An Edge Computing Application of Fundamental Frequency Extraction for Ocean Currents and Waves.

This paper describes the design and optimization of a smart algorithm based on artificial intelligence to increase the accuracy of an ocean water current meter. The main purpose of water current meters is to obtain the fundamental frequency of the ocean waves and currents. The limiting factor in those underwater applications is power consumption and that is the reason to use only ultra-low power microcontrollers. On the other hand, nowadays extraction algorithms assume that the processed signal is defined in a fixed bandwidth. In our approach, belonging to the edge computing research area, we use a deep neural network to determine the narrow bandwidth for filtering the fundamental frequency of the ocean waves and currents on board instruments. The proposed solution is implemented on an 8 MHz ARM Cortex-M0+ microcontroller without a floating point unit requiring only 9.54 ms in the worst case based on a deep neural network solution. Compared to a greedy algorithm in terms of computational effort, our worst-case approach is 1.81 times faster than a fast Fourier transform with a length of 32 samples. The proposed solution is 2.33 times better when an artificial neural network approach is adopted.

Ten-Year Results of Accelerated Partial-Breast Irradiation with Interstitial Multicatheter Brachytherapy after Breast-Conserving Surgery for Low-Risk Early Breast Cancer.

Patients with an early carcinoma of the breast are commonly treated by breast-conserving surgery (BCS) and postoperative radiotherapy. Partial-breast irradiation has gained acceptance in the last few years. Between December 2008 and December 2017, 182 low-risk breast cancer patients treated by BCS in the four university hospitals of the province of Las Palmas and treated with APBI using interstitial multicatheter brachytherapy were included in this study. After a mean follow-up for survivors of 10 years, the treatment was shown to be safe, as no severe acute/late toxicity (grade ≥ 3) was observed. The 10-year IBTR was 1.7% (95%CI: 0.7-2.7%), and the cause-specific survival was 94.9% (95%CI: 93.2-96.6%). We suggest that multicatheter brachytherapy after BCS is safe and effective in early breast cancer patients.

Integer Arithmetic Algorithm for Fundamental Frequency Identification of Oceanic Currents.

Underwater sensor networks play a crucial role in collecting valuable data to monitor offshore aquaculture infrastructures. The number of deployed devices not only impacts the bandwidth for a highly constrained communication environment, but also the cost of the sensor network. On the other hand, industrial and literature current meters work as raw data loggers, and most of the calculations to determine the fundamental frequencies are performed offline on a desktop computer or in the cloud. Belonging to the edge computing research area, this paper presents an algorithm to extract the fundamental frequencies of water currents in an underwater sensor network deployed in offshore aquaculture infrastructures. The target sensor node is based on a commercial ultra-low-power microcontroller. The proposed fundamental frequency identification algorithm only requires the use of an integer arithmetic unit. Our approach exploits the mathematical properties of the finite impulse response (FIR) filtering in the integer domain. The design and implementation of the presented algorithm are discussed in detail in terms of FIR tuning/coefficient selection, memory usage and variable domain for its mathematical formulation aimed at reducing the computational effort required. The approach is validated using a shallow water current model and real-world raw data from an offshore aquaculture infrastructure. The extracted frequencies have a maximum error below a 4%.

Valorization of Seaweed Wracks: Inclusion as Additive in Diets for Grass Carp (Ctenopharyngodon idella).

Macroalgae have been recently described as a potential ingredient for aquafeeds, exerting several physiological benefits. Grass carp (Ctenopharyngodon idella) is a freshwater species, which has been the major fish species produced in the world in the last years. In order to determine the potential use of macroalgal wracks in fish feeding, C. idella juveniles were fed with an extruded commercial diet (CD) or the CD supplemented with 7% of a wind dried-powder (1 mm) from either a multispecific macroalgal wrack (CD + MU7) or a monospecific macroalgal wrack (CD + MO7) obtained from Gran Canaria island (Spain) coasts. After 100 days of feeding, survival, fish weight, and body indexes were determined, and muscle, liver, and digestive tract samples were collected. The total antioxidant capacity of macroalgal wracks was analyzed by assesing the antioxidant defense response and digestive enzymes activity in fish. Finally, muscle proximate composition, lipid classes (LC), and fatty acid (FA) profiles were also studied. Our results suggest that dietary inclusion of macroalgal wracks does not have negative effects on growth, proximate, and lipid composition, antioxidative status, or digestive capacity of C. idella. In fact, both macroalgal wracks caused a general lower fat deposition, and the multispecific wrack enhanced catalase activity in the liver.

Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer.

Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008-December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3-1.9) and 98.3% (95% CI 97.3-99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness.

AIM: Neuropsychiatric disorders including depression, bipolar and schizophrenia frequently exhibit a neuroprogressive course from prodrome to chronicity. There are a range of agents exhibiting capacity to attenuate biological mechanisms associated with neuroprogression. This review will update the evidence for putative neuroprotective agents including clinical efficacy, mechanisms of action and limitations in current assessment tools, and identify novel agents with neuroprotective potential. METHOD: Data for this review were sourced from online databases PUBMED, Embase and Web of Science. Only data published since 2012 were included in this review, no data were excluded based on language or publication origin. RESULTS: Each of the agents reviewed inhibit one or multiple pathways of neuroprogression including: inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling. Some demonstrate clinical efficacy in preventing neural damage or loss, relapse or cognitive/functional decline. Agents include: the psychotropic medications lithium, second generation antipsychotics and antidepressants; other pharmacological agents such as minocycline, aspirin, cyclooxygenase-2 inhibitors, statins, ketamine and alpha-2-delta ligands; and others such as erythropoietin, oestrogen, leptin, N-acetylcysteine, curcumin, melatonin and ebselen. CONCLUSIONS: Signals of evidence of clinical neuroprotection are evident for a number of candidate agents. Adjunctive use of multiple agents may present a viable avenue to clinical realization of neuroprotection. Definitive prospective studies of neuroprotection with multimodal assessment tools are required.

Ovarian Hormone-Dependent Effects of Dietary Lipids on APP/PS1 Mouse Brain.

The formation of senile plaques through amyloid-ß peptide (Aß) aggregation is a hallmark of Alzheimer's disease (AD). Irrespective of its actual role in the synaptic alterations and cognitive impairment associated with AD, different therapeutic approaches have been proposed to reduce plaque formation. In rodents, daily intake of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) is required for neural development, and there is experimental and epidemiological evidence that their inclusion in the diet has positive effects on several neurodegenerative diseases. Similarly, estradiol appears to reduce senile plaque formation in primary mouse cell cultures, human cortical neurons and mouse AD models, and it prevents Aß toxicity in neural cell lines. We previously showed that differences in dietary n-6/n-3 LC-PUFAs ratios modify the lipid composition in the cerebral cortex of female mice and the levels of amyloid precursor protein (APP) in the brain. These effects depended in part on the presence of circulating estradiol. Here we explored whether this potentially synergistic action between diet and ovarian hormones may influence the progression of amyloidosis in an AD mouse model. Our results show that a diet with high n-3 LC-PUFA content, especially DHA (22:6n-3), reduces the hippocampal accumulation of Aß1 - 4 0, but not amyloid Aß1 - 42 in female APPswe/PS1 E9A mice, an effect that was counteracted by the loss of the ovaries and that depended on circulating estradiol. In addition, this interaction between dietary lipids and ovarian function also affects the composition of the brain lipidome as well as the expression of certain neuronal signaling and synaptic proteins. These findings provide new insights into how ovarian hormones and dietary composition affect the brain lipidome and amyloid burden. Furthermore, they strongly suggest that when designing dietary or pharmacological strategies to combat human neurodegenerative diseases, hormonal and metabolic status should be specifically taken into consideration as it may affect the therapeutic response.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex.

Different dietary ratios of n-6/n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n-6/n-3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n-3 and n-6 LC-PUFAs.

Hierarchical Control of Nitrite Respiration by Transcription Factors Encoded within Mobile Gene Clusters of Thermus thermophilus.

