bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffuse lipomatosis of the thyroid with amyloid deposition
Authors: Jacques T A , Stearns M P
Published: January 2013

Background:

The authors present a case of diffuse fatty infiltration of the thyroid gland with coexistent deposition of amyloid protein.

Method:

A case history and brief literature review concerning amyloid goitre and fatty infiltration of the thyroid are presented, and the relationship between these two phenomena is discussed.

Results:

A patient with AA amyloidosis presented with a slowly enlarging goitre, which on histological examination was extensively infiltrated with adipose tissue. Amyloid protein was found on Congo red staining.

Conclusion:

To our best knowledge, this patient represents the first reported case of diffuse lipomatosis of the thyroid gland causing goitre in a patient with AA amyloidosis. The presence of amyloid protein within the thyroid was not sufficient to cause enlargement per se, and was therefore of unclear significance. Together with previous reports of the concurrent deposition of amyloid and fat, this case raises questions as to the relationship between these two phenomena.
A new era in the Arctic Council's external relations? Broader consequences of the Nuuk observer rules for Arctic governance
Authors: Graczyk Piotr , Koivurova Timo
Published: January 2013

This article studies the role of observers under both the Arctic Environmental Protection Strategy (AEPS) and the Arctic Council (AC) before the Nuuk ministerial meeting that took place in May 2011. In this meeting, the AC actors were able to find consensus on criteria for admitting new observers, an issue that has received much media attention, given that China and the European Union, for example, are queuing to become observers in the AC. It is of importance to examine the content of these recently adopted Nuuk observer rules and their potential to impact decision-making on whether the external actors can be included as observers. Moreover, this article studies how, if at all, the Nuuk observer rules might affect the position of the AC in the broader setting of circumpolar cooperation.
Person-Centered Care Training in Long-Term Care Settings: Usefulness and Facility of Transfer into Practice
Authors: Viau-Guay Anabelle , Bellemare Marie , Feillou Isabelle , Trudel Louis , Desrosiers Johanne , Robitaille Marie-Josée
Published: January 2013

Les approches de soins centrées sur la personne sont de plus en plus recommandées en vue d’améliorer la qualité des soins de longue durée. Au Québec (Canada), l’approche relationnelle de soins a été implantée dans plusieurs établissements. Cette étude porte sur le point de vue des soignants formés sur l’utilité de cette approche ainsi que sur leur capacité à la transférer en pratique. Des questionnaires comportant des questions ouvertes ont été administrés un mois après la formation (n=392). Les réponses ont été catégorisées selon une approche qualitative. Les répondants perçoivent que certaines dimensions de l’approche sont hors de leur portée ou s’opposent à leurs croyances. Ils rapportent des pressions liées aux contraintes temporelles, à leurs collègues ainsi qu’aux familles des résidents. Ces résultats indiquent que la formation ne suffit pas à transformer les pratiques. Il faut également agir sur les croyances des individus ainsi que sur les situations de travail
Financial Management of the UK Pension Protection Fund
Authors: Charmaille J-P. , Clarke M.G. , Harding J. , Hildebrand C. , Mckinlay I.W. , Rice S.R. , Reynolds P.
Published: January 2013

The UK Pension Protection Fund (PPF) was established in April 2005 to protect the pensions of members of UK private sector defined benefit pension schemes which have insufficient assets and whose corporate sponsor fails. The Fund takes over the pension scheme assets and assumes responsibility for the payment of compensation to the former members of the scheme. The PPF is funded by a levy on the population of eligible schemes. This paper discusses the application of Enterprise Risk Management principles and techniques to the unique situation of the PPF. The elements of the financial management of the Fund have been developed by reference to practice within proprietary insurance institutions and within pension funds. The paper will be of interest and, we hope, of some value to students, researchers and analysts and also to the PPF's own stakeholder groups that have a stake in an effective pension protection regime.
Reflexivity, relative autonomy and the embedded individual in economics
Authors: FULLER CHRIS
Published: January 2013

This paper is about the mind of the embedded individual in heterodox economics. Beginning from Margaret Archer's analysis of modes of reflexivity and following the respective contributions of Geoff Hodgson and John Davis, the paper seeks to integrate into Archer's approach a place for habitual beliefs and an analysis of the ‘relative autonomy’ of the embedded individual. Archer's identification of modes of reflexivity is endorsed but her avoidance of any dispositional place for habit in the mind is questioned. It is argued that by excluding habits in this way, Archer, unlike Davis, implausibly assumes most individuals have achieved relative autonomy in their group associations. The essay develops an approach to the mind that articulates underlying relationships between habits and internal conversation, potentially enriching Archer's explanation of modes of reflexivity while locating Davis's notion of relative autonomy within that framework. Specific economic implications are then briefly considered.
Glutamate Metabolism is Impaired in Transgenic Mice with Tau Hyperphosphorylation
Authors: Nilsen Linn Hege , Rae Caroline , Ittner Lars M , Götz Jürgen , Sonnewald Ursula
Published: January 2013

In neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia, the protein tau is hyperphosphorylated and eventually aggregates to develop neurofibrillary tangles. Here, the consequences of tau hyperphosphorylation on both neuronal and astrocytic metabolism and amino-acid neurotransmitter homeostasis were assessed in transgenic mice expressing the pathogenic mutation P301L in the human tau gene (pR5 mice) compared with nontransgenic littermate controls. Mice were injected with the neuronal and astrocytic substrate [1-13C]glucose and the astrocytic substrate [1,2-13C]acetate. Hippocampus and cerebral cortex extracts were analyzed using 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry and high-performance liquid chromatography. The glutamate level was reduced in the hippocampus of pR5 mice, accompanied by reduced incorporation of 13C label derived from [1-13C]glucose in glutamate. In the cerebral cortex, glucose utilization as well as turnover of glutamate, glutamine, and GABA, were increased. This was accompanied by a relative increase in production of glutamate via the pyruvate carboxylation pathway in cortex. Overall, we revealed that astrocytes as well as glutamatergic and GABAergic neurons in the cortex of pR5 mice were in a hypermetabolic state, whereas in the hippocampus, where expression levels of mutant human tau are the highest, glutamate homeostasis was impaired.
An inducible transgenic mouse model for familial hypertension with hyperkalaemia (Gordon's syndrome or pseudohypoaldosteronism type II)
Authors: Chowdhury Jabed A. , Liu Che-Hsiung , Zuber Annie M. , O’Shaughnessy Kevin M.
Published: January 2013

Mutations in the novel serine/threonine WNK [With No lysine (=K)] kinases WNK1 and WNK4 cause PHAII (pseudohypoaldosteronism type II or Gordon's syndrome), a rare monogenic syndrome which causes hypertension and hyperkalaemia on a background of a normal glomerular filtration rate. Current animal models for PHAII recapitulate some aspects of the disease phenotype, but give no clues to how rapidly the phenotype emerges or whether it is reversible. To this end we have created an inducible PHAII transgenic animal model that expresses a human disease-causing WNK4 mutation, WNK4 Q565E, under the control of the Tet-On system. Several PHAII inducible transgenic mouse lines were created, each with differing TG (transgene) copy numbers and displaying varying degrees of TG expression (low, medium and high). Each of these transgenic lines demonstrated similar elevations of BP (blood pressure) and plasma potassium after 4 weeks of TG induction. Withdrawal of doxycycline switched off mutant TG expression and the disappearance of the PHAII phenotype. Western blotting of microdissected kidney nephron segments confirmed that expression of the thiazide-sensitive NCC (Na+–Cl− co-transporter) was increased, as expected, in the distal convoluted tubule when transgenic mice were induced with doxycycline. The kidneys of these mice also do not show the morphological changes seen in the previous transgenic model expressing the same mutant form of WNK4. This inducible model shows, for the first time, that in vivo expression of a mutant WNK4 protein is sufficient to cause the rapid and reversible appearance of a PHAII disease phenotype in mice.
Low‐power, wide‐range time‐to‐digital converter for all digital phase‐locked loops
Authors: Jeong C.‐H. , Kwon C.‐K. , Kim H. , Hwang I.‐C. , Kim S.‐W.
Published: January 2013

A time‐to‐digital converter (TDC) for a low‐power, wide‐range all digital phase‐locked loop (ADPLL) is presented. The proposed TDC uses an enabling signal with variable duration to achieve low power and wide range. For verification purpose, the ADPLL is fabricated in a 0.11 µm CMOS technology. The ADPLL dissipates 6.02mW at an output frequency of 1.68GHz and its output frequency is measured as 0.24–1.68 GHz from a 1.2 V supply.
VLSI implementation of low‐power cost‐efficient lossless ECG encoder design for wireless healthcare monitoring application
Authors: Chen S.‐L. , Wang J.‐G
Published: January 2013

An efficient VLSI architecture of a lossless ECG encoding circuit is proposed for wireless healthcare monitoring applications. To reduce the transmission and storage data, a novel lossless compression algorithm is proposed for ECG signal compression. It consists of a novel adaptive rending predictor and a novel two‐stage entropy encoder based on two Huffman coding tables. The proposed lossless ECG encoder design was implemented using only simple arithmetic units. To improve the performance, the proposed ECG encoder was designed by pipeline technology and implemented the two‐stage entropy encoder by the architecture of a look‐up table. The VLSI architecture of this work contains 3.55 K gate counts and its core area is 45987 µm2 synthesised by a 0.18 µm CMOS process. It can operate at 100 MHz processing rate with only 36.4 µW. The data compression rate reaches an average value 2.43 for the MIT‐BIH Arrhythmia Database. Compared with the previous low‐complexity and high performance techniques, this work achieves lower hardware cost, lower power consumption, and a better compression rate than other lossless ECG encoder designs.
Using gait symmetry to virtually align a triaxial accelerometer during running and walking
Authors: Avvenuti M. , Casella A. , Cesarini D.
Published: January 2013

During running and walking the human centre of mass experiences a symmetric acceleration along the mediolateral direction. This reported work shows how to exploit this knowledge to correct misalignments of the axes of a trunk‐mounted accelerometer with respect to the body axes. After vertical alignment, based on the gravitational component of the signal, the technique computes the virtual rotation angle of the axes lying in the horizontal plane. The chosen angle minimises the autocorrelation of the signal along the mediolateral direction.
EMI susceptibility of DTMOS opamps
Authors: Richelli A.
Published: January 2013

