Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced annotations and features for comparing thousands of Pseudomonas genomes in the Pseudomonas genome database

The Pseudomonas Genome Database (http://www.pseudomonas.com) is well known for the application of community-based annotation approaches for producing a high-quality Pseudomonas aeruginosa PAO1 genome annotation, and facilitating whole-genome comparative analyses with other Pseudomonas strains. To aid analysis of potentially thousands of complete and draft genome assemblies, this database and analysis platform was upgraded to integrate curated genome annotations and isolate metadata with enhanced tools for larger scale comparative analysis and visualization. Manually curated gene annotations are supplemented with improved computational analyses that help identify putative drug targets and vaccine candidates or assist with evolutionary studies by identifying orthologs, pathogen-associated genes and genomic islands. The database schema has been updated to integrate isolate metadata that will facilitate more powerful analysis of genomes across datasets in the future. We continue to place an emphasis on providing high-quality updates to gene annotations through regular review of the scientific literature and using community-based approaches including a major new Pseudomonas community initiative for the assignment of high-quality gene ontology terms to genes. As we further expand from thousands of genomes, we plan to provide enhancements that will aid data visualization and analysis arising from whole-genome comparative studies including more pan-genome and population-based approaches.
Spatial mismatch of phylogenetic diversity across three vertebrate groups and protected areas in Europe

We investigate patterns of phylogenetic diversity in relation to species diversity for European birds, mammals and amphibians to evaluate their congruence and highlight areas of particular evolutionary history. We estimate the extent to which the European network of protected areas (PAs) network retains interesting evolutionary history areas for the three groups separately and simultaneously.
A Survey of the Timestamping Problem

The timestamping problem is one of showing that one possessed a document before a certain time. In this paper several protocols are discussed for solving this problem. These protocols were developed by Haber and Stornetta [11] and by Benaloh and de Mare [5, 6]. In addition, this paper discusses the Byzantine Generals’ Problem, which is necessary for the protocols to operate and discusses the relative strength of the protocols and ways to avoid certain types of attacks.
Anonymity in Wireless Broadcast Networks

Systems that provide network traffic anonymity typically focus on wide-area network topologies, and exploit the infeasibility of eavesdropping on all links to prevent attackers from determining communication peers. This approach is inappropriate for high-security wireless localarea networks, since it does not obscure the traffic volume, allowing attackers to identify critical nodes (e.g., a military HQ) and, given the ability of an attacker to obtain a global view of all communications, the relative ease of identifying the source and destination of traffic flows. These weaknesses derive from the fact that, whereas in wide-area networks the sender, the receiver and the adversary are on different physical links, in wireless networks they may share a single broadcast link. Moreover, the adversary can easily find the physical location of the transmitter and thereby identify the entity sending the traffic, not just its network identity. We introduceWireless Anonymous Routing (war), an approach to achieve anonymity in a broadcast network. We describe a formal threat model for war and compare it to the traditional anonymity approaches. We show that these are inadequate when applied to the broadcast model, and describe new protocols that preserve security with better performance, adequately addressing the requirements of security-critical environments. We provide analytical and some preliminary experimental evidence that our protocols achieve anonymity at a reasonable cost.
Towards an axiomatic approach to hierarchical clustering of measures

We propose some axioms for hierarchical clustering of probability measures and investigate their ramifications. The basic idea is to let the user stipulate the clusters for some elementary measures. This is done without the need of any notion of metric, similarity or dissimilarity. Our main results then show that for each suitable choice of user-defined clustering on elementary measures we obtain a unique notion of clustering on a large set of distributions satisfying a set of additivity and continuity axioms. We illustrate the developed theory by numerous examples including some with and some without a density.
Novel actuation design of a gait trainer with shadow leg approach

