Miracle-dz/UniFAR-FTUs huggingface dataset:
CNS Delivery Via Adsorptive Transcytosis

Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of medicines across the blood-brain barrier (BBB). The BBB is readily equipped for the AMT process: it provides both the potential for binding and uptake of cationic molecules to the luminal surface of endothelial cells, and then for exocytosis at the abluminal surface. The transcytotic pathways present at the BBB and its morphological and enzymatic properties provide the means for movement of the molecules through the endothelial cytoplasm. AMT-based drug delivery to the brain was performed using cationic proteins and cell-penetrating peptides (CPPs). Protein cationization using either synthetic or natural polyamines is discussed and some examples of diamine/polyamine modified proteins that cross BBB are described. Two main families of CPPs belonging to the Tat-derived peptides and Syn-B vectors have been extensively used in CPP vector-mediated strategies allowing delivery of a large variety of small molecules as well as proteins across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from several limitations such as toxicity and immunogenicity—like the cationization strategy—as well as the instability of peptide vectors in biological media. The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics.
Synuclein-γ Is Closely Involved in Perineural Invasion and Distant Metastasis in Mouse Models and Is a Novel Prognostic Factor in Pancreatic Cancer

Purpose: Perineural invasion is associated with the high incidence of local recurrence and a dismal prognosis in pancreatic cancer. We previously reported a novel perineural invasion model and distinguished high– and low–perineural invasion groups in pancreatic cancer cell lines. This study aimed to elucidate the molecular mechanism of perineural invasion. Experimental Design: To identify key biological markers involved in perineural invasion, differentially expressed molecules were investigated by proteomics and transcriptomics. Synuclein-γ emerged as the only up-regulated molecule in high–perineural invasion group by both analyses. The clinical significance and the biological property of synuclein-γ were examined in 62 resected cases of pancreatic cancer and mouse models. Results: Synuclein-γ overexpression was observed in 38 (61%) cases and correlated with major invasive parameters, including perineural invasion and lymph node metastasis (P < 0.05). Multivariate analyses revealed synuclein-γ overexpression as the only independent predictor of diminished overall survival [hazard ratio, 3.4 (95% confidence interval, 1.51-7.51)] and the strongest negative indicator of disease-free survival [2.8 (1.26-6.02)]. In mouse perineural invasion and orthotopic transplantation models, stable synuclein-γ suppression by short hairpin RNA significantly reduced the incidence of perineural invasion (P = 0.009) and liver/lymph node metastasis (P = 0.019 and P = 0.020, respectively) compared with the control. Conclusions: This is the first study to provide in vivo evidence that synuclein-γ is closely involved in perineural invasion/distant metastasis and is a significant prognostic factor in pancreatic cancer. Synuclein-γ may serve as a promising molecular target of early diagnosis and anticancer therapy.
Changes in Earth’s Energy Budget during and after the “Pause” in Global Warming: An Observational Perspective

This study examines changes in Earth’s energy budget during and after the global warming “pause” (or “hiatus”) using observations from the Clouds and the Earth’s Radiant Energy System. We find a marked 0.83 ± 0.41 Wm−2 reduction in global mean reflected shortwave (SW) top-of-atmosphere (TOA) flux during the three years following the hiatus that results in an increase in net energy into the climate system. A partial radiative perturbation analysis reveals that decreases in low cloud cover are the primary driver of the decrease in SW TOA flux. The regional distribution of the SW TOA flux changes associated with the decreases in low cloud cover closely matches that of sea-surface temperature warming, which shows a pattern typical of the positive phase of the Pacific Decadal Oscillation. Large reductions in clear-sky SW TOA flux are also found over much of the Pacific and Atlantic Oceans in the northern hemisphere. These are associated with a reduction in aerosol optical depth consistent with stricter pollution controls in China and North America. A simple energy budget framework is used to show that TOA radiation (particularly in the SW) likely played a dominant role in driving the marked increase in temperature tendency during the post-hiatus period.
Identification of Coxiella burnetii surface‐exposed and cell envelope associated proteins using a combined bioinformatics plus proteomics strategy

The Gram‐negative pathogen Coxiella burnetii is an intracellular bacterium that replicates within the phagolysosomal vacuoles of eukaryotic cells. This pathogen can infect a wide range of hosts, and is the causative agent of Q fever in humans. Surface‐exposed and cell envelope associated proteins are thought to be important for both pathogenesis and protective immunity. Herein, we propose a complementary strategy consisting of (i) in silico prediction and (ii) inventory of the proteomic composition using three enrichment approaches coupled with protein identification. The efficiency of classical Triton X‐114 phase partitioning was compared with two novel procedures; isolation of alkaline proteins by liquid‐phase IEF, and cell surface enzymatic shaving using biofunctional magnetic beads. Of the 2026 protein sequences analyzed using seven distinct bioinformatic algorithms, 157 were predicted to be outer membrane proteins (OMP) and/or lipoproteins (LP). Using the three enrichment protocols, we identified 196 nonredundant proteins, including 39 predicted OMP and/or LP, 32 unknown or poorly characterized proteins, and 17 effectors of the Type IV secretion system. We additionally identified eight proteins with moonlighting activities, and several proteins apparently peripherally associated with integral or anchored OMP and/or LP.
Technological Change as Monetary a Phenomenon

