Miracle-dz/UniFAR-FTUs huggingface dataset:
Exponential quadruplex priming amplification for DNA‐based isothermal diagnostics

Polymerase chain reaction (PCR) is a method of choice for molecular diagnostics. However, PCR relies on thermal cycling, which is not compatible with the goals of point‐of‐care diagnostics. A simple strategy to turn PCR into an isothermal method would be to use specific primers, which upon polymerase elongation can self‐dissociate from the primer‐binding sites. We recently demonstrated that a monomolecular DNA quadruplex, GGGTGGGTGGGTGGG, meets these requirements, which led to the development of the linear versions of quadruplex priming amplification (QPA). Here we demonstrate exponential version of isothermal QPA, which allows an unprecedented 1010‐fold amplification of DNA signal in less than 40 min. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 88–95, 2015.
Collar Sign in Incompletely Occluded Aneurysms after Pipeline Embolization: Evaluation with Angiography and Optical Coherence Tomography

BACKGROUND AND PURPOSE: Flow diversion with the Pipeline Embolization Device has emerged as an attractive treatment for cerebral aneurysms. Processes involved in aneurysm occlusion include changes in intra-aneurysmal hemodynamics and endothelialization of the device. Here, we call attention to a radiographic sign not previously reported that is detected in incompletely occluded aneurysms after treatment with the Pipeline Embolization Device at angiographic follow-up and referred to as the “collar sign. ” MATERIALS AND METHODS: A retrospective review of all patients who underwent placement of a Pipeline Embolization Device for cerebral aneurysms between January 2014 and May 2016 was performed. All aneurysms found to show the collar sign at follow-up were included. Optical coherence tomography was performed in 1 case. RESULTS: One hundred thirty-five aneurysms were treated in 115 patients. At angiographic follow-up, 17 (10.7%) aneurysms were found to be incompletely occluded. Ten (58.8%) of these aneurysms (average diameter, 7.9 ± 5.0 mm) were found to have the collar sign at angiographic follow-up (average, 5.5 ± 1.0 months). Four (40.0%) of the aneurysms underwent a second angiographic follow-up (average, 11.0 ± 0.9 months) after treatment, and again were incompletely occluded and showing the collar sign. Two patients underwent retreatment with a second Pipeline Embolization Device. Optical coherence tomography showed great variability of endothelialization at the proximal end of the Pipeline Embolization Device. CONCLUSIONS: The collar sign appears to be indicative of endothelialization, but continued blood flow into the aneurysm. This is unusual given the processes involved in aneurysm occlusion after placement of the Pipeline Embolization Device and has not been previously reported.
What's "Quickest and Easiest?" Parental Perspectives of the Trip To and From School

This study examined perspectives of the trip to/from school and travel mode choice among parents who differed in socio-economic status (SES), and whose children attended schools located in different areas (i.e., urban vs. inner-suburban) across Toronto. Thirty-seven parents (20 active and 17 non-active travelers) of grade four to six students from four elementary schools (capturing diversity with respect to built environment and SES) participated in qualitative interviews after taking photos of their trip to/from school. Data were analyzed using thematic analysis linking the text and visual data. School travel was a habitual behaviour involving a 2step parental decision-making process; these decisions were influenced by different factors. While escort decisions were dictated by safety concerns, the behavioural cost and reinforcing value of travel mode alternatives dictated mode choice. Strategies addressing these behavioural cost and reinforcing value factors may be helpful in making walking to/from school the quickest and most convenient choice.
Evaluation of Knowledge Management Application on Bank Central Asia (BCA)

