This review paper discusses the role of haptics within virtual medical training applications, particularly, where it can be used to aid a practitioner to learn and practice a task. The review summarizes aspects to be considered in the deployment of haptics technologies in medical training. First, both force/torque and tactile feedback hardware solutions that are currently produced commercially and in academia are reviewed, followed by the available haptics-related software and then an in-depth analysis of medical training simulations that include haptic feedback. The review is summarized with scrutiny of emerging technologies and discusses future directions in the field.


Bob Greene shows us a side of Michael Jordan that doesn't make the sports page...the inside. Journalist and bestselling author Bob Greene stepped into Michael Jordan's world just as Jordan was reaching the apex of his talent and his fame. With Greene, Jordan let down his guard. In an extraordinary book that transcends sports biography, Greene takes the reader along with Jordan over two seasons with the Chicago Bulls, during glorious championship surges and trying personal moments. With rare insight, Greene reveals the person inside the icon: a man who makes millions but cannot go for a quiet walk around the block without getting mobbed, a man who competes ferociously on the court, but who performs some of his most remarkable and unexpected feats away from the limelight. Drawn from inside Michael Jordan's daily life, rich with the sound of Jordan's own voice, "Hang Time" is a startlingly candid and intimate story of time spent with a champion, and of the growing friendship between two men.


We explore various pitfalls and challenges in determining the equation of state $(w)$ of the dark energy component that dominates the universe and causes the current accelerated expansion. We demonstrated in an earlier paper the existence of a degeneracy that makes it impossible to resolve well the value of w or its time derivative with supernovae data. Here we consider standard practices, such as assuming that w is constant or greater than $\ensuremath{-}1,$ and show that they also can lead to gross errors in estimating the true equation of state. We further consider combining measurements of the cosmic microwave background anisotropy and the Alcock-Paczynski test with supernovae data and find that the improvement in resolving the time derivative of w is marginal, although the combination can constrain its present value perhaps to 20% uncertainty.


Does a state's use of indiscriminate violence incite insurgent attacks? Nearly all existing theories and empirical studies conclude that such actions only fuel insurgencies by provoking insurgent mobilization. This proposition is tested using a natural experiment that draws on random artillery strikes by Russian forces in Chechnya (2000-05) to estimate the impact of indiscriminate violence on subsequent insurgent violence. A difference-in-difference (DD) estimation method is adopted in which shelled villages are matched with similar non-repressed settlements over identical time periods to estimate treatment effects. The findings are counterintuitive. Shelled villages and their home districts (raiony) exhibit less post-treatment violence than control groups. In addition, commonly-cited "triggers" for insurgent retaliation, including the lethality and duration of indiscriminate violence, are either insignificant or negatively correlated with insurgent attack propensity.


The paper presents a new Russian-language instrument measuring existential fulfillment within the theory of 4 existential fundamental motivations developed by A. Langle. Based on phenomenological descriptions of the constructs and expert discussions, we developed an original Russian-language set of 94 items, which was validated in 2 online samples (N=818 and N=215). Using hierarchical cluster analysis and confirmatory factor analysis with cross-validation in an independent sample, we arrived at a set of 36 items grouped into 4 scales and 12 subscales (corresponding to theoretical prerequisites of fundamental motivations). The scales demonstrate acceptable reliability (α in the .79-.88 range, .93 for the general score). We sought evidence of convergent and discriminant validity of the scales by using correlational and multiple regression analyses of their associations with indicators of emotional, social, and psychological well-being, subjective happiness, satisfaction with life, basic psychological need satisfaction, self-esteem, internal locus of control, as well as alienation and psychopathology. The findings support the convergent validity of existential fulfillment indicators against well-being measures based on different theoretical approaches, as well as discriminant validity of specific existential fundamental motivation scales. The new instrument opens up new possibilities for empirical research in the field of existential psychology and, in a broader context, the psychology of self-actualization, well-being, and life satisfaction. The questionnaire can also be used in assessment, counseling, and psychotherapy.


A curious fusion between chlorite dismutase-like and antibiotic biosynthesis monooxygenase-like domains within a single open reading frame has been revealed by both sequence homology and structural modeling in Haloferax volcanii PitA and its homologues in other halophilic archaea. While this fusion may reflect an environmental adaptation to life in hypersaline environments and hence one specific to haloarchaea, PitA and its homologues may represent a paradigm of biologically-relevant interplay between these two distinct activities in accordance with the Rosetta Stone approach. Contact: firstname.lastname@example.com


We have examined, repeated and extended earlier numerical calculations of Berger and Moncrief for the evolution of unpolarized Gowdy cosmological models. Our results are consistent with theirs and we support their claim that the models exhibit AVTD behaviour, even though spatial derivatives cannot be neglected. The behaviour of the curvature invariants and the formation of structure through evolution both backwards and forwards in time is discussed.


The relationship between communication and education can be understood in both directions, exploring the role of communication in education as well as the one played by education in the communication field. First of all, both communication and education aim at promoting a change in the addressee, an habit change as it was meant by Ch.S. Peirce. In fact, the education of human beings could not be possible without communication, be it non verbal or verbal, and one of the most important goal/outcome of education is language acquisition through dialogue. Education is further required to acquire and master all the "technologies of the word", giving birth to media education, digital literacy activities and so on. Moreover, all kinds of communication may (should) be soundly integrated in educational activities, encompassing listening and dialogical settings - let us think, for instance, to counselling/learning and logo therapy - as well as one-to many communication (lectures), up to the use of printed, electric and electronic media. Every communication setting, strategy and technology has found in education a role as well as one of the most important test-beds. The article sketches a map of the aforementioned links between communication and education, and explores in more detail the role of ICTs in education.


Routability or wiring congestion in a very large scale integration chip is becoming increasingly important as chip complexity increases. Congestion has a significant impact on performance, yield, and chip area. Although advances in placement algorithms have attempted to alleviate this problem, the inherent structure of the logic netlist has a significant impact on the routability irrespective of the placement algorithm used. Placement algorithms find optimal assignments of locations to the logic and do not have the ability to change the netlist structure. Significant decisions regarding the circuit structure are made early in synthesis during the technology-independent logic-optimization step. Optimizations in this step use literal count as a metric for optimization and do not adequately capture the intrinsic entanglement of the netlist. Two circuits with identical literal counts may have significantly different congestion characteristics after placement. In this paper, we postulate that a property of the network structure called adhesion can make a significant contribution to routing congestion. We then provide a metric to measure this property. We evaluate the utility of adhesion as measured by this metric to estimate and optimize postrouting congestion early in the design flow. A heuristic for measuring adhesion is evaluated as well.


The results of an experimental study of two confined masonry walls and two reinforced masonry walls with reduced quantity of reinforcement are presented. The full scale walls were made of hollow concrete blocks and were tested with horizontal cyclic loads. The dimensions of the walls were 3650x2250 mm and the thickness of the walls was 140 mm. The cross-sectional area of horizontal reinforcement is 0.0003 times the gross-sectional area of the reinforced masonry wall. The cracking and damage patterns, strength and stiffness degradation and deterioration, energy dissipation capacity and displacement capacity after the cracking are analyzed. The conclusions are useful for the seismic design of one and two stories masonry dwellings.


Despite providing health care to others every day, people who work in a hospital are usually ignored about their healthy issue. This study is aimed to investigate the prevalence of sick building syndrome (SBS)-related symptoms among hospital workers. All participants in this study completed questionnaires during the year 2013. Indoor air pollutants, Carbon monoxide (CO), Carbon Dioxide (CO2), particulate matter (PM) and Volatile organic compounds (VOCs), as well as bacteria and fungi concentrations were recorded during sampling. Associations between SBS-related symptoms, individual characteristics, and chemical concentrations were evaluated by multiple linear regression. About 84% of the subjects suffered from at least one SBS-related symptom, among which the most frequently reported symptom was nasal symptoms, accounting for 66%. Chemicals such as CO2, PM, VOCs tended to be significantly associated with SBS-related symptoms. There are various effects depending on the type of chemicals present and whether the working spaces are open or confined.


The paper stresses the need for user-research and use studies at the individual library level; defines related terms and concepts like user, use, need, want, demand and requirement; reviews some important studies on use of library collections and interaction of scientists, engineers and technicians of libraries with their respective primary libraries. It enumerates the relationships found in past studies between characteristics of scientists, engineers and technicians and their use of library collections as well as their interactions with library. Finally, lack of sound use studies based on critical incident data in the country is pointed out.


Longlining operations for Dissostichus eleginoides off South Georgia were assessed for interactions with seabirds and the effectiveness of measures employed by CCAMLR to mitigate seabird mortality. Following an agreement between the Governments of the United Kingdom and Chile, a UK observer was placed aboard a Chilean longliner, the BF Cisne Verde, fishing in CCAMLR Subarea 48.3 during the 1996/97 season. In this study 61 lines were laid from March to May 1997 using the Spanish double-line method. In accordance with CCAMLR conservation measures, lines were set at night, weights (6-7 kg) were set at 50 m intervals along the line, all deck lights were extinguished and no offal was discarded during setting. A streamer line made to CCAMLR specifications was also used, except during an experiment that attempted to assess the effectiveness of the streamer line in mitigating incidental mortality of seabirds during night-time setting. Data were recorded during hauling using a randomised cluster sampling method, developed to allow representative data to be collected when 100% observer coverage could not be achieved: A total of 12 dead seabirds were recorded, giving an average mortality rate/night of 0.099 birds/l 000 observed hooks, substantially lower than other vessels fishing around South Georgia during the same period. Mortalities consisted of nine white-chinned petrels, two black-browed albatrosses and one unidentifiable bird caught on hooks. One giant petrel was also killed as a result of flying into the side of the vessel. Generally, few birds were seen following the vessel during setting operations. During April, however, large numbers of white-chinned petrels were seen occasionally, and large numbers of black-browed albatrosses were seen when the moon was full. Live birds were observed to become caught on hooks during hauling on 23 occasions; all birds were released alive. Black-browed albatrosses concentrated on taking returning bait off the line and accounted for 18 birds caught; giant petrels concentrated on taking discarded offal, and accounted for five birds caught.


