Digital Signal Processing: State-of-the-Art at CERN and Recommendations

Dramatic hardware performance improvements over the last decades have paved the way to the ascent of digital techniques for processing signals, with a concurrent and parallel interest in Digital Signal Processing (DSPing) and in the use of Digital Signal Processors (DSPs). Recent discussions within PS showed that there are needs for DSP-qualified manpower in new projects that cannot be fully satisfied internally. In order to determine how PS can best profit from the growing importance and efficiency of DSP technologies, with an effort compatible with the available divisional resources, a DSP working group was created. Its mandate is to advise PS management on the best way to proceed in the DSPs and DSPing domains. In particular, the issues targeted are wide-ranging, from evaluating the state-of-the-art at CERN to hardware standardisation and required training. This report gives the findings of the working group and presents its closing recommendations

Development of an Activity Patterns Scale (APS)

Six activity patterns were identified across various self-report measures in participants with chronic pain: Pain Avoidance, Activity Avoidance; Task Contingent Persistence; Excessive Persistence, Pain Contingent Persistence and Pacing (Kindermans et al., 2011). It was proposed that instruments assessing “pacing” should include items addressing one specific pacing behavior (breaking tasks into smaller pieces; taking frequent short rests and speeding up or slowing down) with a single goal (increasing activity level, conserve energy for valued activities and pain reduction) (Nielson et al., 2013). The aim of the present study was to develop an instrument to assess the activity patterns identified by Kindermans et al. (2011). The instrument also included three pacing scales one for each of the aforementioned goals. Methods A sample of 229 patients with fibromyalgia and 62 suffering other rheumatic diseases answered online the APS and the “Patterns of Activity Measure-Pain” (POAM-P) (Cane et al., 2007). Three alternative factor structures were tested by confirmatory factor analyses performed via structural equation modelling. . Results The structure with the best fit had 8 factors corresponding to the hypothesized scales: Pain Avoidance (α=.60), Activity Avoidance (α=.60); Task Contingent Persistence (α=.81); Excessive Persistence (α=.84), Pain Contingent Persistence (α=.70), Pacing for increasing activity (α=.76), Pacing for energy conservation (α=.72) and Pacing for pain reduction (α=.65). The correlations with the POAM-P scales were high and in the postulated direction. Conclusions The APS showed adequate reliability and structural validity. According to these results, Avoidance, Persistence and Pacing seem to be multidimensional constructs.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Video Endoscopy for Laser Photoresection in Tracheobronchial Pathology: Some Considerations After 9 Years Experience With 2105 Treatments

Between 1984 and 1993 we performed 2105 laser treatments in 1210 patients: 52% of treatments were done for malignant pathology, 45% for benign tracheal stenoses and 3% were in a miscellaneous group. The procedure was carried out with a rigid bronchoscope under general anaesthesia. In patients with malignant tumors, it is a good palliative treatment—safe, well tolerated and with immediate results; it can be repeated as many times as needed with and is well accepted by the patient. In patients without tumors, this method avoids emergency tracheotomies. The long term results are now under evaluation

The IgA Isotype of Anti-β2 Glycoprotein I Antibodies Recognizes Epitopes in Domains 3, 4, and 5 That Are Located in a Lateral Zone of the Molecule (L-Shaped)

Background: Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with presence of anti-phospholipid antibodies (aPL). The APS classification criteria only consider the aPL of IgG/IgM isotype, however testing of aPL of IgA isotype is recommended when APS is suspected and consensus aPL are negative. IgA anti-βeta-2 glycoprotein-I (B2GP1) has been clearly related with occurrence of thrombotic events. Antibodies anti-B2GP1 of IgG/M isotypes recognize an epitope in Domain 1 (R39-G43), the epitopes that recognize IgA anti-B2GP1 antibodies are not well-identified.Aim: To determine the zones of B2GP1 recognized by antibodies of IgA isotype from patients with APS symptomatology and positive for IgA anti-B2GP1.Methods: IgA antibodies to Domain-1(D1) and Domain-4/5(D4/5) of B2GP1 (ELISA) and epitope mapping on oligopeptide arrays of B2GP1 were evaluated in sera from a group of 93 patients with at least one thrombotic and with isolated positivity for IgA anti-B2GP1 antibodies (negative for other aPL).Results: A total of 47 patients (50.5%) were positive for anti-D4/5 and 23(25%) were positive for anti-D1. When peptide arrays were analyzed, three zones of B2GP1 reactivity were identified for more than 50% of patients. The center of these zones corresponds to amino acids 140(D3), 204(D4), and 264(D5). The peptides recognized on D3 and D4 contain amino acid sequences sharing high homology with proteins of microorganism that were previously related with a possible APS infectious etiology. In the three-dimensional structure of B2GP1, the three peptides, as the R39-G43 epitope, are located on the right side of the molecule (L-shape). The left side (J-shape) does not bind the antibodies.Conclusions: Patients with thrombotic APS clinical-criteria, and isolated IgA anti-B2GP1 positivity appear to preferentially bind, not to the D1 or D4/5 domains of B2GP1, but rather to three sites in D3, D4, and D5. The sites on D3 and D4 were previously described as the target identified by human monoclonal antibodies derived from patients that were capable of inducing APS in animal models. The localization of these epitopes opens a new route to explore to increase understanding of the patholophysiology of the APS and to propose new alternatives and therapeutic targets

