Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunogenicity and Protection of a Recombinant Human Adenovirus Serotype 35-Based Malaria Vaccine against Plasmodium yoelii in Mice

ABSTRACT Given the promise of recombinant adenovirus type 5 (rAd5) as a malaria vaccine carrier in preclinical models, we evaluated the potency of rAd35 coding for Plasmodium yoelii circumsporozoite protein (rAd35PyCS). We chose rAd35 since a survey with serum samples from African subjects demonstrated that human Ad35 has a much lower seroprevalence of 20% and a much lower geometric mean neutralizing antibody titer (GMT) of 48 compared to Ad5 (seroprevalence, 85%; GMT, 1,261) in countries with a high malaria incidence. We also demonstrated that immunization with rAd35PyCS induced a dose-dependent and potent, CS-specific CD8+ cellular and humoral immune response and conferred significant inhibition (92 to 94%) of liver infection upon high-dose sporozoite challenge. Furthermore, we showed that in mice carrying neutralizing antibody activity against Ad5, mimicking a human situation, CS-specific T- and B-cell responses were significantly dampened after rAd5PyCS vaccination, resulting in loss of inhibition of liver infection upon sporozoite challenge. In contrast, rAd35 vaccine was as potent in naive mice as in Ad5-preimmunized mice. Finally, we showed that heterologous rAd35-rAd5 prime-boost regimens were more potent than rAd35-rAd35 because of induction of anti-Ad35 antibodies after rAd35 priming. The latter data provide a further rationale for developing rAd prime-boost regimens but indicate that priming and boosting Ad vectors must be immunologically distinct and also should be distinct from Ad5. Collectively, the data presented warrant further development of rAd35-based vaccines against human malaria.
Assessment of VoIP quality over access networks

This paper assesses VoIP quality over access networks in Pakistan using a delay jitter measurement methodology for evaluating the perceptual quality of voice calls using the ITU-T G.107 speech quality E-model. Passive measurements for voice calls in the presence of background Internet data traffic for G.723. 1 and G.729a codecs are carried out using a non-intrusive parametric model. The R-factor and resultant Mean Opinion Scores (MOS) were calculated at different link loads and congestion hot spots were identified. The study highlights the inadequacy of access networks for handling VoIP traffic at current in Pakistan and suggests alleviating congestion by increasing capacity in access networks
Clinical Application of Development of Nonantibiotic Macrolides That Correct Inflammation-Driven Immune Dysfunction in Inflammatory Skin Diseases

Background. Inflammation-driven immune dysfunction supports the development of several chronic human disorders including skin diseases. Nonantibiotic macrolides have anti-inflammatory and/or immunomodulatory activity that suggests the exploitation of these in the treatment of skin diseases characterized by inflammatory disorders. Materials and Methods. We performed an extensive review of the nonantibiotic macrolide literature published between 2005 and 2012, including cross-references of any retrieved articles. We also included some data from our own experience. Results. Calcineurin antagonists such as tacrolimus and ascomycins (e.g., pimecrolimus) act by inhibiting the activation of the nuclear factor for activated T cells (NFAT). There are new applications for these macrolides that have been available for several years and have been applied to skin and hair disorders such as atopic dermatitis, oral lichen planus, vitiligo, chronic autoimmune urticaria, rosacea, alopecia areata, pyoderma gangrenosum, Behcet's disease, neutrophilic dermatosis, and lupus erythematosus. We also reviewed new macrolides, like rapamycin, everolimus, and temsirolimus. In addition to the literature review, we report a novel class of nonantibiotic 14-member macrocycle with anti-inflammatory and immunomodulatory effects. Conclusions. This paper summarizes the most important clinical studies and case reports dealing with the potential benefits of nonantibiotic macrolides which have opened new avenues in the development of anti-inflammatory strategies in the treatment of cutaneous disorders.
On characterizing Inclusion of Bayesian Networks

