bluuebunny/crossref_metadata_2025 huggingface dataset:
The MADS box genes SEEDSTICK and ARABIDOPSIS Bsister play a maternal role in fertilization and seed development
Authors: Mizzotti Chiara , Mendes Marta Adelina , Caporali Elisabetta , Schnittger Arp , Kater Martin M. , Battaglia Raffaella , Colombo Lucia
Published: December 2011

The haploid generation of flowering plants develops within the sporophytic tissues of the ovule. After fertilization, the maternal seed coat develops in a coordinated manner with formation of the embryo and endosperm. In the arabidopsis bsister (abs) mutant, the endothelium, which is the most inner cell layer of the integuments that surround the haploid embryo sac, does not accumulate proanthocyanidins and the cells have an abnormal morphology. However, fertility is not affected in abs single mutants. SEEDSTICK regulates ovule identity redundantly with SHATTERPROOF 1 (SHP1) and SHP2 while a role in the control of fertility was not reported previously. Here we describe the characterization of the abs stk double mutant. This double mutant develops very few seeds due to both a reduced number of fertilized ovules and seed abortions later during development. Morphological analysis revealed a total absence of endothelium in this double mutant. Additionally, massive starch accumulation was observed in the embryo sac. The phenotype of the abs stk double mutant highlights the importance of the maternal‐derived tissues, particularly the endothelium, for the development of the next generation.
Epoxycarotenoid cleavage by NCED5 fine‐tunes ABA accumulation and affects seed dormancy and drought tolerance with other NCED family members
Authors: Frey Anne , Effroy Delphine , Lefebvre Valérie , Seo Mitsunori , Perreau François , Berger Adeline , Sechet Julien , To Alexandra , North Helen M. , Marion‐Poll Annie
Published: December 2011

Carotenoid cleavage, catalyzed by the 9‐cis‐epoxycarotenoid dioxygenase (NCED) constitutes a key step in the regulation of ABA biosynthesis. In Arabidopsis, this enzyme is encoded by five genes. NCED3 has been shown to play a major role in the regulation of ABA synthesis in response to water deficit, whereas NCED6 and NCED9 have been shown to be essential for the ABA production in the embryo and endosperm that imposes dormancy. Reporter gene analysis was carried out to determine the spatiotemporal pattern of NCED5 and NCED9 gene expression. GUS activity from the NCED5 promoter was detected in both the embryo and endosperm of developing seeds with maximal staining after mid‐development. NCED9 expression was found at early stages in the testa outer integument layer 1, and after mid‐development in epidermal cells of the embryo, but not in the endosperm. In accordance with its temporal‐ and tissue‐specific expression, the phenotypic analysis of nced5 nced6 nced9 triple mutant showed the involvement of the NCED5 gene, together with NCED6 and NCED9, in the induction of seed dormancy. In contrast to nced6 and nced9, however, nced5 mutation did not affect the gibberellin required for germination. In vegetative tissues, combining nced5 and nced3 mutations reduced vegetative growth, increased water loss upon dehydration, and decreased ABA levels under both normal and stressed conditions, as compared with nced3. NCED5 thus contributes, together with NCED3, to ABA production affecting plant growth and water stress tolerance.
Probiotics, dendritic cells and bladder cancer
Authors: Feyisetan Oladapo , Tracey Christopher , Hellawell Giles O.
Published: December 2011

What's known on the subject? and What does the study add?

The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti‐tumour effector cells involved and NK cell activity correlates with the observed anti‐tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity.

The current use of intravesical bacille Calmette‐Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer.

Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo‐rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti‐cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette‐Guérin).
Reliability of heart rate variability in patients with Type 2 diabetes mellitus
Authors: Sacre J. W. , Jellis C. L. , Marwick T. H. , Coombes J. S.
Published: December 2011

Diabet. Med. 29, e33–e40 (2012)

Aims  Heart rate variability may be used to assess diabetic cardiac autonomic neuropathy. The aim of the present study was to determine the reliability of standard short‐term clinical measurements of heart rate variability in patients with Type 2 diabetes.

Methods  In 24 patients with Type 2 diabetes (11 male, age 61 ± 9 years), parameters of heart rate variability in the time domain (standard deviation of RR intervals, coefficient of variation of RR intervals and root mean square of successive RR interval differences) and frequency domain (very low frequency, low frequency, high frequency and total spectral power) were derived from a 5‐min electrocardiograph recorded during two laboratory visits separated by 16 ± 8 days. Absolute and relative reliability were assessed by 95% limits of random variation and the intraclass correlation coefficient, respectively. Categorical agreement of classifications of heart rate variability and sample size estimates for clinical trials were calculated.

Results  Despite no significant difference in mean heart rate variability between tests, 95% limits of random variation indicated that repeated measurements were between 58% higher/37% lower (most reliable parameter; coefficient of variation of RR intervals) and 443% higher/82% lower (least reliable parameter; very low frequency power) than the first measure. The intraclass correlation coefficient ranged from 0.58 to 0.90 and sample size requirements from 20 to 93 patients per group. Agreement of categories of heart rate variability ranged from 79 to 96%.

