Transcriptional and posttranslational plasticity and the generation of inflammatory pain

Inflammatory pain manifests as spontaneous pain and pain hypersensitivity. Spontaneous pain reflects direct activation of specific receptors on nociceptor terminals by inflammatory mediators. Pain hypersensitivity is the consequence of early posttranslational changes, both in the peripheral terminals of the nociceptor and in dorsal horn neurons, as well as later transcription-dependent changes in effector genes, again in primary sensory and dorsal horn neurons. This inflammatory neuroplasticity is the consequence of a combination of activity-dependent changes in the neurons and specific signal molecules initiating particular signal-transduction pathways. These pathways phosphorylate membrane proteins, changing their function, and activate transcription factors, altering gene expression. Two distinct aspects of sensory neuron function are changed as a result of these processes, basal sensitivity, or the capacity of peripheral stimuli to evoke pain, and stimulus-evoked hypersensitivity, the capacity of certain inputs to generate prolonged alterations in the sensitivity of the system. Posttranslational changes largely alter basal sensitivity. Transcriptional changes both potentiate the system and alter neuronal phenotype. Potentiation occurs as a result of the up-regulation in the dorsal root ganglion of centrally acting neuromodulators and simultaneously in the dorsal horn of their receptors. This means that the response to subsequent inputs is augmented, particularly those that induce stimulus-induced hypersensitivity. Alterations in phenotype includes the acquisition by A fibers of neurochemical features typical of C fibers, enabling these fibers to induce stimulus-evoked hypersensitivity, something only C fiber inputs normally can do. Elucidation of the molecular mechanisms responsible provides new opportunities for therapeutic approaches to managing inflammatory pain.

Entanglement induced by spontaneous emission in spatially extended two-atom systems

The role of the collective antisymmetric state in entanglement creation by spontaneous emission in a system of two non-overlapping two-level atoms has been investigated. Populations of the collective atomic states and the Wootters entanglement measure (concurrence) for two sets of initial atomic conditions are calculated and illustrated graphically. Calculations include the dipole-dipole interaction and a spatial separation between the atoms that the antisymmetric state of the system is included throughout even for small interatomic separations. It is shown that spontaneous emission can lead to a transient entanglement between the atoms even if the atoms were prepared initially in an unentangled state. It is found that the ability of spontaneous emission to create transient entanglement relies on the absence of population in the collective symmetric state of the system. For the initial state of only one atom excited, entanglement builds up rapidly in time and reaches a maximum for parameter values corresponding roughly to zero population in the symmetric state. On the other hand, for the initial condition of both atoms excited, the atoms remain unentangled until the symmetric state is depopulated. A simple physical interpretation of these results is given in terms of the diagonal states of the density matrix of the system. We also study entanglement creation in a system of two non-identical atoms of different transition frequencies. It is found that the entanglement between the atoms can be enhanced compared to that for identical atoms, and can decay with two different time scales resulting from the coherent transfer of the population from the symmetric to the antisymmetric state. In addition, it was found that a decaying initial entanglement between the atoms can display a revival behaviour.

Pattern generation by dissipative parametric instability

Nonlinear instabilities are responsible for spontaneous pattern formation in a vast number of natural and engineered systems, ranging from biology to galaxy buildup. We propose a new instability mechanism leading to pattern formation in spatially extended nonlinear systems, which is based on a periodic antiphase modulation of spectrally dependent losses arranged in a zigzag way: an effective filtering is imposed at symmetrically located wave numbers k and -k in alternating order. The properties of the dissipative parametric instability differ from the features of both key classical concepts of modulation instabilities, i.e., the Benjamin-Feir instability and the Faraday instabiltyity. We demonstrate how the dissipative parametric instability can lead to the formation of stable patterns in one- and two-dimensional systems. The proposed instability mechanism is generic and can naturally occur or can be implemented in various physical systems.

