Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery of pyrrolo[2,3- b ]pyrazines derivatives as submicromolar affinity activators of wild-type, G551D and F508del CFTR chloride channels

The cystic fibrosis transmembrane conductance regulator (CFTR) represents the main Cl channel in the apical membrane of epithelial cells for cAMP-dependent Cl - secretion. Here we report on the synthesis and screening of a small library of 6-phenylpyrrolo[2,3- b ]pyrazines (named RP derivatives) evaluated as activators of wild-type CFTR, G551D-CFTR and F508del-CFTR Cl - channels. Iodide efflux and whole-cell patch clamp recordings analysis identified RP-107 as a submicromolar activator of wt-CFTR (human airway epithelial Calu-3 and wtCFTR-CHO cells), G551D-CFTR (G551D-CFTR-CHO cells) and F508del-CFTR (in temperature corrected human airway epithelial F508del/F508del CF15 cells). The structural analogue RP-108 (4-chlorophenyl), contrary to RP-107 (4-hydroxyphenyl), was less potent being activator only at micromolar concentrations. RP-107 and RP-108 did not have any effect on the cellular cAMP level. Activation was potentiated by low concentration of forskolin and inhibited by glibenclamide and CFTR inh -172 but not by calixarene or DIDS. Finally, we found significant stimulation of short circuit current (Isc) by RP-107 (EC 50 = 89 nM) and RP-108 (EC 50 = 103 µM) on colon of Cftr +/+ but not of Cftr -/- mice mounted in Ussing chamber. Stimulation of Isc was inhibited by glibenclamide but not affected by DIDS. These results show that RP-107 stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Our preliminary structure-activity relationship study identified 4-hydroxyphenyl and 7- n -butyl as determinants required for activation of CFTR. The potency of these agents indicates that 9.90 (bs, 1H), 8.35 and 8.15 (2d, 1H each, J = 2.6 Hz), 7.50 and 6.95 (2d, 2H each, J = 7 Hz), 3.10-1.70 (m, 2H), 2.00-1.05 (m, 6H), 0.80 (t, 3H, J = 7 Hz). Anal. Calcd for C 17 H 19 N 3 O (281.36): C, 72.57; H, 6.81; N, 14.93. Found: C, 72.35; H, 6.78; N, 14.75. graphs with GraphPad chain, RP-106 having the butyl chain but not the OH-phenyl or RP-14 having the Cl-phenyl but not the butyl chain are not activators. These observations suggest that both determinants (OH-phenyl and butyl are required for CFTR activation. These very preliminary data provide some interesting clues to improve the potency of future 6-phenylpyrrolo[2,3-b ]pyrazines.
BIOINFORMATICS Fractionation, rearrangement and subgenome dominance

Motivation: Fractionation is arguably the greatest cause of gene order disruption following whole genome duplication, causing severe biases in chromosome rearrangement-based estimates of evolutionary divergence. Results: We show how to correct for this bias almost entirely by means of a ‘consolidation’ algorithm for detecting and suitably transforming identiﬁable regions of fractionation. We characterize the process of fractionation and the performance of the algorithm through realistic simulations. We apply our method to a number of core eudicot genomes, we and by studying the fractionation regions detected, are able to address topical issues in polyploid evolution. Availability and implementation: Code for the consolidation algorithm, and sample data, is available at: http://137.122. 149.195/ Software/Fractionation/fractionation.html
Exposure to Parental Smoking in Childhood Is Associated With Increased Risk of Carotid Atherosclerotic Plaque in Adulthood Epidemiology

and mediating variables, the relative risk of developing carotid plaque in adulthood increased among those children with 1 or both parents who smoked (relative risk, 1.7; 95% confidence interval, 1.0–2.8; P =0.04). Although children whose parents exercised good “smoking hygiene” (smoking parents whose children had nondetectable cotinine levels) had increased risk of carotid plaque compared with children with nonsmoking parents (relative risk, 1.6; 95% confidence interval, 0.6–4.0; P =0.34), children of smoking parents with poor smoking hygiene (smoking parents whose children had detectable serum cotinine levels) had substantially increased risk of plaque as adults (relative risk, 4.0; 95% confidence interval, 1.7–9.8; P =0.002). Conclusions —Children of parents who smoke have increased risk of developing carotid atherosclerotic plaque in adulthood. However, parents who exercise good smoking hygiene can lessen their child’s risk of developing plaque. ( Circulation . 2015;131:1239-1246. DOI: 10.1161/CIRCULATIONAHA.114.013485.)
Modality use in joint between hearing parents and deaf children.

