288 research outputs found
Cocoa and cocoa bean shells role in human health: An updated review
No full textCocoa is derived from the seeds of Theobroma cacao L., an evergreen tree typical of tropical regions. It contains
numerous phytochemicals, with polyphenols representing the largest groups of compounds inside the seed, and
has been implicated in numerous biological properties, such as antioxidant, antiproliferative, antiapoptotic, antiinflammatory,
anti-cancer. Moreover, cocoa has been investigated in different health conditions, including heart
diseases, dyspepsia, nervous system diseases, circulation problems, and many others. Given its high consumption
in many countries all over the world, it is important to know and understand its effects on human health. In
addition, the cocoa bean shell, a by-product of the process of cocoa preparation, has been gaining remarkable
interest due to its high content of phytochemicals. This review summarizes the available literature and works on
the health benefits of cocoa and cocoa bean shells. Moreover, the current review focuses on studies investigating
their possible therapeutic roles in cancer and the underlining potential mechanisms of action
Microcephaly associated with a familial balanced translocation t(5;18)(q35.2;q22.3):gene expression studies in lymphoblastoid cell‐lines.
No full textBackground Autosomal dominant non‐syndromic microcephaly is a rare and heterogenous condition of unknown genetic etiology. However, chromosomal imbalances that have repeatedly been associated with microcephaly may offer a way to identify novel genes for non‐syndromic microcephaly. One such region is 5q35.2. Microdeletions in 5q35.2 including the gene NKX2.5 are associated to congenital heart defects and microcephaly. Since mutations in NKX2.5 are causal for congenital heart defects but are never associated with microcephaly, 5q35.2 deletions cause a contiguous gene deletion syndrome. Thus, in this chromosomal region a gene or regulatory element associated to dominant microcephaly is present. Methods We present a unique family where a balanced translocation t(5;18)(q35.2;q22.3) segregates with microcephaly in 4 out of 7 carriers. Fine mapping of the breakpoints was performed by use of 1 Mb BAC/PAC array Comparative Genome Hybridisation (array‐CGH), Fluorescent In Situ Hybridisation (FISH) and consecutive rounds of quantitative Real Time PCR (qRT‐PCR). Rigorous gene expression studies of all genes within a 4Mb region flanking the intergenic breakpoint on chromosome 5q35.2 were carried out on EBV‐transformed lymphoblastoid cell‐lines from 5 carriers by means of qRT‐PCR. Results Fine mapping of the breakpoints revealed that the breakpoint on chromosome 5q35.2 was located in an intergenic region previously associated with non‐syndromic microcephaly. Of the 27 genes in this region, only 11 revealed a reliably detectable expression pattern in these cells. However, in contrast to a positive control carrying a deletion in the region, for none of these genes, a significantly altered expression was observed. Conclusions The clinical and genetic findings support the observation that chromosome region 5q35.2 harbors a gene implicated in microcephaly, but also illustrate the limitations of the use of EBV‐transformed lymphoblastoid cell‐lines in expression studies of genes involved in brain growth.Autosomal dominant non‐syndromic microcephaly is a rare and heterogenous condition of unknown
genetic etiology. However, chromosomal imbalances that have repeatedly been associated with
microcephaly may offer a way to identify novel genes for non‐syndromic microcephaly. One such
region is 5q35.2. Microdeletions in 5q35.2 including the gene NKX2.5 are associated to congenital
heart defects and microcephaly. Since mutations in NKX2.5 are causal for congenital heart defects
but are never associated with microcephaly, 5q35.2 deletions cause a contiguous gene deletion
syndrome. Thus, in this chromosomal region a gene or regulatory element associated to dominant
microcephaly is present
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Tackling Credit Assignment Using Memory and Multilevel Optimization for Multiagent Reinforcement Learning
No full textThere is growing commercial interest in the use of multiagent systems in real world applications. Some examples include inventory management in warehouses, smart homes, planetary exploration, search and rescue, air-traffic management and autonomous transportation systems. However, multiagent coordination is an extremely challenging problem. First, information relevant for coordination is often distributed across the team members, and fragmented amongst each agent's observation histories (past states). Second, the coordination objective is often sparse and noisy from the perspective of an agent. Designing general mechanisms of generating agent-specific reward functions that incentivizes an agent to collaborate towards the shared global objective is extremely difficult. From a learning perspective, both difficulties can be linked to the difficulty of credit assignment - the process of accurately associating rewards with actions.
The primary contribution of this dissertation is to tackle credit assignment in multiagent systems in order to enable better multiagent coordination. First we leverage memory as a tool in enabling better credit assignment by facilitating associations between rewards and actions separated across time. We achieve this by introducing Modular Memory Units (MMU), a memory-augmented neural architecture that can reliably retain and propagate information over an extended period of time. We then use MMU to augment individual agents' policies in solving dynamic tasks that require adaptive behavior from a distributed multiagent team. We also introduce Distributed MMU (DMMU) which uses memory as a shared knowledge base across a team of distributed agents to enable distributed one-shot decision making.
Switching our attention from the agent to the learning algorithm, we then introduce Evolutionary Reinforcement Learning (ERL), a multilevel optimization framework that blends the strength of policy gradients and evolutionary algorithms to improve learning. We further extend the ERL framework to introduce Collaborative ERL (CERL) which employs a collection of policy gradient learners (portfolio), each optimizing over varying resolution of the same underlying task. This leads to a diverse set of policies that are able to reach diverse regions within the solution space. Results in a range of continuous control benchmarks demonstrate that ERL and CERL significantly outperform their composite learners while remaining overall more sample-efficient.
