Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins

Abstract The expression of the cysteine protease cathepsin B is increased in early stages of human breast cancer. To assess the potential role of cathepsin B in premalignant progression of breast epithelial cells, we employed a 3D reconstituted basement membrane overlay culture model of MCF10A human breast epithelial cells and isogenic variants that replicate the in vivo phenotypes of hyperplasia (MCF10AneoT) and atypical hyperplasia (MCF10AT1). MCF10A cells developed into polarized acinar structures with central lumens. In contrast, MCF10AneoT and MCF10AT1 cells form larger structures in which the lumens are filled with cells. CA074Me, a cell-permeable inhibitor selective for the cysteine cathepsins B and L, reduced proliferation and increased apoptosis of MCF10A, MCF10AneoT and MCF10AT1 cells in 3D culture. We detected active cysteine cathepsins in the isogenic MCF10 variants in 3D culture with GB111, a cell-permeable activity-based probe, and established differential inhibition of cathepsin B in our 3D cultures. We conclude that cathepsin B promotes proliferation and premalignant progression of breast epithelial cells. These findings are consistent with studies by others showing that deletion of cathepsin B in the transgenic MMTV-PyMT mice, a murine model that is predisposed to development of mammary cancer, reduces malignant progression.
A new wine Torulaspora delbrueckii killer strain with broad antifungal activity and its toxin-encoding double-stranded RNA virus

Wine Torulaspora delbrueckii strains producing a new killer toxin (Kbarr-1) were isolated and selected for wine making. They killed all the previously known Saccharomyces cerevisiae killer strains, in addition to other non-Saccharomyces yeasts. The Kbarr-1 phenotype is encoded by a medium-size 1.7 kb dsRNA, TdV-Mbarr-1, which seems to depend on a large-size 4.6 kb dsRNA virus (TdV-LAbarr) for stable maintenance and replication. The TdV-Mbarr-1 dsRNA was sequenced by new generation sequencing techniques. Its genome structure is similar to those of S. cerevisiae killer M dsRNAs, with a 5′-end coding region followed by an internal A-rich sequence and a 3′-end non-coding region. Mbarr-1 RNA positive strand carries cis acting signals at its 5′ and 3′ termini for transcription and replication respectively, similar to those RNAs of yeast killer viruses. The ORF at the 5′ region codes for a putative preprotoxin with an N-terminal secretion signal, potential Kex2p/Kexlp processing sites, and N-glycosylation sites. No relevant sequence identity was found either between the full sequence of Mbarr-1 dsRNA and other yeast M dsRNAs, or between their respective toxin-encoded proteins. However, a relevant identity of TdV-Mbarr-1 RNA regions to the putative replication and packaging signals of most of the M-virus RNAs suggests that they are all evolutionarily related.
Relax and Localize: From Value to Algorithms

We show a principled way of deriving online learning algorithms from a minimax analysis. Various upper bounds on the minimax value, previously thought to be non-constructive, are shown to yield algorithms. This allows us to seamlessly recover known methods and to derive new ones. Our framework also captures such "unorthodox" methods as Follow the Perturbed Leader and the R^2 forecaster. We emphasize that understanding the inherent complexity of the learning problem leads to the development of algorithms. We define local sequential Rademacher complexities and associated algorithms that allow us to obtain faster rates in online learning, similarly to statistical learning theory. Based on these localized complexities we build a general adaptive method that can take advantage of the suboptimality of the observed sequence. We present a number of new algorithms, including a family of randomized methods that use the idea of a "random playout". Several new versions of the Follow-the-Perturbed-Leader algorithms are presented, as well as methods based on the Littlestone's dimension, efficient methods for matrix completion with trace norm, and algorithms for the problems of transductive learning and prediction with static experts.
Characterization of Escherichia coli Isolates from Hospital Inpatients or Outpatients with Urinary Tract Infection

