bluuebunny/crossref_metadata_2025 huggingface dataset:
Why the International Criminal Court Must Pretend to Ignore Politics
Authors: Struett Michael J.
Published: April 2012

Since the International Criminal Court (ICC) prosecutes crimes of mass violence that are inherently political in nature, its actions will inevitably have political consequences about which the prosecutor and judges should be as well informed as possible. As some of the other contributors to this roundtable note, the ICC's actions and inactions may even have life-and-death consequences in the real world. It is ethically irresponsible for the ICC's officers to ignore those concerns. At the same time, the court's moral and legal authority derives entirely from its claim that it applies universal rules wherever it has jurisdiction. In order for the International Criminal Court to build legitimacy over time, it must both act and be seen to act in a neutral way that transcends political pressures. Rule-of-law courts do not derive their authority from their ability to command the use of force. Nor do they have the legitimacy of elected political officials who act as the representatives of a political community. The legitimacy of courts is a function of their claim to uphold universal rules of law that the community has chosen to adopt, regardless of whether doing so is popular or even prudent in a particular case with particular constituencies. Consequently, court officers in their formal actions—including prosecutorial requests for investigations, issuing arrest warrants, and filing charges, as well as in the judges' decisions on those questions—should always ground the rationale for their decisions in the pretense that they act only to uphold the law and without regard for political considerations.
Derivation and validation of clinical prediction rules for reduced vancomycin susceptibility in Staphylococcus aureus bacteraemia
Authors: HAN J. H. , BILKER W. B. , EDELSTEIN P. H. , MASCITTI K. B. , LAUTENBACH E.
Published: April 2012

Reduced vancomycin susceptibility (RVS) may lead to poor clinical outcomes in Staphylococcus aureus bacteraemia. We conducted a cohort study of 392 patients with S. aureus bacteraemia within a university health system. The association between RVS, as defined by both Etest [vancomycin minimum inhibitory concentration (MIC) >1·0 μg/ml] and broth microdilution (vancomycin MIC ⩾1·0 μg/ml), and patient and clinical variables were evaluated to create separate predictive models for RVS. In total, 134 (34·2%) and 73 (18·6%) patients had S. aureus isolates with RVS by Etest and broth microdilution, respectively. The final model for RVS by Etest included methicillin resistance [odds ratio (OR) 1·51, 95% confidence interval (CI) 0·97–2·34], non-white race (OR 0·67, 95% CI 0·42–1·07), healthcare-associated infection (OR 0·56, 95% CI 0·32–0·96), and receipt of any antimicrobial therapy ⩽30 days prior to the culture date (OR 3·06, 95% CI 1·72–5·44). The final model for RVS by broth microdilution included methicillin resistance (OR 2·45, 95% CI 1·42–4·24), admission through the emergency department (OR 0·54, 95% CI 0·32–0·92), presence of an intravascular device (OR 2·24, 95% CI 1·30–3·86), and malignancy (OR 0·51, 95% CI 0·26–1·00). The availability of an easy and rapid clinical prediction rule for early identification of RVS can be used to help guide the timely and individualized management of these serious infections.
Biological production in the NE Pacific and its influence on air‐sea CO2 flux: Evidence from dissolved oxygen isotopes and O2/Ar
Authors: Juranek L. W. , Quay P. D. , Feely R. A. , Lockwood D. , Karl D. M. , Church M. J.
Published: April 2012

We determine rates of gross photosynthetic O2 production (GOP) and net community O2 production (NCP) using the triple oxygen isotope and O2/Ar approach on two spring and two late summer meridional transects of the NE Pacific. Observed GOP and NCP in the subtropical (89 ± 9 and 8.3 ± 1.3 mmol O2 m−2 d−1, respectively) and subarctic (193 ± 16 and 16.3 ± 3.8 mmol O2 m−2 d−1) were in agreement with rates previously determined at time series stations in each region, validating the regional representativeness of these sites. At the transition zone chlorophyll front (TZCF), which migrates seasonally from 32°N in spring to 40°N in summer, GOP and NCPwere elevated by 2–4× compared to adjacent areas. Coincident with the TZCF, increases in surface nitrate concentration and extensive changes in phytoplankton community composition were observed. HPLC pigment data indicated substantial increases in a prymnesiophyte (e.g., coccolithophore) biomarker at the TZCF on a spring and summer cruise, and a diatom biomarker on the spring cruise. Increases in remotely sensed surface particulate inorganic carbon concentration were also observed at the TZCF on all four cruises, indicating that coccolithophore production may contribute to increased productivity at the TZCF. Meridional trends in observed air‐sea CO2 flux on each cruise resembled those of the biologically induced CO2 flux (NCP), but with an overprinting of the response of air‐sea CO2 exchange to summer warming. A simple carbon budget based on regional CO2 flux climatology demonstrates the importance of NCPfor net annual air‐sea CO2uptake, although slow air‐sea equilibration and seasonal solubility effects obscure this term.
A spatially distributed model for the long‐term suspended sediment discharge and delivery ratio of drainage basins
Authors: Pelletier Jon D.
Published: April 2012

