bluuebunny/crossref_metadata_2025 huggingface dataset:
The water footprint of land grabbing
Authors: Rulli Maria Cristina , D'Odorico Paolo
Published: November 2013

The increasing global demand for food, fibers, and biofuels has made investments in agriculture a priority for some governments and corporations eager to expand their agricultural production while securing good profits. Here we calculate the water appropriation associated with land deals at different negotiation and implementation stages. Using estimates of actual and potential evapotranspiration for the crops planted in the acquired land, we calculate the green and blue water appropriated by land investors under a variety of irrigation scenarios. We also determine the grey water footprint as the amount of water required to dilute to allowable standards the pollution resulting from fertilizer applications. We found that about 380 × 109 m3 yr−1 of rainwater is appropriated with the 43 million ha of reported contract area acquired by agri‐investors (>240 × 109 m3 yr−1 in the 29 million ha of foreign acquisitions only). This water would be sufficient to feed ≈ 300–390 million people.
Origins of wind‐driven intraseasonal sea level variations in the North Indian Ocean coastal waveguide
Authors: Suresh I. , Vialard J. , Lengaigne M. , Han W. , McCreary J. , Durand F. , Muraleedharan P. M.
Published: November 2013

In this paper, we show that a linear, continuously stratified ocean model reproduces observed wind‐driven intraseasonal sea level variability in the coastal waveguide of the Northern Indian Ocean (NIO). Sensitivity experiments with intraseasonal wind forcing selectively applied in the equatorial region, Bay of Bengal, and Arabian Sea show that a large part of the basin‐scale sea level variations are driven by zonal wind fluctuations along the equator. Within the NIO coastal waveguide, the contribution of remote equatorial forcing decreases from ~80–90% in the Andaman Sea to ~50% northeast of Sri Lanka and then increases to ~60–70% along the west coast of India. During the southwest monsoon, intraseasonal wind variations become stronger over the NIO, resulting in a larger contribution of local wind forcing to sea level variability along the west (up to 60%) and east (up to 40%) coasts of India.
Downdrafts in the near cloud environment of deep convective updrafts
Authors: Glenn Ian B. , Krueger Steven K.
Published: November 2013

We used a large domain, large eddy simulation (LES) of tropical deep convection to investigate the properties of 3‐D cloudy updrafts and the near cloud environment (NCE) directly adjacent to them. We show for the first time that the properties of the air in the NCE of deep convection imply the existence of a subsiding shell like that which is already known to exist around shallow convection. We show that there is negative buoyancy in the NCE due to mixing and evaporative cooling, and that there is significant negative net mass flux in the NCE relative to the cloudy updraft mass flux. This demonstrates that the “subsiding shell” viewpoint of the NCE region of shallow cumulus updrafts can and should be applied to deep convective updrafts as well.
Watershed size effects on applicability of regression‐based methods for fluvial loads estimation
Authors: Kumar Saurav , Godrej Adil N. , Grizzard Thomas J.
Published: November 2013

Fluvial loads for total nitrogen, total oxidized nitrogen, total phosphorus, orthophosphate phosphorus, and total suspended solids were estimated for three watersheds of different sizes using a regression‐based method and compared with loads computed by a method based on direct hydrologic and water quality observations. Statistically significant differences between the fluvial loads estimated by the two methods were observed in all cases. Using the direct method as the basis for comparison, the regression method was found to underpredict the annual fluvial load for the watersheds analyzed. A representative “magnitude‐of‐difference” measure was computed. The larger watershed (area > 104 km2) had a lower magnitude‐of‐difference compared to the two smaller watersheds (area ∼102 km2). The five constituents analyzed also had statistically significant effect on the magnitude‐of‐difference, with higher magnitude‐of‐difference observed for total suspended solids and total phosphorus compared to other parameters. For the watersheds analyzed, estimates for the magnitudes‐of‐difference obtained by long‐term fluvial load analysis (15 years for larger, and 9 and 12 years for two smaller watersheds) may be evaluated by shorter‐term comparisons. The time required to obtain a stable magnitude‐of‐difference was found to vary with the watershed size and the constituent of interest in the study watersheds. Although the results from this study represent the watersheds analyzed and are not likely to be directly applicable for other watersheds, the comparison between fluvial loads estimated by regression and intensive sampling may be applied to assess the applicability of the regression method in other watersheds.
Fenestrane in der Synthese: einzigartige und inspirierende Grundgerüste
Authors: Boudhar Aicha , Charpenay Mélanie , Blond Gaëlle , Suffert Jean
Published: November 2013

Das Gerüst von Fenestranen ist einzigartig, da es vier kondensierte Ringe und ein verzerrtes vierfach koordiniertes zentrales Kohlenstoffatom aufweist, dessen Bindungswinkel größer als die regulären 109°28′′ sind. In diesem Kurzaufsatz wird eine detaillierte Übersicht über die Entwicklungen bezüglich dieser Verbindungsklasse, einschließlich ihrer Synthese, für den Zeitraum seit 2006 gegeben. In den vergangenen Jahren wurden Naturstoffe, die als Heterofenestrane klassifiziert werden können, isoliert, und deren Synthesen werden ebenfalls diskutiert.
Catching an Entatic State—A Pair of Copper Complexes
Authors: Hoffmann Alexander , Binder Stephan , Jesser Anton , Haase Roxana , Flörke Ulrich , Gnida Manuel , Salomone Stagni Marco , Meyer‐Klaucke Wolfram , Lebsanft Benjamin , Grünig Lara Elena , Schneider Simon , Hashemi Maryam , Goos Arne , Wetzel Alina , Rübhausen Michael , Herres‐Pawlis Sonja
Published: November 2013