The inclusion problem deals with how to characterize (in graphical terms) whether all independence statements in the model induced by a DAG K are in the model induced by a second DAG L. Meek (1997) conjectured that this inclusion holds iff there exists a sequence of DAGs from L to K such that only certain 'legal' arrow reversal and 'legal' arrow adding operations are performed to get the next DAG in the sequence. In this paper we give several characterizations of inclusion of DAG models and verify Meek's conjecture in the case that the DAGs K and L differ in at most one adjacency. As a warming up a rigorous proof of graphical characterizations of equivalence of DAGs is given.
International Journal of Health Geographics Open Access Current Practices in the Spatial Analysis of Cancer: Flies in the Ointment

While many lessons have been learned from the spatial analysis of cancer, there are several caveats that apply to many, if not all such analyses. As "flies in the ointment", these can substantially detract from a spatial analysis, and if not accounted for, can lead to weakened and erroneous conclusions. This paper discusses several assumptions and limitations of spatial analysis, identifies problems of scientific inference, and concludes with potential solutions and future directions.
Alternating Towers and Piecewise Testable Separators

Two languages are separable by a piecewise testable language if and only if there exists no infinite tower between them. An infinite tower is an infinite sequence of strings alternati ng between the two languages such that every string is a subsequence (scattered substring) of all the strings that f ollow. For regular languages represented by nondeterministic finite automata, the existence of an infinite tower is decidab le in polynomial time. In this paper, we investigate the complexity of a particular method to compute a piecewise testable separator. We show that it is closely related to the height of maximal finite towers, and provide the upper and lower bounds with respect to the size of the given nondeterministic automata. Specifically, we show that the u pper bound is polynomial with respect to the number of states with the cardinality of the alphabet in the exponen t. Concerning the lower bound, we show that towers of exponential height with respect to the cardinality of the alphabet exist. Since these towers mostly turn out to be sequences of prefixes, we also provide a comparison with towe rs of prefixes.
Relative contribution of Prevotella intermedia and Pseudomonas aeruginosa to lung pathology in airways of patients with cystic fibrosis

Background Patients with cystic fibrosis (CF) with Pseudomonas aeruginosa lung infections produce endobronchial mucus plugs allowing growth of obligate anaerobes including Prevotella spp. Whether obligate anaerobes contribute to the pathophysiology of CF lung disease is unknown. Methods The virulence of Prevotella intermedia and Ps aeruginosa was investigated in vitro and in mice, antibodies against P intermedia in CF sera were assessed and a culture-independent detection method for P intermedia/P nigrescens in CF sputum was tested. Results P intermedia reached cell numbers of >105–>107 colony-forming units (CFU)/ml sputum. The majority of patients with CF (16/17; 94.1%) produced antibodies against two immunoreactive antigens of P intermedia. Culture supernatant fluids, collected from 109 P intermedia cells, were more cytotoxic to respiratory epithelial cells in vitro and inflammatory in mouse lungs than respective fluids from anaerobically grown Ps aeruginosa, while fluids from aerobically grown Ps aeruginosa had the highest cytotoxicity and inflammation. Both pathological effects were largely reduced when culture supernatant fluids from 107 cells of either species were used. P intermedia cells (∼106CFU/lung) did not induce mortality in the agar beads lung infection mouse model, while Ps aeruginosa cells caused death in 30% of mice due to rapid multiplication. A P intermedia/P nigrescens-specific PNA probe was significantly more sensitive than culture-dependent diagnostic assays to detect these strict anaerobes. Conclusion Ps aeruginosa and P intermedia become significantly virulent in vitro and in vivo when cell numbers exceed 108 CFU/lung.
The OWLlink API: Teaching OWL Components a Common Protocol

We introduce the OWLlink API that implements the OWLlink protocol on top of the Java-based OWL API. Besides providing an API to access remote OWLlink reasoning engines, it turns any OWL API aware reasoner into an OWLlink server. As such the OWLlink API provides the missing piece to replace the outdated DIG protocol by OWLlink in applications such as Protege.
An investigation into the usability of the STAR training and re-skilling website for carers of persons with dementia

