Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Langerhans’ cells and dermal‐type dendritic cells generated from CD34 stem cells express different toll‐like receptors and secrete different cytokines in response to toll‐like receptor ligands

Langerhans’ cells (LC) and dermal dendritic cells (dDC) are located in the superficial and deeper layers of the skin respectively and represent the main dendritic cell (DC) populations of the skin. LC‐like and dDC‐like DC can be generated from CD34 stem cells and this system is widely used as a model for investigating these cells and in therapeutic vaccination. Here we report toll‐like receptor (TLR) expression in human LC and dDC derived from CD34 stem cells. In vitro‐generated DC expressed TLR‐1, 2, 4, 6, 8 and 10. LC, but not dDC, expressed TLR‐5, whereas only dDC expressed TLR‐3. Maturation of LC was mediated by TLR‐2, 4 and 5 ligands, but not by a TLR‐3 ligand. dDC maturation was induced by TLR‐3 and ‐4, but not with TLR‐5 ligand and only weakly by a TLR‐2 ligand. Stimulated LC secreted interleukin (IL)‐1β, low levels of tumour necrosis factor‐α (TNF‐α) and IL‐8, but not IL‐6 or IL‐10. dDC secreted TNF‐α, IL‐6, IL‐8 and IL‐10, but little IL‐1β. IL‐12p70 was not produced by ligand‐stimulated dDC or LC, but was secreted by monocyte‐derived DC (mdDC) stimulated with lipopolysaccharide (LPS). Thus, in vitro‐generated LC and dDC detect different pathogen‐associated molecules and show different cytokine‐secretion profiles in response to TLR ligands.
Retrieving the spatial distribution of cavity modes in ZnO nanowires by near-field imaging and electrodynamics simulations

Scanning near-field optical microscopy (SNOM) has become nowadays a very powerful technique for investigating the optical properties of nanostructures with a sub-wavelength spatial resolution below 100 nm, such as waveguiding effects in ZnO nanowires (NWs). A spatially resolved study of the electromagnetic field distributions of different cavity modes in ZnO NWs is still lacking. In this work, a near-field optical microscope was used to map out the evanescent fields of optically excited single-crystal ZnO NWs grown on quartz substrates by the vapour transport method using Au as catalyst. The SNOM measurements were performed at room temperature in transmission-collection mode using four different laser wavelengths (378, 514, 633 and 785 nm). They reveal a different spatial distribution of the electromagnetic fields associated to each cavity mode, which are unique properties of the NWs depending primarily on their size and the wavelength of the mode. The SNOM patterns obtained are quite different. Whereas for UV illumination the pattern exhibits two well defined bright lines running along the edges of the upper hexagonal facet of the wire, for red laser excitation the SNOM pattern displays a strong but wider maximum at the center of the facet. The latter also exhibits a periodic modulation of the near-field intensity all along the axis of the wire. In order to interpret the experimental findings, electrodynamics simulations were perforemd using the discrete dipole approximation (DDA), which is an accurate numerical method in which the object of interest is represented as a cubic lattice of N polarizable points. About 890000 dipoles were used to describe the ZnO NW, out of a total of 1.5 million for taking also the substrate into account.
Current ripple reduction of aircraft start generators in the starting mode with variable switching frequency method

This paper proposes a method of variable switching frequency pulse-width-modulation (PWM) to suppress current ripple when aircraft start generator (SG) operates in the starting mode. Compared with the widely used constant switching frequency PWM, the method can work evidently, especially in the range of low speed. Based on analysis of dead-time effects in the two-level voltage source inverter, relationship between the three-phase voltage error and dead time is acquired. Through adjusting switching frequency of switching devices with the SG speed, the dead-time effects can be weakened in order to reduce voltage distortion and current ripple. The proposed method is applied to a 75kVA SG drive system and implemented in a digital signal processor (DSP). Simulation and experimental results demonstrate the effectiveness of the proposed method.
Evidence-Based Medicine in Otolaryngology, Part 2

