Sonnet 35

Oh, my Tubby Wubbins! Beautiful cat! How did I get so lucky in this world That it\u27s my humble home in which you\u27 re curled, Silvery tabby tom, so fine and fat. Your pale green eyes are rimmed with kohl, or so It seems. Your face is tigerish and square. A mink, or a movie star, would love to wear A coat like yours. You\u27ve blessed my life, you know

Ligands in crystal structures that aid in functional characterization

An overview and commentary on the value of liganded structures emerging from the JCSG structural genomics initiative

The benefit of context for facial-composite construction

Purpose - The aim of this study was to investigate whether the presence of a whole-face context during facial composite production facilitates construction of facial composite images. Design/Methodology - In Experiment 1, constructors viewed a celebrity face and then developed a facial composite using PRO-fit software in one of two conditions: either the full-face was visible while facial features were selected, or only the feature currently being selected. The composites were named by different participants. We then replicated the study using a more forensically-valid procedure: In Experiment 2 non-football fans viewed an image of a premiership footballer and 24 hours later constructed a composite of the face with a trained software operator. The resulting composites were named by football fans. Findings - In both studies, the presence of the facial context promoted more identifiable facial composites. Research limitations/implications - Current composite software was deployed in a conventional and unconventional way to demonstrate the importance of facial context. Practical implications - Results confirm that composite software should have the whole-face context visible to witnesses throughout construction. Although some software systems do this, there remain others that present features in isolation and these findings show that these systems are unlikely to be optimal. Originality/value - This is the first study to demonstrate the importance of a full-face context for the construction of facial composite images. Results are valuable to police forces and developers of composite software

A Shotgun Proteomic Method for the Identification of Membrane-Embedded Proteins and Peptides

Integral membrane proteins perform crucial cellular functions and are the targets for the majority of pharmaceutical agents. However, the hydrophobic nature of their membrane-embedded domains makes them difficult to work with. Here, we describe a shotgun proteomic method for the high-throughput analysis of the membrane-embedded transmembrane domains of integral membrane proteins which extends the depth of coverage of the membrane proteome

Creating Opportunities for Improving Lake-Focused Stakeholder Engagement: Knowledge–Action Systems, Pro-Environment Behavior and Sustainable Lake Management

Managers, policymakers, non-government organizations and community groups are increasingly relying on stakeholder participation to bolster lake management efforts. The growing portfolio of lake-focused stakeholder engagement cases offers valuable information about the efficacy of alternative stakeholder engagement strategies. While attention has been devoted to inventorying these instances, lesser emphasis has been given to evaluating the effectiveness of different participation and engagement approaches. There is arguably no panacea for involving stakeholders in lake and basin management. Lake management challenges in distinct natural and human systems necessitate diverse approaches for interacting with stakeholders. As calls for stakeholder participation increase and management budget constraints tighten, the urgency of exploring and documenting the effectiveness of alternative approach rises. This paper examines lake-focused stakeholder participation activities targeting individuals and households, summarizes and shares recent findings from research of knowledge–action processes and pro-environment behaviours, and offers encouragement and guidance for lake managers to create opportunities for improving lake-focused stakeholder engagement

Infrared and Raman screening of seized novel psychoactive substances:a large scale study of >200 samples

The potential of IR absorption and Raman spectroscopy for rapid identification of novel psychoactive sub- stances (NPS) has been tested using a set of 221 unsorted seized samples suspected of containing NPS. Both IR and Raman spectra showed large variation between the different sub-classifications of NPS and smaller, but still distinguishable, differences between closely related compounds within the same class. In initial tests, screening the samples using spectral searching against a limited reference library allowed only 41% of the samples to be fully identified. The limiting factor in the identification was the large number of active compounds in the seized samples for which no reference vibrational data were available in the libraries rather than poor spectral quality. Therefore, when 33 of these compounds were independently identified by NMR and mass spectrometry and their spectra used to extend the libraries, the percentage of samples identified by IR and Raman screening alone increased to 76%, with only 7% of samples having no identifiable constituents. This study, which is the largest of its type ever carried out, therefore demon- strates that this approach of detecting non-matching samples and then identifying them using standard analytical methods has considerable potential in NPS screening since it allows rapid identification of the constituents of the majority of street quality samples. Only one complete feedback cycle was carried out in this study but there is clearly the potential to carry out continuous identification/updating when this system is used in operational settings

Androgen receptor as a mediator and biomarker of radioresistance in triple-negative breast cancer.

