Miracle-dz/UniFAR-FTUs huggingface dataset:
Visualizing Herpesvirus Procapsids in Living Cells

ABSTRACT A complete understanding of herpesvirus morphogenesis requires studies of capsid assembly dynamics in living cells. Although fluorescent tags fused to the VP26 and pUL25 capsid proteins are available, neither of these components is present on the initial capsid assembly, the procapsid. To make procapsids accessible to live-cell imaging, we made a series of recombinant pseudorabies viruses that encoded green fluorescent protein (GFP) fused in frame to the internal capsid scaffold and maturation protease. One recombinant, a GFP-VP24 fusion, maintained wild-type propagation kinetics in vitro and approximated wild-type virulence in vivo. The fusion also proved to be well tolerated in herpes simplex virus. Viruses encoding GFP-VP24, along with a traditional capsid reporter fusion (pUL25/mCherry), demonstrated that GFP-VP24 was a reliable capsid marker and revealed that the protein remained capsid associated following entry into cells and upon nuclear docking. These dual-fluorescent viruses made possible the discrimination of procapsids during infection and monitoring of capsid shell maturation kinetics. The results demonstrate the feasibility of imaging herpesvirus procapsids and their morphogenesis in living cells and indicate that the encapsidation machinery does not substantially help coordinate capsid shell maturation. IMPORTANCE The family Herpesviridae consists of human and veterinary pathogens that cause a wide range of diseases in their respective hosts. These viruses share structurally related icosahedral capsids that encase the double-stranded DNA (dsDNA) viral genome. The dynamics of capsid assembly and maturation have been inaccessible to examination in living cells. This study has overcome this technical hurdle and provides new insights into this fundamental stage of herpesvirus infection.
Growth and Metabolism of Human Hepatocytes on Biomodified Collagen Poly(lactic-co-glycolic acid) Three-Dimensional Scaffold

Hepatic tissue engineering offers a promising approach toward alleviating the need for donor liver, yet many challenges must be overcome including choice of scaffold, cell source, and immunologic barriers. Poly(lactic-co-glycolic acid) (PLGA) polymers are innovative biodegradable materials that have been shown to be useful as scaffolds for seeding and culturing various types of cells. In this study, a porous sponge scaffold of modified PLGA polymer with collagen was investigated for its ability to improve the growth and metabolism of human hepatocytes. We evaluated the biocompatibility of collagen-modified PLGA (C-PLGA) scaffolds with hepatocytes isolated from human liver. Cell adhesion and function (cell density, culture lifespan, albumin synthesis, urea synthesis, and ammonia elimination and diazepam clearance) were assessed during different culture periods. The number of hepatocytes cultured in C-PLGA scaffolds was higher compared with those cultured in PLGA scaffolds without collagen modification, and the lifespan of hepatocytes cultured in C-PLGA scaffolds was longer than that of cells cultured in PLGA scaffolds. Albumin and urea synthesis and ammonia elimination from attached hepatocytes were greater in C-PLGA than in PLGA scaffolds, with the exception of diazepam clearance. Collagen-modified PLGA scaffold is a promising biomaterial for hepatic tissue engineering.
Glacial Iron Sources Stimulate the Southern Ocean Carbon Cycle

Icebergs and glacial meltwater have been observed to significantly affect chlorophyll concentrations, primary production, and particle export locally, yet the quantitative influence of glacial iron on the carbon cycle of the Southern Ocean remains unknown. We analyze the impact of icebergs and glacial meltwater on the Southern Ocean carbon cycle in a global Earth System Model. We consider several simulations spanning low and high bounds of current estimates of glacial iron concentration. We find that a high glacial iron input produces the best agreement with observed iron and chlorophyll distributions. These high glacial iron input results indicate that about 30% of the Southern Ocean particle export production, that is, the flux of particulate organic matter through the 100 m depth level, is driven by glacial iron sources. This export production is associated with an uptake of 0.14 Pg carbon per year, which reduces carbon outgassing in the Southern Ocean by 30%.
Distinct Targeting and Fusion Functions of the PX and SNARE Domains of Yeast Vacuolar Vam7p*

