Miracle-dz/UniFAR-FTUs huggingface dataset:
Aligning Design and Development Processes for Additive Manufacturing

Rapid Prototyping has transitioned from only being able to produce delicate prototypes to being capable of producing robust production parts. As part of this transition, it has been renamed Additive Manufacturing (AM). As a true manufacturing technology, it has become important to deliberately design parts for Additive Manufacturing, and research has begun in how best to achieve this. This thesis explores the background of Additive Manufacturing, the growth in its use as a manufacturing technology, and the advantages and challenges of the technology. Following background information, this thesis progresses to different design approaches and technologies that promise to be effective when paired with AM. A design methodology using topology optimization is proposed, detailed and then tested on two case studies. The first case is a high-speed mirror for imaging and the second case is an aircraft bracket for the 2013 GrabCAD-GE design challenge. This thesis also includes an examination of the implementation of the proposed methodology on these case studies and the resulting designs. The design from both case studies achieved a greater than 60% weight reduction through the use of design methodology tailored for AM. The final section of the thesis shifts from the design process to the development process where the impact of AM is examined. In order to gain an understanding of the influence that Additive Manufacturing has on production, this thesis includes a synthesis of the literature from Additive Manufacturing as well as Design and Management. The benefits are approached from an economic perspective, reviewing the first order benefits that have been extensively studied and then progressing to the second order benefits, and indirect benefits, which have not been examined in detail before. To understand the full effect of Additive Manufacturing on product development, the consideration of advantages such as high fidelity prototypes, decreased risk, faster time to market and late stage design flexibility are assessed. Thesis Supervisor: Maria C. Yang Tide: Associate Professor of Mechanical Engineering 3
Positron Emission Tomography 18F-Fluorodeoxyglucose Uptake and Prognosis in Patients with Surgically Treated, Stage I Non-small Cell Lung Cancer: A Systematic Review

Background: 18F-fluorodeoxyglucose (FDG) uptake holds potential as a noninvasive biomarker in patients with non-small cell lung cancer (NSCLC). We aimed to investigate the association between tumor FDG uptake and survival in patients with surgically resected, stage I NSCLC. Methods: We used systematic methods to identify studies for inclusion, assess methodological quality, and abstract relevant data about study design and results. Results: Our literature search identified 1578 citations, of which nine retrospective, cross-sectional studies met eligibility criteria. In all studies, higher degrees of FDG uptake in the primary tumor were associated with worse overall or disease free survival after 2 to 5 years of follow-up, but these differences were statistically significant in only five studies. Across studies, the median overall or disease free survival was 70% for patients with higher FDG uptake compared with 88% for patients with lower FDG uptake. In three studies that performed multivariable analysis, the adjusted hazard of death or recurrence was 1.9 to 8.6 times greater in patients with higher FDG uptake. Conclusion: Current evidence suggests that increasing tumor FDG uptake is associated with worse survival in patients with stage I NSCLC. FDG uptake has the potential to be used as a biomarker for identifying stage I patients who are at increased risk of death or recurrence and therefore could identify candidates for participation in future trials of adjuvant therapy.
ENVIRONMENTAL AND GENETIC MATERNAL EFFECTS ON SEED CHARACTERS IN NEMOPHILA MENZIESII

Nuclear genetic, maternal genetic and maternal environmental effects on seed characters were estimated in the California native annual plant Nemophila menziesii using two greenhouse crosses. In one cross, according to a nested mating design, the narrow sense heritability of seed weight was small (3.9%). A subset of full‐sib progenies produced in this cross was grown singly and in competition with the introduced grass Bromus diandrus. In a second cross, these plants were used as mothers (dams) and were each mated to the same three sires. Seeds produced by mothers competing with B. diandrus showed a significant reduction in weight, increase in time to germination, and increase in the incidence of dormancy, when compared to seeds from mothers grown singly. Significant sire components were found for time to germination and incidence of dormancy. Maternal genetic variation for seed weight was largely expressed as maternal genotype by maternal environment interaction, and showed no significant maternal genetic main effect. Time to germination and dormant fraction showed a relatively large maternal genetic effect. Evolution of seed characters in N. menziesii is more likely to occur via indirect response to selection among maternal plants than among the seeds themselves. Maternal genotype by maternal environment interaction could potentially contribute to the maintenance of maternal genetic variation in seed weight, but this does not appear likely for dormancy.
Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation

Significance Stem-cell microenvironment has been identified as an important modulator of plasticity, self-renewal, and differentiation. This work details the development of a hydrogel system tailored to promote human pluripotent stem cell (HPSC) self-renewal with a simple chemical microenvironmental switch to direct differentiation. Furthermore, the timing of switching post hydrogel fabrication can promote specific lineage differentiation as in vivo. This system highlights the role of microenvironment on fate choices of pluripotent cells and demonstrates that it may be tailored to control differentiation in vitro. Importantly, this approach may improve the generation of fully differentiated tissues, as demonstrated for cardiogenic differentiation. Our combination of hydrogels allows dense tissue structures to be produced from HPSCs by using a single-step process inaccessible to any current methodology. The ability of materials to define the architecture and microenvironment experienced by cells provides new opportunities to direct the fate of human pluripotent stem cells (HPSCs) [Robinton DA, Daley GQ (2012) Nature 481(7381):295–305]. However, the conditions required for self-renewal vs. differentiation of HPSCs are different, and a single system that efficiently achieves both outcomes is not available [Giobbe GG, et al. (2012) Biotechnol Bioeng 109(12):3119–3132]. We have addressed this dual need by developing a hydrogel-based material that uses ionic de-cross-linking to remove a self-renewal permissive hydrogel (alginate) and switch to a differentiation-permissive microenvironment (collagen). Adjusting the timing of this switch can preferentially steer the HPSC differentiation to mimic lineage commitment during gastrulation to ectoderm (early switch) or mesoderm/endoderm (late switch). As an exemplar differentiated cell type, we showed that directing early lineage specification using this single system can promote cardiogenesis with increased gene expression in high-density cell populations. This work will facilitate regenerative medicine by allowing in situ HPSC expansion to be coupled with early lineage specification within defined tissue geometries.
Monitoring Real-time Metabolite Trafficking in the Brain using Microelectrochemical Biosensors

In a first series of experiments a glucose oxidase-based biosensor implanted in the striatum of freely moving rats was used to determine the concentration of brain extracellular (ECF) glucose in two distinct ways. With a modification of the zero-net-flux method, in which different concentrations of glucose are infused through a dialysis probe glued to the biosensor, the concentration at which there was no change in glucose current was calculated by regression analysis; this gave an ECF concentration of 351 ± 16 μM. The concentration calculated from the basal current and the in vitro calibration of the biosensor was not significantly different from this. The basal extracellular glucose concentration determined by either method remained constant over a period of several days. In a second series of experiments rats were implanted in the striatum with a Pt/Ir electrode for measurement of regional cerebral blood flow (rCBF, H 2 clearance technique), a carbon paste electrode for monitoring tissue oxygen, and a glucose biosensor for monitoring extracellular glucose. There was a parallel increase in rCBF and oxygen in response to neuronal activation (5 min tail pinch). During the neuronal activation there was a decrease in ECF glucose which was followed by a slow rise that took 30 min to return to basal levels. Finally, a group of rats implanted with a combined glucose biosensor and dialysis probe were given a 5 min tail pinch while the dialysis probe was perfused with either artificial cerebrospinal fluid (aCSF) alone or aCSF with the addition of the β -adrenoceptor antagonist propranolol. Perfusion with aCSF once again produced an initial reduction in extracellular glucose, which was co- extensive with the period of stimulation, followed by a delayed and long-lasting increase in glucose. Propranolol had no effect on basal levels of glucose but suppressed the delayed increase. These results suggests that extracellular glucose in the brain is not derived directly from the blood vascular system but from some other source which is most likely to be astrocytes
Scheduling of Single-Arm Multi-cluster Tools With Wafer Residency Time Constraints in Semiconductor Manufacturing

This paper studies the challenging problem of scheduling single-arm multi-cluster tools with wafer residency time constraints. They have a linear topology and their bottleneck tool is process-bound. This work aims to find an optimal one-wafer cyclic schedule. With the Petri net model developed in our previous work and the minimal cycle time for a multicluster tool without wafer residency time constraints, it derives the necessary and sufficient schedulability conditions for multicluster tools with wafer residency time constraints for the first time. Then, it gives an algorithm to find an optimal one-wafer cyclic schedule if schedulable. This is done by simply setting the robots' waiting time for each tool. Thus, it is very computationally efficient and applicable to practical problems. An example is presented to illustrate the proposed method.
Mutations of the Opsin Gene (Y102H and I307N) Lead to Light-induced Degeneration of Photoreceptors and Constitutive Activation of Phototransduction in Mice*

