Miracle-dz/UniFAR-FTUs huggingface dataset:
Promoter Engineering Reveals the Importance of Heptameric Direct Repeats for DNA Binding by Streptomyces Antibiotic Regulatory Protein–Large ATP-Binding Regulator of the LuxR Family (SARP-LAL) Regulators in Streptomyces natalensis

ABSTRACT The biosynthesis of small-size polyene macrolides is ultimately controlled by a couple of transcriptional regulators that act in a hierarchical way. A Streptomyces antibiotic regulatory protein–large ATP-binding regulator of the LuxR family (SARP-LAL) regulator binds the promoter of a PAS-LuxR regulator-encoding gene and activates its transcription, and in turn, the gene product of the latter activates transcription from various promoters of the polyene gene cluster directly. The primary operator of PimR, the archetype of SARP-LAL regulators, contains three heptameric direct repeats separated by four-nucleotide spacers, but the regulator can also bind a secondary operator with only two direct repeats separated by a 3-nucleotide spacer, both located in the promoter region of its unique target gene, pimM. A similar arrangement of operators has been identified for PimR counterparts encoded by gene clusters for different antifungal secondary metabolites, including not only polyene macrolides but peptidyl nucleosides, phoslactomycins, or cycloheximide. Here, we used promoter engineering and quantitative transcriptional analyses to determine the contributions of the different heptameric repeats to transcriptional activation and final polyene production. Optimized promoters have thus been developed. Deletion studies and electrophoretic mobility assays were used for the definition of DNA-binding boxes formed by 22-nucleotide sequences comprising two conserved heptameric direct repeats separated by four-nucleotide less conserved spacers. The cooperative binding of PimRSARP appears to be the mechanism involved in the binding of regulator monomers to operators, and at least two protein monomers are required for efficient binding. IMPORTANCE Here, we have shown that a modulation of the production of the antifungal pimaricin in Streptomyces natalensis can be accomplished via promoter engineering of the PAS-LuxR transcriptional activator pimM. The expression of this gene is controlled by the Streptomyces antibiotic regulatory protein–large ATP-binding regulator of the LuxR family (SARP-LAL) regulator PimR, which binds a series of heptameric direct repeats in its promoter region. The structure and importance of such repeats in protein binding, transcriptional activation, and polyene production have been investigated. These findings should provide important clues to understand the regulatory machinery that modulates antibiotic biosynthesis in Streptomyces and open new possibilities for the manipulation of metabolite production. The presence of PimR orthologues encoded by gene clusters for different secondary metabolites and the conservation of their operators suggest that the improvements observed in the activation of pimaricin biosynthesis by Streptomyces natalensis could be extrapolated to the production of different compounds by other species.
Adhesion of Geopolymer Bonded Joints Considering Surface Treatments

In this study the adhesion properties of a geopolymer-based adhesive on metallic substrates are investigated, considering different surface conditions. Mechanical treatments (grit-blasting and sand-blasting) and chemical treatments (nitro-phosphoric acid and silanization) were performed on steel and aluminium plates. Single lap joint specimens were tested in order to access the influence of these pretreatments on the shear bond strength. The surfaces were scanned and the average surface roughness parameters were used in order to assess their effect on bond strength. The results indicated that the effect of individual surface roughness parameters alone is not statistically significant when correlated with bond strength. In general, chemical treatments were usually less effective than mechanical treatments alone for both steel and aluminium joints with geopolymers as adhesives.
A single frequency method for duct detection in reinforced concrete

In this work we propose to apply a model, already developed by the authors for the detection of faults inside a known grid of PEC scatterers, to the detection of ducts in reinforced concrete. The concrete is considered as a homogeneous lossless dielectric. Numerical results with noisy data in a configuration typical of a pillar show the applicability of the model.
HSRL-2 aerosol optical measurements and microphysical retrievals vs. airborne in situ measurements during DISCOVER-AQ 2013: an intercomparison study