Understanding and quantifying the long‐term suspended sediment discharge of drainage basins is a key goal of geomorphology, with important implications for the study of water quality, agricultural sustainability, and the evolution of landscapes and sedimentary basins over geologic timescales. Previous studies have highlighted the importance of relief/slope, precipitation, temperature, vegetation, and soil texture in controlling suspended sediment discharge in natural/undisturbed landscapes. However, globally applicable models currently used to predict suspended sediment discharges are limited because they are based on basin‐averaged versions of these properties and do not incorporate all of the controlling variables into a single model. In this paper, I propose a spatially distributed, globally applicable model for the long‐term suspended sediment discharge of drainage basins that includes all of the principal controls on suspended sediment discharge previously documented in the geomorphic literature. The model explicitly distinguishes the detachment of sediment on hillslopes and in low‐order valleys from the transport of sediment in higher‐order alluvial channels. The model uses slope, soil texture, mean monthly rainfall, and mean monthly leaf area index as controlling parameters for the detachment component. The transport component is modeled using a Rouse number–dependent transport criterion that explicitly includes the effects of slope and soil texture. The model is capable of reproducing the long‐term sediment yield of 128 global rivers with a Pearson correlation coefficient (R value) of 0.79 using just two free parameters. The model also predicts sediment delivery ratios consistent with those measured in natural drainage basins.
Unusual shallow normal‐faulting earthquake sequence in compressional northeast Japan activated after the 2011 off the Pacific coast of Tohoku earthquake
Authors: Imanishi Kazutoshi , Ando Ryosuke , Kuwahara Yasuto
Published: April 2012

After the occurrence of the 2011 Mw9.0 off the Pacific coast of Tohoku earthquake, an unusual shallow normal‐faulting earthquake sequence occurred near the Pacific coast at the Ibaraki‐Fukushima prefectural border. We have investigated why normal‐faulting earthquakes were activated in northeast (NE) Japan, which is otherwise characterized by E–W compression. We computed the stress changes associated with the mainshock on the basis of a finite fault slip model, which showed that the amount of additional E–W tensional stresses in the study area was up to 1 MPa, which might be too small to generate normal‐faulting earthquakes in the pre‐shock compressional stress regime. We thus determined focal mechanisms of microearthquakes that occurred in the area before the mainshock, which indicated that the pre‐shock stress field in the area showed a normal‐faulting stress regime in contrast to the overall reverse‐faulting regime in NE Japan. We concluded that the 2011 Tohoku earthquake triggered the normal‐faulting earthquake sequence in a limited area in combination with a locally formed pre‐shock normal‐faulting stress regime. We also explored possible mechanisms for localization of a normal‐faulting stress field at the Ibaraki‐Fukushima prefectural border.
IL‐6 Triggers IL‐21 production by human CD4+ T cells to drive STAT3‐dependent plasma cell differentiation in B cells
Authors: Diehl Sean A , Schmidlin Heike , Nagasawa Maho , Blom Bianca , Spits Hergen
Published: April 2012

Interleukin (IL)‐21‐producing CD4+T cells are central to humoral immunity. Deciphering the signals that induce IL‐21 production in CD4+ T cells and those triggered by IL‐21 in B cells are, therefore, of importance for understanding the generation of antibody (Ab) responses. Here, we show that IL‐6 increased IL‐21 production by human CD4+ T cells, particularly in those that express the transcriptional regulator B cell lymphoma (BCL)6, which is required in mice for the development of C‐X‐C chemokine receptor type 5 (CXCR5+) IL‐21‐producing T follicular helper (TFH) cells. However, retroviral overexpression of BCL6 in total human CD4+ T cells only transiently increased CXCR5, the canonical TFH‐defining surface marker. We show here that IL‐21 was required for the induction of Ab production by IL‐6. In IL‐21‐treated B cells, signal transducer and activator of transcription (STAT)3 was required for optimal immunoglobulin production and upregulation of PR domain containing 1 (PRDM1+), the master plasma cell factor. These results, therefore, demonstrate the critical importance of STAT3 activation in B cells during IL‐21‐driven humoral immunity and suggest that BCL6 expression, although not sufficient, may serve as a platform for the acquisition of a TFH‐like phenotype by human CD4+ T cells.
Experimental study of multichromatic terahertz wave propagation through planar micro-channels
Authors: Shin Young-Min , Baig Anisullah , Barchfeld Robert , Gamzina Diana , Barnett Larry R. , Luhmann Neville C.
Published: April 2012

Previous theoretical and numerical studies [Y. M. Shin and L. R. Barnett, Appl. Phys. Lett. 92, 091501 (2008) and Y. M. Shin et al., Appl. Phys. Lett. 93, 221504 (2008)] have reported that a planar micro-channel with an asymmetric corrugation array supports strongly confined propagation of broadband THz plasmonic waves. The highly broad spectral response is experimentally demonstrated in the near-THz regime of 0.19–0.265 THz. Signal reflection and transmission tests on the three designed micro-channels including directional couplers resulted in a full-width-half-maximum bandwidth of ∼50-60 GHz with an insertion loss of approximately −5 dB, which is in good agreement with simulation data. These micro-structures can be utilized for free electron beam and electronic/optic integrated devices.
Analysis of the forward and reverse bias I-V and C-V characteristics on Al/PVA:n-PbSe polymer nanocomposites Schottky diode
Authors: Tripathi S. K. , Sharma Mamta
Published: April 2012