Finally, we introduce Multiagent ERL (MERL), a hybrid algorithm that leverages the multilevel optimization framework of ERL to enable improved multiagent coordination without requiring explicit alignment between local and global reward functions. MERL uses fast, policy-gradient based learning for each agent by utilizing their dense local rewards. Concurrently, evolution is used to recruit agents into a team by directly optimizing the sparser global objective. Experiments in multiagent coordination benchmarks demonstrate that MERL's integrated approach significantly outperforms the state-of-the-art multiagent policy-gradient algorithms
A novel common variant in DCST2 is associated with length in early life and height in adulthood
No full textCommon genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N=28,459). We identified 7 independent top SNPs (P<1x10-6) for birth length, of which 3 were novel and 4 were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The 3 novel SNPs were followed-up in 9 replication studies (Stage 2; N=11,995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1+2; ß=0.046, S.E.=0.008, P=2.46x10?8, explained variance=0.05%). Rs905938 was also associated with infant length (N=28,228; P=5.54x10-4) and adult height (N=127,513; P=1.45x10-5). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height
Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57
No full textBackgroundTransient neonatal diabetes mellitus 1 (TNDM1) is a rare imprinting disorder characterized by intrautering growth retardation and diabetes mellitus usually presenting within the first six weeks of life and resolves by the age of 18 months. However, patients have an increased risk of developing diabetes mellitus type 2 later in life. Transient neonatal diabetes mellitus 1 is caused by overexpression of the maternally imprinted genes PLAGL1 and HYMAI on chromosome 6q24. One of the mechanisms leading to overexpression of the locus is hypomethylation of the maternal allele of PLAGL1 and HYMAI. A subset of patients with maternal hypomethylation at PLAGL1 have hypomethylation at additional imprinted loci throughout the genome, including GRB10, ZIM2 (PEG3), MEST (PEG1), KCNQ1OT1 and NESPAS (GNAS-AS1). About half of the TNDM1 patients carry mutations in ZFP57, a transcription factor involved in establishment and maintenance of methylation of imprinted loci. Our objective was to investigate whether additional regions are aberrantly methylated in ZFP57 mutation carriers.MethodsGenome-wide DNA methylation analysis was performed on four individuals with homozygous or compound heterozygous ZFP57 mutations, three relatives with heterozygous ZFP57 mutations and five controls. Methylation status of selected regions showing aberrant methylation in the patients was verified using bisulfite-sequencing.ResultsWe found large variability among the patients concerning the number and identity of the differentially methylated regions, but more than 60 regions were aberrantly methylated in two or more patients and a novel region within PPP1R13L was found to be hypomethylated in all the patients. The hypomethylated regions in common between the patients are enriched for the ZFP57 DNA binding motif.ConclusionsWe have expanded the epimutational spectrum of TNDM1 associated with ZFP57 mutations and found one novel region within PPP1R13L which is hypomethylated in all TNDM1 patients included in this study. Functional studies of the locus might provide further insight into the etiology of the disease.<br/
Novelty seeking multiagent evolutionary reinforcement learning
No full textCoevolving teams of agents promises effective solutions for many coordination tasks such as search and rescue missions or deep ocean exploration. Good team performance in such domains generally relies on agents discovering complex joint policies, which is particularly difficult when the fitness functions are sparse (where many joint policies return the same or even zero fitness values). In this paper, we introduce Novelty Seeking Multiagent Evolutionary Reinforcement Learning (NS-MERL), which enables agents to more efficiently explore their joint strategy space. The key insight of NS-MERL is to promote good exploratory behaviors for individual agents using a dense, novelty-based fitness function. Though the overall team-level performance is still evaluated via a sparse fitness function, agents using NS-MERL more efficiently explore their joint action space and more readily discover good joint policies. Our results in complex coordination tasks show that teams of agents trained with NS-MERL perform significantly better than agents trained solely with task-specific fitnesses. Interactive Intelligenc
Pension reform in Latin America : quick fixes or sustainable reform?
No full textBecause of better health and higher standards of living, people are living longer. By 2030, more than 16 percent of the world's population will be older than 60, compared with 9 percent today. As a result, pension systems will need reform. Most current systems have substantial unfunded liabilities that will impose significant financial burdens onfuture generations without providing adequate protection for older individuals and lower-income workers. Pension reform is inevitable because of demographic imperatives and because many pension systems are financially unsustainable. Unfunded public pension systems pose political risk if promises to future retirees cannot be met. Pension reform is both technically and politically complex but more and more countries are beginning to address the problem. The question is whether to adopt quick fixes or sustainable changes that will benefit the macroeconomy and protect elderly and lower-income citizens. Quick fixes--typical in many economies--generally involve changes in eligibility (such as retirement age), changes in the rate of contribution or the population of workers on which contributions are calculated, or changes in the structure of benefits. Countries in Latin America have been ahead of other regions in undertaking major reform from pay-as-you-go defined-benefit pension plans to fully funded, defined-contribution pension plans. Because of the successful Chilean pension model, a notable number of Latin American countries have undertaken deep pension reform. The author highlights reform efforts in a sample of countries: Argentina, Brazil, Chile, Mexico, and Peru. Vigilance is still needed, says the author. Effective oversight is essential, and so is complementary reform in the banking, insurance, and securities markets. In capital markets, for example, regulation must be strengthened and the requirement that pension fund investments be made only in government-related securities must be eliminated. New types of insurance must be made available and there must be increased competition among insurance providers. More work must be done but the region's pension systems have started on the right course.Banks&Banking Reform,Payment Systems&Infrastructure,Public Health Promotion,Pensions&Retirement Systems,Environmental Economics&Policies,Pensions&Retirement Systems,Economic Stabilization,Banks&Banking Reform,Environmental Economics&Policies,Economic Theory&Research
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