Abstract. We present a detailed evaluation of remotely sensed aerosol microphysical properties obtained from an advanced, multi-wavelength high-spectral-resolution lidar (HSRL-2) during the 2013 NASA DISCOVER-AQ field campaign. Vertically resolved retrievals of fine-mode aerosol number, surface-area, and volume concentration as well as aerosol effective radius are compared to 108 collocated, airborne in situ measurement profiles in the wintertime San Joaquin Valley, California, and in summertime Houston, Texas. An algorithm for relating the dry in situ aerosol properties to those obtained by the HSRL at ambient relative humidity is discussed. We show that the HSRL-2 retrievals of ambient fine-mode aerosol surface-area and volume concentrations agree with the in situ measurements to within 25 and 10 %, respectively, once hygroscopic growth adjustments have been applied to the dry in situ data. Despite this excellent agreement for the microphysical properties, extinction and backscatter coefficients at ambient relative humidity derived from the in situ aerosol measurements using Mie theory are consistently smaller than those measured by the HSRL, with average differences of 31 ± 5 % and 53 ± 11 % for California and Texas, respectively. This low bias in the in situ estimates is attributed to the presence of coarse-mode aerosol that are detected by HSRL-2 but that are too large to be well sampled by the in situ instrumentation. Since the retrieval of aerosol volume is most relevant to current regulatory efforts targeting fine particle mass (PM2. 5), these findings highlight the advantages of an advanced 3β + 2α HSRL for constraining the vertical distribution of the aerosol volume or mass loading relevant for air quality.
Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction

Chlamydia trachomatis is an obligate intracellular pathogen that resides in a membrane-bound compartment, the inclusion. The bacteria secrete a unique class of proteins, Incs, which insert into the inclusion membrane and modulate the host-bacterium interface. We previously reported that IncE binds specifically to the Sorting Nexin 5 Phox domain (SNX5-PX) and disrupts retromer trafficking. Here, we present the crystal structure of the SNX5-PX:IncE complex, showing IncE bound to a unique and highly conserved hydrophobic groove on SNX5. Mutagenesis of the SNX5-PX:IncE binding surface disrupts a previously unsuspected interaction between SNX5 and the cation-independent mannose-6-phosphate receptor (CI-MPR). Addition of IncE peptide inhibits the interaction of CI-MPR with SNX5. Finally, C. trachomatis infection interferes with the SNX5:CI-MPR interaction, suggesting that IncE and CI-MPR are dependent on the same binding surface on SNX5. Our results provide new insights into retromer assembly and underscore the power of using pathogens to discover disease-related cell biology. DOI: http://dx.doi. org/10.7554/eLife.22709. 001
Delay aversion in attention deficit/hyperactivity disorder is mediated by amygdala and prefrontal cortex hyper‐activation

BACKGROUND Experimental research supports delay aversion as a motivational feature of attention deficit/hyperactivity disorder (ADHD). To investigate the neurobiology of delay aversion in ADHD, this study examined whether adolescents with ADHD display an unusually strong activation in affective brain regions in response to cues predicting forthcoming delay and whether these effects are (a) delay-dose dependent and (b) statistically mediate the association between ADHD and self-reported delay aversion. METHODS Twenty-nine right-handed male adolescents with combined type ADHD and 32 typically developing controls (ages 10-18 years) performed a reaction time task in an MRI scanner. Pretarget cues indicated delay-related response consequences. One indicated that delay would follow the response irrespective of response speed (CERTAIN DELAY), a second that delay would only follow if the response was too slow (CONDITIONAL DELAY), and a third that no delay would follow the response whatever its speed (NO DELAY). Delay levels were 2, 6, or 14 s. Participants also rated their own delay aversion in everyday life. RESULTS Individuals with ADHD rated themselves as more delay averse than controls. Significantly greater activation to CERTAIN DELAY cues relative to NO DELAY cues was found in participants with ADHD compared to controls (bilaterally) in amygdala, anterior insula, temporal pole, dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex. Amygdala and DLPFC activation strength were strongly and delay-dose dependently correlated with delay aversion ratings, and statistically mediated the relationship between ADHD status and delay aversion. CONCLUSIONS When presented with cues predicting impending delay, adolescents with ADHD, relative to controls, displayed a delay-related increase in activation in amygdala and DLPFC, regions known to be implicated in the processing of aversive events. Future studies should examine the specificity of these effects to delay aversion compared to aversive events in general.
Arabidopsis EMB1990 Encoding a Plastid-Targeted YlmG Protein Is Required for Chloroplast Biogenesis and Embryo Development