Gamma-shaped long-cavity normal-dispersion mode-locked Er-fiber laser for sub-nanosecond high-energy pulsed generation

We propose the design of a novel ?-shaped fiber laser resonator and apply it to build a long-cavity normaldispersion mode-locked Er-fiber laser which features enhanced functionalities for management and optimization of pulsed lasing regimes. We report the generation of sub-nanosecond pulses with the energy of ~0.5 µJ at a kilohertz-scale repetition rate in an all-fiber system based on the new laser design. A combination of special design solutions in the laser, such as polarization instability compensation in the ultra-long arm of the resonator, intra-cavity spectral selection of radiation with a broadband fiber Bragg grating, and polarization selection by means of a tilted refractive index grating, ensures low amplified spontaneous emission (ASE) noise and high stability of the laser system output parameters.

Gamma-shaped long-cavity normal-dispersion mode-locked Er-fiber laser for sub-nanosecond high-energy pulsed generation

We propose the design of a novel ?-shaped fiber laser resonator and apply it to build a long-cavity normaldispersion mode-locked Er-fiber laser which features enhanced functionalities for management and optimization of pulsed lasing regimes. We report the generation of sub-nanosecond pulses with the energy of ~0.5 µJ at a kilohertz-scale repetition rate in an all-fiber system based on the new laser design. A combination of special design solutions in the laser, such as polarization instability compensation in the ultra-long arm of the resonator, intra-cavity spectral selection of radiation with a broadband fiber Bragg grating, and polarization selection by means of a tilted refractive index grating, ensures low amplified spontaneous emission (ASE) noise and high stability of the laser system output parameters.

Soliton's eigenvalue based analysis on the generation mechanism of rogue wave phenomenon in optical fibers exhibiting weak third order dispersion

One of the extraordinary aspects of nonlinear wave evolution which has been observed as the spontaneous occurrence of astonishing and statistically extraordinary amplitude wave is called rogue wave. We show that the eigenvalues of the associated equation of nonlinear Schrödinger equation are almost constant in the vicinity of rogue wave and we validate that optical rogue waves are formed by the collision between quasi-solitons in anomalous dispersion fiber exhibiting weak third order dispersion.

An Efficient Protocol For The Generation Of Monocyte Derived Dendritic Cells Using Serum-free Media For Clinical Applications In Post Remission Aml Patients.

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on good manufacture practices (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.

Extreme Harmonic Generation In Electrically Driven Spin Resonance.

We report the observation of multiple harmonic generation in electric dipole spin resonance in an InAs nanowire double quantum dot. The harmonics display a remarkable detuning dependence: near the interdot charge transition as many as eight harmonics are observed, while at large detunings we only observe the fundamental spin resonance condition. The detuning dependence indicates that the observed harmonics may be due to Landau-Zener transition dynamics at anticrossings in the energy level spectrum.

The Basic Reproduction Number Obtained From Jacobian And Next Generation Matrices - A Case Study Of Dengue Transmission Modelling.

The basic reproduction number is a key parameter in mathematical modelling of transmissible diseases. From the stability analysis of the disease free equilibrium, by applying Routh-Hurwitz criteria, a threshold is obtained, which is called the basic reproduction number. However, the application of spectral radius theory on the next generation matrix provides a different expression for the basic reproduction number, that is, the square root of the previously found formula. If the spectral radius of the next generation matrix is defined as the geometric mean of partial reproduction numbers, however the product of these partial numbers is the basic reproduction number, then both methods provide the same expression. In order to show this statement, dengue transmission modelling incorporating or not the transovarian transmission is considered as a case study. Also tuberculosis transmission and sexually transmitted infection modellings are taken as further examples.

Patient With Numerous Papules And Spontaneous Pneumothorax.

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Direct And Non-destructive Proof Of Authenticity For The 2nd Generation Of Brazilian Real Banknotes Via Easy Ambient Sonic Spray Ionization Mass Spectrometry.

Using a desorption/ionization technique, easy ambient sonic-spray ionization coupled to mass spectrometry (EASI-MS), documents related to the 2nd generation of Brazilian Real currency (R$) were screened in the positive ion mode for authenticity based on chemical profiles obtained directly from the banknote surface. Characteristic profiles were observed for authentic, seized suspect counterfeit and counterfeited homemade banknotes from inkjet and laserjet printers. The chemicals in the authentic banknotes' surface were detected via a few minor sets of ions, namely from the plasticizers bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP), most likely related to the official offset printing process, and other common quaternary ammonium cations, presenting a similar chemical profile to 1st-generation R$. The seized suspect counterfeit banknotes, however, displayed abundant diagnostic ions in the m/z 400-800 range due to the presence of oligomers. High-accuracy FT-ICR MS analysis enabled molecular formula assignment for each ion. The ions were separated by 44 m/z, which enabled their characterization as Surfynol® 4XX (S4XX, XX=40, 65, and 85), wherein increasing XX values indicate increasing amounts of ethoxylation on a backbone of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (Surfynol® 104). Sodiated triethylene glycol monobutyl ether (TBG) of m/z 229 (C10H22O4Na) was also identified in the seized counterfeit banknotes via EASI(+) FT-ICR MS. Surfynol® and TBG are constituents of inks used for inkjet printing.