Due to the successes in medical science people are now beginning to live much longer. With this brings increased problems associated with ageing, with one exemplar being dementia. Persons with dementia require care with activities of daily living, for example, with washing, dressing and eating. This requires additional care, which is usually provided by family and friends who assume the role of informal carers. Provision of care by informal carers brings irreversible changes to their lives that can lead to depression and feelings of loneliness. In part, these changes are linked with carers having insufficient understanding and training with dementia. The EU funded STAR project created an web portal that aims to provide the necessary online training that carers need, however, the usability of such a provision warrants investigation. This paper presents the findings of a usability test conducted on five carers of people with dementia while using the STAR Training Website. For the 21 usability issues identified, the paper outlines proposed solutions.
Prolonged studies of perfluorocarbon associated gas exchange and of the resumption of conventional mechanical ventilation.

OBJECTIVE To determine whether oxygenation and lung mechanics are preserved during perfluorocarbon associated gas exchange of 24 hrs duration and after evaporation of perfluorocarbon. DESIGN Prospective, experimental animal trials. SETTING Animal laboratory in a university setting. SUBJECTS Ten normal, neonatal piglets weighing 2.5 to 4.5 kg. INTERVENTIONS Ten piglets were anesthetized with fentanyl (25 micrograms/kg/hr), paralyzed with metocurine iodide (0.3 mg/kg) and placed on volume regulated continuous positive pressure breathing instituted at an FIO2 setting of 1.0, tidal volume of 15 mL/kg, respiratory rate of 25 breaths/min and positive end-expiratory pressure of 4 cm H2O. Perfluorocarbon associated gas exchange was initiated by intratracheal instillation of perflouorooctylbromide (30 mL/kg) followed by gas ventilation at the same settings. Evaporative losses were replaced by intratracheal instillation of 2.5 mL/kg/hr of perfluorocarbon. In one group of five piglets, evaporative losses were replaced for 24 hrs until the end of the study. In the other group of five piglets, replacement of perfluorocarbon was discontinued after 2 hrs, although gas ventilation was continued for 24 hrs. Blood gases and lung mechanics were measured in both groups. Histologic evaluation of lungs from both groups of animals was performed. MEASUREMENTS AND MAIN RESULTS Airway pressures and blood gases were stable throughout the 24-hr study period in both groups. Airway pressures in the evaporative group increased as evaporation of perfluorocarbon neared completion. There was no hemodynamic deterioration during the 24-hr study period. Histology showed good preservation of lung architecture in both groups. CONCLUSIONS Perfluorocarbon associated gas exchange was safe and effective in normal piglets for a period of 24 hrs. Evaporation of perfluorocarbon and resumption of continuous positive pressure breathing was well tolerated.
Ring Confidential Transactions

This article introduces a method of hiding transaction amounts in the strongly decentralized anonymous cryptocurrency Monero. Similar to Bitcoin, Monero is a cryptocurrency which is distributed through a proof-of-work “mining” process having no central party or trusted setup. The original Monero protocol was based on CryptoNote, which uses ring signatures and one-time keys to hide the destination and origin of transactions. Recently the technique of using a commitment scheme to hide the amount of a transaction has been discussed and implemented by Bitcoin Core developer Gregory Maxwell. In this article, a new type of ring signature, A Multilayered Linkable Spontaneous Anonymous Group signature is described which allows one to include a Pedersen Commitment in a ring signature. This construction results in a digital currency with hidden amounts, origins and destinations of transactions with reasonable efficiency and verifiable, trustless coin generation. The author would like to note that early drafts of this were publicized in the Monero Community and on the #bitcoin-wizards IRC channel. Blockchain hashed drafts are available showing that this work was started in Summer 2015, and completed in early October 2015. An eprint is also available at http://eprint.iacr. org/2015/1098 .
The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell migration