The susceptibility to electromagnetic interference (EMI) of an amplifier based on dynamic threshold voltage MOS transistors (DTMOSs) has been analysed and improved thanks to an easy modification of the input differential stage. The final opamp has been designed in a 0.18μm standard CMOS process.
Plasma processing of low-k dielectrics
Authors: Baklanov Mikhail R. , de Marneffe Jean-Francois , Shamiryan Denis , Urbanowicz Adam M. , Shi Hualiang , Rakhimova Tatyana V. , Huang Huai , Ho Paul S.
Published: January 2013

This paper presents an in-depth overview of the present status and novel developments in the field of plasma processing of low dielectric constant (low-k) materials developed for advanced interconnects in ULSI technology. The paper summarizes the major achievements accomplished during the last 10 years. It includes analysis of advanced experimental techniques that have been used, which are most appropriate for low-k patterning and resist strip, selection of chemistries, patterning strategies, masking materials, analytical techniques, and challenges appearing during the integration. Detailed discussions are devoted to the etch mechanisms of low-k materials and their degradation during the plasma processing. The problem of k-value degradation (plasma damage) is a key issue for the integration, and it is becoming more difficult and challenging as the dielectric constant of low-k materials scales down. Results obtained with new experimental methods, like the small gap technique and multi-beams systems with separated sources of ions, vacuum ultraviolet light, and radicals, are discussed in detail. The methods allowing reduction of plasma damage and restoration of dielectric properties of damaged low-k materials are also discussed.
Off-shell Jost solutions for Coulomb and Coulomb-like interactions in all partial waves
Authors: Laha U. , Bhoi J.
Published: January 2013

By exploiting the theory of ordinary differential equations, with judicious use of boundary conditions, interacting Green's functions and their integral transforms together with certain properties of higher transcendental functions, useful analytical expressions for the off-shell Jost solutions for motion in Coulomb and Coulomb-nuclear potentials are derived in maximal reduced form through different approaches to the problem in the representation space. The exact analytical expressions for the off-shell Jost solutions for Coulomb and Coulomb-like potentials are believed to be useful for the description of the charged particle scattering/reaction processes.
Does scandium resemble transition or rare earth metals when it is grown on silicon surfaces?
Authors: Shiu H. W. , Chang L. Y. , Lou J. L. , Wu C. P. , Chen C.-H.
Published: January 2013

Scandium (Sc) has long been considered a rare earth (RE) element rather than a transition metal (TM) when grown on silicon (Si) surfaces, although little experimental evidence supports it. When scandium nitride (ScN) grown on Si is a promising buffer material for combining gallium nitride (GaN) and Si, a thin Sc silicide layer may be formed at the ScN/Si interface and, therefore, the electronic properties of Sc on Si are becoming an important issue to address. In this study, the interfacial atomic and electronic properties of Sc on n-type Si (111)-7 × 7 reconstructed surfaces have been studied by low energy electron diffraction and synchrotron radiation based high-resolution X-ray photoemission spectroscopy. By varying the Sc overlayer thickness, different silicide phases were observed and the Schottky barrier (SB) evolution was obtained. The SB evolution of Sc on Si is closer to TM than RE. This barrier may interfere with carrier transportation if GaN/ScN/Si tri-layered heterostructures are grown.
Ferroelectric/ferromagnetic ceramic composite and its hybrid permittivity stemming from hopping charge and conductivity inhomogeneity
Authors: Zheng Hui , Li Lu , Xu Zhaojun , Weng Wenjian , Han Gaorong , Ma Ning , Du Piyi
Published: January 2013

Exploring the nature of multiferroic ceramic composite with dual high performances is much important to take full advantage of its novel dielectric properties. In this paper, Ni0.5Zn0.5291Fe2O4/BaTiO3 ceramic composite is proposed and successfully prepared from BTO and NZFO powders which are obtained by sol-gel process and citric acid combustion method, respectively. Results show that with increasing BTO content from 0 to 25 vol. % in the matrix of NZFO, the permittivity of the composite decreases from 220 k to 100 k at low frequencies (∼40 Hz) and contrarily from 20 to 100 at high frequencies (∼100 MHz). It is mainly ascribed to the instant polarization in NZFO at low frequencies and the polarization in the perovskite phase of BTO at sufficiently high frequencies. The permittivity of the ferrite and composite is shown to be compatible with a hybrid model proposed, which concerns hopping charges between Fe2+ and Fe3+, conductivity heterogeneity at the grain boundaries of the ferrite, and changes in the conductivities of the two phases induced by interdiffusion of the ions between the two phases. The composition dependence of the permittivity is agreeable with Kirkpatrick's compound law with the percolation threshold of NZFO to be about 55 vol. %.
Alkali-induced hydrogenation of epitaxial graphene by water splitting at 100 K
Authors: Politano A. , Chiarello G.
Published: January 2013

The coadsorption of potassium with water at 100 K on graphene/Pt(111) has been studied by high-resolution electron energy loss spectroscopy. The adsorption of alkali metals induces water splitting and the formation of C–H and C–OH groups. Such finding is of great interest for tailoring graphene-Pt electro-catalysts. Furthermore, the alkali-promoted dissociation of water molecules offers the possibility to attain a partial hydrogenation of the graphene sheet even at low temperature.
Photothermoelectric effect as a means for thermal characterization of nanocomposites based on intrinsically conducting polymers and carbon nanotubes
Authors: Kuriakose Maju , Depriester Michael , Chan Yu King Roch , Roussel Frédérick , Hadj Sahraoui Abdelhak
Published: January 2013