In higher plants, embryo development originated from fertilized egg cell is the first step of the life cycle. The chloroplast participates in many essential metabolic pathways, and its function is highly associated with embryo development. However, the mechanisms and relevant genetic components by which the chloroplast functions in embryogenesis are largely uncharacterized. In this paper, we describe the Arabidopsis EMB1990 gene, encoding a plastid-targeted YlmG protein which is required for chloroplast biogenesis and embryo development. Loss of the EMB1990/YLMG1-1 resulted in albino seeds containing abortive embryos, and the morphological development of homozygous emb1990 embryos was disrupted after the globular stage. Our results showed that EMB1990/YLMG1-1 was expressed in the primordia and adaxial region of cotyledon during embryogenesis, and the encoded protein was targeted to the chloroplast. TEM observation of cellular ultrastructure showed that chloroplast biogenesis was impaired in emb1990 embryo cells. Expression of certain plastid genes was also affected in the loss-of-function mutants, including genes encoding core protein complex subunits located in the thylakoid membrane. Moreover, the tissue-specific genes of embryo development were misexpressed in emb1990 mutant, including genes known to delineate cell fate decisions in the SAM (shoot apical meristem), cotyledon and hypophysis. Taken together, we propose that the nuclear-encoded YLMG1-1 is targeted to the chloroplast and required for normal plastid gene expression. Hence, YLMG1-1 plays a critical role in Arabidopsis embryogenesis through participating in chloroplast biogenesis.
A Hidden Markov Model for Seismocardiography

We propose a hidden Markov model approach for processing seismocardiograms. The seismocardiogram morphology is learned using the expectation-maximization algorithm, and the state of the heart at a given time instant is estimated by the Viterbi algorithm. From the obtained Viterbi sequence, it is then straightforward to estimate instantaneous heart rate, heart rate variability measures, and cardiac time intervals (the latter requiring a small number of manual annotations). As is shown in the conducted experimental study, the presented algorithm outperforms the state-of-the-art in seismocardiogram-based heart rate and heart rate variability estimation. Moreover, the isovolumic contraction time and the left ventricular ejection time are estimated with mean absolute errors of about 5 [ms] and ${\text{9 [ms]}}$, respectively. The proposed algorithm can be applied to any set of inertial sensors; does not require access to any additional sensor modalities; does not make any assumptions on the seismocardiogram morphology; and explicitly models sensor noise and beat-to-beat variations (both in amplitude and temporal scaling) in the seismocardiogram morphology. As such, it is well suited for low-cost implementations using off-the-shelf inertial sensors and targeting, e.g., at-home medical services.
Hard and Easy Problems for Supersingular Isogeny Graphs

We consider the endomorphism ring computation problem for supersingular elliptic curves, constructive versions of Deuring’s correspondence, and the security of Charles-Goren-Lauter’s cryptographic hash function. We show that constructing Deuring’s correspondence is easy in one direction and equivalent to the endomorphism ring computation problem in the other direction. We also provide a collision attack for special but natural parameters of the hash function, and we prove that for general parameters its preimage and collision resistance are also equivalent to the endomorphism ring computation problem. Our reduction and attack techniques are of independent interest and may find further applications in both cryptanalysis and the design of new protocols.
Indoor localization with incomplete observation using set-membership filter

Indoor localization is a popular topic because of the poor performance of GPS in the indoor environment. This paper has provided a new method to achieve the goal of indoor localization. Combining the usage of posture sensors with the Radio Frequency Identification (RFID) technology, we solved the problem of plentiful tags in the traditional RFID indoor localization. The relative localization subsystem is based on posture sensors and the absolute localization subsystem is based on RFID. A set-membership theory based data fusion algorithm is proposed to fuse the data of relative localization and absolute localization. Experimental results show that the proposed data fusion algorithm could significantly reduce the accumulated error of our indoor localization system.
MHC-I genotype drives early immune selection of oncogenic mutations