Conclusions  Short‐term clinical measurements of heart rate variability in patients with Type 2 diabetes are characterized by poor absolute reliability, but substantial to good relative reliability, suggesting greater clinical utility in diagnosis than in sequential follow‐up.
Perceptual Nonconceptualism: Disentangling the Debate Between Content and State Nonconceptualism
Authors: Duhau Laura
Published: December 2011

In this paper I argue, against recent claims by Bermúdez (2007) and Toribio (2008), that within the debate about whether perceptual experiences are nonconceptual, ‘state nonconceptualism’ (or the ‘state view’) can be a coherent and plausible position. In particular, I explain that state nonconceptualism and content nonconceptualism, when understood in their most plausible and motivated form, presuppose different notions of content. I argue that state nonconceptualism can present a plausible way of unpacking the claim that perceptual experiences are nonconceptual once the notion of content it should presuppose is taken into account; and once this notion of content is clearly distinguished from the one usually presupposed by content nonconceptualism, the criticisms that Bermúdez and Toribio place against state nonconceptualism become ineffective.
The Shadow Economy in German Regions: An Empirical Assessment
Authors: Buehn Andreas
Published: December 2011

Despite the increasing number of contributions to the literature, regional variations of the shadow economy have been hardly studied. This article analyses the determinants and derives the size of the shadow economy on the district level in Germany. I find that an inferior local labour market and the burden of taxation significantly contribute to the existence of the shadow economy, while a better enforcement of tax rules and regulations has the potential to deter such activities. Districts in the affluent south of Germany experience on average smaller shadow economies.
Dual REST‐dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells
Authors: Mikulak Joanna , Negrini Sara , Klajn Andrijana , D’Alessandro Rosalba , Mavilio Domenico , Meldolesi Jacopo
Published: December 2011

J. Neurochem (2012) 120, 699–709.

L1 cell adhesion molecule (L1CAM), an adhesion/signaling protein encoded by a gene target of the transcription repressor RE‐1‐Silencing Transcription factor (REST), is expressed in two alternatively spliced isoforms. The full‐length isoform, typical of low‐REST neural cells, plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity; the isoform missing two mini‐exons, abundant in a few high‐REST non‐neural cells, maintains some effect on migration and proliferation. To investigate whether and how L1CAM alternative splicing depends on REST we used neural cell models expressing low or high levels of REST (PC12, SH‐SY5Y, differentiated NT2/D1 and primary neurons transduced or not with REST). The short isoform was found to rise when the low‐REST levels of neural cells were experimentally increased, while the full‐length isoform increased in high‐REST cells when the repressor tone was attenuated. These results were due to Nova2, a neural cell‐specific splicing factor shown here to be repressed by REST. REST control of L1CAM occurs therefore by two mechanisms, transcription and alternative splicing. The splicing mechanism, affecting not only L1CAM but all Nova2 targets (∼7% of brain‐specific splicing, including the mRNAs of other adhesion and synaptic proteins) is expected to be critical during development and important also for the structure and function of mature neural cells.
Relationship between Substance Use and Body Mass Index in Young Males
Authors: Blüml Victor , Kapusta Nestor , Vyssoki Benjamin , Kogoj Dagmar , Walter Henriette , Lesch Otto M.
Published: December 2011

Recent findings in basic scientific research, such as neurobiological and neuroimaging studies, have suggested common pathways for food and drug intake. It was hypothesized that both compete for the same brain reward sites, and that a higher body mass index (BMI) may be associated with lower substance use. The aim of this study was to investigate the relationship between BMI and substance use in a large sample of young male adults. The sample consisted of 1,902 18‐year‐old males from a province of Austria in a naturalistic cross‐sectional setting. Questionnaires were administered to assess alcohol abuse and dependence (CAGE) and nicotine dependence (Heavy Smoking Index). Urine samples were collected to assess the prevalence of recent illicit drug use. Associations between BMI and substance use were calculated by means of logistic regression analyses. An inverse relationship between BMI and recent illicit drug use was found. This relationship remained significant after adjusting for possible confounding factors such as level of education, nicotine dependence, breath carbon monoxide (CO) levels, and alcohol abuse and dependence. No significant association was found between BMI and nicotine and alcohol dependence. A higher BMI was associated with lower illicit drug use in our sample of young adult males. These results provide further evidence for the hypothesis that food and drugs may compete for the same brain reward sites. (Am J Addict 2011;21:72–77)
Adaptation of the Patient Feedback Survey at a Community Treatment Setting
Authors: Kolodziej Monika E. , Muchowski Patrice M. , Hamdi Nayla R. , Morrissette Paula , McGowan Alicen J. , Weiss Roger D.
Published: December 2011

The Patient Feedback Survey is a performance improvement measure designed to assess the quality of outpatient substance abuse treatment. We modified and administered this measure to 500 individuals at a multisite treatment provider. Although the feedback scores were high in general, analyses of variance showed score variability in relation to type and length of treatment. Moreover, respondents who reported any use of marijuana, cravings for substances, or mutual‐support group attendance (ie, Alcoholics Anonymous or Narcotics Anonymous) had lower feedback scores than respondents without these experiences. We highlight the importance of investigating treatment evaluations in the context of other recovery experiences. (Am J Addict 2011;21:63–71)
What to Do If a Transesophageal Echocardiography Probe Buckled in Esophagus?
Authors: Dişibeyaz Selçuk , Parlak Erkan , Köksal Aydın Şeref , Önder Fatih Oğuz , Şahin Burhan
Published: December 2011

