Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple elements in the 5' untranslated region down-regulate c-sis messenger RNA translation.

Expression of the platelet derived growth factor (PDGF) B-chain, the product of the c-sis proto-oncogene, is regulated both at the transcriptional and translational level. Previous studies have shown that the long 5' untranslated region (UTR) of the c-sis mRNA strongly inhibits synthesis of the PDGF-B chain. However, the assignments of down-regulatory regions within the 5' UTR were ambiguous. Expression of several site-directed point and deletion mutants of the 5' UTR of the c-sis mRNA in COS1 cells revealed that the UTR inhibited PDGF-B chain synthesis in a more complex manner than indicated by the previous studies. Abrogation of the three upstream short open reading frames by mutating each of the AUGs did not have any effect on the synthesis of the PDGF-B chain. Expression of deletion mutants revealed two partially overlapping regions, nucleotides 1-651 and 475-1022, each of which independently inhibited c-sis mRNA translation as effectively as the entire 5' UTR. Each of these regions contains a potentially strong stem-loop structure and a GC-rich element. These elements of the alternate down-regulatory regions could interact within the same region and/or with the elements of the other regulatory region to block c-sis mRNA translation. We show, in contrast to the previous reports, that the inhibition of c-sis mRNA translation cannot be attributed exclusively to any particular predicted secondary structure or a GC-rich element within the 5' UTR. (ABSTRACT TRUNCATED AT 250 WORDS)
Resistance of stem‐like cells from neuroblastoma cell lines to commonly used chemotherapeutic agents

Cancer stem cell theory suggests that the presence of tumor initiating stem‐like cells in cancers may be responsible for cancer progression and relapse. CD133 cell surface maker expression has been used to identify stem‐like cells in cancer cell lines. Our goal was to identify such cells in neuroblastoma cell lines and to study the cytotoxicity of common anticancer drugs for those cells.
ISAR Imaging Enhancement Using Vernier Ranging Method

In radar imaging, one of the important steps includes target ranging. The Vernier ranging method (VRM) integrated into a stepped frequency chirp waveform (SFCW) radar is able to provide high ranging accuracy up to the order of millimeters without the need for increased bandwidth but with an increased computational complexity. The choice of system parameter is also discussed. This method is suitable for measuring range in inverse synthetic aperture radar (ISAR). With a higher precision and accurate ranging system, an enhanced ISAR image can be obtained
Delignification of Date Palm Fronds using Modified Organosolv Technique

In this study, modified organic solvent (organosolv) method was applied to remove high lignin content in the date palm fronds (type Al-Zahdi) which was taken from the Iraqi gardens. In modified organosolv, lignocellulosic material is fractionated into its constituents (lignin, cellulose and hemicellulose). In this process, solvent (organic)-water is brought into contact with the lignocellulosic biomass at high temperature, using stainless steel reactor (digester). Therefor; most of hemicellulose will remove from the biomass, while the solid residue (mainly cellulose) can be used in various industrial fields. Three variables were studied in this process: temperature, ratio of ethanol to water and digestion time. Statistical experimental design type Central Composite Design (CCD) has been used to find a mathematical relationship between the variables and the remaining lignin percent as dependent variable. The results obtained in this study were represented by a polynomial mathematical equation of the second degree. The results showed that the best digestion time was (80 minutes), which gave the best percent remaining concentration of lignin (3%) at temperature of 185C and ratio of ethanol: water equal to 50: 50 wt/wt. In order to reduce digesting time, the effect of using different catalysts have been studied such as (NaOH, H2SO4, Ca (OH) 2) at low concentration (0.025, 0.025, 0.05M) respectively. It was found that the best catalyst is sodium hydroxide at concentration (0.025) mol/L which gave the same percent of lignin 3% but with low digestion time about 30 min.
Deuterium astration in the local disc and beyond

