Malic acid production from renewables: a review

Malic acid derived from fossil resources is currently applied in the food and beverage industries with a medium global production capacity. However, in the transition from a fossil-based to a bio-based economy, biotechnologically produced l -malic acid may become an important platform chemical with many new applications, especially in the field of biopolymers. In this review, currently used petrochemical production routes to dl -malic acid are outlined and insights into possible bio-based alternatives for microbial l -malic acid production are provided. Besides ecological reasons, the possibility to produce enantiopure l -malic acid by microbial fermentation is the biggest advantage over chemical synthesis. State-of-the-art and open challenges concerning production host engineering, substrate choice and downstream processing are addressed. With regard to production hosts, a literature overview is given covering the leading natural production strains of Aspergillus, Ustilago and Aureobasidium, as well as Escherichia coli as the most important engineered recombinant host. The utilization of renewable substrates as an alternative to glucose is emphasized in particular as a key aspect for a competitive bio-based production. Out of the alternative substrates discussed in this review, the industrial side-streams crude glycerol and molasses seem to be most promising for large-scale l -malic acid production. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Regression of severe atherosclerotic plaque in patients with mild elevation of LDL cholesterol

BACKGROUND: Intensive risk factor reduction in patients with dyslipidemias and coronary atherosclerosis has been shown to result in alterations in coronary artery morphology and reduced clinical events. However, the impact of such interventions in populations with relatively normal levels of low-density lipoproteins (LDL) is unclear. METHODS: To test the hypothesis that intensive risk factor reduction results in angiographic regression in patients with only mildly elevated levels of LDL, 14 patients with angiographically proven coronary atherosclerosis were entered into the University of California Davis Coronary Artery Disease Regression Program and intensively treated with pharmacologic and nonpharmacologic interventions for 2 years. Quantitative angiography was performed prior to and after 2 years of therapy to determine changes in coronary artery diameter. RESULTS: As a result of this program, dietary fat intake was reduced by 58% and LDL fell from 120 +/- 7 mg/dL to 104 +/- 6 mg/dL (p = 0.05). The average diameter of the measured arterial locations (including all 53 stenoses and 292 nondiscrete regions) on study entry was 2.74 +/- 0.05 mm. After 24 months, there was a net increase in arterial diameter (regression) of +0.05 +/- 0.04 mm to 2.81 +/- 0.05 mm (p = 0.01). While there was no significant change in the average diameter of discrete stenoses, all 8 lesions > or = 50% initial diameter narrowing regressed, with a mean diameter change of + 0.2 mm. Conversely, only 1 of 8 mild lesions < or = 20% regressed, while 4 progressed. Intermediate lesions (20% to 50%, n = 37) had balanced progression and regression. CONCLUSIONS: When examined as a continuous variable, there was a significant linear correlation between initial lesion severity (% stenosis) and the extent of regression (mm). Therefore, risk factor reduction (dietary therapy, exercise, psycho-social counseling, and lipid lowering therapy) in patients with only mild dyslipidemia results in angiographic regression of more severe lesions (> 50% initial stenosis), but does not prevent progression of mild lesions (< 20%). These findings demonstrate that intensive risk factor reduction in patients with only mild elevation of lipids beneficially influences the morphology of the most severe lesions.     

Towards the automatic generation of software diagrams

The authors formulate the criteria for drawing dataflow diagrams and describe the placement and routing algorithms used in a system called MONDRIAN. A generalized approach to the question of software diagrams is proposed based on the authors' experience with MONDRIAN and a metasystem approach to the creation of CASE (computer-aided software engineering) environments. A formal approach to the definition of software objects and their graphical representation is given. The use of location constraints as a basis for generalized layout algorithms is discussed     

A peptide sequence from platelet factor 4 (CT-112) is effective in the treatment of type II collagen induced arthritis in mice