Deleted in liver cancer 1 (DLC1) is a multi-modular Rho-GTPase-activating protein (RhoGAP) and a tumor suppressor. Besides its RhoGAP domain, functions of other domains in DLC1 remain largely unknown. By protein precipitation and mass spectrometry, we identified eukaryotic elongation factor 1A1 (EF1A1) as a novel partner for the sterile alpha motif (SAM) domain of DLC1 but not the SAM domain of DLC2. The solution structure of DLC1 SAM revealed a new monomeric fold with four parallel helices, similar to that of DLC2 SAM but distinct from other SAM domains. Mutating F38, L39 and F40 within a hydrophobic patch retained its overall structure but abolished its interaction with EF1A1 with F38 and L39 forming an indispensable interacting motif. DLC1 SAM did not localize to and was not required for DLC1 to suppress the turnover of focal adhesions. Instead, DLC1 SAM facilitated EF1A1 distribution to the membrane periphery and ruffles upon growth factor stimulation. Compared with wild-type DLC1, the non-interactive DLC1 mutant is less potent in suppressing cell migration, whereas overexpression of the DLC1 SAM domain alone, but not the non-interactive mutant SAM or DLC2 SAM, greatly enhanced cell migration. This finding reveals a novel contribution of the SAM-EF1A1 interaction as a potentially important GAP-independent modulation of cell migration by DLC1.
Rapid Core-to-Peripheral Tissue Heat Transfer During Cutaneous Cooling

Perioperative thermal manipulations are usually directed at the skin surface because methods of directly warming the core are invasive or ineffective.However, inadequate heat flow between peripheral and core compartments will decrease the rate at which core temperature changes. We therefore determined whether core hypothermia is delayed after initiation of surface cooling. Six volunteers were anesthetized with propofol and midazolam, and maintained under three layers of passive insulation for 2.5-4 h. Subsequently, the skin surface was cooled using forced air, 1000 L/min, at 10 degrees C. Isoflurane was added as necessary to maintain arteriovenous shunt vasodilation. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Average arm and leg (peripheral) tissue temperatures were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. Overall body heat content decreased approximate equals 234 kcal during 2.5 h of active cooling. Core temperature, which was nearly constant before active cooling, decreased approximate equals 1.3 degrees C/h. There was no delay between initiation of active cooling and the decrease in core temperature. Furthermore, peripheral (arm and leg) and core (trunk and head) tissue heat contents decreased at virtually the same rates: approximate equals 50 kcal/h and approximate equals 47 kcal/h, respectively. These data indicate that there is little restriction of heat flow between peripheral and core tissues in vasodilated, anesthetized subjects. (Anesth Analg 1996;82:925-30)
Cardiac Stem Cells for Myocardial Regeneration: They Are Not Alone

Heart failure is the number one killer worldwide with ~50% of patients dying within 5 years of prognosis. The discovery of stem cells, which are capable of repairing the damaged portion of the heart, has created a field of cardiac regenerative medicine, which explores various types of stem cells, either autologous or endogenous, in the hope of finding the “holy grail” stem cell candidate to slow down and reverse the disease progression. However, there are many challenges that need to be overcome in the search of such a cell candidate. The ideal cells have to survive the harsh infarcted environment, retain their phenotype upon administration, and engraft and be activated to initiate repair and regeneration in vivo. Early bench and bedside experiments mostly focused on bone marrow-derived cells; however, heart regeneration requires multiple coordinations and interactions between various cell types and the extracellular matrix to form new cardiomyocytes and vasculature. There is an observed trend that when more than one cell is coadministered and cotransplanted into infarcted animal models the degree of regeneration is enhanced, when compared to single-cell administration. This review focuses on stem cell candidates, which have also been tested in human trials, and summarizes findings that explore the interactions between various stem cells in heart regenerative therapy.
Finding Protein-Coding Genes through Human Polymorphisms

Human gene catalogs are fundamental to the study of human biology and medicine. But they are all based on open reading frames (ORFs) in a reference genome sequence (with allowance for introns). Individual genomes, however, are polymorphic: their sequences are not identical. There has been much research on how polymorphism affects previously-identified genes, but no research has been done on how it affects gene identification itself. We computationally predict protein-coding genes in a straightforward manner, by finding long ORFs in mRNA sequences aligned to the reference genome. We systematically test the effect of known polymorphisms with this procedure. Polymorphisms can not only disrupt ORFs, they can also create long ORFs that do not exist in the reference sequence. We found 5,737 putative protein-coding genes that do not exist in the reference, whose protein-coding status is supported by homology to known proteins. On average 10% of these genes are located in the genomic regions devoid of annotated genes in 12 other catalogs. Our statistical analysis showed that these ORFs are unlikely to occur by chance.
Keying material based key pre-distribution scheme