This paper presents the fabrication and characterization of the Al/PVA:n-PbSe Schottky diode. I-V characteristics have been measured at different temperatures in the forward bias. The behavior study of the series resistance (RS), the ideality factor (n), the effective barrier height (Φb), the Richardson constant (A*), and the leakage current with the temperature have emphasized an inhomogeneity of the barrier height and a tunneling mechanism assisted by traps in the SBD. In C-V measurements, in the reverse bias, the Al/PVA:n-PbSe has been performed as a function of temperature and frequency. The values of barrier height (ΦC-V), the built-in–voltage (Vbi) and carrier concentration (ND) and depletion layer width (W) have been calculated at different temperatures in reverse bias. The barrier inhomogeneities of the Al/PVA:n-PbSe contact has been explained on an assumption of a Gaussian distribution of barrier heights by using the potential fluctuation model.
Combining active-space coupled-cluster methods with moment energy corrections via the CC(P;Q) methodology, with benchmark calculations for biradical transition states
Authors: Shen Jun , Piecuch Piotr
Published: April 2012

We have recently suggested the CC(P;Q) methodology that can correct energies obtained in the active-space coupled-cluster (CC) or equation-of-motion (EOM) CC calculations, which recover much of the nondynamical and some dynamical electron correlation effects, for the higher-order, mostly dynamical, correlations missing in the active-space CC/EOMCC considerations. It is shown that one can greatly improve the description of biradical transition states, both in terms of the resulting energy barriers and total energies, by combining the CC approach with singles, doubles, and active-space triples, termed CCSDt, with the CC(P;Q)-style correction due to missing triple excitations defining the CC(t;3) approximation.
Qualitative determination of surface roughness by in situ reflection high energy electron diffraction
Authors: Boschker J. E. , Tybell T.
Published: April 2012

We demonstrate that a qualitative measure of the surface roughness can be obtained by using in situ reflection high energy electron diffraction. The in situ measurements of the surface roughness are found to be in agreement with the topography, as determined by ex situ atomic force microscopy. Relying on this method, we study the surface roughening during pulsed laser deposition of La0.7Sr0.3MnO3 and investigate the quality of (001)-oriented SrTiO3 substrates with a TiO2 termination.
Strength of hydrogen bonds of water depends on local environment
Authors: Huš Matej , Urbic Tomaz
Published: April 2012

In-depth knowledge of water-water potential is important for devising and evaluating simple water models if they are to accurately describe water properties and reflect various solvation phenomena. Water-water potential depends upon inter-molecular distance, relative orientation of water molecules, and also local environment. When placed at a favorable distance in a favorable orientation, water molecules exhibit a particularly strong attractive interaction called hydrogen bond. Although hydrogen bond is very important for its effects on the elements of life, industrial applications, and bulk water properties, there is no scientific consensus on its true nature and origin. Using quantum-mechanical methods, hydrogen bond strength was calculated in different local environments. A simple empirical linear relationship was discovered between maximum hydrogen bond strength and the number of water molecules in the local environment. The local environment effect was shown to be considerable even on the second coordination shell. Additionally, a negative linear correlation was found between maximum hydrogen bond strength and the distance, at which it was observed. These results provide novel insights into the nature of hydrogen bonding.
Molybdenum disulphide/titanium dioxide nanocomposite-poly 3-hexylthiophene bulk heterojunction solar cell
Authors: Shanmugam Mariyappan , Bansal Tanesh , Durcan Chris A. , Yu Bin
Published: April 2012

Demonstration of hybrid bulk heterojunction (BHJ) solar photovoltaic cell employing molybdenum disulfide (MoS2)/titanium dioxide (TiO2) nanocomposite (∼15 μm thick) and poly 3-hexylthiophene (P3HT) active layers is presented in this letter. The dominant Raman peak at 146 cm−1 confirmed TiO2, while two other peaks observed at 383 cm−1 and 407 cm−1 asserted MoS2 in the nanocomposite film. The demonstrated BHJ solar cell, having a stacked structure of indium tin oxide/TiO2/MoS2/P3HT/gold, exhibits a short circuit current density of 4.7 mA/cm2, open circuit voltage of 560 mV, and photoconversion efficiency of 1.3% under standard AM1.5 illumination condition. We observe that the quality of TiO2/MoS2/P3HT interfaces, as reflected in the dark saturation current in low- and medium-forward-bias region, plays a key role in impacting solar cell performance due to interfacial recombination effect.
An Early History of the Gestalt Factors of Organisation
Authors: Vezzani Stefano , Marino Barbara F M , Giora Enrico
Published: April 2012

Wertheimer's (1923, Psychologische Forschung 4 301–350) idea that the perceptual world is articulated according to factors of organisation is widely acknowledged as one of the most original contributions of Gestalt psychology and stands as a milestone in the history of vision research. An inquiry focused on the forerunners of some of Wertheimer's factors of perceptual organisation is documented here. In fact, in 1900 Schumann described grouping by proximity and by vertical symmetry, and in 1903 G E Müller identified the factors of sameness/similarity and contour. Other authors contributed to the early description of these factors, such as Rubin, who in 1922 originally illustrated grouping by similarity. Even though Wertheimer himself granted these authors due recognition, later psychologists have paid little attention to their contributions. Some possible reasons for this negligence are briefly discussed.
Are the Responses Generated during a Psychophysical Task Independent of Previously Presented Stimuli or Do They Depend on Earlier Stimulus Presentations?
Authors: Quinn Sandra C M , Watt Roger J
Published: April 2012

