups. The first group was receiving antiretroviral therapy while the second group was therapy naive. The following parameters were examined: probing pocket depth, gingival recession, clinical attachment level, papilla bleeding score, periodontal screening index and the index for decayed, missed and filled teeth. A questionnaire concerning oral hygiene, dental care and smoking habits was filled out by the patients.

Results

There were no significant differences regarding the periodontal parameters between the groups except in the clinical marker for inflammation, the papilla bleeding score, which was twice as high (P < 0.0001) in the antiretroviral untreated group (0.58 ± 0.40 versus 1.02 ± 0.59). The participants of this investigation generally showed a prevalence of periodontitis comparable to that in healthy subjects. The results of the questionnaire were comparable between the two groups.

Conclusion

There is no indication for advanced periodontal damage in HIV-infected versus non-infected patients in comparable age groups. Due to their immunodeficiency, HIV-infected patients should be monitored closely to prevent irreversible periodontal damage. Periodontal monitoring and early therapy is recommended independent of an indication for highly active antiretroviral therapy.
Validation of the Gail model for predicting individual breast cancer risk in a prospective nationwide study of 28,104 Singapore women
Authors: Chay Wen Yee , Ong Whee Sze , Tan Puay Hoon , Jie Leo Nicholas Qi , Ho Gay Hui , Wong Chia Siong , Chia Kee Seng , Chow Khuan Yew , Tan MinHan , Ang Peter
Published: January 2012

Introduction

The Gail model (GM) is a risk-assessment model used in individual estimation of the absolute risk of invasive breast cancer, and has been applied to both clinical counselling and breast cancer prevention studies. Although the GM has been validated in several Western studies, its applicability outside North America and Europe remains uncertain. The Singapore Breast Cancer Screening Project (SBCSP) is a nation-wide prospective trial of screening mammography conducted between Oct 1994 and Feb 1997, and is the only such trial conducted outside North America and Europe to date. With the long-term outcomes from this study, we sought to evaluate the performance of GM in prediction of individual breast cancer risk in a Asian developed country.

Methods

The study population consisted of 28,104 women aged 50 to 64 years who participated in the SBSCP and did not have breast cancer detected during screening. The national cancer registry was used to identify incident cases of breast cancer. To evaluate the performance of the GM, we compared the expected number of invasive breast cancer cases predicted by the model to the actual number of cases observed within 5-year and 10-year follow-up. Pearson's Chi-square test was used to test the goodness of fit between the expected and observed cases of invasive breast cancers.

Results

The ratio of expected to observed number of invasive breast cancer cases within 5 years from screening was 2.51 (95% confidence interval 2.14 - 2.96). The GM over-estimated breast cancer risk across all age groups, with the discrepancy being highest among older women aged 60 - 64 years (E/O = 3.53, 95% CI = 2.57-4.85). The model also over-estimated risk for the upper 80% of women with highest predicted risk. The overall E/O ratio for the 10-year predicted breast cancer risk was 1.85 (1.68-2.04).

Conclusions

The GM over-predicts the risk of invasive breast cancer in the setting of a developed Asian country as demonstrated in a large prospective trial, with the largest difference seen in older women aged between 60 and 64 years old. The reason for the discrepancy is likely to be multifactorial, including a truly lower prevalence of breast cancer, as well as lower mammographic screening prevalence locally.
Phospho-ibuprofen (MDC-917) suppresses breast cancer growth: an effect controlled by the thioredoxin system
Authors: Sun Yu , Rowehl Leahana M , Huang Liqun , Mackenzie Gerardo G , Vrankova Kvetoslava , Komninou Despina , Rigas Basil
Published: January 2012

Introduction

We have recently synthesized phospho-ibuprofen (P-I; MDC-917), a safer derivative of ibuprofen, which has shown anti-cancer activity. We investigated its efficacy and mechanism of action in the treatment of breast cancer in preclinical models.