The present study examined differences in modality use during episodes of joint attention between hearing parent-hearing child dyads and hearing parent-deaf child dyads. Hearing children were age-matched to deaf children. Dyads were video recorded in a free play session with analyses focused on uni- and multimodality use during joint attention episodes. Results revealed that adults in hearing parent-deaf child dyads spent a signiﬁcantly greater proportion of time interacting with their children using multiple communicative modalities than adults in hearing parent-hearing child dyads, who tended to use the auditory modality (e.g., oral language) most often. While these ﬁndings demonstrate that hearing parents accommodate their children’s hearing status, we observed greater overall time spent in joint attention in hearing parent-hearing child dyads than hearing parent-deaf child dyads. Our results point to important avenues for future research on how parents can better accommodate their child’s hearing status through the use of multimodal communication strategies.
Neuropsychologia Agnosia for bird calls

The cognitive organisation of nonverbal auditory knowledge remains poorly de ﬁ ned. De ﬁ cits of environmental sound as well as word and visual object knowledge are well-recognised in semantic dementia. However, it is unclear how auditory cognition breaks down in this disorder and how this relates to de ﬁ cits in other knowledge modalities. We had the opportunity to study a patient with a typical syndrome of semantic dementia who had extensive premorbid knowledge of birds, allowing us to assess the impact of the disease on the processing of auditory in relation to visual and verbal attributes of this speci ﬁ c knowledge category. We designed a novel neuropsychological test to probe knowledge of particular avian characteristics (size, behaviour [migratory or nonmigratory], habitat [whether or not primarily water-dwelling]) in the nonverbal auditory, visual and verbal modalities, based on a uniform two-alternative-forced-choice procedure. The patient's performance was com- pared to healthy older individuals of similar birding experience. We further compared his performance on this test of bird knowledge with his knowledge of familiar human voices and faces. Relative to healthy birder controls, the patient showed marked de ﬁ cits of bird call and bird name knowledge but relatively preserved knowledge of avian visual attributes and retained knowledge of human voices and faces. In both the auditory and visual modalities, his knowledge of the avian characteristics of size and behaviour was intact whereas his knowledge of the associated characteristic of habitat was de ﬁ cient. This case provides further evidence that nonverbal auditory knowledge has a fractionated organisation that can be di ﬀ erentially targeted in semantic dementia.
Entity-based Message Bus for SaaS Integration

The rising popularity of SaaS allows individuals and enterprises to leverage various services (e.g. Dropbox, Github, GDrive and Yammer) for everyday processes. Concequently, an enormous amount of Application Programming Interfaces (APIs) were generated since the demand of cloud services, allowing third-party developers to integrate these services into their processes. However, the explosion of APIs and the heterogeneous interfaces makes the discovery and integration of Web services a complex technical issue. Moreover, these disparate services do not in general communicate with each other, rather used in an ad-hoc manner with little or no customizable process support. This inevitably leads to “shadow processes”, often only informally managed by e-mail or the like. We propose a framework to simplify the integration of disparate services and effectively build customized processes. We propose a platform for managing API-related knowledge and a declarative language and model for composing APIs. The implementation of the proposed framework includes an Knowledge Graph for APIs called APIBase and an agile services integration platform, called: CaseWalls. We provide a knowledge-based event-bus for unified interactions between disparate services, while allowing process participants to interact and collaborate on relevant cases.
Advances in the Deﬁnition of Needs and Speciﬁcations for a Climate Service Tool Aimed at Small Hydropower Plants’ Operation and Management

