Miracle-dz/UniFAR-FTUs huggingface dataset:
ssDNA Pairing Accuracy Increases When Abasic Sites Divide Nucleotides into Small Groups

Accurate sequence dependent pairing of single-stranded DNA (ssDNA) molecules plays an important role in gene chips, DNA origami, and polymerase chain reactions. In many assays accurate pairing depends on mismatched sequences melting at lower temperatures than matched sequences; however, for sequences longer than ~10 nucleotides, single mismatches and correct matches have melting temperature differences of less than 3°C. We demonstrate that appropriately grouping of 35 bases in ssDNA using abasic sites increases the difference between the melting temperature of correct bases and the melting temperature of mismatched base pairings. Importantly, in the presence of appropriately spaced abasic sites mismatches near one end of a long dsDNA destabilize the annealing at the other end much more effectively than in systems without the abasic sites, suggesting that the dsDNA melts more uniformly in the presence of appropriately spaced abasic sites. In sum, the presence of appropriately spaced abasic sites allows temperature to more accurately discriminate correct base pairings from incorrect ones.
Mechanism of Selective VEGF-A Binding by Neuropilin-1 Reveals a Basis for Specific Ligand Inhibition

Neuropilin (Nrp) receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF) family of proangiogenic cytokines and the semaphorin 3 (Sema3) family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.
A parallel-SSHI rectifier for ultra-low-voltage piezoelectric vibration energy harvesting

An idling scheme of Synchronous Switch Harvesting on Inductor (SSHI) is proposed for piling up output voltage of the piezoelectric energy (PE) harvester cycle by cycle, to deal with the PE harvester’s low output voltage. The proposed rectifier integrates active diodes and a parallel-SSHI technique with a simple control scheme, and therefore has a high efficiency. The simulation results demonstrate the feasibility of proposed rectifier, which is able to extract energy from a ultra-low-voltage PE harvester.
In Search of a Cure for a Psychosis in Information Systems Design: Co-created Design and Metaphorical Appreciation

We postulate that a disconnect between stakeholders and designers, often rooted in an understandable preoccupation with technical rationality, limits how design research is conceptualized in the design science research community. We posit co-creation as a way to overcome this limitation that engages reflective design practice fostering a shared understanding of value among the designers/developers, users, analysts and others. Thus, co-creation is an essential ingredient for design satisfaction in many design endeavors. We proffer a theoretical foundation for envisioning design success as an artefact that realizes co-created conceptual metaphors compositing the objective and subjective qualities shaping the stakeholders’ appreciative systems. This paper positions and advocates for a critical perspective on designer transcendence where design choices and actions are centered on a shared, but evolving, composite understanding of value and quality – satisfaction. Successful co-creative design emancipates users from concern for unnecessary technically rational aspects of artefact design. Further we propose a framework, grounded in semiotics, to hone and revitalize designer transcendence with a design emphasis on efficient and ideally frictionless interfaces – conceptual metaphors – to reduce asymmetry among stakeholder concerns.
Nonlinear Spectroscopic Study of Porphyrin Under cw and Femto-second Laser Pulse Excitation

Single Beam Transmittance (SBT) was used as nonlinear spectroscopic tool to investigate the absorption cross-sections and lifetimes of Tetra Phenyl porphyrin (H2TPP) and its OH- group derivative (H2TPP(OH)4) doped in boric acid glass (BAG). We have used 671 nm wavelength as exciting wavelength for both CW (incident intensity up to 1010 W/cm2) and femto-second laser pulse (up to fluence of 102 mJ/cm2). Under cw laser excitation, H2TPP doped BAG demonstrates Double Saturable Absorber (DSA) behavior whereas H2TPP(OH)4 doped BAG act as Revere Saturable Absorber (RSA). Rate equation model espouses to extract the spectroscopic parameters from the experimental data. Excited state life times and absorption cross-sections were obtained as parameters for theoretical fit on SBT data. Porphyrin molecules act as four level systems under cw laser excitation, whereas in the presence of femto-second laser excitation they act as a two level system. We have derived the equations for transmitted energy through the material in the presence of femto-second laser illumination. Both systems viz., H2TPP and H2TPP(OH)4 doped BAG behaves as saturable absorbers when excited by femto-second laser pulses.
Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus–Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak

A substantial increase in the number of mumps outbreaks and outbreak-associated cases has occurred in the United States since late 2015 (1,2). To address this public health problem, the Advisory Committee on Immunization Practices (ACIP) reviewed the available evidence and determined that a third dose of measles, mumps, rubella (MMR) vaccine is safe and effective at preventing mumps. During its October 2017 meeting, ACIP recommended a third dose of a mumps virus-containing vaccine* for persons previously vaccinated with 2 doses who are identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak. The purpose of the recommendation is to improve protection of persons in outbreak settings against mumps disease and mumps-related complications. This recommendation supplements the existing ACIP recommendations for mumps vaccination (3).
Hepatic Gi signaling regulates whole-body glucose homeostasis