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the most common cause of community- and hospital-acquired urinary tract infections (UTIs). Isolates from uncomplicated community-acquired UTIs express a variety of virulence traits that promote the efficient colonization of the urinary tract. In contrast, nosocomial UTIs can be caused by E. coli strains that differ in their virulence traits from the community-acquired UTI isolates. UPEC virulence markers are used to distinguish these facultative extraintestinal pathogens, which belong to the intestinal flora of many healthy individuals, from intestinal pathogenic E. coli (IPEC). IPEC is a diarrheagenic pathogen with a characteristic virulence gene set that is absent in UPEC. Here, we characterized 265 isolates from patients with UTIs during inpatient or outpatient treatment at a hospital regarding their phylogenies and IPEC or UPEC virulence traits. Interestingly, 28 of these isolates (10.6%) carried typical IPEC virulence genes that are characteristic of enteroaggregative E. coli (EAEC), Shiga toxin-producing E. coli (STEC), and atypical enteropathogenic E. coli (aEPEC), although IPEC is not considered a uropathogen. Twenty-three isolates harbored the astA gene coding for the EAEC heat-stable enterotoxin 1 (EAST1), and most of them carried virulence genes that are characteristic of UPEC and/or EAEC. Our results indicate that UPEC isolates from hospital patients differ from archetypal community-acquired isolates from uncomplicated UTIs by their spectrum of virulence traits. They represent a diverse group, including EAEC, as well as other IPEC pathotypes, which in addition contain typical UPEC virulence genes. The combination of typical extraintestinal pathogenic E. coli (ExPEC) and IPEC virulence determinants in some isolates demonstrates the marked genome plasticity of E. coli and calls for a reevaluation of the strict pathotype classification of EAEC.
Water Vapor, Clouds, and Saturation in the Tropical Tropopause Layer

The goal of this investigation is to understand the mechanism behind the observed high relative humidity with respect to ice (RHi) in the tropical region between ~14 km (150 hPa) and the tropopause, often referred to as the tropical tropopause layer (TTL). As shown by satellite, aircraft, and balloon observations, high (>80%) RHi regions are widespread within the TTL. Regions with the highest RHi are colocated with extensive cirrus. During boreal winter, the TTL RHi is highest over the Tropical Western Pacific (TWP) with a weaker maximum over South America and Africa. In the winter, TTL temperatures are coldest and upward motion is the greatest in the TWP. It is this upward motion, driving humid air into the colder upper troposphere that produces the persistent high RHi and cirrus formation. Back trajectory calculations show that comparable adiabatic and diabatic processes contribute to this upward motion. We construct a bulk model of TWP TTL water vapor transport that includes cloud nucleation and ice microphysics that quantifies how upward motion drives the persistent high RHi in the TTL region. We find that atmospheric waves triggering cloud formation regulate the RHi and that convection dehydrates the TTL. Our forward domain‐filling trajectory model is used to more precisely simulate the TTL spatial and vertical distribution of RHi. The observed RHi distribution is reproduced by the model, and we show that convection increases RHi below the base of the TTL with little impact on the RHi in the TTL region.
Integrative Physiology/Experimental Medicine Therapeutic Neovascularization by Nanotechnology- Mediated Cell-Selective Delivery of Pitavastatin Into the Vascular Endothelium

Objective—Recent clinical studies of therapeutic neovascularization using angiogenic growth factors demonstrated smaller therapeutic effects than those reported in animal experiments. We hypothesized that nanoparticle (NP)-mediated cell-selective delivery of statins to vascular endothelium would more effectively and integratively induce therapeutic neovascularization. Methods and Results—In a murine hindlimb ischemia model, intramuscular injection of biodegradable polymeric NP resulted in cell-selective delivery of NP into the capillary and arteriolar endothelium of ischemic muscles for up to 2 weeks postinjection. NP-mediated statin delivery significantly enhanced recovery of blood perfusion to the ischemic limb, increased angiogenesis and arteriogenesis, and promoted expression of the protein kinase Akt, endothelial nitric oxide synthase (eNOS), and angiogenic growth factors. These effects were blocked in mice administered a nitric oxide synthase inhibitor, or in eNOS-deficient mice. Conclusions—NP-mediated cell-selective statin delivery may be a more effective and integrative strategy for therapeutic neovascularization in patients with severe organ ischemia. (Arterioscler Thromb Vasc Biol. 2009;29:796-801.)
DNA Damage and Transcriptional Changes in the Gills of Mytilus galloprovincialis Exposed to Nanomolar Doses of Combined Metal Salts (Cd, Cu, Hg)