Recent advances in nanostructured materials have spurred the development of improved thermoelectric (TE) devices. Performances of these systems are strongly linked to their thermal conductivities. Accurate measurement techniques of thermal parameters are therefore required to assess the efficiency of new thermoelectric materials. In this work, thermal parameters (thermal diffusivity, thermal conductivity, and thermal effusivity) of nanostructured thermoelectric composites based on oxidised or unoxidised carbon nanotubes at 6.6 wt. % mixed with doped nanofibrous polyaniline have been measured with a novel photothermal method called photothermoelectricity. The thermal parameters are obtained from analyses of the phase and amplitude of the thermoelectric signal generated by the sample when it is periodically heated by a laser beam. Figure of merits are calculated from these results which indicate that the best nanocomposite exhibits almost four order of magnitude improvement compared with that of the pure doped matrix at room temperature.
Interferometric measurement of the pyroelectric coefficient in lithium niobate
Authors: Popescu S. T. , Petris A. , Vlad V. I.
Published: January 2013

We report the measurement of pyroelectric field in LiNbO3 by introducing a new method, based on optical interferometry. The pyroelectric coefficient of the congruent LiNbO3 crystals has been determined by this method and the value obtained for it, ∼95 μC/(m2 · K), is consistent with previous results reported in literature, obtained by other methods.
Investigating dielectric properties of different stages of syngeneic murine ovarian cancer cells
Authors: Salmanzadeh Alireza , Sano Michael B. , Gallo-Villanueva Roberto C. , Roberts Paul C. , Schmelz Eva M. , Davalos Rafael V.
Published: January 2013

In this study, the electrical properties of four different stages of mouse ovarian surface epithelial (MOSE) cells were investigated using contactless dielectrophoresis (cDEP). This study expands the work from our previous report describing for the first time the crossover frequency and cell specific membrane capacitance of different stages of cancer cells that are derived from the same cell line. The specific membrane capacitance increased as the stage of malignancy advanced from 15.39 ± 1.54 mF m−2 for a non-malignant benign stage to 26.42 ± 1.22 mF m−2 for the most aggressive stage. These differences could be the result of morphological variations due to changes in the cytoskeleton structure, specifically the decrease of the level of actin filaments in the cytoskeleton structure of the transformed MOSE cells. Studying the electrical properties of MOSE cells provides important information as a first step to develop cancer-treatment techniques which could partially reverse the cytoskeleton disorganization of malignant cells to a morphology more similar to that of benign cells.
Judging Whether it is Aesthetic: Does Equilibrium Compensate for the Lack of Symmetry?
Authors: Samuel Françoise , Kerzel Dirk
Published: January 2013

In two experiments, we explored whether compositions made up of two or three rectangles received high aesthetics ratings when the composition was equilibrated, that is, when the center of mass of the weights represented by the areas of the rectangles were in the center of the composition. We supposed that equilibrated stimuli might be appreciated as much as symmetric stimuli. We further wanted to find out whether aesthetics ratings, balance ratings, and weight ratings differ from each other, and which stimulus characteristics influence each rating. We observed that the position of the center of mass of the compositions influenced the aesthetics ratings only slightly whereas it influenced the weight ratings more strongly. In contrast with this, the variation of the overall shape of the rectangles making up the compositions influenced the aesthetics ratings more strongly than the weight ratings. At first sight, balance ratings appeared intermediate between the aesthetics ratings and the weight ratings. However, when we varied the area ratio of the rectangles making up the composition, we observed that the balance ratings were independent of the two other ratings.
Basic Research for Development of a Communication Support Device Using Air-Conducted Sound Localization
Authors: Chishima Makoto , Otani Makoto , Kayama Mizue , Hashimoto Masami , Itoh Kazunori , Arai Yoshiaki
Published: January 2013

We have been engaged in the development of a new support device for subjects whose independent daily activities are limited due to severe progressive neuromuscular disease. In this study, we examined the possibility of developing a P300-type BCI (brain–computer interface) using orientation discrimination of stimulus sound with auditory lateralisation using a virtual sound source for air-conducted sound presented to the subject bitemporally. Sound stimulation with sound localization used in the study had a level difference of approximately 10 dB and time difference of approximately 0.6 ms, and was fixed at 60° to the left and to the right from the median. It was suggested that a virtual sound source with sound image fixed in left and right directions with added difference between the left and right ears can be used for development of a P300-type BCI by applying auditory stimulation. To further proceed to the development of a P300-type BCI system using auditory stimulation with comfort and convenience with the aim of reducing user burden in a clinical setting, we will reexamine the extraction algorithm for the target waveform, and examine the effects of the interval between stimulus presentation to make this a daily life supporting system to realise a faster and more efficient multiple command sending mechanism.
The Effect of Auditory Stream Segregation on Synchronized Tapping
Authors: Ashitani Yui
Published: January 2013

