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\"Few mental disorders have been met with more controversy in recent years than Attention deficit-hyperactivity disorder. An estimated 4.7% of adults, and up to 16% of children are living with ADHD in the US. However, some allege that doctors are handing out prescriptions indiscriminately. Thousands of patients respond poorly to stimulant medication, which is at times prescribed to individuals without the condition. There have been countless reports of students and professionals abusing Adderall or Ritalin to enhance their performance in the classroom and at work. Meanwhile, pharmaceutical companies have found a goldmine. Yet the symptoms of attention-deficit and hyperactivity are all-too-real for many individuals who are frequently unable to function without treatment. The controversy surrounding the medication has left these patients and their families at a frustrating standstill, with no alternative options available to them. In ADHD Does Not Exist Dr. Richard Saul offers a groundbreaking solution. After thousands of clinical trials, he has determined that ADHD is not an entity on its own, but in fact a cluster of symptoms stemming from 12 other conditions, each of which requires a separate treatment. The comprehensive list ranges from harmless conditions (poor eyesight and giftedness) to more severe illnesses (bipolar disorder). Dr. Saul takes the reader through clinical examples in which he alters peoples' lives by diagnosing the underlying cause of their attention-deficit symptoms. ADHD Does Not Exist will serve as a handbook for doctors, practitioners, educators, and individuals who are seeking an honest approach to treating ADHD. The book will also be of cultural importance, as it aims to deconstruct one of the most elusive medical conditions of our time\"-- Provided by publisher.

Supervillin isoforms have been implicated in cell proliferation, actin filament-based motile processes, vesicle trafficking, and signal transduction. However, an understanding of the roles of these proteins in cancer metastasis and physiological processes has been limited by the difficulty of obtaining specific antibodies against these highly conserved membrane-associated proteins. To facilitate research into the biological functions of supervillin, monoclonal antibodies were generated against the bacterially expressed human supervillin N-terminus. Two chimeric monoclonal antibodies with rabbit Fc domains (clones 1E2/CPTC-SVIL-1; 4A8/CPTC-SVIL-2) and two mouse monoclonal antibodies (clones 5A8/CPTC-SVIL-3; 5G3/CPTC-SVIL-4) were characterized with respect to their binding sites, affinities, and for efficacy in immunoblotting, immunoprecipitation, immunofluorescence microscopy and immunohistochemical staining. Two antibodies (1E2, 5G3) recognize a sequence found only in primate supervillins, whereas the other two antibodies (4A8, 5A8) are specific for a more broadly conserved conformational epitope(s). All antibodies function in immunoblotting, immunoprecipitation and in immunofluorescence microscopy under the fixation conditions identified here. We also show that the 5A8 antibody works on immunohistological sections. These antibodies should provide useful tools for the study of mammalian supervillins.

The presence of cancer stem cells (CSCs) and the induction of epithelial-to-mesenchymal transition (EMT) in tumors are associated with tumor aggressiveness, metastasis, drug resistance, and poor prognosis, necessitating the development of reagents for unambiguous detection of CSC- and EMT-associated proteins in tumor specimens. To this end, we generated novel antibodies to EMT- and CSC-associated proteins, including Goosecoid, Sox9, Slug, Snail, and CD133. Importantly, unlike several widely used antibodies to CD133, the anti-CD133 antibodies we generated recognize epitopes distal to known glycosylation sites, enabling analyses that are not confounded by differences in CD133 glycosylation. For all target proteins, we selected antibodies that yielded the expected target protein molecular weights by Western analysis and the correct subcellular localization patterns by immunofluorescence microscopy assay (IFA); binding selectivity was verified by immunoprecipitation-mass spectrometry and by immunohistochemistry and IFA peptide blocking experiments. Finally, we applied these reagents to assess modulation of the respective markers of EMT and CSCs in xenograft tumor models by IFA. We observed that the constitutive presence of human hepatocyte growth factor (hHGF) in the tumor microenvironment of H596 non-small cell lung cancer tumors implanted in homozygous hHGF knock-in transgenic mice induced a more mesenchymal-like tumor state (relative to the epithelial-like state when implanted in control SCID mice), as evidenced by the elevated expression of EMT-associated transcription factors detected by our novel antibodies. Similarly, our new anti-CD133 antibody enabled detection and quantitation of drug-induced reductions in CD133-positive tumor cells following treatment of SUM149PT triple-negative breast cancer xenograft models with the CSC/focal adhesion kinase (FAK) inhibitor VS-6063. Thus, our novel antibodies to CSC- and EMT-associated factors exhibit sufficient sensitivity and selectivity for immunofluorescence microscopy studies of these processes in preclinical xenograft tumor specimens and the potential for application with clinical samples.

