Miracle-dz/UniFAR-FTUs huggingface dataset:
Maximization of cell viability rather than biocatalyst activity improves whole‐cell ω‐oxyfunctionalization performance

It is a common misconception in whole‐cell biocatalysis to refer to an enzyme as the biocatalyst, thereby neglecting the structural and metabolic framework provided by the cell. Here, the low whole‐cell biocatalyst stability, that is, the stability of specific biocatalyst activity, in a process for the terminal oxyfunctionalization of renewable fatty acid methyl esters was investigated. This reaction, which is difficult to achieve by chemical means, is catalyzed by Escherichia coli featuring the monooxygenase system AlkBGT and the uptake facilitator AlkL from Pseudomonas putida GPo1. Corresponding products, that is, terminal alcohols, aldehydes, and acids, constitute versatile bifunctional building blocks, which are of special interest for polymer synthesis. It could clearly be shown that extensive dodecanoic acid methyl ester uptake mediated by high AlkL levels leads to whole‐cell biocatalyst toxification. Thus, cell viability constitutes the primary factor limiting biocatalyst stability and, as a result, process durability. Hence, a compromise had to be found between low biocatalyst activity due to restricted substrate uptake and poor biocatalyst stability due to AlkL‐mediated toxification. This was achieved by the fine‐tuning of heterologous alkL expression, which, furthermore, enabled the identification of the alkBGT expression level as another critical factor determining biocatalyst stability. Controlled synthesis of AlkL and reduced alkBGT expression finally enabled an increase of product titers by a factor of 4.3 up to 229 g Lorg−1 in a two‐liquid phase bioprocess setup. Clearly, ω‐oxyfunctionalization process performance was determined by cell viability and thus biocatalyst stability rather than the maximally achievable specific biocatalyst activity. Biotechnol. Bioeng. 2017;114: 874–884. © 2016 Wiley Periodicals, Inc.
Heaven can wait.

The apparently unlimited demand for health care, finite supply of resources, the internal social market and continuous technological advances have given rise to increasing concern about the performance of health services. We examine an important measure of health care performance--avoidable mortality. Studies extending the scope of avoidable mortality and other outcome indicators are discussed. Although avoidable mortality is limited to providing a warning signal of possible health care deficiencies and is not an appropriate measure for all types of intervention, it still provides us with one of the best guides to the performance of health services.
An empirical examination of factors driving the offshore renminbi market

ABSTRACT Following the 2010 establishment of the offshore renminbi market in Hong Kong, renminbi deposits there quickly rose above RMB 1 trillion. In this article, we examine fluctuations between the offshore value of the renminbi in Hong Kong and its onshore value in mainland China. The size of the spot market spread appears to be influenced by stock market sentiment as reflected in the spread between A-shares listed in Shanghai and H-shares listed in Hong Kong. There is also some evidence of a link between the spread and the pace of renminbi deposit growth in Hong Kong.
Service and infrastructure needs to support recovery programmes for Indigenous community mental health consumers

Mental health is a major concern in Indigenous communities, as Indigenous people experience poorer health outcomes generally, and poorer social and emotional well-being throughout their lives, compared to non-Indigenous populations. Interviews were conducted with 20 mental health workers from a housing assistance programme for Indigenous clients with mental illness. Service and infrastructure needs identified to support clients were classified under the following overarching theme 'supports along the road to recovery'. Subthemes were: (i) It is OK to seek help; (ii) linking in to the local community; (iii) trusting the workers; and (iv) help with goal setting and having activities that support their achievement. This paper highlights the importance of targeted housing and accommodation support programmes for Indigenous people to prevent homelessness, and the essential services and infrastructure required to support Indigenous clients' mental health needs. These insights may inform service review, workforce development, and further research.
Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis.