A 65‐year‐old man was consulted because of buckling of transesophageal echocardiography (TEE) probe in the esophagus. A forward‐viewing endoscope was inserted to the esophagus alongside the TEE probe. TEE probe was pushed to the stomach while the retroflexed tip portion was pushed by the endoscope in order to prevent retroflexion. The TEE probe was advanced into the stomach by this method where the buckled part was unfolded and then withdrawn. Cardiologists performing TEE and the referred gastroenterologists could perform such a method of solution in case of buckling of TEE probe in the esophagus. (Echocardiography 2012;29:E85‐E86)
Delineation of the Free‐Floating Left Atrial Ball Mass with Real Time Three‐Dimensional Transesophageal Echocardiography in a Patient with Mechanical Mitral Valve Prosthesis
Authors: Ozkan Mehmet , Ali Astarcioglu Mehmet , Tuncer, M.D. Altug , Yildiz Mustafa
Published: December 2011

We describe here a very unusual case of a large free floating left atrial thrombus detected by incidental echocardiography, in which symptoms and complications of ball thrombus were absent. The patient's only symptom was mild dyspnea attributed to prosthetic mitral heart valve. He had no syncope or arrhythmia‐induced embolic event. Real time 3D‐TEE imaging provided exact spatial information about the shape and surface of intracardiac mass.
Advocating for Ethnographic Work in Early Childhood Federal Policy: Problems and Possibilities
Authors: ADAIR JENNIFER KEYS
Published: December 2011

Initiated as part of the Council on Anthropology and Education's Policy Engagement Working Group, the policy brief “Ethnographic Knowledge For Early Childhood” focused on making the case for ethnography as evidence within early childhood federal policy. This article describes the creation and distribution of the policy brief as well as the challenges and possibilities we have as educational anthropologists to make our work accessible to local and national policymakers. [ethnography, early childhood education, policy, anthropological knowledge for policymakers]
Performance of a semiochemical‐baited autoinoculation device treated with Metarhizium anisopliae for control of Frankliniella occidentalis on French bean in field cages
Authors: Niassy S. , Maniania N. K. , Subramanian S. , Gitonga L. M. , Ekesi S.
Published: December 2011

The performance of an autoinoculation device was evaluated in field cage experiments for control of Western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), in French bean, Phaseolus vulgaris L. var. Samantha (Fabaceae). Treatments consisted of a fungus‐treated device with and without semiochemical (Lurem‐TR), and a fungus‐free device as control; the fungus used was Metarhizium anisopliae (Metchnikoff) Sorokin (Hypocreales: Clavicipitaceae). The overall mean number of conidia acquired by a single insect was higher in the fungus‐treated semiochemical‐baited device than in the device without semiochemical: 5.0 ± 0.6 × 104 vs. 2.2 ± 0.4 × 104 conidia per insect. The overall thrips mortality was also higher in the semiochemical‐baited device than in the device without the semiochemical: 59.3 ± 3.9 vs. 41.7 ± 3.5%. Conidial viability was not affected in the M. anisopliae‐treated device without semiochemicals, 7 days after treatment, whereas it was considerably decreased – from 81.0 ± 1.3 to 6.5 ± 1.1%, 2 and 7 days post‐inoculation – in the M. anisopliae‐treated semiochemical‐baited device. Thrips mortality was positively correlated with M. anisopliae conidial viability, and conidial viability was negatively correlated with conidial acquisition. This suggests that the semiochemical volatiles reduced the conidial viability, which in turn resulted in significant reduction in thrips mortality, despite the highest conidial acquisition in the semiochemical‐baited fungus‐treated device. Thrips density per plant was significantly reduced in both fungus‐treated treatments (with semiochemical: 8.7 ± 1.7 adults per plant; without semiochemical: 6.6 ± 1.4 adults per plant) compared with the fungus‐free control (19.8 ± 2.6 adults per plant). These results demonstrate the potential for an autoinoculation device strategy for the control of thrips, particularly in screenhouses.
Cobalt release from implants and consumer items and characteristics of cobalt sensitized patients with dermatitis
Authors: Thyssen Jacob P. , Menné Torkil , Lidén Carola , Julander Anneli , Jensen Peter , Jakobsen Stig S. , Søballe Kjeld , Gotfredsen Klaus , Jellesen Morten S. , Johansen Jeanne D.
Published: December 2011

Background. Cobalt allergy is prevalent in dermatitis patients. Very little documentation exists about current sources of cobalt exposure.

Objectives. To investigate and discuss putative sources of cobalt exposure and to present selected epidemiological data on cobalt allergy from patch‐tested dermatitis patients in an attempt to better understand cobalt allergy.

Materials and methods. 19 780 dermatitis patients aged 4–99 years were patch tested with nickel, chromium or cobalt between 1985 and 2010. The cobalt spot test was used to test for cobalt ion release from mobile phones as well as cobalt‐containing dental alloys and revised hip implant components.

Results. Six of eight dental alloys and 10 of 98 revised hip implant components released cobalt in the cobalt spot test, whereas none of 50 mobile phones gave positive reactions. The clinical relevance of positive cobalt test reactions was difficult to determine in the majority of patients. Isolated patch test reactivity to cobalt was less associated with occupational dermatitis and hand eczema than patch test reactivity to cobalt in combination with other contact allergies.