Estimates of the interstellar deuterium abundance span a wide range of values. Until recently, it was customary to adopt the abundance of deuterium measured in the Local Bubble as representative of the local one. Now, it is becoming unclear whether the true local deuterium abundance is significantly higher or lower than this value, depending on the interpretation given to current data. It is important to deal with the issue of the deuterium variation and see whether it challenges our current understanding of the Galaxy evolution. To this aim, we study the evolution of deuterium in the framework of successful models for the chemical evolution of the Milky Way able to reproduce the majority of the observational constraints for the solar neighbourhood and for the Galactic disc. We show that, in the framework of our models, the lowest D/H (deuterium-to-oxygen) values observed locally cannot be explained in terms of simple astration processes occurring during the Galaxy evolution. Indeed, the combination of a mild star formation and a continuous infall of unprocessed gas required to fit all the available observational data allows only a modest variation of the deuterium abundance from its primordial value. Therefore, we suggest that depletion of deuterium on to dust grains is the most likely physical mechanism proposed so far to explain the observed dispersion in the local data.
Heterogeneity of the blood-brain barrier

ABSTRACT The brain microvascular network is comprised of capillaries, arterioles and venules, all of which retain – although to a different extent – blood-brain barrier (BBB) properties. Capillaries constitute the largest and tightest microvasculature. In contrast, venules have a looser junctional arrangement, while arterioles have a lower expression of P-gp. Development and maintenance of the BBB depends on the interaction of cerebral endothelial cells with pericytes and astrocytes, which are all heterogeneous in different regions of the central nervous system. At the level of circumventricular organs microvessels are permeable, containing fenestrations and discontinuous tight junctions. In addition, the blood-spinal cord barrier – where the number of pericytes is lower and expression of junctional proteins is reduced – is also more permeable than the BBB. However, much less is known about the cellular, molecular and functional differences among other regions of the brain. This review summarizes our current knowledge on the heterogeneity of the brain microvasculature.
Feasibility of MR-guided High Intensity Focused Ultrasound for Thrombolysis of Brain Intraventricular Hemorrhagic Thrombus

Due to pre-mature birth, 10-25% of infants born with low birth weight (<1kg) are susceptible to intraventricular hemorrhage (IVH), where 15% will develop post hemorrhagic hydrocephalus and require cerebrospinal fluid (CSF) diversion. No therapy to date to remove or dissolve the blood clot such as with Tissue Plasminogen Activator (TPA) has proven effective largely due to complications. MR-guided focused ultrasound (MRgFUS) is a potential non-invasive therapy as thinner neonatal skulls reduce ultrasonic aberration, which requires simpler transducers and obviates the need for fixation. The hypothesis of this thesis is: MRgFUS can be used to perform thrombolysis in a porcine IVH model where it will decrease the IVH thrombus by at least 50% without injury to the surrounding brain or blood vessels. The spatial pressure distribution of the MRgFUS (Sonalleve, Philips) platform through a neonatal skull was characterized. The ultrasonic focus had a diameter of 1.7 mm and a depth of 9.2 mm and the transmission through the neonatal skull had minimal impact to focus shape and location. A porcine IVH model was created. A semi-autonomous segmentation algorithm calculated an average clot size of 3987 mm. The chronic porcine model developed progressive hydrocephalus over 21 days with ventricles increased >50% in size.
Consistent CMT solutions before the 2010 Maule, Chile earthquake

In this paper, we define the angle between P, B, and T axes of focal mechanisms and three stress axes of tectonic stress field as the consistent parameter, to research the dynamic changes of stress field in earthquake preparation area before great earthquake. We mainly studied the change of the consistent parameter before the 2010 Maule, Chile earthquake using the CMT solutions. The result shows that the consistent parameter decrease before the earthquake, and the area of the lower consistent parameter in coincided with the distribution of aftershocks. It should be a phenomenon of predictive significance. When the accumulated earthquake examples are sufficient, uniform judgment criteria and prediction principles can be stipulated.
Harmonizing a distributed operating system with parallel and distributed applications

This paper presents several methods for harmonizing a distributed operating system with parallel and distributed applications. 'Harmonization' means that the system does not conflict with the parallel/distributed applications and enables them to control mapping and scheduling for speedup and reliability. In conventional distributed operating systems, one of the most important goals is to achieve network transparency. However, parallel/distributed applications have to bypass the facilities for network transparency because they require information on the locations and usage of system resources. Harmonization between the system and parallel/distributed applications are realized by putting some parts of the system into the same position as the applications. <<ETX>>
Automatic Recognition of Emotionally Coloured Speech