Aiming at an integrated and mechanistic view of the early biological effects of selected metals in the marine sentinel organism Mytilus galloprovincialis, we exposed mussels for 48 hours to 50, 100 and 200 nM solutions of equimolar Cd, Cu and Hg salts and measured cytological and molecular biomarkers in parallel. Focusing on the mussel gills, first target of toxic water contaminants and actively proliferating tissue, we detected significant dose-related increases of cells with micronuclei and other nuclear abnormalities in the treated mussels, with differences in the bioconcentration of the three metals determined in the mussel flesh by atomic absorption spectrometry. Gene expression profiles, determined in the same individual gills in parallel, revealed some transcriptional changes at the 50 nM dose, and substantial increases of differentially expressed genes at the 100 and 200 nM doses, with roughly similar amounts of up- and down-regulated genes. The functional annotation of gill transcripts with consistent expression trends and significantly altered at least in one dose point disclosed the complexity of the induced cell response. The most evident transcriptional changes concerned protein synthesis and turnover, ion homeostasis, cell cycle regulation and apoptosis, and intracellular trafficking (transcript sequences denoting heat shock proteins, metal binding thioneins, sequestosome 1 and proteasome subunits, and GADD45 exemplify up-regulated genes while transcript sequences denoting actin, tubulins and the apoptosis inhibitor 1 exemplify down-regulated genes). Overall, nanomolar doses of co-occurring free metal ions have induced significant structural and functional changes in the mussel gills: the intensity of response to the stimulus measured in laboratory supports the additional validation of molecular markers of metal exposure to be used in Mussel Watch programs.
Fast monitoring of traffic subpopulations

Network accounting, forensics, security, and performance monitoring applications often need to examine detailed traces from subsets of flows ("subpopulations"), where the application desires flexibility in specifying the subpopulation (e.g., to detect a portscan, the application must observe many packets between a source and a destination with one packet to each port). However, the dynamism and volume of network traffic on many high-speed links necessitates traffic sampling, which adversely affects subpopulation monitoring: because many subpopulations of interest to operators are low-volume flows, conventional sampling schemes (e.g., uniform random sampling) miss much of the subpopulation's traffic. Today's routers and network devices provide scant support for monitoring specific traffic subpopulations. This paper presents the design, implementation, and evaluation of FlexSample, a traffic monitoring engine that dynamically extracts traffic from subpopulations that operators define using conditions on packet header fields. FlexSample uses a fast, flexible counter array to provide rough estimates of packets' membership in respective subpopulations. Based on these coarse estimates, FlexSample then makes per-packet sampling decisions to sample proportionately from each subpopulation (as specified by a network operator), subject to an overall sampling constraint. We apply FlexSample to extract subpopulations such as port scans and traffic to high-degree nodes and find that it is able to capture significantly more packets from these subpopulations than conventional approaches.
Incidence of Aeromonas spp. infection in fish and chicken meat and its related public health hazards: A review

Aeromonas is recognized to cause a variety of diseases in man. In humans, they are associated with intestinal and extra-intestinal infections. With the growing importance of Aeromonas as an emerging pathogen, it is important to combat this organism. It is indisputable that Aeromonas strains may produce many different putative virulence factors such as enterotoxins, hemolysins or cytotoxins, and antibiotic resistance against different antibiotics. The ability of these bacteria to grow competitively at 5°C may be indicative of their potential as a public health hazard. Comprehensive enteric disease surveillance strategies, prevention and education are essential for meeting the challenges in the years ahead. It is important for us to promote the value of enteric cultures when patients have a gastrointestinal illness or bloody diarrhea or when multiple cases of enteric disease occur after a common exposure. With the growing importance of Aeromonas as an emerging pathogen, it is important to combat this organism. It is indisputable that Aeromonas strains may produce many different putative virulence factors, such as enterotoxins, hemolysins or cytotoxins. It has been established that aerolysin is a virulence factor contributing to the pathogenesis of Aeromonas hydrophila infection. Fish and chicken play an important role in the transmission of this pathogen to humans. In the present study, the high prevalence of toxin-producing strains was found among the Aeromonas isolates. The ability of these bacteria to grow competitively at 5°C may be indicative of their potential as a public health hazard. The present review was constructed with a view to highlight the zoonotic importance of Aeromonas pathogen in fish and chicken meat.
AP-1 Transcription Factors, Mucin-Type Molecules and MMPs Regulate the IL-11 Mediated Invasiveness of JEG-3 and HTR-8/SVneo Trophoblastic Cells