Spontaneous puberty in girls with early diagnosis of Turner syndrome

OBJECTIVE: To verify if the frequency of spontaneous pubertal development among girls with Turner syndrome (TS) diagnosed in infancy and childhood is greater than that of patients diagnosed later. SUBJECTS AND METHODS: Thirty three girls aged < 10 years at the time of diagnosis were evaluated regarding pubertal development. The frequency of spontaneous puberty was compared with that of girls aged > 13 years diagnosed at the same service. RESULTS: Sixteen of 32 informative patients had signs of spontaneous puberty, a frequency greater than that of patients diagnosed later. In six patients, there was no progression of puberty; menarche occurred in six, and one became pregnant, but the fetus was a stillborn. Spontaneous puberty was absent in all cases with 45,X karyotype. CONCLUSIONS: The greater prevalence of spontaneous puberty in girls whose diagnosis was not based on pubertal delay suggests that, among those diagnosed later, there is a bias towards patients with hypogonadism. Arq Bras Endocrinol Metab. 2012;56(9):653-7

Array-CGH testing in spontaneous abortions with normal karyotypes

In about 50% of first trimester spontaneous abortion the cause remains undetermined after standard cytogenetic investigation. We evaluated the usefulness of array-CGH in diagnosing chromosome abnormalities in products of conception from first trimester spontaneous abortions. Cell culture was carried out in short- and long-term cultures of 54 specimens and cytogenetic analysis was successful in 49 of them. Cytogenetic abnormalities (numerical and structural) were detected in 22 (44.89%) specimens. Subsequent, array-CGH based on large insert clones spaced at ~1 Mb intervals over the whole genome was used in 17 cases with normal G-banding karyotype. This revealed chromosome aneuplodies in three additional cases, giving a final total of 51% cases in which an abnormal karyotype was detected. In keeping with other recently published works, this study shows that array-CGH detects abnormalities in a further ~10% of spontaneous abortion specimens considered to be normal using standard cytogenetic methods. As such, array-CGH technique may present a suitable complementary test to cytogenetic analysis in cases with a normal karyotype.

Catalytic enantioselective arylations: boron to zinc exchange as a powerful tool for the generation of transferable aryl groups

The transmetalation between boron and zinc is of great importance for application in organic synthesis, since it allows the formation of new carbon-carbon bonds between organometallic units and electrophiles. The direct arylation of aldehydes or more scarcely ketones, in a catalytic, enantioselective manner using chiral catalysts has been described recently. The enantiomerically enriched diarylmethanols obtained in these reactions are valuable precursors for important bioactive molecules. This review provides a synopsis of this ever-growing field and highlights some of the challenges that still remain.

Behavior and viability of spontaneous oxidative stress-resistant Lactococcus lactis mutants in experimental fermented milk processing

Previously, we isolated two strains of spontaneous oxidative (SpOx2 and SpOx3) stress mutants of Lactococcus lactis subsp cremoris. Herein, we compared these mutants to a parental wild- type strain (J60011) and a commercial starter in experimental fermented milk production. Total solid contents of milk and fermentation temperature both affected the acidification profile of the spontaneous oxidative stress- resistant L. lactis mutants during fermented milk production. Fermentation times to pH 4.7 ranged from 6.40 h (J60011) to 9.36 h (SpOx2); V(max) values were inversely proportional to fermentation time. Bacterial counts increased to above 8.50 log(10) cfu/mL. The counts of viable SpOx3 mutants were higher than those of the parental wild strain in all treatments. All fermented milk products showed post-fermentation acidification after 24 h of storage at 4 degrees C; they remained stable after one week of storage.