Methods

We evaluated the anti-breast-cancer efficacy of P-I alone or incorporated into liposomes (Lipo-P-I) in human estrogen receptor-positive (MCF-7) and triple-negative, i.e., estrogen receptor-negative, progesterone receptor-negative and HER2-negative (MDA-MB231) breast cancer cell lines - as they represent the most frequent (estrogen receptor-positive) and the most difficult-to-treat (triple-negative) subtypes of breast cancer - and their xenografts in nude mice. We assessed the effect of P-I on the levels of reactive oxygen nitrogen species in response to P-I using molecular probes, on the thioredoxin system (expression and redox status of thioredoxin-1 (Trx-1) and thioredoxin reductase activity), on cyclooxygenase 2, NF-κB and mitogen-activated protein kinase cell signaling; and on the growth of xenografts with stably knocked-down Trx-1.

Results

Compared with controls, P-I 400 mg/kg/day inhibited the growth of MDA-MB231 xenografts by 266%, while the growth of MCF-7 xenografts was inhibited 51% byP-I 300 mg/kg/day and 181% by Lipo-P-I 300 mg/kg/day. In both cell lines, P-I induced oxidative stress and suppressed the thioredoxin system (oxidized Trx-1 and decreased its expression; inhibited thioredoxin reductase activity). These changes triggered downstream redox signaling: the activity of NF-κB was suppressed and the Trx-1-ASK1 complex was dissociated, activating the p38 and JNK mitogen-activated protein kinase cascades. Trx-1 knockdown abrogated the anti-cancer effect of P-I in vitro and in vivo.

Conclusion

P-I is safe and effective against breast cancer. Liposomal formulation enhances its efficacy; the effect is heavily dependent on the induction of oxidative stress and the suppression of the thioredoxin system. P-I merits further evaluation as an agent for the treatment of breast cancer.
Uberon, an integrative multi-species anatomy ontology
Authors: Mungall Christopher J , Torniai Carlo , Gkoutos Georgios V , Lewis Suzanna E , Haendel Melissa A
Published: January 2012

We present Uberon, an integrated cross-species ontology consisting of over 6,500 classes representing a variety of anatomical entities, organized according to traditional anatomical classification criteria. The ontology represents structures in a species-neutral way and includes extensive associations to existing species-centric anatomical ontologies, allowing integration of model organism and human data. Uberon provides a necessary bridge between anatomical structures in different taxa for cross-species inference. It uses novel methods for representing taxonomic variation, and has proved to be essential for translational phenotype analyses. Uberon is available at http://uberon.org
ARID5B Genetic Polymorphisms Contribute to Racial Disparities in the Incidence and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia
Authors: Xu Heng , Cheng Cheng , Devidas Meenakshi , Pei Deqing , Fan Yiping , Yang Wenjian , Neale Geoff , Scheet Paul , Burchard Esteban G. , Torgerson Dara G. , Eng Celeste , Dean Michael , Antillon Frederico , Winick Naomi J. , Martin Paul L. , Willman Cheryl L. , Camitta Bruce M. , Reaman Gregory H. , Carroll William L. , Loh Mignon , Evans William E. , Pui Ching-Hon , Hunger Stephen P. , Relling Mary V. , Yang Jun J.
Published: January 2012

Purpose

Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome.

Patients and Methods

We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials.

Results

Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10−20 in whites; P = 1 × 10−6 in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10−8). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics.

Conclusion

ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.
ASYMMETRIC-LEAVES2 and an ortholog of eukaryotic NudC domain proteins repress expression of AUXIN-RESPONSE-FACTOR and class 1 KNOX homeobox genes for development of flat symmetric leaves in Arabidopsis
Authors: Ishibashi Nanako , Kanamaru Kyoko , Ueno Yoshihisa , Kojima Shoko , Kobayashi Tetsuo , Machida Chiyoko , Machida Yasunori
Published: January 2012

