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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.07.031 Byline: Kevin C. Miranda (1), Tien Huynh (1), Yvonne Tay (2), Yen-Sin Ang (2), Wai-Leong Tam (2), Andrew M. Thomson (2), Bing Lim (2)(3), Isidore Rigoutsos (1) Abstract: We present rna22, a method for identifying microRNA binding sites and their corresponding heteroduplexes. Rna22 does not rely upon cross-species conservation, is resilient to noise, and, unlike previous methods, it first finds putative microRNA binding sites in the sequence of interest, then identifies the targeting microRNA. Computationally, we show that rna22 identifies most of the currently known heteroduplexes. Experimentally, with luciferase assays, we demonstrate average repressions of 30% or more for 168 of 226 tested targets. The analysis suggests that some microRNAs may have as many as a few thousand targets, and that between 74% and 92% of the gene transcripts in four model genomes are likely under microRNA control through their untranslated and amino acid coding regions. We also extended the method's key idea to a low-error microRNA-precursor-discovery scheme; our studies suggest that the number of microRNA precursors in mammalian genomes likely ranges in the tens of thousands. Author Affiliation: (1) Bioinformatics and Pattern Discovery Group, IBM Thomas J. Watson Research Center, Yorktown Heights, P.O. Box 218, NY 10598, USA (2) Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, 138672, Singapore (3) Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02215, USA Article History: Received 5 April 2006; Revised 16 June 2006; Accepted 26 July 2006 Article Note: (miscellaneous) Published: September 21, 2006

A pattern-based ma22 approach for the discovery of microRNA binding sites and their corresponding microRNA/mRNA complexes is presented. The findings suggest that some microRNAs might have as many as a few thousand targets, and that between 74% and 92% of the gene transcripts in four model genomes are likely under microRNA control through their untranslated and amino acid coding regions.

Venous thromboembolism (VTE) is a leading cause of maternal death in the United Kingdom. To address this problem guidance from the Royal College of Obstetricians and Gynaecologists (RCOG) has been developed that recommends the assessment of a woman's risk of thrombosis at specific time-points during pregnancy and postnatally at the time of delivery. The RCOG guidelines provide clinicians with a framework to inform decision-making on the use of thromboprophylaxis and are based on the premise that the higher risk a woman has for VTE, the more likely she is to benefit from prophylaxis – determining her level of risk is based on the number and characteristics of the risk factors that she has. This article will address the pathophysiology of VTE in pregnancy, evidence behind the risk factors for VTE and the use of thromboprophylactic agents. Further, it will reflect on the rationale behind the RCOG guidance. [ABSTRACT FROM AUTHOR]

Abstract Biotransformation monitoring involves tracking drug modification occurring during in-life studies. Critical Quality Attribute monitoring from forced degraded drug material or in-life sample sets can provide an in-depth assessment of product quality for support in early- or late-stage drug development. For Critical Quality Attribute analysis, biotherapeutic monoclonal antibody (mAb) subunit analysis and peptide mapping liquid chromatography–mass spectrometry (LC-MS) approaches are used, although typically from an in vitro setting (e.g., formulation buffer) not involving biological samples or material. Here, samples from a high-dose rat study (in vivo) are subjected to analysis by ligand binding assay, mAb subunit LC-MS, and peptide mapping by LC-MS. Taken together, data from the 3 analytical approaches provide information regarding drug concentration in circulation, biotransformation, and biotherapeutic drug product quality. The concept of a multitier workflow for preclinical or clinical sample sets can be applied to other biotherapeutic mAb products such as bispecific mAbs, fusions proteins, or antibody-drug conjugates. [ABSTRACT FROM AUTHOR]