Regulated membrane fusion requires organelle tethering, enrichment of selected proteins and lipids at the fusion site, bilayer distortion, and lipid rearrangement. Yeast vacuole homotypic fusion requires regulatory lipids (ergosterol, diacylglycerol, and phosphoinositides), the Rab family GTPase Ypt7p, the multisubunit Ypt7p-effector complex HOPS (homotypic fusion and vacuole protein sorting), and four SNAREs. One SNARE, Vam7p, has an N-terminal PX domain which binds to phosphatidylinositol 3-phosphate (PI(3)P) and to HOPS and a C-terminal SNARE domain but no apolar membrane anchor. We have exploited an in vitro reaction of vacuole fusion to analyze the functions of each domain, removing the PX domain or mutating it to abolish its PI(3)P affinity. Lowering the PI(3)P affinity of the PX domain, or even deleting the PX domain, affects the fusion Km for Vam7p but not the maximal fusion rate. Fusion driven by the SNARE domain alone is strikingly enhanced by the PLC inhibitor U73122 through enhanced binding of Vam7p SNARE domain to vacuoles, and the further addition of Plc1p blocks this U73122 effect. The PX domain, through its affinities for phosphoinositides and HOPS, is thus exclusively required for enhancing the targeting of Vam7p rather than for execution of the Vam7p functions in HOPS·SNARE complex assembly and fusion.
Modulation of leading edge vorticity and aerodynamic forces in flexible flapping wings

In diverse biological flight systems, the leading edge vortex has been implicated as a flow feature of key importance in the generation of flight forces. Unlike fixed wings, flapping wings can translate at higher angles of attack without stalling because their leading edge vorticity is more stable than the corresponding fixed wing case. Hence, the leading edge vorticity has often been suggested as the primary determinant of the high forces generated by flapping wings. To test this hypothesis, it is necessary to modulate the size and strength of the leading edge vorticity independently of the gross kinematics while simultaneously monitoring the forces generated by the wing. In a recent study, we observed that forces generated by wings with flexible trailing margins showed a direct dependence on the flexural stiffness of the wing. Based on that study, we hypothesized that trailing edge flexion directly influences leading edge vorticity, and thereby the magnitude of aerodynamic forces on the flexible flapping wings. To test this hypothesis, we visualized the flows on wings of varying flexural stiffness using a custom 2D digital particle image velocimetry system, while simultaneously monitoring the magnitude of the aerodynamic forces. Our data show that as flexion decreases, the magnitude of the leading edge vorticity increases and enhances aerodynamic forces, thus confirming that the leading edge vortex is indeed a key feature for aerodynamic force generation in flapping flight. The data shown here thus support the hypothesis that camber influences instantaneous aerodynamic forces through modulation of the leading edge vorticity.
Segmentation of merged characters by neural networks and shortest-path

One major problem with neural network-based ap preach to printed character recognition is the segmentation of merged characters. This paper proposes a hybrid method which combines a neural network-based de ferred segmentation scheme with conventional immediate segmentation techniques. In the deferred segmentation, a neural network is employed to distinguish single characters from composites. To find a proper vertical cut that separates a composite, a shortest-path alg~ rithm seeking minimal-penalty curved cuts is used. Integrating those components with a multiresolution neural network OCR and an efficient spelling checker, the resulting system significantly improves its ability to read omnifont document text.
Design and Construction of a Big Data Analytics Framework for Health Applications

We propose to establish a framework for supporting Big Data Analytics (BDA) on real healthcare big data. To test the analytic framework, we used UVic WestGrid (4412 cores computer cluster) to analyze the emulation of 10 billion healthcare records that represented the main hospital system and its reporting via its data warehouse stored at Vancouver Island Health Authority (VIHA). The study showed that the build of the BDA platform requires changes to the configurations to the MapReduce component of Hadoop (HDFS) and to the indexing of HBASE. The ingestion and replication of the data over a large volume iteratively offers a method for data migration of large volumes of real healthcare data via HDFS and to query in that some distributed filing system. Furthermore, the query performance was very satisfied via Apache Phoenix layer that is run in parallel across all nodes on HBASE. The study has demonstrated that the proposed BDA process and configuration met patient data security and performance requirements of healthcare BDA.
Ranking queries on uncertain data: a probabilistic threshold approach