Conclusions. It is often difficult to interpret the relevance of a positive patch test reaction to cobalt, and there is a need for further studies to determine sources of cobalt exposure.
Effect of estrus synchronization treatment after luteolysis on Holstein heifers as embryo transfer recipients
Authors: YOSHIDA Tatsuyuki , SATO Taro , CHIBA Koji , YOSHIMURA Itaru , OSADA Masahiro , OKADA Konosuke , FURUTA Hiroki , OHTA Akihiko , USHIJIMA Hitoshi
Published: December 2011

This study was designed to evaluate the effect of estrus synchronization treatments on recipient heifers for embryo transfer (ET). Holstein heifers were separated into the following three groups: (i) an administration of 50 µg GnRH (gonadotropin‐releasing hormone) analog was given to heifers at a random stage of the estrus cycle, followed 7 days later by two administrations of 7.5 mg prostaglandin F2 alfa analog (PG) as control; (ii) another administration of 100 µg GnRH was given to the control group at 48 h after the administration of PG as the second GnRH group; and (iii) an administration of 0.75 mg estradiol benzoate (E2) was given to the control group at 24 h after the administration of PG as the E2 group. Each method caused estrus synchronization. Fresh embryos were nonsurgically transferred into the suitable recipients that had a functional corpora lutea (CL) 7 days after estrus. The E2 group showed a significantly higher (P < 0.01) rate of estrus synchronization (98.9%) at 1–3 days after PG administration and the final pregnancy rate of the E2 group (50.6%) was also significantly higher than the other groups (37.1%, P < 0.05 and 30.9%, P < 0.01, respectively). These findings demonstrate that E2 administration 24 h after PG protocol is effective for estrus synchronization of Holstein heifers, thus improving the productivity of ET.
Conserved domains and evolution of secreted phospholipases A2
Authors: Nevalainen Timo J. , Cardoso João C. R. , Riikonen Pentti T.
Published: December 2011

Secreted phospholipases A2 (sPLA2s) are lipolytic enzymes present in organisms ranging from prokaryotes to eukaryotes but their origin and emergence are poorly understood. We identified and compared the conserved domains of 333 sPLA2s and proposed a model for their evolution. The conserved domains were grouped into seven categories according to the in silico annotated conserved domain collections of ‘cd00618: PLA2_like’ and ‘pfam00068: Phospholip_A2_1’. PLA2s containing the conserved domain cd04706 (plant‐specific PLA2) are present in bacteria and plants. Metazoan PLA2s of the group (G) I/II/V/X PLA2 collection exclusively contain the conserved domain cd00125. GIII PLA2s of both vertebrates and invertebrates contain the conserved domain cd04704 (bee venom‐like PLA2), and mammalian GIII PLA2s also contain the conserved domain cd04705 (similar to human GIII PLA2). The sPLA2s of bacteria, fungi and marine invertebrates contain the conserved domain pfam09056 (prokaryotic PLA2) that is the only conserved domain identified in fungal sPLA2s. Pfam06951 (GXII PLA2) is present in bacteria and is widely distributed in eukaryotes. All conserved domains were present across mammalian sPLA2s, with the exception of cd04706 and pfam09056. Notably, no sPLA2s were found in Archaea. Phylogenetic analysis of sPLA2 conserved domains reveals that two main clades, the cd‐ and the pfam‐collection, exist, and that they have evolved via gene‐duplication and gene‐deletion events. These observations are consistent with the hypothesis that sPLA2s in eukaryotes shared common origins with two types of bacterial sPLA2s, and their persistence during evolution may be related to their role in phospholipid metabolism, which is fundamental for survival.
Design and Synthesis of N‐Substituted Indazole‐3‐Carboxamides as Poly(ADP‐ribose)polymerase‐1 (PARP‐1) Inhibitors†
Authors: Patel Maulik R. , Pandya Kashyap G. , Lau‐Cam Cesar A. , Singh Satyakam , Pino Maria A. , Billack Blase , Degenhardt Kurt , Talele Tanaji T.
Published: December 2011

A group of novel N‐1‐substituted indazole‐3‐carboxamide derivatives were synthesized and evaluated as inhibitors of poly(ADP‐ribose)polymerase‐1 (PARP‐1). A structure‐based design strategy was applied to a weakly active unsubstituted 1H‐indazole‐3‐carboxamide 2, by introducing a three carbon linker between 1H‐indazole‐3‐carboxamide and different heterocycles, and led to compounds 4 [1‐(3‐(piperidine‐1‐yl)propyl)‐1H‐indazole‐3‐carboxamide, IC50 = 36 μm] and 5 [1‐(3‐(2,3‐dioxoindolin‐1‐yl)propyl)‐1H‐indazole‐3‐carboxamide, IC50 = 6.8 μm]. Compound 5 was evaluated in rats for its protective action against diabetes induced by a treatment with streptozotocin, a known diabetogenic agent. In addition to preserving the ability of the pancreas to secrete insulin, compound 5 was also able to attenuate the ensuing hyperglycemic response to a significant extent.
Design and Synthesis of 3,5‐Disubstituted‐1,2,4‐Oxadiazoles as Potent Inhibitors of Phosphodiesterase4B2
Authors: Kumar Dalip , Patel Gautam , Vijayakrishnan Lalitha , Dastidar Sunanda G. , Ray Abhijit
Published: December 2011