Emotion in speech is an issue that has been attracting the interest of the speech community for many years, both in the context of speech synthesis as well as in automatic speech recognition (ASR). In spite of the remarkable recent progress in Large Vocabulary Recognition (LVR), it is still far behind the ultimate goal of recognising free conversational speech uttered by any speaker in any environment. Current experimental tests prove that using state of the art large vocabulary recognition systems the error rate increases substantially when applied to spontaneous/emotional speech. This paper shows that recognition rate for emotionally coloured speech can be improved by using a language model based on increased representation of emotional utterances. Keywords—Statistical language model, N-grams, emotionally coloured speech
209 Attainment of low disease activity and remission with atacicept in patients with systemic lupus erythematosus and high disease activity in the phase IIb ADDRESS II study and its long-term extension

Background Low disease activity (LDA) and remission are important goals in the treatment of patients with SLE.1 2 Lupus Low Disease Activity State (LLDAS) is associated with reduced damage accrual,2 and has been shown to be a feasible clinical trial endpoint.3 In patients with high disease activity (HDA; SLEDAI-2K ≥10) enrolled in the ADDRESS II study, atacicept improved SLE responder index (SRI)-6 response rates and flare prevention at Week 24 vs placebo. Atacicept also demonstrated an acceptable safety profile.4 We present a post-hoc analysis of data from ADDRESS II and its long-term extension, describing 48-week LDA and remission rates in patients with HDA at Screening. Methods In ADDRESS II, patients were randomized (1:1:1) to weekly subcutaneous atacicept 75 or 150 mg or placebo for 24 weeks. Atacicept-completers continued at the same dose in the extension study, while placebo-treated patients were switched to atacicept 150 mg (placebo/atacicept 150 mg). This post-hoc analysis assessed: LDA (SLEDAI-2K ≤2), LLDAS (SLEDAI-2K ≤4 without major organ activity, no new disease activity vs previous visit, Physician’s Global Assessment [PGA] ≤1, prednisone-equivalent ≤7.5 mg/day, and stable immunosuppressants),2 and remission (clinical SLEDAI-2K=0, PGA <0.5, prednisone ≤5 mg/day), as proposed by the task force on definitions of remission in SLE (DORIS). 1 Results Of 306 ADDRESS II patients, 158 (51.6%) had HDA at Screening. At Week 24, 42.4% achieved SRI-6, 23.4% attained LDA, 15.8% LLDAS and 10.8% remission. At Week 48, 52.5% achieved SRI-6, 26.6% attained LDA, 19.0% LLDAS and 10.8% remission. Among 83 patients with HDA at Screening who had an SRI-6 response at Week 48, 49.4% (n=41) attained LDA, 34.9% (n=29) LLDAS and 20.5% (n=17) remission. At 48 weeks, LDA, LLDAS and remission rates were higher in patients treated with atacicept 150 mg vs atacicept 75 mg and vs placebo/atacicept 150 mg (figure 1). Abstract 209 Figure 1 Conclusions ADDRESS II patients with HDA at Screening who received atacicept 150 mg were more likely to attain LDA, LLDAS and remission at Week 48 than those treated with atacicept 75 mg or placebo/atacicept 150 mg. These endpoints were more stringent and discriminatory than SRI-6, confirming LLDAS, LDA, and remission to be robust and meaningful endpoints for SLE trials. In addition, these data further support future studies of atacicept in SLE. Funding Source(s): Merck KGaA, Darmstadt, Germany References Van Vollenhoven et al. Ann Rheum Dis 2017. Franklyn et al. Ann Rheum Dis 2016. Morand et al. Ann Rheum Dis 2018. Merrill et al. Arthritis Rheum 2018.
Junctional adhesion molecule (JAM)‐B supports lymphocyte rolling and adhesion through interaction with α4β1 integrin