BACKGROUND Idiopathic pulmonary fibrosis is a progressive lung disease with a high mortality rate. Because the signaling pathways activated by several tyrosine kinase receptors have been shown to be involved in lung fibrosis, it has been suggested that the inhibition of these receptors may slow the progression of idiopathic pulmonary fibrosis. METHODS In a 12-month, phase 2 trial, we assessed the efficacy and safety of four different oral doses of the tyrosine kinase inhibitor BIBF 1120 as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Secondary end points included acute exacerbations, quality of life (measured with the St. George's Respiratory Questionnaire [SGRQ]), and total lung capacity. RESULTS A total of 432 patients underwent randomization to receive one of four doses of BIBF 1120 (50 mg once a day, 50 mg twice a day, 100 mg twice a day, or 150 mg twice a day) or placebo. In the group receiving 150 mg of BIBF 1120 twice a day, FVC declined by 0.06 liters per year, as compared with 0.19 liters per year in the placebo group, a 68.4% reduction in the rate of loss with BIBF 1120 (P = 0.06 with the closed testing procedure for multiplicity correction; P = 0.01 with the hierarchical testing procedure). This dose also resulted in a lower incidence of acute exacerbations, as compared with placebo (2.4 vs. 15.7 per 100 patient-years, P = 0.02) and a small decrease in the SGRQ score (assessed on a scale of 0 to 100, with lower scores indicating better quality of life) as compared with an increase with placebo (-0.66 vs. 5.46, P = 0.007). Gastrointestinal symptoms (which led to more discontinuations in the group receiving 150 mg twice a day than in the placebo group) and increases in levels of liver aminotransferases were more frequent in the group receiving 150 mg of BIBF 1120 twice daily than in the placebo group. CONCLUSIONS In patients with idiopathic pulmonary fibrosis, BIBF 1120 at a dose of 150 mg twice daily, as compared with placebo, was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00514683 .).
A genetic algorithm for a workforce scheduling and routing problem

The Workforce Scheduling and Routing Problem refers to the assignment of personnel to visits across various geographical locations. Solving this problem demands tackling scheduling and routing constraints while aiming to minimise the total operational cost. This paper presents a Genetic Algorithm (GA) tailored to tackle a set of real-world instances of this problem. The proposed GA uses a customised chromosome representation to maintain the feasibility of solutions. The performance of several genetic operators is investigated in relation to the tailored chromosome representation. This paper also presents a study of parameter settings for the proposed GA in relation to the various problem instances considered. Results show that the proposed GA, which incorporates tailored components, performs very well and is an effective baseline evolutionary algorithm for this difficult problem.
Time-Intensity and the Composition of Consumption

Beckers theory of home production was the rst to systematically incorporate time in economic models, and the theory generated much empirical research in a wide variety of areas. However, the direct applications of Beckers home production theory in empirical research are scarce because of the innate immeasurability of commodities. In this paper, I recover unobservable commodities from the cost functions under certain assumptions about production technologies. Then, using the Philippine Bukidnon panel study of rural households, I test for the core of the Becker model: negative substitution e¤ects between a time-intensive and a goods-intensive commodity arising from wage increases. The estimates of the structural form as well as the reduced form relative demand between childcare, which represents a time-intensive commodity, and meal consumption, which represents a goods-intensive commodity, support the major predictions of the model (JEL: D13, J13, J22). Michigan State University, Department of Economics, 110 Marshall-Adams Hall, East Lansing, MI 48824. E-mail: chinym@msu.edu. I am indebted to Andrew Foster for his guidance and insight. I am grateful to Mark Pitt and Nancy Qian for their helpful comments and encouragement. I also thank Oded Galor, Vernon Henderson, Daniel Hamermesh, and Erik Thorbecke for their bene cial advice. Special thanks to Mee jin Cho, Delia Furtado, Chisoo Kim, Natsuko Kiso, Irina Paley, Doug Park, Almudena Sevilla-Sanz. All remaining errors are mine.
Newly diagnosed early breast cancer - an update on pre-operative assessment and staging.