: The operation feasibility of small hydropower plants in mountainous sites is subjected to the run-of-river ﬂow, which is also dependent on a high variability in precipitation and snow cover. Moreover, the management of this kind of system has to be performed with some particular operation conditions of the plant (e.g., turbine minimum and maximum discharge) but also some environmental ﬂow requirements. In this context, a technological climate service is conceived in a tight connection with end users, perfectly answering the needs of the management of small hydropower systems in a pilot area, and providing a forecast of the river streamﬂow together with other operation data. This paper presents an overview of the service but also a set of lessons learnt related to the features, requirements, and considerations to bear in mind from the point of view of climate service developers. In addition, the outcomes give insight into how this kind of service could change the traditional management (normally based on past experience), providing a probability range of the future river ﬂow based on future weather scenarios according to the range of future weather possibilities. This highlights the utility of the co-generation process to implement climate services for water and energy ﬁelds but also that seasonal climate forecasting could improve the business as usual of this kind of facility. the user), which shows the di ﬀ erent elements of the system and the relations among them.
CLOSED LOOP CONTROL OF THREE PORT CONVERTER WITH HIGH VOLTAGE GAIN

Photovoltaic (PV) system is one of the best renewable energy sources for power generation system due to their pollution free and low cost properties. The PV cells has less efficiency compared to other source of power generation. The system efficiency is improved by reducing components count, which reduces the losses. In this paper a new three port converter (TPC) is proposed for stand-alone renewable power applications. The proposed converter has three switches to achieve the power flow control. Single inductor is used for common energy transfer element for two different sources. The coupled inductor is used to increase the voltage conversion ratio with reasonable duty cycle. Thus the proposed converter has high voltage gain with less components count. The output voltage is regulated through feedback network. The system performance is verified through simulation results.
Marine Ecology Progress Series 535:185

The marine migration of post-spawning anadromous fish remains poorly understood. The present study examined survival and progression rates of anadromous brown trout Salmo trutta L. after spawning (kelts) during downriver, fjord, and sea migration. Kelts (n = 49) were captured in the Danish River Gudenaa, tagged with acoustic transmitters and subsequently recorded by automatic receivers. Kelts spent on average 25 d moving down the 45 km river and through the brackish fjord. The fish entered the Kattegat Sea between 14 April and 30 May. Eighteen of the 49 kelts disappeared in the river and fjord during outward migration, likely due to mortality. Survival was not significantly related to gill Na+/K+-ATPase activity, suggesting that physiological adaptation to saltwater may be less critical for adults compared to juveniles (smolts). Of the 31 fish that entered the Kattegat Sea, 45% survived and returned to the fjord. The duration of the entire marine migration, from leaving to entering the river, was on average 163 d. The fish returned from the Kattegat Sea to the fjord between 22 July and 21 October. Upon return, the fish spent 1−90 d passing through Randers Fjord, with most individuals completing the reach within 4 d, suggesting that the kelts spent limited time foraging after returning to the fjord. The total survival during the entire marine migration, including the fjord, was a minimum of 29%. Our study provides data that are important for management of anadromous brown trout, and the high survival highlights that kelts may represent a valuable resource for both population reproduction and recreational fisheries.
Identiﬁcation of New Repetitive Element in Leptospira interrogans Serovar Copenhageni and Its Application to PCR-Based Differentiation of Leptospira Serogroups

A new repetitive DNA element was identiﬁed in an isolate of Leptospira interrogans serovar copenhageni from a patient in Salvador, Brazil. A Sau 3A genomic library from this strain was constructed and screened for repetitive DNA elements. An insert of 438 bp (Rep1) from one library clone hybridized to multiple chromo- somal DNA fragments resolved electrophoretically after digestion with Bam HI, Hin dIII, and Mfe I. A single oligonucleotide primer, designated iRepl, was designed to generate multiple PCR amplicons of various elec- trophoretic mobilities in a PCR typing method. The method distinguished strains belonging to the eight pathogenic and three saprophytic species of the genus Leptospira . Clinical isolates obtained during urban epidemics between 1996 and 1998 in Salvador, Brazil, were analyzed by this PCR method. Although the iRep1 primer was unable to discriminate strains among L. interrogans serovar copenhageni isolates, it
Facial Emotion and Gender Recognition System