What is the current state of evidence-based medicine in otolaryngology? This question inquires about the state of our literature, our attitudes and capabilities, and our patients’ desires. Thus, this installment of “Evidence-Based Medicine in Otolaryngology” focuses on these 3 topics. First, the authors consider the literature relative to benchmarks for study design. Second, the data regarding otolaryngologists’ and other surgical specialists’ attitudes and understanding of clinical data are discussed. Third, patient-based efforts to promote and participate in evidence-based practice are explored. In addition, a discussion of the relevant supportive efforts made by our professional organizations is included.
Proteome analysis reveals antiangiogenic environments in chronic wounds of diabetes mellitus type 2 patients

In contrast to normal healing wounds, chronic wounds commonly show disturbances in proteins regulating wound healing processes, particularly those involved in cell proliferation and protein degradation. Multidimensional protein identification technology MS/MS was conducted to investigate and compare the protein composition of chronic diabetic foot exudates to exudates from split‐skin donor sites of burn victims otherwise healthy. Spectral counting revealed 188 proteins differentially expressed (more than twofold and p‐value <0.05) in chronic wounds. Most were involved in biological processes including inflammation, angiogenesis, and cell mortality. Increased expression of the inflammatory response stimulating S100 proteins, predominantly S100A8 and S100A9 (almost tenfold), was identified. Matrix metalloproteinases (MMPs) MMP1, MMP2, and MMP8 were identified to be elevated in chronic wounds with significant impact on collagen degradation and tissue destruction. Further, proteins with antiangiogenic properties were found at higher expression levels in chronic wounds. Reduced angiogenesis leads to drastic shortage in nutrition supply and causes increased cell death, demonstrated by Annexin A5 exclusively found in chronic wound exudates. However, excessive nucleic and cytosolic material infers cell death occurring not only by apoptosis but also by necrosis. In conclusion, mass spectrometric investigation of exudates from chronic wounds demonstrated dramatic impairment in wound repair with excessive inflammation, antiangiogenic environment, and accelerated cell death.
Sleep Disorders Associated with Parkinson's Disease: Role of Dopamine, Epidemiology, and Clinical Scales of Assessment

ABSTRACT Sleep dysfunction is common among patients with Parkinson's disease and occurs in approximately two thirds of patients. The problems range from nocturnal issues such as difficulty with sleep initiation, sleep fragmentation, disturbance of circadian rhythm, and rapid eye movement sleep behavior disorder, to daytime problems such as excessive daytime sleepiness. Frequent nighttime awakening and sleep disruption are the most common sleep problems in Parkinson's disease. Dopamine plays an important role in maintaining wakefulness. To improve sleep in Parkinson's disease, it is important to achieve the critical balance of adequate dopaminergic therapy and control of symptoms. Increased dopaminergic agents can cause dyskinesias and painful dystonia, and undertreatment can cause nighttime akinesia, rigidity, and worse quality of sleep. Other nondopaminergic drugs commonly used in Parkinson's disease can also affect sleep. In patients with advanced Parkinson's disease, deep brain stimulation of the subthalamic nucleus has a favorable impact on sleep quality and sleep architecture.
Redox Regulation of the DNA Binding Activity in Transcription Factor PEBP2

Transcription factor PEBP2/CBF consists of a DNA binding subunit, α, and a regulatory subunit, β. The α subunit has an evolutionarily conserved 128-amino acid region termed “Runt domain” that is responsible for both DNA binding and heterodimerization with the β subunit. The Runt domain in all mammalian submembers of the α subunit contains two conserved cysteine residues, and its DNA binding activity undergoes redox regulation. To investigate the mechanism of this redox regulation, we performed site-directed mutagenesis of the two conserved cysteines in the Runt domain of the mouse PEBP2αA homolog. Substitution of Cys-115 to serine resulted in a partially impaired DNA binding, which remained highly sensitive to a thiol-oxidizing reagent, diamide. Conversely, the corresponding substitution of Cys-124 caused an increased DNA binding concomitant with an increased resistance to diamide. In contrast, substitution of either cysteine to aspartate was destructive to DNA binding to marked extents. These results have revealed that both Cys-115 and Cys-124 are responsible for the redox regulation in their own ways with low and high oxidizabilities, respectively. We have also found that two cellular thiol-reactive proteins, thioredoxin and Ref-1, work effectively and synergistically for activation of the Runt domain. Interestingly, the β subunit further enhanced the activation by these proteins and reciprocally prevented the oxidative inactivation by diamide. These findings collectively suggest the possibility that the Runt domain’s function in vivo could be dynamically regulated by the redox mechanism with Trx, Ref-1, and the β subunit as key modulators.
Standard filter approximations for low power Continuous Wavelet Transforms