Robotic gait training has developed since the end of the 20th century, yet there is much room for improvement in the design of the robots. With the conventional exoskeleton structures, donning of patients in a gait trainer usually is a cumbersome process due to the need of joint alignments and normal walking is often hindered due to obstructed arm swing. Our goal was to design a gait training robots that overcomes these limitations. We propose a novel design in which these drawbacks are reduced to a great amount. By using a parallel structure behind the patient (shadow leg) that is connected to the patient joints with rods, little alignment is needed, the area lateral to the hip is left free, and thus arm swing is not obstructed. The construction is lightweight, because the actuators are mounted on a fixed base and the transmission of power is executed with light weight rods. An end stop in the shadow leg prevents hyper extension of the patient's knee. The relationship between motor displacement and human joint rotations is nonlinear. In this paper we derive the nonlinear relationships between motors and patient joints and verify these. calculations with a measurement. The device has been built, now tests with subjects are required to assess if subjects can indeed walk normally in the robot.
Interspecies physiological variation as a tool for cross-species assessments of global warming-induced endangerment: validation of an intrinsic determinant of macroecological and phylogeographic structure

Global warming is now recognized as the dominant threat to biodiversity because even protected populations and habitats are susceptible. Nonetheless, current criteria for evaluating species' relative endangerment remain purely ecological, and the accepted conservation strategies of habitat preservation and population management assume that species can mount ecological responses if afforded protection. The insidious threat from climate change is that it will attenuate or preclude ecological responses by species that are physiologically constrained; yet, quantitative, objective criteria for assessing relative susceptibility of diverse taxa to warming-induced stress are wanting. We explored the utility of using interspecies physiological variation for this purpose by relating species' physiological phenotypes to landscape patterns of ecological and genetic exchange. Using a salamander model system in which ecological, genetic and physiological diversity are well characterized, we found strong quantitative relationships of basal metabolic rates (BMRs) to both macroecological and phylogeographic patterns, with decreasing BMR leading to dispersal limitation (small contemporary ranges with marked phylogeographic structure). Measures of intrinsic physiological tolerance, which vary systematically with macroecological and phylogeographic patterns, afford objective criteria for assessing endangerment across a wide range of species and should be incorporated into conservation assessment criteria that currently rely exclusively upon ecological predictors.
Embedded Vision System (EVS)

This paper describes a simple low cost embedded vision system which has been developed and can satiate the requirement of a small vision system in various surveillance and control systems and in applications which require an artificial vision to be embedded in them. This system utilizes a low cost CMOS camera module and all image data is processed by a high speed, low cost AVR microcontroller. The embedded vision system implements simple image processing algorithms and taps the processing power of the AVR microcontrollers with the firmware which in turn also helps to reduce the hardware cost. This system being simple and portable can be used in applications where on board image processing is a fundamental requirement and use of a traditional vision system is not possible.
An intrinsic time limit between genesis and death of individual neurons in the developing retinal ganglion cell layer

We tested the possibility that a temporal relationship exists between genesis and death of individual neurons dying during development. For this purpose, we labeled neurons born in limited time intervals and determined when they die in the ganglion cell layer (GCL) of the rat retina. We found that most neurons that die do so within a maximal interval of 5 d after their birth, irrespective of the age of genesis or of the cell type. These findings suggest the existence of a cellular clock regulating neuronal death during development. We found also that neurons migrate in no less than 3 d to the GCL, where a majority of cells that die remain a maximum of 2 d. This fast cellular turnover implies that the magnitude of neuronal death is far greater than previously believed.
Identification of Soluble Candidate Biomarkers of Therapeutic Response to Sunitinib in Medullary Thyroid Carcinoma in Preclinical Models