This article attempts to study the function of monetary systems as networks of communication, which facilitate the channelling of social effort in the presence of exogenous conditions. A model of monetary system is being proposed, where monetary balances are algorithms of response, built up in the presence of uncertainty induced by technological change. Empirical research brought in support to that model demonstrates strong and negative a correlation between the velocity of money and the share of aggregate depreciation in current output, with intriguing links to exogenous mechanisms of energy absorption in the local social system.
Informed consent for human genetic and genomic studies: a systematic review

As genetic and genomic studies grow in scale, there are ethical concerns related to the collection and use of genetic information. The emergence of large public databases potentially redefine the terms of participation in genetic and genomic research, and suggests the changing application of traditional ethical principles such as privacy or consent. For this study, we wanted to see whether such developments are reflected in the informed consent processes in human genetic and genomic studies. Therefore, we performed a systematic review of the empirical studies that examined informed consent involving large genetic databases in human genetic and genomic studies, grouped the identified issues related to the different stakeholders (including subjects, researchers, and institutional review boards) and discussed the limitations and implications of these findings. Major themes related to the place of bioethical considerations, procured tissues, people involved, process of informed consent and study procedures. Frequently raised issues included confidentiality of participants, documentation of informed consent, public attitudes, future use of participant samples or data, and disclosure of results. Awareness and attention to these bioethical issues as well as assiduousness in managing these concerns in genetic/genomic research would further strengthen and safeguard the rights, safety and well‐being of genetic research participants.
Marauding Terrorist Firearms’ Attacks

Emotive scenes on television screens herald a new genre of increasingly frequent terrorist attacks. Events across the globe highlight the potential lethality of asymmetrical belligerents, either operating alone or as part of an organised team, causing carnage and widespread fatalities with firearms. With the increased likelihood of this type of attack in the UK, David Graham asks whether response plans are both appropriate and effective in their pre-planning in the view of professional emergency service commanders who will be responsible for dealing with these incidents.
Evolution, plasticity and evolving plasticity of phenology in the tree species Alnus glutinosa

Both traits and the plasticity of these traits are subject to evolutionary change and therefore affect the long‐term persistence of populations and their role in local communities. We subjected clones from 12 different populations of Alnus glutinosa, located along a latitudinal gradient, to two different temperature treatments, to disentangle the distribution of genetic variation in timing of bud burst and bud burst plasticity within and among genotypes, populations, and regions. We calculated heritability and evolvability estimates for bud burst and bud burst plasticity and assessed the influence of divergent selection relative to neutral drift. We observed higher levels of heritability and evolvability for bud burst than for its plasticity, whereas the total phenological heritability and evolvability (i.e. combining timing of bud burst and bud burst plasticity) suggest substantial evolutionary potential with respect to phenology. Earlier bud burst was observed for the low‐latitudinal populations than for the populations from higher latitudes, whereas the high‐latitudinal populations did not show the expected delayed bud burst. This countergradient variation can be due to evolution towards increased phenological plasticity at higher latitudes. However, because we found little evidence for adaptive differences in phenological plasticity across the latitudinal gradient, we suggest differential frost tolerance as the most likely explanation for the observed phenological patterns in A. glutinosa.
Best optimal route cover search using spatial keyword covering

Business features are indicated with the help of keywords in spatial database. While retrieving data from spatial database a problem occurs and named as Closest Keyword Cover Search, problem occurs due to set of query keywords and minimum inter object distance between them. Object evaluation for the best decision making depends on the increase of availability and keyword rating. Closest keywords search is extended to Best Keyword Cover deals with inter object distance and keyword rating in more standard manner. Initially baseline algorithm is used to overcome the problem mentioned and it is not applicable for real time databases, in order to overcome this a new algorithm is proposed and named as Keyword Nearest Neighbor Expansion it reduces the number of candidate keyword covers compared to baseline algorithm. With the help of K-NNE algorithm local best solution is obtained and generates less new candidate keyword covers compared to baseline algorithm.
Parkville virus: A novel genetic variant of human calicivirus in the Sapporo virus clade, associated with an outbreak of gastroenteritis in adults