Denitrification in Thermus thermophilus is encoded by the nitrate respiration conjugative element (NCE) and nitrite and nitric oxide respiration (nic) gene clusters. A tight coordination of each cluster's expression is required to maximize anaerobic growth, and to avoid toxicity by intermediates, especially nitric oxides (NO). Here, we study the control of the nitrite reductases (Nir) and NO reductases (Nor) upon horizontal acquisition of the NCE and nic clusters by a formerly aerobic host. Expression of the nic promoters PnirS, PnirJ, and PnorC, depends on the oxygen sensor DnrS and on the DnrT protein, both NCE-encoded. NsrR, a nic-encoded transcription factor with an iron-sulfur cluster, is also involved in Nir and Nor control. Deletion of nsrR decreased PnorC and PnirJ transcription, and activated PnirS under denitrification conditions, exhibiting a dual regulatory role never described before for members of the NsrR family. On the basis of these results, a regulatory hierarchy is proposed, in which under anoxia, there is a pre-activation of the nic promoters by DnrS and DnrT, and then NsrR leads to Nor induction and Nir repression, likely as a second stage of regulation that would require NO detection, thus avoiding accumulation of toxic levels of NO. The whole system appears to work in remarkable coordination to function only when the relevant nitrogen species are present inside the cell.

Role of Archaeal HerA Protein in the Biology of the Bacterium Thermus thermophilus.

Intense gene flux between prokaryotes result in high percentage of archaeal genes in the genome of the thermophilic bacteria Thermus spp. Among these archaeal genes a homolog to the Sulfolobus spp. HerA protein appears in all of the Thermus spp. strains so far sequenced (HepA). The role of HepA in Thermus thermophilus HB27 has been analyzed using deletion mutants, and its structure resolved at low resolution by electron microscopy. Recombinant HepA shows DNA-dependent ATPase activity and its structure revealed a double ring, conically-shaped hexamer with an upper diameter of 150 Å and a bottom module of 95 Å. A central pore was detected in the structure that ranges from 13 Å at one extreme, to 30 Å at the other. Mutants lacking HepA show defective natural competence and DNA donation capability in a conjugation-like process termed "transjugation", and also high sensitivity to UV and dramatic sensitivity to high temperatures. These data support that acquisition of an ancestral archaeal HerA has been fundamental for the adaptation of Thermus spp. to high temperatures.

The transjugation machinery of Thermus thermophilus: Identification of TdtA, an ATPase involved in DNA donation.

In addition to natural competence, some Thermus thermophilus strains show a high rate of DNA transfer via direct cell-to-cell contact. The process is bidirectional and follows a two-step model where the donor cell actively pushes out DNA and the recipient cell employs the natural competence system to take up the DNA, in a hybrid transformation-dependent conjugation process (transjugation). While the DNA uptake machinery is well known as in other bacterial species that undergo transformation, the pushing step of transjugation remains to be characterized. Here we have searched for hypothetical DNA translocases putatively involved in the pushing step of transjugation. Among candidates encoded by T. thermophilus HB27, the TdtA protein was found to be required for DNA pushing but not for DNA pulling during transjugation, without affecting other cellular processes. Purified TdtA shows ATPase activity and oligomerizes as hexamers with a central opening that can accommodate double-stranded DNA. The tdtA gene was found to belong to a mobile 14 kbp-long DNA element inserted within the 3' end of a tRNA gene, flanked by 47 bp direct repeats. The insertion also encoded a homolog of bacteriophage site-specific recombinases and actively self-excised from the chromosome at high frequency to form an apparently non-replicative circular form. The insertion also encoded a type II restriction endonuclease and a NurA-like nuclease, whose activities were required for efficient transjugation. All these data support that TdtA belongs to a new type of Integrative and Conjugative Element which promotes the generalized and efficient transfer of genetic traits that could facilitate its co-selection among bacterial populations.

Comparative study on fatty acid metabolism of early stages of two crustacean species: Artemia sp. metanauplii and Grapsus adscensionis zoeae, as live prey for marine animals.