We can tap in synchrony with a simple sequence of auditory tones, but our taps generally precede it by several tens of milliseconds(“negative mean asynchrony”). A simple sequence of sounds sometimes causes auditory perceptual organization different from the physical sequence. However little is known about interactions between the auditory perceptual organization and sensorimotor synchronization. The present study aimed at investigating effects of the auditory stream segregation (one stream or two) on the synchronized tapping. Participants listened to a sequence of two different auditory tones presented alternately, and were asked to tap in synchrony with one group of tones (ie, high tones or low) with index fingers. After that, they were also asked whether the tones were perceived one or two streams. The results showed that negative mean asynchrony was caused both in perceived one stream and two. However, the amplitude of the asynchrony was smaller when they perceived the tones as one stream than as two. This indicates that auditory perceptual organization affects sensorimotor synchronization even if auditory tones were presented with the same timing. When we synchronize bodily with auditory tones as in the case of a motor rehabilitation, we have to take account of auditory perceptual organization.
In sacco evaluation of ruminal degradability of waste vinegar residue as a feedstuff for ruminants
Authors: Song Zengting , Dong Xiaofang , Tong Jianming , Wang Zhihong
Published: January 2013

Waste vinegar residue (WVR) is a by-product of vinegar processing by solid-state fermentation. In this study, two experiments were conducted to determine chemical composition and ruminal degradability of WVR and whether WVR can be used as a feedstuff for ruminants. In Experiment 1, 14 WVR samples were incubated in the rumen of three Inner Mongolia White Cashmere Goats to determine the in sacco ruminal degradability parameters for DM, crude protein (CP) and neutral detergent fibre (NDF). The NDF, CP and ether extract (EE) contents of the WVR samples were 796.6, 125.2 and 93.3 g/kg, respectively. The greatest variation was observed for lactic acid, which ranged from 150.39 to 4391.12 mg/kg with an average of 1023.84 mg/kg. The average A, B and C fractions of DM for the 14 samples of WVR were 122, 350, and 528 g/kg, respectively. The effective degradability of DM, CP and NDF were 275, 550 and 211 g/kg, respectively. In Experiment 2, the in sacco degradation parameters for DM, CP and NDF of Chinese leymus, corn stalk and WVR were evaluated in a 3 × 3 Latin-square design. The rapidly degradable fraction of the DM and NDF for WVR was significantly (P < 0.01) greater than that of Chinese leymus and corn stalk. No difference in rumen-degraded DM, rumen-degraded CP and rumen-degraded NDF was found between Chinese leymus and WVR (P > 0.05). It is concluded that, WVR is not well digested ruminally but is a good source of protein for ruminants giving it value as an ingredient in ruminant diets.
Income diversification and risk for fishermen
Authors: Kasperski Stephen , Holland Daniel S.
Published: January 2013

Catches and prices from many fisheries exhibit high interannual variability, leading to variability in the income derived by fishery participants. The economic risk posed by this may be mitigated in some cases if individuals participate in several different fisheries, particularly if revenues from those fisheries are uncorrelated or vary asynchronously. We construct indices of gross income diversification from fisheries at the level of individual vessels and find that the income of the current fleet of vessels on the US West Coast and in Alaska is less diverse than at any point in the past 30 y. We also find a dome-shaped relationship between the variability of individuals' income and income diversification, which implies that a small amount of diversification does not reduce income risk but that higher levels of diversification can substantially reduce the variability of income from fishing. Moving from a single fishery strategy to a 50-25-25 split in revenues reduces the expected coefficient of variation of gross revenues between 24% and 65% for the vessels included in this study. The increasing access restrictions in many marine fisheries through license reductions and moratoriums have the potential to limit fishermen's ability to diversify their income risk across multiple fisheries. Catch share programs often result in consolidation initially and may reduce diversification. However, catch share programs also make it feasible for fishermen to build a portfolio of harvest privileges and potentially reduce their income risk. Therefore, catch share programs create both threats and opportunities for fishermen wishing to maintain diversified fishing strategies.
Dependence receptor TrkC is a putative colon cancer tumor suppressor
Authors: Genevois Anne-Laure , Ichim Gabriel , Coissieux Marie-May , Lambert Marie-Pierre , Lavial Fabrice , Goldschneider David , Jarrosson-Wuilleme Loraine , Lepinasse Florian , Gouysse Géraldine , Herceg Zdenko , Scoazec Jean-Yves , Tauszig-Delamasure Servane , Mehlen Patrick
Published: January 2013

The TrkC neurotrophin receptor belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Such a trait has been hypothesized to confer tumor-suppressor activity. Indeed, cells that express these receptors are thought to be dependent on ligand availability for their survival, a mechanism that inhibits uncontrolled tumor cell proliferation and migration. TrkC is a classic tyrosine kinase receptor and therefore generally considered to be a proto-oncogene. We show here that TrkC expression is down-regulated in a large fraction of human colorectal cancers, mainly through promoter methylation. Moreover, we show that TrkC silencing by promoter methylation is a selective advantage for colorectal cell lines to limit tumor cell death. Furthermore, reestablished TrkC expression in colorectal cancer cell lines is associated with tumor cell death and inhibition of in vitro characteristics of cell transformation, as well as in vivo tumor growth. Finally, we provide evidence that a mutation of TrkC detected in a sporadic cancer is a loss-of-proapoptotic function mutation. Together, these data support the conclusion that TrkC is a colorectal cancer tumor suppressor.
Specular reflections and the estimation of shape from binocular disparity
Authors: Muryy Alexander A. , Welchman Andrew E. , Blake Andrew , Fleming Roland W.
Published: January 2013

Binocular stereopsis is a powerful visual depth cue. To exploit it, the brain matches features from the two eyes’ views and measures their interocular disparity. This works well for matte surfaces because disparities indicate true surface locations. However, specular (glossy) surfaces are problematic because highlights and reflections are displaced from the true surface in depth, leading to information that conflicts with other cues to 3D shape. Here, we address the question of how the visual system identifies the disparity information created by specular reflections. One possibility is that the brain uses monocular cues to identify that a surface is specular and modifies its interpretation of the disparities accordingly. However, by characterizing the behavior of specular disparities we show that the disparity signals themselves provide key information (“intrinsic markers”) that enable potentially misleading disparities to be identified and rejected. We presented participants with binocular views of specular objects and asked them to report perceived depths by adjusting probe dots. For simple surfaces—which do not exhibit intrinsic indicators that the disparities are “wrong”—participants incorrectly treat disparities at face value, leading to erroneous judgments. When surfaces are more complex we find the visual system also errs where the signals are reliable, but rejects and interpolates across areas with large vertical disparities and horizontal disparity gradients. This suggests a general mechanism in which the visual system assesses the origin and utility of sensory signals based on intrinsic markers of their reliability.
Small open reading frames associated with morphogenesis are hidden in plant genomes
Authors: Hanada Kousuke , Higuchi-Takeuchi Mieko , Okamoto Masanori , Yoshizumi Takeshi , Shimizu Minami , Nakaminami Kentaro , Nishi Ranko , Ohashi Chihiro , Iida Kei , Tanaka Maho , Horii Yoko , Kawashima Mika , Matsui Keiko , Toyoda Tetsuro , Shinozaki Kazuo , Seki Motoaki , Matsui Minami
Published: January 2013

It is likely that many small ORFs (sORFs; 30–100 amino acids) are missed when genomes are annotated. To overcome this limitation, we identified ∼8,000 sORFs with high coding potential in intergenic regions of the
Arabidopsis thaliana
genome. However, the question remains as to whether these coding sORFs play functional roles. Using a designed array, we generated an expression atlas for 16 organs and 17 environmental conditions among 7,901 identified coding sORFs. A total of 2,099 coding sORFs were highly expressed under at least one experimental condition, and 571 were significantly conserved in other land plants. A total of 473 coding sORFs were overexpressed; ∼10% (49/473) induced visible phenotypic effects, a proportion that is approximately seven times higher than that of randomly chosen known genes. These results indicate that many coding sORFs hidden in plant genomes are associated with morphogenesis. We believe that the expression atlas will contribute to further study of the roles of sORFs in plants.
Subtropical High predictability establishes a promising way for monsoon and tropical storm predictions
Authors: Wang Bin , Xiang Baoqiang , Lee June-Yi
Published: January 2013

Monsoon rainfall and tropical storms (TSs) impose great impacts on society, yet their seasonal predictions are far from successful. The western Pacific Subtropical High (WPSH) is a prime circulation system affecting East Asian summer monsoon (EASM) and western North Pacific TS activities, but the sources of its variability and predictability have not been established. Here we show that the WPSH variation faithfully represents fluctuations of EASM strength (
r
= –0.92), the total TS days over the subtropical western North Pacific (
r
= –0.81), and the total number of TSs impacting East Asian coasts (
r
= –0.76) during 1979–2009. Our numerical experiment results establish that the WPSH variation is primarily controlled by central Pacific cooling/warming and a positive atmosphere-ocean feedback between the WPSH and the Indo-Pacific warm pool oceans. With a physically based empirical model and the state-of-the-art dynamical models, we demonstrate that the WPSH is highly predictable; this predictability creates a promising way for prediction of monsoon and TS. The predictions using the WPSH predictability not only yields substantially improved skills in prediction of the EASM rainfall, but also enables skillful prediction of the TS activities that the current dynamical models fail. Our findings reveal that positive WPSH–ocean interaction can provide a source of climate predictability and highlight the importance of subtropical dynamics in understanding monsoon and TS predictability.
Linking animal-borne video to accelerometers reveals prey capture variability
Authors: Watanabe Yuuki Y. , Takahashi Akinori
Published: January 2013

Understanding foraging is important in ecology, as it determines the energy gains and, ultimately, the fitness of animals. However, monitoring prey captures of individual animals is difficult. Direct observations using animal-borne videos have short recording periods, and indirect signals (e.g., stomach temperature) are never validated in the field. We took an integrated approach to monitor prey captures by a predator by deploying a video camera (lasting for 85 min) and two accelerometers (on the head and back, lasting for 50 h) on free-swimming Adélie penguins. The movies showed that penguins moved the heads rapidly to capture krill in midwater and fish (
Pagothenia borchgrevinki
) underneath the sea ice. Captures were remarkably fast (two krill per second in swarms) and efficient (244 krill or 33
P. borchgrevinki
in 78–89 min). Prey captures were detected by the signal of head acceleration relative to body acceleration with high sensitivity and specificity (0.83–0.90), as shown by receiver-operating characteristic analysis. Extension of signal analysis to the entire behavioral records showed that krill captures were spatially and temporally more variable than
P. borchgrevinki
captures. Notably, the frequency distribution of krill capture rate closely followed a power-law model, indicating that the foraging success of penguins depends on a small number of very successful dives. The three steps illustrated here (i.e., video observations, linking video to behavioral signals, and extension of signal analysis) are unique approaches to understanding the spatial and temporal variability of ecologically important events such as foraging.
Experiments and simulations show how long-range contacts can form in expanded unfolded proteins with negligible secondary structure
Authors: Meng Wenli , Lyle Nicholas , Luan Bowu , Raleigh Daniel P. , Pappu Rohit V.
Published: January 2013