Analogue domain implementations of the Continuous Wavelet Transform (CWT) have proved popular in recent years as they can be implemented at very low power consumption levels. This is essential for use in wearable, long term physiological monitoring systems. Present analogue CWT implementations rely on taking mathematical a approximation of the wanted mother wavelet function to give a filter transfer function that is suitable for circuit implementation. This paper investigates the use of standard filter approximations (Butterworth, Chebyshev, Bessel) as an alternative wavelet approximation technique. This extends the number of approximation techniques available for generating analogue CWT filters. An example ECG analysis shows that signal information can be successfully extracted using these CWT approximations.
A 2-deoxyglucose study of the effects of dopamine agonists on the parkinsonian primate brain. Implications for the neural mechanisms that mediate dopamine agonist-induced dyskinesia.

The neural mechanisms that underlie both the anti-parkinsonian effects of dopamine agonists and dopamine agonist-induced dyskinesia were studied in parkinsonian primates, using the regional brain uptake of [3H]2-deoxyglucose (2-DG). Parkinsonian symptoms were induced in monkeys by the administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Some of the animals received chronic dopamine replacement therapy for at least 3 mths, which resulted in the appearance of peak-dose dyskinesia. The remaining animals spent an equivalent period of time relatively unexposed to dopaminergic agents, receiving only therapeutic doses, and at no time showed any signs of dopamine agonist-induced dyskinesia. The 2-DG metabolic mapping technique was applied to all of these animals shortly following the administration of a dose of dopamine agonist which was sufficient to alleviate their parkinsonian symptoms and to induce dyskinesia in those prone to this complication. The 2-DG uptake technique permits the autoradiographic measurement of local cerebral glucose uptake which was used as an index of regional synaptic activity. The resultant autoradiographs were compared with those from a previous study which examined 2-DG uptake in parkinsonian and normal brains from animals which had not received dopamine agonists prior to the terminal 2-DG uptake procedure. The pattern of 2-DG uptake in the animals which received a dopamine agonist prior to the terminal procedure was strikingly different to both of the other groups. The most affected structure was the subthalamic nucleus which showed a dramatic increase in 2-DG uptake in animals exposed to dopamine agonist immediately prior to the terminal procedure, especially in the ventral tip of the nucleus. The medial pallidal segment also showed relatively greater levels of 2-DG uptake in the dopamine agonist group compared with the untreated parkinsonian state whereas, in contrast, the lateral pallidal segment showed decreased levels of 2-DG uptake. The parkinsonian animals which had been sacrificed after receiving a dopamine agonist were split into three groups on the basis of their response to the agonist. The first group had their parkinsonism reversed and appeared clinically normal. The remaining animals had their parkinsonism reversed by the dopamine agonist but showed dyskinesia at peak dose. These animals were allotted to two further groups depending on whether their dyskinesia was of a choreic or dystonic nature. (ABSTRACT TRUNCATED AT 400 WORDS)
Rapid and simple method for purification of nucleic acids