The increasingly global business competition has an impact on the increasing demands of competitiveness among companies in Indonesia in order to survive, the ability of decision making and solving a problem and effective managerial capability requires the company has strong intellectual capital and embrace open system to be able to respond more easily to the needs and needs of stakeholders in the company. Knowledge Management System (KMS) is a system created to facilitate the capture, storage, retrieval, transfer and reuse of knowledge. The purpose of making KMS is to create and build technology that can help users to reduce the tacit knowledge into explicit knowledge to be used in dealing with a problem with knowledge in accordance with the procedures of a company or organization in the action to handle the problem. Every company or organization has done the implementation of knowledge management system, not least in Bank Central Asia (BCA). BCA's strategy focuses on growth, credit quality and efficiency that enable BCA to achieve high-quality growth and enhance its role as a transactional Bank providing payment settlement services in support of achieving a strong Indonesian economy and national development goals. This research explains how far the application of knowledge management system conducted by BCA.
When Do Structural Holes in Employees' Networks Improve Their Radical Creativity? A Moderated Mediation Model

Previous research has found a relationship between structural holes of knowledge networks, tie strength of knowledge networks, and creativity. Our study extends these findings by proposing that characteristics of R&D employees' team knowledge networks influence their acquired diversified knowledge from the team, which is critical to creativity. Our results based on 558 members of 92 R&D teams demonstrated that, in order to benefit from their broker position in acquiring diversified knowledge, R&D employees should maintain their tie strength toward the team members with whom they are connected.
The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics

Intrinsic resistance to antibiotics is a serious therapeutic problem in the case of many bacterial species. The Gram‐positive human pathogen Listeria monocytogenes is intrinsically resistant to broad spectrum cephalosporin antibiotics, which are commonly used in therapy of bacterial infections. Besides three penicillin‐binding proteins the intrinsic cephalosporin resistome of L. monocytogenes includes multidrug resistance transporter transporters, proteins involved in peptidoglycan biosynthesis and modification, cell envelope proteins with structural or general detoxification function, cytoplasmic proteins with unknown function and regulatory proteins. Analysis of the regulation of the expression of genes involved in the intrinsic resistance of L. monocytogenes to cephalosporins highlights the high complexity of control of the intrinsic resistance phenotype. The regulation of the transcription of the intrinsic resistome determinants involves the activity of eight regulators, namely LisR, CesR, LiaR, VirR, σB, σH, σL and PrfA, of which the most prominent role play LisR, CesR and σB. Furthermore, the vast majority of the intrinsic resistome determinants contribute to the tolerance of different stress conditions and virulence. A study indicates that O‐acetyltransferase OatA is the most promising candidate for co‐drug development since an agent targeting OatA should sensitize L. monocytogenes to certain antibiotics, therefore improving the efficacy of listeriosis treatment as well as food preservation measures.
Chronic Spinal Nerve Ligation Induces Changes in Response Characteristics of Nociceptive Spinal Dorsal Horn Neurons and in Their Descending Regulation Originating in the Periaqueductal Gray in the Rat

We studied whether a chronic neuropathy induced by unilateral spinal nerve ligation changes the response characteristics of spinal dorsal horn wide-dynamic range (WDR) neurons or their periaqueductal gray (PAG)-induced descending modulation. Experiments were performed in rats with behaviorally demonstrated allodynia induced by spinal nerve ligation and in a group of nonneuropathic control rats. The stimulus-response functions of WDR neurons for mechanical and thermal stimuli and the modulation of their peripherally evoked responses by electrical stimulation of the PAG were determined under pentobarbital anesthesia. The results showed that neuropathy caused a significant leftward shift in stimulus-response functions for mechanical stimuli. In contrast, stimulus-response functions for noxious heat stimuli in the neuropathic limb were, if anything, shifted rightward, although this shift was short of statistical significance. In neuropathic rats, PAG stimulation produced a significantly stronger attenuation of spinal neuronal responses induced by noxious heat in the unoperated than in the operated side. At the intensity that produced attenuation of noxious heat stimuli, PAG stimulation did not produce any significant change in spinal neuronal responses evoked by mechanical stimuli either from the operated or the nonoperated hindlimb of the neuropathic rats. Spontaneous activity of WDR neurons was higher in the operated side of neuropathic rats than in control rats. Afterdischarges evoked by peripheral stimuli were observed in 1/16 of the WDR neurons ipsilateral to spinal nerve ligation and not at all in other experimental groups. The WDR neurons studied were not activated by innocuous or noxious cold stimuli. The results indicate that spinal nerve ligation induces increased spontaneous activity and enhanced responses to mechanical stimuli in the spinal dorsal horn WDR neurons, whereas noxious heat-evoked responses are not significantly changed or if anything, attenuated. Moreover, the inhibition of noxious heat stimuli by PAG stimulation is attenuated in the neuropathic side. It is proposed that the observed changes in the response characteristics of the spinal dorsal horn WDR neurons and in their descending modulation may contribute to the neuropathic symptoms in these animals.
Pitch perception beyond the traditional existence region of pitch