The structures of two types of guanidine–quinoline copper complexes have been investigated by single‐crystal X‐ray crystallography, K‐edge X‐ray absorption spectroscopy (XAS), resonance Raman and UV/Vis spectroscopy, cyclic voltammetry, and density functional theory (DFT). Independent of the oxidation state, the two structures, which are virtually identical for solids and complexes in solution, resemble each other strongly and are connected by a reversible electron transfer at 0.33 V. By resonant excitation of the two entatic copper complexes, the transition state of the electron transfer is accessible through vibrational modes, which are coupled to metal–ligand charge transfer (MLCT) and ligand–metal charge transfer (LMCT) states.
Noise stress and the development of benzodiazepine dependence in the rat
Authors: File Sandra E. , Fernandes Cathy
Published: November 2013

Rats housed in conditions of noise stress were given daily injections of diazepam (4 mg/kg). Significant tolerance developed to the sedative effects within 5 days of treatment, as measured by head dipping and motor activity in the holeboard and by the number of closed arm entries in the plus‐maze. These results are in agreement with other reports of rapid tolerance to sedative effects. However, in contrast to the usual finding of tolerance to anxiolytic actions after 2–3 weeks of treatment, in this study no tolerance developed after 23 days of treatment to diazepam's anxiolytic effects in the plus‐maze. On withdrawal front the 23 days of diazepam treatment, there was no anxiogenic response in the plus‐maze. Therefore, it seems that when chronic administration of diazepam is accompanied by chronic stress, tolerance does not occur to the anxiolytic effects, although it does develop to the sedative effects. Anxiety 1:8–12 (1994). © 1994 Wiley‐Liss, Inc.
Panic attacks, complex partial seizures, and multiple meningiomas
Authors: Nickel1 P. V.
Published: November 2013

A 39‐year‐old woman presented with typical panic disorder symptoms of two years duration. Imipramine (IMI) treatment yielded complete remission of her symptoms for three years. At that time, however, her symptoms recurred. Neither increasing the IMI dose nor an adequate trial of fluoxetine controlled her symptoms., Further history revealed subtle changes in her symptoms suggestive of complex partial seizures. Scalp EEG was normal, but an MRI revealed multiple meningiomas. Her symptoms remitted completely on carbamazepine. This case illustrates the phenomenologic overlap between panic attacks and complex partial seizures, and a neuroanatomic overlap between the two syndromes is hypothesized. Anxiety 1:40‐42 (1994). © 1994 Wiley‐Liss, Inc.
Serum interleukin‐2 and soluble interleukin‐2 receptor levels in generalized social phobia
Authors: Rapaport Mark Hyman , Stein Murray B.
Published: November 2013

Alterations in immune function have been described in a variety of psychiatric disorders including schizophrenia and depression; however, we do not know of any research involving social phobia and the immune system. This preliminary study explores the relationship between social phobia and two well‐established immune parameters, serum interleukin‐2 (IL‐2) levels, a potent immune and central nervous system modulator, and soluble interleukin‐2 receptors (SIL‐2Rs), a well‐known marker of T‐cell activation. Fifteen subjects with generalized social phobia and 15 healthy volunteers had serum IL‐2, and SIL‐2Rs measured by enzyme‐linked immunoassay. Subjects with social phobia and normal volunteers had similar mean serum IL‐2 and SIL‐2R levels. The data suggest that, unlike other psychiatric disorders, these immune measures may not be used to differentiate patients with generalized social phobia from normal volunteers. Anxiety 1:50–53 (1994). © 1994 Wiley‐Liss, Inc.
Social rhythm in anxiety disorder patients
Authors: Shear M. Katherine , Randall Jeff , Monk Timothy H. , Ritenour Angela , Frank Xin Tu, Ellen , Reynolds Charles , Kupfer David J.
Published: November 2013

The social rhythm metric (SRM) is a self‐report diary instrument, which generates a numerical measure of rhythmicity of daily life behaviors. Depression researchers have proposed that life events cause disruption of social rhythmicity and this leads to disturbance in the sense of well being and to disruption of physiologic rhythmicity known to be related to depressive episodes. We hypothesized that low rhythmicity of daily activities might also be characteristic of anxiety disorder patients. Subjects: Forty‐eight patients who met DSM III‐R criteria for an anxiety disorder were recruited and compared with 41 previously monitored normal controls. Procedures: All patients and controls completed at least two weeks of daily monitoring with the SRM. Anxiety patients underwent structured diagnostic assessment and completed demographic and clinical rating scales. SRM was analyzed according to a previously developed algorithm. Results: Anxiety disorder patients report significantly lower regularity of daily activities than normal controls. The low SRM scores were not accounted for by the presence of comorbid affective disorder. Conclusions: We identify a new type of abnormality in anxiety disorder patients, which has potential clinical as well as theoretical interest. Anxiety 1:90–95 (1994). © 1994 Wiley‐Liss, Inc.
High‐dose subchronic imipramine treatment: Effects on anxiety‐like (conflict) behavior in rats
Authors: Commissaris Randall L. , Hill Timothy J.
Published: November 2013