Quinn and Watt (2006 Perception 35 267–280) showed that the optimal tempi for pieces of music (ie the appropriate speed for a melody) vary from melody to melody. The current study tested if such tempi responses depend on previous stimulus presentations. To do this, we ran a many-participants single-presentation version of the Quinn and Watt experiment. 616 visitors to the Glasgow Science Centre participated. We found that the results substantially matched those obtained earlier, and demonstrate that participants' responses are essentially independent of previously presented stimuli.
The Effect of Contour Closure on Shape Recognition
Authors: Garrigan Patrick
Published: April 2012

Recent research on the Gestalt principle of closure has focused on how the presence of closure affects the ability to detect contours hidden in cluttered visual arrays. Some of the earliest research on closure, however, dealt with encoding and recognizing closed and open shapes, rather than detection. This research re-addresses the relation between closure and shape memory, focusing on how contour closure affects the ability to learn to recognize novel contour shapes. Of particular interest is whether closed contour shapes are easier to learn to recognize and, if so, whether this benefit is due to better encoding of closed contour shapes or easier comparison of closed contour shapes to already learned shapes. The results show that closed contours are indeed easier to recognize and, further, that this advantage appears to be related to better encoding.
Dynamical quantum Hall effect in the parameter space
Authors: Gritsev V. , Polkovnikov A.
Published: April 2012

Geometric phases in quantum mechanics play an extraordinary role in broadening our understanding of fundamental significance of geometry in nature. One of the best known examples is the Berry phase [M.V. Berry (1984), Proc. Royal. Soc. London A, 392:45], which naturally emerges in quantum adiabatic evolution. So far the applicability and measurements of the Berry phase were mostly limited to systems of weakly interacting quasi-particles, where interference experiments are feasible. Here we show how one can go beyond this limitation and observe the Berry curvature, and hence the Berry phase, in generic systems as a nonadiabatic response of physical observables to the rate of change of an external parameter. These results can be interpreted as a dynamical quantum Hall effect in a parameter space. The conventional quantum Hall effect is a particular example of the general relation if one views the electric field as a rate of change of the vector potential. We illustrate our findings by analyzing the response of interacting spin chains to a rotating magnetic field. We observe the quantization of this response, which we term the rotational quantum Hall effect.
Transcription from the second heavy-strand promoter of human mtDNA is repressed by transcription factor A in vitro
Authors: Lodeiro Maria F. , Uchida Akira , Bestwick Megan , Moustafa Ibrahim M. , Arnold Jamie J. , Shadel Gerald S. , Cameron Craig E.
Published: April 2012

Cell-based studies support the existence of two promoters on the heavy strand of mtDNA: heavy-strand promoter 1 (HSP1) and HSP2. However, transcription from HSP2 has been reported only once in a cell-free system, and never when recombinant proteins have been used. Here, we document transcription from HSP2 using an in vitro system of defined composition. An oligonucleotide template representing positions 596–685 of mtDNA was sufficient to observe transcription by the human mtRNA polymerase (POLRMT) that was absolutely dependent on mitochondrial transcription factor B2 (TFB2M). POLRMT/TFB2M-dependent transcription was inhibited by concentrations of mitochondrial transcription factor A (TFAM) stoichiometric with the transcription template, a condition that activates transcription from the light-strand promoter (LSP) in vitro. Domains of TFAM required for LSP activation were also required for HSP2 repression, whereas other mtDNA binding proteins failed to alter transcriptional output. Binding sites for TFAM were located on both sides of the start site of transcription from HSP2, suggesting that TFAM binding interferes with POLRMT and/or TFB2M binding. Consistent with a competitive binding model for TFAM repression of HSP2, the impact of TFAM concentration on HSP2 transcription was diminished by elevating the POLRMT and TFB2M concentrations. In the context of our previous studies of LSP and HSP1, it is now clear that three promoters exist in human mtDNA. Each promoter has a unique requirement for and/or response to the level of TFAM present, thus implying far greater complexity in the regulation of mammalian mitochondrial transcription than recognized to date.
Inoculation of bats with European
Geomyces destructans
supports the novel pathogen hypothesis for the origin of white-nose syndrome
Authors: Warnecke Lisa , Turner James M. , Bollinger Trent K. , Lorch Jeffrey M. , Misra Vikram , Cryan Paul M. , Wibbelt Gudrun , Blehert David S. , Willis Craig K. R.
Published: April 2012

White-nose syndrome (WNS) is an emerging disease of hibernating bats associated with cutaneous infection by the fungus
Geomyces destructans
(
Gd
), and responsible for devastating declines of bat populations in eastern North America. Affected bats appear emaciated and one hypothesis is that they spend too much time out of torpor during hibernation, depleting vital fat reserves required to survive the winter. The fungus has also been found at low levels on bats throughout Europe but without mass mortality. This finding suggests that
Gd
is either native to both continents but has been rendered more pathogenic in North America by mutation or environmental change, or that it recently arrived in North America as an invader from Europe. Thus, a causal link between
Gd
and mortality has not been established and the reason for its high pathogenicity in North America is unknown. Here we show that experimental inoculation with either North American or European isolates of
Gd
causes WNS and mortality in the North American bat,
Myotis lucifugus
. In contrast to control bats, individuals inoculated with either isolate of
Gd
developed cutaneous infections diagnostic of WNS, exhibited a progressive increase in the frequency of arousals from torpor during hibernation, and were emaciated after 3–4 mo. Our results demonstrate that altered torpor-arousal cycles underlie mortality from WNS and provide direct evidence that
Gd
is a novel pathogen to North America from Europe.
Trigger loop dynamics mediate the balance between the transcriptional fidelity and speed of RNA polymerase II
Authors: Larson Matthew H. , Zhou Jing , Kaplan Craig D. , Palangat Murali , Kornberg Roger D. , Landick Robert , Block Steven M.
Published: April 2012