This report describes the characterization of Parkville virus, the etiologic agent of an outbreak of foodborne gastroenteritis, that has the morphology of a calicivirus and genetic properties that distinguish it from previously identified strains in the Sapporo/Manchester virus clade. Sequence analysis of the Parkville virus genome showed it contained the RNA‐dependent RNA polymerase motifs GLPSG and YGDD characteristic of members of the family Caliciviridae with an organization identical to that reported for the Manchester virus where the capsid region of the polyprotein is fused to the RNA polymerase. Parkville virus however, demonstrates considerable sequence divergence from both the Manchester and Sapporo caliciviruses, providing the first indications that genetic diversity exists within caliciviruses of this previously homogeneous clade. On the basis of recent advances in the genetic characterization of members of the family Caliciviridae, we propose a new interim phylogenetic classification system in which Parkville virus would be included with Manchester and Sapporo virus as a separate group distinct from the small round‐structured viruses (Norwalk‐like viruses) that also cause diarrhea in humans. J. Med. Virol. 52:173–178, 1997. © 1997 Wiley‐Liss, Inc.
The Determinants of External debt in Sub Saharan Africa

Determining the factors that influence external indebtedness in developing countries became an important focus for research following the damaging external debt crises of the early 1970s. While the resulting research has provided valuable insights, there has been a tendency to rely solely on economic factors and surprisingly little concern has been given to political factors that may be important determinants of debt. This paper investigates the main contributing factors to debt accumulation using panel data methods and focusing on a group of 36 Sub Saharan Africa countries (SSA) over the period 1975 to 2012. Instead of relying only on economic variables, the paper introduces a number of political variables that are found to be important and show the need to nuance the economic arguments. Democratically administered governments in the region are found to accumulate more debt than autocratic ones and parliamentary systems seem to accumulate more debt than presidential democracies. Furthermore, countries with a constrained executive and countries with more open and competitive electoral systems tend to lead to the accumulation of less debt. Finally, countries that received debt relief seem to accumulate less debt relative to those that did not while economic activity and openness are important in reducing debt in the region.
Systematic Multivariable H-infinity Control Design for Primary Frequency Regulation in Stand-alone Microgrids with High Penetration of Renewable Energy Sources

In this paper, a systematic design of a robust multi-variable control structure for primary frequency regulation in microgrids with high rate of renewable source penetration is proposed. The considered microgrid represents a diesel-photovoltaic-supercapacitor hybrid power generation system operating in stand-alone mode. The proposed control structure relies on a two-level architecture: classical PI-based current tracking controllers are placed on the low control level and receive references from anH∞-control-based upper level. A comprehensive methodology that casts the specific engineering demands of microgrid operation into H∞ control formalism is detailed. It is also shown how closed-loop dynamical performance requirements must at their turn be taken into account in the initial microgrid setup and sizing, namely in choosing and rating the energy storage system. Numerical simulations carried out in MATLAB R ©/Simulink R © show the effectiveness of the proposed H∞ robust control strategy on a MVA-rated microgrid.
A global analysis of xylem vessel length in woody plants.

UNLABELLED PREMISE OF THE STUDY Vessels are the chief conduit for long-distance water transport in the majority of flowering plants. Vessel length is a key trait that determines plant hydraulic efficiency and safety, yet relatively little is known about this xylem feature. • METHODS We used previously published studies to generate a new global data set of vessel length in woody plants. These data were used to examine how evolutionary history, plant habit, environment, and growth ring porosity influenced vessel length. We also examined the relationship between mean vessel length and mean vessel diameter and maximum vessel length. • KEY RESULTS Data on mean vessel length were available for stems of 130 species and on maximum vessel length for stems of 91 species. A phylogenetic analysis indicated that vessel length did not exhibit significant phylogenetic signal. Liana species had longer vessel lengths than in tree or shrub species. Vessel diameter was not predictive of mean vessel length, but maximum vessel length strongly predicted mean vessel length. Vessel length did not vary between species that differed in growth ring porosity. • CONCLUSIONS Many traits often assumed to be linked to vessel length, including growth ring porosity and vessel diameter, are not associated with vessel length when compared interspecifically. Sampling for vessel length has been nonrandom, e.g., there are virtually no data available for roots, and sampling for environment has been confounded with sampling for habit. Increased knowledge of vessel length is key to understanding the structure and function of the plant hydraulic pathway.
2D-DCT on FPGA by polynomial transformation in two-dimensions

A 2D discrete cosine transform implementation on FPGA, using polynomial transformation algorithm on two dimensions is presented. The precision and area results are reported to be compared with the classical row-column implementation. Advantages and drawbacks are commented. Since one dimension DCT is a basic block for the implementation of two dimensions, we first show two 1D-DCT implementations to be selected for use on 2D. A modification to the polynomial transform is also shown in order to get a normalized 2D-DCT. All the designs are synthesized and implemented on Xilinx Virtex FPGAs.
An evaluation of educational outreach to improve evidence-based prescribing in Medicaid: a cautionary tale.