Uncertain data is inherent in a few important applications such as environmental surveillance and mobile object tracking. Top-k queries (also known as ranking queries) are often natural and useful in analyzing uncertain data in those applications. In this paper, we study the problem of answering probabilistic threshold top-k queries on uncertain data, which computes uncertain records taking a probability of at least p to be in the top-k list where p is a user specified probability threshold. We present an efficient exact algorithm, a fast sampling algorithm, and a Poisson approximation based algorithm. An empirical study using real and synthetic data sets verifies the effectiveness of probabilistic threshold top-k queries and the efficiency of our methods.
Exploring high-speed low-power hybrid arithmetic units at scaled supply and adaptive clock-stretching

Meeting power and performance requirement is a challenging task in high speed ALUs. Supply voltage scaling is promising because it reduces both switching and active power but it also degrades robustness. Recently, researchers have proposed novel design technique for linear time complexity adders that maintain high yield and high clock frequency even at scaled supply voltage. The idea is based on the fact that the critical paths of arithmetic units are exercised rarely. The technique (a) predicts the set of critical paths, (b) reduces the supply voltage to operate non-critical paths at rated frequency, and; (c) avoids possible delay failures in the critical paths by dynamically stretching the clock period (to say, two-cycles assuming all standard operations are single-cycle), when they are activated. This allows circuits to operate at scaled supply with minimal performance degradation. The off-critical paths operate in single clock cycle while critical paths are operated in stretched clock period. Different classes of adders may benefit differently using such technique. For example, ripple carry adders can reap the benefits more effectively than say, tree adders (balanced paths). However, logic modification may ease the application of supply voltage scaling. In this paper, we explore various arithmetic units for possible use in high speed, high yield ALU design at scaled supply voltage with variable latency operation. We demonstrate that careful logic optimization of the existing arithmetic units indeed make them further suitable for supply voltage scaling with tolerable area overhead Simulation results on different adder and multiplier topologies in BPTM 70nm technology show 18-60% extra improvement in power with only 2-8% increase in die-area at iso-yield We also extend our studies to design low power and high yield multipliers. These optimized low power datapath units can be used to construct low power and robust ALU that can operate at high clock frequency with minimal performance degradation due to occasional clock stretching.
Checking in or checked in: comparing large-scale manual and automatic location disclosure patterns

Studies on human mobility are built on two fundamentally different data sources: manual check-in data that originates from location-based social networks and automatic check-in data that can be automatically collected through various smartphone sensors. In this paper, we analyze the differences and similarities of manual check-ins from Foursquare and automatic check-ins from Nokia's Mobile Data Challenge. Several new findings follow from our analysis: (1) While automatic checking-in overall results in more visits than manual checking-in, the check-in levels are comparable when visiting new places. (2) Daily and weekly check-in activity patterns are similar for both systems except for Saturdays -- when manual check-ins are relatively more probable. (3) A recently proposed rank distribution to describe human mobility, so far validated on manual check-in data, also holds for automatic check-in data given a slight modification to the definition of rank. (4) The patterns described by automatic check-ins are in general more predictable. We also address the question of whether it is possible to find matching places across the two check-in systems. Our analysis shows that while this is challenging in areas such as city centers, our method achieves an accuracy of 51% for places that are not homes of phone users.
Intellectual Origins of Genomics Genomic Perspective and Cancer

