Chemical Genetic Programming -Coevolution Between Genotypic Strings and Phenotypic Trees

Abstract. Chemical Genetic Programming (CGP) is a new method of genetic programming that introduced collision-based biochemical processes and realized dynamic mapping from genotypic strings to phenotypic trees. Chemical Genetic Programming (CGP) An initial set of rewriting rules is supplied that provides the system with the syntactical structure within which all programs must be generated. These rules allow only executable programs to be generated, but do not place any artificial limitations on the complexity or structure of these programs. Individuals are initially randomly generated, then evolved to form the population of successive generations. The fitness value of an individual is calculated using a correlation function that compares the target function with the individual's generated function. Based on their fitness values, cells, including both the DNA and the rewriting rules, are selected and then evolved. Evolution consists of mutation of DNA units, single point DNA crossover and molecular exchange between two cells, and selection of cells. Evolution adaptively changes not only the DNA information, but also the rewriting rules in cells. This enables the evolutionary optimization of the genotype (DNA) to phenotype (tree) mapping, by which we expect CGP to find the best translation grammar for creating a solution from the one-dimensional genotypic information. To examine the effectiveness of CGP, it was applied to a selected symbolic regression problem, and the results were compared against those of Grammatical Evolution (GE

Increased IP-10 production by blood–nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy

Objective Dysfunction of the blood–nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN. Methods We determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system. Results The induced protein (IP)10 level in the cells in both the MADSAM and MMN groups was markedly increased in comparison with the typical CIDP, ALS and HC groups. The other cytokines, including granulocyte colony-stimulating factor, vascular endothelial growth factor (VEGF) and interleukin-7, were also significantly upregulated in the MADSAM group. The increase of IP-10 produced by PnMECs was correlated with the presence of conduction block in both the MADSAM and MMN groups. Conclusion The autocrine secretion of IP-10 induced by patient sera in PnMECs was markedly upregulated in both the MADSAM and MMN groups. The overproduction of IP-10 by PnMECs leads to the focal breakdown of the BNB and may help to mediate the transfer of pathogenic T cells across the BNB, thereby resulting in the appearance of conduction block in electrophysiological studies of patients with MADSAM and MMN

Expressions of Vascular Endothelial Growth Factor (VEGF)-D and VEGF Receptor-3 in Colorectal Cancer: Relationship to Lymph Node Metastasis

Angiogenic factors play a major role in tumor growth and metastasis. Vascular endothelial growth factor (VEGF)- D is a ligand for VEGF receptor-3 (VEGFR-3/Flt-4), which mainly expressed on the lymphatic endothelium. Recent experimental studies have shown that VEGF-D induces tumor lymphangiogenesis and promote metastatic spread of tumor cells via lymphatic vessels. However, the contribution of VEGFD to lymph node metastasis in human colorectal cancer is less understood. We therefore examined VEGF-D and VEGFR-3 expression in patients with colorectal cancer. Sections of formalin-fixed and paraffin-embedded specimens from 76 colorectal cancers were immunohistochemically stained for VEGF-D and VEGFR-3. Staining for VEGF-D was positive in the cytoplasm of tumor cells in 43 of 76 examined tumors (56.6%). Staining for VEGFR-3 was positive in endothelial cells in 38 (50.0%) tumors. Univariate analysis showed that both VEGF-D and VEGFR-3 expressions correlated significantly with lymph node metastasis, histological type and depth of tumor invasion. However, logistic regression analysis indicated that VEGF-D expression, but not that of VEGFR-3, was an independent predictor for lymph node metastasis. Our data suggest that VEGF-D plays an important role in lymph node metastasis in colorectal cancer

Pulse compression and beam focusing with segmented diffraction gratings in a high-power chirped-pulse amplification glass laser system

This paper was published in Optics Letters and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://dx.doi.org/10.1364/OL.35.001783 Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law

Value of systematic intervention for chronic obstructive pulmonary disease in a regional Japanese city based on case detection rate and medical cost

Objective: We established a COPD taskforce for early detection, diagnosis, treatment, and intervention. We implemented a pilot intervention with a prospective and longitudinal design in a regional city. This study evaluates the usefulness of the COPD taskforce and intervention based on COPD case detection rate and per capita medical costs. Method: We distributed a questionnaire to all 8,878 inhabitants aged 50?89 years, resident in Matsuura, Nagasaki Prefecture in 2006. Potentially COPD-positive persons received a pulmonary function test and diagnosis. We implemented ongoing detection, examination, education, and treatment interventions, performed follow-up examinations or respiratory lessons yearly, and supported the health maintenance of each patient. We compared COPD medical costs in Matsuura and in the rest of Nagasaki Prefecture using data from 2004 to 2013 recorded by the association of Nagasaki National Health Insurance Organization, assessing 10-year means and annual change. Results: As of 2014, 256 people have received a definitive diagnosis of COPD; representing 31% of the estimated total number of COPD patients. Of the cases detected, 87.5% were mild or moderate in severity. COPD medical costs per patient in Matsuura were significantly lower than the rest of Nagasaki Prefecture, as was rate of increase in cost over time. Conclusion: The COPD program in Matsuura enabled early detection and treatment of COPD patients and helped to lower the associated burden of medical costs. The success of this program suggests that a similar program could reduce the economic and human costs of COPD morbidity throughout Japan

Elevated Expression of Poly(ADP-Ribose) Polymerase-1 is Associated with Liver Metastasis in Colorectal Cancer.