The relative humidity of indoor air influences the health and wellbeing of building occupants and the integrity of the building fabric. One potential solution for regulating relative humidity is provided by the plaster used for finishing internal spaces if it has the ability to passively buffer moisture through adsorption and desorption of vapour. During the adsorption and desorption, the water vapour will only penetrate to a certain depth of the plaster. Therefore, it is important to know the minimum thickness of plaster required for the maximum buffering effect. Uniquely, this paper presents a method for determining the optimal thickness from experimental measurements on specimens of varying thickness. In this paper it is demonstrated through a novel method, that there is a thickness of material beyond which there is no increase in moisture buffering capacity. Below the optimal thickness moisture sorption increases linearly as a product of the density and specific moisture capacity. Significantly, existing numerical methods were found to overestimate the performance when compared to empirical measurements. The expected impact of this work is the increased knowledge of surrounding material performance and use, that will ultimately improve the indoor environment quality of buildings and occupant health. [ABSTRACT FROM AUTHOR]

High accuracy of yield prediction is of utmost importance for commercial scale photovoltaic systems. One key parameter crucial to the prediction accuracy is the choice and availability of reliable solar radiation data. In this work we investigate the impact of two fundamentally different irradiance data sources on the calculation of the yearly yield and performance ratio for five locations in different climatic regions of Australia. We find an overestimation of the yield calculation of up to 9.3% for satellite-based climate irradiance data compared against one-minute ground-based irradiance data. The yield overestimation shows a general correlation with the number of cloudy days. We propose a linear correction of the yield calculation which allows to improve the prediction accuracy based on more broadly available satellite-based irradiance data. [ABSTRACT FROM AUTHOR]

Agmatine deiminases (AgDs) catalyze the hydrolytic conversion of agmatine (decarboxylated arginine) to N -carbamoylputrescine with concomitant release of ammonia. These enzymes, which are encoded by some pathogenic bacterial species, confer a competitive survival advantage by virtue of energy production and acid tolerance through agmatine catabolism. Herein we report the development of a clickable activity-based protein profiling (ABPP) probe that targets the AgD encoded by Streptococcus mutans with high selectivity and sensitivity. [ABSTRACT FROM AUTHOR]

Cereal straw, including wheat, barley and rice, offers a renewable and sustainable resource stream for a variety of construction products, including compressed board panels, thatched roofing and bales. The successful use of straw bales as thermal insulation within the external envelope of buildings has been demonstrated by the increasing number of successful contemporary projects around the world. However, the warranty, insurance and financing of such projects is often still not as straightforward as competing solutions, which can be attributed to concerns relating to the long-term durability of the straw. This paper presents findings from an on-going experimental study into the condition monitoring of modern straw bale construction, and also reports on a study investigating the degradation behaviour of wheat straw cyclically exposed to elevated humidity levels. The findings of the study provide encouraging insight into the robustness of straw bale construction. [ABSTRACT FROM AUTHOR]

Photoconductance (PC) measurements of the diffused-region recombination-current pre-factor J 0d make the approximation of excess-carrier Δ n density uniformity. That is, from the front illuminated surface to the rear the Δ n is constant. Kane and Swanson outlined acceptable sample parameters such that the error caused by this approximation is small when performing transient J 0d measurements. For quasi-steady state (QSS) PC measurements, where there is generation, the uniform carrier-density approximation leads to a larger J 0d under-estimation compared to the transient approach. We avoid this approximation by numerically solving the J 0d accounting for depthwise generation, recombination and carrier diffusion in the quasi-neutral bulk that occurs during a QSS PC measurement. We demonstrate the application of the technique to samples with surface-diffusion sheet resistances 10–140 Ω/sq., formed by etch back, and a sample where the surface passivation degrades with damp heat exposure. We find, for the samples tested, the direct application of the Kane and Swanson method: i) under-estimates the J 0d by 2% to 8% when the sample bulk is lightly doped (boron doping of 1.3×10 14 cm -3 ), and ii) under-estimates the J 0d by 10% to 80% when the wafer is moderately doped (phosphorus doping of 1.5×10 15 cm -3 ), for samples with J 0d 350 to 2200 fA/cm 2 ; compared with an experimental uncertainty of 6%. For both samples sets the under-estimation increases as J 0d increases. [ABSTRACT FROM AUTHOR]