The still living ancient festivals which are mysterious, colourful and fun evolved in course of time due to the highest popularity of the paramount deities belonging to the two great religions: Hinduism and the Buddhism. Their rites and rituals possess the background of interesting myths, delightful legends, and captivating folktales. Every year, the Newars celebrate wonderful fairs and festivals on different auspicious days in Bhaktapur. Every festive event of Bhaktapur has its own specialties. This study examines myths and current practice of Biska Jatra in the cultural backdrop of Bhaktapur from the perspective of semiology. The common belief is that celebrating the festival will ward off evil spirits and dangers, boost growth in agriculture production and the economy; maintain peace and prosperity and ensure the protection of the country from the outside invaders. This study argues that the celebration of Biska Jatra depicts its rationality and significance in the socio-cultural lives of the residents of Bhaktapur.


Background: In 2018, malaria produced an estimated 272,000 deaths in children <5 years of age, accounting for 67% of all malaria deaths worldwide, with a majority in the WHO African Region. Malnutrition is an important risk factor for malaria. Wasting, Stunting and Underweight are crucial indicators of malnutrition. Annually, 14 million children <5 are classified as wasted and 59 million children are classified as stunted.
Objective: The objective of this study is to determine the association between each of the major manifestations of severe malaria (SM) and nutritional parameters – weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) – in children from the Ugandan cities Mulago and Jinja.
Methods: To assess differences in WAZ, HAZ, and WHZ by the five types of SM and community controls (CC), we evaluated Z-scores from children <5 years old enrolled in a prospective cohort study (NDI, Neurodevelopmental Impairment in Children with Severe Malaria) at enrollment and 12-month follow-up.
Results: WAZ and WHZ at baseline were significantly lower among SM groups than in CC (p<0.001), but there were no significant differences observed at 12-month follow-up. There were no major differences in HAZ between the SM and CC groups. WAZ and HAZ at baseline were significantly lower among High Mortality (HM) versus Low Mortality (LM) groups (p<0.01). At 12-month follow-up, HAZ remained significantly lower in HM versus LM (p<0.01). There were no major differences in WHZ between the HM and LM groups. Compared to those who survived, the 27 children who died had significantly lower WAZ (p<0.05), but no major differences in HAZ or WHZ.
Conclusion: Underweight, stunting, and wasting may be risk factors for SM. Overall, a more comprehensive understanding of how SM elicits adverse effects in children is necessary. Nutrition intervention programs must be implemented to prevent child stunting, wasting, underweight, and mortality.


Small land owners are now faced with multiple challenges. Apart from their daily survival, they confront an often fragile environment, consequence of either years of single-crop farming or climate change, drought, poor quality yet expensive seeds, and scarcity of land. Needless to say, addressing these issues requires a holistic approach, where social, economic, community, and policy measures have to be considered. Rare are the programs able to join these spheres in a symbiosis, especially when it comes to gathering all the key actors. Through recognizing the difficult path ahead, Southeast Asian civil society organizations have taken crucial initiatives to reinvigorate the agricultural practices, thus protecting the fragile biodiversity while launching capacitybuilding processes with farmers. The Community Biodiversity Development and Conservation–Biodiversity Use of Conservation in Asia Programme (CBDC-BUCAP), conceptualized and implemented by SEARICE, is one of such initiatives. This article offers a comprehensive assessment of the nature of and the work undertaken by CBDCBUCAP, presenting an overview of its components, participants, contributions, main results, and the challenges to be addressed in the future.


The precision of tile image edge detection has great influence on the dimension detection and defect detection of tile. A parallel model of Back-Propagation (BP) neural network for edge detection of binary image was proposed in this paper, and it was applied to edge detection of gray image. It solved the problem that the convergence speed was too slow to meet the need of training if the BP neural network was used directly to edge detection of gray image because a too huge training sample set was needed. The BP neural network was optimized and solved the problem of unstable detection precision for tile dimension detection. This parallel model was applied to dimension and defect detection of tile, and the precision and speed can meet the requirement of detection precision in tile factories.


This research has been an art-based practice-led project focused on Chinese "inside painting" in glass art. It has attempted to create a "new model" for Chinese traditional inside painting through the creation of contemporary glass artworks. This is timely because Chinese academic glass teaching is emerging in universities, and cast glass techniques dominate the curriculum. The research offers an example of how traditional methods might be revitalized by one artist to extend the options for Chinese University glass teaching. Potential recipients are glass artists and students as well as curators and collectors.
This research mainly used studio-based art practices, inspired by traditional inside painting of Chinese snuff bottles, traditional Chinese painting and calligraphy, influenced by Taoism, together with Western glass painting, printing and calligraphy in order to reduce some of the existing limitations of traditional methods.
The methods of glass making for this research covered blowing, casting, flame work, fusing, slumping, incorporating "outside" painting combined with "inside" painting, and printing combined with inside painting.
Traditional inside painting techniques have developed over more than 200 years into a popular form of Chinese folk art, often based on glass snuff bottles with painted decoration on the inside. The craftsmen who make these pieces usually pay more attention to inside painting skills and overlook their own artistic expression. The designs used tend to be repetitive and copies of existing designs from other media such as ink painting or photographs. In this research, a body of inside painted glass works was produced to show how the glass form and painted content were combined. This work also helped to establish possible ways to reduce the limitations of traditional inside painting of Chinese snuff bottles.
Contextual aspects were supported by study visits to key collections and conferences, and interviews with other makers and collectors. It is hoped that this research will promote the development of traditional inside painting and lead to inside glass painting developing as a strand of the contemporary Chinese glass arts.


Intravascular ultrasound imaging offers the potential to provide more detailed information about vessel and lesion morphology and physiology than is currently available from angiography. The greatest impact of intravascular ultrasound upon clinical decisions may be in the area of cardiac and vascular interventions. To evaluate the utility of intravascular ultrasound, we prospectively studied 45 patients, 11 of whom underwent interventional procedures. Intravascular ultrasound imaging was performed before and after interventions using a 20 MHz, mechanically rotating transducer on either 6.5 Fr or 8.0 Fr catheter systems. Interventions included seven peripheral vessel balloon angioplasties (Femoral artery‐two, Renal artery‐two, Arteriovenous fistula‐two, Aortic coarctation‐one), two Femoral artery rotational atherectomies, and two balloon valvuloplasties (Pulmonic valve‐1, Mitral valve‐1). Intravascular ultrasound and digital angiography provided similar information about vessel size. However, morphological information about the vessel wall, plaque composition, plaque topography, luminal thrombus, and vessel dissections was better appreciated by intravascular ultrasound. Intravascular ultrasound was determined to have provided unique and clinically useful information in 10/11 (91%) interventions. These preliminary data illustrate the potential value of intravascular ultrasound for the evaluation of the vascular system and in particular its value in interventional procedures.


OBJECTIVES: To evaluate long term intraocular pressure (IOP) following phacoemulsification with intraocular lens implantation in glaucoma and normal patients.

MATERIAL AND METHODS: A retrospective analysis of 208 patients who had undergone phacoemulsification by the same surgeon at Panyananthaphikkhu Chonprathan Medical Center between February 2011 and February 2015. The patients were divided into 3 groups: no glaucoma (NG), primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Preoperative and postoperative best-corrected visual acuity (VA), IOP, and the number of glaucoma medications were recorded. IOP was evaluated before surgery and post-surgery for 1 month, 3 months, and last follow-up (mean 40 months). Repeated measure ANOVA and Post hoc by Scheffe test was used to compare IOP between 3 groups over time. Paired t-test was conducted to determine the relationship between preoperative IOP and postoperative IOP. The p-value of less than 0.05 was set for statistically significant.

RESULT: There were 86 patients in the NG group, 61 patients in the POAG group, and 61 patients in the PACG group. The first month saw the mean IOP significantly decrease in all groups (p < 0.001): NG group decreased 2.06 ± 2.21mmHg, POAG group 2.97 ± 3.25 mmHg, and PACG group 3.18 ± 2.77 mmHg. At 3 months the mean IOP was significantly decrease in all group(p < 0.001):NG group decreased 2.44 ± 2.14 mmHg, POAG group 2.72 ± 2.73 mmHg, and PACG group 3.51 ± 2.78 mmHg. At the final follow-up visit the mean IOP still significantly decrease in all group (p < 0.001): NG group decreased 1.45 ± 1.96 mmHg, POAG group 2.17 ± 2.98 mmHg, and PACG group 3.32 ± 2.84 mmHg. Eye with higher preoperative IOP has the greatest IOP- lowering effect. The number of glaucoma medication slightly decreased even though they are both the groups of open and closed angle (p = 0.002 VS p < 0.001). Visual acuity was significantly improved after phacoemulsification in all group.

CONCLUSION: Phacoemulsification not only improves the visual acuity but also provides a long term significant decrease in IOP and glaucoma medication. This IOP-lowering effect is proportional to preoperative IOP.


OBJECTIVE
The aim of this in vivo study was to compare the performance of light-emitting diode (LED)- and laser fluorescence (LF)-based devices with that of visual inspection (VI) in the diagnosis of occlusal caries.

METHODS
A total of 156 occlusal surfaces were investigated. Each occlusal surface was assessed with LED- and LF-based devices after a VI was performed. Pit and fissure opening was applied to the occlusal surfaces in which opacity or discoloration was distinctly visible after airdrying. The inter-examiner reliability of caries examination was assessed using the weighted κ statistics. The sensitivity, specificity, and accuracy of occlusal caries diagnosis using these methods were calculated according to the appropriate thresholds.