ABSTRACT MHC-I exposes the intracellular contents to immune cells for surveillance of cellular health. Due to high genomic variation, individuals' immune systems differ in their ability to expose and eliminate cancer-causing mutations. These personalized immune blind spots create specific oncogenic mutation predispositions within patients and influence their prevalence across populations.
The green valley is a red herring: Galaxy Zoo reveals two evolutionary pathways towards quenching of star formation in early-and late-type galaxies

We use SDSS+GALEX+Galaxy Zoo data to study the quenching of star formation in low-redshift galaxies. We show that the green valley between the blue cloud of star-forming galaxies and the red sequence of quiescent galaxies in the colour-mass diagram is not a single transitional state through which most blue galaxies evolve into red galaxies. Rather, an analysis that takes morphology into account makes clear that only a small population of blue early-type galaxies move rapidly across the green valley after the morphologies are transformed from disc to spheroid and star formation is quenched rapidly. In contrast, the majority of blue star-forming galaxies have significant discs, and they retain their late-type morphologies as their star formation rates decline very slowly. We summarize a range of observations that lead to these conclusions, including UV-optical colours and halo masses, which both show a striking dependence on morphological type. We interpret these results in terms of the evolution of cosmic gas supply and gas reservoirs. We conclude that late-type galaxies are consistent with a scenario where the cosmic supply of gas is shut off, perhaps at a critical halo mass, followed by a slow exhaustion of the remaining gas over several Gyr, driven by secular and/or environmental processes. In contrast, early-type galaxies require a scenario where the gas supply and gas reservoir are destroyed virtually instantaneously, with rapid quenching accompanied by a morphological transformation from disc to spheroid. This gas reservoir destruction could be the consequence of a major merger, which in most cases transforms galaxies from disc to elliptical morphology, and mergers could play a role in inducing black hole accretion and possibly active galactic nuclei feedback.
Experimental Analysis of a Biologically Inspired Thermal-Structural Satellite Panel

Recently, there has been a surge in interest in biologically inspired or bio-mimetic structures where living organisms are used to provide guidance to improve overall performance of aerospace systems. In this study, an isogrid architecture for satellite electronics panels was investigated. Fluidic channels were incorporated into the structure, thus providing thermal management capability, in addition to structural support. To provide the surface area for heat transfer, a thin facesheet was mounted on the outside of the isogrid, also containing fluidic channels. The fluidic channels are analogous to a circulatory system in a biological organism. The primary supporting ribs act as arteries by providing the main flow supply and channels in the facesheet act as capillaries by providing the area coverage for heat transfer. Also incorporated into the structure was a passive-reactive valve designed to regulate coolant flow. The base of the valve was fabricated directly onto the thermal-structural panel and could be placed anywhere on the panel. This valve was designed to operate on the same principle as traditional automotive thermostats for regulating engine temperature. In addition, the valve was designed to utilize paraffin expansion properties for actuation. Although designed and built, the valve was not tested in these experiments and the results are focused on the thermal structural panel. Results indicate that this thermal control method provides satisfactory thermal management for standard satellite bus components.
Review for Identifying Online Opinion Leaders

Nowadays, Internet enables its users to share the information online and to interact with others. Facing with numerous information, these Internet users are confused and begin to rely on the opinion leaders’ recommendations. The online opinion leaders are the individuals who have professional knowledge, who utilize the online channels to spread word-of-mouth information and who can affect the attitudes or even the behavior of their followers to some degree. Because utilizing the online opinion leaders is seen as an important approach to affect the potential consumers, how to identify them has become one of the hottest topics in the related field. Hence, in this article, the concepts and characteristics are introduced, and the researches related to identifying opinion leaders are collected and divided into three categories. Finally, the implications for future studies are provided. Keywords—Online opinion leaders, user attributes analysis, text mining analysis, network structure analysis.
Outpatient Therapeutic Feeding Program Outcomes and Determinants in Treatment of Severe Acute Malnutrition in Tigray, Northern Ethiopia: A Retrospective Cohort Study