RATIONALE, AIMS AND OBJECTIVES Evidence suggests that educational outreach ('academic detailing') improves evidence-based prescribing. We evaluated the impact of an academic detailing programme intended to increase new statin prescriptions. METHODS In a 2 x 2 factorial design we evaluated the effect of an academic detailing programme with/without telephonic care management for patients. Eligible patients were continuously enrolled Medicaid members at high risk for cardiovascular disease utilization who were not receiving statin medication in the 18 months prior to the intervention. All primary care prescribers assigned to these patients were randomized by clinic to academic detailing. Two trained nurses provided the detailing to prescribers, including specific discussion about the use of statins in this high-risk patient population. Nurses left the prescribers with a summary of clinical practice guidelines, a one-page detailing sheet and a list of patients under the care of the prescriber who were candidates for statins. The primary outcome was the incidence of a new statin prescription claim during the 6-month intervention period and the subsequent 6 months. Logistic regression models were used to estimate main effects of the interventions and to adjust for potential confounding variables in the study. RESULTS Forty-eight clinics were randomized, effectively randomizing a total of 284 patients and 128 prescribers. Among the 284 patients, 46 (16%) received a new statin claim during the evaluation period. Controlling for significant bivariate associations, the academic detailing intervention had no significant effect on new statin prescriptions compared with the control group (odds ratio = 0.8, 95% confidence interval: 0.4-1.6, P = 0.5). CONCLUSION Among this Medicaid population at high risk for cardiovascular events, an academic detailing programme to increase statin prescriptions was not effective. To assist others to learn from our failed effort, we identify and discuss critical elements in the design and implementation of the programme that could account for these results.
Annealed high band gap tunnel junctions with peak current densities above 800 A/cm2

The development of high-performance high band gap tunnel junctions is critical for producing efficient multijunction photovoltaic cells that can operate at high solar concentrations. The n-InGaP/GaAs/p-AlGaAs TJ has been demonstrated to produce peak tunneling currents (Jpk) above 1000 A/cm2 with minimal absorption losses due to the use of thin (<50 Â) GaAs layer. We will report on the growth and device modeling of these structures as well as the effect of high temperature annealing on Jpk. A method to grow TJ structures resistant to annealing will be described, which has resulted in thermally annealed TJ with Jpk above 800 A/cm2. This is the highest value ever reported for an annealed high band gap TJ. Device modeling has been used to investigate the source of the high tunneling current, as well as the behavior of the annealed TJ.
Agreement and reliability of pelvic floor measurements during contraction using three‐dimensional pelvic floor ultrasound and virtual reality

Virtual reality is a novel method of visualizing ultrasound data with the perception of depth and offers possibilities for measuring non‐planar structures. The levator ani hiatus has both convex and concave aspects. The aim of this study was to compare levator ani hiatus volume measurements obtained with conventional three‐dimensional (3D) ultrasound and with a virtual reality measurement technique and to establish their reliability and agreement.
[Identification of a fibrinolytic enzyme producing Bacillus pseudomycoides and purification and characterization of the enzyme].

OBJECTIVE To purify a single fibrinolytic enzyme from Bacillus pseudomycoides B-60 and to determine its N-terminal sequence and to characterize the fibrinolytic enzyme. METHODS We examined the fibrinolytic enzyme activity by fibrin plate and purified fibrinolytic enzyme by ammonium sulfate fractional precipitation and DEAE anion exchange chromatography. RESULTS Obtained a single protein fraction with fibrinolytic activity (BpFE) from B. pseudomycoides B-60. It appeared as a single band in the SDS-PAGE with a relative molecular weight of 34 kDa. The fibrinolytic activity of the protein was stable at 4-50 degrees C and at pH 5-10. The activity sharply decreased above 50 degrees C, and the total loss of activity at pH 3.0. The enzymatic activity was slightly enhanced by the ions of Ca2+, Mg2+, Mn2+, whereas strongly inhibited by Cu2+ ion. Phenylmethyl sulfonyl fluoride (PMSF) could completely inhibit its activity. In addition, the activity improved when the protein was enzymatically hydrolyzed using trypsin and pepsin. The first 15 amino acids of the N-terminal sequence of the enzyme were determined to be VTGTNAVGTGKGVLG. The partial amino acids sequence alignment study of the enzyme from B-60 strain with bacillolysin, neutral protease and hydrolase which were from B. cereus, B. thuringiensis, B. anthracis and Lactobacillus sp. was carried out, and there is a 100% homogeneity between them. CONCLUSION We obtained a single fibrinolytic enzyme. Through its N-terminal sequence alignment study, a plasmin with high homogeneity to this protein was not found yet. This provided a basis for further study of new thrombolytic drugs.