Junctional adhesion molecule‐A (JAM‐A), JAM‐B and JAM‐C have been implicated in leucocyte transmigration. As JAM‐B binds to very late activation antigen (VLA)‐4, a leucocyte integrin that contributes to rolling and firm adhesion of lymphocytes to endothelial cells through binding to vascular cell adhesion molecule (VCAM)‐1, we hypothesized that JAM‐B is also involved in leucocyte rolling and firm adhesion. To test this hypothesis, intravital microscopy of murine skin microvasculature was performed. Rolling interactions of murine leucocytes were significantly affected by blockade of JAM‐B [which reduced rolling interactions from 9·1 ± 2·6% to 3·2 ± 1·2% (mean ± standard deviation)]. To identify putative ligands, T lymphocytes were perfused over JAM‐B‐coated slides in a dynamic flow chamber system. JAM‐B‐dependent rolling and sticking interactions were observed at low shear stress [0·3 dyn/cm2: 220 ± 71 (mean ± standard deviation) versus 165 ± 88 rolling (P < 0·001; Mann–Whitney rank sum test) and 2·6 ± 1·3 versus 1·0 ± 0·7 sticking cells/mm2/min (P = 0·026; Mann–Whitney rank sum test) on JAM‐B‐ compared with baseline], but not at higher shear forces (1·0 dyn/cm2). As demonstrated by antibody blocking experiments, JAM‐B‐mediated rolling and sticking of T lymphocytes was dependent on α4 and β1 integrin, but not JAM‐C expression. To investigate whether JAM‐B‐mediated leucocyte–endothelium interactions are involved in a disease‐relevant in vivo model, adoptive transfer experiments in 2,4,‐dinitrofluorobenzene (DNFB)‐induced contact hypersensitivity reactions were performed in mice in the absence or in the presence of a function‐blocking JAM‐B antibody. In this model, JAM‐B blockade during the sensitization phase impaired the generation of the immune response to DNFB, which was assessed as the increase in ear swelling in untreated, DNFB‐challenged mice, by close to 40% [P = 0·037; analysis of variance (anova)]. Overall, JAM‐B appears to contribute to leucocyte extravasation by facilitating not only transmigration but also rolling and adhesion.
Altered structural hub connectivity and its clinical relevance in glioma

Background and Purpose Structural network analysis of diffusion imaging is increasingly used to study neurological disease, its pathophysiology and symptoms. We therefore evaluate structural hub connectivity in glioma patients and its association with molecular subtype and clinical status. Materials and Methods Using retrospective diffusion imaging, structural connectivity was investigated in 65 newly diagnosed glioma patients (36 males; mean age 52 ± 14 years) and 60 healthy controls (23 males; mean age 50 ± 7 years). Probabilistic tractography was performed between 39 cortical nodes per hemisphere. In patients, tumors were drawn in to exclude each tumor-containing voxel from analysis. As previous connectomic research in glioma and other neurological diseases has shown particular importance of ‘hub’ nodes and connections, the numbers of connections between hubs, hubs and non-hubs, and non-hubs were calculated for each hemisphere separately. Clinical and molecular characteristics were assessed as part of routine clinical care. Group differences in connectivity and its associations with performance and molecular subtypes were tested non-parametrically through Mann-Whitney U-tests, corrected for multiple comparisons. Results Glioma patients had more hub-related connections in the hemisphere contralateral to the tumor (hub-hub P = 0.002, hub-non-hub P = 0.005), despite being comparable to controls in terms of total and ipsilateral connections. Within patients, hub-related connectivity related to performance status (P = 0.009) and molecular subtype (P = 0.045). Conclusion We present experimental evidence for the relevance of structural connectomics as a tool to pick up on the clinical impact of glioma on the rest of the brain.
Design of a Novel Microstrip Franklin Leaky-Wave Antenna Using the Eigenstate Approach

This paper presents the design of a novel periodic leaky-wave antenna (LWA) using modified microstrip Franklin unit cells. Two additional quarter-wave couple-line sections are used to allow the cell to work with the <inline-formula> <tex-math notation="LaTeX">$n =-2$ </tex-math></inline-formula> fast-wave harmonic. It allows the use of low-<inline-formula> <tex-math notation="LaTeX">$\epsilon _{\mathrm {r}}$ </tex-math></inline-formula> substrates so the designed LWA is cost-effective, can be easily integrated with radar front-end circuits, and avoids the excitation of surface waves. A novel application of eigenstate analysis leads to a simpler and more intuitive approach for the implementation of the reflection cancellation concept to eliminate open-stopband (OSB) effects. This is realized in the proposed structure with the use of a pair of interdigital fingers and different widths for the two lines forming the coupled section. A general design flow is also proposed for the design of the unit cell and LWA. Finally, a 40 cell LWA is fabricated on a Rogers 3003 substrate with <inline-formula> <tex-math notation="LaTeX">$\epsilon _{\mathrm {r}} = 3$ </tex-math></inline-formula>. The measured results show that the beam scans continuously from −54° to +55° when frequency is varied from 54.7 to 70 GHz, and no visible OSB effect is observed near the broadside direction.
When Less Is More: Non-monotonic Spike Sequence Processing in Neurons