We have developed a simple, rapid, and reliable protocol for the small-scale purification of DNA and RNA from, e.g., human serum and urine. The method is based on the lysing and nuclease-inactivating properties of the chaotropic agent guanidinium thiocyanate together with the nucleic acid-binding properties of silica particles or diatoms in the presence of this agent. By using size-fractionated silica particles, nucleic acids (covalently closed circular, relaxed circular, and linear double-stranded DNA; single-stranded DNA; and rRNA) could be purified from 12 different specimens in less than 1 h and were recovered in the initial reaction vessel. Purified DNA (although significantly sheared) was a good substrate for restriction endonucleases and DNA ligase and was recovered with high yields (usually over 50%) from the picogram to the microgram level. Copurified rRNA was recovered almost undegraded. Substituting size-fractionated silica particles for diatoms (the fossilized cell walls of unicellular algae) allowed for the purification of microgram amounts of genomic DNA, plasmid DNA, and rRNA from cell-rich sources, as exemplified for pathogenic gram-negative bacteria. In this paper, we show representative experiments illustrating some characteristics of the procedure which may have wide application in clinical microbiology.
Early Central Catheter Infections May Contribute to Hepatic Fibrosis in Children Receiving Long-term Parenteral Nutrition

Background: Bacterial infections in infants constitute a risk factor for parenteral nutrition (PN)–related cholestasis. The possible role of infections in the development of liver fibrosis, the most severe long-term complication, has yet to be documented. This study retrospectively compares the incidence of sepsis in children with and without severe liver fibrosis. Patients and Methods: Medical reports of 30 children in prolonged PN programs between March 1985 and March 2000 were reviewed. Starting at birth, the mean PN duration was 65 months (range, 8–150 months). According to the results of liver biopsy (LB), patients were split into 2 groups: group A (n = 16) with severe liver fibrosis (ie, septal fibrosis involving >50% of portal fields or cirrhosis) and group B (n = 14) with normal hepatic architecture or mild fibrosis (<50% of portal fields). Results: Duration of PN at the time of LB was shorter in group A (30.5 months; range, 8–96 months) than in group B (105 months; range, 37–150 months; P < 0.001). In group A the incidence of sepsis was significantly higher than in group B (3.2 ± 0.3/year vs 1.5 ± 0.2/year) and the first infection occurred earlier (group A, 1 month [range, 1–2 months]; group B, 4 months [range, 1–19 months]). By contrast, both groups were similar in terms of pregnancy duration, birth weight, age of PN onset, underlying diseases, mode of PN delivery, and number of cholestasis episodes. Conclusions: Incidence and early onset of infections may contribute to the development of liver fibrosis in cases of long-term PN. New strategies are required in prevention and treatment of infections in children receiving PN.
Overview of Biacore Systems and Their Applications

Surface plasmon resonance (SPR) allows for the investigation of the functional nature of binding interactions and provides detailed kinetic information across a wide range of molecular weights, including small molecules, all without the use of labels. Here the various Biacore instrument platforms and their primary uses, ranging from semi‐automated systems designed for simple, flexible basic research to fully automated, high‐throughput systems, and systems designed to function in regulated environments, are all highlighted. The available sensor chip surfaces and immobilization techniques are also discussed. Biacore SPR biosensors can be used for a wide variety of assays, including specificity, active concentration measurement, kinetics, and affinity and thermodynamic parameters. Biacore SPR biosensors, which measure real‐time analysis of biospecific interactions without the use of labeled molecules, can be used for a wide variety of protein interaction assays. In this unit, examples and recommendations for studying protein interactions with a variety of molecules are provided. This unit also shows how the technology can be used to determine binding specificity, active concentration measurements, and the determination of kinetic and thermodynamic parameters.
Un método sencillo para seleccionar puntos de muestreo con el objetivo de inventar taxones hiperdiversos: el caso práctivo de las familias Araneidae y Thomisidae (Araneae) en la comunidad de Madrid, España

