Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of genetic vaccines for pathogenic genes: construction of attenuated vif DNA immunization cassettes

Objective:To develop a putative immunization cassette using HIV-1 vif accessory gene derived from HIV-1 clinical specimens as a component of a DNA vaccine for HIV-1. Methods:vif genes were cloned from HIV-1-infected patients and the sequence variation present within the patients was analyzed. Prototypic genetic variants were selected and the ability of these clones to induce humoral and cellular immune responses was studied in animals. The selected protective genetic variants were biologically characterized through transcomplementation assays using primary cells infected with a vif-defective HIV-1 proviral clone. Results:Analysis of vif variants from different patients revealed that vif is highly conserved with the open reading frame remaining intact in vivo. It was shown that attenuated vif clones from HIV-1-infected subjects can effectively induce both humoral and cellular responses against Vif protein in mice. Evaluation of the cellular responses in vitro using human cellular targets infected with a clinical HIV-1 isolate showed that vif clones could induce cellular responses capable of destroying the virus. Conclusions:The vif variants developed in this study exhibited non-productive phenotypes, yet were capable of inducing specific immune responses against HIV-1. These constructs could be used as part of a DNA vaccine strategy for HIV-1. This vaccine adaptation strategy could be used for the development of immunogens for any pathogen resulting in cross-reactive immunity and attenuated gene pathogenesis.
Turbulent Flow of Non-Newtonian Tailings in Self Formed Channels on Tailings Stacks

One of the key requirements for estimating the storage capacity of tailings stacks is the ability to predict the stack profile or overall slope. As it has been observed (Williams and Meynick, 1986) that centrally discharged thickened tailings tend to confine themselves to self formed channels when transporting tailings down a beach, this provides strong clues that the channel slope may, in part, be dictating the final stack slope. Earlier work has pointed to the channel slope determining overall beach slope (Pirouz et al., 2005). The aim of this project is to develop a technique for estimating beach slope for non-segregating thickened tailings from laboratory size samples. This requires the development of a model of particle transport in self contained channels, and to further demonstrate what type of role the observed self formed channels play in beach slope formation.
RBF ensemble based on reduction of DAG structure

Binary classifiers are grouped into an ensemble to solve multi-class problems. One of proposed ensemble structure is a directed acyclic graph. In this structure, a classifier is created for each pair of classes. The number of classifiers can be reduced if groups of classes will be separated instead of individual classes. The proposed method is based on the similarity of classes defined as a distance between classes. For near classes the structure of DAG stays immutable. For the distant classes more than one is separated with a single classifier. In this paper, the proposed method is tested in variants based on various metrics. For the tests, several datasets from UCI repository was used and the results were compared with published works. The tests proved that grouping of radial basis functions into such ensemble reduces the classification cost and the recognition accuracy is not reduced significantly.
CSF Concentrations of cAMP and cGMP Are Lower in Patients with Creutzfeldt-Jakob Disease but Not Parkinson's Disease and Amyotrophic Lateral Sclerosis

BACKGROUND The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) are important second messengers and are potential biomarkers for Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Creutzfeldt-Jakob disease (CJD). METHODOLOGY/PRINCIPAL FINDINGS Here, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS) the cerebrospinal fluid (CSF) concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15) had lower cAMP (-70%) and cGMP (-55%) concentrations in CSF compared with controls (n = 11). There was no difference in PD, PD dementia (PDD) and ALS cases. Receiver operating characteristic (ROC) curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC) of 0.86 (cAMP) and 0.85 (cGMP). We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92) and to 93% and 100% for the ratio tau/cAMP (AUC 0.99). CONCLUSIONS/SIGNIFICANCE We conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.
Gout-causing Q141K mutation in ABCG2 leads to instability of the nucleotide-binding domain and can be corrected with small molecules

The multidrug ATP-binding cassette, subfamily G, 2 (ABCG2) transporter was recently identified as an important human urate transporter, and a common mutation, a Gln to Lys substitution at position 141 (Q141K), was shown to cause hyperuricemia and gout. The nature of the Q141K defect, however, remains undefined. Here we explore the Q141K ABCG2 mutation using a comparative approach, contrasting it with another disease-causing mutation in an ABC transporter, the deletion of Phe-508 (ΔF508) in the cystic fibrosis transmembrane conductance regulator (CFTR). We found, much like in ΔF508 CFTR, that the Q141K mutation leads to instability in the nucleotide-binding domain (NBD), a defect that translates to significantly decreased protein expression. However, unlike the CFTR mutant, the Q141K mutation does not interfere with the nucleotide-binding domain/intracellular loop interactions. This investigation has also led to the identification of critical residues involved in the protein–protein interactions necessary for the dimerization of ABCG2: Lys-473 (K473) and Phe-142 (F142). Finally, we have demonstrated the utility of using small molecules to correct the Q141K defect in expression and function as a possible therapeutic approach for hyperuricemia and gout.
A COMPARATIVE STUDY OF THE AMOUNT OF APICALLY EXTRUDED DEBRIS AFTER USING DIFFERENT TYPES OF GLIDE PATH FILES