Agmatine deiminases (AgDs) belong to a family of enzymes known as guanidinium group modifying enzymes (GMEs). Many pathogenic bacteria encode an AgD that participates in the catabolism of agmatine (decarboxylated arginine). This catabolism may confer a competitive survival advantage, by virtue of energy production and increased acid tolerance, making this sub-family of enzymes a potential therapeutic target that warrants further study. Herein we report the development of an activity-based protein profiling (ABPP) probe that selectively targets the AgD from Streptococcus mutans . Due to the selectivity and covalent nature of the modification, this probe could prove to be a valuable tool for the study of other AgD family members. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Recent reviews lament the lack of evidence on the efficacy of regenerative procedures to induce further root maturation despite claims of a paradigm shift in the way infected, necrotic immature teeth with arrested root development can be endodontically treated. The majority of reports are either case series or successful case reports where nonstandardized images may make interpretation uncertain. Methods: This prospective clinical study reports on preliminary outcomes of regenerative endodontic procedures carried out on 16 teeth, 3 mandibular premolars and 13 traumatized central incisors, after 18-month reviews. Qualitative analysis of resolution of periapical radiolucencies and apical closure was undertaken. Quantitative analysis compared preoperative and recall radiographs by using a geometrical imaging program that calculated percentage changes in root length and dentin wall thickness. Results: Qualitative assessment showed 90.3% resolution of the periapical radiolucency. Apical closure was assessed as incomplete in 47.2% and complete apical closure in 19.4% of cases. Quantitative assessment showed change in root length varying from −2.7% to 25.3% and change for root dentin thickness of −1.9% to 72.6%. Conclusions: Patterns of continued root maturogenesis were variable at 18-month review. Reviews at 36 months showed continued root maturogenesis for 2 cases. Quantitative analysis can control for changes in angulation but may introduce other measurement errors. However, not all anterior teeth were suitable for TurboReg assessment because overlapping of the cementoenamel junctions and/or further eruption of teeth often precluded stable landmark positioning. Discoloration of the crown was a common consequence, with unaesthetic results in 10 of the 16 cases. [Copyright &y& Elsevier]

Summary: Background & aims: Central venous access device (CVAD)-related complications such as catheter-related sepsis, occlusion and breakage contribute to both mortality and morbidity in home parenteral nutrition (HPN) patients. Prospectively collected data in these patients are scarce. Methods: Data on all CVAD-related complications in four tertiary referral centres in Australia and New Zealand were prospectively collected between 01/01/2009 and 31/12/2009 together with costs of each episode that required admission. Results: Of 53 patients (42 adults and 11 children), 27 suffered a total of 49 episodes of CVAD-associated complications (line infection 36, catheter blockage 5, line fracture 1, line migration 7), giving an incidence of 3.6 per 1000 CVAD days (11.6 per 1000 in patients with a multi-use CVAD). Thirty seven episodes resulted in hospital admission for a median duration of 8 days (range 1–29). Responsible microbes were mainly enteric with klebsiella being the most commonly isolated organism (10 episodes). The average cost of care per episode of CVAD-associated complication requiring inpatient admission was $A9,710 (€6480 approximately). Conclusion: CVAD complications, in particular line infection are still a major source of potentially avoidable HPN morbidity and mortality with a high cost to the healthcare system. The predominance of enteric organisms in our series raises the possibility of bacterial translocation as a significant component of the pathogenesis of line sepsis in HPN patients. [Copyright &y& Elsevier]

Abstract: A pH shuttle has been developed in which the mean position of the macrocycle can be switched between dialkylammonium stations of differing acidities. With only the most basic binding site protonated (dibenzylammonium), the macrocycle resides almost exclusively on the protonated station; when the second ammonium group (diethylammonium) is generated by further protonation, a mixture of translational diastereomers is observed in CD2Cl2 at 298K, with the diethylammonium binding site preferred by the crown ether macrocycle in a ratio of ∼2:1. [Copyright &y& Elsevier]