Background Outpatient Therapeutic feeding Program (OTP) brings the services for management of Severe Acute Malnutrition (SAM) closer to the community by making services available at decentralized treatment points within the primary health care settings, through the use of ready-to-use therapeutic foods, community outreach and mobilization. Little is known about the program outcomes. This study revealed the levels of program outcome indictors and determinant factors to recovery rate. Methods A retrospective cohort study was conducted on 628 children who had been managed for SAM under OTP from April/2008 to January/2012. The children were selected using systematic random sampling from 12 health posts and 4 health centers. The study relied on information of demographic characteristics, anthropometries, Plumpy'Nut, medical problems and routine medications intakes. The results were estimated using Kaplan-Meier survival curves, log-rank test and Cox-regression. Results The recovery, defaulter, mortality and weight gain rates were 61.78%, 13.85%, 3.02% and 5.23 gm/kg/day, respectively. Routine medications were administered partially and children with medical problems were managed inappropriately under the program. As a child consumed one more sachet of Plumpy'Nut, the recovery rate from SAM increased by 4% (HR = 1.04, 95%-CI = 1.03, 1.05, P<0.001). The adjusted hazard ratios to recovery of children with diarrhea, appetite loss with Plumpy'Nut and failure to gain weight were 2.20 (HR = 2.20, 95%-CI = 1.31, 3.41, P = 0.001), 4.49 (HR = 1.74, 95%-CI = 1.07, 2.83, P = 0.046) and 3.88 (HR = 1.95, 95%-CI = 1.17, 3.23, P<0.001), respectively. Children who took amoxicillin and de-worming had 95% (HR = 1.95, 95%-CI = 1.17, 3.23) and 74% (HR = 1.74, 95%-CI = 1.07, 2.83) more probability to recover from SAM as compared to those who didn't take them. Conclusions The OTP was partially successful. Management of children with comorbidities under the program and partial administration of routine drugs were major threats for the program effectiveness. The stakeholders should focus on creating the capacity of the OTP providers on proper management of SAM to achieve fully effective program.
Should Atrial Fibrillation Patients With Only 1 Nongender-Related CHA2DS2-VASc Risk Factor Be Anticoagulated?

Background and Purpose— There is some uncertainty about treating patients with atrial fibrillation (AF) with 1 nongender-related (NGR) stroke risk factor (CHA2DS2-VASc [ie, congestive heart failure, hypertension, age (≥75 years; 2 points), diabetes, stroke/transient ischemic attack (2 points), vascular disease, age (65–74 years), sex (female)] score of 1 in males and 2 in females) with oral anticoagulation (OAC). Methods— We investigated adverse outcomes and calculated the net clinical benefit of OAC use in a community-based cohort of unselected AF patients with 0 compared with 1 NGR stroke risk factor (CHA2DS2-VASc 0 versus 1 in males; and 1 versus 2 in females). Among 8962 patients with AF, 2208 (25%) had 0 or 1 NGR stroke risk factors, of which 45% were not prescribed OAC. Results— During a follow-up of 1028±1189 days (median, 495; interquartile range, 5–1882 days), the yearly rate of the combined end point of stroke/systemic embolism in nonanticoagulated AF patients with 1 NGR stroke risk factor was 2.09% (95% confidence interval, 1.37–3.18). This corresponded to an adjusted hazard ratio of 2.82 (95% confidence interval, 1.32–6.04) relative to the group with 0 NGR stroke risk factor. When the benefit of ischemic stroke reduction was balanced against the increased risk of intracranial hemorrhage among patients with 1 NGR stroke risk factor, the net clinical benefit was positive in favor of OAC use versus no antithrombotic therapy or antiplatelet therapy use. The net clinical benefit was negative for antiplatelet therapy use versus no antithrombotic therapy. Conclusions— Among AF patients with 1 NGR stroke risk factor (ie, CHA2DS2-VASc 1 in males or 2 in females), OAC use as indicated according to the guidelines was associated with a positive net clinical benefit for the prevention of stroke and thromboembolic events.