Elaborar estrategias de conservacion eficaces requiere poseer informacion faunistica bien repartida a lo largo del espectro de condiciones ambientales de una region. Ello os posible si la toma de datos se ha realizado mediante el desarrollo do protocolos de muestreo bien disenados, eficientes y especificos para cada grupo biologico. En este trabajo se presenta una metodologia sencilla para la seleccion de puntos de muestreo, especialmente util en el caso de grupos hiperdiversos en los que la recoleccion de informacion faunistica requiere un esfuerzo notable y la determinacion taxonomica del material colectado no es posible en el campo. El metodo se basa en la clasificacion de las unidades territoriales de una region de acuerdo a los valores de una serle de variables ambientales y espaciales, previamente seleccionadas por su conocida influencia sobre la distribucion del grupo de organismos considerado y compiladas en un Sistema de Informacion Geografica. Tras definir la superficie y el numero de unidades territoriales en las que es posible obtener inventarios fiables, se utiliza la estrategia de agrupamiento k-medias a fin de obtener una clasificacion de la region en tantas subregiones como unidades territoriales se vayan a muestrear. Dentro de cada subregion, la unidad territorial puede ser seleccionada teniendo en cuenta diversos criterios, como su distancia espacio-ambiental al centroide de la subregion, su facilidad de acceso o el volumen de informacion previamente existente. Se ofrece un ejemplo practico de esta metodologia con las familias de aranas en la Comunidad do Madrid.
Identification of Brucella suis Genes Affecting Intracellular Survival in an In Vitro Human Macrophage Infection Model by Signature-Tagged Transposon Mutagenesis

ABSTRACT Bacteria of the genus Brucella are facultative intracellular pathogens which have developed the capacity to survive and multiply in professional and nonprofessional phagocytes. The genetic basis of this aspect of Brucella virulence is still poorly understood. To identify new virulence factors, we have adapted signature-tagged transposon mutagenesis, which has been used essentially in animal models, to an in vitro human macrophage infection model. A library of 1,152 Brucella suis 1330 tagged mini-Tn5 Km2 mutants, in 12 pools, was screened for intracellular survival and multiplication in vitamin D3-differentiated THP1 cells. Eighteen mutants were identified, and their attenuation was confirmed in THP1 macrophages and HeLa cells. For each avirulent mutant, a genomic fragment containing the transposon was cloned. The genomic DNA sequence flanking the transposon allowed us to assign functions to all of the inactivated genes. Transposon integration had occurred in 14 different genes, some of which were known virulence genes involved in intracellular survival or biosynthesis of smooth lipopolysaccharide (the virBoperon and manB), thus validating the model. Other genes identified encoded factors involved in the regulation of gene expression and enzymes involved in biosynthetic or metabolic pathways. Possible roles in the virulence of Brucella for the different factors identified are discussed.
Termination of Reentry by a Long‐Lasting AC Shock in a Slice of Canine Heart: A Computational Study

AC Cardioversion in a Canine Slice. Introduction: A heart in fibrillation can be entrained by long‐lasting alternating current (AC) stimuli, leading to defibrillation. To investigate the role entrainment plays in defibrillation, computer simulations of AC cardioversion in a three‐dimensional slice of the canine heart were performed.
Vibrio cholerae ParE2 Poisons DNA Gyrase via a Mechanism Distinct from Other Gyrase Inhibitors*

DNA gyrase is an essential bacterial enzyme required for the maintenance of chromosomal DNA topology. This enzyme is the target of several protein toxins encoded in toxin-antitoxin (TA) loci as well as of man-made antibiotics such as quinolones. The genome of Vibrio cholerae, the cause of cholera, contains three putative TA loci that exhibit modest similarity to the RK2 plasmid-borne parDE TA locus, which is thought to target gyrase although its mechanism of action is uncharacterized. Here we investigated the V. cholerae parDE2 locus. We found that this locus encodes a functional proteic TA pair that is active in Escherichia coli as well as V. cholerae. ParD2 co-purified with ParE2 and interacted with it directly. Unlike many other antitoxins, ParD2 could prevent but not reverse ParE2 toxicity. ParE2, like the unrelated F-encoded toxin CcdB and quinolones, targeted the GyrA subunit and stalled the DNA-gyrase cleavage complex. However, in contrast to other gyrase poisons, ParE2 toxicity required ATP, and it interfered with gyrase-dependent DNA supercoiling but not DNA relaxation. ParE2 did not bind GyrA fragments bound by CcdB and quinolones, and a set of strains resistant to a variety of known gyrase inhibitors all exhibited sensitivity to ParE2. Together, our findings suggest that ParE2 and presumably its many plasmid- and chromosome-encoded homologues inhibit gyrase in a different manner than previously described agents.