A key pre-distribution scheme is a method by which initially an off-line trusted authority T A distributes pieces of information among a set of users. Later, each member of a group of users can compute a common key for secure communication. In this paper we present a Keying Material Based Key Pre-distribution Scheme, i.e., a group of users, using secret information preloaded in their memory and some public information retrieved from a keying material server, can compute a common key. We first formally define the keying material based key pre-distribution scheme in terms of the entropy, and give lower bounds on the amount of information each user has to keep secret. Then, we describe its applications for sensor networks.
How alcohol industry organisations mislead the public about alcohol and cancer

INTRODUCTION AND AIMS Alcohol consumption increases the risk of several types of cancer, including several common cancers. As part of their corporate social responsibility activities, the alcohol industry (AI) disseminates information about alcohol and cancer. We examined the information on this which the AI disseminates to the public through its 'social aspects and public relations organizations' and related bodies. The aim of the study was to determine its comprehensiveness and accuracy. DESIGN AND METHODS Qualitative analysis of websites and documents from 27 AI organisations. All text relating to cancer was extracted and analysed thematically. RESULTS Most of the organisations were found to disseminate misrepresentations of the evidence about the association between alcohol and cancer. Three main industry strategies were identified: (i) denial/omission: denying, omitting or disputing the evidence that alcohol consumption increases cancer risk; (ii) distortion: mentioning cancer, but misrepresenting the risk; and (iii) distraction: focussing discussion away from the independent effects of alcohol on common cancers. Breast cancer and colorectal cancer appeared to be a particular focus for this misrepresentation. DISCUSSION AND CONCLUSIONS The AI appears to be engaged in the extensive misrepresentation of evidence about the alcohol-related risk of cancer. These activities have parallels with those of the tobacco industry. This finding is important because the industry is involved in developing alcohol policy in many countries, and in disseminating health information to the public, including schoolchildren. Policymakers, academics, public health and other practitioners should reconsider the appropriateness of their relationships to these AI bodies.
Susceptibility of Different Hepatitis B Virus Isolates to Interferon-Alpha in a Mouse Model Based on Hydrodynamic Injection

Interferon alpha (IFN-α) is commonly used for the treatment of chronic hepatitis B (CHB) patients. Many factors including viral genetics may determine the outcome of IFN-α therapy. In this study, we tested whether the expression of IFN-α directly in the liver inhibits HBV gene expression and replication using a HBV hydrodynamic injection (HI) mouse model. Two replication-competent clones from different HBV isolates that belonging to HBV genotype A and B based on a pAAV vector (pAAV-HBV-A and pAAV-HBV-B) were compared for their susceptibility to IFN-α. HBV clones were injected into mice either alone or in combination with a murine (m) IFN-α expression plasmid (pmIFN-α). HBsAg and HBeAg concentrations and HBV DNA levels in mice differed after injection of these two HBV clones. Co-application of pmIFN-α together with the two distinct isolates resulted in markedly different kinetics of decline of HBsAg, HBeAg, and HBV DNA levels in the mice. Immunohistochemical staining of liver sections with anti-HBc showed that mIFN-α application completely inhibited the expression of HBcAg in mice inoculated with pAAV-HBV-B, whereas the expression of HBcAg was only reduced in mice with pAAV-HBV-A. Consistently, mice injected with pAAV-HBV-B and pmIFN-α showed higher expression levels of the IFN-stimulated genes (ISGs) ISG15, OAS, PKR as well as proinflammatory cytokine IL-6 in the liver. In addition, expression levels of anti-inflammatory cytokine IL-10 was down-regulated significantly in liver of the mice injected with pAAV-HBV-B and pmIFN-α. Our data demonstrate that IFN-α exerts antiviral activity in HBV mouse model, but different HBV isolates may have diverse susceptibility to IFN-α.