A Case Study in Refactoring Functional Programs

Refactoring is the process of redesigning existing code without changing its functionality. Refactoring has recently come to prominence in the OO community. In this paper we explore the prospects for refactoring functional programs. Our paper centres on the case study of refactoring a 400 line Haskell program written by one of our students. The case study illustrates the type and variety of program manipulations involved in refactoring. Similarly to other program transformations, refactorings are based on program equivalences, and thus ultimately on language semantics. In the context of functional languages, refactorings can be based on existing theory and program analyses. However, the use of program transformations for program restructuring emphasises a different kind of transformation from the more traditional derivation or optimisation: characteristically, they often require wholesale changes to a collection of modules, and although they are best controlled by programmers, their application may require nontrivial semantic analyses. The paper also explores the background to refactoring, provides a taxonomy for describing refactorings and draws some conclusions about refactoring for functional programs

Refactoring Functional Programs

Refactoring is the process of redesigning existing code without changing its functionality. Refactoring has recently come to prominence in the OO community. In this paper we explore the prospects for refactoring functional programs. Our paper centres on the case study of refactoring a 400 line Haskell program written by one of our students. The case study illustrates the type and variety of program manipulations involved in refactoring. Similarly to other program transformations, refactorings are based on program equivalences, and thus ultimately on language semantics. In the context of functional languages, refactorings can be based on existing theory and program analyses. However, the use of program transformations for program restructuring emphasises a different kind of transformation from the more traditional derivation or optimisation: characteristically, they often require wholesale changes to a collection of modules, and although they are best controlled by programmers, their application may require nontrivial semantic analyses. The paper also explores the background to refactoring, provides a taxonomy for describing refactorings and draws some conclusions about refactoring for functional programs

Multi-Parameter Analysis of Biobanked Human Bone Marrow Stromal Cells Shows Little Influence for Donor Age and Mild Comorbidities on Phenotypic and Functional Properties

Heterogeneous populations of human bone marrow-derived stromal cells (BMSC) are among the most frequently tested cellular therapeutics for treating degenerative and immune disorders, which occur predominantly in the aging population. Currently, it is unclear whether advanced donor age and commonly associated comorbidities affect the properties of ex vivo-expanded BMSCs. Thus, we stratified cells from adult and elderly donors from our biobank (n = 10 and n = 13, mean age 38 and 72 years, respectively) and compared their phenotypic and functional performance, using multiple assays typically employed as minimal criteria for defining multipotent mesenchymal stromal cells (MSCs). We found that BMSCs from both cohorts meet the standard criteria for MSC, exhibiting similar morphology, growth kinetics, gene expression profiles, and pro-angiogenic and immunosuppressive potential and the capacity to differentiate toward adipogenic, chondrogenic, and osteogenic lineages. We found no substantial differences between cells from the adult and elderly cohorts. As positive controls, we studied the impact of in vitro aging and inflammatory cytokine stimulation. Both conditions clearly affected the cellular properties, independent of donor age. We conclude that in vitro aging rather than in vivo donor aging influences BMSC characteristics

Green buildings as sustainability education tools

Purpose – The purpose of this paper is to provide an overview of green building technologies and practices and illustrate how public libraries can use them as tools to teach their communities about sustainability and foster behavior change. Design/methodology/approach – Through literature searches, case studies analysis, and individual phone and e-mail interviews, the author identified ways that public libraries can use their buildings to demonstrate green technologies and practices and show their patrons how to apply them at home, at work, and in the community. Findings – Education is a component of LEED certification. Many LEED certified libraries publicize a list of the green technologies used in their building projects. Some sponsor programs related to the green building and include permanent displays in the library to explain how the technology works. The Fayetteville Public Library went beyond these basic techniques to not only improve the sustainability of their operations but also become a community test bed for a renewable energy project. Originality/value – This paper sheds light on how building projects can be used not only to educate the public about green technologies and practices, but also inspire others to begin using similar techniques at home, at work, and in the community.published or submitted for publicationis peer reviewe