Activation of poly(ADP-ribose) polymerase-1 (PARP-1) and its subsequent cleavage are early markers of apoptosis. PARP-1 is associated with DNA repair and so chromosome stability, cell cycle regulation, as well as tumorigenesis. To investigate the role of PARP-1 expression in colorectal carcinoma and its metastasis of liver, we compared the expression of PARP-1 in primary colorectal cancers with (n=15) and without liver metastasis (n=17) using a semi-quantitative reverse transcription - polymerase chain reaction. We also examined the expressions of poly(ADP-ribose) (PAR) and p53 in these tumors by immunohistochemistry. A significantly higher PARP-1 mRNA expression was noted in tumors with liver metastasis than those without liver metastasis (p<0.01). Colorectal cancers positively stained for p53 exhibited significantly higher PARP-1 mRNA expression than p53-negative tumors (p<0.01). The PAR labeling index (LI) of tumors with metastasis (0.33 ﾂｱ 0.33) was not significantly different (p=0.35) from that of tumors without liver metastasis (0.38 ﾂｱ 0.19). p53-positive tumors tended to have higher PAR LI levels than p53-negative tumors (p=0.08). Our findings suggest that PARP-1 may contribute to liver metastasis due to its DNA repair activity, resulting in survival of the tumor cells with accumulation of metastaticrelated gene\u27s damages. Detailed analysis of PARP-1 may be useful in cancer research and/or cancer therapy

Primary Omental Myxoid Leiomyosarcoma: Report of a Case and a Review of the Literature

A 41-year-old Japanese woman who presented with right lower abdominal pain underwent partial omental resection with tumor excision, leaving no residual tumor. The tumor was diagnosed as a myxoid leiomyosarcoma that apparently originated in the greater omentum. A recurrent omental tumor was excised at 4.5 months after the first operation, and then at 5.5 months after this, CT revealed metastatic sarcoma at the surface of the liver (S7) and the left upper abdomen. She died 20 months after the last operation despite treatment of the metastases with MAID therapy (mesna, adriamycin, ifosfamide, dacarbazine). A literature review revealed that this tumor mainly occurs in the uterus, soft tissue, and cardiovascular system, with a preponderance among middle-aged to elderly women. The present report is the first description of primary omental myxoid leiomyosarcoma

Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing

Background: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT. Methods: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package. Results: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive. Conclusions: Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women

High Level Expression of Platelet-derived Endothelial Cell Growth Factor predicts Good Prognosis in Colorectal Cancer Patients

Platelet-derived endothelial cell growth factor (PD-ECGF) is one of the angiogenic factors. PD-ECGF expression is elevated in colorectal carcinoma, but its prognostic value does not reach a consensus. The aim of this study is to clarify the prognostic value of the PD-ECGF expression in colorectal carcinomas. PD-ECGF expression was measured by enzyme- linked immunosorbent assay in frozen materials from 71 colorectal cancer patients who had recived curative resection. Patients were divided into high expression and low expression groups based on cut-off value. Correlations among PD-ECGF expression, clinicopathologic features, and disease-free interval were studied by univariate and multivariate analysis. To evaluate the origin of PD-ECGF, serial sections of 71 tumors were stained for PD-ECGF and CD68. PD-ECGF expression in normal mucosa was 34.4 ﾂｱ 15.5 (Units/mg protein) and the cut-off value was 65.4 (mean+2SD). There were no significant correlations between clinicopathological features and PD-ECGF expression. The disease-free interval for high PD-ECGF expression group was significantly longer than that of low expression group (P=0.006). A multivariate Cox\u27s regression analysis revealed a high PD-ECGF expression as an independent factor for better outcome. In immunohistochemical study, almost all tumor cells were negative for PD-ECGF, but stromal macrophages were predominantly positive for PD-ECGF. In conclusion, the PD-ECGF expression measured in this study was derived from stromal macrophages. High PD-ECGF expression was a predictor for favorable outcome after curative resection for colorectal cancer

Memory Immune Responses against Pandemic (H1N1) 2009 Influenza Virus Induced by a Whole Particle Vaccine in Cynomolgus Monkeys Carrying Mafa-A1*052∶02

We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA) non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009) H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052∶02, were used to analyze peptide-specific CD8+ T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1) than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1) in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8+ T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052∶02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses to macaques against pandemic influenza virus infection than did the split vaccine