RESULTS
Acceptable inter-examiner agreement was found for the LED- and LF-based devices and VI (κ=0.61, κ=0.76, and κ=0.87, respectively). Higher specificity values were achieved at a T2 threshold for the LF-based device (0.76 and 0.80) and at a T1 threshold for the LED-based readings (0.60 and 0.62) and VI (0.90 and 0.93) for both observers. With regard to VI, higher sensitivity values were found at both thresholds for the two observers in comparing the three caries detection methods (0.98 at T1 and 0.96 at T2). The accuracy values for T1 were higher than those for the T2 values, for all three caries detection methods.

CONCLUSIONS
Caries lesions may be detected more accurately than clinically sound areas by both caries detection devices.


Nitrogen-doped graphene (NG) has been fabricated and used as a carbon matrix for sulfur impregnation to construct cathodes for lithium–sulfur (Li–S) batteries. Atomic layers of TiO2 were further deposited on the electrode and the thickness was controlled by adjusting the number of deposition cycles to 0, 5, 20 and 40. The results showed that all the surface modified electrodes demonstrate high capacity, good rate capability, and enhanced cyclability compared to the bare electrode. Specifically, the electrode contained 59% (by weight, wt%) sulfur and with the addition of 20 cycle-TiO2 it demonstrated a superior boost in the active sulfur utilization (discharge capacity: 1374 mA h g−1 at 0.1C). It also delivered initial discharge capacity up to 1069.5 mA h g−1 and 918.3 mA h g−1 after 500 cycles at 1C with an average coulombic efficiency of about 99.7%. Moreover, the capacity retention increased from 42% to 61% from 0.1C to 4C with the addition of 20 cycle-TiO2. The improved electrochemical performance could be attributed to the on-site TiO2 absorption for polysulfide retention as well as the charge transfer enhancement. Theoretical calculations revealed that TiO2 exhibits a strong binding energy for lithium polysulfide species. These results suggest that the TiO2 modified NG has potential to be used as a cathode for high-performance Li–S batteries.


A halo merger tree forms the essential backbone of a semi-analytic model for galaxy formation and evolution. Recent studies have pointed out that extracting merger trees from numerical simulations of structure formation is non-trivial; different tree building algorithms can give differing merger histories. These differences should be carefully understood before merger trees are used as input for models of galaxy formation. We investigate the impact of different halo merger trees on a semi-analytic model. We find that the z = 0 galaxy properties in our model show differences between trees when using a common parameter set. The star formation history of the universe and the properties of satellite galaxies can show marked differences between trees with different construction methods. Independently calibrating the semi-analytic model for each tree can reduce the discrepancies between the z = 0 global galaxy properties, at the cost of increasing the differences in the evolutionary histories of galaxies. Furthermore, the underlying physics implied can vary, resulting in key quantities such as the supernova feedback efficiency differing by factors of 2. Such a change alters the regimes where star formation is primarily suppressed by supernovae. Therefore, halo merger trees extracted from a common halo catalogue using different, but reliable, algorithms can result in a difference in the semi-analytic model. Given the uncertainties in galaxy formation physics, however, these differences may not necessarily be viewed as significant.


Metal foams are two-phase compounds of a gas and a solid with several interesting physical and mechanical properties; in particular they have very low density, good rigidity, excellent energy absorption, high vibration damping. At now, the final shape of foamed devices is directly obtained through the foaming process itself and no further shaping steps are expected. Anyway, the plastic formability of metal foams, in order to both characterize the material itself and to produce more complex parts, seems to be useful for several industrial applications. Since metal foams are quite new products, the basic aspects ruling plastic deformation processes are still partially unknown and FEM methods may represent a valid tool for deepening these topics. This work deals with the formability of Aluminum Foam Sandwich (AFS) panels and it is focused on the FEM simulation of a compression processes. A numerical model was set up by using the FEM code Deform 2D v10.1. Foam behaviour was simulated by means of a compressible (porous) material model and the foam cracking was simulated using a damage model based on the foam density parameter. Some FEM routines were implemented into the FEM code to take into account both the non-homogeneous distribution and the strain hardening effect of the foam cells. An experimental campaign based on the compression of AFS panels made of close cells foam was carried out to fine tune and to validate the model. In particular, experimental data regarding load stroke curves and foam density were used to optimize the material description. An innovative solution, based on a non-linear relation between foam density and effective strain of the foam, was implemented into the FEM code.


Policy Diffusion and Drinking Water Services in Latin America, 1980-2014 Florence Larocque Understanding how domestic institutions and actors interplay with international and foreign influences is key not only to understand the politics of decision-making in the globalized world we live in, but also to understand why global policies – or policies promoted by transnational and international actors – may (or may not) be implemented and have the intended effects "on the ground." This dissertation sets to disentangle the all too often conflated parts of these dynamics by separately addressing the domestic processes of adopting, enforcing, as well as, in certain cases, preparing policy change influenced from abroad. It does so through the lens of the politics of drinking water and sanitation in Latin America from 1980 to 2014 and consists in three independent papers. The first paper addresses the diffusion of politicized policies, and more precisely the privatization of drinking water and sanitation services. This paper highlights one overlooked dimension of policy diffusion processes and more specifically of privatization processes: the preparatory measures adopted (or not) by governments prior to privatization. It suggests that the ability of governments to adopt gradual preparatory measures depends on the time horizon of privatization deciders and the political cost this preparatory gradual policy change may entail for the process. Theoretically, it contributes to the neo-institutionalist literature by adding a "preparatory" type of change to the existing framework of gradual institutional policy changes. Substantively, it underlines the redistributive consequences of privatization processes and the political dynamics behind the level of political risk these reforms may entail. The second and third papers underline the multifaceted effects of state capacity on policy diffusion for non-politicized (or technical) policies through the empirical analysis of the domestic adoption and implementation of drinking-water quality standards following the promotion of the World Health Organization's drinking-water quality guidelines. The second paper argues that strong state capacity tends to limit the adoption of a diffused policy that represents a strong domestic challenge. It contributes to the institutionalist literature by underlining the relevance to compare and measure state capacity on the basis of its resources (required to project its power), rather than on its ends or outcomes (which depend on the political choices that were made by the state). The third paper presents the other side of the coin of the impact of state capacity on diffusion of non-politicized policies, at the implementation step. At this step, strong state capacity gives the capacity to extensively implement a diffused policy, but implementation will remain partial if there are no external pressures on the sector. In weak states, policy diffusion can be both windowdressing and frame-shaping, depending on political dynamics. To be frame-shaping, it needs a sustained foreign capacity support (that can compensate for the weakness of the state) and strong external pressures. Overall, this thesis disentangles the policy diffusion process by highlighting that receiving states and actors are not only passive agents but also proactive ones, regarding the adoption, enforcement, and preparation of policy changes influenced from abroad. It also contributes to the understanding of two dimensions of water reforms in Latin America largely overlooked by the literature and policy studies: measures lessening the privatization shock and drinking-water quality standards. These issues, less salient than strongly politicized ones (like privatization itself), are as consequential in the life of states and their citizens, especially for their health and wellbeing.


In this study, effects of adhesive and additive's type and ratio on burning characteristics of particleboard (PB) added glass wool (GW) and rock wool (RW) were researched. PB's furnish was derived from 50% Crimean pine, 30% Eastern Black Sea oak, 15% quaking aspen, and 5% residues of wood machining, and moisture content of furnish was 1.5 to 3%. Seventy PBs with 0.64 g/cm3 density, urea formaldehyde (UF)/melamine formaldehyde (MF) fixed amount, 14 mm thickness, 45x45 cm2 dimensions and 10%, 15%, 20% SW/GW additives were produced. The 150 oC pressing temperature with 25 kg/cm2 compression pressure was constant. Burning tests for determination of ignition time, flaming combustion temperature, flaming combustion duration, smoldering combustion duration, and mass loss during burning were made according to DIN4102 standards. According to the results of the tests, adhesive type did not affect ignition time and mass loss. While flaming combustion temperature of PB with UF was 19% higher, flaming combustion duration and smoldering combustion duration was 32% and 29% lower than those of PB with MF, respectively. While ignition time of PB with GW was 50% higher than that of PB with RW, changes in burning properties were similar for both PBs. An increase in the content of GW and RW affected burning properties of PB positively and an increase of ignition time up to 196% were obtained.


Recent research in robust optimization has shown an overfitting-like phenomenon in which models trained against adversarial attacks exhibit higher robustness on the training set compared to the test set. Although previous work provided theoretical explanations for this phenomenon using a robust PAC-Bayesian bound over the adversarial test error, related algorithmic derivations are at best only loosely connected to this bound, which implies that there is still a gap between their empirical success and our understanding of adversarial robustness theory. To close this gap, in this paper we consider a different form of the robust PAC-Bayesian bound and directly minimize it with respect to the model posterior. The derivation of the optimal solution connects PAC-Bayesian learning to the geometry of the robust loss surface through a Trace of Hessian (TrH) regularizer that measures the surface flatness. In practice, we restrict the TrH regularizer to the top layer only, which results in an analytical solution to the bound whose computational cost does not depend on the network depth. Finally, we evaluate our TrH regularization approach over CIFAR-10/100 and ImageNet using Vision Transformers (ViT) and compare against baseline adversarial robustness algorithms. Experimental results show that TrH regularization leads to improved ViT robustness that either matches or surpasses previous state-of-the-art approaches while at the same time requires less memory and computational cost.