Humans’ ability to recognize musical melodies is generally limited to pure-tone frequencies below 4 or 5 kHz. This limit coincides with the highest notes on modern musical instruments and is widely believed to reflect the upper limit of precise stimulus-driven spike timing in the auditory nerve. We tested the upper limits of pitch and melody perception in humans using pure and harmonic complex tones, such as those produced by the human voice and musical instruments, in melody recognition and pitch-matching tasks. We found that robust pitch perception can be elicited by harmonic complex tones with fundamental frequencies below 2 kHz, even when all of the individual harmonics are above 6 kHz—well above the currently accepted existence region of pitch and above the currently accepted limits of neural phase locking. The results suggest that the perception of musical pitch at high frequencies is not constrained by temporal phase locking in the auditory nerve but may instead stem from higher-level constraints shaped by prior exposure to harmonic sounds.
Haemodynamic changes during anaesthesia induced and maintained with propofol.

The haemodynamic effects of propofol, given as a single dose of 2 mg kg-1 immediately followed by a continuous infusion of 6 mg kg-1 h-1, were studied in 10 elderly patients premedicated with lorazepam 1 mg i.v. All patients breathed room air spontaneously. Unconsciousness was successfully induced in all patients and persisted during the 60 min of the infusion. Statistically significant decreases in systolic and diastolic arterial pressures were observed 2 min after induction (28% and 19%, respectively) and during infusion (30% and 25%, respectively) and were related to decreases in systemic vascular resistance (21% following induction and 30% during infusion). Cardiac output was not affected at any time nor were stroke volume and heart rate. We conclude that the arterial hypotension associated with the induction and infusion of propofol is mainly a result of a decrease in afterload without compensatory increases in heart rate or cardiac output.
The Common Core of Administrative Laws in Europe: a research agenda

This paper aims at ascertaining whether, despite many differences between European systems of administrative law, there are some connecting elements, or a “common core”, and, if so, whether such ‘connecting elements’ can be formulated in legal terms, as opposed to generic idealities. After a quick introduction, the paper is divided into three parts. Part 2 illustrates the background, in two respects: the transformation of administrative law within European countries and the variety of views about the possibility to compare them. In Part 3, it is argued that there are two main difficulties with traditional approaches to comparative administrative law: the tendency to juxtapose a variety of legal systems, without comparing them, and the excessive emphasis on institutional design. In part 4, the main choices of the research are explained; that is its purpose is that of the advancement of knowledge, as opposed to the attempt to harmonize national laws, the focus on administrative procedure, and the choice of legal systems. Last but not least, there is a combination of a synchronic comparison, based on a ‘factual’ approach which draws on the experience gathered in the context of the ‘Common Core of European private law’, with a diachronic comparison; that is, a retrospective that sheds light on some aspects of history of legal institutions that look particularly relevant for understanding the processes of cross-fertilization.
Enantioselectivity of bunitrolol 4-hydroxylation is reversed by the change of an amino acid residue from valine to methionine at position 374 of cytochrome P450-2D6.