Abstract: The Escherichia coli fumarate and nitrate reductase (FNR) regulator protein is an important transcriptional regulator that controls the expression of a large regulon of more than 100 genes in response to changes in oxygen availability. FNR is active when it acquires a [4Fe‐4S]2+ cluster under anaerobic conditions. The presence of the [4Fe‐4S]2+ cluster promotes protein dimerization and site‐specific DNA binding, facilitating activation or repression of target promoters. Oxygen is sensed by the controlled disassembly of the [4Fe‐4S]2+ cluster, ultimately resulting in inactive, monomeric, apo‐FNR. The FNR [4Fe‐4S]2+ cluster is also sensitive to nitric oxide, such that under anaerobic conditions the protein is inactivated by nitrosylation of the iron‐sulfur cluster, yielding a mixture of monomeric and dimeric dinitrosyl‐iron cysteine species. This chapter describes some of the methods used to produce active [4Fe‐4S] FNR protein and investigates the reaction of the [4Fe‐4S]2+ cluster with nitric oxide and oxygen in vitro. [Copyright &y& Elsevier]

Summary: The diagnosis of borderline ovarian tumours is problematic. Traditionally, the absence of stromal invasion has distinguished borderline ovarian tumours from their malignant counterparts. The recent recognition of microinvasion associated with borderline neoplasms, the analysis of peritoneal implants (PIs), and issues associated with tumour nomenclature contribute to this diagnositc challenge. Furthermore, a proposed reclassification of serous ovarian tumours abandoning the borderline category in favour of atypical proliferative serous tumour (APST) and micropapillary serous carcinoma (MPSC); the latter being subdivided into invasive (invasive MPSC or low-grade serous carcinoma) and non-invasive (non-invasive MPSC or intraepithelial low-grade serous carcinoma) variants, has resulted in the inconsistent use of tumour nomenclature. To facilitate understanding, both the old and new terminologies of serous tumours will be used in this review. Unfortunately, diagnostic dilemmas are not restricted to serous ovarian tumours, in mucinous ovarian tumours, benign, borderline and malignant epithelium can co-exist in the same lesion and metastatic mucinous carcinoma from the gastrointestinal tract can mimic a primary mucinous ovarian tumour. Pseudomyxoma peritonei, which was originally considered as the peritoneal lesion (or implant) associated with a borderline mucinous ovarian tumour, is now believed to be secondary to a low-grade primary mucinous tumour of the appendix. Finally, accurate and complete histological assessment requires the pathologist to be aware of newly described lesions e.g. the seromucinous tumours. In this article, the difficulties associated with the histological diagnosis of the above tumours will be considered with emphasis on the identification of early invasion. [Copyright &y& Elsevier]

