Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of applying modes of the polymer microneedle-roller on the permeation of l-ascorbic acid in rats

Despite the advantages of drug delivery through skin, transdermal drug delivery is only used with a small subset of drugs because most compounds cannot cross the skin at therapeutically useful rates. Recently, a new concept known as microneedle was introduced and could be used to pierce effectively to deliver drugs using micron-sized needles in a minimally invasive and painless manner. In this study, the polymer microneedle-roller was fabricated so that it can be applied into the permeation of l-ascorbic acid. Moreover, a recent publication suggested the possibility of ascorbic acid 2-phosphate as a hair restorer; hence, this study was carried out to check the effect of l-ascorbic acid itself on the hair growing rate in rats according to the presence of various application frequencies of the polymer microneedle-roller. When the polymer microneedle-roller was applied nine times with four directions into rat’s shaved skin, the permeation of l-ascorbic acid increased by 10.54-fold compared to that of the absence of the polymer microneedle-roller. The histological examination revealed that the skin pretreated with various application frequencies of the polymer microneedle-roller had more transport pathways. The faster hair growing phenomenon was observed in the presence of polymer microneedle-roller compared to the absence of the polymer microneedle-roller.
Cadaveric study validating in vitro monitoring techniques to measure the failure mechanism of glenoid implants against clinical CT

Definite glenoid implant loosening is identifiable on radiographs, however, identifying early loosening still eludes clinicians. Methods to monitor glenoid loosening in vitro have not been validated to clinical imaging. This study investigates the correlation between in vitro measures and CT images. Ten cadaveric scapulae were implanted with a pegged glenoid implant and fatigue tested to failure. Each scapulae were cyclically loaded superiorly and CT scanned every 20,000 cycles until failure to monitor progressive radiolucent lines. Superior and inferior rim displacements were also measured. A finite element (FE) model of one scapula was used to analyze the interfacial stresses at the implant/cement and cement/bone interfaces. All ten implants failed inferiorly at the implant‐cement interface, two also failed at the cement‐bone interface inferiorly, and three showed superior failure. Failure occurred at of 80,966 ± 53,729 (mean ± SD) cycles. CT scans confirmed failure of the fixation, and in most cases, was observed either before or with visual failure. Significant correlations were found between inferior rim displacement, vertical head displacement and failure of the glenoid implant. The FE model showed peak tensile stresses inferiorly and high compressive stresses superiorly, corroborating experimental findings. In vitro monitoring methods correlated to failure progression in clinical CT images possibly indicating its capacity to detect loosening earlier for earlier clinical intervention if needed. Its use in detecting failure non‐destructively for implant development and testing is also valuable. The study highlights failure at the implant‐cement interface and early signs of failure are identifiable in CT images. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2524–2532, 2018.
Biguanide-associated lactic acidosis. Case report and review of the literature.

PURPOSE The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis. PATIENT We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia. RESULTS Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital. CONCLUSIONS Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.
Pathogenic mtDNA mutations causing mitochondrial myopathy: The need for muscle biopsy

Pathogenic mitochondrial tRNA (mt-tRNA) gene mutations represent a prominent cause of primary mitochondrial DNA (mtDNA)-related disease despite accounting for only 5%–10% of the mitochondrial genome.1,2 Although some common mt-tRNA mutations, such as the m.3243A>G mutation, exist, the majority are rare and have been reported in only a small number of cases.3 The MT-TP gene, encoding mt-tRNAPro, is one of the less polymorphic mt-tRNA genes, and only 5 MT-TP mutations have been reported as a cause of mitochondrial muscle disease to date (table e-1 at Neurology.org/ng, P6–10). We report 5 patients with myopathic phenotypes, each harboring different pathogenic mutations in the MT-TP gene, highlighting the importance of MT-TP mutations as a cause of mitochondrial muscle disease and the requirement to study clinically relevant tissue.
Concept of the Existence of Human Papillomavirus (HPV) DNA in Histologically Normal Squamous Epithelium of the Genital Tract Should be Re‐Evaluated

Because of the crucial importance of guiding current thinking in the field of HPV epidemiology, the concept of the existence of HPV DNA in histologically normal squamous epithelium was re‐evaluated. A series of 102 randomly collected cervical punch biopsies, previously proved to contain the DNA of HPV types 6, 11, 16, 18, 31 or 33 by in situ hybridization were subjected to analysis for the localization of HPV DNA, i.a. , whether found in the normal epithelium or at the lesion site only. This material consisted of a representative series of flat, endophytic and papillary HW lesions with all histological grades from HPV‐NCIN to HPV‐CIN 111, and the six HPV types in the same proportions as they occur in non‐selected series of HPV lesions. Weak signals of HW DNA were found in the basal cells in 6/102 (5.8%) of the biopsies. HPV DNA was constantly present in the parabasal cells in 25/102 (25.4%). in the intermediate cell layers in (98/102, 96%), and in the superficial cells of all 102 lesions. Noteworthy was the constant failure to reveal even weak signals of HPV DNA (of any of the six types) in histologically normal squamous epithelium of any of the 87 lesions, where such an epithelium was detectable. The present findings confirm our previous ‘impression’ that HW DNA rarely if ever appears in the histologically normal squamous (or columnar) epithelium in the genital tract, when analysed using the in situ hybridization. Thus, great care should be exercised in interpreting results that suggest the discovery of HW DNA in normal genital tract epithelium, unless based on firm documentation by in situ hybridization.
Characterization of Enamel Incremental Markings and Crown Growth Parameters in Minipig Molars

We studied the structure and periodicity of regular incremental markings in third molar enamel of minipigs. Light microscopy of ground sections revealed the presence of incremental markings matching the description of laminations. Their number within the section planes closely paralleled crown formation time (CFT) in days reported for minipig third molars, thereby indicating the daily nature of laminations. Spacing of consecutive laminations increased from lowest values in the inner to highest values in the outer enamel, where mean daily secretion rates of about 20 µm were recorded. Mean enamel extension rates determined for deciles along the enamel‐dentin junction varied between highest values (155 µm/day) in the most cuspally located and lowest values (19 µm/day) in cervical enamel. Backscattered electron imaging in the SEM revealed the presence of thin, regularly spaced hypermineralized incremental lines in the outer enamel portion. These lines exhibited the same spacing as the laminations and were, thus, likewise regarded as daily incremental markings. Between two successive daily incremental markings, subdaily growth marks were discernible in light microscopic and in BSE‐SEM images. These subdaily growth marks closely resembled the (daily) prism‐cross striations of human enamel. Supra‐daily growth marks were not identified in the minipig enamel. The results of this study parallels previous findings in sheep enamel. It is cautioned that CFT of ungulate teeth may be considerably overestimated if the periodicity established for growth marks in human enamel is uncritically transferred to the analysis of morphologically similar growth marks in ungulate enamel. Anat Rec, 297:1935–1949, 2014. © 2014 Wiley Periodicals, Inc.
Why the 'last drinking occasion' approach to measuring alcohol consumption should be avoided.

INTRODUCTION AND AIMS There has been debate about which type of measurement instrument gives the best alcohol consumption estimates. This study used alcohol consumption data for a simulated population to compare the last drinking occasion (LDO) method against the true alcohol consumption. The LDO method requires respondents to indicate the quantity consumed at the LDO, and this information is used to calculate population estimates. DESIGN AND METHODS We simulated three hypothetical distributions of alcohol consumption, each with different underlying drinking patterns and each representing an idealised example of the distribution of alcohol consumption in Norway, Russia and France under specified conditions. We investigated the level of agreement between LDO consumption and the within-person average consumption, and the expected bias that arises when parameters of interest such as means, percentiles, exceedance proportions, differences in group means, correlation and regression coefficients, attributable fractions, and estimated disease risk functions, are calculated from LDO consumption. RESULTS Severe bias was found when LDO consumption was used to calculate common parameters of interest in alcohol and health research. The bias is caused by poor agreement between consumption at the LDO and the within-person 'true' or average consumption. The asymptotically expected bias is particularly problematic because it is unpredictable in terms of direction and magnitude, it varies across groups and populations, and it is probably impossible to adjust for. DISCUSSION AND CONCLUSION Future data collections should avoid relying on the LDO method as a measure of typical alcohol consumption, despite its ease of administration. [Østhus S, Brunborg GS. Why the 'last drinking occasion' approach to measuring alcohol consumption should be avoided. Drug Alcohol Rev 2015;34:549-58].
Objective based modelling and simulation within a context of an electric vehicle development program

Modelling and simulation have become inseparable activities in any applied science or engineering research and development endeavour. The nature of inseparability is even more evident in the case of the automotive industry. Adding to the modelling complexity are the electric vehicles with a rich interplay of previously well demarcated disciplines of electrical-electronics engineering and mechanical-automotive engineering (and to a lesser extent chemical engineering). A traditional internal combustion engine vehicle development program has very well segmented and well defined set of modelling and simulation activities. The modelling and simulation tools used are mature and have been tested and proven. However, an electric vehicle program often suffers if a decision to pursue the traditional approach is accepted. The complex interplay of different disciplines, the lack of expert/mature modelling and simulation tools and constantly changing landscape of electric vehicles tend to keep the electric vehicle modelling and simulation groups small, esoteric and often lacking in direction. In this work we define three guiding principles for a modelling and simulation group in the context of an electric vehicle development program. The interaction between three connected but dissimilar facets of modelling and simulation, i.e., vehicle level simulation, sub-system level modelling and simulation and model inspired in-vehicle algorithms are explored based on objectives that are defined before the start of the modelling and simulation exercise. The importance of finding the right common thread, model fidelity and continuous learning are discussed.
Regional nitrogen dynamics in the TERENO Bode River catchment, Germany, as constrained by stable isotope patterns

Interactions between hydrological characteristics and microbial activities affect the isotopic composition of dissolved nitrate in surface water. Nitrogen and oxygen isotopic signatures of riverine nitrate in 133 sampling locations distributed over the Bode River catchment in the Harz Mountains, Germany, were used to identify nitrate sources and transformation processes. An annual monitoring programme consisting of seasonal sampling campaigns in spring, summer and autumn was conducted. δ15N and δ18O of nitrate and corresponding concentrations were measured as well as δ2H and δ18O of water to determine the deuterium excess. In addition, precipitation on 25 sampling stations was sampled and considered as a potential input factor. The Bode River catchment is strongly influenced by agricultural land use which is about 70 % of the overall size of the catchment. Different nitrogen sources such as ammonia (NH4) fertilizer, soil nitrogen, organic fertilizer or nitrate in precipitation show partly clear nitrate isotopic differences. Processes such as microbial denitrification result in fractionation and lead to an increase in δ15N of nitrate. We observed an evident regional and partly temporal variation of nitrate isotope signatures which are clearly different between main landscape types. Spring water sections within the high mountains contain nitrate in low concentrations with low δ15NNO3 values of −3 ‰ and high δ18ONO3 values up to 13 ‰. High mountain stream water sub-catchments dominated by nearly undisturbed forest and grassland contribute nitrate with δ15NNO3 and δ18ONO3 values of −1 and −3.5 ‰, respectively. In the further flow path, which is affected by an increasing agricultural land use and urban sewage, we recognized an increase in δ15NNO3 and δ18ONO3 up to 22 and 18 ‰, respectively, with high variations during the year. A correlation seems to exist between the percentage of agricultural land use area and the corresponding δ15NNO3 values for sub-catchments. A shift towards heavier isotope values in stream water samples taken in July 2012 is significant (p-value = 6 · 10−6) compared to samples from March and October 2012. We also see a season-depending impact of microbial denitrification. Denitrification, especially evident in the lowlands, predominantly takes place in the riverbeds. In addition, mixing processes of different nitrate sources and temperature-depending biological processes such as nitrification have to be taken into consideration. Constant-tempered groundwater does not play a noticeable role in the processes of the stream water system. As constrained from oxygen isotope signatures, precipitation associated with low nitrate concentrations does not have an obvious impact on stream water nitrate in the high mountain region.
[Long-term hemodynamic compromise in internal carotid artery dissection: quantitative blood volume flow evaluation using 2D Cine phase-contrast MR imaging].

PURPOSE To use the magnetic resonance (MR) phase-contrast technique as a non-invasive method to determine blood volume flow in internal carotid artery (ICA) dissection, which has variable initial volume flow reduction and long term hemodynamic compromise. ICA dissection can lead to partial or complete recanalization or persistent occlusion, and strong clinical motivation exists for reliable assessment of the blood flow, in particular blood volume flow, in the carotid artery circulation after ICA dissection. MATERIALS AND METHODS Blood volume flow in the carotid artery circulation was quantified in 28 patients with unilateral ICA dissection and 20 age-matched normal controls. Blood volume flow was measured in the ICAs and the common carotid arteries (CCAs) using 2D cine phase-contrast MR imaging. Final measurements were performed until after at least 6 months the hemodynamic compromise showed no changes by ultrasound and MRA. RESULTS In long term follow up, 11/28 patients demonstrated remaining vessel occlusion, 10/28 partial and 7/28 complete recanalizations. Patients with ICA occlusion showed a significant contralateral volume flow increase (mean 56 %, p < 0.001) in comparison to normal controls. Patients with partial recanalization demonstrated volume flow rates between 24 ml/min and 188 ml/min in the dissected ICA and a less but significant (p < 0.001) increase in the contralateral volume flow. In patients with complete recanalization, normal volume flow conditions were found for both ICAs and CCAs. CONCLUSION In ICA dissection, quantitative volume flow determination using 2D cine phase-contrast MR imaging is helpful in the initial assessment and long term follow-up of hemodynamic compromise. ICA dissection demonstrated a partial or complete recanalization in nearly (2/3) of the investigated patients and a persisting vessel occlusion in little more than (1/3). Compensatory contralateral increase in volume flow was found.
Contribution à la modélisation numérique des interfaces dans les structures maçonnées

Le but de cette these est la modelisation des interfaces dans des structures maconnees en prenant en consideration les principaux phenomenes mecaniques qui gouvernent leur rupture tels que l'adhesion, le glissement, le frottement, l'endommagement,… Dans cette optique, nous avons mene dans la premiere partie de ce travail une etude experimentale sur les differents composants de la maconnerie a savoir les briques et le mortier et sur des prismes de maconnerie composes de deux et de trois briques (pleines et creuses) connectees par des joints du mortier afin de determiner les caracteristiques mecaniques de chaque materiau ainsi que les lois de comportement de ces structures. Le comportement mecanique observe sur les differents couplets et triplets composes de briques pleines et de briques creuses testes est caracterise par un comportement tres rigide dans le domaine elastique. Lorsque la contrainte maximale est atteinte on obtient un comportement fragile sur les prismes en briques pleines, contrairement a la reponse des prismes en briques creuses qui est caracterise par un comportement d'adoucissement suivi par un mouvement de glissement entre les briques adjacentes. La dispersion des resultats obtenus sur les memes types de prismes conduit a des modes de ruptures tres variables. Cependant, nous avons distingue deux types de fissures. Soit les fissures sont developpees au niveau des interfaces brique-mortier soit les fissures sont produites au niveau de l'interface brique-mortier et au niveau du mortier simultanement. Au niveau de ces interfaces se developpent des non linearites qui fragilisent le comportement de l'ensemble jusqu'a la rupture totale. La seconde partie de ce travail est dediee a la modelisation numerique du comportement de ces structures maconnees a l'aide du code de calcul LMGC90. Plus precisement, la validation d'un modele d'interface RCCM qui prenne en compte ces non linearites notamment l'endommagement. Nous avons commence par valider ce modele d'interface a l'echelle locale sur les assemblages testes experimentalement. Ensuite, nous avons elargi l'application du modele RCCM a d'autres structures (murs de diverses tailles). Les resultats obtenus nous ont permis de mettre en evidence la puissance de l'outil de calcul a reproduire le comportement de ce type de structure
Stability of J-integral calculation in the crack growth of copper/low-K stacked structures

As the technology of the semiconductor process continues to move forward, the next generation IC chip with copper/low-k stacked structures is being developed for reducing the RC delay in order to obtain high-speed signal communication. However, there is a high potential that in doing so it may contribute to interfacial cracks occurring or propagating between the copper interconnections and the low-k material as a result of poor adhesion and lower fracture toughness of the low-k material when temperature loads are applied during the wafer level and the packaging level stages. This fracturing problem is one of the most urgent issues for the thermo-mechanical reliability of a copper/low-k damascene module, and it needs to be resolved urgently. With the simulation of an interfacial fracture based on J-integral value estimation, the interfacial crack growth can be modeled using a finite element analysis (FEA) and compared it to Jc, which is interfacial fracture toughness that must be determined experimentally. Therefore, the stability of the J-integral value obtained from the FEA is crucial so as to avoid a misunderstanding of the cracking energy. In order to discuss the mesh density affecting the convergence of the J-value, various paths with an integral contour surrounding the crack tip are considered in this research. The interfacial crack is constructed using the element birth and death technique to suppose that an actual crack developed between copper/low-k interfaces. The analytic results show that the J-value will converge toward unity when a rectangular contour with a proper ratio of length/width, and multi-layers of element close to the delaminating surfaces are applied to reduce the loss of numerical analysis in precise. It should be noted that the crack tip must be at the center of the integral contour. The long side of the rectangular contour needs to be parallel to the direction of the fracture propagation. On the other hand, the curve of the J-value versus the increase of the crack length calculated from the model with the actual crack embedded shows good agreement with the simulated results with the virtual crack by means of the element birth and death technique