Mutations in the Rhodopsin (Rho) gene can lead to autosomal dominant retinitis pigmentosa (RP) in humans. Transgenic mouse models with mutations in Rho have been developed to study the disease. However, it is difficult to know the source of the photoreceptor (PR) degeneration in these transgenic models because overexpression of wild type (WT) Rho alone can lead to PR degeneration. Here, we report two chemically mutagenized mouse models carrying point mutations in Rho (Tvrm1 with an Y102H mutation and Tvrm4 with an I307N mutation). Both mutants express normal levels of rhodopsin that localize to the PR outer segments and do not exhibit PR degeneration when raised in ambient mouse room lighting; however, severe PR degeneration is observed after short exposures to bright light. Both mutations also cause a delay in recovery following bleaching. This defect might be due to a slower rate of chromophore binding by the mutant opsins compared with the WT form, and an increased rate of transducin activation by the unbound mutant opsins, which leads to a constitutive activation of the phototransduction cascade as revealed by in vitro biochemical assays. The mutant-free opsins produced by the respective mutant Rho genes appear to be more toxic to PRs, as Tvrm1 and Tvrm4 mutants lacking the 11-cis chromophore degenerate faster than mice expressing WT opsin that also lack the chromophore. Because of their phenotypic similarity to humans with B1 Rho mutations, these mutants will be important tools in examining mechanisms underlying Rho-induced RP and for testing therapeutic strategies.
The Use of Ultrasound Imaging to Demonstrate Reduced Movement of the Median Nerve during Wrist Flexion in Patients with Non-Specific Arm Pain

Following clinical screening, we examined movement of the median nerve at the wrist using high-resolution (10–22 MHz) ultrasound in 16 controls and 12 patients with non-specific arm pain (also referred to as repetitive strain injury). Imaging was performed just proximal to the carpal tunnel with the wrist in neutral, 30 degrees of extension and 30 degrees of flexion. In control subjects the position of the median nerve was 4.8 (SE=0.4) mm more radial with the wrist flexed than with the wrist extended. In the twelve arm pain patients the average change was only 1.2 (SE=0.5) mm. It appears that ultrasound imaging may be helpful in diagnosing non-specific arm pain, a condition for which there are no well-defined diagnostic tests at present. The reduced nerve movement seen with ultrasound imaging confirms previous work with magnetic resonance imaging.
Cationic surfactants-modified natural zeolites: improvement of the excipients functionality

Context: In this study an investigation of cationic surfactants-modified natural zeolites as drug formulation excipient was performed. Objective: The aim of this work was to carry out a study of the purified natural zeolitic tuff with high amount of clinoptilolite as a potential carrier for molecules of pharmaceutical interest. Materials and methods: Two cationic surfactants (benzalkonium chloride and hexadecyltrimethylammonium bromide) were used for modification of the zeolitic surface in two levels (equal to and twice as external cation-exchange capacity of the zeolitic tuff). Prepared samples were characterized by Fourier transform infrared spectroscopy, thermogravimetric, high-performance liquid chromatography analysis, and powder flow determination. Different surfactant/zeolite composites were used for additional investigation of three model drugs: diclofenac diethylamine, diclofenac sodium, and ibuprofen by means of adsorption isotherm measurements in aqueous solutions. Results: The modified zeolites with two levels of surfactant coverage within the short activation time were prepared. Determination of flow properties showed that modification of zeolitic surface reflected on powder flow characteristics. Investigation of the model drugs adsorption on the obtained composites revealed that a variation between adsorption levels was influenced by the surfactant type and the amount present at the surface of the composites. Discussion and conclusion: In vitro release profiles of the drugs from the zeolite-surfactant-drug composites revealed that sustained drug release could be attained over a period of 8 hours. The presented results for drug uptake by surfactant-zeolite composites and the afterward drug release demonstrated the potential use of investigated modified natural zeolite as excipients for advanced excipients in drug formulations.
Drug—Drug Interactions in the Elderly

OBJECTIVE: To detect the frequency of potential drug—drug interactions (DDIs) in an outpatient group of elderly people in 6 European countries, as well as to describe differences among countries. DATA SOURCES AND METHODS: Drug use data were collected from 1601 elderly persons living in 6 European countries. The study population participated in a controlled intervention study over 18 months investigating the impact of pharmaceutical care. Potential DDIs were studied using a computerized detection program. RESULTS: The elderly population used on average 7.0 drugs per person; 46% had at least 1 drug combination possibly leading to a DDI. On average, there were 0.83 potential DDIs per person. Almost 10% of the potential DDIs were classified to be avoided according to the Swedish interaction classification system, but nearly one-third of them were to be avoided only for predisposed patients. The risk of subtherapeutic effect as a result of a potential DDI was as common as the risk of adverse reactions. Furthermore, we found differences in the frequency and type of potential DDIs among the countries. CONCLUSIONS: Potential DDIs are common in elderly people using many drugs and are part of a normal drug regimen. Some combinations are likely to have negative effects; more attention must be focused on detecting and monitoring patients using such combinations. As differences in potential DDIs among countries were found, the reasons for this variability need to be explored in further studies.
Understanding the effect of mean pore size on cell activity in collagen-glycosaminoglycan scaffolds

Mean pore size is an essential aspect of scaffolds for tissue-engineering. If pores are too small cells cannot migrate in towards the center of the construct limiting the diffusion of nutrients and removal of waste products. Conversely, if pores are too large there is a decrease in specific surface area available limiting cell attachment. However the relationship between scaffold pore size and cell activity is poorly understood and as a result there are conflicting reports within the literature on the optimal pore size required for successful tissue-engineering. Previous studies in bone tissue-engineering have indicated a range of mean pore sizes (96–150 µm) to facilitate optimal attachment. Other studies have shown a need for large pores (300–800 µm) for successful bone growth in scaffolds. These conflicting results indicate that a balance must be established between obtaining optimal cell attachment and facilitating bone growth. In this commentary we discuss our recent investigations into the effect of mean pore size in collagen-glycosaminoglycan (CG) scaffolds with pore sizes ranging from 85–325 μm and how it has provided an insight into the divergence within the literature.
Anthropometric and cardiopulmonary parameters in Bulgarian and Romany children: cross-sectional study.