Public attitudes towards the police have received considerable attention over recent years as politicians and policy makers have emphasised the importance of public confidence in policing (Home Office 2009a; Home Office 2010c). Academic interest has also been strong; scholars have produced evidence identifying a wide range of correlates of confidence in policing and putative causal mechanisms underpinning it. However, what is missing from this evidence base is a consideration of the way in which confidence might be shaped by the strategies the police employ, the organisation of the police and their effectiveness at preventing and solving crime. Moreover, by focusing on the ways in which confidence differs between groups, academics have neglected to empirically consider the way in which confidence has changed over time and the factors that might account for such changes. Using a variety of data sources and advanced quantitative methods to address these gaps in knowledge, the thesis finds that the public lose confidence in the police if the volume of crime and disorder is either high, or thought to be high. The degree to which the police are effective at solving crimes, the manner in which they are thought to behave during encounters with the public and the frequency with which they are perceived to patrol the streets were also found to be important factors in shaping confidence. It is notable, in light of recent police cuts, that the numbers of police officers employed were not associated with confidence in policing, although this is not to say that such cuts will not have indirect effects on confidence through their potential impacts on crime, crime detection, police visibility and so on. Finally, the thesis finds less clarity surrounding the role played by worry about crime, victimisation and perceptions of social cohesion and informal social control in shaping public confidence in policing, the use of different methods and data producing varied results.


Microinjection is an effective technique to introduce foreign materials into a biological cell. Although great developments have been achieved, a full understanding of the mechanical response of biological cells to injection operation remains deficient. In this paper, a mechanical model based on membrane theory is proposed. This model utilizes the Mooney-Rivlin material to model the deformation of biomembrane. The relationship between the injection force and the deformation of biological cells is established through the quasi-static equilibrium equations, which are solved by the Runge-Kutta numerical method. To verify the mechanical model, experiments are performed on microinjection of zebrafish and medaka embryos. It is demonstrated that the modeling results agree well with the experimental data, which shows that the proposed model can be used to estimate the mechanical properties of cell biomembranes.


The effect of 3-(4-pyridyl)-1,2,4-triazolyl-5-mercaptoacetic acid morpholinium salt (rumosol) and potassium salt (drug 2) on the liver microsomal reductase activity was studied in adult (aged 10-12 months) and old (22-25 months) Wistar rats under immobilization stress conditions. In the group of adult rats, both drugs showed comparable moderate inhibiting effect. In the group of old rats, rumosol injections produced the reductase activation up to a level characteristic of the intact old animals.


The proton exchange membrane fuel cell (PEMFC) has many advantages, such as low operating temperature, fast reaction, and high energy density, etc. It is a very potential energy source. During battery operation, PEMFC will produce a large amount of water in the catalyst layer where the reaction occurs. The catalyst layer and gas diffusion layer (GDL) inside the battery are made of porous media. The water produced during the reaction will be discharged through these porous media structures, but the narrow gaps of the porous media structures will complicate the process. For example, too much water will flood the internal structure of the battery, making liquid water unable to drain smoothly. The above process may cause the reaction rate of the battery to decrease or even stop. Studying and understanding the water transportation process inside PEMFC is of great help in solving the above problems. Lattice Boltzmann method (LBM) is a promising numerical method for simulating the flows in porous media. Compared with the traditional CFD method, the lattice Boltzmann method (LBM) can deal with the pore structure of fine-scale better. In this paper, the lattice Boltzmann method (LBM) is employed to simulate the flow in the PEMFC. In order to reconstruct the porous media structure in PEMFC, the numerical reconstruction technique is used to generate porous media structures with different porosity. By simulating the flow of water in porous media, the transport laws of water in different porosity rates can be obtained. It provides a reference for improving the operating efficiency of proton exchange membrane fuel cells.


While there has been significant study of the relationship between police legitimacy and its key antecedents - procedural justice (PJ) and police effectiveness (PE) at the individual level, little attention has been paid to what impacts general evaluations of PJ and PE. Our paper focuses on these perceptions at places. Our analyzes utilize survey data collected on 447 street segments in Baltimore City, MD, in two waves. We first used EFA to determine the latent structure of PJ and PE measures. We then used mixed effects OLS regression modeling techniques to examine the antecedents of a "scorecard" of perceptions of the police. The results of the EFA show a single latent structure that we term the scorecard for PJ and PE. While we find that experiences with the police and street conditions that the police are presumed to impact influence the scorecard, street conditions that are less likely to be influenced by police (collective efficacy and concentrated disadvantage) also have strong influence. Both the research and policy-oriented literature often view the police as primarily responsible for their public image. Our data suggest that at the place level, such perceptions are also strongly impacted by factors primarily outside police influence.


This paper explores the state of the art of m-banking in Germany. It initially presents a brief discussion of the main characteristics of German banking practices, which is followed by an overview of the mobile services offered by the top 100 banks in the country. In addition, a detailed analysis of the m-services offered by Postbank, Hamburg's Saving Bank, and the DZ Bank is presented. Finally, a discussion of the results is guided by a comparison with the findings obtained in previous studies undertaken in Germany, Japan and New Zealand. The paper concludes with a discussion about the future of mobile banking in Germany.


The aim of this article is to present an analytical history of the Attahashi family of Turkish ancestry by illustrating its genealogy, whose members claim to be descendants of a Turkish ruler who is supposed to have arrived in Aceh in the late decades of the 16th or beginning of the 17th century. This attempt considers the connection to Sungai Iyu partly aligned with the eco-political developments in the 19th century and beginning of the 20th century. According to the argumentation of the current generation of the family, some individuals in the family became local rulers in Lam Kabeu and Sungai Iyu during the last century of the Sultanate of Aceh Darussalam. The relevant data, which sheds new light upon the traces of the Turkish existence in the region, has been acquired from various authentic written documents, oral information from various individuals including family members, and observations in field trips throughout the last decade. During the research, the author has put all his efforts to classify and comparatively examine the data from the various versions of relevant manuscripts, collected from Banda Aceh, Aceh Besar, Sungai Iyu and Medan, with each other.


Hepatic microsomal testosterone/androstenedione 2 alpha-hydroxylase (i.e., cytochrome P450(2)alpha) was purified from female CD-1 mice. Protein purification was monitored in eluates from Fractogel, DEAE-sephacel, and hydroxylapatite columns at heme absorbing 417 nm and by cytochrome P450 content, reactivity to a monoclonal antibody against female-specific rat cytochrome P450 2C12, and testosterone 2 alpha-hydroxylase activity. The catalytic activity of the purified cytochrome P450(2)alpha, exhibiting a high degree of regioselectivity and stereospecificity, was basically restricted to the 2 alpha-hydroxylation of testosterone and androstenedione; representing > 96% and > 92% of these respective metabolites. Polyclonal antibodies against cytochrome P450(2)alpha exhibited a dose-dependent and very selective inhibition of testosterone 2 alpha-hydroxylation. The specific cytochrome P450 content of the purified cytochrome P450(2)alpha fraction was 12.06 nmol/mg protein. The specific testosterone 2 alpha-hydroxylase activity of the purified protein was 14 nmol/min/nmol cytochrome P450, which was about 60-fold higher than the respective microsomes. The apparent subunit molecular weight of cytochrome P450(2)alpha was 51,000 and the protein appeared as a single band on sodium dodecyl sulfate polyacrylamide gels. The amino-terminal sequence analysis indicates that cytochrome P450(2)alpha is a member of the murine cytochrome P450 2d family.


Large amounts of nuclear waste await final disposal worldwide. A combination of waste overpacks (e.g. metal canisters, concrete), engineered barriers such as bentonite, and natural barriers such as clay rocks, constitutes the elements of the so-called " multiple-barrier system " between the waste matrix and the biosphere. The number, types and assigned safety functions of these various barriers depend on the chosen repository concept, the waste form, the radionuclide inventory in the waste, the selected host rock, the hydrogeological and geochemical settings of the repository site, etc.(Apted and Ahn, 2010). These barrier properties will evolve with time in response to the physical and chemical interactions between the various constituents of the barriers and the surrounding environment. Consequently, predicting how these properties evolve is of prime importance for performance and safety evaluations of the repository concepts. As a prerequisite, initial properties of the materials used in the disposal have to be understood, to better predict their long term behavior. Although micro imaging techniques are more and more sophisticated and powerful (Gaboreau et al., 2016), few techniques allow in-situ characterization of both the evolution of the different phases's mineralogy and their 3D spatial arrangement. To tackle this issue, X-Ray diffraction computed tomography (XRD-CT, see Fig1) that allows to record in each voxel of the recorded volume an X-ray diffraction pattern, has been successfully applied to investigate hydration and microstructural development in cements (Voltolini et al., 2013). Here we present results obtained by synchrotron XRD-CT on a cement paste formulation, which is constituted of blended Portland, fly ash, blast furnace slag cement (Chen et al., 2012), foreseen to be used for nuclear waste disposal application. The mineralogy (including spatial distribution) of a cured cement paste and of a cement paste undergoing in-situ and time-resolved hydration will be compared and discussed. In addition, special care will be taken to analyze the evolution of cement porosity as a function of time and of associated spatially-and time-resolved carbonation mechanism.


This paper introduced a straightforward and effective chromatographic data pre-processing method developing for utilization prior to chemometric analysis of large metabonomic dataset arising from high performance liquid chromatography. Nucleotides chromatographic fingerprinting in human urines was employed to validate the proposed method. Performance for discrimination cancer samples from healthy urinary sample with principal component analysis was advanced by this method. The first and second principal components could discriminate the two groups by a straight line with precision rate of 75% for cancer samples and 92% for normal samples. Using unprocessed data only 50% cancer samples could be discriminated from healthy cluster. This method was proved to be an effective chromatographic data pre-processing procedure in metabonomics


Human vaccinia-related kinase (VRK) 1 is a novel serine-threonine kinase that regulates several transcription factors, nuclear envelope assembly, and chromatin condensation and is also required for cell cycle progression. The regulation of this kinase family is unknown. Mass spectrometry has permitted the identification of Ran as an interacting and regulatory protein of the VRK serine-threonine kinase activities. The stable interaction has been validated by pulldown of endogenous proteins as well as by reciprocal immunoprecipitations. The three members of the VRK family stably interact with Ran, and the interaction was not affected by the bound nucleotide, GDP or GTP. The interaction was stronger with the RanT24N that is locked in its inactive conformation and cannot bind nucleotides. None of the kinases phosphorylated Ran or RCC1. VRK1 does not directly interact with RCC1, but if Ran is present they can be isolated as a complex. The main effect of the interaction of inactive RanGDP with VRK1 is the inhibition of its kinase activity, which was detected by a reduction in VRK1 autophosphorylation and a reduction in phosphorylation of histone H3 in residues Thr-3 and Ser-10. The kinase activity inhibition can be relieved by the interaction with the constitutively active RanGTP or RanL43E, which locks Ran in its GTP-bound active conformation. In this complex, the interaction with VRK proteins does not alter the effect of its guanine exchange factor, RCC1. Ran is a novel negative regulator of nuclear VRK1 and VRK2 kinase activity, which may vary in different subcellular localizations generating an asymmetric intracellular distribution of kinase activity depending on local protein interactions.


The aims of this study were to evaluate the dissolution performance of solid dosage forms using the open and closed modes of the FTC Apparatus 4 under different flow rates and provide examples to demonstrate the advantages of the FTC method, in particular the possibility of changing the pH during experiments, in studying the release mechanisms of extended-release products. Immediate-release (IR) paracetamol and extended-release (ER) theophylline formulations were used in this study. Results from commercially available IR paracetamol tablets using FTC Apparatus 4 have shown similar dissolution behavior in the closed and open systems, reflecting well-maintained apparent sink conditions and controlled hydrodynamics in the test cells. The flow rate of FTC Apparatus 4 significantly affected the disintegration process of IR tablets. This information can be used as a discriminating tool to support formulation development and to set quality control standards and specifications. To mimic the continuous absorption of theophylline during the passage at different pH values through the whole gastrointestinal tract, dissolution tests were conducted using FTC Apparatus 4 with pH-dependent media for three different commercially available theophylline formulations. Two formulations of Uniphyllin 200-mg tablets and Nuelin SA 175-mg tablets provided a constant release rate during the course of medium pH changes, and their release behavior was predicted with accuracy by appropriate mathematical models. However, wide intervariability and biphasic release in the dissolution profiles were found for Slo-Phyllin 125-mg capsules.


This thesis is based on five parts. The first and second chapters describes two synthetic routes, employing different protecting group strategies for synthesis of uridine 3'-(ethyl, 2-ethoxyethyl, 2-chloroethyl, 2,2-dichloroethyl and 2,2,2-trichloroethyl) phosphate. In the first synthetic route, uridine was protected with acid labile protecting groups, 4-methoxytetrahydropyran-4-yl for the 2'-OH group and 4-methoxytriphenylmethyl for the 5'-OH group. In the second synthesis route the tert-butyldimethylsilyl (TBDMS) was used for protection of the 2'- and 5'- hydroxyls. Silyl deprotection was performed using triethylamine trihydrofluoride. In the third chapter a method for O- and S-palmitoylation of non-protected peptides is described. The procedure consists of treatment of the peptides with excess of palmitoyl chloride in neat trifluoroacetic acid for 10 minutes at room temperature. The tripeptides Gly-Cys-Phe and Gly-Ser-Phe were S- and O-palmitoylated and the hydrophobic Pulmonary Surfactant Protein-C model peptides were converted to the respective S,S- and O,O-dipalmitoylated peptides. The production of S-citronellyl-L-cysteine and S-dolicyl-L-cysteines for use as mass spectrometry standards is described in chapter four. For formation of the thioether linkage, a mesylated citronellol and/or mesylated dolichols and L-cysteine ethyl ester were employed. Finally, in the last chapter a route for synthesis of 8-aminoadenosine 5'-(aminoalkyl phosphates), analogues of aminoacyl adenylates is described. The 5'-H-phosphonate of 2', 3'-O, O-benzylidene-8-bromoadenosine, with unprotected base was condensed with benzyloxycarbonyl (Z) protected amino alcohols (L-isoleucinol, L-histidinol and L-methioninol), in the presence of bis(2-oxo-oxazoline-3-yl)phosphonic chloride. After oxidation the 8-bromo was transformed into the 8-azido moiety by sodium azide in dimethyl sulfoxide. Deprotection of the benzylidene and benzyloxycarbonyl (Z) groups as well as reduction of the azido to the desired amino function was accomplished in a single step by catalytic transfer hydrogenation (palladium-carbon or palladium black in 80% acetic acid).


Tools for the genomic evaluation of goats have generally lagged behind those for other species. However, the recent availability of the goat SNP50 consortium bead chip has marked a positive change for this small ruminant species. Polymorphic loci can differ greatly between breeds of the same species. Exclusion of fibre-producing breeds, such as the Angora goat, during the development of this genotyping array necessitates the validation of SNPs included on the chip to allow for genomic applications that would accelerate genetic progress in mohair yield and quality. Forty eight unrelated Angora goats, displaying phenotypic variation in two important price-determining traits, namely fibre diameter and fleece weight, were genotyped with the goat SNP50 consortium bead chip. Results revealed that 46 983 SNP (88.1%) of the 53 347 called SNPs were polymorphic (MAF>0.05). After quality control, 3 960 SNP were filtered from further analysis for violating Hardy-Weinberg and call-rate parameter thresholds, leaving 43 759 (82%) of the 53 347 SNPs to be validated for downstream analysis. Observed and expected heterozygosity values of 0.365 and 0.370, respectively, were obtained for polymorphic SNPs. A total of 30 357 SNPs in linkage disequilibrium (LD) were removed to obtain a set of independent markers, resulting in a final SNP density of 1 SNP/ ~226 kb. Results indicate that the goat SNP50 bead chip was informative in the Angora goats that were studied, and should be useful in examining the underlying genetic variation.


The constant search for solutions to improve performance and resource efficiency in Cloud platforms has led to the introduction of new virtualization technologies and deployment paradigms. From container-based virtualization to micro virtual machines, new virtualization solutions claim to offer a performance close to bare-metal, with quick deployment and startup times. Furthermore, serverless computing has recently emerged as an alternative deployment model for Cloud workloads, providing scalability and cost reduction without requiring any additional configuration overhead from developers. In this work, we present a performance comparison of well-known virtualization technologies, e.g., virtual machines or containers, together with new, serverless-oriented virtualization solutions, all of them applied to deploy a real monitoring architecture for multi-site 5G platforms. The analysis shows that serverless technologies do not achieve the same performance than well-known virtualization technologies, evaluating as a result the suitability of these new virtualization technologies for production environments, extracting useful conclusions to lay the ground for future work related to this novel paradigm,


Counterfeit electronics constitute a fast-growing threat to global supply chains as well as national security. With rapid globalization, the supply chain is growing more and more complex with components coming from a diverse set of suppliers. Counterfeiters are taking advantage of this complexity and replacing original parts with fake ones. Moreover, counterfeit integrated circuits (ICs) may contain circuit modifications that cause security breaches. Out of all types of counterfeit ICs, recycled and remarked ICs are the most common. Over the past few years, a plethora of counterfeit IC detection methods have been created; however, most of these methods are manual and require highly-skilled subject matter experts (SME). In this paper, an automated bent and corroded pin detection methodology using image processing is proposed to identify recycled ICs. Here, depth map of images acquired using an optical microscope are used to detect bent pins, and segmented side view pin images are used to detect corroded pins.


Vi antigen is the capsular polysaccharide of Salmonella typhi, which can cause typhoid fever. With the increasing threat of antiboitic resistance, vaccination against Salmonella typhi is a preferred way to prevent this disease. Chemical synthesis of fragments of Vi antigen is in urgent need for the development of structure-homogeneous and quality-controlled oligosaccharide vaccines. However, it is extremely challenging to synthesize large oligosaccharide fragments of Vi antigen owing to the exclusive α-1,4-linkage of polyaminogalacturonates. Herein, a series of Vi oligosaccharides ranging from pentamer to octamer were efficiently prepared using 2,3-N,O-oxazolidinone protected glycosides as building blocks based on the preactivation protocol. The heptasaccharide and octasaccharide fragments were synthesized for the first time. The competitive ELISA evaluation suggested that the hexasaccharide might be the minimum epitope of Vi antigen, which provides a significant guidance for the future development of Vi oligosaccharide vaccines.


During the past ten years the mobile radio communications industry has significantly grown. The miniaturization technologies have allowed smaller and smaller portable terminal radio equipment. People throughout the world have been adhering to the wireless communications methods and services mainly of the public cellular mobile network. The digital cellular mobile networks already implemented all over the world such as for instance, the GSM, PDC and IS-95 provide a very low bit rate which is inefficient for data and video services. Higher bit rate mobile networks are now under research and development. This paper describes a base station transceiver for a higher bit rate digital wireless local loop communications system.


Solid-state electronic devices can be engineered to detect and manipulate biological molecules and cells by using electric or magnetic interactions. The integrated circuits, which can contain a large number of such devices, may then potentially be developed into low-cost chip-scale platforms to perform bioanalytical tasks in a multiplexed manner for applications in biology, biotechnology, and personalized medicine. This paper reviews some recent developments in this solid-state electronic and biological systems interface.