Background: Biochemical markers of ERCP-related myocardial injury have not previously been investigated. Objective: To evaluate ERCP-related cardiac troponin I (cTnI) release, myocardial ischemia, hemodynamic changes, and arterial hypoxemia in a series of consecutive patients according to age and to determine their relationship to preexisting cardiovascular risk factors (RF) and the development of post-ERCP pancreatitis. Design: Prospective cohort study. Setting: Tertiary teaching hospital, Canberra, Australia. Patients: Data were collected on 130 consecutive ERCPs performed on 100 unselected patients (aged 18-93 years) by one endoscopist. Patients were divided into two groups: 65 years of age and older (group 1, n = 53; 27 women) and less than 65 years of age (group 2, n = 47; 33 women). Interventions: ERCP. Main Outcome Measurements: Cardiovascular RFs were identified, and electrocardiogram (ECG), cTnI, creatine kinase (CK), amylase, and lipase were measured before and 24 hours after ERCP. Oxygen saturation (SpO2), heart rate (HR), blood pressure (BP), and ECG were monitored continuously during each procedure. Results: New ECG changes (ischemia, arrhythmias) occurred in 24% of procedures in group 1 and in 9.3% in group 2 (p = 0.168), and episodic arterial hypoxemia (SpO2 < 90%) in 16.2% (group 1) and 21.4% (group 2) (p = 0.596). A post-ERCP rise in cTnI levels was documented in 6 patients in the older group. Two of these patients died: one from acute myocardial infarction and one from undiagnosed ascending aortic aneurysm. A cTnI rise was not related to any comorbid conditions, total number of RFs, hemodynamic or ECG changes, or arterial desaturation. In patients with a new cTnI rise, the duration of ERCP was significantly longer (59.5 vs. 26.4 minutes, p = 0.026), being 30 minutes or longer in 5 of 6 patients. Post-ERCP pancreatitis was associated with desaturation (relative risk [RR] = 5.9; 95% confidence interval [CI] [1.2, 32.0], p = 0.027) and myocardial ischemia/injury (RR = 4.4; 95% CI [1.4, 7.8]; p = 0.009). Conclusions: Although the majority of older patients tolerated ERCP well, in 8% of procedures, most of which were prolonged (>30 minutes), myocardial injury, as defined by the release of cTnI, occurred. Desaturation and myocardial ischemia/injury were associated with post-ERCP pancreatitis. [Copyright &y& Elsevier]

Intracellular levels of the light (L) and heavy (H) ferritin subunits are regulated by iron at the level of message translation via a modulated interaction between the iron regulatory proteins (IRP1 and IRP2) and a 5′-untranslated region. Iron-responsive element (IRE). Here we show that iron and interleukin-1β (IL-1β) act synergistically to increase H- and L-ferritin expression in hepatoma cells. A GC-rich cis-element, the acute box (AB), located downstream of the IRE in the H-ferritin mRNA 5′-untranslated region, conferred a substantial increase in basal and IL-1β-stimulated translation over a similar time course to the induction of endogenous ferritin. A scrambled version of the AB was unresponsive to IL-1. Targeted mutation of the AB altered translation; reverse orientation and a deletion of the AB abolished the wild-type stem-loop structure and abrogated translational enhancement, whereas a conservative structural mutant had little effect. Labeled AB transcripts formed specific complexes with hepatoma cell extracts that contained the poly(C)-binding proteins, iso-αCP1 and -αCP2, which have well defined roles as translation regulators. Iron influx increased the association of αCP1 with ferritin mRNA and decreased the αCP2-ferritin mRNA interaction, whereas IL-1β reduced the association of αCP1 and αCP2 with H-ferritin mRNA. In summary, the H-ferritin mRNA AB is a key cis-acting translation enhancer that augments H-subunit expression in Hep3B and HepG2 hepatoma cells, in concert with the IRE. The regulated association of H-ferritin mRNA with the poly(C)-binding proteins suggests a novel role for these proteins in ferritin translation and iron homeostasis in human liver. [ABSTRACT FROM AUTHOR]

