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

Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion

<p>Abstract</p> <p>Background</p> <p>The cell tropism of <it>Brucella abortus</it>, a causative agent of brucellosis and facultative intracellular pathogen, in the placenta is thought to be a key event of infectious abortion, although the molecular mechanism for this is largely unknown. There is a higher degree of bacterial colonization in the placenta than in other organs and many bacteria are detected in trophoblast giant (TG) cells in the placenta. In the present study, we investigated mechanism of <it>B. abortus </it>invasion into TG cells.</p> <p>Results</p> <p>We observed internalization and intracellular growth of <it>B. abortus </it>in cultured TG cells. A monoclonal antibody that inhibits bacterial internalization was isolated and this reacted with heat shock cognate protein 70 (Hsc70). Depletion and over expression of Hsc70 in TG cells inhibited and promoted bacterial internalization, respectively. IFN-γ receptor was expressed in TG cells and IFN-γ treatment enhanced the uptake of bacteria by TG cells. Administering the anti-Hsc70 antibody to pregnant mice served to prevent infectious abortion.</p> <p>Conclusion</p> <p><it>B. abortus </it>infection of TG cells in placenta is mediated by Hsc70, and that such infection leads to infectious abortion.</p

T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non–small cell lung cancer

AbstractObjective: Among the TNM criteria, tumor size is a well-assessed factor in the prognosis of small tumors. A 3-cm cutoff point separates T1 from T2 tumors, whereas a size larger than 3 cm is not ascribed any prognostic value. Instead, N2 is considered to be the worst prognostic factor for intrathoracic extended disease. Method: The prognosis of 545 patients with non–small cell lung cancer larger than 3 cm in diameter (T2, T3, and T4) was studied. These tumors were completely resected by pneumonectomy (n = 126) or lobectomy (n = 411) or were partially resected (n = 8). Survivals were compared according to the following factors: tumor size (3.1-5 cm, 5.1-7 cm, >7 cm), nodal status, age, sex, histologic type, degree of pleural involvement, operative procedure, stage, and T factor. For the multivariate analysis, the Cox proportional hazard model was used with the same variables. Results: The univariate analysis showed that age, sex, degree of pleural involvement, operative procedure, tumor size, nodal status, and stage were all significant prognostic factors. Further comparison of survival between different tumor sizes (≤5 cm vs >5 cm) in the same nodal category demonstrated a significantly poor prognosis for larger tumors in N0 (P =.00374) and N2+N3 (P =.0157), but not in N1 (P =.3452). T2 tumors (n = 349) were divided, according to size, into T2a (n = 238) and T2b (n = 111), and survival was compared with those in T3 and T4. The 5-year survivals were 51.3%, 35.1%, 47.8%, and 25.3%, respectively. The difference between T2a and T2b was statistically significant (log-rank P =.0170, Breslow P =.0055). Conclusions: A tumor size of more than 5 cm in diameter was indicative of a poor prognosis in non–small cell lung cancer, because patients with T2b tumors had a significantly different survival from that of patients with T2a tumors, and the survival curve was located between those for patients with T3 and T4 tumors. Consequently, T2b might be upgraded to at least T3.J Thorac Cardiovasc Surg 2001;122:907-1

The Usefulness of Pre-Radiofrequency Ablation SUVmax in 18F-FDG PET/CT to Predict the Risk of a Local Recurrence of Malignant Lung Tumors after Lung Radiofrequency Ablation

The aim of the present study was to assess the diagnostic usefulness of Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the prediction of local recurrence of malignant lung tumors by analyzing the pre-radiofrequency ablation (RFA) maximal standardized uptake value (SUVmax). We performed a historical cohort study of consecutive malignant lung tumors treated by RFA from January 2007 to May 2008 at Okayama University Hospital. We selected only lung tumors examined by PET/CT within 90 days before RFA and divided them (10 primary and 29 metastatic) into 3 groups according to their tertiles of SUVmax. We calculated recurrence odds ratios in the medium group and the high group compared to the low group using multivariate logistic analysis. After we examined the relationship between SUVmax and recurrence in a crude model, we adjusted for some factors. Tumors with higher SUVmax showed higher recurrence odds ratios (medium group;1.84, high group;4.14, respectively). The tumor size also increased the recurrence odds ratio (2.67);we thought this was mainly due to selection bias because we excluded tumors less than 10mm in diameter. This study demonstrated the pre-RFA SUVmax in PET/CT may be a prognostic factor for local recurrence of malignant lung tumors

Therapeutic regimen of l-arginine for MELAS: 9-year, prospective, multicenter, clinical research

