CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.     

Discrete Time Non-Homogeneous Semi-Markov Reliability Transition Credit Risk Models and the Default Distribution Functions

This paper shows how to apply discrete time non-homogeneous semi-Markov processes (DTNHSMP) with an age index to credit risk. The idea is to consider the credit risk problem as a reliability model indexed by the age and in this way, many semi-Markov results could be adapted to describe credit risk problem. The default state is seen as a “non working state”. As the semi-Markov process is a generalization of Markov process, the presented model can be seen as a more general migration model. In fact, in semi-Markov environment the distribution function (d.f.) of the waiting time before a transition can be of any type and without the strong constraints of the Markov model. Furthermore, some results on the asymptotic behavior of the presented model are given. This permits the construction of the d.f. of the default random variable for each “working state”. An example, constructed manipulating some Standard & Poor’s (S&P) data, is presented.     

Optimal correlation attack on the multiplexer generator

The security of the well-known multiplexer generator with respect to correlation attacks on the data shift register is investigated. Apart from the basic correlation attack exploiting the bitwise correlation between the output sequence and any data input sequence, two new correlation attacks are introduced. One is based on computing the a posteriori probabilities and is statistically optimal, whereas the other makes use of the accumulated bitwise correlation to all data input sequences. It is theoretically argued and experimentally confirmed that the optimal attack requires a significantly shorter output sequence to be successful than the basic attack. The experiments also show that the less complex accumulated correlation attack requires a somewhat longer output sequence than the optimal attack.     

A polyfluoroalkyl imidazolium ionic liquid as iodide ion source in dye sensitized solar cells

We report on the use of a fluorinated imidazolium ionic liquid as a source of iodide ions in solvent-based electrolytes for DSSCs. Efficient dye regeneration and fast charge transport in the fluorinated electrolyte result in an overall improvement of the device performances compared to conventional hydrogenated ionic liquids.     

A ticket to ride: Education and migration from lagging areas

National policies may have heterogeneous effects at the regional level. When coming to programmes aimed at increasing human capital, worker mobility from poorer to richer regions can reduce the benefits of the policy for the former areas. We focus on Italy and estimate the impact of education on the probability of migrating from a lagging area to a leading one. Endogeneity is addressed by exploiting an increase in the minimum school-leaving age in an instrumental variable framework. We find that one additional year of education increases the probability to migrate by 1.7 percentage points (9% of the average migration rate).     

Searching for Inefficiencies in Exchange Rate Dynamics

This paper develops a new pair trading method to detect inefficiencies in exchange rates movements and arbitrage opportunities using a convergence/divergence indicator (CDI) belonging to the oscillatory class. The proposed technique is applied to 11 exchange rates over the period 2010–2015, and trading rules based on CDI signals are obtained. The CDI indicator is shown to outperform others of the oscillatory class and in some cases (for EURAUD and AUDJPY) to generate profits. The suggested approach is of general interest and can be applied to different financial markets and assets.     

A smartphone-based fall detection system

Falls are a major cause of injuries and hospital admissions among elderly people. Thus, the caregiving process and the quality of life of older adults can be improved by adopting systems for the automatic detection of falls. This paper presents a smartphone-based fall detection system that monitors the movements of patients, recognizes a fall, and automatically sends a request for help to the caregivers. To reduce the problem of false alarms, the system includes novel techniques for the recognition of those activities of daily living that could be erroneously mis-detected as falls (such as sitting on a sofa or lying on a bed). To limit the intrusiveness of the system, a small external sensing unit can also be used for the acquisition of movement data.     

Role of brown adipose tissue in thermogenesis induced by overfeeding a diet containing medium chain triglyceride

The role of brown adipose tissue in the mechanism of medium chain triglyceride (MCT)-induced thermogenesis was investigated. Under anesthesia, the interscapular brown adipose tissue (IBAT) was excised in male Sprague-Dawley rats, and the animals were fitted with gastrostomy tubes. After a 10-day recovery period, the animals were divided into two groups: one group received a diet containing MCT as 50% of calories, and the other group received an isocaloric diet containing long chain triglyceride (LCT). The diets were fed for 6 wk at a level of calorie intake that was 150% of the ad libitum intake of a parallel control group. During the last week of the study, resting and norepinephrine (NE)-stimulated O₂ consumption and CO₂ production were measured in a Noyons diaferometer. At the end of 6 wk, the animals were weighed and killed. The individual fat pads were dissected and weighed, and an aliquot of the right retroperitoneal fat pad was used to measure adipocyte size and number. The results showed that body weight and adipocyte size (but not adipocyte number) were significantly smaller in the MCT-fed compared to the LCT-fed animals. Resting as well as maximal NE-stimulated oxygen consumption values were significantly higher in the MCT-fed than the LCT-fed rats. It is concluded that the enhanced thermogenesis induced by MCT persists despite the absence of IBAT and that the phenomenon is likely related to more extensive oxidation of MCT-in contrast to LCT-derived fatty acids, thus leading to increased oxygen consumption, enhanced dissipation of energy as heat and diminished efficiency of weight gain and deposition of body fat. Presented at the symposium on “Specialty Lipids and Their Biofunctionality” at the annual meeting of the American Oil Chemists' Society, Philadelphia, May 1985.