Prostaglandin D2/J2 signaling pathway in a rat model of neuroinflammation displaying progressive parkinsonian-like pathology: potential novel therapeutic targets

Background: Prostaglandins are products of the cyclooxygenase pathway, which is implicated in Parkinson’s disease (PD). Limited knowledge is available on mechanisms by which prostaglandins contribute to PD neurodegeneration. To address this gap, we focused on the prostaglandin PGD2/J2 signaling pathway, because PGD2 is the most abundant prostaglandin in the brain, and the one that increases the most under pathological conditions. Moreover, PGJ2 is spontaneously derived from PGD2. Methods: In this study, we determined in rats the impact of unilateral nigral PGJ2-microinfusions on COX-2, lipocalin-type PGD2 synthase (L-PGDS), PGD2/J2 receptor 2 (DP2), and 15 hydroxyprostaglandin dehydrogenase (15-PGDH). Nigral dopaminergic (DA) and microglial distribution and expression levels of these key factors of the prostaglandin D2/J2 pathway were evaluated by immunohistochemistry. PGJ2-induced motor deficits were assessed with the cylinder test. We also determined whether oral treatment with ibuprofen improved the PD-like pathology induced by PGJ2. Results: PGJ2 treatment induced progressive PD-like pathology in the rats. Concomitant with DA neuronal loss in the substantia nigra pars compacta (SNpc), PGJ2-treated rats exhibited microglia and astrocyte activation and motor deficits. In DA neurons, COX-2, L-PGDS, and 15-PGDH levelsincreased significantly in PGJ2-treated rats compared to controls, while DP2 receptor levels were unchanged. In microglia, DP2 receptors were basically non-detectable, while COX-2 and L-PGDS levels increased upon PGJ2-treatment, and 15-PGDH remained unchanged. 15-PGDH was also detected in oligodendrocytes. Notably, ibuprofen prevented most PGJ2-induced PD-like pathology. Conclusions: The PGJ2-induced rat model develops progressive PD pathology, which is a hard-to-mimic aspect of this disorder. Moreover, prevention of most PGJ2-induced PD-like pathology with ibuprofen suggests a positive feedback mechanism between PGJ2 and COX-2 that could lead to chronic neuroinflammation. Notably, this is the first study that analyzes the nigral dopaminergic and microglial distribution and levels of factors of the PGD2/J2 signaling pathway in rodents. Our findings support the notions that upregulation of COX-2 and L-PGDS may be important in the PGJ2 evoked PD-like pathology, and that neuronal DP2 receptor antagonists and L-PGDS inhibitors may be novel pharmacotherapeutics to relieve neuroinflammation-mediated neurodegeneration in PD, circumventing the adverse side effects of cyclooxygenase inhibitors

The genome-wide structure of two economically important indigenous Sicilian cattle breeds

Genomic technologies, such as high-throughput genotyping based on SNP arrays, provided background information concerning genome structure in domestic animals. The aim of this work was to investigate the genetic structure, the genome-wide estimates of inbreeding, coancestry, effective population size (Ne), and the patterns of linkage disequilibrium (LD) in two economically important Sicilian local cattle breeds, Cinisara (CIN) and Modicana (MOD), using the Illumina Bovine SNP50K v2 BeadChip. In order to understand the genetic relationship and to place both Sicilian breeds in a global context, genotypes from others 134 domesticated bovid breeds were used. Principal component analysis showed that the Sicilian cattle breeds were closer to individuals of B. t. taurus from Eurasia and formed non-overlapping clusters with other breeds. Between the Sicilian cattle breeds, MOD was the most differentiated, whereas the animals belonging to CIN breed showed a lower value of assignment, the presence of substructure and genetic links with MOD breed. The average molecular inbreeding and coancestry coefficients were moderately high, and the current estimates of Ne were low in both breeds. These values indicated a low genetic variability. Considering levels of LD between adjacent markers, the average r2 in MOD breed was comparable to those reported for others cattle breeds, whereas CIN showed a lower value. Therefore, these results support the need of more dense SNP arrays for a high power association mapping and genomic selection efficiency in particular for CIN cattle breed. Controlling molecular inbreeding and coancestry would restrict inbreeding depression, the probability of losing beneficial rare alleles, and therefore, the risk of extinction. The results generated from this study have important implications for the development of conservation and/or selection breeding programs in these two local cattle breeds