The mobile phone has received global attention primarily as a personal consumer technology. However, we believe that mobile information technology in general will play a significant role in organisational efforts to innovate current practices and have significant economic impact. Enterprise mobility signals new ways of managing how people work together using mobile information technology and will form an integral part of the efforts to improve the efficiency and effectiveness of information work. This belief is, however, not reflected in the current selection of books and collections exploring the issue of enterprise mobility. The aim of this paper is to highlight some of the key challenges in the application of mobile information technology to improve organisational efficiency. This is accomplished through comparing and contrasting findings from a selection of 11 empirical studies of enterprise mobility with information technology conducted between 2001 and 2007. The paper argues that the debate so far has largely failed to embed glowing accounts for technological potential in a sound discussion of organisational realities. In particular, there has been a lack of balanced accounts of the implicit and explicit trade-offs involved in mobilising the interaction between members of the workforce.


Geographic variability in call structure indicates that four largely allopatric populations of leopard frogs are present in the central United States. These forms appear to maintain their distinctness in narrow zones of sympatry, and most adult males can be separated morphologically. It is suggested that the four forms represent distinct species and that the idea of gradual clinal variability in one wide-ranging species is wrong.


The retargeting of lymphocytes is an important new strategy in immunotherapy of cancer. One can currently isolate naturally refined, high affinity specificities from antibodies and T-cell receptors (TCRs) to use in engineered applications. We have developed two new molecules that have specificity for the overexpressed tumor antigen HER2/neu. The specificity derived from an anti-HER2 antibody variable fragment was used to create a single chain Fv (scFv). A HER2 reactive TCR was also used to develop a single chain TCR (scTCR). The HER2 binding elements were linked to an intracellular signaling module, active only in the T cell signaling pathway, providing a novel molecule to retarget lymphocytes. We demonstrate here that these molecules can be expressed in several cell lines as well as in hematopoietic stem cells (HSCs). In a transplant setting, these new receptors can be expressed in multiple cells types derived from repopulating HSCs. These new chimeric receptors will be valuable tools for further research of immune function of retargeted hematopoietic cells.


Abstract Protein–DNA binding plays a central role in gene regulation and by that in all processes in the living cell. Novel experimental and computational approaches facilitate better understanding of protein–DNA binding preferences via high-throughput measurement of protein binding to a large number of DNA sequences and inference of binding models from them. Here we review the state of the art in measuring protein–DNA binding in vitro, emphasizing the advantages and limitations of different technologies. In addition, we describe models for representing protein–DNA binding preferences and key computational approaches to learn those from high-throughput data. Using large experimental data sets, we test the performance of different models based on different measuring techniques. We conclude with pertinent open problems.


The paper presents the derivation of a deformation stiffness matrix for an asymmetric thin-walled beam-column element. This matrix KD is a function of element deformation and incorporates the coupling between axial stretching and the lateral and torsional deformations. The stiffness matrix derived and the solution procedure proposed may be used together with the linear and geometric stiffness matrices for thin-walled beam-column elements to analyze large deflection behavior of space frames comprising members in which the influence of sectorial warping in the section can be neglected. These include members with solid, tubular hollow, or angle type sections. The formulation has been applied to a variety of sample problems involving arbitrarily large deflections. Results obtained from the approach using only one element per member in most cases agree very well with independent analytical and other published finite element solutions. The proposed method is suitable for analyzing the nonlinear behavior of large space frames, such as transmission towers.


The protein FcpA is a unique component of the flagellar filament of spirochete bacteria belonging to the genus Leptospira. Although it plays an essential role in translational motility and pathogenicity, no structures of FcpA homologues are currently available in the PDB. Its three-dimensional structure will unveil the novel motility mechanisms that render pathogenic Leptospira particularly efficient at invading and disseminating within their hosts, causing leptospirosis in humans and animals. FcpA from L. interrogans was purified and crystallized, but despite laborious attempts no useful X ray diffraction data could be obtained. This challenge was solved by expressing a close orthologue from the related saprophytic species L. biflexa. Three different crystal forms were obtained: a primitive and a centred monoclinic form, as well as a hexagonal variant. All forms diffracted X-rays to suitable resolutions for crystallographic analyses, with the hexagonal type typically reaching the highest limits of 2.0 Å and better. A variation of the quick-soaking procedure resulted in an iodide derivative that was instrumental for single-wavelength anomalous diffraction methods.


The economical and environment impacts of fossil energies increased the interest for hybrid, battery and fuel-cell electric vehicles. Several demanding engineering challenges must be faced, motivated by different physical domains integration. This paper aims to present an overview on hybrid (HEV) and electric vehicles (EV) basic structures and features. In addition, it will try to point out some of the most relevant challenges to overcome for HEV and EV may be a solid option for the mobility issue. New developments in energy storage devices and energy management systems (EMS) are crucial to achieve this goal.


Two quick and efficient, metal catalyst free conjugation routes for the covalent attachment of functional compounds to functionalized surfaces by scanning probe lithography methods are compared in the presented work. The studied methods are thiol‐yne coupling (TYC) and thiol‐ene Michael addition (TEMA). First, the surface of hydroxyl‐terminated glass is thiolated using (3‐mercaptopropyl)trimethoxysilane (MPTMS). Then, in the distinct experiments, the thiol‐terminated surface is spotted by microchannel cantilever spotting with different fluorescent and nonfluorescent inks containing cycloalkyne (dibenzocyclooctyne (DBCO)) or alkene (maleimide) groups. Experiments with different fluorophores show that both routes are successful in coupling functional moieties to the surface in a short time and low temperature. Comparing the protein binding experiments for biotin‐DBCO and biotin‐maleimide reveals a higher surface density of immobilized biotin via the TEMA route. The results from this study are applicable in design and fabricating of biosensors, appropriate for protein detection and other biomedical/biological applications.


The study aimed at assessing the impact of working capital management on cash holdings. Theoretical perspective, empirical studies and conceptual framework were considered. In data and collection, interviews for collection of primary data and the use of companies' financial statements and annual reports for the collection of the 2011 to 2013 data. The study was empirically analyzed and statistics were tested by using t-test, ANOVA and F-test. The study revealed that there is positive relationship between firms' growth opportunity and firms' cash holding. It also revealed that working capital expenditure to a degree is responsible for reducing cash balances in companies in Tanzania. From the findings obtained, the researcher recommends that management of firms should take into account the role of working capital expenditure, length of the cash conversion cycle, firms' growth opportunities and other factors when planning and controlling for liquidity in the firms.


Vinylogous (Groups III and V) and acetylenologous (Group IV) analogs of the classical beta-adrenergic agents--stimulants and blockers--were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III, which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II, retained beta 1-adrenoceptor antagonist activity albeit substantially less potent (50-200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists (5a, 5d, 5g), with KB's ranging from 73-93 nM while 3,4-dichloro substitution (5e) markedly reduced antagonist potency (KB = 2,400 nM). Agonist activity was also noted for 5b and 5d, suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the beta 1-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen.


Group sparsity has shown great potential in various low-level vision tasks (e.g, image denoising, deblurring and inpainting). In this paper, we propose a new prior model for image denoising via group sparsity residual constraint (GSRC). To enhance the performance of group sparse-based image denoising, the concept of group sparsity residual is proposed, and thus, the problem of image denoising is translated into one that reduces the group sparsity residual. To reduce the residual, we first obtain some good estimation of the group sparse coefficients of the original image by the first-pass estimation of noisy image, and then centralize the group sparse coefficients of noisy image to the estimation. Experimental results have demonstrated that the proposed method not only outperforms many state-of-the-art denoising methods such as BM3D and WNNM, but results in a faster speed.