During transcription, RNA polymerase II (RNAPII) must select the correct nucleotide, catalyze its addition to the growing RNA transcript, and move stepwise along the DNA until a gene is fully transcribed. In all kingdoms of life, transcription must be finely tuned to ensure an appropriate balance between fidelity and speed. Here, we used an optical-trapping assay with high spatiotemporal resolution to probe directly the motion of individual RNAPII molecules as they pass through each of the enzymatic steps of transcript elongation. We report direct evidence that the RNAPII trigger loop, an evolutionarily conserved protein subdomain, serves as a master regulator of transcription, affecting each of the three main phases of elongation, namely: substrate selection, translocation, and catalysis. Global fits to the force-velocity relationships of RNAPII and its trigger loop mutants support a Brownian ratchet model for elongation, where the incoming NTP is able to bind in either the pre- or posttranslocated state, and movement between these two states is governed by the trigger loop. Comparison of the kinetics of pausing by WT and mutant RNAPII under conditions that promote base misincorporation indicate that the trigger loop governs fidelity in substrate selection and mismatch recognition, and thereby controls aspects of both transcriptional accuracy and rate.
Single-molecule imaging of DNA curtains reveals mechanisms of KOPS sequence targeting by the DNA translocase FtsK
Authors: Lee Ja Yil , Finkelstein Ilya J. , Crozat Estelle , Sherratt David J. , Greene Eric C.
Published: April 2012

FtsK is a hexameric DNA translocase that participates in the final stages of bacterial chromosome segregation. Here we investigate the DNA-binding and translocation activities of FtsK in real time by imaging fluorescently tagged proteins on nanofabricated curtains of DNA. We show that FtsK preferentially loads at 8-bp KOPS (Fts
K O
rienting
P
olar
S
equences) sites and that loading is enhanced in the presence of ADP. We also demonstrate that FtsK locates KOPS through a mechanism that does not involve extensive 1D diffusion at the scale of our resolution. Upon addition of ATP, KOPS-bound FtsK translocates in the direction dictated by KOPS polarity, and once FtsK has begun translocating it does not rerecognize KOPS from either direction. However, FtsK can abruptly change directions while translocating along DNA independent of KOPS, suggesting that the ability to reorient on DNA does not arise from DNA sequence-specific effects. Taken together, our data support a model in which FtsK locates KOPS through random collisions, preferentially engages KOPS in the ADP-bound state, translocates in the direction dictated by the polar orientation of KOPS, and is incapable of recognizing KOPS while translocating along DNA.
Greater focus needed on methane leakage from natural gas infrastructure
Authors: Alvarez Ramón A. , Pacala Stephen W. , Winebrake James J. , Chameides William L. , Hamburg Steven P.
Published: April 2012

Natural gas is seen by many as the future of American energy: a fuel that can provide energy independence and reduce greenhouse gas emissions in the process. However, there has also been confusion about the climate implications of increased use of natural gas for electric power and transportation. We propose and illustrate the use of technology warming potentials as a robust and transparent way to compare the cumulative radiative forcing created by alternative technologies fueled by natural gas and oil or coal by using the best available estimates of greenhouse gas emissions from each fuel cycle (i.e., production, transportation and use). We find that a shift to compressed natural gas vehicles from gasoline or diesel vehicles leads to greater radiative forcing of the climate for 80 or 280 yr, respectively, before beginning to produce benefits. Compressed natural gas vehicles could produce climate benefits on all time frames if the well-to-wheels CH
4
leakage were capped at a level 45–70% below current estimates. By contrast, using natural gas instead of coal for electric power plants can reduce radiative forcing immediately, and reducing CH
4
losses from the production and transportation of natural gas would produce even greater benefits. There is a need for the natural gas industry and science community to help obtain better emissions data and for increased efforts to reduce methane leakage in order to minimize the climate footprint of natural gas.
Active contractility in actomyosin networks
Authors: Wang Shenshen , Wolynes Peter G.
Published: April 2012

Contractile forces are essential for many developmental processes involving cell shape change and tissue deformation. Recent experiments on reconstituted actomyosin networks, the major component of the contractile machinery, have shown that active contractility occurs above a threshold motor concentration and within a window of cross-link concentration. We present a microscopic dynamic model that incorporates two essential aspects of actomyosin self-organization: the asymmetric load response of individual actin filaments and the correlated motor-driven events mimicking myosin-induced filament sliding. Using computer simulations, we examine how the concentration and susceptibility of motors contribute to their collective behavior and interplay with the network connectivity to regulate macroscopic contractility. Our model is shown to capture the formation and dynamics of contractile structures and agree with the observed dependence of active contractility on microscopic parameters, including the contractility onset. Cooperative action of load-resisting motors in a force-percolating structure integrates local contraction/buckling events into a global contractile state via an active coarsening process, in contrast to the flow transition driven by uncorrelated kicks of susceptible motors.
Role of autophagy in histone deacetylase inhibitor-induced apoptotic and nonapoptotic cell death
Authors: Gammoh Noor , Lam Du , Puente Cindy , Ganley Ian , Marks Paul A. , Jiang Xuejun
Published: April 2012

Autophagy is a cellular catabolic pathway by which long-lived proteins and damaged organelles are targeted for degradation. Activation of autophagy enhances cellular tolerance to various stresses. Recent studies indicate that a class of anticancer agents, histone deacetylase (HDAC) inhibitors, can induce autophagy. One of the HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA), is currently being used for treating cutaneous T-cell lymphoma and under clinical trials for multiple other cancer types, including glioblastoma. Here, we show that SAHA increases the expression of the autophagic factor LC3, and inhibits the nutrient-sensing kinase mammalian target of rapamycin (mTOR). The inactivation of mTOR results in the dephosphorylation, and thus activation, of the autophagic protein kinase ULK1, which is essential for autophagy activation during SAHA treatment. Furthermore, we show that the inhibition of autophagy by RNAi in glioblastoma cells results in an increase in SAHA-induced apoptosis. Importantly, when apoptosis is pharmacologically blocked, SAHA-induced nonapoptotic cell death can also be potentiated by autophagy inhibition. Overall, our findings indicate that SAHA activates autophagy via inhibiting mTOR and up-regulating LC3 expression; autophagy functions as a prosurvival mechanism to mitigate SAHA-induced apoptotic and nonapoptotic cell death, suggesting that targeting autophagy might improve the therapeutic effects of SAHA.
Client Attitudes toward Alcohol Use Self-Report
Authors: Book Sarah W. , Thomas Suzanne E. , Stewart Scott H. , Miller Peter M.
Published: April 2012

Because psychiatric illnesses and problematic alcohol use frequently co-occur and heavy alcohol use can exacerbate depression and anxiety, mental health clinicians should perform alcohol-use screenings. The aim of this study was to determine if psychiatric patients would be accepting of their mental health clinician screening them for heavy alcohol use. Using a written survey, patients rated their levels of agreement with 9 statements regarding opinions about alcohol screening by their mental-health providers. They also completed the Alcohol Use Disorders Identification Test-C (AUDIT-C), a screening instrument for heavy alcohol use. One hundred fifty-four patients were surveyed in 2 psychiatric outpatient clinics. Nearly 40% screened positively for heavy alcohol use on the AUDIT-C. Nearly 8 out of 10 psychiatric patients were in favor of being screened for alcohol use by either self-report or biomarkers, independent of AUDIT-C status and gender. Thus, mental health clinicians should not be deterred from alcohol screening by perceived negative attitudes from patients.
Psychosis Induced by the Interaction between Disulfiram and Methylphenidate May be Dose Dependent
Authors: Grau-López Lara , Roncero Carlos , Navarro Maria C. , Casas Miquel
Published: April 2012

There are few studies describing psychiatric symptoms occurring when methylphenidate and disulfiram are used together. The authors report a case of disulfiram and methylphenidate interaction in which psychotic symptoms could be dose dependent. The patient, diagnosed of alcohol and cocaine dependence and attention deficit hyperactivity disorder (ADHD), started treatment with methylphenidate increasing doses and disulfiram 250 mg/day over 4 weeks. During the first 2 weeks at doses of 36 mg/day of methylphenidate and maintaining disulfiram, side effects were not observed. However, by increasing to 54 mg/day, psychotic symptoms were detected.

The authors reported that the effects are dose dependent. This is the first report about dose-dependent side effects in substance use disorder with ADHD.
Using Standardized Patients in Continuing Medical Education Courses on Proper Prescribing of Controlled Substances
Authors: Swiggart William H. , Ghulyan Marine V. , Dewey Charlene M.
Published: April 2012

Controlled prescription drug (CPD) abuse is an increasing threat to patient safety and health care providers (HCPs) are not adequately prepared nor do they routinely employ proper screening techniques. Using standardized patients (SPs) as an instructional strategy, the trained physicians on proper prescribing practices and SBIRT (Screening, Brief Intervention, and Referral to Treatment) in a continuing medical education (CME) course. The authors compared two physician cohorts receiving standard CME course (control) versus CME plus SP practice. They measured knowledge and attitudes in all participants and skills and perceived competence in the SP group only. Knowledge and attitudes improved significantly for both groups. Screening behaviors for CPD use also improved. Participants overestimated their performance but increased their use of SBIRT with practice. The SP comfort levels with physician's competence improved after 2 practice sessions. Standardized patients can be an effective teaching tool in CME courses. Impact on knowledge or attitudes did not increase significantly over controls.
Developing and Implementing a Multispecialty Graduate Medical Education Curriculum on Screening, Brief Intervention, and Referral to Treatment (SBIRT)
Authors: Tetrault Jeanette M. , Green Michael L. , Martino Steve , Thung Stephen F. , Degutis Linda C. , Ryan Sheryl A. , Martel Shara , Pantalon Michael V. , Bernstein Steven L. , O'Connor Patrick G. , Fiellin David A. , D'Onofrio Gail
Published: April 2012

The authors sought to evaluate the feasibility and acceptability of initiating a Screening, Brief Intervention, and Referral to Treatment (SBIRT) for alcohol and other drug use curriculum across multiple residency programs. SBIRT project faculty in the internal medicine (traditional, primary care internal medicine, medicine/pediatrics), psychiatry, obstetrics and gynecology, emergency medicine, and pediatrics programs were trained in performing and teaching SBIRT. The SBIRT project faculty trained the residents in their respective disciplines, accommodating discipline-specific implementation issues and developed a SBIRT training Web site. Post-training, residents were observed performing SBIRT with a standardized patient. Measurements included number of residents trained, performance of SBIRT in clinical practice, and training satisfaction. One hundred and ninety-nine residents were trained in SBIRT: 98 internal medicine, 35 psychiatry, 18 obstetrics and gynecology, 21 emergency medicine, and 27 pediatrics residents. To date, 338 self-reported SBIRT clinical encounters have occurred. Of the 196 satisfaction surveys completed, the mean satisfaction score for the training was 1.60 (1 = very satisfied to 5 = very dissatisfied). Standardized patient sessions with SBIRT project faculty supervision were the most positive aspect of the training and length of training was a noted weakness. Implementation of a graduate medical education SBIRT curriculum in a multispecialty format is feasible and acceptable. Future efforts focusing on evaluation of resident SBIRT performance and sustainability of SBIRT are needed.
Self-Directed Speech Affects Visual Search Performance
Authors: Lupyan Gary , Swingley Daniel
Published: April 2012

People often talk to themselves, yet very little is known about the functions of this self-directed speech. We explore effects of self-directed speech on visual processing by using a visual search task. According to the label feedback hypothesis (Lupyan, 2007a), verbal labels can change ongoing perceptual processing—for example, actually hearing “chair” compared to simply thinking about a chair can temporarily make the visual system a better “chair detector”. Participants searched for common objects, while being sometimes asked to speak the target's name aloud. Speaking facilitated search, particularly when there was a strong association between the name and the visual target. As the discrepancy between the name and the target increased, speaking began to impair performance. Together, these results speak to the power of words to modulate ongoing visual processing.
Lexical Decision in Children: Sublexical Processing or Lexical Search?
Authors: van den Boer Madelon , de Jong Peter F. , Haentjens-van Meeteren Marleen M.
Published: April 2012

Length effects in the lexical decision latencies of children might indicate that children rely on sublexical processing and essentially approach the task as a naming task. We examined this possibility by means of the effects of neighbourhood size and articulatory suppression on lexical decision performance. Sixty-six beginning and 62 advanced readers performed a lexical decision task in a standard, articulatory suppression, or tapping condition. We found length effects on words and nonwords in the children's lexical decisions. However, the effects of neighbourhood size were similar to those reported for adult lexical decisions, rather than the effects previously found in children's naming. In addition, no effect was found of articulatory suppression. Both findings suggest that, despite clear length effects, children do not adopt a naming task approach but, like adults, base lexical decisions mainly on a lexical search. These results pose a challenge for several computational models of reading.
The Arp2/3 complex is required for lamellipodia extension and directional fibroblast cell migration
Authors: Suraneni Praveen , Rubinstein Boris , Unruh Jay R. , Durnin Michael , Hanein Dorit , Li Rong
Published: April 2012

The Arp2/3 complex nucleates the formation of the dendritic actin network at the leading edge of motile cells, but it is still unclear if the Arp2/3 complex plays a critical role in lamellipodia protrusion and cell motility. Here, we differentiated motile fibroblast cells from isogenic mouse embryonic stem cells with or without disruption of the ARPC3 gene, which encodes the p21 subunit of the Arp2/3 complex. ARPC3−/− fibroblasts were unable to extend lamellipodia but generated dynamic leading edges composed primarily of filopodia-like protrusions, with formin proteins (mDia1 and mDia2) concentrated near their tips. The speed of cell migration, as well as the rates of leading edge protrusion and retraction, were comparable between genotypes; however, ARPC3−/− cells exhibited a strong defect in persistent directional migration. This deficiency correlated with a lack of coordination of the protrusive activities at the leading edge of ARPC3−/− fibroblasts. These results provide insights into the Arp2/3 complex’s critical role in lamellipodia extension and directional fibroblast migration.
Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus
Authors: Palendira Umaimainthan , Low Carol , Bell Andrew I. , Ma Cindy S. , Abbott Rachel J.M. , Phan Tri Giang , Riminton D. Sean , Choo Sharon , Smart Joanne M. , Lougaris Vassilios , Giliani Silvia , Buckley Rebecca H. , Grimbacher Bodo , Alvaro Frank , Klion Amy D. , Nichols Kim E. , Adelstein Stephen , Rickinson Alan B. , Tangye Stuart G.
Published: April 2012

