Pilin expression and processing in pilus mutants of Neisseria gonorrhoeae : critical role of Gly -1 in assembly

Spontaneous mutants of Neisseria gonorrheae failing to express pili or having diminished levels of piliation were studied with regard to pilin expression. All mutants displayed altered pilin processing detectable as the release of soluble, truncated pilin molecules (S-pilin). Of particular interest was the finding, in one mutant, that substitution of serine for glycine at position -1 of propilin, a highly conserved residue among N -metPhe and related pilins, abolished pilus expression but not S-pilin release. The degree of S-pilin processing and the levels of membrane-associated pilin varied among the different classes of mutants, suggesting that each was blocked at a distinct step of pilus biogenesis. The data support a model in which increased S-pilin processing is a result of a decreased rate of pilus polymerization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74951/1/j.1365-2958.1991.tb02108.x.pd

Energy-Efficient Algorithms

We initiate the systematic study of the energy complexity of algorithms (in addition to time and space complexity) based on Landauer's Principle in physics, which gives a lower bound on the amount of energy a system must dissipate if it destroys information. We propose energy-aware variations of three standard models of computation: circuit RAM, word RAM, and transdichotomous RAM. On top of these models, we build familiar high-level primitives such as control logic, memory allocation, and garbage collection with zero energy complexity and only constant-factor overheads in space and time complexity, enabling simple expression of energy-efficient algorithms. We analyze several classic algorithms in our models and develop low-energy variations: comparison sort, insertion sort, counting sort, breadth-first search, Bellman-Ford, Floyd-Warshall, matrix all-pairs shortest paths, AVL trees, binary heaps, and dynamic arrays. We explore the time/space/energy trade-off and develop several general techniques for analyzing algorithms and reducing their energy complexity. These results lay a theoretical foundation for a new field of semi-reversible computing and provide a new framework for the investigation of algorithms.Comment: 40 pages, 8 pdf figures, full version of work published in ITCS 201

Big Data Analysis

The value of big data is predicated on the ability to detect trends and patterns and more generally to make sense of the large volumes of data that is often comprised of a heterogeneous mix of format, structure, and semantics. Big data analysis is the component of the big data value chain that focuses on transforming raw acquired data into a coherent usable resource suitable for analysis. Using a range of interviews with key stakeholders in small and large companies and academia, this chapter outlines key insights, state of the art, emerging trends, future requirements, and sectorial case studies for data analysis

Structural alterations in a type IV pilus subunit protein result in concurrent defects in multicellular behaviour and adherence to host tissue

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72384/1/j.1365-2958.2001.02629.x.pd

Suppression of an absolute defect in Type IV pilus biogenesis by loss-of-function mutations in pilT, a twitching motility gene in Neisseria gonorrhoeae

Type IV pili of Neisseria gonorrhoeae, the Gram-negative etiologic agent of gonorrhea, facilitate colonization of the human host. Gonococcal PilT, a protein belonging to a large family of molecules sharing a highly conserved nucleotide binding domain motif, has been shown to be dispensable for organelle biogenesis but essential for twitching motility and competence for genetic transformation. Here, we show that the defect in pilus biogenesis resulting from mutations in the pilC gene, encoding a putative pilus-associated adhesin for human tissue, can be suppressed by the absence of functional PilT. These data conclusively demonstrate that PilT influences the Type IV pilus biogenesis pathway and strongly suggest that organelle expression is a dynamic process. In addition, these findings imply that PilT antagonizes the process of organelle biogenesis and provide the basis for a model for how the counteractive roles of PilT and PilC might relate mechanistically to the phenomenon of twitching motility

Clinically Relevant Latent Space Embedding of Cancer Histopathology Slides through Variational Autoencoder Based Image Compression

In this paper, we introduce a Variational Autoencoder (VAE) based training approach that can compress and decompress cancer pathology slides at a compression ratio of 1:512, which is better than the previously reported state of the art (SOTA) in the literature, while still maintaining accuracy in clinical validation tasks. The compression approach was tested on more common computer vision datasets such as CIFAR10, and we explore which image characteristics enable this compression ratio on cancer imaging data but not generic images. We generate and visualize embeddings from the compressed latent space and demonstrate how they are useful for clinical interpretation of data, and how in the future such latent embeddings can be used to accelerate search of clinical imaging data

Neisseria gonorrhoeae PilV, a type IV pilus-associated protein essential to human epithelial cell adherence

Type IV pili (Tfp) of Neisseria gonorrhoeae, the Gram-negative etiologic agent of gonorrhea, facilitate colonization of the human host. Tfp are assumed to play a key role in the initial adherence to human epithelial cells by virtue of the associated adhesin protein PilC. To examine the structural and functional basis for adherence in more detail, we identified potential genes encoding polypeptides sharing structural similarities to PilE (the Tfp subunit) within the N. gonorrhoeae genome sequence database. We show here that a fiber subunit-like protein, termed PilV, is essential to organelle-associated adherence but dispensable for Tfp biogenesis and other pilus-related phenotypes, including autoagglutination, competence for natural transformation, and twitching motility. The adherence defect in pilV mutants cannot be attributed to reduced levels of piliation, defects in fiber anchoring to the bacterial cell surface, or to unstable pilus expression related to organelle retraction. PilV is expressed at low levels relative to PilE and copurifies with Tfp fibers in a PilC-dependent fashion. Purified Tfp from pilV mutants contain PilC adhesin at reduced levels. Taken together, these data support a model in which PilV functions in adherence by promoting the functional display of PilC in the context of the pilus fiber

The State of Applying Artificial Intelligence to Tissue Imaging for Cancer Research and Early Detection

Artificial intelligence represents a new frontier in human medicine that could save more lives and reduce the costs, thereby increasing accessibility. As a consequence, the rate of advancement of AI in cancer medical imaging and more particularly tissue pathology has exploded, opening it to ethical and technical questions that could impede its adoption into existing systems. In order to chart the path of AI in its application to cancer tissue imaging, we review current work and identify how it can improve cancer pathology diagnostics and research. In this review, we identify 5 core tasks that models are developed for, including regression, classification, segmentation, generation, and compression tasks. We address the benefits and challenges that such methods face, and how they can be adapted for use in cancer prevention and treatment. The studies looked at in this paper represent the beginning of this field and future experiments will build on the foundations that we highlight

MISCELLANEOUS ELECTRICITY USE IN U.S. HOMES

ABSTRACT Historically, residential energy and carbon saving efforts have targeted conventional end uses such as water heating, lighting and refrigeration. The emergence of new household appliances has transformed energy use from a few large and easily identifiable end uses into a broad array of "miscellaneous" energy services. This group of so called miscellaneous appliances has been a major contributor to growth in electricity demand in the past two decades. We use industry shipment data, lifetimes, and wattage and usage estimates of over 90 individual products to construct a bottom-up end use model . The model is then used to analyze historical and forecasted growth trends, and to identify the largest individual products within the miscellaneous end use. We also use the end use model to identify and analyze policy priorities. Our forecast projects that over the period 1996 to 2010, miscellaneous consumption will increase 115 TWh, accounting for over 90% of future residential electricity growth. A large portion of this growth will be due to halogen torchiere lamps and consumer electronics, making these two components of miscellaneous electricity a particularly fertile area for efficiency programs. Approximately 20% (40 TWh) of residential miscellaneous electricity is "leaking electricity" or energy consumed by appliances when they are not performing their principal function. If the standby power of all appliances with a standby mode is reduced to one watt, the potential energy savings equal 21 TWh/yr, saving roughly $1-2 billion dollars annually