discovery of the double-helical structure of DNA, and the concomitant realization that DNA molecules carry genetic information digitally encoded in their nucleotide sequences (Watson and Crick 1953a,b,c), neatly divide the history of biology in the 20th century. The first half featured the rise of classical genetics: analysis of the inheritance of traits obtained at first from natural variation and later by induced or selected mutations. Much was learned from breeding studies in plants and simple " model " organisms such as Drosophila and Neurospora, including quite detailed genetic linkage maps. The second half saw the rise of molecular biology: the elucida-tion, in considerable detail, of the information pathway that begins with the nucleotide sequence in DNA and ends with the specification of the phenotypes of cells and organisms. The determination of the complete nucleotide sequences of the human, mouse, and many bacterial and eu-karyotic model organism genomes is the logical culmination of both molecular biology and classical genetics. Just as the DNA structure transformed classical genetics into a molecular science, the genomic sequences are transforming molecular biology into an information science, marking the beginning of a third era in the history of biology. In each case, the newer science is of necessity firmly based in its predecessor, but thinking and research become transformed both in style and substance; each era adds a new perspective to our understanding of biology. The ideas underlying the science of genomics can be traced back to the early years of molecular biology. The first truly " genomic " paper was presented at the Cold Spring Harbor Symposium in 1963; it summarized the results of a deliberate program to identify all the genes of bacteriophage T4 (Epstein et al. 1964). The paper described , in a general way, what each of the T4 genes does for the organism. This program was based on the idea that one might be able to obtain mutations in all the essential T4 genes by isolating conditional-lethal mutations. Two kinds of conditional-lethal mutations (chain-terminating and temperature-sensitive) had recently been described; strong arguments were made for the idea that either or both of these kinds of mutations could be found in any essential phage gene if one looked hard enough for them. The T4 genes themselves were then defined and enumerated genetically: The mutations were classified into genes by complementation and recombination mapping using their common conditional-lethal phenotypes. This was clearly a …
Outer-membrane lipoprotein LpoB spans the periplasm to stimulate the peptidoglycan synthase PBP1B

Significance Bacteria surround their cytoplasmic membrane with an essential heteropolymer, the peptidoglycan (PG) sacculus, to maintain osmotic stability and cell shape. Cells enlarge their sacculus by using cytoplasmic membrane-anchored PG synthases, which are guided by cytoskeletal elements. Gram-negative bacteria have a thin, mainly single-layered sacculus, connected to the outer membrane. Outer-membrane–anchored lipoproteins were recently found to be essential for PG growth. Here, we present the structure of the outer membrane protein LpoB of Escherichia coli, which is required for the function of the major PG synthase PBP1B. LpoB has a long, flexible N-terminal stretch enabling it to span the periplasm and reach its docking site in PBP1B, the noncatalytic UvrB domain 2 homolog domain, to stimulate PG growth. Bacteria surround their cytoplasmic membrane with an essential, stress-bearing peptidoglycan (PG) layer. Growing and dividing cells expand their PG layer by using membrane-anchored PG synthases, which are guided by dynamic cytoskeletal elements. In Escherichia coli, growth of the mainly single-layered PG is also regulated by outer membrane-anchored lipoproteins. The lipoprotein LpoB is required for the activation of penicillin-binding protein (PBP) 1B, which is a major, bifunctional PG synthase with glycan chain polymerizing (glycosyltransferase) and peptide cross-linking (transpeptidase) activities. Here, we report the structure of LpoB, determined by NMR spectroscopy, showing an N-terminal, 54-aa–long flexible stretch followed by a globular domain with similarity to the N-terminal domain of the prevalent periplasmic protein TolB. We have identified the interaction interface between the globular domain of LpoB and the noncatalytic UvrB domain 2 homolog domain of PBP1B and modeled the complex. Amino acid exchanges within this interface weaken the PBP1B–LpoB interaction, decrease the PBP1B stimulation in vitro, and impair its function in vivo. On the contrary, the N-terminal flexible stretch of LpoB is required to stimulate PBP1B in vivo, but is dispensable in vitro. This supports a model in which LpoB spans the periplasm to interact with PBP1B and stimulate PG synthesis.
Utility of liver allograft biopsy obtained at procurement