The enantioselectivity of 4-hydroxylation of bunitrolol (BTL), a beta-adrenoceptor blocking drug, was studied in microsomes from human liver, human hepatoma (Hep G2) cells expressing CYP2D6, and lymphoblastoid cells expressing CYP2D6. Kinetics in human liver microsomes showed that the Vmax value for (+)-BTL was 2.1-fold that of (-)-BTL, and that the Km value for (+)-BTL was lower than that for the (-)-antipode, resulting in the intrinsic clearance (Vmax/Km) of (+)-BTL being 2.1-fold over its (-)-antipode. CYP2D6 (CYP2D6-met) expressed in Hep G2 cells had a methionine residue at position 373 of the amino acid sequence and a rat-type N-terminal peptide (MELLNGTGLWSM) instead of the human-type (MGLEALVPLAVIV), and showed enantioselectivity of [(+)-BTL < (-)-BTL] for the rate of BTL 4-hydroxylation. In contrast, enantioselectivity [(+)-BTL > (-)-BTL] for Hep G2-CYP2D6 (CYP2D6-val) with a human-type N-terminal peptide that had a valine residue at 374, which corresponds to the methionine of the CYP2D6-met variant, was the same as that for human liver microsomes. We further confirmed that CYP2D6-met and CYP2D6-val expressed in human lymphoblastoid cells, both of which have methionine and valine, respectively, at position 374 and a human-type N-terminal peptide, exhibited the same enantioselectivities as those obtained from CYP2D6-met and CYP2D6-val expressed in the Hep G2 cell system. These results indicate that the amino acid at 374 of CYP2D6 is one of the key factors influencing the enantioselectivity of BTL 4-hydroxylation.
Arsenic neurotoxicity — A review

Arsenic (As) is one of the oldest poisons known to men. Its applications throughout history are wide and varied: murder, make-up, paint and even as a pesticide. Chronic As toxicity is a global environmental health problem, affecting millions of people in the USA and Germany to Bangladesh and Taiwan. Worldwide, As is released into the environment by smelting of various metals, combustion of fossil fuels, as herbicides and fungicides in agricultural products. The drinking water in many countries, which is tapped from natural geological resources, is also contaminated as a result of the high level of As in groundwater. The environmental fate of As is contamination of surface and groundwater with a contaminant level higher than 10 particle per billion (ppb) as set by World Health Organization (WHO). Arsenic exists in both organic and inorganic species and either form can also exist in a trivalent or pentavalent oxidation state. Long-term health effects of exposure to these As metabolites are severe and highly variable: skin and lung cancer, neurological effects, hypertension and cardiovascular diseases. Neurological effects of As may develop within a few hours after ingestion, but usually are seen in 2—8 weeks after exposure. It is usually a symmetrical sensorimotor neuropathy, often resembling the Guillain—Barré syndrome. The predominant clinical features of neuropathy are paresthesias, numbness and pain, particularly in the soles of the feet. Electrophysiological studies performed on patients with As neuropathy have revealed a reduced nerve conduction velocity, typical of those seen in axonal degeneration. Most of the adverse effects of As, are caused by inactivated enzymes in the cellular energy pathway, whereby As reacts with the thiol groups of proteins and enzymes and inhibits their catalytic activity. Furthermore, As-induced neurotoxicity, like many other neurodegenerative diseases, causes changes in cytoskeletal protein composition and hyperphosphorylation. These changes may lead to disorganization of the cytoskeletal framework, which is a potential mechanism of As-induced neurotoxicity. Human & Experimental Toxicology (2007) 26, 823—832
Collective Bargaining Amidst Education Reform

Excerpt] It is increasingly clear that the prospects for educational reform in America and the future of collective bargaining in public education are closely intertwined and becoming more so. The authors of this paper attempt to provide a framework for understanding both sets of developments and their interrelationships. Tracing the evolution of the current reform movement, then discussing the origins of the present system of bargaining in public education, we argue that reformers and bargainers alike are beginning to grapple with the same realities: new issues and new kinds of power that are inherent in the changing labor and product markets, work processes and management system of public education itself.
Building successful franchise partnerships: the importance of communication and trust