Fundamental response properties of neurons centrally underly the computational capabilities of both individual nerve cells and neural networks. Most studies on neuronal input-output relations have focused on continuous-time inputs such as constant or noisy sinusoidal currents. Yet, most neurons communicate via exchanging action potentials (spikes) at discrete times. Here, we systematically analyze the stationary spiking response to regular spiking inputs and reveal that it is generically non-monotonic. Our theoretical analysis shows that the underlying mechanism relies solely on a combination of the discrete nature of the communication by spikes, the capability of locking output to input spikes and limited resources required for spike processing. Numerical simulations of mathematically idealized and biophysically detailed models, as well as neurophysiological experiments confirm and illustrate our theoretical predictions.
In situ models, physico-chemical aspects.

In situ (intra-oral) caries models are used for two purposes. First, they provide information about oral physiological processes. Such information helps to detail our knowledge of the oral ecosystem and to verify conclusions from in vitro experiments. Second, in situ models are utilized to test preventive agents in the phase between laboratory testing and clinical trials. Most investigations involving enamel inserts have been aimed at testing new dentifrices. The experimental designs of such studies usually do not allow one to draw conclusions on physico-chemical processes, e.g., because of single point measurements. Studies of model parameters (lesion type, lesion severity, and de/remineralization in time) constitute only a minority of the research reports. The most striking observation obtained with in situ models has been the significant differences in de/remineralization observed among individuals and, more importantly, within one individual during different time periods and between different sites in the same mouth (for review, see ten Cate et al., 1992). Regardless of this, some general findings can be inferred: During in situ demineralization, up to 62 vol% microns/day may be removed from enamel. For dentin specimens, this value may be as high as 89 vol% microns/day. For remineralization, during fluoride dentifrice treatment, a median deposition rate of 0.7%/day (for lesions with integrated mineral loss values between 2000 and 4000 vol% microns) is found. The rate of deposition seems to be correlated with the extent of the pre-formed lesion. This suggests that the number of sites (crystallite surface) available for calcium phosphate precipitation is an important parameter. (ABSTRACT TRUNCATED AT 250 WORDS)
Designing High-Refractive Index Polymers Using Materials Informatics †

A machine learning strategy is presented for the rapid discovery of new polymeric materials satisfying multiple desirable properties. Of particular interest is the design of high refractive index polymers. Our in silico approach employs a series of quantitative structure–property relationship models that facilitate rapid virtual screening of polymers based on relevant properties such as the refractive index, glass transition and thermal decomposition temperatures, and solubility in standard solvents. Exploration of the chemical space is carried out using an evolutionary algorithm that assembles synthetically tractable monomers from a database of existing fragments. Selected monomer structures that were further evaluated using density functional theory calculations agree well with model predictions.
Testing mined specifications

Specifications are necessary for nearly every software engineering task, but they are often missing or incomplete. "Specification mining" is a line of research promising to solve this problem through automated tools that infer specifications directly from existing programs. The standard practice is one of inductive learning: mining tools make observations about software and inductively generalize them into specifications. Inductive reasoning is unsound, however, and existing tools commonly grapple with the problem of inferring "false" specifications, which must be manually checked. In this work, we introduce a new technique for automatically validating mined specifications that lessens this manual burden. Our technique is not based on heuristics; it rather uses a general, semantic definition of a "true" specification. We perform systematic, targeted program transformations to test a mined specification's necessity for overall correctness. If a "violating" program is correct, the specification is false. We have implemented our technique in a prototype tool that validates temporal properties of Java programs, and we demonstrate it to be effective through a large-scale case study on the DaCapo benchmarks.