RAS genes are frequently mutated in cancer and have for decades eluded effective therapeutic attack. The National Cancer Institute’s RAS Initiative has a focus on understanding pathways and discovering therapies for RAS-driven cancers. Part of these efforts is the generation of novel reagents to enable the quantification of RAS network proteins. Here we present a dataset describing the development, validation (following consensus principles developed by the broader research community), and distribution of 104 monoclonal antibodies (mAbs) enabling detection of 27 phosphopeptides and 69 unmodified peptides from 20 proteins in the RAS network. The dataset characterizes the utility of the antibodies in a variety of applications, including Western blotting, immunoprecipitation, protein array, immunohistochemistry, and targeted mass spectrometry. All antibodies and characterization data are publicly available through the CPTAC Antibody Portal, Panorama Public Repository, and/or PRIDE databases. These reagents will aid researchers in discerning pathways and measuring expression changes in the RAS signaling network.

Deep-water dogfish (sharks) are caught on Australia’s continental shelf as by-products to other deep-water species with revenue derived from fillets for human consumption and from the livers which are sold for their oil content. Deep-water dogfish utilise a large oil-rich liver for buoyancy, which may account for 20–25% of their body weight. An important constituent of certain dogfish liver oil is squalene, a highly unsaturated triterpenoid (C30H50) hydrocarbon which in some species can be up to 90% of the oil, though in the Australian commercial species it is typically around 50%. Squalene (and deep-water dogfish liver oil in general) has a long-standing high value in products, such as cosmetics and nutraceuticals. Manufacturers are increasingly required to demonstrate the sustainability of products, and this is integral to the importance of demonstrating product provenance. Australia’s mid-slope deep-water dogfish fishery is recognised globally as well managed and sustainable; therefore, it is important to be able to distinguish products derived from these regions from other unregulated, unsustainable and cheaper sources in order to protect Australia’s competitive advantages and ensure sustainability. In this study, we have sourced deep-water dogfish liver oil samples originating from Southeast Australia, New Zealand, India, Northeast Africa and the Arabian Sea. The squalene was isolated by commercial or laboratory processing. A compound-specific carbon stable isotope analysis of the derived squalene was then used to determine isotopic resolution and assign the likely origins of a variety of commonly available off-the-shelf nutraceuticals in Australian outlets. Squalene sourced and produced from Southeast Australian and New Zealand dogfish liver oils showed δ13C values in the range of −22.1 to −24.2‰, with all other squalene samples distinguishable at −19.9 to −20.7‰. Many of the off-the-shelf squalene products claiming to be of Australian origin showed δ13C values very distinct from the range of the genuine Southeast Australian- and New Zealand-produced squalene.