BACKGROUND Most breast cancer seen in developed nations is diagnosed at an early stage and surgery is the recommended first line treatment in most cases. OBJECTIVE This article reviews the current approach and related evidence on pre-operative assessment of women with newly diagnosed breast cancer. It discusses the use of conventional assessment tools (mammography, ultrasound and needle biopsy) for staging the breast and axilla, the evidence relating to breast magnetic resonance imaging and the indications for staging investigations for distant metastatic disease. It highlights recent changes in practice, including areas of nonconsensus, and informs general practitioners on evolving issues in the pre-operative care of the newly diagnosed breast cancer patient. DISCUSSION Once a breast cancer diagnosis has been established, appropriate pre-operative evaluation to assess the extent of disease (locally and sometimes systemically) helps guide surgical management and decisions on adjuvant therapy.
PicoPet: "Real World" digital pet on a handheld projector

We created PicoPet, a digital pet game based on mobile handheld projectors. The player can project the pet into physical environments, and the pet behaves and evolves differently according to the physical surroundings. PicoPet creates a new form of gaming experience that is directly blended into the physical world, thus could become incorporated into the player's daily life as well as reflecting their lifestyle. Multiple pets projected by multiple players can also interact with each other, potentially triggering social interactions between players. In this paper, we present the design and implementation of PicoPet, as well as directions for future explorations.
Haemopoietic stem cells: spleen colony‐forming cells are normally actively proliferating

Abstract. The haemopoietic stem cells forming spleen colonies (CFU‐S) had on average 30 to 40% of cells engaged in the DNA synthesis in normal mice continuously over 4 years. A majority of experiments aimed at the suppression of the CFU‐S proliferation, which included suppression of the T‐lymphocytes by means of cyclosporin A or by adult thymectomy, administration of antibacterial and antifungal agents and maintainance of mice in a sterile environment, suppression of antibody‐producing cells by a successive administration of the bacterial lipopolysaccharide and cyclophosphamide and attempts to increase the total number of CFU‐S in the body through massive transfusions of bone marrow cells or by grafting plugs of the bone marrow under the kidney capsulae, have not been sufficiently effective. A transient suppression of CFU‐S proliferation occurred during recovery of the haemopoietic tissue from damage caused by cyclophosphamide. The results support the view that changes in CFU‐S numbers and in the proportion of them in DNA synthesis may be positively correlated when CFU‐S numbers fluctuate physiologically about their normal values. The failure to manipulate the CFU‐S proliferation rate easily suggests that proliferation of these cells may not be under a strong ‘switch on ‐ switch off’ control.
Temporal pole hypometabolism may be linked to a reduction of grey matter in temporal lobe epilepsy

In order to gain further insight into the pathophysiology of temporal pole hypometabolism, we decided to perform a voxel-based automated analysis of structural MRI in epileptic patients with or without temporal pole hypometabolism. After fully automated segmentation of cerebral grey matter from structural T1-weighted MRI scans, we applied the automated technique of statistical parametric mapping (SPM) to the analysis of grey matter of nine control subjects, and 18 patients with right medial temporal lobe epilepsy with (n = 13) or without (n = 5) significant temporal pole hypometabolism. Group comparisons between subject controls and epileptic patients with temporal pole hypometabolism showed a reduction of grey matter located into the superior part of the right temporal pole, the right hippocampus and the left parahippocampal gyrus. Epileptic patients without temporal pole hypometabolism did not exhibit temporal pole grey matter abnormalities. These findings suggest that a reduction of temporal pole neocortical grey matter might contribute to temporal pole hypometabolism in temporal lobe epilepsy.
Forecasting of Turkey natural gas demand using a hybrid algorithm

ABSTRACT The basis of the energy management constitutes the forecasting of the need for energy as much as accurate. In this study, a hybrid genetic algorithm-simulated annealing (GA-SA) algorithm based on linear regression has been developed and coded as software to forecast natural gas demand of Turkey. The linear models, which are constructed by using the amounts of natural gas consumption for years between 1985 and 2000 as dependent variable, and gross national product, population, and growth rate as independent variables, are used to forecast the amount of natural gas consumption for years between 2001 and 2009. Then, the forecasts are compared with real amounts of consumptions and are analyzed statistically. Consequentially, it is observed that the GA-SA hybrid algorithm made forecasts with less statistical error against linear regression. The models were used to forecast Turkey’s natural gas demand under two different scenarios for years between 2010 and 2030.
Effect of calyculin A on the surface structure of unfertilized sea urchin eggs.