—Emotions plays a very important role in expressing our thoughts. Facial expressions can display emotions and indicate an individual’s intentions within a situation. They are extremely important to the social interaction of individuals. Various research has proved that almost 90 percent of our communication can be non verbal. Our overall body language along with our emotions says a lot about our thought process. Hence recognizing emotions becomes a vital task. There a six types of emotions namely, happy, sad, anger, smile, neutral and fear. To effectively identify these would help to decipher the thinking. Hence the importance and need of recognizing emotions is necessary. Also, gender plays an equally important part. Recognizing and effectively analyzing these human characteristics is becoming important with time. This study helps in the field of medical as well as security and surveillance.It is also helpful in better customer service and future predictions.
Special Section: Blood-Based Biomarkers for Alzheimer’s Disease and Related Dementias Plasma tau complements CSF tau and P-tau in the diagnosis of Alzheimer’s disease

Introduction: Plasma tau may be an accessible biomarker for Alzheimer’s disease (AD), but the correlation between plasma and cerebrospinal ﬂuid (CSF) tau and the value of combining plasma tau with CSF tau and phospho-tau (P-tau) are still unclear. Methods: Plasma-tau, CSF-tau, and P-tau were measured in 97 subjects, including elderly cognitively normal controls (n 5 68) and patients with AD (n 5 29) recruited at the NYU Center for Brain Health, with comprehensive neuropsychological and magnetic resonance imaging evaluations. Results: Plasma tau was higher in patients with AD than cognitively normal controls ( P , .001, area under the receiver operating characteristic curve 5 0.79) similarly to CSF tau and CSF P-tau and was negatively correlated with cognition in AD. Plasma and CSF tau measures were poorly correlated. Adding plasma tau to CSF tau or CSF P-tau signiﬁcantly increased the areas under the receiver operating characteristic curve from 0.80 and 0.82 to 0.87 and 0.88, respectively. Discussion: Plasma tau is higher in AD independently from CSF-tau. Importantly, adding plasma tau to CSF tau or P-tau improves diagnostic accuracy, suggesting that plasma tau may represent a useful biomarker for AD, especially when added to CSF tau measures. (cid:1) BY-NC-ND
Inferential Statistics Using Partial Least Square Regression (PLSR) for Chemical Processes. Case Study: A Fixed Bed Catalytic Reactor

The complexity of processes in the modern industry (many kinetics and fluid dynamic variables) makes to think in few data due to high costs for experimental data collection. Therefore, it is important to consider statistical models, such as the partial least square regression (PLSR) method that provide an adequate solution to the multicollinearity in regression models, due to the minimum requirements in terms of measurement scales, sample size, and residual distribution. This work has shown for first time the application of the PLSR method to a fixed bed catalytic reactor for cracking of t-pentene-2 to obtain light olefins. Results show a correlation of R 2predictive > 0.85, which was validated with other experimental data of the same chemical process indicating the robustness of the method as a powerful statistical tool to infer the behavior in chemical process. The importance of this research lies to present the use of PLSR in engineering applications as such rating and design of chemical processes as a novel alternative method to predictive behaviors with few experimental data tests.
Institutional Knowledge at Singapore Management University Institutional Knowledge at Singapore Management University Two-view Transductive Support Vector Machines Two-view Transductive Support Vector Machines

Obtaining high-quality and up-to-date labeled data can be diﬃcult in many real-world machine learning applications, especially for Internet classiﬁcation tasks like review spam detection, which changes at a very brisk pace. For some problems, there may exist multiple perspectives, so called views, of each data sample. For example, in text classiﬁcation, the typical view contains a large number of raw content features such as term frequency, while a second view may contain a small but highly-informative number of do-main speciﬁc features. We thus propose a novel two-view transductive SVM that takes advantage of both the abun-dant amount of unlabeled data and their multiple representations to improve the performance of classiﬁers. The idea is fairly simple: train a classiﬁer on each of the two views of both labeled and unlabeled data, and impose a global constraint that each classiﬁer assigns the same class label to each labeled and unlabeled data. We applied our two-view transductive SVM to the WebKB course dataset, and a real-life review spam classiﬁcation dataset. Experimental results show that our proposed approach performs up to 5% better than a single view learning algorithm, especially when the amount of labeled data is small. The other advantage of our two-view approach is its signiﬁcantly improved stability, which is especially useful for noisy real world data.
Lupus lpr MRL/Regulated by B7-1 and B7-2 Costimulation in Autoantibody Responses and Pathology