In the management of both anxiety and depression, agents such as imipramine (IMI) are noted for their 3–5 week delay to onset of clinical effect. A similar delay to onset has been reported for the anxiolytic‐like (i.e., anticonflict) effect of chronic IMI treatment (2.5 mg/kg, BID for 5 weeks) in the Conditioned Suppression of Drinking (CSD) conflict paradigm; similar effects have been reported with other antidepressants and in other conflict procedures. In contrast, in the Forced Swim Test (FST) model of depression, antidepressant‐like effects are reported immediately following subchronic treatment with relatively high doses of these agents (e.g., 30 mg/kg IMI, 3 times in 24 hr). The present study examined the effects of this high‐dose, subchronic treatment with IMI on CSD conflict behavior. Conflict‐trained female Sprague Dawley rats were divided into three groups with comparable pretreatment baselines for shocks received. Treatments (0, 15, and 30 mg/kg IMI) were administered intraperitoneally (IP) at 23, 5, and 1 hr prior to CSD conflict testing on day 1; CSD conflict behavior was then monitored daily (Mon‐Fri) for 5 weeks following treatment. IMI treatment (30 and, to a lesser extent, 15 mg/kg) significantly reduced shocks received (punished responding) and water intake (unpunished responding) on day 1; although water intake was also slightly reduced in both IMI treatment groups for the remainder of test week 1, there was no difference in shocks received between the various treatments for this period. Subjects receiving 30 mg/kg IMI (but not those receiving 15 mg/kg IMI or vehicle) accepted significantly more shocks than controls on weeks 2–4 (maximal increase at week 3) and returned to pretreatment baseline levels by week 5. Thus, subchronic high‐dose treatment with IMI (and perhaps other antidepressants) produces anxiolytic‐like effects which are delayed in nature and persist for several weeks after treatment. Anxiety 1:109–113 (1994/1995). © 1995 Wiley‐Liss, Inc.
Dose‐response effects of intravenous caffeine in normal volunteers
Authors: Nickell P. V. , Uhde Thomas W.
Published: November 2013

The administration of caffeine has been developed as a chemical model for the study of anxiety. However, previous researchers investigating caffeine‐induced anxiety states in humans have administered oral caffeine. In this dose‐response study, we investigated the effects of blindly administered intravenous caffeine (3, 5, and 7 mg/kg) versus placebo in normal control subjects. We report the first series of subjects experiencing olfactory hallucinations (10 of 10 subjects, 24 of 30 infusions) immediately following intravenous caffeine infusion. In addition, consistent with our previous work with oral caffeine, we found dose‐related increases in ratings of anxiety and blood levels of cortisol and lactate. One subject experienced a DSM‐III‐R panic attack. Further questioning revealed that his mother suffers panic attacks. Our findings of olfactory hallucinations are discussed within the context of localized limbic system dysfunction, noting the phenomenologic and possible neuroanatomic overlap between panic disorder and complex partial seizures. Anxiety 1:161–168 (1994/1995). © 1995 Wiley‐Liss, Inc.

This article is a US Government work and, as such, is in the public domain in the United States of America.
Familial transmission of panic disorder: Effect of major depression comorbidity
Authors: Mannuzza Salvatore , Chapman Tim F. , Klein Donald F. , Fyer Abby J.
Published: November 2013

This study assesses the effect of major depressive disorder (MDD) comorbidity on familial transmission of panic disorder (PD). The following questions are addressed: (1) is PD familial, i.e., do relatives of patients with PD show an increased risk for PD? (2) do PD and MDD share a common diathesis, i.e., do relatives of patients with PD without MDD show an increased risk for MDD? (3) is lifetime comorbid PD with MDD conjointly familial, i.e., do relatives of patients with PD and MDD show an increased risk for the combined syndrome? Subjects were: (1) 152 relatives of 54 anxiety clinic patients with PD and MDD; (2) 193 relatives of 72 patients with PD without MDD; (3) 231 relatives of 77 not ill controls. Relatives were interviewed by clinicians, and best estimate DSM‐III‐R diagnoses were formulated by senior staff. Relatives of PD with MDD (13%) and PD without MDD probands (9%) showed significantly higher rates of PD than relatives of controls (3%). Relatives of PD with MDD probands (37%) showed significantly higher rates of MDD than relatives of PD without MDD (24%) and controls (21%), with no difference between the latter two groups. Relatives of PD with MDD probands (9%) showed significantly higher rates of PD with MDD than relatives of PD without MDD (3%) and controls (1%). We conclude that: (1) PD is familial; (2) PD in the absence of MDD does not incur increased risk of MDD to relatives; and (3) PD with MDD may represent a distinct, complex syndrome. Anxiety 1:180–185 (1994/1995). © 1995 Wiley‐Liss, Inc.
Clinical characteristics of familial generalized anxiety disorder
Authors: Kendler Kenneth S. , Neale Michael C. , Kessler Ronald C. , Heath Andrew C. , Eaves Lindon J.
Published: November 2013

The authors seek to determine whether the clinical characteristics of generalized anxiety disorder (GAD) differ in individuals with a high vs. low familial vulnerability to illness. We identified 486 personally interviewed female twins from a population‐based register who had both an interviewed co‐twin and a lifetime history of GAD using modified DSM‐III‐R criteria which required a one‐month minimum duration of illness. We attempted to predict risk for GAD in the co‐twin from the clinical features of the GAD in the proband twin using the Cox proportional hazard model, controlling for year of birth and zygosity. Only two variables uniquely predicted an increased risk for GAD in the co‐twin: number of GAD symptoms endorsed and comorbidity with bulimia. Variables that did not uniquely predict risk of illness in the co‐twin included age at onset, duration of the longest episode and number of episodes. The familial vulnerability to GAD can be meaningfully indexed by clinical features of the syndrome. These results suggest that if the syndrome of GAD is to be narrowed, it would, from a familial perspective, be more valid to increase the minimum number of required symptoms rather than to increase the minimum duration of illness. Anxiety 1:186–191 (1994/1995). © 1995 Wiley‐Liss, Inc.
Increased mRNA for corticotrophin releasing hormone in the amygdala of Fawn‐hooded rats: A potential animal model of anxiety
Authors: Altemus Margaret , Smith Mark A. , Diep Vinh , Aulakh Charanjit S. , Murphy Dennis L.
Published: November 2013