AIM To examine anthropometric parameters and cardiopulmonary function in Bulgarian and Romany children. METHODS Two hundred and ten healthy children (153 Bulgarian and 57 Romany) of similar age (10.5-/+0.5 years, mean-/+standard deviation) underwent an anthropometric and pulmonary function assessment and performed an exercise test on a treadmill, using the modified Balke protocol. RESULTS Bulgarian children were significantly taller (145-/+7 vs 142-/+7 cm) and heavier (39-/+9 vs 35-/+8 kg) than Romany children. They also had more body fat (20.5-/+8.1% vs 17.8-/+7.6% in Romanies). In a subset of the whole sample, it was established that Bulgarian children had significantly higher birth weight in comparison with Romanies (3,358-/+513 vs 3,095-/+435 g; P=0.006). Mean absolute values of vital capacity (VC), forced expiratory volume in 1 s (FEV(1)) and transfer factor (T(L,CO)) were lower for Romany than for Bulgarian children, 7.8%, 7.3%, and 10.2%, respectively. The data from the incremental treadmill test showed that peak oxygen uptake (VO(2)peak) did not differ significantly between the two ethnic groups (1,341-/+293 vs 1,260-/+280 mL/min). The level of physical exertion was almost the same in the studied groups (respiratory exchange ratio (RER)=1.08-/+0.08 vs 1.08-/+0.06), but the perception of exertion was higher in Bulgarian children (Borg score=4.9-/+1.5 vs 3.2-/+1.5; P<0.001). CONCLUSIONS There are significant differences between Bulgarian and Romany children with regard to anthropometric parameters, including stature, lung function indices, and perception of exertion.
Inner Ear Vestibular Signals Regulate Bone Remodeling via the Sympathetic Nervous System

The inner ear vestibular system has numerous projections on central brain centers that regulate sympathetic outflow, and skeletal sympathetic projections affect bone remodeling by inhibiting bone formation by osteoblasts and promoting bone resorption by osteoclasts. In this study, we show that bilateral vestibular lesions in mice cause a low bone mass phenotype associated with decreased bone formation and increased bone resorption. This reduction in bone mass is most pronounced in lower limbs, is not associated with reduced locomotor activity or chronic inflammation, and could be prevented by the administration of the β‐blocker propranolol and by genetic deletion of the β2‐adrenergic receptor, globally or specifically in osteoblasts. These results provide novel experimental evidence supporting a functional autonomic link between central proprioceptive vestibular structures and the skeleton. Because vestibular dysfunction often affects the elderly, these results also suggest that age‐related bone loss might have a vestibular component and that patients with inner ear pathologies might be at risk for fracture. Lastly, these data might have relevance to the bone loss observed in microgravity, as vestibular function is altered in this condition as well. © 2015 American Society for Bone and Mineral Research.
Activation of an enhancer on the syndecan-1 gene is restricted to fibroblast growth factor family members in mesenchymal cells

Fibroblast growth factors (FGFs) induce a variety of biological effects on different cell types. They activate a number of genes, including immediate-early genes, such as the transcription factors Fos and Jun, which are also common targets for other tyrosine kinase receptor-activating growth factors. Here we describe a secondary far-upstream enhancer on the syndecan-1 gene that is activated only by members of the FGF family in NIH 3T3 cells, not by other receptor tyrosine kinase-activating growth factors (e.g., epidermal growth factor, platelet-derived growth factor, insulin-like growth factor, or serum). This FGF-inducible response element (FiRE) consists of a 170-bp array of five DNA motifs which bind two FGF-inducible Fos-Jun heterodimers, one inducible AP-2-related protein, a constitutively expressed upstream stimulatory factor, and one constitutive 46-kDa transcription factor. Mutational analysis showed that both AP-1 binding motifs are required, but not sufficient, for FiRE activation. Moreover, agents such as 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or forskolin, which are known to activate AP-1 complexes and AP-1-driven promoters, fail to activate FiRE. However, FiRE can be activated by the tyrosine kinase phosphatase inhibitor orthovanadate. Taken together, this data implies a differential activation of growth factor-initiated signaling on AP-1-driven regulatory elements.