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

There is a vast amount of information about a city which is invisible to the human eye – crime levels, transportation patterns, cell phone use and air quality to name just a few. If a city was able to be defined by these characteristics, what form would it take? How could it be mapped? Nadia Amoroso tackles these questions by taking statistical urban data and exploring how they could be transformed into innovative new maps. The \"unseen\" elements of the city are examined in groundbreaking images throughout the book, which are complemented by interviews with Winy Maas and James Corner, comments by Richard Saul Wurman, and sections by the SENSEable City Lab group and Mark Aubin, co-founder of Google Earth. Foreword Richard Saul Wurman Part 1: Essays 1. Map or Drawing? The Visual Expressions of Hugh Ferriss 2. Graphic Integrity of the Urban Complexity- Lynch, Wurman and Tufte 3. The DATAscapes: the Works of MVRDV 4. The Map-Art: Creative Measures in Landscape Mapping, the Works of James Corner Part 2: Drawings: the Map-Landscape 5.1 The Creative Map 5.2 The Map-Landscapes Afterword Mapping the Invisibles by SENSEable City Lab Carlo Ratti Google Earth: the Global Mapping Search Tool Mark Aubin Nadia Amoroso specializes in visual representation as it relates to architecture, landscape architecture and the urban environment. She is a Lecturer at the University of Toronto, John H. Daniels Faculty of Architecture, Landscape, and Design. Amoroso was also a recent Visiting Fellow at Cornell University and Visiting Professor at the University of Arkansas. She has a Ph.D. in Architectural Studies, and degrees in Urban Design and Landscape Architecture. Amoroso is a principal of Orange + Blue Consulting, specializing in urban design, mapping and visual representation (digital and traditional means). '[Amoroso] has brought to the forefront a visually exciting way to view information that has spatial, creative and suggestive outcomes. With a background in landscape architecture, urban design and architecture, she crafts maps as some kind of landscape form perceived by the data type. Maps as metaphor, the data as metaphor, map as art, data as art.' – Richard Saul Wurman, Information Architect 'We are on a cusp and Nadia Amoroso is one of the team players on this cusp of the New Map ... showing patterns with great clarity and singularity, combining scientific, physical structures, atmospheric conditions and showing these patterns over time, a day, a week, a month, a year or a decade.' – Richard Saul Wurman, Information Architect 'Nadia Amoroso takes the art and science of transforming statistical urban data into innovative maps to the next level in her recent book The Exposed City: Mapping the Urban Invisibles ... The author provides guiding principles to suggest a selection process that proves useful to achieving the right balance between aesthetics and empirical evidence in the process of creating a a map.' - Amit Patel, Journal of Planning Education and Research

Prediction No. 1: More contextual information On an ideal trip, my universe is a 10- or 15-minute walk from the front door of the hotel. Therefore I think it's the obligation and the service of each hotel individually to provide me with an understandable, dynamic map that gives me possibilities and availabilities from the front door of my hotel.

[...]says Dr RICHARD SAUL, the symptoms can have routine causes such as poor eyesight or hearing. Attention Deficit Hyperactivity Disorder -- and been taking medication for a year but, to the despair of his teachers and mother, his behaviour had not improved at all.

As the size and complexity of hardware designs increases and their time to market decreases, validation via case by case testing is more and more being seen as inadequate. Formal verification, which provide mathematically sound proofs about design properties, is increasingly being turned to. However, formal verification suffers from capacity limitations. Industrial designs must often be partitioned to meet these limitations, which creates a plethora of interfaces that need to be modeled. In this work, we focus on this modeling problem. Conducting verification in the presence of input constraints is the unifying theme of this thesis. Our first approach is to model hardware designs as networks of interacting, finite state machines (FSMs), and synthesize abstractions of these networks that preserve trace equivalence at the boundary of a given component machine. Verification can then be performed on that component composed with the abstract network. We reduce the concrete state space by computing a new type of simulation relation called a forward-backward relation, and choosing representative states on its basis. We make further reductions by removing component FSMs that exhibit language universality over their outputs while exhibiting input independence from certain of their inputs. We give algorithms for detecting both these conditions. In the second part of the thesis, we focus on low cost methods for determining state reachability. These techniques allow an incremental incorporation of a concrete environment, in contrast to abstracting it. We give algorithmic improvements for techniques known as bounded model checking, in which a propositional formula is created encoding all computation paths of a state transition system over a finite time interval, and satisfiability solving is used to derive witnesses or counterexamples for temporal logic specifications from the formula. We give experimental results which demonstrate the effectiveness of these techniques, not only for functional verification, but also in the areas of timing analysis and sequential fault test generation.