Compared to the outbred Wistar rat strain, the Fawn‐hooded rat strain has several characteristics which suggest that the Fawn‐hooded strain is hyperaroused. Fawn‐hooded rats exhibit more freezing behavior in response to stress, have an increased preference for alcohol, develop adult onset hypertension, and have elevated urinary catecholamine levels. We used quantitative in situ hybridization to investigate central components of the corticotropin releasing hormone (CRH), arginine vasopressin (AVP) and noradrenergic stress response and arousal systems in these rats. We also measured basal corticosterone levels and adrenal weights to assess tonic hypothalamic‐pituitary‐adrenal axis activity. Compared to Wistar rats, Fawn‐hooded rats had significantly increased CRH mRNA in the central nucleus of the amygdala and reduced CRH mRNA in the paraventricular nucleus of the hypothalamus. Fawn‐hooded rats also had reduced AVP mRNA expression in the parvocellular cells of the hypothalamic paraventricular nucleus. There were no differences between strains in glucocorticoid receptor mRNA in the hippocampus or the paraventricular nucleus or in mineralocorticoid receptor mRNA in the hippocampus. There was also no difference between strains in tyrosine hydroxylase mRNA in the locus ceruleus. Finally, adrenal weights were significantly reduced in the Fawn‐hooded rats while basal corticosterone levels were similar in the two strains, which suggests central hypoactivity of the hypothalamic‐pituitary‐adrenal axis in Fawn‐hooded rats compared to Wistar rats. Increased CRH mRNA in the central nucleus of the amygdala and reduced tonic hypothalamic‐pituitary‐adrenal axis activity may play a role in the unique behavioral and physiological characteristics of Fawn‐hooded rats. Anxiety 1:251–257 (1994/1995). © 1995 Wiley‐Liss, Inc.

This article is a US Government work and, as such, is in the public domain in the United States of America.
Peptides and anxiety: A dose‐response evaluation of pentagastrin in healthy volunteers
Authors: McCann Una D. , Slate Shiyoko O. , Geraci Marilla , Uhde Thomas W.
Published: November 2013

A large body of data suggest that brain cholecystokinin (CCK) systems are involved in the regulation of anxiety, and numerous studies have demonstrated that CCK‐4, a CCKB agonist, reliably induces panic attacks in patients with panic disorder. Recently, pentagastrin, a commercially available CCKB agonist, has been reported to have similar anxiogenic properties. To further explore the utility of pentagastrin as a challenge agent and to determine whether its effects are dose‐related, a dose‐response study was conducted in ten healthy volunteers. Pentagastrin (0.2 μg kg, 0.6 μg/kg and 1.0 μg/kg) and inactive placebo were infused over one minute on four separate challenge days in a double‐blind fashion. Subjects received pentagastrin while participating in a structured social interaction task. Repeated measures of anxiety, blood pressure, pulse, ACTH, and cortisol were taken at baseline and postinfusion. Pentagastrin administration led to increases in anxiety, pulse, ACTH, cortisol and physical symptoms of panic, in a dose‐related manner. Participation in the social interaction task led to increases in measures of anxiety as well as increases in pulse and blood pressure. Few differences were found between the 0.2 μg/kg dose of pentagastrin and placebo, or between the 0.6 μg/kg and the 1.0 μg/kg doses of pentagastrin. These findings support the notion that CCK systems are involved in the regulation of anxiety, and suggest that the 0.6 μg/kg dose may be optimal for increasing symptoms of anxiety while minimizing unpleasant side effects. The powerful anxiogenic effects of the social interaction task underscore the importance of contextual variables in challenge studies. Anxiety 1:258–267 (1994/1995). © 1995 Wiley‐Liss, Inc.

This article is a US Government work and, as such, is in the public domain in the United States of America.
Patterns of obsessive compulsive symptoms in tourette subjects are independent of severity
Authors: de Groot Christopher M. , Bornstein Robert A. , Janus Mark‐David , Mavissakalian Matig R.
Published: November 2013

Studies have examined the expression of obsessive compulsive (OC) symptoms in obsessive compulsive disorder (OCD), OCD with co‐occurring Tourette's Syndrome (TS) or chronic motor tic disorder (CMT) and TS alone. In adult samples, there appears to be a relatively consistent OC symptom thematic content that characterizes OCD alone and OCD in conjunction with tics or TS. Previous studies have controlled for the severity of OC symptoms in OCD and TS groups. In the current study, it was our objective to determine whether patterns of OC symptoms in TS are independent of OC symptom severity.

The current exploratory study examined OC symptom expression in a nonclinically based TS sample with a broad range of OC symptoms and severity and a selected clinical OCD sample without TS/tics. Univariate and multivariate statistical analysis explored patterns of OC symptom expression between the two groups.