Calyculin A, a potent inhibitor of type 1 and type 2A protein phosphatases, induces contractile ring formation when applied to unfertilized sea urchin eggs [Tosuji et al., 1992: Proc. Natl. Acad. Sci. USA 89:10613-10617]. We report here the elongation of microvilli in the unfertilized eggs exposed to calyculin A. The elongated microvilli and associated sperm-egg binding sites (egg receptor for sperm) then became concentrated into a constriction site corresponding to the cleavage furrow. The egg receptor for sperm was also in close connection to the microfilaments. Okadaic acid is another known inhibitor of protein phosphatase type-1 and type-2A. Its effect, however, is about a hundredfold feebler for type-1 phosphatase than type-2A. Even after treatment with okadaic acid, no change was observed, suggesting that these morphological changes were induced by calyculin A solely though its inhibitory effect on the type-1 protein phosphatase.
Living in deprived urban districts increases perinatal health inequalities

Objective: Analyses of the effects of place of residence, socioeconomic status and ethnicity on perinatal mortality and morbidity in the Netherlands. Methods: Epidemiological analysis of all singleton deliveries > 22 gestational weeks (871,889 live born and 5927 stillborn) from the Dutch National Perinatal Registry 2002–2006. Multiple logistic regression analysis was used to determine whether place of residence (deprived neighborhood, or not) contributed to the adverse perinatal outcome (defined as perinatal mortality, preterm birth, small for gestational age, congenital abnormalities or Apgar score <7, 5 min after birth), additional to individual pregnancy characteristics, demographic characteristics, ethnic background and socioeconomic class. Results: Incidence of adverse perinatal outcome was 16.7%. After adjustment the excess risk for perinatal mortality in deprived districts was 21%, for preterm birth 16%, for small-for-gestational age 11%, and for Apgar score <7 after 5 min 11%. Conclusions: Perinatal inequalities appear impressive in both urban and nonurban areas, with a significant additive risk of living in a deprived neighborhood. Excess risk for perinatal mortality generally outranges that for morbidity, suggesting both an etiological and prognostic pathway for neighborhood effects. A distinct pattern exists for congenital anomalies, for which first trimester adverse selection effects may be responsible.
A Conserved Mechanism for Steroid Receptor Translocation to the Plasma Membrane*

Multiple steroid receptors (SR) have been proposed to localize to the plasma membrane. Some structural elements for membrane translocation of the estrogen receptor α (ERα) have been described, but the mechanisms relevant to other steroid receptors are entirely unknown. Here, we identify a highly conserved 9 amino acid motif in the ligand binding domains (E domains) of human/mouse ERα and ERβ, progesterone receptors A and B, and the androgen receptor. Mutation of the phenylalanine or tyrosine at position–2, cysteine at position 0, and hydrophobic isoleucine/leucine or leucine/leucine combinations at positions +5/6, relative to cysteine, significantly reduced membrane localization, MAP and PI 3-kinase activation, thymidine incorporation into DNA, and cell viability, stimulated by specific SR ligands. The localization sequence mediated palmitoylation of each SR, which facilitated caveolin-1 association, subsequent membrane localization, and steroid signaling. Palmitoylation within the E domain is therefore a crucial modification for membrane translocation and function of classical sex steroid receptors.
Profiling of Chemonaive Osteosarcoma and Paired-Normal Cells Identifies EBF2 as a Mediator of Osteoprotegerin Inhibition to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis

Purpose: Osteosarcoma is the most prevalent bone tumor in children and adolescents. At present, the mechanisms of initiation, maintenance, and metastasis are poorly understood. The purpose of this study was to identify relevant molecular targets in the pathogenesis of osteosarcoma. Experimental Design: Tumor chemonaive osteoblastic populations and paired control normal osteoblasts were isolated and characterized phenotypically from seven osteosarcoma patients. Global transcriptomic profiling was analyzed by robust microarray analysis. Candidate genes were confirmed by real-time PCR and organized in molecular pathways. EBF2 and osteoprotegerin (OPG) levels were determined by real-time PCR and OPG protein levels were assessed by ELISA. Immunohistochemical analysis was done in a panel of 46 osteosarcoma samples. Silencing of EBF2 was achieved by lentiviral transduction of short hairpin RNA. Apoptosis was determined by caspase-3/7 activity. Results: A robust clustered transcriptomic signature was obtained in osteosarcoma. Transcription factor EBF2, a known functional bone regulator, was among the most significantly overexpressed genes. Immunohistochemical analysis showed that osteosarcoma is expressed in ∼70% of tumors analyzed. Because EBF2 was shown previously to act as a transcriptional activator of OPG, elevated levels of EBF2 were associated with high OPG protein levels in osteosarcoma samples compared with normal osteoblastic cells. Knockdown of EBF2 led to stunted abrogation of OPG levels and increased sensitivity to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis. Conclusions: These findings suggest that EBF2 represents a novel marker of osteosarcoma. EBF2 up-regulation may be one of the mechanisms involved in the high levels of OPG in osteosarcoma, contributing to decrease TRAIL-induced apoptosis and leading to TRAIL resistance. (Clin Cancer Res 2009;15(16):5082–91)
IMPLICATIONS OF SIMIAN RETROVIRUSES FOR CAPTIVE PRIMATE POPULATION MANAGEMENT AND THE OCCUPATIONAL SAFETY OF PRIMATE HANDLERS

Abstract Nonhuman primates can be naturally infected with a plethora of viruses with zoonotic potential, including retroviruses. These simian viruses present risks to both captive nonhuman primate populations and persons exposed to nonhuman primates. Simian retroviruses, including simian immunodeficiency virus, simian type D retrovirus, simian T-lymphotropic virus, and gibbon ape leukemia virus, have been shown to cause clinical disease in nonhuman primates. In contrast, simian foamy virus, a retrovirus that is highly prevalent in most nonhuman primates, has not been associated with clinical disease in naturally infected primates. Although it has been shown that human retrovirus infections with human T-lymphotropic virus and human immunodeficiency virus originated through multiple independent introductions of simian retroviruses into human populations that then spread globally, little is known about the frequency of such zoonotic events. In this article, exogenous simian retroviruses are reviewed as a concern for zoo and wildlife veterinarians, primate handlers, other persons in direct contact with nonhuman primates, and other nonhuman primates in a collection. The health implications for individual animals as well as managed populations in zoos and research institutions are discussed, the cross-species transmission and zoonotic disease potential of simian retroviruses are described, and suggestions for working safely with nonhuman primates are provided.
The Dimensions of Public Service Motivation and Sector Work Preferences

Public service motivation (PSM) is a needs-based approach to motivation. People may sate this need in different ways, including direct government service. This article investigates the relationship between individuals’ PSM and their work sector (pubic, nonprofit, or for-profit) preferences. It asks, “Does PSM affect an individual’s preference for the sector of the economy in which they would ideally be employed? ” Our findings indicate that PSM, measured in dimensional form, is a moderate indicator of an individual’s sector preference: as PSM increases (particularly, the Self-Sacrifice dimension), the attractiveness of working in the public and nonprofit sector, relative to the for-profit sector, also increases. Focusing on a preservice sample of undergraduate students allows us to conclude that PSM is a need people have prior to entering the workplace, and it may indeed drive whether an individual works in the government, nonprofit, or for-profit sector.