Leaf primordia form around the shoot apical meristem, which consists of indeterminate stem cells. Upon initiation of leaf development, adaxial-abaxial patterning is crucial for appropriate lateral expansion, via cellular proliferation, and the formation of flat symmetric leaves. Many genes that specify such patterning have been identified, but regulation by upstream factors of the expression of relevant effector genes remains poorly understood. In Arabidopsis thaliana, ASYMMETRIC LEAVES2 (AS2) and AS1 play important roles in repressing transcription of class 1 KNOTTED1-like homeobox (KNOX) genes and leaf abaxial-determinant effector genes. We report here a mutation, designated enhancer of asymmetric leaves2 and asymmetric leaves1 (eal), that is associated with efficient generation of abaxialized filamentous leaves on the as2 or as1 background. Levels of transcripts of many abaxial-determinant genes, including ETTIN (ETT)/AUXIN RESPONSE FACTOR3 (ARF3), and all four class 1 KNOX genes were markedly elevated in as2 eal shoot apices. Rudimentary patterning in as2 eal leaves was suppressed by the ett mutation. EAL encodes BOBBER1 (BOB1), an Arabidopsis ortholog of eukaryotic NudC domain proteins. BOB1 was expressed in plant tissues with division potential and bob1 mutations resulted in lowered levels of transcripts of some cell-cycle genes and decreased rates of cell division in shoot and root apices. Coordinated cellular proliferation, supported by BOB1, and repression of all class 1 KNOX genes, ETT/ARF3 by AS2 (AS1) and BOB1 might be critical for repression of the indeterminate state and of aberrant abaxialization in the presumptive adaxial domain of leaf primordia, which might ensure the formation of flat symmetric leaves.
Recognition of a C–C Mismatch in a DNA Duplex Using a Fluorescent Small Molecule with Application for “Off–On” Discrimination of C/G Mutation
Authors: Hu Liangliang , Wang Yunxiang , Wang Wei , Gao Qiang , Qi Honglan , Zhang Chengxiao
Published: January 2012

The fluorescent small molecule 2-amino-7-methyl-1,8-naphthyridine (AMND) can selectively bind to a cytosine (C) at a C–C mismatch in double-stranded DNA (dsDNA). The interactions between AMND and C–C mismatch-containing dsDNA were investigated by measuring ultraviolet (UV) absorption as a function of temperature to obtain melting curves as well as circular dichroism and fluorescence spectra. Results show that AMND strongly stabilizes C–C mismatch-containing dsDNA, whereas fully matched duplexes are not stabilized under the same conditions. The fluorescence of AMND was efficiently quenched when it was bound to a C–C mismatch in dsDNA. Binding constants ( K11), obtained by fluorescence titration, were 1.2 × 105 M−1. Although sensing functions depend on the sequences flanking the mismatch site, the change in AMND fluorescence intensity can be utilized to detect the C–C mismatch-containing dsDNA. Accordingly, discrimination of the C/G mutation in the model sequence ( PGR gene rs1255998) was achieved by visualizing fluorescence of AMND. A probe DNA molecule was designed to contain a C opposite the C/G base in the target DNA, and this probe was used to hybridize the target DNA. The fluorescence of AMND was “on” for a C–G match, while the fluorescence was “off” for a C–C mismatch. This assay is simple and does not require DNA labeling.
Femtosecond Stimulated Raman Spectroscopy Using a Scanning Multichannel Technique
Authors: Challa J. Reddy , Du Yong , McCamant David W.
Published: January 2012

A scanning multichannel technique (SMT) has been implemented in femtosecond stimulated Raman spectroscopy (FSRS). By combining several FSRS spectra detected at slightly different positions of the spectrograph via SMT, we have eliminated the systematic noise patterns (“fixed pattern noise”) due to the variation in sensitivity and noise characteristics of the individual charge-coupled device (CCD) pixels. In nonresonant FSRS, solvent subtraction can effectively remove the systematic noise pattern even without SMT. However, in the case of resonant FSRS, we show that a similar solvent subtraction procedure is ineffective at removing the noise patterns without SMT. Application of SMT results in averaged FSRS spectra with improved signal-to-noise ratios that approach the shot-noise limit.
Refractive-Index Matching Avoids Local Field Corrections and Scattering Bias in Solid-State Na2SO4 Ultraviolet Raman Cross-Section Measurements
Authors: Wang Luling , Asher Sanford A.
Published: January 2012