OBJECTIVE: Platelet factor 4 (PF-4) is a critical alpha chemokine in inflammation and injury responses, with multiple effects upon cellular activities. Discrete peptide sequences of the PF-4 molecule have been shown to retain biological activity. Our aim was to examine the influence of the PF-4 derived octapeptide (CT-112; TTSQVRPR) on type II collagen induced arthritis in mice, to determine if this peptide exhibited antiinflammatory properties. METHODS: DBA/1 mice were treated with CT-112 from either the time of immunization with type II collagen or from the initial onset of arthritis. RESULTS: CT-112 both prevented the development of arthritis in mice treated prophylactically and reduced progression of disease in animals treated therapeutically, and was active when delivered by either subcutaneous injection or oral gavage. No marked immunosuppressive effects were observed during CT-112 treatment, with only moderate decrease in antibody levels and mitogen responses. A significant reduction of the circulating levels of IL-1 was a consistent finding in mice treated therapeutically with CT-112. CONCLUSION: These data suggest PF-4 derived octapeptide exerts antiinflammatory effects of experimental arthritis in mice.     

Train Tracks and Confluent Drawings

Confluent graphs capture the connection properties of train tracks, offering a very natural generalization of planar graphs, and—as the example of railroad maps shows—are an important tool in graph visualization. In this paper we continue the study of confluent graphs, introducing strongly confluent graphs and tree-confluent graphs. We show that strongly confluent graphs can be recognized in NP (the complexity of recognizing confluent graphs remains open). We also give a natural elimination ordering characterization of tree-confluent graphs, and we show that this class coincides with the (6,2)-chordal bipartite graphs. Finally, we define outerconfluent graphs and identify the bipartite permutation graphs as a natural subclass.     

The effects of withholding feed and water on carcass shrinkage and meat quality in beef cattle

Eighty beef crossbred steers with an average weight of 493 kg (4·66 kg SD) were allocated at random to one of five treatments to assess the effects of withholding feed and water on carcass shrinkage and meat quality. The five treatments were: slaughter from the feedlot (T1); and 12, 24, 36 and 48 h periods without feed and water prior to slaughter (T2-5).Weights were taken of the live animal and the carcass to monitor shrinkage along with relevant meat quality measurements. There were no treatment differences (P > 0·05) in initial farm weight, but plant weight shrinkage increased from 31gkg(-1) for T1 to 106 g kg(-1) for T5. Warm carcass weight decreased (P < 0·05) from 278·8 kg for T1, to 270·7 kg for T3 and 261·9 kg for T5. Liver, alimentary tract components, hide and head decreased as a proportion of farm weight as time without feed and water increased. Muscle pH at 6 days post mortem was increased (P < 0·05) in T3-5 compared to T1, with the result that muscle colour became darker, and steaks had less drip loss. Shear values increased (P < 0·05) from 6·3 kg in T1 to 7·7 kg in T4 and T5 indicating an increase in muscle toughness as time without feed and water increased. It was concluded that steers lose live weight rapidly within the first 24 h without feed and water, and that these relatively short periods of time (24 h) can have detrimental effects on carcass shrinkage and muscle quality.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

Utilising semantic technologies for intelligent indexing and retrieval of digital images

The proliferation of digital media has led to a huge interest in classifying and indexing media objects for generic search and usage. In particular, we are witnessing a colossal growth in digital image repositories that are difficult to navigate using free-text search mechanisms, which often return inaccurate matches as they in principle rely on statistical analysis of query keyword recurrence in the image annotation or surrounding text. In this paper we present a semantically-enabled image annotation and retrieval engine that is designed to satisfy the requirements of the commercial image collections market in terms of both accuracy and efficiency of the retrieval process. Our search engine relies on methodically structured ontologies for image annotation, thus allowing for more intelligent reasoning about the image content and subsequently obtaining a more accurate set of results and a richer set of alternatives matchmaking the original query. We also show how our well-analysed and designed domain ontology contributes to the implicit expansion of user queries as well as the exploitation of lexical databases for explicit semantic-based query expansion.