The activation of T lymphocytes requires both Ag-mediated signaling through the TCR as well as costimulatory signals trans-mitted through B7-1 and/or B7-2 with CD28. The interference of B7-mediated costimulatory signals has been proposed as one immunotherapeutic intervention for the prevention autoimmune disease. This study has examined autoantibody responses and autoimmune pathology in a murine model of human systemic lupus erythematosus (SLE), the MRL- lpr/lpr mouse, genetically deﬁcient in B7-1 or B7-2, or in mice treated with B7-1/B7-2 blocking Abs. In contrast to other studies of murine models of SLE, MRL- lpr/lpr mice treated with B7 blocking Abs exhibit strong anti-small nuclear ribonucleoprotein (snRNP) and anti-DNA autoantibody responses with some changes in isotype switching as compared with untreated animals. All MRL- lpr/lpr mice deﬁcient in B7-1 or B7-2 produce anti-snRNP and anti-DNA titers with isotypes virtually identical with wild-type animals. However, the absence of B7-2 costimulation did interfere with the spontaneous activation and the accumulation of memory CD4 1 or CD8 1 T lymphocytes characteristic of wild-type MRL- lpr/lpr mice. IgG and C3 complement deposition was less pronounced in the kidneys of B7-2 deﬁcient MRL- lpr/lpr mice, reﬂecting their lessor degree of glomerulonephritis. By comparison, B7-1-deﬁcient MRL- lpr/lpr mice had more severe IgG and C3 deposits in glomeruli. The Journal of Immunology, 2000, 165: 3436–3443.
Needs and opportunities in mineral evolution research this benefits you.

Progress in understanding mineral evolution, Earth’s changing near-surface mineralogy through 27 time, depends on the availability of detailed information on mineral localities of known ages and 28 geologic settings. A comprehensive database including this information, employing the 29 mindat.org website as a platform, is now being implemented. This resource will incorporate 30 software to correlate a range of mineral occurrences and properties versus time, and it will thus 31 facilitate studies of the changing diversity, distribution, associations, and characteristics of 32 individual minerals as well as mineral groups. The Mineral Evolution Database thus holds the 33 prospect of revealing mineralogical records of important geophysical, geochemical, and 34 biological events in Earth history.
and cognitive in initially adults.

Objective To assess whether global or regional changes in amyloid burden over 4 years predict early declines in episodic memory in initially amyloid-negative adults. Methods One hundred twenty-six initially amyloid-negative, cognitively normal participants (age 30 – 89 years) were included from the Dallas Lifespan Brain Study who completed ﬂ orbetapir PET and a cognitive battery at baseline and 4-year follow-up. Standardized uptake value ratio (SUVR) change was computed across 8 bilateral regions of interest. Using general linear models, we examined the relationship between change in global and regional SUVR and change in episodic memory, controlling for baseline SUVR, baseline memory, age, sex, education, and APOE status. In initially amyloid-negative adults, we detected a regionally speci ﬁ c relationship between declining episodic memory and increasing amyloid accumulation across multiple posterior cortical regions. In addition, these amyloid-related changes in memory persisted when we focused on middle-aged adults only and after controlling for atrophy in global cortical, hippocampal, and Alzheimer disease signature cortical volume. Our results indicate that assessing regional changes in amyloid, particularly in posterior cortical regions, can aid in the early detection of subclinical amyloid-related decline in episodic memory as early as middle age. Future research incorporating tau and other markers of neuro-degeneration is needed to clarify the sequence of events that lead to this early, subclinical memory decline.