The present study compared the lipid composition and in vivo capability of Artemia sp. metanauplii (the main live prey used in aquaculture) and Grapsus adscensionis zoeae (as a wild zooplankton model) to metabolise unsaturated fatty acids. The two species were incubated in vivo with 0.3µM of individual [1-14C]fatty acids (FA) including 18:1n-9, 18:2n-6, 18:3n-3, 20:4n-6 (ARA), 20:5n-3 (EPA) and 22:6n-3 (DHA) bound to bovine serum albumin (BSA). Compared to metanauplii, zoeae contained twice the content of polar lipids (PL) and eight-fold the content of long-chain polyunsaturated fatty acids (LC-PUFA). Artemia sp. metanauplii showed increased short chain fatty acid de novo synthesis from beta-oxidation of [1-14C]LC-PUFA, preferentially DHA. Of the LC-PUFA, DHA showed the highest esterification rate into Artemia sp. triacylglycerols. In contrast, in Grapsus zoeae [1-14C]DHA displayed the highest transformation rate into longer chain-length FAs and was preferentially esterified into PL. EPA and ARA, tended to be more easily incorporated and/or retained than DHA in Artemia sp. Moreover, both EPA and ARA were preferentially esterified into Artemia PL, which theoretically would favour their bioavailability to the larvae. In addition to the inherent better nutritional value of Grapsus zoeae due to their intrinsic lipid composition, the changes taking place after the lipid incorporation, point at two distinct models of lipid metabolism that indicate zoeae as a more suitable prey than Artemia sp. for the feeding of marine animals.

Composition and metabolism of phospholipids in Octopus vulgaris and Sepia officinalis hatchlings.

The objective of the present study was to characterise the fatty acid (FA) profiles of the major phospholipids, of Octopus vulgaris and Sepia officinalis hatchlings, namely phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylethanolamine (PE); and to evaluate the capability of both cephalopod species on dietary phospholipid remodelling. Thus, O. vulgaris and S. officinalis hatchlings were in vivo incubated with 0.3µM of L-∝-1-palmitoyl-2-[1-(14)C]arachidonyl-PC or L-∝-1-palmitoyl-2-[1-(14)C]arachidonyl-PE. Octopus and cuttlefish hatchlings phospholipids showed a characteristic FA profiles with PC presenting high contents of 16:0 and 22:6n-3 (DHA); PS having high 18:0, DHA and 20:5n-3 (EPA); PI a high content of saturated FA; and PE showing high contents of DHA and EPA. Interestingly, the highest content of 20:4n-6 (ARA) was found in PE rather than PI. Irrespective of the phospholipid in which [1-(14)C]ARA was initially bound (either PC or PE), the esterification pattern of [1-(14)C]ARA in octopus lipids was similar to that found in their tissues with high esterification of this FA into PE. In contrast, in cuttlefish hatchlings [1-(14)C]ARA was mainly recovered in the same phospholipid that was provided. These results showed a characteristic FA profiles in the major phospholipids of the two species, as well as a contrasting capability to remodel dietary phospholipids, which may suggest a difference in phospholipase activities.

Early life stress accelerates behavioral and neural maturation of the hippocampus in male mice.

Early life stress (ELS) increases the risk for later cognitive and emotional dysfunction. ELS is known to truncate neural development through effects on suppressing cell birth, increasing cell death, and altering neuronal morphology, effects that have been associated with behavioral profiles indicative of precocious maturation. However, how earlier silencing of growth drives accelerated behavioral maturation has remained puzzling. Here, we test the novel hypothesis that, ELS drives a switch from growth to maturation to accelerate neural and behavioral development. To test this, we used a mouse model of ELS, fragmented maternal care, and a cross-sectional dense sampling approach focusing on hippocampus and measured effects of ELS on the ontogeny of behavioral development and biomarkers of neural maturation. Consistent with previous work, ELS was associated with an earlier developmental decline in expression of markers of cell proliferation (Ki-67) and differentiation (doublecortin). However, ELS also led to a precocious arrival of Parvalbumin-positive cells, led to an earlier switch in NMDA receptor subunit expression (marker of synaptic maturity), and was associated with an earlier rise in myelin basic protein expression (key component of the myelin sheath). In addition, in a contextual fear-conditioning task, ELS accelerated the timed developmental suppression of contextual fear. Together, these data provide support for the hypothesis that ELS serves to switch neurodevelopment from processes of growth to maturation and promotes accelerated development of some forms of emotional learning.

Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk groups.