We report a refractive-index matching method to measure nonabsorbing solid ultraviolet (UV) Raman cross-sections that avoids the local field correction and interface scattering of incident light. We used refractiveindex-matched chloroform as an internal standard to determine the solid-state 995 cm−1 Na2SO4 244 nm Raman cross-sections. The pure liquid chloroform 668 cm−1 244 nm Raman cross-section was determined by using acetonitrile as an internal standard and by calculating the local field corrections for the observed Raman intensities. Our measured 244 nm UV Raman cross-section of the solid-state 995 cm−1 SO42– band of 1.97 ± 0.07 × 10−28 cm2/(molc·sr) is about half of its aqueous solution Raman cross-section, indicating interactions between the sulfate species in the solid that decrease the Raman polarizability.
Effects of Metallic, Semiconducting, and Insulating Substrates on the Coupling Involving Radiative Polaritons in Thin Oxide Films
Authors: Vincent-Johnson Anita J. , Vasquez Kyle A. , Scarel Giovanna , Hammonds James S. , Francoeur Mathieu
Published: January 2012

Through simulations, this work explores the effects of conducting, semiconducting, and insulating substrates on the absorption of infrared radiation by radiative polaritons in oxide layers with thicknesses that range from 30 nm to 9 μm. Using atomic layer deposition, oxide layers can be formed in the nanometer scale. Our results suggest that the chemistry and conductivity of the substrate determine the amount of absorption by radiative polaritons in oxide layers thinner than the skin depth. The effects of the chemistry and conductivity of the substrate are especially effective for oxide films thinner than about 250 nm, which we label as the substrate sensitive thickness of the oxide film.
Speciation of U(VI) sorbed onto ZrP2O7 in the presence of citric and oxalic acid
Authors: García-González N. , Ordoñez-Regil E. , Almazán-Torres M. G. , Solis Dora , Simoni E.
Published: January 2012

In the field of nuclear waste management, prediction of radionuclide migration through the geosphere has to take into account the effects of organic matter. This work deals with the effects of organic acids (citric and oxalic acid) on speciation of uranium(VI) sorbed onto zirconium diphosphate (ZrP2O7). Surface properties of zirconium diphosphate and its uranium(VI) sorption capability in the presence and absence of organic acids were previously studied. The preliminary study suggested that organic acids take part in the sorption equilibria. In order to understand the interactions between organic ligands (citrate or oxalate), uranium(VI) and zirconium diphosphate, a luminescence spectroscopy study was carried out. Luminescence measurements indicated that only one uranium(VI) surface complex is formed when citric or oxalic acid is present. Moreover, the total carbon content in the studied samples indicated that organic ligands remain on the surface when uranium(VI) sorption is carried out. Uranium sorption edges were then fitted with the FITEQL4.0 code [15] and the constant capacitance model (CCM). Spectroscopy information was used to constraint the modeling. The best fit for the U(VI)/citrate/ZrP2O7 and U(VI)/oxalate/ZrP2O7 systems considered the formation of a ternary surface complex.
Compressibility of microporous materials with CHA topology: 2. ALPO-34
Authors: Leardini Lara , Quartieri S. , Martucci A. , Vezzalini G. , Dmitriev Vladimir
Published: January 2012

The HP behavior of ALPO-34 as-synthesized was investigated by means of in-situ synchrotron X-ray powder diffraction, in the frame of a wider project aimed at understanding the role of the framework/extraframework content in the P-induced deformation mechanisms of natural and synthetic microporous materials with CHA framework topology. ALPO-34 compressibility under non-penetrating P-transmitting medium was determined up to 6.0 GPa and upon decompression to P
amb. After an initial large structure deformation at P < 0.4 GPa, a regular volume reduction was observed up to about 3 GPa. Above 3.1 GPa, an abrupt change in the behavior of all cell parameters was observed, accompanied by an evident decrease in compressibility. The isothermal Equation of State (EoS), refined with a II-order Birch–Murnaghan EoS from 0.4 to 3.1 GPa, yielded the following parameters: V
0 = 755(1) Å3, K
0 = 54(3) GPa. No complete X-ray amorphization was achieved up to the highest investigated P value. A complete reversibility of the unit cell parameters was observed upon P release. The compressibility behavior of ALPO-34 was compared with that of the other CHA-type zeolites. The volume reduction observed for natural chabazite, and for SAPO-34 and ALPO-34 as-synthesized, was 6.2%, 9.4%, and 6.0%, respectively. Notwithstanding the presence of morpholine molecules, as a structure directing agent, in the two as-synthesized phases, they exhibited significantly different compressibility. This can be interpreted as due to the octahedral coordination of part of the ALPO-34 framework aluminum, leading to a more rigid framework compared to that of SAPO-34, which contains only tetrahedral aluminum.
The role of the Pb2+ lone electron pair for bond valence sum analysis in mullite-type PbMBO4 (M = Al, Mn and Fe) compounds
Authors: Murshed M. Mangir , Fischer Reinhard X. , Gesing Thorsten M.
Published: January 2012

The bond valence sums (BVS) of the constituent atoms of three series of mullite-type compounds PbMn
x
Al1–x
BO4, PbFe
x
Al1–x
BO4 and PbMn
x
Fe1–x
BO4 (x = 0 – 1) were analyzed with particular emphasis on lead. While the formal BVS of one bridging oxygen atom in the edge-sharing MO6 octahedron was found to be under-bonded, the other bridging atom is over-bonded. The lead atom showed always an over-bonded nature throughout the series and exhibited a different bonding strength than that of the expected valence. The stereoactivity of the 6s
2 lone electron pair (LEP) of the Pb2+ cation was monitored in terms of the absolute value of the eccentricity parameter (|Φ

i
|). Both calculated BVS and bond valence parameter (r
0i
) of Pb2+ cation showed a linear correlation with |Φ

i
|, thus corroborated the Wang–Liebau [Z. Kristallogr. 211 (1996) 437] hypothesis concerning the influence of lone-pair electrons on bond-valence parameters.
Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenoma kindreds
Authors: Tichomirowa Maria A , Lee Misu , Barlier Anne , Daly Adrian F , Marinoni Ilaria , Jaffrain-Rea Marie-Lise , Naves Luciana A , Rodien Patrice , Rohmer Vincent , Faucz Fabio Rueda , Caron Philippe , Estour Bruno , Lecomte Pierre , Borson-Chazot Françoise , Penfornis Alfred , Yaneva Maria , Guitelman Mirtha , Castermans Emily , Verhaege Catherine , Wémeau Jean-Louis , Tabarin Antoine , Fajardo Montañana Carmen , Delemer Brigitte , Kerlan Veronique , Sadoul Jean-Louis , Cortet Rudelli Christine , Archambeaud Françoise , Zacharieva Sabine , Theodoropoulou Marily , Brue Thierry , Enjalbert Alain , Bours Vincent , Pellegata Natalia S , Beckers Albert
Published: January 2012

Familial isolated pituitary adenoma (FIPA) occurs in families and is unrelated to multiple endocrine neoplasia type 1 and Carney complex. Mutations inAIPaccount only for 15–25% of FIPA families.CDKN1Bmutations cause MEN4 in which affected patients can suffer from pituitary adenomas. With this study, we wanted to assess whether mutations inCDKN1Boccur among a large cohort ofAIPmutation-negative FIPA kindreds. Eighty-eightAIPmutation-negative FIPA families were studied and 124 affected subjects underwent sequencing ofCDKN1B. Functional analysis of putativeCDKN1Bmutations was performed usingin silicoandin vitroapproaches. GermlineCDKN1Banalysis revealed two nucleotide changes: c.286A>C (p.K96Q) and c.356T>C (p.I119T).In vitro, the K96Q change decreased p27 affinity for Grb2 but did not segregate with pituitary adenoma in the FIPA kindred. The I119T substitution occurred in a female patient with acromegaly. p27I119Tshows an abnormal migration pattern by SDS–PAGE. Three variants (p.S56T, p.T142T, and c.605+36C>T) are likely nonpathogenic becauseIn vitroeffects were not seen. In conclusion, two patients had germline sequence changes inCDKN1B, which led to functional alterations in the encoded p27 proteinsin vitro. Such rareCDKN1Bvariants may contribute to the development of pituitary adenomas, but their low incidence and lack of clear segregation with affected patients makeCDKN1Bsequencing unlikely to be of use in routine genetic investigation of FIPA kindreds. However, further characterization of the role ofCDKN1Bin pituitary tumorigenesis in these and other cases could help clarify the clinicopathological profile of MEN4.
Molecular and functional characterization of cionin receptors in the ascidian, Ciona intestinalis: the evolutionary origin of the vertebrate cholecystokinin/gastrin family
Authors: Sekiguchi Toshio , Ogasawara Michio , Satake Honoo
Published: January 2012

Cholecystokinin (CCK) and gastrin are vertebrate brain–gut peptides featured by a sulfated tyrosine residue and a C-terminally amidated tetrapeptide consensus sequence. Cionin, identified in the ascidian,Ciona intestinalis, the closest species to vertebrates, harbors two sulfated tyrosines and the CCK/gastrin consensus tetrapeptide sequence. While a putative cionin receptor,cior, was cloned, the ligand–receptor relationship between cionin and CioR remains unidentified. Here, we identify two cionin receptors, CioR1 and CioR2, which are the aforementioned putative cionin receptor and its novel paralog respectively. Phylogenetic analysis revealed that CioRs are homologous to vertebrate CCK receptors (CCKRs) and diverged from a common ancestor in theCiona-specific lineage. Cionin activates intracellular calcium mobilization in cultured cells expressing CioR1 or CioR2. Monosulfated and nonsulfated cionin exhibited less potent or no activity, indicating that CioRs possess pharmacological features similar to the vertebrate CCK-specific receptor CCK1R, rather than its subtype CCK2R, given that a sulfated tyrosine in CCK is required for binding to CCK1R, but not to CCK2R. Collectively, the present data reveal that CioRs share a common ancestor with vertebrate CCKRs and indicate that CCK and CCK1R form the ancestral ligand–receptor pair in the vertebrate CCK/gastrin system. Cionin is expressed in the neural complex, digestive organs, oral siphon and atrial siphons, whereas the expression ofciors was detected mainly in these tissues and the ovary. Furthermore, cioninergic neurons innervate both of the siphons. These results suggest that cionin is involved in the regulation of siphonal functions.
Intrapartum Temperature Elevation, Epidural Use, and Adverse Outcome in Term Infants
Authors: Greenwell Elizabeth A. , Wyshak Grace , Ringer Steven A. , Johnson Lise C. , Rivkin Michael J. , Lieberman Ellice
Published: January 2012

OBJECTIVES:

To examine the association of intrapartum temperature elevation with adverse neonatal outcome among low-risk women receiving epidural analgesia and evaluate the association of epidural with adverse neonatal outcome without temperature elevation.

METHODS:

We studied all low-risk nulliparous women with singleton pregnancies ≥37 weeks delivering at our hospital during 2000, excluding pregnancies where infants had documented sepsis, meningitis, or a major congenital anomaly. Neonatal outcomes were compared between women receiving (n = 1538) and not receiving epidural analgesia (n = 363) in the absence of intrapartum temperature elevation (≤99.5°F) and according to the level of intrapartum temperature elevation within the group receiving epidural (n = 2784). Logistic regression was used to evaluate neonatal outcome while controlling for confounders.