Human hypertension is the biggest contributor to the global burden of cardiovascular disease and it is the most prevalent modifiable risk factor for cardiovascular morbidity and mortality. The causation of hypertension is multifactorial and is related to perturbation in the pathways that regulate blood pressure. The known blood pressure regulating pathways include those that regulate intravascular volume, vascular tone and peripheral vascular resistance through renal, the renin-angiotensin-aldosterone and autonomic systems, which are targets of the commonly used antihypertensive drugs. In the largest investigation of blood pressure using a metabolomics approach, a novel pathway for blood pressure regulation was identified, involving a dicarboxylic acid, hexadecanedioate. Hexadecanedioate is a long chain dicarboxylic acid, which is generated during fatty acid omega-oxidation pathway (ω-oxidation). Higher circulating levels of hexadecanedioate were significantly associated with both high blood pressure and mortality.
This research project aimed to examine the functional role of hexadecanedioate and investigate its underpinning mechanisms in blood pressure regulation using in-vivo, ex-vivo and metabolomics studies in two animal models; the Wistar Kyoto (WKY) and the Spontaneously Hypertensive Stroke Prone rats (SHRSP).
In the first results chapter (chapter 3), we conducted three independent interventional studies to examine the effects of hexadecanedioate on blood pressure regulation. Circulating levels of hexadecanedioate were significantly increased in WKY rats after treatment with oral hexadecanedioic acid leading to blood pressure elevation and impairment of vascular function in WKY rats. However, hexadecanedioic acid treatment was unable to further increase circulating hexadecanedioate levels or blood pressure in SHRSP rats, indicating that hexadecanedioate levels may already be maximally elevated in the hypertensive model. The data also show an increase in adiposity index despite reduced body weight in SHRSP rats after treatment with hexadecanedioic acid. These results may indicate muscle wasting and altered cellular energy homeostasis such as an impairment of the beta-oxidation pathway (β-oxidation).
In the second results chapter (chapter 4), a global metabolomics study was carried out in WKY rats to demonstrate the metabolic effect of hexadecanedioic acid treatment in cardiovascular tissues (i.e. heart, kidney, liver, aorta, adipose and brain) in order to identify the metabolic pathways leading to hexadecanedioate-induced blood pressure elevation. Several alterations in metabolic readouts, including changes in metabolites related to lipid and glucose metabolisms, bile acid metabolism, redox homeostasis, and uric acid cycle were observed after hexadecanedioic acid treatment. Hexadecanedioate increased in all tested tissues of hexadecanedioic acid-treated WKY rats except brain, where this metabolite was below the threshold of detection. Our data indicated significant increases in peroxisomal ω-oxidation metabolites (i.e. dicarboxylic fatty acids) along with marked changes in mitochondrial fatty acid β-oxidation metabolites such as phospholipids, lysolipid, sphingolipid, monoacylglycerol and acyl carnitine in all tested tissues. These changes in fatty acid availability indicate that hexadecanedioic acid treatment induced changes in mitochondrial β-oxidation and a shift toward increased use of peroxisomal ω-oxidation.
In the third results chapter (chapter 5), the ω- oxidation pathway was investigated by measuring the expression levels of the different enzymes involved in the pathway (i.e. CYP4A, alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in two different rat strains; the normotensive WKY and hypertensive SHRSP rat models. The gene expression results show significant reduction in expression of the ALDH isoform, ALDH1L2, in the liver tissues of SHRSP rats compared to WKY. In addition, the levels of ALDH enzyme were measured in the liver tissues using ELISA assay, which showed a trend towards an increase in SHRSP rats compared to WKY rats.
Blood pressure was assessed after modulation of endogenous hexadecanedioate levels by perturbing the ω-oxidation pathway in both WKY and SHRSP by either inhibition or stimulation of enzymes critical to ω-oxidation. Inhibition of the final ω-oxidation pathway enzyme, ALDH by disulfiram resulted in a significant lowering of blood pressure in the hypertensive SHRSP rat. A pilot study was also conducted to examine the effect of HET0016 (CYP4A antagonist) on blood pressure of SHRSP rats, which showed no significant changes. However, stimulation of the ω-oxidation pathway enzyme, CYP4A by fenofibrate caused a significant reduction of blood pressure in WKY rats, along with significant increase in the CYP4A expression in kidney and liver tissues.
In the final results chapter (chapter 6), an alternative mechanism was examined that may lead to elevated circulating levels of hexadecanedioate via altered activity of the solute carrier organic anion transporter (SLCO), which encodes the protein organic anion transporting polypeptide (OATP). It has been found that the human SLCO1B1 gene is associated with elevated levels of circulating hexadecanedioate. SLCO1B1 may have a role in hexadecanedioate elimination from the body, and any alteration in this liver transporter may cause increases in circulating hexadecanedioate levels leading to blood pressure elevation. A preliminary investigation was performed to identify the sequence variants in the rat homolog, the Slco1b2 gene. Genotype analysis of the SHRSPGla and WKYGla genome sequence identified an insertion of 9 nucleotides (GTCTATCTA) within an intronic region (intron 3/14) on chromosome 4 at position 240,062,637 bp, band 4q44 forward strand in the WKYGla strain rather than a G nucleotide in the SHRSPGla strain. The deletion of 4 nucleotides (TATC) within the 3'untranslated region (UTR) was also detected on chromosome 4 at position 240,102,755 bp of the WKYGla genome sequence. Total Slco1b2 mRNA expression was measured in liver tissues of WKY and SHRSP, which showed significantly decreased levels in SHRSP compared to WKY. These genetic variants within the Slco1b2 gene may contribute to altered function of the Oatp1b2 transporter, which may in turn contribute to elevated levels of circulating hexadecanedioate in the SHRSP rat model of hypertension.
In summary, we have investigated the functional role of hexadecandioate in blood pressure regulation. The findings presented in this thesis demonstrate novel targets associated with hexadecandioate; including the ω-oxidation pathway and the solute carrier organic anion mechanism in regulation of blood pressure.


In order to be "competitive" as a railway, operating efficiency counts as an important imperative. In the context of railway carriage interior planning this is often made subordinate to other substantial aspects such as for example, expediency. This leads in practice to the opposite wished for result. Misunderstood operating efficiency concepts such as a maximal utilization of space for seating can in reality lead to a decline in operating efficiency, operational problems and in incidents to serious safety risks.


Numerical methods for fluxes with strong
density variations but with speeds much lower
than the sound speed, known as low Mach
flows, present some particularities with respect to
incompressible formulations. Despite having similar
application ranges, incompressible formulations
using the Boussinesq approximation with constant
fluid properties cannot correctly describe fluxes with
high density variations. According to Gray and
Giorgini [1], use of the Boussinesq approximation
can be considered valid for variations of the density
up to 10% with respect to the mean value, so when
strong density variations are present, variable density
formulations are required. In the low Mach number
Navier-Stokes equations the velocity divergence is
not zero and acoustic waves are not considered. Also,
the pressure is split into a dynamic pressure and a
thermodynamic part. The latter is used to evaluate
the density, by means of the ideal gas state law.
Here will be presented an extension of an
incompressible pressure projection-type algorithm
(fractional-step) to simulate low Mach fluxes, using
a Runge-Kutta/Crank-Nicolson time integration
scheme, similar to the one presented by Najm
et al. [2] and Nicoud in [3]. The use of
a predictor-corrector substeps is related to the
instabilities introduced by the density time derivative
into the constant coefficient Poisson equation, as
reported in [2, 3]. The spatial discretisation is
performed by means of an unstructured finite volume
technique, using both the collocated formulation by
Felten [4] and the staggered formulation by Perot [5].
Finally, the algorithm is tested against benchmark
test cases, such as the differentially heated cavity
with large temperature differences and cases with
reactive fluxes.


Isodar theory was applied to the analysis of habitat selection by a diurnal folivorous gerbil species, Psammomys obesus, in the Central Negev Desert, Israel. In this site, the species demonstrated seasonal habitat shifts, from densely vegetated and well protected dry river beds (wadi) in winter and spring to open and less protected flat terraces in summer and autumn. These shifts were associated with different phenologies of the main foraging plants in the two microhabitats (winter vegetation of Atriplex halimus in the first and summer vegetation of Anabasis articulata in the second). The life history of P. obesus, thus, suggests that in winter and spring the wadi is better both quantitatively and qualitatively, whereas in summer and autumn, river beds are quantitatively poorer but qualitatively better than the flat terraces. Thus, the winter distribution of P. obesus should fit the divergent model of population regulation for quantitatively different habitats while the summer distribution should fit the convergent or crossover model. The analysis of long-term data supports the predictions for summers and winters following dry autumn conditions but supported the divergent model of population regulation for winters following autumn seasons with high precipitation. The result is consistent with foraging by P. obesus in winters after wet autumns not only on Atriplex and Anabasis, but also on fresh annual plants that are abundant during such winters in both habitats. This assumption was tested and supported by the analysis of annual data on micro-habitat distribution and diet composition. Thus, the isodar analysis can be used not only as a descriptive technique for habitat selection patterns, but also as a powerful tool for natural history studies. The tight connection between food plants and habitat use is clear evidence that foraging and habitat selection are linked through their joint interactions with the ultimate mechanism maximizing fitness.


This paper studies impact of changing mobility speed on the performance of a reactive routing protocol AODV with reference to varying network load. For experimental purposes, initially we observed the performance of AODV with increasing Network Load from 4 packets to 24 packets at the maximum mobility speed of 10 m/s. In another scenario we observed the performance of AODV with increasing Network Load from 4 packets to 24 packets at maximum mobility speed of 20 m/s. The performance of AODV is observed across Packet Delivery Ratio, Loss Packet Ratio and Routing overhead parameters. Our simulation results show that AODV is performing better with higher mobility speed at higher network load.


This paper evaluates the security of wireless communication network based on the fuzzy logic in Mat lab. A new algorithm is proposed and evaluated which is the hybrid algorithm. We highlight the valuable assets in designing of wireless network communication system based on network simulator (NS2), which is crucial to protect security of the systems. Block cipher algorithms are evaluated by using fuzzy logics and a hybrid algorithm is proposed. Both algorithms are evaluated in term of the security level. Logic (AND) is used in the rules of modelling and Mamdani Style is used for the evaluations


The selection methods of party leaders in Israel have gone through a gradual shift during the last 30 years. Like parties in several other democracies (Canada, United Kingdom, Japan), the major Israeli parties have changed their internal distribution of power to give their members a role in candidate and leadership selection. In Israel, as elsewhere, among the reasons for this reform was the desire to reduce the oligarchic tendencies of parties by creating a participatory revolution and by providing the rank-and-file members a chance to make a difference. This study maps the various methods used by Israeli parties for selecting their leaders and asks what the positive and negative consequences of the opening of the selection process are. The first section presents the various methods used by parties for selecting their leaders. The following three sections deal with the gradual process of democratization in leadership selection that occurred in the two major Israeli parties, and in other parties. The final section discusses the consequences of this democratization and tries to assess whether there is an ideal method for selecting party leaders.


OBJECTIVES: To assess the reliability, validity, and responsiveness of a new quality of life measure, the patient generated index (PGI) of quality of life, in patients with four common clinical conditions. DESIGN: Prospective one year follow up study. SETTING: Outpatient departments and four general practices in Grampian, Scotland. SUBJECTS: 1746 patients consulting a general practitioner in one of four practices, or referred to outpatients from all Grampian practices over a four month period, with low back pain, menorrhagia, suspected peptic ulcer, and varicose veins. MAIN OUTCOME MEASURES: Postal questionnaire including the PGI, SF-36 health survey, and clinically derived condition specific measures of disease severity. RESULTS: Test-retest reliability was satisfactory for group comparisons (intraclass correlation coefficient 0.65). Validity was confirmed by the observed association of the PGI with the SF-36, condition specific instruments, and sociodemographic variables. For low back pain, the PGI and the SF-36 pain scale were found to be most responsive to clinical change. For patients with menorrhagia and suspected peptic ulcer, only the condition specific instruments detected larger changes than the PGI. CONCLUSIONS: It is possible to develop a patient generated index of quality of life that not only assesses the extent to which patients' expectations are matched by reality but also satisfies criteria of reliability and responsiveness to change. Further work is required to make the PGI more acceptable and meaningful to patients, but it is believed that it offers an exciting new approach to the evaluation of medical care.