A series of 3,5‐disubstituted‐1,2,4‐oxadiazoles has been prepared and evaluated for phosphodiesterase inhibition (PDE4B2). Among the prepared 3,5‐disubstituted‐1,2,4‐oxadiazoles, compound 9a is the most potent inhibitor (PDE4B2 IC50 = 5.28 μm). Structure–activity relationship studies of 3,5‐disubstituted‐1,2,4‐oxadiazoles revealed that substituents 3‐cyclopentyloxy‐4‐methoxyphenyl group at 3‐position and cyclic ring bearing heteroatoms at 5‐position are important for activity. Molecular modeling study of the 3,5‐disubstituted‐1,2,4‐oxadiazoles with PDE4B has shown similar interactions of 3‐cyclopentyloxy‐4‐methoxyphenyl group; however, heteroatom ring is slightly deviating when compared to Piclamilast. 3‐(3‐Cyclopentyloxy‐4‐methoxyphenyl)‐5‐(piperidin‐4‐yl)‐1,2,4‐oxadiazole (9a) exhibited good analgesic and antiinflammatory activities in formalin‐induced pain in mice and carrageenan‐induced paw edema model in rat.
Insights to drug addiction derived from ultrastructural views of the mesocorticolimbic system
Authors: Morales Marisela , Pickel Virginia M.
Published: December 2011

Drugs of abuse increase the release of dopamine from mesocorticolimbic neurons in the ventral tegmental area. Thus, insights into the cytoarchitecture and the synaptic circuitry affecting the activity of dopaminergic neurons in this area are fundamental for understanding the commonalities produced by mechanistically distinct drugs of abuse. Electron microscopic immunolabeling has provided these insights and also shown the critical relationships between the dopaminergic axon terminals and their targeted neurons in the prefrontal cortex and in the both the dorsal and ventral striatum. These brain regions are among those where dopamine and associated neurotransmitters are most implicated in the transition from recreational to compulsive consumption of reinforcing drugs. Thus, the synaptic circuitry and drug‐induced plasticity occurring in the ventral tegmental area and in dopamine‐targeted regions are reviewed, as both are essential for understanding the long‐lasting changes produced by addictive substances.
Optos‐guided pattern scan laser (Pascal)‐targeted retinal photocoagulation in proliferative diabetic retinopathy
Authors: Muqit Mahiul M. K. , Marcellino George R. , Henson David B. , Young Lorna B. , Patton Niall , Charles Stephen J. , Turner George S. , Stanga Paulo E.
Published: December 2011

Purpose:  To investigate the clinical effects and safety of targeted pattern scan laser (Pascal) retinal photocoagulation (TRP) in proliferative diabetic retinopathy (PDR).

Methods:  Prospective and non‐randomized study of 28 eyes with treatment‐naive proliferative diabetic retinopathy (PDR). Single‐session 20‐ms‐Pascal TRP strategy applied 1500 burns to zones of retinal capillary non‐perfusion and intermediate retinal ischaemia guided by wide‐field fluorescein angiography (Optos). Main outcome measures at 12 and 24 weeks included; PDR grade (assessed by two masked retina specialists); central retinal thickness (CRT); mean deviation (MD) using 24‐2 Swedish interactive threshold algorithm (SITA)‐standard visual fields (VF); and ETDRS visual acuity (VA).

Results:  Following primary TRP, there was PDR regression in 76% of patients at 12 weeks (κ = 0.70; p < 0.001). No laser re‐treatment was required at 4 weeks, and 10 eyes underwent repeat TRP at 12 weeks. Wide‐field Optos angiography at 24 weeks showed complete disease regression in 37% and partial regression in 33%. Additional panretinal laser photocoagulation (PRP) was planned for active PDR in 30%. There were significant reductions in CRT over time (10.4 μm at 12‐weeks, p = 0.007; 12.1 μm at 24‐weeks, p = 0.0003). The MD on VFs improved after 12 weeks (+1.25 dB; p = 0.015) and 24 weeks (+1.26 dB, p = 0.01). The VA increased by +3 letters at 24 weeks (95% CI, 1.74–5.01; p < 0.0001).

Conclusions:  This pilot study reports that Optos‐guided Pascal 20‐ms TRP using 1500 burns for treatment‐naive PDR is a promising procedure with favourable safety profile.
Hepatic arterial infusion chemotherapy using 5‐fluorouracil and systemic interferon‐α for advanced hepatocellular carcinoma in combination with or without three‐dimensional conformal radiotherapy to venous tumor thrombosis in hepatic vein or inferior vena cava
Authors: Murakami Eisuke , Aikata Hiroshi , Miyaki Daisuke , Nagaoki Yuko , Katamura Yoshio , Kawaoka Tomokazu , Takaki Shintaro , Hiramatsu Akira , Waki Koji , Takahashi Shoichi , Kimura Tomoki , Kenjo Masahiro , Nagata Yasushi , Ishikawa Masaki , Kakizawa Hideaki , Awai Kazuo , Chayama Kazuaki
Published: December 2011

Aim:  We investigated the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5‐fluorouracil (5‐FU) and systemic interferon (IFN)‐α (HAIC‐5‐FU/IFN) for advanced hepatocellular carcinoma (HCC) with venous tumor thrombosis (VTT) in the hepatic vein trunk (Vv2) or inferior vena cava (Vv3).