BACKGROUND & AIMS: The incidence of hepatocellular carcinoma (HCC) and associated risk factors in patients with alcoholic cirrhosis are not well defined. Surveillance for HCC among patients with cirrhosis who do not have hepatitis B is cost effective only if the expected risk of HCC exceeds 1.5% per year. We performed a prospective study to determine the incidence of HCC among patients with alcoholic cirrhosis and to identify risk factors. METHODS: We analyzed data from a surveillance program of 450 patients, aged 40 to 75 years, with alcoholic cirrhosis of Child-Pugh class A or B; patients were enrolled at the liver unit of a tertiary center from September 1992 through March 2010. Data were collected on 20 demographic, clinical, and laboratory variables at the start of the study. Patients were examined every 3 to 6 months for 5 years to identify risk factors for HCC; incidence was determined from a median follow-up time of 42 months. RESULTS: Over the follow-up period, 62 patients developed HCC (43 in the first 5 y of follow-up evaluation), with an annual incidence of 2.6%. By using multivariate analysis, age 55 years and older (hazard ratio, 2.39; 95% confidence interval, 1.27-4.51) and platelet counts less than 125 × 10(3)/mm(3) (hazard ratio, 3.29; 95% confidence interval, 1.39-7.85) were associated independently with the development of HCC. These variables were used to define 3 risk groups. The annual incidence of HCC in the group without either of these factors was 0.3% (n = 93), the annual incidence with 1 factor was 2.6% (n = 228), and the annual incidence with both factors was 4.8% (n = 129) (P < .0001). CONCLUSIONS: The annual incidence of HCC among patients with alcoholic cirrhosis of Child-Pugh class A or B is around 2.5%. Age and platelet count can be used to classify the patients in 3 different risk groups for HCC development within the next 5 years.

Isolation and characterization of enterocytes along the intestinal tract of the gilthead seabream (Sparus aurata L.).

Epithelial cells were successfully isolated along the intestine of the gilthead seabream using a dissociation method based on intracellular-like solutions. Biochemical and physiological tests revealed highly viable cells from all intestinal segments. Image analysis was used to identify cell types in the epithelial preparations which were highly enriched in enterocytes (>95%) over mucous cells. Several digestive hydrolases were determined in the isolated cells. Maltase (M), sucrase (S), leucine aminopeptidase (LA), 5'nucleotidase (5'N), but not gamma-glutamyl transferase (gamma-GT) or alkaline phosphatase (AP) activities were found to be enriched in the epithelial preparations versus the corresponding intestinal homogenates. Comparison of digestive hydrolases revealed the existence of a clear heterogeneity in their expression pattern in the enterocytes, along the intestine. Na(+)-K(+)-ATPase, Na(+)-ATPase and Cl(-)-ATPase activities were also determined in the membrane fraction of isolated cells. Analyses of enzymatic profiles revealed a clear asymmetry in the distribution of all Mg(2+)-dependent ATPases; that is, maximal Na(+)-K(+)- and Na(+)-ATPase activities were observed in the enterocytes from pyloric caeca, while Cl(-)-ATPase activity was about twice as high in the enterocytes from anterior and posterior intestines compared with pyloric caeca. This is the first report demonstrating the existence of heterogeneous metabolic and enzymatic profiles in different enterocyte populations from euryhaline teleosts.

Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis.

Better knowledge of the risk factors associated with the appearance of hepatocellular carcinoma (HCC) could improve the efficacy of surveillance programs. A total of 463 patients aged 40 to 65 years with liver cirrhosis in Child-Pugh class A or B were included in a program of early diagnosis. The predictive value of different risk factors was evaluated using the Kaplan-Meier method and Cox regression model. Thirty-eight patients developed HCC. In the multivariate analysis, 4 variables showed an independent predictive value for the development of HCC: age 55 years or older, antibody to hepatitis C virus (anti-HCV) positivity, prothrombin activity 75% or less, and platelet count less than 75 x 10(3)/mm(3). According to the contribution of each of these factors to the final model, a score ranging between 0 and 4.71 points was constructed to allow the division of patients into 2 different risk groups. The low-risk group included those with a score of 2.33 points or less (n = 270; 4 with HCC; cumulative incidence of HCC at 4 years, 2.3%), and the high-risk group included those with a score greater than 2.33 (n = 193; 34 with HCC; cumulative incidence of HCC at 4 years, 30.1%) (P =.0001). In conclusion, a simple score made up of 4 clinical and biological variables allowed us to distinguish 2 groups of cirrhotic patients at high and low risk for the development of HCC. We believe this score can be useful in establishing a subset of cirrhotic patients in whom a surveillance program for early detection of HCC could be unjustified.