A new and versatile method for tissue viability imaging based on polarization spectroscopy of blood in superficial tissue structures such as the skin is presented in this paper. Linearly polarized light in the visible wavelength region is partly reflected directly by the skin surface and partly diffusely backscattered from the dermal tissue matrix. Most of the directly reflected light preserves its polarization state while the light returning from the deeper tissue layers is depolarized. By the use of a polarization filter positioned in front of a sensitive CCD-array, the light directly reflected from the tissue surface is blocked, while the depolarized light returning from the deeper tissue layers reaches the detector array. By separating the colour planes of the detected image, spectroscopic information about the amount of red blood cells (RBCs) in the microvascular network of the tissue under investigation can be derived. A theory that utilizes the differences in light absorption of RBCs and bloodless tissue in the red and green wavelength region forms the basis of an algorithm for displaying a colour coded map of the RBC distribution in a tissue. Using a fluid model, a linear relationship (cc. = 0.99) between RBC concentration and the output signal was demonstrated within the physiological range 0–4%. In-vivo evaluation using transepidermal application of acetylcholine by the way of iontophoresis displayed the heterogeneity pattern of the vasodilatation produced by the vasoactive agent. Applications of this novel technology are likely to be found in drug and skin care product development as well as in the assessment of skin irritation and tissue repair processes and even ultimately in a clinic case situation.


Summary We tested a phenomenological hypothesis about theoretical and practical rationality in people with schizophrenia. This hypothesis states that in schizophrenia there is an enhancement of theoretical rationality Our case–control experiment supported this hypothesis. Philosophical models of rationality that prioritise theoretical over practical rationality may thereby apply more in schizophrenic than in healthy states. The study is an example of how experimental psychopathology can illuminate areas of philosophical dispute that are difficult to settle by thought alone.


All disciplines have their own jargon intended to promote accurate communication. Deal making is no exception. Forward and reverse triangular mergers, backend mergers, cash-out statutory mergers, asset purchases, and leveraged buyouts are just a few of the terms used to describe deal structures. Firms undergoing significant downsizing may engage in spin-offs, split-offs, and equity carve-outs. Firms attempting to discourage unwanted suitors may implement staggered board elections and dual class recapitalizations. Investment bankers routinely talk about enterprise values and multiples in estimating values for target firms. Although these terms are meaningful to some, they often are bewildering to others.


A non-invasive method of imaging and assessing inflammatory bowel disease is described. 111Indium labelled leucocyte scans were performed on 33 patients with a wide variety of inflammatory bowel diseases and 25 control patients. All patients with moderate or severe inflammatory bowel disease had positive scans with localisation of abnormal activity corresponding to the sites assessed to be diseased by radiology in either small or large bowel. No false positives were recorded in the control patients. Faecal excretion of 111In labelled leucocytes was increased in patients with inflammatory bowel disease according to disease severity and correlated with disease activity assessed by serum C-reactive protein levels (r = 0.74, p less than 0.001) or in those patients with Crohn's disease by Crohn's Disease Activity Index (r = 0.78, p less than 0.001). These data suggest that 111In labelled leucocytes may be used to provide a safe, non-invasive method of imaging diseased bowel and objectively assessing disease activity.


In a combined experimental and theoretical study we probe the transient anion states (resonances) in cyanogen. Experimentally, we utilize electron energy loss spectroscopy which reveals the resonance positions by monitoring the excitation functions for vibrationally inelastic electron scattering. Four resonances are visible in the spectra, centered around 0.36 eV, 4.1, 5.3 and 7.3 eV. Theoretically, we explore the resonant states by using the regularized analytical continuation method. A very good agreement with the experiment is obtained for low-lying resonances, however, the computational method becomes unstable for higher-lying states. The lowest shape resonance (2Πu) is independently explored by the complex adsorbing potential method. In the experiment, this resonance is manifested by a pronounced boomerang structure. We show that the naive picture of viewing NCCN as a pseudodihalogen and focusing only on the CC stretch is invalid.


STUDY QUESTION
Do freezing and in vitro culture procedures enhance the expression of proteins involved in apoptotic or autophagic pathways in murine pre-pubertal testicular tissue?

SUMMARY ANSWER
IVM strongly modified apoptosis- and autophagy-related relative protein levels in mice testicular tissue whereas the impact of cryopreservation procedures was minimal at the end of the culture.

WHAT IS KNOWN ALREADY
In vitro spermatogenesis remains a challenging technical issue as it imposes to find a very close balance between survival and death of germ cell natural precursors (i.e. gonocytes and spermatogonia), which will eventually undergo a complete spermatogenesis close to in vivo conditions. The establishment of efficient culture conditions coupled with suitable cryopreservation procedures (e.g. controlled slow freezing [CSF] and solid surface vitrification [SSV]) of pre-pubertal testicular tissue is a crucial step in the fields of fertility preservation and restoration to improve the spermatic yield obtained in vitro.

STUDY DESIGN, SIZE, DURATION
Here, we study cryopreservation procedures (i.e. CSF or SSV) and the impact of culture media compositions. A first set of 66 mouse pre-pubertal testes were directly cultured during 30, 36, 38 and 60 days (D) from 2.5 to 6.5-day-old CD-1 mice to evaluate the impact of time-aspect of culture and to endorse the reverse phase protein microarrays (RPPM) technique as an adapted experimental tool for the field of in vitro spermatogenesis. Ninety others fresh, slow-frozen and vitrified pre-pubertal testes were cultured during 30 days for the principal study to evaluate the impact of cryopreservation procedures before and after culture. Thirty-four testes dissected from 2.5, 6.5, 36.5, 40.5, 42.5 and 62.5 days postpartum (dpp) mice, corresponding to the time frames of spermatogenesis orchestrated in vitro, were used as in vivo controls.

PARTICIPANTS/MATERIALS, SETTING, METHODS
After in vitro culture, testicular tissue samples originated from 2.5 or 6.5-day-old CD-1 male mice were analyzed using RPPM. This targeted proteomic technique allowed us to assess the expression level of 29 apoptosis- and autophagy-related factors by normalizing blank-corrected signal values. In addition, morphological analyses (e.g. HES, PAS, TRA98 and CREM) and DNA fragmentation in intra-tubular cells (i.e. terminal deoxynucleotidyl transferase dUTP nick end labeling; TUNEL) were assessed for the distinct experimental conditions tested as well as for in vivo control mouse testes.

MAIN RESULTS AND THE ROLE OF CHANCE
A validation of the RPPM procedure in the field of in vitro spermatogenesis was completed with assay and array robustness before a principal study concerning the evaluation of the impact of in vitro culture and cryopreservation procedures. The proportion of elongated spermatids and the total cell number per seminiferous tubule tended to be very different between the in vivo and in vitro conditions (P < 0.05), suggesting the presence of a beneficial regulation on the first spermatogenesis wave by intrinsic apoptosis (Caspase_9) and autophagy (Atg5) factors (P < 0.0003 and r2 = 0.74). Concerning the impact of culture media compositions, a basic medium (BM) composed of αMEM plus 10% KnockOut™ serum replacement and gentamicin supplemented with retinol (Rol) and vitamin E (Vit. E) was selected as the best culture medium for fresh 6.5 dpp tissue cultured during 30D with 27.7 ± 8.10% of seminiferous tubules containing elongated spermatids. Concerning the impact of cryopreservation procedures, SSV did not have any impact on the morphological parameters evaluated after culture in comparison to fresh tissue (FT) controls. The proportion of tubules with elongated spermatids on testicular explants cultured with BMRol+Vit. E was not different between SSV (6.6 ± 1.6%) and CSF (5.3 ± 1.9%); however, round spermatids were observed more frequently for SSV (19 ± 6.2%) than CSF (3.3 ± 1.9%, P = 0.0317). Even if the proportion of TUNEL-positive cells for BMRol+Vit. E was higher at D30 after SSV (4.12 ± 0.26%) than CSF (1.86 ± 0.12%, P = 0.0022) and FT (2.69 ± 0.33%, P = 0.0108), the DNA damages observed at the end of the culture (i.e. D30) were similar to respective 6.5 dpp controls. In addition, the relative protein level expression ratio of an apoptotic factor, the phosphorylated FADD on Fas, was reduced by 64-fold in vitrified testes cultured with BMRol+Vit. E. Furthermore, we found in this study that the StemPro®-34 SFM culture medium supplemented with growth factors (e.g. EGF, bFGF, GDNF and LIF) prevented the differentiation of spermatogonial stem cells in favor of a significant proliferation with a better architectural pattern than in vivo 6.5 dpp controls with an increase of seminiferous tubules area for FT (P = 0.0357) and CSF (P = 0.0317).

LIMITATIONS REASONS FOR CAUTION
Despite our promising results, the evaluation of apoptotic- and autophagic-related proteins was studied for a limited amount of proteins and on global testicular tissue.

WIDER IMPLICATIONS OF THE FINDINGS
The data presented herein will help to improve apoptotic and autophagic understanding during the first spermatogenic wave. Moreover, our findings illustrate for the first time that, using finely-tuned experimental conditions, a testicular in vitro culture combined with proteomic technologies may significantly facilitate the study of cryopreservation procedures and in vitro culture evaluations. This study may also contribute to improve work on testicular tissues from pre-pubertal and adolescent cancer survivors.

STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by a Ph.D. grant from the Rouen Normandie Université and a financial support from 'la Ligue nationale contre le cancer' (both awarded to L.D.), funding from Institute for Research and Innovation in Biomedicine (IRIB), Agence de la Biomédecine, and co-supported by European Union and Région Normandie. Europe gets involved in Normandie with European Regional Development Fund (ERDF). The authors declare that there is no conflict of interest.