Methods:  Thirty‐three patients with HCC/Vv2/3 underwent HAIC with 5‐FU (500 mg/body weight/day, into hepatic artery on days 1–5 on the first and second weeks) and IFN‐α (recombinant IFN‐α‐2b 3 000 000 U or natural IFN‐α 5 000 000 U, intramuscularly on days 1, 3 and 5 of each week). Three‐dimensional conformal radiotherapy (3D‐CRT) was used in combination with HAIC‐5‐FU/IFN in 14 of 33 patients to reduce VTT.

Result:  The median survival time (MST) was 7.9 months, and 1‐ and 2‐year survival rates were 30% and 20%, respectively. Evaluation of intrahepatic response after two cycles of HAIC‐5‐FU/IFN showed complete response (CR) in three (9%) and partial response (PR) in seven (21%), with an objective response rate of 30%. Multivariate analysis identified reduction of VTT (P = 0.0006), size of largest tumor (P = 0.013) and intrahepatic response CR/PR (P = 0.030) as determinants of survival. CR/PR correlated significantly with tumor liver occupying rate (P = 0.016) and hepatitis C virus Ab (P = 0.010). Reduction of VTT correlated significantly with radiotherapy (P = 0.021) and platelet count (P = 0.015). Radiotherapy‐related reduction in VTT significantly improved survival of 16 patients with Vv3 and non‐CR/PR response of HAIC‐5‐FU/IFN (P = 0.028).

Conclusion:  As for advanced HCC with VTT of Vv2/3, HAIC‐5‐FU/IFN responsive patients could obtain favorable survival. Despite ineffective HAIC‐5‐FU/IFN, the combination with effective radiotherapy to VTT might improve patients' prognosis.
Resolution of impact‐related microstructures in lunar zircon: A shock‐deformation mechanism map
Authors: TIMMS Nicholas E. , REDDY Steven M. , HEALY David , NEMCHIN Alexander A. , GRANGE Marion L. , PIDGEON Robert T. , HART Robert
Published: December 2011

Abstract– The microstructures of lunar zircon grains from breccia samples 72215, 73215, 73235, and 76295 collected during the Apollo 17 mission have been characterized via optical microscopy, cathodoluminescence imaging, and electron backscatter diffraction mapping. These zircon grains preserve deformation microstructures that show a wide range in style and complexity. Planar deformation features (PDFs) are documented in lunar zircon for the first time, and occur along {001}, {110}, and {112}, typically with 0.1–25 μm spacing. The widest PDFs associated with {112} contain microtwin lamellae with 65°/<110> misorientation relationships. Deformation bands parallel to {100} planes and irregular low‐angle (<10°) boundaries most commonly have <001> misorientation axes. This geometry is consistent with a dislocation glide system with <100>{010} during dislocation creep. Nonplanar fractures, recrystallized domains with sharp, irregular interfaces, and localized annealing textures along fractures are also observed. No occurrences of reidite were detected. Shock‐deformation microstructures in zircon are explained in terms of elastic anisotropy of zircon. PDFs form along a limited number of specific {hkl} planes that are perpendicular to directions of high Young’s modulus, suggesting that PDFs are likely to be planes of longitudinal lattice damage. Twinned {112} PDFs also contain directions of high shear modulus. A conceptual model is proposed for the development of different deformation microstructures during an impact event. This “shock‐deformation mechanism map” is used to explain the relative timing, conditions, and complexity relationships between impact‐related deformation microstructures in zircon.
Experience Design Is the Only Design
Authors: Grefé Richard
Published: December 2011

Thoughts on the new face of product design from the executive director of AIGA and the CEO of IDSA.
The Sudden Death of Brands
Authors: Formosa Daniel
Published: December 2011

You're shopping for a new vacuum cleaner, or a TV. Whose advice carries more weight for you—your friends, users who post online, or the marketing material you find on the brand's website?
From Products to Services: Understanding the New Rules of Engagement
Authors: Hudson Colin , Fudge Carl , Rae Jeneanne
Published: December 2011

New services are changing the product‐design game for consumers and manufacturers alike. Here is a look at four current models in which services are supplanting the traditional role of the physical product.
Representation, Generation, and Analysis of Mechanical Assembly Sequences With k-ary Operations
Authors: Wang Haixia , Ceglarek Dariusz
Published: December 2011

A new methodology is presented to generate all of the assembly sequences for a production system configured as a N-station assembly line with kn (n  = 1, 2,…, N) parts or subassemblies to be assembled at stations 1, 2,…, N, respectively. This expands current approaches in sequence generation applicable for binary assembly process to a k-ary assembly process by including: (i) nonbinary state between two parts, i.e., multiple joints between two parts or subassemblies, is taken into consideration, and (ii) simultaneous assembly of Y (Y≥3) parts or subassemblies. The methodology is based upon proposed k-piece graph and k-piece mixed graph approaches for the assemblies without and with assembly precedence relationship, respectively. Compared with the currently used liaisons graph (or datum flow chain) representation which shows part-to-part assembly relations, the k-piece graph (or k-piece mixed graph) shows all of the feasible subassemblies and their constituent parts and joints (pairs of mating features). Based upon the k-piece graph or k-piece mixed-graph approach, all of the feasible subassemblies for a predetermined assembly line configuration are identified, and all of the sequences for a k-ary assembly process are generated. Case studies are presented to illustrate the advantages of the presented methodology over the state-of-the-art research in assembly sequence generation.
Statistical bias in the assessment of binaural benefit relative to the better ear
Authors: van Hoesel Richard J. M. , Litovsky Ruth Y.
Published: December 2011

