Nonlinear inverse optimization approach for determining the weights of objective function in standing reach tasks

This paper presents a nonlinear inverse optimization approach to determine the weights for the joint displacement function in standing reach tasks. This inverse optimization problem can be formulated as a bi-level highly nonlinear optimization problem. The design variables are the weights of a cost function. The cost function is the weighted summation of the differences between two sets of joint angles (predicted posture and the actual standing reach posture). Constraints include the normalized weights within limits and an inner optimization problem to solve for joint angles (predicted standing reach posture). The weight linear equality constraints, obtained through observations, are also implemented in the formulation to test the method. A 52 degree-of-freedom (DOF) human whole body model is used to study the formulation and visualize the prediction. An in-house motion capture system is used to obtain the actual standing reach posture. A total of 12 subjects (three subjects for each percentile in stature of 5th percentile female, 50th percentile female, 50th percentile male and 95th percentile male) are selected to run the experiment for 30 tasks. Among these subjects one is Turkish, two are Chinese, and the rest subjects are Americans. Three sets of weights for the general standing reach tasks are obtained for the three zones by averaging all weights in each zone for all subjects and all tasks. Based on the obtained sets of weights, the predicted standing reach postures found using the direct optimization-based approach have good correlation with the experimental results. Sensitivity of the formulation has also been investigated in this study. The presented formulation can be used to determine the weights of cost function within any multi-objective optimization (MOO) problems such as any types of posture prediction and motion prediction.     

Theoretical method for the study of plasmon generation in hybrid multilayer-optical fiber structures

A theoretical method is presented for the determination of the behavior of devices based on the deposition of multilayer structures on polished optical fibers. Plasmon generation in metallic layers is modeled. The method is based on the Rayleigh expansion of the electric fields and permits us to determine their distribution over the whole structure by an application of boundary conditions. Once the distribution is known, the power transmitted by the fiber can be computed as a function of the geometrical and refractive parameters of the device. The method is versatile and can be used as a theoretical tool for the design of devices of that type used for many different purposes. We present real experimental results obtained with an operative sensor that agree with the theoretical predictions of our technique and prove its suitability.     

Diagnosing Czech Patients with Inherited Platelet Disorders

A single-center study was conducted on 120 patients with inherited disorders of primary hemostasis followed at our hematological center. These patients presented a variety of bleeding symptoms; however, they had no definitive diagnosis. Establishing a diagnosis has consequences for the investigation of probands in families and for treatment management; therefore, we aimed to improve the diagnosis rate in these patients by implementing advanced diagnostic methods. According to the accepted international guidelines at the time of study, we investigated platelet morphology, platelet function assay, light-transmission aggregometry, and flow cytometry. Using only these methods, we were unable to make a definitive diagnosis for most of our patients. However, next-generation sequencing (NGS), which was applied in 31 patients, allowed us to establish definitive diagnoses in six cases (variants in ANKRD26, ITGA2B, and F8) and helped us to identify suspected variants (NBEAL2, F2, BLOC1S6, AP3D1, GP1BB, ANO6, CD36, and ITGB3) and new suspected variants (GFI1B, FGA, GP1BA, and ITGA2B) in 11 patients. The role of NGS in patients with suspicious bleeding symptoms is growing and it changes the diagnostic algorithm. The greatest disadvantage of NGS, aside from the cost, is the occurrence of gene variants of uncertain significance.     

A Role of DNA Methylation within the CYP17A1 Gene in the Association of Genetic and Environmental Risk Factors with Stress-Related Manifestations of Schizophrenia

As genetic and environmental influences on schizophrenia might converge on DNA methylation (DNAm) within loci which are both associated with the disease and implicated in response to environmental stress, we examined whether DNAm within CYP17A1, a hypothalamus–pituitary–adrenal axis gene which is situated within the schizophrenia risk locus 10q24.32, would mediate genetic and environmental effects on stress-related schizophrenia symptoms. DNAm within an exonic–intronic fragment of CYP17A1 was assessed in the blood of 66 schizophrenia patients and 63 controls using single-molecule real-time bisulfite sequencing. Additionally, the VNTR polymorphism of the AS3MT gene, a plausible causal variant within the 10q24.32 locus, was genotyped in extended patient and control samples (n = 700). The effects of local haplotype, VNTR and a polyenviromic risk score (PERS) on DNAm, episodic verbal memory, executive functions, depression, and suicidality of patients were assessed. Haplotype and PERS differentially influenced DNAm at four variably methylated sites identified within the fragment, with stochastic, additive, and allele-specific effects being found. An allele-specific DNAm at CpG-SNP rs3781286 mediated the relationship between the local haplotype and verbal fluency. Our findings do not confirm that the interrogated DNA fragment is a place where genetic and environmental risk factors converge to influence schizophrenia symptoms through DNAm.     

Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity

Longevity is a unique human phenomenon and a highly stable trait, characterized by polygenicity. The longevity phenotype occurs due to the ability to successfully withstand the age-related genomic instability triggered by Alu elements. The purpose of our cross-sectional study was to evaluate the combined contribution of ACE*Ya5ACE, CDH4*Yb8NBC516, COL13A1*Ya5ac1986, HECW1*Ya5NBC182, LAMA2*Ya5-MLS19, PLAT*TPA25, PKHD1L1*Yb8AC702, SEMA6A*Yb8NBC597, STK38L*Ya5ac2145 and TEAD1*Ya5ac2013 Alu elements to longevity. The study group included 2054 unrelated individuals aged from 18 to 113 years who are ethnic Tatars from Russia. We analyzed the dynamics of the allele and genotype frequencies of the studied Alu polymorphic loci in the age groups of young (18–44 years old), middle-aged (45–59 years old), elderly (60–74 years old), old seniors (75–89 years old) and long-livers (90–113 years old). Most significant changes in allele and genotype frequencies were observed between the long-livers and other groups. The search for polygenic predictors of longevity was performed using the APSampler program. Attaining longevity was associated with the combinations LAMA2*ID + CDH4*D (OR = 2.23, P_Bonf = 1.90 × 10⁻²) and CDH4*DD + LAMA2*ID + HECW1*D (OR = 4.58, P_Bonf = 9.00 × 10⁻³) among persons aged between 18 and 89 years, LAMA2*ID + CDH4*D + SEMA6A*I for individuals below 75 years of age (OR = 3.13, P_Bonf = 2.00 × 10⁻²), LAMA2*ID + HECW1*I for elderly people aged 60 and older (OR = 3.13, P_Bonf = 2.00 × 10⁻²) and CDH4*DD + LAMA2*D + HECW1*D (OR = 4.21, P_Bonf = 2.60 × 10⁻²) and CDH4*DD + LAMA2*D + ACE*I (OR = 3.68, P_Bonf = 1.90 × 10⁻²) among old seniors (75–89 years old). The key elements of combinations associated with longevity were the deletion alleles of CDH4 and LAMA2 genes. Our results point to the significance for human longevity of the Alu polymorphic loci in CDH4, LAMA2, HECW1, SEMA6A and ACE genes, involved in the integration systems.     

Association between LAG3/CD4 Genes Variants and Risk for Multiple Sclerosis

Several recent works have raised the possibility of the contribution of the lymphocyte activation gene 3 (LAG3) protein in the inflammatory processes of multiple sclerosis (MS). Results of studies on the possible association between LAG3 gene variants and the risk of MS have been inconclusive. In this study, we tried to show the possible association between the most common single nucleotide variants (SNVs) in the CD4 and LAG3 genes (these two genes are closely related) and the risk of MS in the Caucasian Spanish population. We studied the genotypes and allelic variants CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 in 300 patients diagnosed with MS and 400 healthy patients using specific TaqMan-based qPCR assays. We analyzed the possible influence of the genotype frequency on age at the onset of MS, the severity of MS, clinical evolutive subtypes of MS, and the HLADRB1*1501 genotype. The frequencies of the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants were not associated with the risk of MS and were unrelated to gender, age at onset and severity of MS, the clinical subtype of MS, and HLADRB1*1501 genotype. The results of the current study showed a lack of association between the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 SNVs and the risk of developing MS in the Caucasian Spanish population.     

Coherent interaction of atoms with a beam of light confined in a light cage

Controlling coherent interaction between optical fields and quantum systems in scalable, integrated platforms is essential for quantum technologies. Miniaturise...