Experiences in the Integration of Design Across the Mechanical Engineering Curriculum

The Faculty of the School of Mechanical Engineering at Purdue University have effected a major change in the Purdue Mechanical Engineering program by integrating design throughout the curriculum. In doing so, a significant level of faculty interaction has been achieved as well. The goals of the curriculum revision are: (1) to improve student skills in how to solve open-ended design problems, (2) to reduce the core of the curriculum to allow flexibility in course selection, and allow time for solving design problems, (3) to improve student skills in team work and communications, and (4) to improve student skills in using computers as tools for solving engineering problems. Reduction of the core allowed the addition of a sophomore cornerstone design course. This cornerstone course teaches students how to solve open-ended problems, bridging the gap between solution strategies that are effective for the science and mathematics courses, and those needed to solve open-ended engineering problems. The design fundamentals taught in the cornerstone course are applied in the core courses, such as heat transfer, thermodynamics, instrumentation, and machine design. The senior design experience comes primarily from a design elective and the capstone design course. This paper presents an overview of the curriculum revision process, and the changes which resulted from it. It also discusses the issues associated with infusing design projects into core courses which have traditionally focused on teaching engineering science fundamentals. Plans for the future evolution of the curriculum are also discussed

Autistic traits and individual brain differences: functional network efficiency reflects attentional and social impairments, structural nodal efficiencies index systemising and theory-of-mind skills

Background: Autism is characterised not only by impaired social cognitive 'empathising' but also by superior rule-based 'systemising'. These cognitive domains intertwine within the categorical diagnosis of autism, yet behavioural genetics suggest largely independent heritability, and separable brain mechanisms. We sought to determine whether quantitative behavioural measures of autistic traits are dimensionally associated with structural and functional brain network integrity, and whether brain bases of autistic traits vary independently across individuals. Methods: 30 right-handed neurotypical adults (12 females) were administered psychometric (Social Responsiveness Scale, Autism Spectrum Quotient, and Systemising Quotient) and behavioural (Attention Network Test and theory-of-mind reaction time) measures of autistic traits, and structurally (diffusion tensor imaging) and functionally (500 s of 2 Hz eyes-closed resting fMRI) derived graph-theoretic measures of efficiency of information integration were computed throughout the brain and within subregions. Results: Social impairment was positively associated with functional efficiency (r=.47, p=.006), globally and within temporo-parietal and prefrontal cortices. Delayed orienting of attention likewise associated with greater functional efficiency (r=-.46., p=.0133). Systemising was positively associated with global structural efficiency (r=.38, p=0.018), driven specifically by temporal pole; theory-of-mind reaction time was related to structural efficiency (r=-.40, p=0.0153) within right supramarginal gyrus. Limitations: Interpretation of these relationships is complicated by the many senses of the term 'connectivity', including, functional, structural, and computational; by the approximation inherent in group functional anatomical parcellations when confronted with individual variation in functional anatomy; and by the validity, sensitivity and specificity of the several survey and experimental behavioural measures applied as correlates of brain structure and function. Conclusions: Functional connectivities highlight distributed networks associated with domain-general properties such as attentional orienting and social cognition broadly, associating more impaired behaviour with more efficient brain networks that may reflect heightened feedforward information flow subserving autistic strengths and deficits alike. Structural connectivity results highlight specific anatomical nodes of convergence, reflecting cognitive and neuroanatomical independence of systemising and theory-of-mind. In addition, this work shows that individual differences in theory-of-mind related to brain structure can be measured behaviourally, and offers neuroanatomical evidence to pin down the slippery construct of ‘systemising’ as the capacity to construct invariant contextual associations

Controlling particle size in the Stöber process and incorporation of calcium

The Stӧber process is commonly used for synthesising spherical silica particles. This article reports the first comprehensive study of how the process variables can be used to obtain monodispersed particles of specific size. The modal particle size could be selected within in the range 20 – 500 nm. There is great therapeutic potential for bioactive glass nanoparticles, as they can be internalised within cells and perform sustained delivery of active ions. Biodegradable bioactive glass nanoparticles are also used in nanocomposites. Modification of the Stӧber process so that the particles can contain cations such as calcium, while maintaining monodispersity, is desirable. Here, while calcium incorporation is achieved, with a homogenous distribution, careful characterisation shows that much of the calcium is not incorporated. A maximum of 10 mol% CaO can be achieved and previous reports are likely to have overestimated the amount of calcium incorporated