Extended‐donor criteria (EDC) liver allografts potentiate the role of procurement biopsy in organ utilization. To expedite allocation, histologic evaluation is routinely performed upon frozen‐section (FS) specimens by local pathologists. This descriptive study compares FS reports by local pathologists with permanent‐section (PS) evaluation by dedicated hepatopathologists, identifies histologic characteristics underrepresented by FS evaluation, and evaluates the efficacy of a biopsy decision analysis based on organ visualization. Fifty‐two liver transplants using EDC allografts evaluated by FS with PS were studied. Pathologic worksheets created by an organ procurement organization were applied in 34 FS. PS analysis included 7 staining procedures for 8 histologic criteria. PS from 56 additional allografts determined not to require donor biopsy were also analyzed. A high correlation was observed between FS and PS. Underestimation of steatosis by FS was associated with allograft dysfunction. Surgical assessment of cholestasis, congestion, and steatosis was accurate whereas inflammation, necrosis, and fibrosis were underestimated in allografts suffering parenchymal injury. In conclusion, the correlation between FS and PS is high, and significant discrepancies are rare. Biopsy is not a prerequisite for EDC utilization but is suggested in hepatitis C, hypernatremia, donation after cardiac death, or multiple EDC indications. Implementation of a universal FS worksheet could standardize histologic reporting and facilitate data collection, allocation, and research. Liver Transpl 2008. © 2008 AASLD.
The roles of adenosine and related substances in exercise hyperaemia

The role of adenosine in exercise hyperaemia has been controversial. Accumulating evidence now demonstrates that adenosine is released into the venous efflux of exercising muscle and that adenosine is responsible for 20–40% of the maintained phase of the muscle vasodilatation that accompanies submaximal and maximal contractions. This adenosine is mainly generated from AMP that is released from the skeletal muscle fibres and dephosphorylated by ecto 5′nucleotidase bound to the sarcolemma. During exercise, the concentration of ecto 5′nucleotidase may be increased by translocation from the cytosol, while release of AMP and affinity of ecto 5′nucleotidase for AMP are increased by acidosis. The adenosine so formed, acts on extraluminal A2A receptors on the vascular smooth muscle. In addition, ATP is released from red blood cells into the plasma during exercise, in association with the unloading of O2 from haemoglobin, while ATP and adenosine may be released from endothelium as a consequence of local hypoxia. It is unlikely that this intraluminal ATP, or adenosine, contributes significantly to exercise hyperaemia, for muscle vasodilatation induced by intraluminal ATP or adenosine is strongly nitric oxide dependent, while vasodilatation induced by adenosine in hypoxia is mediated by A1 receptors. Neither is a recognized feature of exercise hyperaemia.
The Prognostic Significance of Cancer-Associated Fibroblasts in Esophageal Squamous Cell Carcinoma

Background Cancer-associated fibroblasts (CAF) are activated fibroblasts in the cancer stroma and play an important role in cancer progression. Some reports have indicated the correlation between the expression of CAF markers and adverse prognosis in several cancers. However, no reports have studied CAF phenotype and its clinical relevance in esophageal squamous cell carcinoma (ESCC). Methods We investigated CAF phenotype of ESCC based on histology and immunohistochemical expressions of five CAF markers such as fibroblast activation protein (FAP), smooth muscle actin (SMA), fibroblast-specific protein-1 (FSP1), platelet-derived growth factor receptor (PDGFRα), and PDGFRβ in 116 ESCC tissue samples. Besides, we also examined the correlation of the CAF phenotype with clinical relevance as well as other cancer-microenvironment related factors. Results Histologically immature CAF phenotype was correlated with poor prognosis (p<0.001) and associated with increased microvessel density, increased tumor associated macrophages, and epithelial to mesenchymal transition. CAF markers were characteristically expressed in stromal fibroblast close to tumor cells and the expression pattern of 5 CAF markers was highly heterogeneous in every individual cases. Of five CAF markers, SMA, FSP1, and PDGFRα were unfavorable prognostic indicators of ESCC. The number of positive CAF markers was greater in ESCC with immature CAFs than in those with mature ones. Conclusions Our results demonstrate that histologic classification of CAF phenotype is a reliable and significant prognostic predictor in ESCC. CAF markers have the potential to be diagnostic and therapeutic targets in ESCC.