Purpose: Medullary thyroid carcinoma (MTC), an aggressive rare tumor due to activating mutations in the proto-oncogene RET, requires new therapeutic strategies. Sunitinib, a potent inhibitor of RET, VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and platelet-derived growth factor receptor (PDGFR)α/β, has been reported as clinically effective in some patients with advanced MTC. In this study, we examine molecular mechanisms of action of sunitinib and identify candidate soluble biomarkers of response. Experimental Design: Both in vitro and in vivo assays, using the human TT RETC634W MTC cell line, were done to assess the activity of sunitinib. Kinetic microarray studies were used to analyze molecular pathways modified by sunitinib and to identify candidate biomarkers that were subsequently investigated in the serum of patients. Results: Sunitinib displayed antiproliferative and antiangiogenic activities and inhibited RET autophosphorylation and activation of downstream signaling pathways. We showed that sunitinib treatment induced major changes in the expression of genes involved in tissue invasion and metastasis including vimentin (VIM), urokinase plasminogen (PLAU), tenascin-C (TN-C), SPARC, and CD44. Analyzing downregulated genes, we identified those encoding secreted proteins and, among them, interleukin (IL)-8 was found to be modulated in the serum of xenografted mice under sunitinib treatment. Furthermore, we demonstrated that metastatic MTC patients presented increased serum levels of IL-8 and TGF-β2. Conclusions: Experimental models confirm the clinical efficacy of sunitinib observed in a few studies. Molecular pathways revealed by genomic signatures underline the impact of sunitinib on tissue invasion. Selected soluble candidate biomarkers could be of value for monitoring sunitinib response in metastatic MTC patients. Clin Cancer Res; 17(7); 2044–54. ©2011 AACR.
Immune Responses in the Central Nervous System

Immune responses occurring within the central nervous system (CNS) have unique features attributable to the cellular and functional organization of the CNS and to the presence of the blood-brain barrier. Immune responses to viral infection of the CNS involve the participation of most immunologically important cells: T and B lymphocytes, monocytes, and natural killer cells. Normally, helper/inducer T lymphocytes are predominant in the cerebrospinal fluid (CSF) and in perivascular cuffs. After stimulation with antigen in tissue, these cells produce lymphokines, which stimulate mast cells to open capillary tight junctions, stimulate proliferation of lymphocytes, and attract monocytes and B lymphocytes. B lymphocytes mature into immunoglobulin-producing cells that secrete antibody locally which appears in the CSF. Cytotoxic/suppressor T lymphocytes, which damage antigen-containing cells, are predominant in immunopathologic reactions. In other situations the immune response targets normal CNS tissue rather than foreign antigens. Two general types of reactions may be seen: (1) vasculitis with destruction of vessel walls and infarction, and (2) perivascular inflammation with demyelination. The former is associated with immune complex deposition, and the cellular infiltrate includes polymorphonuclear leukocytes. The inflammation associated with perivenular demye-lination is composed almost exclusively of mononuclear leukocytes. In the diseases for which pathogenetic mechanisms are understood, cells become sensitized to myelin constituents and induce local demyelinating lesions in which the damage is effected by macrophages. It is not clear whether macrophages are directed in this destructive effort by lymphokines or immunoglobulins or both.
Iron and immunity: a double‐edged sword

Iron is a crucial element for many central metabolic pathways of the body. Lack of iron leads to growth arrest and anaemia while increased accumulation of this metal, as it occurs in highly frequent inherited diseases such as hereditary haemochromatosis and thalassaemia, is associated with toxic radical formation and progressive tissue damage. As shown by several groups, iron also modulates immune effector mechanisms, such as cytokine activities (IFN‐γ effector pathways towards macrophages), nitric oxide (NO) formation or immune cell proliferation, and thus host immune surveillance. Therefore, gaining control over iron homeostasis is one of the central battlefields in deciding the fate of an infection with intracellular pathogens or a malignant disease. Thus, the reticulo‐endothelial system has evoked sophisticated strategies to control iron metabolism in general and especially the handling of the metal within immune cells.
Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis. Results of two phase II studies. The CD5 Plus Rheumatoid Arthritis Investigators Group.