• Using DFT we calculated the mixing of ca-pv and bdg into a single phase perovskite. • Iron-free Pyrolitic and basaltic compositions do not mix in the lower mantle. • Fe(II) or increased temperature increases miscibility, Al(III) decreases it. • Mixing is predicted to cause a decrease in V s and an increase in V Φ. Calcium silicate perovskite and bridgmanite are two phases believed to coexist throughout the lower mantle, which at some temperature, at least theoretically, dissolve into each other to form a single perovskite solid solution (Ca x Mg 1− x SiO 3). This may have large seismic and geochemical implications due to the changes in density, elasticity and element partition coefficients between single and mixed phase perovskites. DFT Molecular Dynamics has been used to estimate the miscibility of bridgmanite and calcium perovskite at pressures between 25 and 125 GPa. At 125 GPa (where mixing is the greatest in our pressure range) to mix 1% of Ca-pv into bridgmanite requires a temperature of 2042 K, 5% 2588 K, 10% 2675 K and 50% 2743 K. Therefore, in a simplified lower mantle chemistry an extensive MgSiO 3 –CaSiO 3 solid solution is not expected to occur. However, a simple model was employed to test whether the presence of other elements might influence this mutual solid solution and it was demonstrated that if sufficient concentrations (>1 at.%) of additional elements are present then miscibility may become favourable. Of the elements likely to be present at these concentrations it appears that ferrous iron promotes, whilst aluminium inhibits, a single-phase perovskite solid solution. To a lesser extent ferric iron may both increase and decrease perovskite miscibility. Modelling for realistic mantle compositions suggests that basaltic lithologies will always retain two perovskite components, whereas a single perovskite solid solution may be preferred in hot and/or iron-rich pyrolytic bulk compositions near the base of the lower mantle. Static calculations indicate perovskite miscibility may cause pyrolytic lithologies (with 12.5% CaSiO 3) to possess lower density (−0.14–0.25%), V s (−1.5–3.5%) and V p (−0.5–1.2%), and higher V Φ (+ 0.00–0.75%) than predicted for assemblages containing two perovskites. These seismic changes, while preliminary, are similar to those observed in the LLSVPs which are also regions that are likely hotter than the surrounding mantle and thus possess conditions promoting the formation of a single perovskite phase. [ABSTRACT FROM AUTHOR]

Two emerging trends in multicrystalline silicon cell texturing are plasma texturing, and metal catalyzed chemical etching. Both processes roughen silicon surfaces in order to increase light absorption. These processes are attractive as they are applicable to diamond-wire sawn wafers. This work investigates the optical properties of these surfaces, and other conventionally textured surfaces like isotropic acidic and random pyramid textures, are investigated for cells in air and after encapsulation for a large range of angles of incidence. We find that the angular optical performance in air varies strongly with cell texture, but when embedded in a module structure these variations are significantly mitigated: the advantages of a high angular absorption of solar cells are not fully transferred to the module level. This is especially notable for plasma etched, black silicon cell structures which suffer comparatively from poorer index matching and light recycling inside a module structure. The losses caused explicitly by the module embedding (described in the cell to module ratio) are in the range of 1–5% for perpendicular incoming light, and increase to 6–15% at an angle of incidence of 70°. Based on these angular performances, we calculate the annual yield of the modules and find that it varies by less than 2% for the cell textures. Nevertheless, the annual optical yield for the black silicon cell structures are the highest, whereas the metal catalyzed chemical etching cell structures show the lowest performance. Further, we find that different annual distributions of the incoming light at the two investigated locations (Melbourne and Alice Springs) only impact the relative performance of the cell textures at high module tilt angles. [ABSTRACT FROM AUTHOR]

Rationale Investigations conducted through Amazon's Mechanical Turk (MTurk) sometimes explicitly note eligibility requirements when recruiting participants; however, the impact of this practice on data integrity is relatively unexplored within the MTurk context. Objective Contextualized in the organ donor registration domain, the current study assessed whether overtly listing eligibility requirements impairs the accuracy of data collected on MTurk. Methods On day 1, the first and third round of data collection did not list eligibility requirements; the second and fourth round overtly listed a qualification requirement: status as a non-registered organ donor. On day 2, the approach was identical, except the order was reversed—the first and third round overtly listed the study qualifications, while the second and fourth did not. These procedures provided eight different waves of data. In addition, all participants were randomly assigned to read an elevating (i.e., morally inspiring) story or a story not intended to elicit any emotion. Regardless of recruitment approach, only participants who were not registered as donors were included in the analysis. Results Results indicated that the recruitment script that explicitly requested non-registered donors resulted in the collection of participants with higher mean intentions scores than the script that did not overtly list the eligibility requirements. Further, even though the elevation induction increased intentions to register as a donor, there was not a significant interaction between recruitment approach and the influence of the elevation manipulation on registration intentions. Conclusion Explicitly listing eligibility requirements can influence the accuracy of estimates derived from data collected through MTurk. [ABSTRACT FROM AUTHOR]