This study examines the IL-11 mediated activation of downstream signaling and expression of effector molecules to resolve the controversies associated with the IL-11 mediated regulation of the invasiveness of two commonly used trophoblastic cell models viz. JEG-3 and HTR-8/SVneo cells. It has been reported that IL-11 increases the invasiveness of JEG-3 cells while, reduces the invasiveness of HTR-8/SVneo cells. Invasion assay performed simultaneously for both the cell lines confirmed the above findings. In addition, HTR-8/SVneo cells showed a higher basal invasiveness than JEG-3 cells. Western blot showed the IL-11 mediated activation of STAT3(tyr705) and STAT1(tyr701) in both the cell lines. However, IL-11 activated the ERK1/2 phosphorylation in JEG-3 cells but, inhibited it in HTR-8/SVneo cells. Within 10 min of IL-11 treatment, p-STAT3(tyr705) was localized inside the nucleus of both the cell lines but, there was enhanced co-localization of protein inhibitor of activated STAT1/3 (PIAS1/3) and p-STAT3(tyr705) in HTR-8/SVneo cells and not in JEG-3 cells. This could be reason for the poor responsiveness of STAT3 responsive genes like mucin 1 (MUC1) in HTR-8/SVneo cells and not in JEG-3 cells. Further, microarray analysis of the IL-11 treated cells revealed differential responsiveness of JEG-3 as compared to HTR-8/SVneo cells. Several family of genes like activator protein-1 (AP-1) transcription factors (Jun and Fos), mucin-type molecules, MMP23B etc showed enhanced expression in IL-11 treated JEG-3 cells while, there was no response or decrease in their expression in IL-11 treated HTR-8/SVneo cells. Expression of these molecules was confirmed by quantitative RT-PCR. In addition, HTR-8/SVneo cells also showed a significant decrease in the expression of MMP2, MMP3 and MMP9 upon IL-11 treatment. Hence, IL-11 mediated differential activation of signaling and expression of effector molecules is responsible for the differential invasive response of JEG-3 and HTR-8/SVneo cells.
Global Stratigraphy and the Fossil Record Validate a Flood Origin for the Geologic Column

The geologic column has been under the scrutiny of numerous creationists for many decades. Critics have claimed the column is intimately tied to the evolutionary worldview and deep time, and cannot be trusted or used by creation scientists. Other creation scientists have argued that the geologic column, although incomplete at most locations, can provide useful correlations of rocks and fossils across the globe. This paper examines the sedimentary rocks across three continents in an attempt to test the validity of the global geologic column. We attempted to assess the data primarily from a lithologic viewpoint, and as independent of the fossil data as possible. To accomplish this, we constructed a new data set of over 1500 local, stratigraphic columns across three continents, recording the detailed lithologic information and Sloss-type megasequence boundaries at each site. A detailed 3-D lithology model was created for each continent using the local columns. We also constructed maps of the basal lithology for each megasequence. Unique lithologic units, like salt and chert-rich layers were also tracked from column to column. Results show extensive lithologic units (i.e. blanket sandstones) covered portions of every continent and are correlative across vast regions and even continent to continent. The correlation of these stacked basal megasequence units, and other unique lithologies (i.e. salt and chert layers) within the megasequences, confirm the validity of the geologic column on a global scale. The observable pattern in the fossil record further confirms these findings. Indeed, a global Flood could produce globally extensive, stacked lithologic units on an intercontinental scale. Creationists should not be critical of the geologic column, but embrace it as evidence of a global Flood event.
EFFECTS OF HIGH DIETARY CALCIUM AND LOW PHOSPHORUS ON URINARY SYSTEM OF BROILER CHICKS