Increased rates of locoregional recurrence have been observed in triple-negative breast cancer despite chemotherapy and radiation therapy. Thus, approaches that combine therapies for radiosensitization in triple-negative breast cancer are critically needed. We characterized the radiation therapy response of 21 breast cancer cell lines and paired this radiation response data with high-throughput drug screen data to identify androgen receptor as a top target for radiosensitization. Our radiosensitizer screen nominated bicalutamide as the drug most effective in treating radiation therapy-resistant breast cancer cell lines. We subsequently evaluated the expression of androgen receptor in >2100 human breast tumor samples and 51 breast cancer cell lines and found significant heterogeneity in androgen receptor expression with enrichment at the protein and RNA level in triple-negative breast cancer. There was a strong correlation between androgen receptor RNA and protein expression across all breast cancer subtypes (R2 = 0.72, p < 0.01). In patients with triple-negative breast cancer, expression of androgen receptor above the median was associated with increased risk of locoregional recurrence after radiation therapy (hazard ratio for locoregional recurrence 2.9-3.2)) in two independent data sets, but there was no difference in locoregional recurrence in triple-negative breast cancer patients not treated with radiation therapy when stratified by androgen receptor expression. In multivariable analysis, androgen receptor expression was most significantly associated with worse local recurrence-free survival after radiation therapy (hazard ratio of 3.58) suggesting that androgen receptor expression may be a biomarker of radiation response in triple-negative breast cancer. Inhibition of androgen receptor with MDV3100 (enzalutamide) induced radiation sensitivity (enhancement ratios of 1.22-1.60) in androgen receptor-positive triple-negative breast cancer lines, but did not affect androgen receptor-negative triple-negative breast cancer or estrogen-receptor-positive, androgen receptor-negative breast cancer cell lines. androgen receptor inhibition with MDV3100 significantly radiosensitized triple-negative breast cancer xenografts in mouse models and markedly delayed tumor doubling/tripling time and tumor weight. Radiosensitization was at least partially dependent on impaired dsDNA break repair mediated by DNA protein kinase catalytic subunit. Our results implicate androgen receptor as a mediator of radioresistance in breast cancer and identify androgen receptor inhibition as a potentially effective strategy for the treatment of androgen receptor-positive radioresistant tumors

The benefit of context for facial composite construction.

Purpose - The aim of this study was to investigate whether the presence of a whole-face context during facial composite production facilitates construction of facial composite images.Design/Methodology - In Experiment 1, constructors viewed a celebrity face and then developed a facial composite using PRO-fit in one of two conditions: either the full-face was visible while facial features were selected, or only the feature currently being selected was visible. The composites were named by different participants. We then replicated the study using a more forensically-valid procedure: In Experiment 2 non-football fans viewed an image of a premiership footballer and 24 hours later constructed a composite of the face with a trained software operator. The resulting composites were named by football fans.Findings - In both studies we found that presence of the facial context promoted more identifiable facial composite images.Research limitations/implications – Though this study uses current software in an unconventional way, this was necessary to avoid error arising from between-system differences.Practical implications - Results confirm that composite software should have the whole-face context visible to witnesses throughout construction. Though some software systems do this, there remain others that present features in isolation and these findings show that these systems are unlikely to be optimal. Originality/value - This is the first study to demonstrate the importance of a full-face context for the construction of facial composite images. Results are valuable to police forces and developers of composite software

Aerobic scope protection reduces ectotherm growth under warming

1. Temperature has a dramatic effect on the physiology of ectothermic animals, impacting most of their biology. When temperatures increase above optimal for an animal, their growth gradually decreases. The main mechanism behind this growth rate reduction is unknown. 2. Here, we suggest the 'aerobic scope protection' hypothesis as a mechanistic explanation for the reduction in growth. 3. After a meal, metabolic rate, and hence oxygen consumption rate, transiently increase in a process called specific dynamic action (SDA). At warmer temperatures, the SDA response usually becomes temporally compressed, leading to a higher peak oxygen consumption rate. This peak in oxygen consumption rate risks taking up much of the animal's aerobic scope (the difference between resting and maximum rates of oxygen consumption), which would leave little residual aerobic scope for other aerobic functions. 4. We propose that water-breathing ectothermic animals will protect their postprandial residual aerobic scope by reducing meal sizes in order to regulate the peak SDA response during times of warming, leading to reductions in growth. 5. This hypothesis is consistent with the published literature on fishes, and we provide predictions that can be tested.Peer reviewe

Hippocampal sequencing mechanisms are disrupted in a maternal immune activation model of schizophrenia risk

Episodic memory requires information to be stored and recalled in sequential order, and these processes are disrupted in schizophrenia. Hippocampal phase precession and theta sequences are thought to provide a biological mechanism for sequential ordering of experience at timescales suitable for plasticity. These phenomena have not previously been examined in any models of schizophrenia risk. Here, we examine these phenomena in a maternal immune activation (MIA) rodent model. We show that while individual pyramidal cells in the CA1 region continue to precess normally in MIA animals, the starting phase of precession as an animal enters a new place field is considerably more variable in MIA animals than in controls. A critical consequence of this change is a disorganization of the ordered representation of experience via theta sequences. These results provide the first evidence of a biological-level mechanism that, if it occurs in schizophrenia, may explain aspects of disorganized sequential processing that contribute to the cognitive symptoms of the disorder