OBJECTIVE To evaluate the safety and activity of an immunoconjugate of ricin A chain and anti-CD5 monoclonal antibody (anti-CD5 IC), with and without concomitant methotrexate and/or azathioprine, in the treatment of rheumatoid arthritis (RA). METHODS Seventy-nine patients with active RA were enrolled in 2 prospective open-label protocols. RESULTS Using composite criteria, response rates were 50-68% at 1 month and 22-25% at 6 months. Transient depletion of CD3/CD5 T cells was observed on days 2 and 5 of treatment, with reconstitution on day 15 or day 29. Treatment-associated adverse effects were common but resolved rapidly without sequelae. CONCLUSION These findings suggest activity of anti-CD5 IC in active RA and warrant confirmation in a multicenter randomized study (currently underway).
Methicillin-resistant Staphylococcus aureus in extended-care facilities: experiences in a Veterans' Affairs nursing home and a review of the literature.

OBJECTIVES To delineate the spread of methicillin-resistant Staphylococcus aureus (MRSA) in a nursing home care unit (NHCU), determine its consequences, and discuss this experience in the context of reports from other nursing homes. DESIGN Observational and descriptive; routine and special surveillance for MRSA, including a facility-wide prevalence survey; characterization of MRSA isolates by disk diffusion and agar dilution susceptibility studies and restriction enzyme analysis of plasmid (REAP) DNA. SETTING AND PATIENTS A 120-bed skilled nursing facility that is an integral part of the Veterans' Affairs Medical Center (VAMC), Portland, Oregon. The patients are predominantly elderly men with severe underlying diseases and functional impairments. RESULTS An asymptomatic carrier brought MRSA into the NHCU in December 1987. During the next 15 months, 24 additional MRSA cases were detected. A prevalence survey conducted in March 1989 indicated that 39 (34%) of the 114 patients and 8 (7%) of the 117 employees were colonized or infected with MRSA. All strains were resistant to ciprofloxacin. REAP DNA indicated that 37 of 41 strains recovered in the March survey had identical patterns. Although 16 episodes of MRSA infection occurred in NHCU residents during 1988 through 1989, the outbreak had little effect on overall patterns of infectious morbidity and mortality in the facility. The outbreak, however, did result in an increased MRSA caseload at the medical center's acute-care division. CONCLUSIONS During the last three years, MRSA colonization and infection have become common in the NHCU at the Portland VAMC; this experience parallels that reported by several nursing homes in other parts of the country.
Mining text snippets for images on the web

Images are often used to convey many different concepts or illustrate many different stories. We propose an algorithm to mine multiple diverse, relevant, and interesting text snippets for images on the web. Our algorithm scales to all images on the web. For each image, all webpages that contain it are considered. The top-K text snippet selection problem is posed as combinatorial subset selection with the goal of choosing an optimal set of snippets that maximizes a combination of relevancy, interestingness, and diversity. The relevancy and interestingness are scored by machine learned models. Our algorithm is run at scale on the entire image index of a major search engine resulting in the construction of a database of images with their corresponding text snippets. We validate the quality of the database through a large-scale comparative study. We showcase the utility of the database through two web-scale applications: (a) augmentation of images on the web as webpages are browsed and (b)~an image browsing experience (similar in spirit to web browsing) that is enabled by interconnecting semantically related images (which may not be visually related) through shared concepts in their corresponding text snippets.
Aneurysmal Rupture During Coiling: Low Incidence and Good Outcomes at a Single Large Volume Center