Similar to previous reports examining OC symptoms in OCD and OCD with TS/tics, subjects with OCD alone were characterized by contamination obsessions and cleaning compulsions. In contrast, TS subjects had more somatic, sexual and symmetry obsessions and more checking, counting and touching/blinking compulsions, independent of OC symptom and tic severity. A discriminant function using obsessive items alone correctly grouped 91.4% of cases.

The current study replicates patterns of OC symptom expression unique to OCD alone. Patterns of OC symptoms, in particular obsessive symptoms, can robustly predict membership in OCD or TS groups, even with a substantial variation in OC symptom severity as measured by the Y‐BOCS score. Anxiety 1:268–274 (1994/1995). © 1995 Wiley‐Liss, Inc.
Development Impacts of Seasonal and Temporary Migration: A Review of Evidence from the Pacific and Southeast Asia
Authors: Gibson John , McKenzie David , Rohorua Halahingano
Published: November 2013

Seasonal and temporary migration programs are widely used around the world, yet there is scant evidence as to their development impacts. Absent such evidence, it is difficult to evaluate whether the proliferation of temporary worker programs in recent years is a useful development. This article reviews studies that attempt to measure impacts of seasonal and temporary migration with a particular focus on evidence from the Pacific and Southeast Asia.
Formation of Periodic γ‐Turns in α/β‐Hybrid Peptides: DFT and NMR Experimental Evidence
Authors: Chandrasekhar Srivari , Rao Kakita Veera Mohana , Seenaiah Mallikanti , Naresh Police , Devi Ambure Sharada , Jagadeesh Bharatam
Published: November 2013

Hybrid peptidic oligomers comprising natural and unnatural amino acid residues that can exhibit biomolecular folding and hydrogen‐bonding mimicry have attracted considerable interest in recent years. While a variety of hybrid peptidic helices have been reported in the literature, other secondary structural patterns such as γ‐turns and ribbons have not been well explored so far. The present work reports the design of novel periodic γ‐turns in the oligomers of 1:1 natural‐α/unnatural trans‐β‐norborenene (TNAA) amino acid residues. Through DFT, NMR, and MD studies, it is convincingly shown that, in the mixed conformational pool, the heterogeneous backbone of the hybrid peptides preferentially adopt periodic 8‐membered (pseudo γ‐turn)/7‐membered (inverse γ‐turn) hydrogen bonds in both polar and non‐polar solvent media. It is observed that the stereochemistry and local conformational preference of the β‐amino acid building blocks have a profound influence on accessing the specific secondary fold. These findings may be of significant relevance for the development of molecular scaffolds that facilitate desired positioning of functional side‐chains.
Synthesis and In Vitro Photodynamic Activities of an Integrin‐Targeting cRGD‐Conjugated Zinc(II) Phthalocyanine
Authors: Ke Mei‐Rong , Ng Dennis K. P. , Lo Pui‐Chi
Published: November 2013

A 1,4‐disubstituted zinc(II) phthalocyanine conjugated with a cyclic Arg‐Gly‐Asp‐D‐Phe‐Lys (cRGDfK) moiety through a triazole linker was prepared and characterized by UV/Vis spectroscopy and high‐resolution ESI‐MS. The conjugate showed a relatively weak fluorescence emission in N,N‐dimethylformamide (ΦF=0.08), but it was a very efficient singlet oxygen generator (ΦΔ=0.80) as a result of the di‐α‐substituted structure. Owing to the presence of the cyclic peptide sequence cRGDfK, which is a well‐known αvβ3‐integrin antagonist, this conjugate exhibited significantly higher cellular uptake toward the αvβ3+ U87‐MG cells compared with the αvβ3− MCF‐7 cells, as determined by flow cytometry and fluorescence microscopy. The photocytotoxicity of this compound against these two cell lines, however, was comparable owing to the similar efficiency of intracellular reactive oxygen species generation. Confocal microscopic studies also revealed that this conjugate localized preferentially in the lysosomes, but not in the nucleus, endoplasmic reticulum, and mitochondria of the U87‐MG cells.
Palladium‐Catalyzed Regio‐ and Stereoselective Chlorothiolation of Terminal Alkynes with Sulfenyl Chlorides
Authors: Iwasaki Masayuki , Fujii Tomoya , Yamamoto Arisa , Nakajima Kiyohiko , Nishihara Yasushi
Published: November 2013

Chlorothiolation of terminal alkynes with sulfenyl chlorides yields anti‐adducts without transition‐metal catalysts. In sharp contrast, transition‐metal‐catalyzed chlorothiolation has not been developed to date, possibly because organosulfur compounds can poison catalyst. Herein, the regio‐ and stereoselective palladium‐catalyzed chlorothiolation of terminal alkynes with sulfenyl chlorides is described. syn‐Chlorothiolation offers a complementary synthetic route to chloroalkenyl sulfides. 2‐Chloroalkenyl sulfides can easily be transformed into various sulfur‐containing products, most of which are often found in natural products and pharmaceuticals.
Identity‐trajectory: Reframing early career academic experience
Authors: McAlpine Lynn , Amundsen Cheryl , Turner Gill
Published: November 2013

Our longitudinal qualitative research program examining doctoral student, post‐PhD researcher and new lecturer experience is situated in an international literature documenting how early career academics learn through experience. In common with others, our work is framed within an identity perspective. What makes our view of identity distinct is a biographical focus: emphasizing individual agency; situating academic work within the personal arena; and encompassing transitions across roles. This paper demonstrates how the construct of ‘identity‐trajectory' which links a narrative approach with identity construction contributes to understanding how early career academics learn through experience and navigate their journeys.
Stratified at seven: in‐class ability grouping and the relative age effect
Authors: Campbell Tammy
Published: November 2013