The sizes of unfolded proteins under highly denaturing conditions scale asN0.59with chain length. This suggests that denaturing conditions mimic good solvents, whereby the preference for favorable chain–solvent interactions causes intrachain interactions to be repulsive, on average. Beyond this generic inference, the broader implications ofN0.59scaling for quantitative descriptions of denatured state ensembles (DSEs) remain unresolved. Of particular interest is the degree to whichN0.59scaling can simultaneously accommodate intrachain attractions and detectable long-range contacts. Here we present data showing that the DSE of the N-terminal domain of the L9 (NTL9) ribosomal protein in 8.3 M urea lacks detectable secondary structure and forms expanded conformations in accord with the expectedN0.59scaling behavior. Paramagnetic relaxation enhancements, however, indicate the presence of detectable long-range contacts in the denatured-state ensemble of NTL9. To explain these observations we used atomistic thermal unfolding simulations to identify ensembles whose properties are consistent with all of the experimental observations, thus serving as useful proxies for the DSE of NTL9 in 8.3 M urea. Analysis of these ensembles shows that residual attractions are present under mimics of good solvent conditions, and for NTL9 they result from low-likelihood, medium/long-range contacts between hydrophobic residues. Our analysis provides a quantitative framework for the simultaneous observation ofN0.59scaling and low-likelihood long-range contacts for the DSE of NTL9. We propose that such low-likelihood intramolecular hydrophobic clusters might be a generic feature of DSEs that play a gatekeeping role to protect against aggregation during protein folding.
Elasticity and wrinkled morphology of
Bacillus subtilis
pellicles
Authors: Trejo Miguel , Douarche Carine , Bailleux Virginie , Poulard Christophe , Mariot Sandrine , Regeard Christophe , Raspaud Eric
Published: January 2013

Wrinkled morphology is a distinctive phenotype observed in mature biofilms produced by a great number of bacteria. Here we study the formation of macroscopic structures (wrinkles and folds) observed during the maturation of
Bacillus subtilis
pellicles in relation to their mechanical response. We show how the mechanical buckling instability can explain their formation. By performing simple tests, we highlight the role of confining geometry and growth in determining the symmetry of wrinkles. We also experimentally demonstrate that the pellicles are soft elastic materials for small deformations induced by a tensile device. The wrinkled structures are then described by using the equations of elastic plates, which include the growth process as a simple parameter representing biomass production. This growth controls buckling instability, which triggers the formation of wrinkles. We also describe how the structure of ripples is modified when capillary effects are dominant. Finally, the experiments performed on a mutant strain indicate that the presence of an extracellular matrix is required to maintain a connective and elastic pellicle.
Fas expression by tumor stroma is required for cancer eradication
Authors: Listopad Joanna J. , Kammertoens Thomas , Anders Kathleen , Silkenstedt Bjoern , Willimsky Gerald , Schmidt Karin , Kuehl Anja A. , Loddenkemper Christoph , Blankenstein Thomas
Published: January 2013

The contribution of molecules such as perforin, IFN-γ (IFNγ), and particularly Fas ligand (FasL) by transferred CD8+effector T (TE) cells to rejection of large, established tumors is incompletely understood. Efficient attack against large tumors carrying a surrogate tumor antigen (mimicking a “passenger” mutation) by TEcells requires action of IFNγ on tumor stroma cells to avoid selection of antigen-loss variants. Because “cancer-driving” antigens (CDAs) are rarely counterselected, IFNγ may be expected to be dispensable in elimination of cancers by targeting a CDA. Here, initial regression of large, established tumors required neither IFNγ, FasL, nor perforin by transferred CD8+TEcells targeting Simian Virus (SV) 40 large T as CDA. However, cytotoxic TEcells lacking IFNγ or FasL could not prevent relapse despite retention of the rejection antigen by the cancer cells. Complete tumor rejection required IFNγ-regulated Fas by the tumor stroma. Therefore, TEcells lacking IFNγ or FasL cannot prevent progression of antigenic cancer because the tumor stroma escapes destruction if its Fas expression is down-regulated.
Structure of ADP-aluminium fluoride-stabilized protochlorophyllide oxidoreductase complex
Authors: Moser Jürgen , Lange Christiane , Krausze Joern , Rebelein Johannes , Schubert Wolf-Dieter , Ribbe Markus W. , Heinz Dirk W. , Jahn Dieter
Published: January 2013