OBJECTIVE: To study the incidence and clinical outcomes of intraoperative aneurysm rupture (IOR) during endovascular coil embolization at a single large volume center and to review the literature on this subject to determine whether IOR rupture rate and mortality correlate with volume of aneurysms treated at a given center and years since the institution of Guglielmi detachable coils as a treatment modality. METHODS: We reviewed the aneurysm database at the Center for Endovascular Surgery since its inception (1997–2003) and reviewed 600 consecutively treated intracranial aneurysms in which coiling was attempted. All patients who sustained an IOR were studied. Procedural and follow-up angiograms as well as clinical outcomes were retrospectively reviewed. A literature review was conducted. RESULTS: Six patients (1.0%) experienced IOR (1.4% in acutely ruptured lesions, 0% in unruptured). All six had presented with diffuse subarachnoid hemorrhage (Fisher Grade 3) and in good clinical grade (Hunt & Hess Grades 1–3). One patient was rendered permanently disabled secondary to delay in controlling the IOR. All others were neurologically unchanged. A review of the literature revealed a trend in correlation between volume of aneurysms treated and IOR rate; no statistically significant correlation was found between volume of aneurysms treated or years since the introduction of GDC technology and IOR rates or mortality. CONCLUSION: IOR remains a serious risk of endosaccular coiling of intracranial aneurysms, with aneurysms presenting with subarachnoid hemorrhage at greater risk for this complication. This risk can be minimized with very low associated morbidity and mortality (incidence 1%, 17% morbidity, 0% mortality at our institution).
More than meets the eye: understanding Trypanosoma brucei morphology in the tsetse

T. brucei, the causative parasite for African trypanosomiasis, faces an interesting dilemma in its life cycle. It has to successfully complete its infection cycle in the tsetse vector to be able to infect other vertebrate hosts. T. brucei has to undergo multiple morphological changes as it invades the alimentary canal of the tsetse to finally achieve infectivity in the salivary glands. In this review, we attempt to elucidate how these morphological changes are possible for a parasite that has evolved a highly robust cell structure to survive the chemically and physically diverse environments it finds itself in. To achieve this, we juxtaposed the experimental evidence that has been collected from T. brucei forms that are cultured in vitro with the observations that have been carried out on tsetse-infective forms in vivo. Although the accumulated knowledge on T. brucei biology is by no means trivial, several outstanding questions remain for how the parasite mechanistically changes its morphology as it traverses the tsetse and how those changes are triggered. However, we conclude that with recent breakthroughs allowing for the replication of the tsetse-infection process of T. brucei in vitro, these outstanding questions can finally be addressed.
Molecular and Biological Characterization of Human Monoclonal Antibodies Binding to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome Coronavirus

ABSTRACT Human monoclonal antibodies (MAbs) were selected from semisynthetic antibody phage display libraries by using whole irradiated severe acute respiratory syndrome (SARS) coronavirus (CoV) virions as target. We identified eight human MAbs binding to virus and infected cells, six of which could be mapped to two SARS-CoV structural proteins: the nucleocapsid (N) and spike (S) proteins. Two MAbs reacted with N protein. One of the N protein MAbs recognized a linear epitope conserved between all published human and animal SARS-CoV isolates, and the other bound to a nonlinear N epitope. These two N MAbs did not compete for binding to SARS-CoV. Four MAbs reacted with the S glycoprotein, and three of these MAbs neutralized SARS-CoV in vitro. All three neutralizing anti-S MAbs bound a recombinant S1 fragment comprising residues 318 to 510, a region previously identified as the SARS-CoV S receptor binding domain; the nonneutralizing MAb did not. Two strongly neutralizing anti-S1 MAbs blocked the binding of a recombinant S fragment (residues 1 to 565) to SARS-CoV-susceptible Vero cells completely, whereas a poorly neutralizing S1 MAb blocked binding only partially. The MAb ability to block S1-receptor binding and the level of neutralization of the two strongly neutralizing S1 MAbs correlated with the binding affinity to the S1 domain. Finally, epitope mapping, using recombinant S fragments (residues 318 to 510) containing naturally occurring mutations, revealed the importance of residue N479 for the binding of the most potent neutralizing MAb, CR3014. The complete set of SARS-CoV MAbs described here may be useful for diagnosis, chemoprophylaxis, and therapy of SARS-CoV infection and disease.