Maternal and cord blood hemoglobin as determinants of placental weight: A cross-sectional study

Background: Both high and low placental weights are associated with adverse pregnancy outcomes. Maternal hemoglobin levels can influence placental weight, but the evidence is conflicting. Since maternal hemoglobin does not invariably correlate with fetal/neonatal blood hemoglobin levels, we sought to determine whether cord blood hemoglobin or maternal hemoglobin status more closely associates with placental weight in women undergoing elective cesarean section at term. Methods: This was a cross-sectional study conducted at the Royal Alexandra Hospital, Edmonton, Canada, involving 202 women with term singleton pregnancies undergoing elective cesarean section. Maternal blood and mixed cord blood hemoglobin levels were analyzed using a HemoCue Hb201+ system. Birth weight, placental weight, one-and five-minute APGAR scores, American Society of Anesthesiologists physical state classification, maternal age, and maternal height were also recorded. Relationships between maternal and cord blood hemoglobin levels with placental weight, birth weight, and birth weight to placental weight ratio were the main outcome measures. Results: A total of 182 subjects were included in the analysis. Regression analysis showed that cord blood hemoglobin, but not maternal hemoglobin, was inversely related with placental weight (β = −2.4, p = 0.001) and positively related with the birth weight to placental weight ratio (β = 0.015, p = 0.001 and p = 0.63, respectively). Conclusions: Our findings suggest that measuring cord blood hemoglobin levels, rather than maternal hemoglobin levels, may provide important diagnostic information about in utero fetal adaptation to suboptimal placental function and neonatal health

A Transcriptomic View of the Proteome Variability of Newborn and Adult Bothrops jararaca Snake Venoms

Bothrops jararaca is one of the most abundant venomous snake species in Brazil. It is primarily a nocturnal and generalist animal, however, it exhibits a notable ontogenetic shift in diet, feeding mainly on arthropods, lizards, and amphibians (ectothermic prey) through its juvenile phase and on small mammals (endothermic animals) during adult life. Due to its broad geographical distribution, this species is responsible for the majority of the accidents by Bothrops genus in Brazil. Studies on envenomation cases with newborn and adult B. jararaca snakes have shown distinct patterns, mainly related to blood coagulation disorders, which seems to be prominent in accidents with newborn specimens. Moreover, it has been demonstrated that the Brazilian commercial antibothropic antivenom, which is produced by immunization with adult venom, is less effective in neutralizing newborn venom effects. In this study we analyzed the venom gland transcriptome of newborn snake specimens and compared the content of toxin transcripts with that of adult specimens. We demonstrate that upon B. jararaca development, its repertoire of mRNAs encoding toxins changes both qualitatively and quantitatively and these alterations are associated with the venom proteome profiles and pharmacological activities displayed by newborn and adult specimens

UVR8 mediated spatial differences as a prerequisite for UV-B induced inflorescence phototropism

In Arabidopsis hypocotyls, phototropins are the dominant photoreceptors for the positive phototropism response towards unilateral ultraviolet-B (UV-B) radiation. We report a stark contrast of response mechanism with inflorescence stems with a central role for UV RESISTANCE LOCUS 8 (UVR8). The perception of UV-B occurs mainly in the epidermis and cortex with a lesser contribution of the endodermis. Unilateral UV-B exposure does not lead to a spatial difference in UVR8 protein levels but does cause differential UVR8 signal throughout the stem with at the irradiated side 1) increase of the transcription factor ELONGATED HYPOCOTYL 5 (HY5), 2) an associated strong activation of flavonoid biosynthesis genes and flavonoid accumulation, 3) increased GA2oxidase expression, diminished gibberellin1 levels and accumulation of DELLA protein REPRESSOR OF GA1 (RGA) and, 4) increased expression of the auxin transport regulator, PINOID, contributing to local diminished auxin signalling. Our molecular findings are in support of the Blaauw theory (1919), suggesting that differential growth occurs trough unilateral photomorphogenic growth inhibition. Together the data indicate phototropin independent inflorescence phototropism through multiple locally UVR8-regulated hormone pathways