Patients with the primary immunodeficiency X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A, are highly susceptible to Epstein-Barr virus (EBV) infection. Nonetheless, some XLP patients demonstrate less severe clinical manifestations after primary infection. SH2D1A encodes the adaptor molecule SLAM-associated protein (SAP), which is expressed in T and natural killer cells and is required for cytotoxicity against B cells, the reservoir for EBV. It is not known why the clinical presentation of XLP is so variable. In this study, we report for the first time the occurrence of somatic reversion in XLP. Reverted SAP-expressing cells resided exclusively within the CD8+ T cell subset, displayed a CD45RA−CCR7− effector memory phenotype, and were maintained at a stable level over time. Importantly, revertant CD8+ SAP+ T cells, but not SAP− cells, proliferated in response to EBV and killed EBV-infected B cells. As somatic reversion correlated with EBV infection, we propose that the virus exerts a selective pressure on the reverted cells, resulting in their expansion in vivo and host protection against ongoing infection.
Foundations of clinical practice
Authors: Hughes Thomas
Published: April 2012

♦ Conscious and unconscious competency

♦ Clinical research and the placebo effect

♦ Trial design and the randomized controlled trial

♦ Critical review of the literature

♦ Clinical governance and audit

♦ Capacity and consent

♦ Principles of teaching and learning.
The musculoskeletal system: structure and function
Authors: J. Singh Parminder , Kotnis Rohit
Published: April 2012

♦ Structure of bone is comprised of cells, matrix, and water

♦ Bone consists broadly of three surfaces (periosteal, endosteal, and Haversian) and two membranes (periosteum and endosteum)

♦ The blood supply of bone is derived from four main routes (nutrient, metaphyseal, epiphyseal, and periosteal arteries)

♦ There are three main types of cells in bone (osteoblast, osteocyte, and osteoclast)

♦ The matrix is a composite material consisting of an organic and an inorganic component

♦ Two types of bone formation are intramembranous and endochondral ossification

♦ The skeleton is also involved in the vital homeostasis of calcium and phosphate.
Injury and repair
Authors: J. Singh Parminder , Kotnis Rohit
Published: April 2012

♦ Types of injury—traumatic and overuse

♦ Importance of determining the energy involved in an injury

♦ The relevance of mechanical load curves

♦ Types of fracture healing—how and why they occur

♦ Healing in articular cartilage, tendon, ligaments, peripheral nerves, and brain tissues.
Haemoglobinopathies
Authors: Giangrande Paul L.F.
Published: April 2012

♦ Haemoglobinopathies are commonly inherited disorders of haemoglobin synthesis

♦ Thalassaemia is commonest around the Mediterranean countries and has skeletal manifestations due to massive marrow expansion with thinning of the cortex

♦ Sickle cell crises occur in homozygotes and are a result of venous occlusion causing avascular necrosis. Infection and exposure to cold can sometimes precipitate these painful events

♦ If surgery is needed blood cross-match must be carefully performed in advance, the theatre should be kept warm, and the hydration and acid/base balance of the patient monitored carefully.
Prevention of thrombosis in orthopaedic surgery
Authors: Warwick David
Published: April 2012

♦ The risk–benefit of thromboprophylaxis in orthopaedic surgery remains unclear

♦ Some conditions, such as major trauma, carry a much higher risk than others, such as routine knee replacement

♦ Some patients appear to be genetically more predisposed than others

♦ In trials of efficacy of thromboembolism, the use of deep vein thrombosis as a surrogate endpoint for death from a pulmonary embolus may not be completely reliable

♦ There is a variety of mechanical and chemical methods available, each of which has real and potential advantages as well as real and potential dangers

♦ Even the length of time that a patient is at risk after major surgery is unclear

♦ Clinicians should adhere to guidelines where possible.
Pain and its control
Authors: McQuay Henry
Published: April 2012

♦ The origin, transmission, and reception of chronic pain is not easy to understand

♦ The perception of pain is altered by mood and itself alters mood. There is, therefore, a close link between chronic pain and depression

♦ Although pain is subjective, pain scales and diaries can be used to provide reproducible measures of pain

♦ The choice of method of pain control is not simply a ladder. New stronger agents need to be added in, not substituted for weaker ones

♦ Neuropathic pain will require unconventional analgesics in combination.
Biomechanics
Authors: Zavatsky Amy B.
Published: April 2012

♦ A knowledge of basic biomechanical principles is key to understanding and developing the practice of orthopaedic surgery

♦ Mathematical models can be used to calculate forces and strains in musculoskeletal tissues

♦ The musculoskeletal system is highly indeterminate

♦ It is important to know the mechanical properties of musculoskeletal tissues so that suitable replacements can be found

♦ Forces in the joints and muscles can be several times larger than the external loads applied to the body.
Gait analysis
Authors: Bulstrode Christopher
Published: April 2012

♦ Gait analysis tries to obtain reliable clinically relevant information from the way in which patients walk

♦ Each technique has its own specific advantages and disadvantages, but all to a greater or lesser degree ‘interfere’ with the patient’s ability to walk

♦ As yet it remains mainly a research tool.
Imaging
Authors: Mo Ahn Joong , Menda Yusuf , El-Khoury Georges Y.
Published: April 2012

♦ Each modality of imaging—digital radiography, multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine studies—has its own advantages and disadvantages

♦ Conventional radiography is the best for initial evaluation of a musculoskeletal problem

♦ MDCT rapid survey of multiple trauma patients is easily performed using the new high speed computed tomography scanners

♦ MRI is the imaging modality of choice for internal derangement of the knee and other soft tissue injuries

♦ Radionuclide bone imaging is most suitable for screening the whole skeleton for metastases

♦ Positron emission tomography is useful for identification of tumour, inflammation, and infection.