The purpose of this paper is to propose a conceptual model for building successful franchise partnerships. The model examines the influence of communication and trust on satisfaction and performance in franchise partnerships, considering that franchises are based on franchisor-franchisee and franchisor-supplier relationships. ,The unit of analysis refers to the relationships that the franchisor maintains with the franchisees and the main supplier, from the franchisor’s perspective. A mail survey of 592 franchises was conducted by means of a structured, self-administered questionnaire for data collection. A total of 98 valid questionnaires were received and analyzed using structural equation modeling. ,Results indicate that communication between franchise partners is related to satisfaction through trust. In fact, communication is a major precursor of trust. Findings also show the direct influence of trust on satisfaction in both relationships. Finally, results evidence that developing satisfactory relationships between partners improves strategic and operational franchise outcomes. ,The use of the questionnaire limits the approach to information gathering. In addition, the study focused on the franchisor’s perspective of the relationships and it would be interesting to include other partners’ opinions. Further, research should broaden the study scope to include other factors of franchise partnerships. ,This study provides franchisors with guidelines to develop satisfactory relationships. It recommends that franchisors design adequate programs to create, maintain, and enhance franchise partnerships, and also to improve a trust-based culture. ,The analysis is conducted taking into consideration the franchisor-franchisee relationship and the franchisor-supplier relationship. Measurement scales are developed and validated for both relationships.
Co‐operation and communication between the human maintenance and de novo DNA (cytosine‐5) methyltransferases

Three different families of DNA (cytosine‐5) methyltransferases, DNMT1, DUMT2, DNMT3a and DNMT3b, participate in establishing and maintaining genomic methylation patterns during mammalian development. These enzymes have a large N‐terminal domain fused to a catalytic domain. The catalytic domain is homologous to prokaryotic (cytosine‐5) methyltransferases and contains the catalytic PC dipeptide, while the N‐terminus acts as a transcriptional repressor by recruiting several chromatin remodeling proteins. Here, we show that the human de novo enzymes hDNMT3a and hDNMT3b form complexes with the major maintenance enzyme hDNMT1. Antibodies against hDNMT1 pull down both the de novo enzymes. Furthermore, the N‐termini of the enzymes are involved in protein–protein interactions. Immunocytochemical staining revealed mostly nuclear co‐localization of the fusion proteins, with the exception of hDNMT3a, which is found either exclusively in cytoplasm or in both nucleus and cytoplasm. Pre‐methylated substrate DNAs exhibited differential methylation by de novo and maintenance enzymes. In vivo co‐expression of hDNMT1 and hDNMT3a or hDNMT3b leads to methylation spreading in the genome, suggesting co‐operation between de novo and maintenance enzymes during DNA methylation.
Rationale and plans for developing a non-replicating, metabolically active, radiation-attenuated Plasmodium falciparum sporozoite vaccine

SUMMARY Annually, malaria causes >300 million clinical cases and 1 million deaths, is responsible for the loss of >1% of gross domestic product (GDP) in Africa and is a serious concern for travelers. An effective vaccine could have a dramatic impact on the disease. For 20 years, scientists have tried to develop modern, recombinant `subunit' malaria vaccines. This has been difficult. In fact, there is only one recombinant protein vaccine on the market for any disease, and no vaccines based on synthetic peptides, recombinant viruses, recombinant bacteria or DNA plasmids. Most vaccines are based on attenuated or inactivated whole pathogens or material derived directly from the infectious agent. It is in that context that our recent report summarizing the protection of humans with attenuated Plasmodium falciparum (Pf) sporozoites produced at four different sites over 25 years is important. In studies utilizing live mosquitoes as the vaccine delivery mechanism, there was complete protection against malaria in 93% of volunteers (13/14) and 94% of challenges (33/35). Sanaria's goal is to develop and commercialize a non-replicating, metabolically active Pf sporozoite vaccine. Three practical questions must be addressed before manufacturing for clinical trials: (1) can one administer the vaccine by a route that is clinically practical; (2) can one produce adequate quantities of sporozoites; and (3) can sporozoites be produced with the physical characteristics that meet the regulatory, potency and safety requirements of regulatory authorities? Once these questions have been answered, Sanaria will demonstrate that the vaccine protects >90% of human recipients against experimental challenge with Pf sporozoites, can be produced with an efficiency that makes it economically feasible, and protects >90% of African infants and children from infection, and thus from severe morbidity and mortality. By producing a vaccine for travelers, Sanaria will provide the infrastructure, regulatory foundation and funds necessary to speed licensure, manufacturing and deployment of the vaccine for the infants and children who need it most.