There is an established body of evidence indicating that a pupil's relative age within their school year cohort is associated with academic attainment throughout compulsory education. In England, autumn‐born pupils consistently attain at higher levels than summer‐born pupils. Analysis here investigates a possible channel of this relative age effect: ability grouping in early primary school. Relatively younger children tend more often to be placed in the lowest in‐class ability groups, and relatively older children in the highest group. In addition, teacher perceptions of pupils' ability and attainment are associated with the child's birth month: older children are more likely to be judged above average by their teachers. Using 2008 data for 5481 English seven‐year‐old pupils and their teachers from the Millennium Cohort Study, this research uses linear regression modelling to explore whether birth month gradation in teacher perceptions of pupils is more pronounced when pupils are in‐class ability grouped than when they are not. It finds an amplification of the already disproportionate tendency of teachers to judge autumn‐born children as more able when grouping takes place. The autumn–summer difference in teacher judgements is significantly more pronounced among in‐class ability grouped pupils than among non‐grouped pupils. Given evidence that teacher perceptions and expectations can influence children's trajectories, this supports the hypothesis that in‐class ability grouping in early primary school may be instrumental in creating the relative age effect.
Berberine induces apoptosis in human multiple myeloma cell line U266 through hypomethylation of p53 promoter
Authors: Qing Yanwei , Hu Haiyan , Liu Yuan , Feng Tao , Meng Wei , Jiang Ling , Sun Yongning , Yao Yang
Published: November 2013

Berberine has multiple pharmacological activities, such as anti‐oxidative, anti‐inflammation and anticancer activity. It reduces the proliferation and induces apoptosis in the multiple myeloma cell line, U266. Here we explored the detailed mechanism by analysing the gene expression profiles in U266 treated with or without berberine. DNMT1 and DNMT3B, encoding for a highly conserved member of the DNA methyltransferases, decreased significantly. By dissection of biochemical network database (BNDB) with Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotation, the p53 signalling pathway related genes were altered. By using epigenetic chromatin modification enzymes PCR Array, gene expression microarray, RT‐PCR and Bisulphite sequencing, the results show that berberine can repress the expression of DNMT1 and DNMT3B, which triggers hypomethylation of TP53 by changing the DNA methylation level and the alteration of p53 dependent signal pathway in human multiple melanoma cell U266.
Direct Synthesis of Ruthenium‐Containing Ordered Mesoporous Carbon with Tunable Embedding Degrees by Using a Boric Acid‐Assisted Approach
Authors: Lan Guojun , Tang Haodong , Zhou Yaping , Han Wenfeng , Liu Huazhang , Li Xiaonian , Li Ying
Published: November 2013

Uniform ruthenium nanoparticles (1–2 nm) confined in ordered mesoporous carbon (Ru‐OMC) with various embedding degrees have been fabricated by using a boric acid‐assisted hard template method. The catalytic performance of Ru‐OMC catalysts was determined through the hydrogenation of toluene at 110 °C and 4.0 MPa. The effects of pore size and embedding degree on the catalytic performance were studied and compared with those of OMC‐supported ruthenium (Ru/OMC) catalysts with various pore sizes. The catalytic activities of embedding Ru‐OMC catalysts are much higher than those of supported Ru/OMC catalysts, which can be attributed to the strong interaction between ruthenium nanoparticles and the carbon support. Furthermore, the activities of Ru‐OMC catalysts are closely related to the embedding degree of ruthenium nanoparticles in the carbon matrix. The Ru‐OMC catalysts with an appropriate embedding degree affords a turnover frequency of up to 4.69 s−1 in toluene hydrogenation.
Rare‐Earth‐Doped Pt/Ba/Ce0.6Zr0.4O2‐Al2O3 for NOx Storage and Reduction: The Effect of Rare‐Earth Doping on Efficiency and Stability
Authors: Wang Xiuyun , Chen Zhilin , Wang Yuling , Wang Ruihu
Published: November 2013

Rare‐earth‐doped Pt/Ba/RO‐CZA (RO=La2O3, Nd2O3 and Y2O3; CZA=Ce0.6Zr0.4O2‐Al2O3) were synthesized and characterized by XRD, N2 physisorption, Raman spectroscopy, H2 temperature‐programmed reduction, extended X‐ray absorption fine structure analysis, scanning transmission electron microscopy, and X‐ray photoelectron spectroscopy. The effect of the addition of rare earths on Pt/Ba/RO‐CZA was explored, and the relationship between their structures and properties was disclosed. In comparison with Pt/Ba/CZA, La and Nd addition, especially La addition, resulted in an apparent increment of oxygen vacancies and the improvement of the reductive capacity of Ce4+, which are favorable for NOx reduction. However, the presence of Y induced a negative effect on NOx storage and reduction (NSR). The NSR performances of Pt/Ba/RO‐CZA were initially evaluated by using NO‐to‐NO2 conversion, NOx storage capacity, and NOx conversion. The NOx conversion in Pt/Ba/La‐CZA and Pt/Ba/Nd‐CZA at 350 °C is up to 98 and 94 %, respectively. Interestingly, the addition of rare earths contributes to the enhancement of the thermal stability, a slight decrement of NOx conversion was observed after Pt/Ba/RO‐CZA were maintained at 350 °C for 100 h, whereas an obvious loss of catalytic activity was found in Pt/Ba/CZA under the same conditions. TEM analysis showed that the presence of La inhibits the agglomeration of Pt and the sintering of particles.
New Calcium‐Selective Smart Contrast Agents for Magnetic Resonance Imaging
Authors: Verma Kirti Dhingra , Forgács Attila , Uh Hyounsoo , Beyerlein Michael , Maier Martin E. , Petoud Stéphane , Botta Mauro , Logothetis Nikos K.
Published: November 2013

Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca2+ levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca2+ in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca2+‐sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca2+ in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd3+‐DO3A (DO3A=1,4,7‐tris(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane) coupled to a Ca2+ chelator o‐amino phenol‐N,N,O‐triacetate (APTRA). The agents are designed to sense Ca2+ present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2–0.8 mM. The determined dissociation constant of the CAs to Ca2+ falls in the range required to sense and report changes in extracellular Ca2+ levels followed by an increase in neural activity. In buffer, with the addition of Ca2+ the increase in relaxivity ranged from 100–157 %, the highest ever known for any T1‐based Ca2+‐sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb3+ analogues, nuclear magnetic relaxation dispersion (NMRD), and 17O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca2+ addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration.
4‐Trifluoromethyl‐Substituted Coumarins with Large Stokes Shifts: Synthesis, Bioconjugates, and Their Use in Super‐Resolution Fluorescence Microscopy
Authors: Schill Heiko , Nizamov Shamil , Bottanelli Francesca , Bierwagen Jakob , Belov Vladimir N. , Hell Stefan W.
Published: November 2013

Bright and photostable fluorescent dyes with large Stokes shifts are widely used as sensors, molecular probes, and light‐emitting markers in chemistry, life sciences, and optical microscopy. In this study, new 7‐dialkylamino‐4‐trifluoromethylcoumarins have been designed for use in bioconjugation reactions and optical microscopy. Their synthesis was based on the Stille reaction of 3‐chloro‐4‐trifluoromethylcoumarins and available (hetero)aryl‐ or (hetero)arylethenyltin derivatives. Alternatively, the acylation of 2‐trifluoroacetyl‐5‐dialkylaminophenols with available (hetero)aryl‐ or (hetero)arylethenylacetic acids followed by intramolecular condensation afforded coumarins with 3‐(hetero)aryl or 3‐[2‐(hetero)aryl]ethenyl groups. Hydrophilic properties were provided by the introduction of a sulfonic acid residue or by phosphorylation of a primary hydroxy group attached at C‐4 of the 2,2,4‐trimethyl‐1,2‐dihydroquinoline fragment fused to the coumarin fluorophore. For use in immunolabeling procedures, the dyes were decorated with an (activated) carboxy group. The positions of the absorption and emission maxima vary in the ranges 413–480 and 527–668 nm, respectively. The phosphorylated dye, 9,CHCH‐2‐py,H, with the 1‐(3‐carboxypropyl)‐4‐hydroxymethyl‐2,2‐dimethyl‐1,2‐dihydroquinoline fragment fused to the coumarin fluorophore bearing the 3‐[2‐(2‐pyridyl)ethenyl] residue (absorption and emission maxima at 472 and 623 nm, respectively) was used in super‐resolution light microscopy with stimulated emission depletion and provided an optical resolution better than 70 nm with a low background signal. As a result of their large Stokes shifts, good fluorescence quantum yields, and adequate photostabilities, phosphorylated coumarins enable two‐color imaging (using several excitation sources and a single depletion laser) to be combined with subdiffractional optical resolution.
Bioconjugation of Proteins with a Paramagnetic NMR and Fluorescent Tag
Authors: Huang Feng , Pei Ying‐Ying , Zuo Hui‐Hui , Chen Jia‐Liang , Yang Yin , Su Xun‐Cheng
Published: November 2013

Site‐specific labeling of proteins with lanthanide ions offers great opportunities for investigating the structure, function, and dynamics of proteins by virtue of the unique properties of lanthanides. Lanthanide‐tagged proteins can be studied by NMR, X‐ray, fluorescence, and EPR spectroscopy. However, the rigidity of a lanthanide tag in labeling of proteins plays a key role in the determination of protein structures and interactions. Pseudocontact shift (PCS) and paramagnetic relaxation enhancement (PRE) are valuable long‐range structure restraints in structural‐biology NMR spectroscopy. Generation of these paramagnetic restraints generally relies on site‐specific tagging of the target proteins with paramagnetic species. To avoid nonspecific interaction between the target protein and paramagnetic tag and achieve reliable paramagnetic effects, the rigidity, stability, and size of lanthanide tag is highly important in paramagnetic labeling of proteins. Here 4′‐mercapto‐2,2′: 6′,2′′‐terpyridine‐6,6′′‐dicarboxylic acid (4MTDA) is introduced as a a rigid paramagnetic and fluorescent tag which can be site‐specifically attached to a protein by formation of a disulfide bond. 4MTDA can be readily immobilized by coordination of the protein side chain to the lanthanide ion. Large PCSs and RDCs were observed for 4MTDA‐tagged proteins in complexes with paramagnetic lanthanide ions. At an excitation wavelength of 340 nm, the complex formed by protein–4MTDA and Tb3+ produces high fluorescence with the main emission at 545 nm. These interesting features of 4MTDA make it a very promising tag that can be exploited in NMR, fluorescence, and EPR spectroscopic studies on protein structure, interaction, and dynamics.
Structure and Biosynthesis of Xenoamicins from Entomopathogenic Xenorhabdus
Authors: Zhou Qiuqin , Grundmann Florian , Kaiser Marcel , Schiell Matthias , Gaudriault Sophie , Batzer Andreas , Kurz Michael , Bode Helge B.
Published: November 2013