Lower-limb internal loading and potential consequences for fracture healing

Introduction: Mechanical loading is known to determine the course of bone fracture healing. We hypothesise that lower limb long bone loading differs with knee flexion angle during walking and frontal knee alignment, which affects fracture healing success. Materials and methods: Using our musculoskeletal in silico modelling constrained against in vivo data from patients with instrumented knee implants allowed us to assess internal loads in femur and tibia. These internal forces were associated with the clinical outcome of fracture healing in a relevant cohort of 178 extra-articular femur and tibia fractures in patients using a retrospective approach. Results: Mean peak forces differed with femoral compression (1,330-1,936 N at mid-shaft) amounting to about half of tibial compression (2,299-5,224 N). Mean peak bending moments in the frontal plane were greater in the femur (71-130 Nm) than in the tibia (from 26 to 43 Nm), each increasing proximally. Bending in the sagittal plane showed smaller mean peak bending moments in the femur (-38 to 43 Nm) reaching substantially higher values in the tibia (-63 to -175 Nm) with a peak proximally. Peak torsional moments had opposite directions for the femur (-13 to -40 Nm) versus tibia (15-48 Nm) with an increase towards the proximal end in both. Femoral fractures showed significantly lower scores in the modified Radiological Union Scale for Tibia (mRUST) at last follow-up (p < 0.001) compared to tibial fractures. Specifically, compression (r = 0.304), sagittal bending (r = 0.259), and frontal bending (r = -0.318) showed strong associations (p < 0.001) to mRUST at last follow-up. This was not the case for age, body weight, or localisation alone. Discussion: This study showed that moments in femur and tibia tend to decrease towards their distal ends. Tibial load components were influenced by knee flexion angle, especially at push-off, while static frontal alignment played a smaller role. Our results indicate that femur and tibia are loaded differently and thus require adapted fracture fixation considering load components rather than just overall load level

Effects of cold winters and roost site stability on population development of non-native Asian ring-necked parakeets (Alexandrinus manillensis) in temperate Central Europe – Results of a 16-year census

Asian ring-necked parakeets (Alexandrinus manillensis, formerly Psittacula krameri, hereafter RNP) first bred in&nbsp;Germany in 1969. Since then, RNP numbers increased in all three major German subpopulations (Rhineland,&nbsp;Rhine-Main, Rhine-Neckar) over the period 2003–2018. In the Rhine-Neckar region, the population increased to more than fivefold within only 15 years. Interestingly, there was no significant breeding range expansion of &nbsp;RNP in the period 2010–2018. In 2018, the total number of RNP in Germany amounted to &gt;16,200 birds. Differences&nbsp;in RNP censuses between years were evident. Surprisingly, cold winters (extreme value, −13.7 °C) and&nbsp;cold weather conditions in the breeding season (coldest month average, −1.36 °C) were not able to explain&nbsp;between-year variation. This finding suggests that in general winter mortality is low – with exceptions for winters&nbsp;2008/2009 and 2009/2010, and a population-relevant loss of broods is low in our study population.&nbsp;Surprisingly, the social behaviour in terms of spatio-temporal stability of roost sites could well explain positive and negative population trends. Years of spatially stable and regularly used roost sites seem to correlate with increasing population sizes. In contrast, known shifts of RNP among different roost sites or the formations of&nbsp;new roost sites by split are related to population stagnation or a decrease in numbers. Climate change may lead&nbsp;to further range expansion as cities not suitable yet for RNP may become so in the near future.

Investigating the health-economic profiles of biomarker-driven immunosuppresion (BIO-DrIM) following solid organ transplantation

Immunosuppression (IS) following solid organ transplantation is indicated to avoid rejection but puts a sig-nificant burden on patients and healthcare systems due to life-long medication dependency and associated costs. Or-gan-tolerance with low or no IS medication has been observed, and might be forecasted with the help of appropriate biomarkers. Individualized treatments raise the question whether benefits of individualization outweigh the costs of stratification. This article outlines the importance of early economic evaluation in the context of biomarker-guided IS and discusses challenges that an economic evaluation should address, using the BIO-DrIM project as a reference exam-ple. We report on design aspects and health-economic study integration into several newly designed biomarker trials. In these studies, health-economic endpoints were defined to measure benefits of individualization and to compare them to the costs associated with stratification. Key economic outcomes to be collected are resource consumption and patient quality of life. Test accuracy of the biomarker-stratification is critical for the clinical success and the health-economic viability of an individualized reduced IS regime. However, IS regimes are not well standardized, rendering comparator choice difficult. The multi-national character of the trials adds further complexity that needs to be addressed. Develop-ers of biomarker tests should stress the importance of integrating health-economic evaluations early into prod-uct-development

Individual Effector/Regulator T Cell Ratios Impact Bone Regeneration

There is increasing evidence that T lymphocytes play a key role in controlling endogenous regeneration. Regeneration appears to be impaired in case of local accumulation of CD8+ effector T cells (TEFF), impairing endogenous regeneration by increasing a primary "useful" inflammation toward a damaging level. Thus, rescuing regeneration by regulating the heightened pro-inflammatory reaction employing regulatory CD4+ T (TReg) cells could represent an immunomodulatory option to enhance healing. Hypothesis was that CD4+ TReg might counteract undesired effects of CD8+ TEFF. Using adoptive TReg transfer, bone healing was consistently improved in mice possessing an inexperienced immune system with low amounts of CD8+ TEFF. In contrast, mice with an experienced immune system (high amounts of CD8+ TEFF) showed heterogeneous bone repair with regeneration being dependent upon the individual TEFF/TReg ratio. Thus, the healing outcome can only be improved by an adoptive TReg therapy, if an unfavorable TEFF/TReg ratio can be reshaped; if the individual CD8+ TEFF percentage, which is dependent on the individual immune experience can be changed toward a favorable ratio by the TReg transfer. Remarkably, also in patients with impaired fracture healing the TEFF/TReg ratio was higher compared to uneventful healers, validating our finding in the mouse osteotomy model. Our data demonstrate for the first time the key-role of a balanced TEFF/TReg response following injury needed to reach successful regeneration using bone as a model system. Considering this strategy, novel opportunities for immunotherapy in patients, which are at risk for impaired healing by targeting TEFF cells and supporting TReg cells to enhance healing are possible

The Influence of Recovery and Training Phases on Body Composition, Peripheral Vascular Function and Immune System of Professional Soccer Players

Professional soccer players have a lengthy playing season, throughout which high levels of physical stress are maintained. The following recuperation period, before starting the next pre-season training phase, is generally considered short but sufficient to allow a decrease in these stress levels and therefore a reduction in the propensity for injury or musculoskeletal tissue damage. We hypothesised that these physical extremes influence the body composition, blood flow, and endothelial/immune function, but that the recuperation may be insufficient to allow a reduction of tissue stress damage. Ten professional football players were examined at the end of the playing season, at the end of the season intermission, and after the next pre-season endurance training. Peripheral blood flow and body composition were assessed using venous occlusion plethysmography and DEXA scanning respectively. In addition, selected inflammatory and immune parameters were analysed from blood samples. Following the recuperation period a significant decrease of lean body mass from 74.4±4.2 kg to 72.2±3.9 kg was observed, but an increase of fat mass from 10.3±5.6 kg to 11.1±5.4 kg, almost completely reversed the changes seen in the pre-season training phase. Remarkably, both resting and post-ischemic blood flow (7.3±3.4 and 26.0±6.3 ml/100 ml/min) respectively, were strongly reduced during the playing and training stress phases, but both parameters increased to normal levels (9.0±2.7 and 33.9±7.6 ml/100 ml/min) during the season intermission. Recovery was also characterized by rising levels of serum creatinine, granulocytes count, total IL-8, serum nitrate, ferritin, and bilirubin. These data suggest a compensated hypo-perfusion of muscle during the playing season, followed by an intramuscular ischemia/reperfusion syndrome during the recovery phase that is associated with muscle protein turnover and inflammatory endothelial reaction, as demonstrated by iNOS and HO-1 activation, as well as IL-8 release. The data provided from this study suggest that the immune system is not able to function fully during periods of high physical stress. The implications of this study are that recuperation should be carefully monitored in athletes who undergo intensive training over extended periods, but that these parameters may also prove useful for determining an individual's risk of tissue stress and possibly their susceptibility to progressive tissue damage or injury

Zinc enrichment and isotopic fractionation in a marine habitat of the c. 2.1 Ga Francevillian Group: A signature of zinc utilization by eukaryotes?

Constraining the timing of eukaryogenesis and the divergence of eukaryotic clades is a major challenge in evolutionary biology. Here, we present trace metal concentration and zinc isotope data for c. 2.1 billion-year-old Francevillian Group pyritized structures, previously described as putative remnants of the first colonial multicellular organisms, and their host black shales. Relative to the host rocks, pyritized structures are strongly enriched in zinc, cobalt and nickel, by at least one order of magnitude, with markedly lighter zinc isotope compositions. A metabolic demand for high concentrations of aqueous zinc, cobalt, and nickel combined with preferential uptake of lighter zinc isotopes may indicate metalloenzyme utilization by eukaryotes in marine habitats c. 2.1 billion years ago. Once confirmed, this would provide a critical calibration point for eukaryogenesis, suggesting that this major evolutionary innovation may have happened contemporaneously with elevated atmospheric oxygen levels during the latter part of the Great Oxidation Event, some 400 million years earlier than is currently widely accepted