The comparison of measured binaural performance with the better of two monaural measures (one from each ear) may lead to underestimated binaural benefit due to statistical sampling bias that favors the monaural condition. The mathematical basis of such bias is reviewed and applied to speech reception thresholds measured in 32 bilateral cochlear implant (CI) users for coincident and spatially separated speech and noise. It is shown that the bias increases with test-retest variation and is maximal for uncorrelated samples of identical underlying performance in each ear. When measured differences between ears were assumed to reflect actual underlying performance differences, the bias averaged across the CI users was about 0.2 dB for coincident target and noise, and 0.1 dB for spatially separated conditions. An upper-bound estimate of the bias, based on the assumption that both ears have the same underlying performance and observed differences were due to test-retest variation, was about 0.7 dB regardless of noise location. To the extent that the test-retest variation in these data is comparable to other studies, the results indicate that binaural benefits in bilateral cochlear implant users are not substantially underestimated (on for average) when binaural performance is compared with the better ear in each listening configuration.
Non-auditory factors affecting urban soundscape evaluation
Authors: Yong Jeon Jin , Jik Lee Pyoung , Young Hong Joo , Cabrera Densil
Published: December 2011

The aim of this study is to characterize urban spaces, which combine landscape, acoustics, and lighting, and to investigate people’s perceptions of urban soundscapes through quantitative and qualitative analyses. A general questionnaire survey and soundwalk were performed to investigate soundscape perception in urban spaces. Non-auditory factors (visual image, day lighting, and olfactory perceptions), as well as acoustic comfort, were selected as the main contexts that affect soundscape perception, and context preferences and overall impressions were evaluated using an 11-point numerical scale. For qualitative analysis, a semantic differential test was performed in the form of a social survey, and subjects were also asked to describe their impressions during a soundwalk. The results showed that urban soundscapes can be characterized by soundmarks, and soundscape perceptions are dominated by acoustic comfort, visual images, and day lighting, whereas reverberance in urban spaces does not yield consistent preference judgments. It is posited that the subjective evaluation of reverberance can be replaced by physical measurements. The categories extracted from the qualitative analysis revealed that spatial impressions such as openness and density emerged as some of the contexts of soundscape perception.
Observation of traveling thermoacoustic shock waves (L)
Authors: Biwa Tetsushi , Takahashi Takuma , Yazaki Taichi
Published: December 2011

Shock waves were explored in the thermoacoustic spontaneous gas oscillations occurring in a gas column with a steep temperature gradient. The results show that a periodic shock occurs in the traveling wave mode in a looped tube but not in the standing wave mode in a resonator. Measurements of the harmonic components of the acoustic intensity reveal a clear difference between them. The temperature gradient acts as an acoustic energy source for the harmonic components of the shock wave in the traveling wave mode but as an acoustic energy sink of the second harmonic in the standing wave mode.
Model and experimental analysis of oblique incident ultrasound in a tissue layer using doublet mechanics theory
Authors: Jiang Xin , Liu Xiaozhou , Gong Xiufeng , Zhang Fei , Wu Rongrong , Wu Junru , Liu Jun
Published: December 2011

The fundamental framework of doublet mechanics (DM) is used to analyze high-frequency ultrasound wave propagation in materials with discrete microstructure. Ultrasonic reflection coefficients were measured from a thin layer of tissue embedded between two glass substrates at oblique incidence. Theoretical calculations for the reflection coefficients of a multi-layered system at oblique angles are performed using both DM theory and the classical continuum mechanics theory (CCM). For example, at the frequency of 10 MHz at incident angle 8° in sample with 30 μm thickness, the discrepancy in the magnitude of the reflection coefficient between experimental results and theoretical prediction is 15.8% for DM but 79.0% for CCM; similar results at other frequencies and incident angle in the samples with 30 and 60 μm thickness have also been obtained, which demonstrates that the DM theory can better describe the wave propagation in tissue. The influence of the incident angles and tissue thickness are also discussed in this paper.
Equilibrative Nucleoside Transporter 3 Deficiency Perturbs Lysosome Function and Macrophage Homeostasis
Authors: Hsu Chia-Lin , Lin Weiyu , Seshasayee Dhaya , Chen Yung-Hsiang , Ding Xiao , Lin Zhonghua , Suto Eric , Huang Zhiyu , Lee Wyne P. , Park Hyunjoo , Xu Min , Sun Mei , Rangell Linda , Lutman Jeff L. , Ulufatu Sheila , Stefanich Eric , Chalouni Cecile , Sagolla Meredith , Diehl Lauri , Fielder Paul , Dean Brian , Balazs Mercedesz , Martin Flavius
Published: December 2011

From Nucleoside Recycling to Histiocytosis

Macrophages remove billions of apoptotic cells daily, releasing their nucleic acid material through lysosomal degradation, which allows the resulting nucleosides to be recycled.