Guts within guts: the microbiome of the intestinal helminth parasite Ascaris suum is derived but distinct from its host

BACKGROUND: Intestinal helminths are extremely prevalent among humans and animals. In particular, intestinal roundworms affect more than 1 billion people around the globe and are a major issue in animal husbandry. These pathogens live in intimate contact with the host gut microbiota and harbor bacteria within their own intestines. Knowledge of the bacterial host microbiome at the site of infection is limited, and data on the parasite microbiome is, to the best of our knowledge, non-existent. RESULTS: The intestinal microbiome of the natural parasite and zoonotic macropathogen, Ascaris suum was analyzed in contrast to the diversity and composition of the infected host gut. 16S sequencing of the parasite intestine and host intestinal compartments showed that the parasite gut has a significantly less diverse microbiome than its host, and the host gut exhibits a reduced microbiome diversity at the site of parasite infection in the jejunum. While the host's microbiome composition at the site of infection significantly determines the microbiome composition of its parasite, microbial signatures differentiate the nematodes from their hosts as the Ascaris intestine supports the growth of microbes that are otherwise under-represented in the host gut. CONCLUSION: Our data clearly indicate that a nematode infection reduces the microbiome diversity of the host gut, and that the nematode gut represents a selective bacterial niche harboring bacteria that are derived but distinct from the host gut

Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated <it>Plasmodium falciparum </it>malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the <it>in vivo </it>efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam^®, Mephaquin^®, and Mefloquina-AC^®Farma) given in combination with artesunate.</p> <p>Methods</p> <p>Thirty-nine non-pregnant adults with <it>P. falciparum </it>mono-infection were randomly assigned to receive artesunate in combination with either (1) Lariam, (2) Mephaquin, or (3) Mefloquina AC. Patients were assessed on Day 0 (with blood samples for pharmacokinetics at 0, 2, 4, and 8 hours), 1, 2, 3, 7, and then weekly until day 56. Clinical and parasitological outcomes were based on the standardized WHO protocol.</p> <p>Whole blood mefloquine concentrations were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined using non-compartmental analysis of concentration versus time data.</p> <p>Results</p> <p>By day 3, all patients had cleared parasitaemia except for one patient in the AC Farma arm; this patient cleared by day 4. No recurrences of parasitaemia were seen in any of the 34 patients. All three MQ formulations had a terminal half-life of 14–15 days and time to maximum plasma concentration of 45–52 hours. The maximal concentration (C_max) and interquartile range was 2,820 ng/ml (2,614–3,108) for Lariam, 2,500 ng/ml (2,363–2,713) for Mephaquin, and 2,750 ng/ml (2,550–3,000) for Mefloquina AC Farma. The pharmacokinetics of the three formulations were generally similar, with the exception of the C_maxof Mephaquin which was significantly different to that of Lariam (<it>p </it>= 0.04).</p> <p>Conclusion</p> <p>All three formulations had similar pharmacokinetics; in addition, the pharmacokinetics seen in this Peruvian population were similar to reports from other ethnic groups. All patients rapidly cleared their parasitaemia with no evidence of recrudescence by Day 56. Continued surveillance is needed to ensure that patients continue to receive optimal therapy.</p

Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair

Background: A delay in surgical nerve repair results in impaired nerve function in humans, but mechanisms behind the weakened nerve regeneration are not known. Activating transcription factor 3 (ATF3) increases the intrinsic growth state of injured neurons early after injury, but the role of long-term changes and their relation to axonal outgrowth after a delayed nerve repair are not well understood. ATF3 expression was examined by immunohistochemistry in motor and sensory neurons and in Schwann cells in rat sciatic nerve and related to axonal outgrowth after transection and delayed nerve repair (repair 0, 30, 90 or 180 days post-injury). Expression of the neuronal cell adhesion molecule (NCAM), which is expressed in non-myelinating Schwann cells, was also examined. Results: The number of neurons and Schwann cells expressing ATF3 declined and the length of axonal outgrowth was impaired if the repair was delayed. The decline was more rapid in motor neurons than in sensory neurons and Schwann cells. Regeneration distances over time correlated to number of ATF3 stained neurons and Schwann cells. Many neurofilament stained axons grew along ATF3 stained Schwann cells. If nerve repair was delayed the majority of Schwann cells in the distal nerve segment stained for NCAM. Conclusion: Delayed nerve repair impairs nerve regeneration and length of axonal outgrowth correlates to ATF3 expression in both neurons and Schwann cells. Mainly non-myelinating Schwann cells (NCAM stained) are present in distal nerve segments after delayed nerve repair. These data provide a neurobiological basis for the poor outcomes associated with delayed nerve repair. Nerve trunks should, if possible, be promptly repaired

Highly degradable porous melt-derived bioactive glass foam scaffolds for bone regeneration

A challenge in using bioactive melt-derived glass in bone regeneration is to produce scaffolds with interconnected pores while maintaining the amorphous nature of the glass and its associated bioactivity. Here we introduce a method for creating porous melt-derived bioactive glass foam scaffolds with low silica content and report in vitro and preliminary in vivo data. The gel-cast foaming process was adapted, employing temperature controlled gelation of gelatin, rather than the in situ acrylic polymerisation used previously. To form a 3D construct from melt derived glasses, particles must be fused via thermal processing, termed sintering. The original Bioglass® 45S5 composition crystallises upon sintering, altering its bioactivity, due to the temperature difference between the glass transition temperature and the crystallisation onset being small. Here, we optimised and compared scaffolds from three glass compositions, ICIE16, PSrBG and 13–93, which were selected due to their widened sintering windows. Amorphous scaffolds with modal pore interconnect diameters between 100–150 µm and porosities of 75% had compressive strengths of 3.4 ± 0.3 MPa, 8.4 ± 0.8 MPa and 15.3 ± 1.8 MPa, for ICIE16, PSrBG and 13–93 respectively. These porosities and compressive strength values are within the range of cancellous bone, and greater than previously reported foamed scaffolds. Dental pulp stem cells attached to the scaffold surfaces during in vitro culture and were viable. In vivo, the scaffolds were found to regenerate bone in a rabbit model according to X-ray micro tomography imaging

An Investigation of Genome-Wide Studies Reported Susceptibility Loci for Ulcerative Colitis Shows Limited Replication in North Indians

Genome-Wide Association studies (GWAS) of both Crohn's Disease (CD) and Ulcerative Colitis (UC) have unearthed over 40 risk conferring variants. Recently, a meta-analysis on UC revealed several loci, most of which were either previously associated with UC or CD susceptibility in populations of European origin. In this study, we attempted to replicate these findings in an ethnically distinct north Indian UC cohort. 648 UC cases and 850 controls were genotyped using Infinium Human 660W-quad. Out of 59 meta-analysis index SNPs, six were not in the SNP array used in the study. Of the remaining 53 SNPs, four were found monomorphic. Association (p<0.05) at 25 SNPs was observed, of which 15 were CD specific. Only five SNPs namely rs2395185 (HLA-DRA), rs3024505 (IL10), rs6426833 (RNF186), rs3763313 (BTNL2) and rs2066843 (NOD2) retained significance after Bonferroni correction. These results (i) reveal limited replication of Caucasian based meta-analysis results; (ii) reiterate overlapping molecular mechanism(s) in UC and CD; (iii) indicate differences in genetic architecture between populations; and (iv) suggest that resources such as HapMap need to be extended to cover diverse ethnic populations. They also suggest a systematic GWAS in this terrain may be insightful for identifying population specific IBD risk conferring loci and thus enable cross-ethnicity fine mapping of disease loci

Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD, and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such a delineation could not be made due to tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a trans-ethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9,272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40,691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analysed the physico-chemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we identified consistent associations across different ethnicities but also identified population-specific signals. We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids such. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins