Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical pharmacogenomics testing in the era of next generation sequencing: challenges and opportunities for precision medicine

ABSTRACT Introduction: The rapid development and dramatic decrease in cost of sequencing techniques have ushered the implementation of genomic testing in patient care. Next generation DNA sequencing (NGS) techniques have been used increasingly in clinical laboratories to scan the whole or part of the human genome in order to facilitate diagnosis and/or prognostics of genetic disease. Despite many hurdles and debates, pharmacogenomics (PGx) is believed to be an area of genomic medicine where precision medicine could have immediate impact in the near future. Areas covered: This review focuses on lessons learned through early attempts of clinically implementing PGx testing; the challenges and opportunities that PGx testing brings to precision medicine in the era of NGS. Expert commentary: Replacing targeted analysis approach with NGS for PGx testing is neither technically feasible nor necessary currently due to several technical limitations and uncertainty involved in interpreting variants of uncertain significance for PGx variants. However, reporting PGx variants out of clinical whole exome or whole genome sequencing (WES/WGS) might represent additional benefits for patients who are tested by WES/WGS.
Pork as a Source of Omega-3 (n-3) Fatty Acids

Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6) to omega-3 (n-3) fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs n-3 fatty acids can increase their contents in pork, and in countries where label claims are permitted, claims can be met with limited feeding of n-3 fatty acid enrich feedstuffs, provided contributions of both fat and muscle are included in pork servings. Pork enriched with n-3 fatty acids is, however, not widely available. Producing and marketing n-3 fatty acid enriched pork requires regulatory approval, development costs, quality control costs, may increase production costs, and enriched pork has to be tracked to retail and sold for a premium. Mandatory labelling of the n-6/n-3 ratio and the n-3 fatty acid content of pork may help drive production of n-3 fatty acid enriched pork, and open the door to population-based disease prevention polices (i.e., food tax to provide incentives to improve production practices). A shift from the status-quo, however, will require stronger signals along the value chain indicating production of n-3 fatty acid enriched pork is an industry priority.
Reactive murine lymph nodes uniquely permit parenchymal access for T cells that enter via the afferent lymphatics

Whereas naïve T cells access the lymph nodes predominantly via the high endothelial venules, their effector counterparts can also enter via the afferent lymphatics. It is unclear if such cells are confined to the lymphatic spaces during their transit through the lymph node or whether they can access the lymphocyte‐ and dendritic cell‐rich parenchyma with its potentially stimulatory environment. We used a flank HSV inoculation model that featured neuronal‐mediated movement of virus to distinct areas of skin to study the lymphatic‐mediated transit of activated T cells between different skin‐draining lymph nodes. These experiments showed that activated T cells released from the brachial lymph node, draining the primary site of inoculation, entered the downstream axillary lymph node. These activated T cells accessed the subcapsular areas of the axillary lymph node via lymphatic vessels exiting the upstream brachial node regardless of whether the former drained skin that was associated with active infection. However, T cells remained within the sinusoidal network of the axillary lymph node unless it was directly associated with peripheral infection. Thus, activated T cells that enter a given lymph node using the afferent lymphatics do not have automatic access to the parenchyma unless it is a reactive node involved with peripheral inflammation or infection. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transdermal buprenorphine for moderate chronic noncancer pain syndromes

ABSTRACT Introduction: Chronic noncancer pain has remained a challenging clinical problem. Opioid analgesics are effective, but they are known to be associated with opioid use disorder and potentially treatment-limiting side effects. Buprenorphine is a Schedule III synthetic opioid in the USA with a chemical structure similar to that of morphine but with a longer duration of action, greater potency, and other unique pharmacological attributes. Its role in treatment of chronic noncancer pain may be broader than currently thought. Areas covered: The pharmacokinetics, pharmacodynamics, clinical efficacy, and safety profile of transdermal buprenorphine in moderate chronic noncancer pain syndromes patients will be discussed. Expert commentary: Buprenorphine offers effective analgesia in the form of a Schedule III drug (rather than Schedule II such as oxycodone or morphine) and transdermal buprenorphine is a convenient, accepted, around-the-clock pain reliever. Its lower potential for abuse should make it a more desirable pain reliever but many payers do not reimburse buprenorphine, driving prescribers and their patients to generic versions of the riskier Schedule II oral opioids such as oxycodone and morphine.
Occlusions and the next view planning

The strategy of acquiring 3-D data of unknown scenes is discussed. The analysis is limited to range images obtained by a light stripe range finder. Prior knowledge given to the system is the knowledge of the sensor geometry. The emphasis on the occluded regions, i.e. their shape and the height of the scene at their borders. Since the system has knowledge of the sensor geometry it can resolve the appearance of occlusions by analyzing them. <<ETX>>
c.light: A Tool for Exploring Light Properties in Early Design Stage

Although a light becomes an important design element, there are little techniques available to explore shapes and light effects in early design stages. We present c.light, a design tool that consists of a set of modules and a mobile application for visualizing the light in a physical world. It allows designers to easily fabricate both tangible and intangible properties of a light without a technical barrier. We analyzed how c.light contributes to the ideation process of light design through a workshop. The results showed that c.light largely expands designers' capability to manipulate intangible properties of light and, by doing so, it facilitates collaborative and inverted ideation process in early design stages. It is expected that the results of this study could enhance our understanding of how designers manipulate light in a physical world in early design stages and could be a good stepping stone for future tool development.
Abstract of: Experimental analysis on the glass-interlayer system in glass masonry arches

In the last decade there has been an increased usage of cast glass as structural element. Within this respect, a 14 m span glass masonry arch bridge is planned to be constructed at the TU Delft Campus. This paper focuses on part of the experimental analysis that was executed to develop the concept of this bridge. Since it is an arch, the applied loads will be transferred as compressive forces, hence the suitability of glass. Adhesive bonding is not required, since the arch isin compression under its own weight. Application of cast glass bricks in a bridge is a new concept, therefore several aspects with respect to the structural behavior are unknown. Two experimental tests are presented in this paper. First, an experiment with a stacked glass column with varying interlayers is loaded to investigate the stiffness of the interlayer. For PVC interlayers the time-dependent behavior is significant, whereas for polyurethane it is minimal. Furthermore the interlayer’s equivalent modulus of elasticity is dependent on the thickness, due to a difference in the occurring contact areas. Second, a small-scale glass masonry arch is loaded till collapse to investigate the failure behavior and the stresses distribution. It was concluded that a certain robustness is present in the system. Furthermore the brick geometry and the occurrence of sliding are the main aspects that determine the stress distribution. Therewith a stiffer interlayer results in higher stresses in the glass.
Dispelling the myth: the use of renin-angiotensin blockade in atheromatous renovascular disease.

BACKGROUND Many physicians retain reservations regarding the routine prescription of renin-angiotensin blockade (RAB) in patients with atheromatous renovascular disease (ARVD). Conversely, these patients are in most need of the cardio- and renal protection offered by RAB. This reservation is mostly because of fear of precipitating acute renal deterioration. We aimed to study whether RAB can be used safely in ARVD patients and whether it altered their outcome. METHODS Prospective observational study of all ARVD patients presenting to our tertiary referral centre from 1999-2009. Data capture included usage and tolerability of RAB, and correlation with endpoints of cardiovascular events, dialysis or death. RESULTS Six hundred and twenty-one subjects were available for analysis. Mean age (SD) of the cohort was 71.3 (8.8) years, median (interquartile range) follow-up 3.1 (2.1, 4.8), range 0.2-10.61 years. Seventy-four patients had an intolerance to RAB at study entry. When utilized prospectively, RAB was tolerated in 357 of 378 patients (92%), and this was even seen in 54/69 (78.3%) patients with bilateral>60% renal artery stenosis (RAS) or occlusion. Patients (4/21) who were intolerant of RAB during follow-up (and 12 retrospectively intolerant), underwent renal revascularization which facilitated safe use of these medications post-procedure. On multivariate time-adjusted analysis, patients receiving RAB were significantly less likely to die (P=0.02). CONCLUSION RAB is well tolerated even in patients with bilateral severe RAS and reduced mortality in a large group of ARVD patients. We recommend all ARVD patients be considered for RAB therapy unless an absolute contra-indication exists. Intolerance of these agents due to renal dysfunction should be considered an emerging indication for renal revascularization to facilitate their re-introduction.
Intellingo: An Intelligible Translation Environment

Translation environments offer various translation aids to support professional translators. However, translation aids typically provide only limited justification for the translation suggestions they propose. In this paper we present Intellingo, a translation environment that explores intelligibility for translation aids, to enable more sensible usage of translation suggestions. We performed a comparative study between an intelligible version and a non-intelligible version of Intellingo. The results show that although adding intelligibility does not necessarily result in significant changes to the user experience, translators can better assess translation suggestions without a negative impact on their performance. Intelligibility is preferred by translators when the additional information it conveys benefits the translation process and when this information is not part of the translator's readily available knowledge.
Red, far-red response & chlorophyll synthesis.

One of the earliest observations on the photomorphogenic development of chlorophyll synthesis was made by Withrow et al. (10). In a preliminary report they noted that pretreatment of leaves with up to 10 millijoules (mj/cm2) of red radiant energy followed by a dark period of from 5 to 15 hours, resulted in the elimination of the latent period in subsequent chlorophyll formation, with some indication that the red induction might be reversed by an exposure to far-red. Virgin verified this observation of the involvement of the photomorphogenic induction effect on the development of the chlorophyll synthesizing mechanism (6) and demonstrated the greater effectiveness of red over blue pretreatment (7). Althouggh the induction response has been clearly demonstrated, the far-red reversal phenomenon associated with chlorophyll synthesis has not been previously shown. The data herein presented establish clearly that chlorophyll synthesis is another of the physiological responses referred to as red, far-red reactions, in which stimulation of plastid pigment synthesis by a short red preirradiation may be nullified by a subsequent far-red pretreatment. However, the red, far-red effect on chlorophyll synthesis is not directly associated with the photoconversion of protochlorophyllide (11). It is, rather, a reflection of metabolic and growth changes affecting the rate of synthesis of protochlorophyllide, these growth and metabolic changes having been induced by means of the primary effect of light on the photomorphogenic pigment receptor (4).
BIGFile: Bayesian Information Gain for Fast File Retrieval

We introduce BIGFile, a new fast file retrieval technique based on the Bayesian Information Gain framework. BIGFile provides interface shortcuts to assist the user in navigating to a desired target (file or folder). BIGFile's split interface combines a traditional list view with an adaptive area that displays shortcuts to the set of file paths estimated by our computationally efficient algorithm. Users can navigate the list as usual, or select any part of the paths in the adaptive area. A pilot study of 15 users informed the design of BIGFile, revealing the size and structure of their file systems and their file retrieval practices. Our simulations show that BIGFile outperforms Fitchett et al.'s AccessRank, a best-of-breed prediction algorithm. We conducted an experiment to compare BIGFile with ARFile (AccessRank instantiated in a split interface) and with a Finder-like list view as baseline. BIGFile was by far the most efficient technique (up to 44% faster than ARFile and 64% faster than Finder), and participants unanimously preferred the split interfaces to the Finder.
Accurate Calibration and Uncertainty Estimation of the Normal Spring Constant of Various AFM Cantilevers

Measurement of force on a micro- or nano-Newton scale is important when exploring the mechanical properties of materials in the biophysics and nanomechanical fields. The atomic force microscope (AFM) is widely used in microforce measurement. The cantilever probe works as an AFM force sensor, and the spring constant of the cantilever is of great significance to the accuracy of the measurement results. This paper presents a normal spring constant calibration method with the combined use of an electromagnetic balance and a homemade AFM head. When the cantilever presses the balance, its deflection is detected through an optical lever integrated in the AFM head. Meanwhile, the corresponding bending force is recorded by the balance. Then the spring constant can be simply calculated using Hooke’s law. During the calibration, a feedback loop is applied to control the deflection of the cantilever. Errors that may affect the stability of the cantilever could be compensated rapidly. Five types of commercial cantilevers with different shapes, stiffness, and operating modes were chosen to evaluate the performance of our system. Based on the uncertainty analysis, the expanded relative standard uncertainties of the normal spring constant of most measured cantilevers are believed to be better than 2%.
CliffoSor: a parallel embedded architecture for geometric algebra and computer graphics

Geometric object representation and their transformations are the two key aspects in computer graphics applications. Traditionally, compute-intensive matrix calculations are involved to model and render 3D scenery. Geometric algebra (a.k.a. Clifford algebra) is gaining growing attention for its natural way to model geometric facts coupled with its being a powerful analytical tool for symbolic calculations. In this paper, the architecture of CliffoSor (Clifford Processor) is introduced. ClifforSor is an embedded parallel coprocessing core that offers direct hardware support to Clifford algebra operators. A prototype implementation on an FPGA board is detailed. Initial test results show more than 4/spl times/ speedup for Clifford products against the analogous operations in GAIGEN, a standard geometric algebra library generator for general purpose processors.
The influence of calcination temperature on structural and optical properties of ZnO nanoparticles via simple polymer synthesis route

A simple polymer synthesis was used to successfully synthesized Zinc Oxide Nanoparticles (ZnO NPs), and the influence of the different calcination temperature on the structural, and optical properties of the material was observed using several techniques. The formation of ZnO NPs was confirmed by FT−IR, EDX, XRD, FESEM and TEM images upon calcination from 500−750 °C. The FESEM images showed the ZNO NPs synthesized possessed a hexagonal shape and tended to become larger at higher calcination temperature. The XRD and FTIR revealed the precursor to be amorphous at room temperature but transform to a crystalline structure during the process of calcination. The crystalline and particle size increase as the temperature was increased. The crystalline size was between 24−49 nm for all samples calcined at 500−750 °C. The optical properties obtained by UV−vis reflectance spectrometer have further confirmed the formation of ZnO NPs. The band gap exhibits typical ZnO wide band gap, and the values decrease with an increase in calcination temperature.
Statistical Modeling and Performance Characterization of Ultrashort Light Pulse Communication System Using Power-Cubic Optical Nonlinear Preprocessor

In this paper, we present an analytical approach in obtaining the probability density function (pdf) of the random decision variable Y, which is formed at the output of the power-cubic all-optical nonlinear preprocessor followed by the photodetector, with applications in ultrafast optical time-division multiplexing and optical code-division multiple-access systems. Our approach can be used to accurately evaluate the performance of ultrafast pulse detection in the presence of Gaussian noise. Through rigorous Monte Carlo simulation, the accuracy of the widely used Gaussian approximation of decision variable Y is refuted. However, in this paper, we show that the so-called log-Pearson type-3 (LP3) pdf is an excellent representation for the decision variable Y. Three distinguishable parameters of the LP3 pdf are obtained through an analytical derivation of three moments of the decision variable Y. Furthermore, toward a more realistic model, in addition to amplified spontaneous emission Gaussian noise, the effects of shot and thermal noises are also included. Finally, using the presented analytical approach, it is shown that the power-cubic preprocessor outperforms its quadratic counterparts, i.e., second-harmonic-generation and two-photon-absorption devices, in the high-power regime where shot and thermal noises can be neglected.
Exploration in POMDP belief space and its impact on value iteration approximation

Decision making under uncertainty is among the most challenging tasks in the artificial intelligence. Although solution methods to this class of problems are intractable in general, some promising approximation methods have been proposed recently. In particular, point-based planning algorithms for solving partially observable Markov decision processes (POMDPs) have demonstrated that a good approximation of the value function can be obtained by interpolating between the values of a selected set of points. The agent must make a choice as to how to sample these points. Ideally, we need to sample in order to build an accurate approximation in less time. In this paper, we relate this problem to the explorationexploitation tradeoff in the space of POMDP reachable beliefs. Furthermore, we show that there exists an influential control parameter for this tradeoff. As a result, we provide a controllable tighter bound for the point-based value iteration (PBVI) approximation [4] based on knowledge about the domain. We study two criteria designed to improve point-based value iteration algorithms when selecting candidate points. The first is based on reachability analysis from the given initial belief state. The second criterion is based on the degree of stochasticity of the problem domain and the topological structure of possible beliefs experienced by the agent. We present an empirical evaluation illustrating the effect of these criteria on the performance of point-based value iteration.
ELANE mutant–specific activation of different UPR pathways in congenital neutropenia

A number of studies have demonstrated induction of the unfolded protein response (UPR) in patients with severe congenital neutropenia (CN) harbouring mutations of ELANE, encoding neutrophil elastase. Why UPR is not activated in patients with cyclic neutropenia (CyN) carrying the same ELANE mutations is unclear. We evaluated the effects of ELANE mutants on UPR induction in myeloid cells from CN and CyN patients, and analysed whether additional CN‐specific defects contribute to the differences in UPR induction between CN and CyN patients harbouring identical ELANE mutations. We investigated CN‐specific p.C71R and p.V174_C181del (NP_001963.1) and CN/CyN‐shared p.S126L (NP_001963.1) ELANE mutants. We found that transduction of haematopoietic cells with p.C71R, but not with p.V174_C181del or p.S126L ELANE mutants induced expression of ATF6, and the ATF6 target genes PPP1R15A, DDIT3 and HSPA5. Recently, we found that levels of secretory leucocyte protease inhibitor (SLPI), a natural ELANE inhibitor, are diminished in myeloid cells from CN patients, but not CyN patients. Combined knockdown of SLPI by shRNA and transduction of ELANE p.S126L in myeloid cells led to elevated levels of ATF6, PPP1R15A and HSPA5 RNA, suggesting that normal levels of SLPI in CyN patients might protect them from the UPR induced by mutant ELANE. In summary, different ELANE mutants have different effects on UPR activation, and SLPI regulates the extent of ELANE‐triggered UPR.
Earliest Carboniferous tetrapod and arthropod faunas from Scotland populate Romer's Gap

Devonian tetrapods (limbed vertebrates), known from an increasingly large number of localities, have been shown to be mainly aquatic with many primitive features. In contrast, the post-Devonian record is marked by an Early Mississippian temporal gap ranging from the earliest Carboniferous (Tournaisian and early Viséan) to the mid-Viséan. By the mid-Viséan, tetrapods had become effectively terrestrial as attested by the presence of stem amniotes, developed an essentially modern aspect, and given rise to the crown group. Up to now, only two localities have yielded tetrapod specimens from the Tournaisian stage: one in Scotland with a single articulated skeleton and one in Nova Scotia with isolated bones, many of uncertain identity. We announce a series of discoveries of Tournaisian-age localities in Scotland that have yielded a wealth of new tetrapod and arthropod fossils. These include both terrestrial and aquatic forms and new taxa. We conclude that the gap in the fossil record has been an artifact of collection failure.