During the search for novel natural products from entomopathogenic Xenorhabdus doucetiae DSM17909 and X. mauleonii DSM17908 novel peptides named xenoamicins were identified in addition to the already known antibiotics xenocoumacin and xenorhabdin. Xenoamicins are acylated tridecadepsipeptides consisting of mainly hydrophobic amino acids. The main derivative xenoamicin A (1) was isolated from X. mauleonii DSM17908, and its structure elucidated by detailed 1 D and 2 D NMR experiments. Detailed MS experiments, also in combination with labeling experiments, confirmed the determined structure and allowed structure elucidation of additional derivatives. Moreover, the xenoamicin biosynthesis gene cluster was identified and analyzed in X. doucetiae DSM17909, and its participation in xenoamicin biosynthesis was confirmed by mutagenesis. Advanced Marfey’s analysis of 1 showed that the absolute configuration of the amino acids is in agreement with the predicted stereochemistry deduced from the nonribosomal peptide synthetase XabABCD. Biological testing revealed activity of 1 against Plasmodium falciparum and other neglected tropical diseases but no antibacterial activity.
Synthesis, Characterization, and Thermal Behavior of Carboranyl–Styrene Decorated Octasilsesquioxanes: Influence of the Carborane Clusters on Photoluminescence
Authors: Ferrer‐Ugalde Albert , Juárez‐Pérez Emilio José , Teixidor Francesc , Viñas Clara , Núñez Rosario
Published: November 2013

Novel polyhedral oligomeric silsesquioxanes (POSS) or octasilsesquioxanes with carboranyl–styrene fragments attached to each corner are described. These compounds have been synthesized by olefin‐metathesis reactions between octavinylsilsesquioxane and carboranyl–styrene compounds that possess different substituents (Ph, Me, or H). In all cases, these reactions, which were catalyzed by the Grubbs catalyst, are highly regioselective and yield exclusively the E isomers. The existence of the carborane cage in the POSS structure induces a remarkable thermal stability in these compounds. After combustion at 1000 °C, these carboranyl–POSS compounds exhibit a mass loss lower than 10 %. The UV/Vis absorption data of these carboranyl–POSS compounds shows a slight bathochromic shift with respect to the carboranyl–styrene monomers, with an absorption maximum around 262 nm. Nevertheless, important differences in the emission spectra of the carboranyl–POSS compounds with regard to their carboranyl–styrene precursors are observed; the phenyl‐o‐carborane‐containing POSS compound exhibits the highest fluorescence intensity (ΦF=44 %), whereas for the POSS compound bearing the methyl substituent, and for the unsubstituted o‐carborane clusters, the fluorescence intensity is much lower (ΦF=9 and 2 %, respectively). This is precisely the reverse of what occurs with the monomers, in which the unsubstituted o‐carboranyl–styrene compound exhibits the highest ΦF, and a quenching of the fluorescence is observed in the phenyl‐o‐carboranyl–styrene compound. In addition, a large red shift of around 100 nm is observed for the POSS compounds with respect to their precursors. These experimental results can only be accounted for by the spatial ordering induced by the POSS core that eases interactions, which otherwise would not occur. These results have been confirmed by time‐dependent density functional theory (TDDFT) calculations that exclude a photoinduced electron transfer (PET) process in the POSS compounds.
Increasing the Bioavailability of RuIIIAnticancer Complexes through Hydrophobic Albumin Interactions
Authors: Webb Michael I. , Wu Boris , Jang Thalia , Chard Ryan A. , Wong Edwin W. Y. , Wong May Q. , Yapp Donald T. T. , Walsby Charles J.
Published: November 2013

A series of pyridine‐based derivatives of the clinically successful RuIII‐based complexes indazolium [trans‐RuCl4(1 H‐indazole)2] (KP1019) and sodium [trans‐RuCl4(1 H‐indazole)2] (KP1339) have been synthesized to probe the effect of hydrophobic interactions with human serum albumin (hsA) on anticancer activity. The solution behavior and protein interactions of the new compounds were characterized by using electron paramagnetic resonance (EPR) and UV/Vis spectroscopy. These studies have revealed that incorporation of hydrophobic substituents at the 4′‐position of the axial pyridine ligand stabilizes non‐coordinate interactions with hsA. As a consequence, direct coordination to the protein is inhibited, which is expected to increase the bioavailability of the complexes, thus potentially leading to improved anticancer activity. By using this approach, the lifetimes of hydrophobic protein interactions were extended from 2 h for the unsubstituted pyridine complex, to more than 24 h for several derivatives. Free complexes were tested for their anticancer activity against the SW480 human colon carcinoma cell line, exhibiting low cytotoxicity. Pre‐treatment with hsA improved the solubility of every compound and led to some changes in activity. Particularly notable was the difference in activity between the methyl‐ and dibenzyl‐functionalized complexes. The former shows reduced activity after incubation with hsA, indicating reduced bioavailability due to protein coordination. The latter exhibits little activity on its own but, following treatment with hsA, exhibited significant cytotoxicity, which is consistent with its ability to form non‐coordinate interactions with the protein. Overall, our studies demonstrate that non‐coordinate interactions with hsA are a viable target for enhancing the activity of RuIII‐based complexes in vivo.