INTRODUCTION: During root canal preparation; irrigants, dentin chips, pulp tissue and microorganisms may be extruded into the periradicular tissues which may cause postoperative pain and complications. OBJECTIVES: The aim of this study was to compare the amount of apically extruded debris in mesio-buccal canals of 30 extracted human mandibular molars instrumented with One-Shape file after preparing a proper glide path using G-files, ProGlider and K-files. MATERIALS AND METHOD: This study was conducted on the mesio-buccal roots of 30 human mandibular molars with curvature of 20 to 35 degrees. All specimens were divided into three groups according to the type of instrument used for glide path management. Group (1): manual instrumentation with K-files (#10, 15), Group (2): G-files: (G1: #0.12mm, G2: #0.17mm), and Group (3): ProGlider: single use rotary file. All teeth were instrumented using One-Shape file. Debris extruded apically from the teeth were collected into pre-weighed Eppendorf tubes. Three consecutive weights were obtained for each tube and the mean value was obtained. The weight of extruded debris was calculated as the difference between the pre and post instrumentation weights of the tubes. RESULTS: The highest amount of debris was found in the k-file group while the lowest amount with ProGlider group with significant differences between them. Moreover, significant difference was found between ProGlider and G -file while there was no significance between G-file and K -file groups. CONCLUSIONS: All techniques showed debris extrusion, although the use of NiTi rotary instruments may be rather beneficial.
Active recovery attenuates the fall in sweat rate but not cutaneous vascular conductance after supine exercise.

The purpose of this study was to identify whether baroreceptor unloading was responsible for less efficient heat loss responses (i.e., skin blood flow and sweat rate) previously reported during inactive compared with active recovery after upright cycle exercise (Carter R III, Wilson TE, Watenpaugh DE, Smith ML, and Crandall CG. J Appl Physiol 93: 1918-1929, 2002). Eight healthy adults performed two 15-min bouts of supine cycle exercise followed by inactive or active (no-load pedaling) supine recovery. Core temperature (T(core)), mean skin temperature (T(sk)), heart rate, mean arterial blood pressure (MAP), thoracic impedance, central venous pressure (n = 4), cutaneous vascular conductance (CVC; laser-Doppler flux/MAP expressed as percentage of maximal vasodilation), and sweat rate were measured throughout exercise and during 5 min of recovery. Exercise bouts were similar in power output, heart rate, T(core), and T(sk). Baroreceptor loading and thermal status were similar during trials because MAP (90 +/- 4, 88 +/- 4 mmHg), thoracic impedance (29 +/- 1, 28 +/- 2 Omega), central venous pressure (5 +/- 1, 4 +/- 1 mmHg), T(core) (37.5 +/- 0.1, 37.5 +/- 0.1 degrees C), and T(sk) (34.1 +/- 0.3, 34.2 +/- 0.2 degrees C) were not significantly different at 3 min of recovery between active and inactive recoveries, respectively; all P > 0.05. At 3 min of recovery, chest CVC was not significantly different between active (25 +/- 6% of maximum) and inactive (28 +/- 6% of maximum; P > 0.05) recovery. In contrast, at this time point, chest sweat rate was higher during active (0.45 +/- 0.16 mg.cm(-2). min(-1)) compared with inactive (0.34 +/- 0.19 mg.cm(-2). min(-1); P < 0.05) recovery. After exercise CVC and sweat rate are differentially controlled, with CVC being primarily influenced by baroreceptor loading status while sweat rate is influenced by other factors.
Objectness to assist salient object detection

When dealing with salient object that contains several regions with different appearances, salient object detection can be a difficult task as often only parts of the salient object are highlighted and consistency between the salient regions is poor. This study tackles this problem by introducing objectness to assist the salient object detection. Rather than treating objectness in the same manner as other low-level cues (e.g. uniqueness, location etc.) for the determination of regional saliency values, the authors emphasise that objectness should also play a significant role in tuning the consistency between salient regions. The authors integrate objectness, uniqueness and centre bias to find potential salient regions and then enforce consistency between these regions using a full-connected Gaussian Markov random field with the weights determined by the objectness score. Experimental results on public benchmark datasets indicate that the authors’ method performs well on many images which cannot be well detected traditionally.
c-Src Signaling Induced by the Adapters Sin and Cas Is Mediated by Rap1 GTPase