Hsu
et al.

(p.
89
, published online 15 December) found that the nucleoside transporter, equilibrative nucleoside transporter 3 (ENT3), was highly expressed in macrophages and showed that mice deficient in this transporter develop histiocytosis and features of lysosomal storage disease. When exposed to apoptotic cells, macrophages carrying human ENT3 mutations accumulated adenosine and increased their lysosomal pH. These changes contributed to an enhanced signaling through macrophage colony-stimulating factor (M-CSF) receptor and, ultimately, to M-CSF–driven myeloproliferative disease.
Eating Right for Immunity
Authors: Mueller Kristen L.
Published: December 2011

Nutrients can shape immune system development function through aryl hydrocarbon receptor signaling.
Complement, Attraction, and Collective Migration
Authors: Foley John F.
Published: December 2011

Complement factor C3a and its receptor are required for the mutual attraction and collective migration of neural crest cells.
Assessment on the effects of the operational conditions on the manufacture of PLA-based composites using an integrated compounding–injection moulding machine
Authors: González Daniel , Campos Ana Rita , Cunha Antonio M. , Santos Valentín , Parajó Juan Carlos
Published: December 2011

Cellulose fibres were employed as reinforcement agent for biodegradable composites using polylactic acid (PLA) as a polymer matrix. PLA can be obtained from renewable resources, and it is attracting much interest owing to its favourable physico-mechanical properties and biodegradability. Prior to composite compounding, two commercial PLA from different suppliers were characterized for apparent density, flow index, crystallinity, thermal properties, melt flow rheology and intrinsic viscosity for comparison. In experiments performed with an integrated compounding–injection moulding machine (ICIM), the effects of the processing conditions on the mechanical properties of composites (tensile strength, stiffness and strain at break) were analyzed using a Taguchi experimental design. Other properties of the composites, such as surface morphology and fibre length distribution, were also considered. ICIM technology provided composites with better mechanical properties and lower fibre degradation than the conventional sequential extrusion and injection moulding (SEIM) technology.
KCNE2 protein is more abundant in ventricles than in atria and can accelerate hERG protein degradation in a phosphorylation-dependent manner
Authors: Zhang Mei , Wang Yuhong , Jiang Min , Zankov Dimitar P. , Chowdhury Sabeeha , Kasirajan Vigneshwar , Tseng Gea-Ny
Published: December 2011

KCNE2 functions as an auxiliary subunit in voltage-gated K and HCN channels in the heart. Genetic variations in KCNE2 have been linked to long QT syndrome. The underlying mechanisms are not entirely clear. One of the issues is whether KCNE2 protein is expressed in ventricles. We use adenovirus-mediated genetic manipulations of adult cardiac myocytes to validate two antibodies (termed Ab1 and Ab2) for their ability to detect native KCNE2 in the heart. Ab1 faithfully detects native KCNE2 proteins in spontaneously hypertensive rat and guinea pig hearts. In both cases, KCNE2 protein is more abundant in ventricles than in atria. In both ventricular and atrial myocytes, KCNE2 protein is preferentially distributed on the cell surface. Ab1 can detect a prominent KCNE2 band in human ventricular muscle from nonfailing hearts. The band intensity is much fainter in atria and in failing ventricles. Ab2 specifically detects S98 phosphorylated KCNE2. Through exploring the functional significance of S98 phosphorylation, we uncover a novel mechanism by which KCNE2 modulates the human ether-a-go-go related gene (hERG) current amplitude: by accelerating hERG protein degradation and thus reducing the hERG protein level on the cell surface. S98 phosphorylation appears to be required for this modulation, so that S98 dephosphorylation leads to an increase in hERG/rapid delayed rectifier current amplitude. Our data confirm that KCNE2 protein is expressed in the ventricles of human and animal models. Furthermore, KCNE2 can modulate its partner channel function not only by altering channel conductance and/or gating kinetics, but also by affecting protein stability.
Brachial artery modifications to blood flow-restricted handgrip training and detraining
Authors: Hunt Julie E. A. , Walton Lucy A. , Ferguson Richard A.
Published: December 2011

Low load resistance training with blood flow restriction (BFR) can increase muscle size and strength, but the implications on the conduit artery are uncertain. We examined the effects of low-load dynamic handgrip training with and without BFR, and detraining, on measures of brachial artery function and structure. Nine male participants (26 ± 4 yr, 178 ± 3 cm, 78 ± 10 kg) completed 4 wk (3 days/wk) of dynamic handgrip training at 40% 1 repetition maximum (1RM). In a counterbalanced manner, one forearm trained under BFR (occlusion cuff at 80 mmHg) and the other under nonrestricted (CON) conditions. Brachial artery function [flow-mediated dilation (FMD)] and structure (diameter) were assessed using Doppler ultrasound. Measurements were made before training (pretraining), after training (posttraining), and after 2-wk no training (detraining). Brachial artery diameter at rest, in response to 5-min ischemia (peak diameter), and ischemic exercise (maximal diameter) increased by 3.0%, 2.4%, and 3.1%, respectively, after BFR training but not after CON. FMD did not change at any time point in either arm. Vascular measures in the BFR arm returned to baseline after 2 wk detraining with no change after CON. The data demonstrate that dynamic low-load handgrip training with BFR induced transient adaptations to conduit artery structure but not function.