The present study was carried out to investigate the effects of high dietary calcium and low phosphorus on urinary system of broiler chicks. A total of 90 (day-old) broiler chicks were divided into three equal groups A, B and C. The chicks were reared for 42 days on three experimental rations. Calcium:phosphorus ratio in the feed for groups A, B and C was maintained as 1:0.5 (control), 2:0.5 and 3:0.5, respectively. Various parameters studied included serum calcium and phosphorus concentrations, FCR, kidney:body weight ratio, and pathological examination of urinary system. The birds fed on high dietary calcium and low phosphorus revealed hypercalcaemia and hypophosphataemia in their sera. The FCR and mean kidney:body weight ratio of treatment groups was higher than the control group. The urinary system of the treated birds, in general, displayed inflammatory lesions, showing abnormalities of colour, size, shape and texture of kidneys and ureters. The ureters also showed occlusion and distention. The microscopic examination of the kidneys showing gross pathological lesions revealed common histopathological changes in glomeruli, tubular cells and interlobular veins.
Baculovirus Vector-Based Varicella-Zoster Virus Vaccine as a Promising Alternative with Enhanced Safety and Therapeutic Functions

Varicella-zoster virus (VZV) poses lifelong risks, causing varicella and herpes zoster (HZ, shingles). Currently, varicella and HZ vaccines are predominantly live attenuated vaccines or adjuvanted subunit vaccines utilizing VZV glycoprotein E (gE). Here, we propose our vaccine candidates involving a comparative analysis between recombinant baculoviral vector vaccines (AcHERV) and a live attenuated vaccine strain, vOka. AcHERV vaccine candidates were categorized into groups encoding gE only, VZV glycoprotein B (gB) only, or both gE and gB (gE-gB) as AcHERV-gE, AcHERV-gB, and AcHERV-gE-gB, respectively. Humoral immune responses were evaluated by analyzing total IgG, IgG1, IgG2a, and neutralizing antibodies. Cell-mediated immunity (CMI) responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and Th1/Th2/Th17 cytokine profiling. In the mouse model, AcHERV-gE-gB elicited similar or higher total IgG, IgG2a, and neutralizing antibody levels than vOka and showed robust VZV-specific CMI responses. From the perspective of antigens encoded in vaccines and their relationship with CMI response, both AcHERV-gB and AcHERV-gE-gB demonstrated results equal to or superior to AcHERV-gE, encoding only gE. Taken together, these results suggest that AcHERV-gE-gB can be a novel candidate for alleviating risks of live attenuated vaccine-induced latency and effectively preventing varicella during early stages of life while providing strong CMI for effective resistance against HZ and therapeutic potential in later stages of life.
Exploiting affinity propagation for automatic acquisition of domain concept in ontology learning

Semantic Web uses domain ontology to bridge the gap among the members of a domain through minimization of conceptual and terminological incompatibilities. However, several barriers must be overcome before domain ontology becomes a practical and useful tool. One important issue is identification and selection of domain concepts for domain ontology learning when several hundreds or even thousands of terms are extracted and available from relevant text documents shared among the members of a domain. We present a novel domain concept acquisition and selection approach for ontology learning that uses affinity propagation algorithm, which takes as input semantic and structural similarity between pairs of extracted terms called data points. Real-valued messages are passed between data points (terms) until high quality set of exemplars (concepts) and cluster iteratively emerges. All exemplars will be considered as domain concepts for learning domain ontologies. Our empirical results show that our approach achieves high precision and recall in selection of domain concepts using less number of iterations.
A Balanced Comparison of Object Invariances in Monkey IT Neurons

Abstract Our ability to recognize objects across variations in size, position, or rotation is based on invariant object representations in higher visual cortex. However, we know little about how these invariances are related. Are some invariances harder than others? Do some invariances arise faster than others? These comparisons can be made only upon equating image changes across transformations. Here, we targeted invariant neural representations in the monkey inferotemporal (IT) cortex using object images with balanced changes in size, position, and rotation. Across the recorded population, IT neurons generalized across size and position both stronger and faster than to rotations in the image plane as well as in depth. We obtained a similar ordering of invariances in deep neural networks but not in low-level visual representations. Thus, invariant neural representations dynamically evolve in a temporal order reflective of their underlying computational complexity.