ObjectiveTo examine the efficacy and safety of the therapeutic regimen using oral and intravenous l-arginine for pediatric and adult patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).MethodsIn the presence and absence of an ictus of stroke-like episodes within 6 h prior to efficacy assessment, we correspondingly conducted the systematic administration of oral and intravenous l-arginine to 15 and 10 patients with MELAS in two, 2-year, prospective, multicenter clinical trials at 10 medical institutions in Japan. Subsequently, patients were followed up for 7 years. The primary endpoint in the clinical trial of oral l-arginine was the MELAS scale, while that for intravenous l-arginine was the improvement rates of headache and nausea/vomiting at 2 h after completion of the initial intravenous administration. The relationships between the ictuses of stroke-like episodes and plasma arginine concentrations were examined.ResultsOral l-arginine extended the interictal phase (p = 0.0625) and decreased the incidence and severity of ictuses. Intravenous l-arginine improved the rates of four major symptoms—headache, nausea/vomiting, impaired consciousness, and visual disturbance. The maximal plasma arginine concentration was 167 μmol/L when an ictus developed. Neither death nor bedriddenness occurred during the 2-year clinical trials, and the latter did not develop during the 7-year follow-up despite the progressively neurodegenerative and eventually life-threatening nature of MELAS. No treatment-related adverse events occurred, and the formulations of l-arginine were well tolerated.ConclusionsThe systematic administration of oral and intravenous l-arginine may be therapeutically beneficial and clinically useful for patients with MELAS

TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2

Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia

Development of an apolipoprotein E mimetic peptide–lipid conjugate for efficient brain delivery of liposomes

Liposomes are versatile carriers that can encapsulate various drugs; however, for delivery to the brain, they must be modified with a targeting ligand or other modifications to provide blood–brain barrier (BBB) permeability, while avoiding rapid clearance by reticuloendothelial systems through polyethylene glycol (PEG) modification. BBB-penetrating peptides act as brain-targeting ligands. In this study, to achieve efficient brain delivery of liposomes, we screened the functionality of eight BBB-penetrating peptides reported previously, based on high-throughput quantitative evaluation methods with in vitro BBB permeability evaluation system using Transwell, in situ brain perfusion system, and others. For apolipoprotein E mimetic tandem dimer peptide (ApoEdp), which showed the best brain-targeting and BBB permeability in the comparative evaluation of eight peptides, its lipid conjugate with serine–glycine (SG)5 spacer (ApoEdp-SG-lipid) was newly synthesized and ApoEdp-modified PEGylated liposomes were prepared. ApoEdp-modified PEGylated liposomes were effectively associated with human brain capillary endothelial cells via the ApoEdp sequence and permeated the membrane in an in vitro BBB model. Moreover, ApoEdp-modified PEGylated liposomes accumulated in the brain 3.9-fold higher than PEGylated liposomes in mice. In addition, the ability of ApoEdp-modified PEGylated liposomes to localize beyond the BBB into the brain parenchyma in mice was demonstrated via three-dimensional imaging with tissue clearing. These results suggest that ApoEdp-SG-lipid modification is an effective approach for endowing PEGylated liposomes with the brain-targeting ability and BBB permeability

Ultrafast Control of Crystal Structure in a Topological Charge-Density-Wave Material

Optical control of crystal structures is a promising route to change physical properties including topological nature of a targeting material. Time-resolved X-ray diffraction measurements using the X-ray free-electron laser are performed to study the ultrafast lattice dynamics of VTe$_2$, which shows a unique charge-density-wave (CDW) ordering coupled to the topological surface states as a first-order phase transition. A significant oscillation of the CDW amplitude mode is observed at a superlattice reflection as well as Bragg reflections. The frequency of the oscillation is independent of the fluence of the pumping laser, which is prominent to the CDW ordering of the first-order phase transition. Furthermore, the timescale of the photoinduced 1$T^{\prime\prime}$ to 1$T$ phase transition is independent of the period of the CDW amplitude mode

The updated retrospective questionnaire study of sporadic inclusion body myositis in Japan

Background: Sporadic inclusion body myositis (sIBM) is the most prevalent muscle disease in elderly people, affecting the daily activities. sIBM is progressive with unknown cause and without effective treatment. In 2015, sIBM was classified as an intractable disease by the Japanese government, and the treatment cost was partly covered by the government. This study aimed to examine the changes in the number of patients with sIBM over the last 10 years and to elucidate the cross-sectional profile of Japanese patients with sIBM. Methods: The number of sIBM patients was estimated through a reply-paid postcard questionnaire for attending physicians. Only patients diagnosed as “definite” or “probable” sIBM by clinical and biopsy sIBM criteria were included in this study (Lancet Neurol 6:620-631, 2007, Neuromuscul Disord 23:1044-1055, 2013). Additionally, a registered selfadministered questionnaire was also sent to 106 patients who agreed to reply via their attending physician, between November 2016 and March 2017. Results: The number of patients diagnosed with sIBM for each 5-year period was 286 and 384 in 2011 and 2016, respectively. Inability to stand-up, cane-dependent gait, inability to open a plastic bottle, choking on food ingestion, and being wheelchair-bound should be included as sIBM milestones. Eight patients were positive for anti-hepatitis C virus antibody; three of them were administered interferon before sIBM onset. Steroids were administered to 33 patients (31.1%) and intravenous immunoglobulin to 46 patients (43.4%). From 2016 to 2017, total of 70 patients applied for the designated incurable disease medical expenses subsidy program. Although the treatment cost was partly covered by the government, many patients expressed psychological/mental and financial anxieties. Conclusions: We determined the cross-sectional profile of Japanese patients with sIBM. Continuous support and prospective surveys are warranted