ABSTRACT Oncogenic Src proteins have been extensively studied to gain insight into the signaling mechanisms of Src. To better understand signaling through wild-type Src, we used an approach that involves activation of Src signaling through the binding of physiologic ligands to the Src SH3 domain. To this end, we used full-length and truncated versions of the multiadapter molecules Cas and Sin to activate c-Src, and we examined the intracellular pathways that mediate Src signaling under these conditions. We show that although all proteins bind to and are phosphorylated by c-Src, quantitative differences exist in the ability of the different ligands to activate c-Src signaling. In addition, we show that Sin- and Cas-induced Src signaling, as assayed by transcriptional activation, is exclusively mediated through a pathway that involves the adapter Crk and the GTP-binding protein Rap1. These data are in contrast to previous observations showing Ras to mediate signaling downstream of transforming Src alleles. In our system, we found that signaling through the oncogenic SrcY527 mutant is indeed mediated by Ras. In addition, we found that Rap1 also mediates oncogenic Src signaling. Our results show for the first time that Rap1 mediates c-Src kinase signaling and reveal mechanistic differences in the signaling properties of wild-type and transforming Src proteins.
Mutations in AKAP5 Disrupt Dendritic Signaling Complexes and Lead to Electrophysiological and Behavioral Phenotypes in Mice

AKAP5 (also referred to as AKAP150 in rodents and AKAP79 in humans) is a scaffolding protein that is highly expressed in neurons and targets a variety of signaling molecules to dendritic membranes. AKAP5 interacts with PKA holoenzymes containing RIIα or RIIβ as well as calcineurin (PP2B), PKC, calmodulin, adenylyl cyclase type V/VI, L-type calcium channels, and β-adrenergic receptors. AKAP5 has also been shown to interact with members of the MAGUK family of PSD-scaffolding proteins including PSD95 and SAP97 and target signaling molecules to receptors and ion channels in the postsynaptic density (PSD). We created two lines of AKAP5 mutant mice: a knockout of AKAP5 (KO) and a mutant that lacks the PKA binding domain of AKAP5 (D36). We find that PKA is delocalized in both the hippocampus and striatum of KO and D36 mice indicating that other neural AKAPs cannot compensate for the loss of PKA binding to AKAP5. In AKAP5 mutant mice, a significant fraction of PKA becomes localized to dendritic shafts and this correlates with increased binding to microtubule associated protein-2 (MAP2). Electrophysiological and behavioral analysis demonstrated more severe deficits in both synaptic plasticity and operant learning in the D36 mice compared with the complete KO animals. Our results indicate that the targeting of calcineurin or other binding partners of AKAP5 in the absence of the balancing kinase, PKA, leads to a disruption of synaptic plasticity and results in learning and memory defects.
A Determinant for Central Nervous System Persistence Localized in the Capsid of Theiler’s Murine Encephalomyelitis Virus by Using Recombinant Viruses

ABSTRACT The demyelinating process in Theiler’s murine encephalomyelitis virus (TMEV) infection in mice requires virus persistence in the central nervous system. Using recombinant TMEV assembled between the virulent GDVII and less virulent BeAn virus cDNAs, we now provide additional evidence supporting the localization of a persistence determinant to the leader P1 (capsid) sequences. Further, recombinant viruses in which BeAn sequences progressively replaced those of GDVII within the capsid starting at the leader NH2 terminus suggest that a conformational determinant requiring homologous sequences in both the VP2 puff and VP1 loop regions, which are in close contact on the virion surface, might underlie persistence.
Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

Background Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers’ structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake. Methods This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers. Results Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus. Conclusion This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future.
Characterization of the cytotoxic effect of a chimeric restriction enzyme , H 1 o-FokI Research

*Correspondence: Donald B. Sittman, Dept. of Biochemistry, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216-4505, USA; Tel: 601-984-1848, Fax: 601-984-1501, E-mail: dsittman@biochem.umsmed. edu
Learning Machine Learning: A Case Study

This correspondence reports on a case study conducted in the Master's-level Machine Learning (ML) course at Blekinge Institute of Technology, Sweden. The students participated in a self-assessment test and a diagnostic test of prerequisite subjects, and their results on these tests are correlated with their achievement of the course's learning objectives.
Systemic leukotriene B4 receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat

Evidence indicates an association between hypertension and chronic systemic inflammation in both human hypertension and experimental animal models. Previous studies in the spontaneously hypertensive rat (SHR) support a role for leukotriene B4 (LTB4), a potent chemoattractant involved in the inflammatory response, but its mode of action is poorly understood. In the SHR, we observed an increase in T cells and macrophages in the brainstem; in addition, gene expression profiling data showed that LTB4 production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. When LTB4 receptor 1 (BLT1) receptors were blocked with CP‐105,696, arterial pressure was reduced in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in systolic blood pressure (BP) indicators. These data provide new evidence for the role of LTB4 as an important neuro‐immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension.
Preventive Effect of Erythropoietin on Cardiac Dysfunction in Doxorubicin-Induced Cardiomyopathy

Background— Doxorubicin is a highly effective antineoplastic drug, but its clinical use is limited by its adverse side effects on the heart. We investigated possible protective effects of erythropoietin against doxorubicin-induced cardiomyopathy. Methods and Results— Cardiomyopathy was induced in mice by a single intraperitoneal injection of doxorubicin (15 mg/kg). In some cases, human recombinant erythropoietin (5000 U/kg) was started simultaneously. Two weeks later, left ventricular dilatation and dysfunction were apparent in mice given doxorubicin but were significantly attenuated by erythropoietin treatment. Erythropoietin also protected hearts against doxorubicin-induced cardiomyocyte atrophy and degeneration, myocardial fibrosis, inflammatory cell infiltration, and downregulation of expression of GATA-4 and 3 sarcomeric proteins, myosin heavy chain, troponin I, and desmin. Cyclooxygenase-2 expression was upregulated in doxorubicin-treated hearts, and that, too, was attenuated by erythropoietin. No doxorubicin-induced apoptotic effects were seen, nor were any changes seen in the expression of tumor necrosis factor-&agr; or transforming growth factor-&bgr;1. Antiatrophic and GATA-4 restoring effects of erythropoietin were demonstrated in the in vitro experiments with cultured cardiomyocytes exposed to doxorubicin, which indicated the direct cardioprotective effects of erythropoietin beyond erythropoiesis. Cardiac erythropoietin receptor expression was downregulated in doxorubicin-induced cardiomyopathy but was restored by erythropoietin. Among the downstream mediators of erythropoietin receptor signaling, activation of extracellular signal-regulated kinase was reduced by doxorubicin but restored by erythropoietin. By contrast, erythropoietin was ineffective when administered after cardiac dysfunction was established in the chronic stage. Conclusions— The present study indicates a protective effect of erythropoietin against doxorubicin-induced cardiomyopathy.
Projection-based motion compensation for gated coronary artery reconstruction from rotational x-ray angiograms

Three-dimensional reconstruction of coronary arteries can be performed during x-ray-guided interventions by gated reconstruction from a rotational coronary angiography sequence. Due to imperfect gating and cardiac or breathing motion, the heart's motion state might not be the same in all projections used for the reconstruction of one cardiac phase. The motion state inconsistency causes motion artefacts and degrades the reconstruction quality. These effects can be reduced by a projection-based 2D motion compensation method. Using maximum-intensity forward projections of an initial uncompensated reconstruction as reference, the projection data are transformed elastically to improve the consistency with respect to the heart's motion state. A fast iterative closest-point algorithm working on vessel centrelines is employed for estimating the optimum transformation. Motion compensation is carried out prior to and independently from a final reconstruction. The motion compensation improves the accuracy of reconstructed vessel radii and the image contrast in a software phantom study. Reconstructions of human clinical cases are presented, in which the motion compensation substantially reduces motion blur and improves contrast and visibility of the coronary arteries.
A Stylometric Inquiry into Hyperpartisan and Fake News

We report on a comparative style analysis of hyperpartisan (extremely one-sided) news and fake news. A corpus of 1,627 articles from 9 political publishers, three each from the mainstream, the hyperpartisan left, and the hyperpartisan right, have been fact-checked by professional journalists at BuzzFeed: 97% of the 299 fake news articles identified are also hyperpartisan. We show how a style analysis can distinguish hyperpartisan news from the mainstream (F1 = 0.78), and satire from both (F1 = 0.81). But stylometry is no silver bullet as style-based fake news detection does not work (F1 = 0.46). We further reveal that left-wing and right-wing news share significantly more stylistic similarities than either does with the mainstream. This result is robust: it has been confirmed by three different modeling approaches, one of which employs Unmasking in a novel way. Applications of our results include partisanship detection and pre-screening for semi-automatic fake news detection.