Photosynthesis uses chlorophylls for the conversion of light into chemical energy, the driving force of life on Earth. During chlorophyll biosynthesis in photosynthetic bacteria, cyanobacteria, green algae and gymnosperms, dark-operative protochlorophyllide oxidoreductase (DPOR), a nitrogenase-like metalloenzyme, catalyzes the chemically challenging two-electron reduction of the fully conjugated ring system of protochlorophyllide
a
. The reduction of the C-17=C-18 double bond results in the characteristic ring architecture of all chlorophylls, thereby altering the absorption properties of the molecule and providing the basis for light-capturing and energy-transduction processes of photosynthesis. We report the X-ray crystallographic structure of the substrate-bound, ADP-aluminium fluoride–stabilized (ADP·AlF
3
-stabilized) transition state complex between the DPOR components L
2
and (NB)
2
from the marine cyanobacterium
Prochlorococcus marinus
. Our analysis permits a thorough investigation of the dynamic interplay between L
2
and (NB)
2
. Upon complex formation, substantial ATP-dependent conformational rearrangements of L
2
trigger the protein–protein interactions with (NB)
2
as well as the electron transduction via redox-active [4Fe–4S] clusters. We also present the identification of artificial “small-molecule substrates” of DPOR in correlation with those of nitrogenase. The catalytic differences and similarities between DPOR and nitrogenase have broad implications for the energy transduction mechanism of related multiprotein complexes that are involved in the reduction of chemically stable double and/or triple bonds.
Antimicrobial drug resistance affects broad changes in metabolomic phenotype in addition to secondary metabolism
Authors: Derewacz Dagmara K. , Goodwin Cody R. , McNees C. Ruth , McLean John A. , Bachmann Brian O.
Published: January 2013

Bacteria develop resistance to many classes of antibiotics vertically, by engendering mutations in genes encoding transcriptional and translational apparatus. These severe adaptations affect global transcription, translation, and the correspondingly affected metabolism. Here, we characterize metabolome scale changes in transcriptional and translational mutants in a genomically characterized
Nocardiopsis
, a soil-derived actinomycete, in stationary phase. Analysis of ultra-performance liquid chromatography–ion mobility–mass spectrometry metabolomic features from a cohort of streptomycin- and rifampicin-resistant mutants grown in the absence of antibiotics exhibits clear metabolomic speciation, and loadings analysis catalogs a marked change in metabolic phenotype. Consistent with derepression, up to 311 features are observed in antibiotic-resistant mutants that are not detected in their progenitors. Mutants demonstrate changes in primary metabolism, such as modulation of fatty acid composition and the increased production of the osmoprotectant ectoine, in addition to the presence of abundant emergent potential secondary metabolites. Isolation of three of these metabolites followed by structure elucidation demonstrates them to be an unusual polyketide family with a previously uncharacterized xanthene framework resulting from sequential oxidative carbon skeletal rearrangements. Designated as “mutaxanthenes,” this family can be correlated to a type II polyketide gene cluster in the producing organism. Taken together, these data suggest that biosynthetic pathway derepression is a general consequence of some antibiotic resistance mutations.
A vector-free microfluidic platform for intracellular delivery
Authors: Sharei Armon , Zoldan Janet , Adamo Andrea , Sim Woo Young , Cho Nahyun , Jackson Emily , Mao Shirley , Schneider Sabine , Han Min-Joon , Lytton-Jean Abigail , Basto Pamela A. , Jhunjhunwala Siddharth , Lee Jungmin , Heller Daniel A. , Kang Jeon Woong , Hartoularos George C. , Kim Kwang-Soo , Anderson Daniel G. , Langer Robert , Jensen Klavs F.
Published: January 2013

Intracellular delivery of macromolecules is a challenge in research and therapeutic applications. Existing vector-based and physical methods have limitations, including their reliance on exogenous materials or electrical fields, which can lead to toxicity or off-target effects. We describe a microfluidic approach to delivery in which cells are mechanically deformed as they pass through a constriction 30–80% smaller than the cell diameter. The resulting controlled application of compression and shear forces results in the formation of transient holes that enable the diffusion of material from the surrounding buffer into the cytosol. The method has demonstrated the ability to deliver a range of material, such as carbon nanotubes, proteins, and siRNA, to 11 cell types, including embryonic stem cells and immune cells. When used for the delivery of transcription factors, the microfluidic devices produced a 10-fold improvement in colony formation relative to electroporation and cell-penetrating peptides. Indeed, its ability to deliver structurally diverse materials and its applicability to difficult-to-transfect primary cells indicate that this method could potentially enable many research and clinical applications.
Simplified protein design biased for prebiotic amino acids yields a foldable, halophilic protein
Authors: Longo Liam M. , Lee Jihun , Blaber Michael
Published: January 2013

A compendium of different types of abiotic chemical syntheses identifies a consensus set of 10 “prebiotic” α-amino acids. Before the emergence of biosynthetic pathways, this set is the most plausible resource for protein formation (i.e., proteogenesis) within the overall process of abiogenesis. An essential unsolved question regarding this prebiotic set is whether it defines a “foldable set”—that is, does it contain sufficient chemical information to permit cooperatively folding polypeptides? If so, what (if any) characteristic properties might such polypeptides exhibit? To investigate these questions, two “primitive” versions of an extant protein fold (the β-trefoil) were produced by top-down symmetric deconstruction, resulting in a reduced alphabet size of 12 or 13 amino acids and a percentage of prebiotic amino acids approaching 80%. These proteins show a substantial acidification of pI and require high salt concentrations for cooperative folding. The results suggest that the prebiotic amino acids do comprise a foldable set within the halophile environment.