RESULTS:

Maternal temperature >100.4°F developed during labor in 19.2% (535/2784) of women receiving epidural compared with 2.4% (10/425) not receiving epidural. In the absence of intrapartum temperature elevation (≤99.5°F), no significant differences were observed in adverse neonatal outcomes between women receiving and not receiving epidural. Among women receiving epidural, a significant linear trend was observed between maximum maternal temperature and all neonatal outcomes examined including hypotonia, assisted ventilation, 1- and 5-min Apgar scores <7, and early-onset seizures. In regression analyses, infants born to women with fever >101°F had a two- to sixfold increased risk of all adverse outcomes examined.

CONCLUSIONS:

The proportion of infants experiencing adverse outcomes increased with the degree of epidural-related maternal temperature elevation. Epidural use without temperature elevation was not associated with any of the adverse outcomes we studied.
Fetal and Maternal Candidate Single Nucleotide Polymorphism Associations With Cerebral Palsy: A Case-Control Study
Authors: O’Callaghan Michael E. , MacLennan Alastair H. , Gibson Catherine S. , McMichael Gai L. , Haan Eric A. , Broadbent Jessica L. , Goldwater Paul N. , Painter Jodie N. , Montgomery Grant W. , Dekker Gus A. ,   for the Australian Collaborative Cerebral Palsy Research Group
Published: January 2012

OBJECTIVE:

Previous studies have suggested associations between certain genetic variants and susceptibility to cerebral palsy (CP). This study was designed to assess established and novel maternal and child genetic and epidemiologic risk factors for CP along with their interactions.

METHODS:

DNA from 587 case and 1154 control mother-child pairs was analyzed. A panel of 35 candidate single nucleotide polymorphisms (SNPs) were examined and included SNPs in genes associated with (1) thrombophilia, (2) inflammation, and (3) risk factors for CP (eg, preterm birth). Comparisons were specified a priori and made by using a χ2 test.

RESULTS:

There were 40 fetal and 28 maternal associations with CP when analyzed by CP subtype, gestational age, genotypes of apolipoprotein E, and haplotypes of mannose-binding-lectin. After Bonferroni correction for multiple testing, no fetal or maternal candidate SNP was associated with CP or its subtypes. Only fetal carriage of prothrombin gene mutation remained marginally associated with hemiplegia in term infants born to mothers with a reported infection during pregnancy. Odds ratio directions of fetal SNP associations were compared with previously reported studies and confirmed no trend toward association.

CONCLUSIONS:

Except for the prothrombin gene mutation, individual maternal and fetal SNPs in our candidate panel were not found to be associated with CP outcome. Past reported SNP associations with CP were not confirmed, possibly reflecting type I error from small numbers and multiple testing in the original reports.
Value of Follow-up Examinations of Children and Adolescents Evaluated for Sexual Abuse and Assault
Authors: Gavril Amy R. , Kellogg Nancy D. , Nair Prakash
Published: January 2012

OBJECTIVE:

The purpose of this study was to determine whether follow-up examinations of suspected victims of child sexual abuse influence medical diagnosis or treatment.

METHODS:

A retrospective chart review of patients with initial and follow-up examinations (examinations 1 and 2, respectively) over a 5-year study period was conducted. Patient and abuse characteristics, interval between examinations and abuse, and examiner experience levels were collected; examination findings and test results for sexually transmitted infections (STIs) were compared for examinations 1 and 2.

RESULTS:

Among 727 patients, examination 2 resulted in a change in interpretation of trauma likelihood in 129 (17.7%) patients and identified STIs in 47 (6.5%) patients. Changes in trauma likelihood and detection of additional STIs during follow-up examinations were more likely in adolescent, female, and sexually active patients and those with a history of genital−genital contact, unknown examination 1 findings, or drug-facilitated sexual assault. Although examination 2 was less likely to affect the interpretation of trauma likelihood and STIs in preadolescent patients, a change in interpretation of trauma likelihood was noted for 49 (15.5%) of these patients, and 16 (5.1%) were diagnosed with a new STI on examination 2. The level of clinician experience during examination 1 did affect the likelihood of changes in examination findings during examination 2.

CONCLUSIONS:

Follow-up examinations by specialists affected the interpretation of trauma and detection of STIs in ∼23% of pediatric patients undergoing sexual abuse assessments.