An increase in hepatic glucose production (HGP) is a key feature of type 2 diabetes. Excessive signaling through hepatic Gs–linked glucagon receptors critically contributes to pathologically elevated HGP. Here, we tested the hypothesis that this metabolic impairment can be counteracted by enhancing hepatic Gi signaling. Specifically, we used a chemogenetic approach to selectively activate Gi-type G proteins in mouse hepatocytes in vivo. Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase in HGP and severely impaired glucose homeostasis. Moreover, increased Gi signaling stimulated glucose release in human hepatocytes. A lack of functional Gi-type G proteins in hepatocytes reduced blood glucose levels and protected mice against the metabolic deficits caused by the consumption of a high-fat diet. Additionally, we delineated a signaling cascade that links hepatic Gi signaling to ROS production, JNK activation, and a subsequent increase in HGP. Taken together, our data support the concept that drugs able to block hepatic Gi–coupled GPCRs may prove beneficial as antidiabetic drugs.
Amphibian‐killing chytrid in Brazil comprises both locally endemic and globally expanding populations

Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is the emerging infectious disease implicated in recent population declines and extinctions of amphibian species worldwide. Bd strains from regions of disease‐associated amphibian decline to date have all belonged to a single, hypervirulent clonal genotype (Bd‐GPL). However, earlier studies in the Atlantic Forest of southeastern Brazil detected a novel, putatively enzootic lineage (Bd‐Brazil), and indicated hybridization between Bd‐GPL and Bd‐Brazil. Here, we characterize the spatial distribution and population history of these sympatric lineages in the Brazilian Atlantic Forest. To investigate the genetic structure of Bd in this region, we collected and genotyped Bd strains along a 2400‐km transect of the Atlantic Forest. Bd‐Brazil genotypes were restricted to a narrow geographic range in the southern Atlantic Forest, while Bd‐GPL strains were widespread and largely geographically unstructured. Bd population genetics in this region support the hypothesis that the recently discovered Brazilian lineage is enzootic in the Atlantic Forest of Brazil and that Bd‐GPL is a more recently expanded invasive. We collected additional hybrid isolates that demonstrate the recurrence of hybridization between panzootic and enzootic lineages, thereby confirming the existence of a hybrid zone in the Serra da Graciosa mountain range of Paraná State. Our field observations suggest that Bd‐GPL may be more infective towards native Brazilian amphibians, and potentially more effective at dispersing across a fragmented landscape. We also provide further evidence of pathogen translocations mediated by the Brazilian ranaculture industry with implications for regulations and policies on global amphibian trade.
Natural history of ovarian cancer

Ovarian cancer is a disease laden with paradigms, and it is a serious health problem. It is important to know its natural history, as it is multifactorial in origin, and also to understand its behaviour given its risk factors which can lead to death from metastasis in patients. It continues to be a challenge for oncologists. An analytical literature review was performed to update the latest concepts of its origin, evolution, risk factors, pre-clinical horizon, and its clinical manifestations; until the death of the patient.
Epigenetic Silencing of Nucleolar rRNA Genes in Alzheimer's Disease

Background Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer's disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation. Methodology/Principal Findings To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter was hypermethylated more in MCI than in advanced AD. The cytosine methylation of total genomic DNA was similar in AD, MCI, and control samples. Consistent with a notion that hypermethylation-mediated silencing of the nucleolar chromatin stabilizes rDNA loci, preventing their senescence-associated loss, genomic rDNA content was elevated in cerebrocortical samples from MCI and AD groups. Conclusions/Significance In conclusion, rDNA hypermethylation could be a new epigenetic marker of AD. Moreover, silencing of nucleolar chromatin may occur during early stages of AD pathology and play a role in AD-related ribosomal deficits and, ultimately, dementia.
Cemeteries Are Effective Sites For Monitoring La Crosse Virus (LACv) and these Environments May Play a Role in LACv Infection

La Crosse encephalitis (LAC) is the leading arboviral disease among children, and was previously limited to the upper Midwest. In 2012 nine pediatric cases of LAC occurred in eastern Tennessee, including one fatal case. In an attempt to identify sites near an active LACv infection and describe the abundance and distribution of potential LACv vectors near a fatal LAC case in the Appalachian region, we initiated an end of season study using a combination of questing and oviposition mosquito traps placed at forty-nine sites consisting of cemeteries and houses within 16 radial kilometers of two pediatric infections. LACv was isolated from three Aedes triseriatus pools collected from cemeteries and spatial clustering analysis identified clusters of Ae. triseriatus and Ae. albopictus populations that overlapped in the same area as the 2012 LACv cases. Results indicate cemeteries are effective sites for monitoring LACv. The role of cemeteries and specific environmental features will be the focus of future investigations.
Application of Bacteriocins and Protective Cultures in Dairy Food Preservation

In the last years, consumers are becoming increasingly aware of the human health risk posed by the use of chemical preservatives in foods. In contrast, the increasing demand by the dairy industry to extend shelf-life and prevent spoilage of dairy products has appeal for new preservatives and new methods of conservation. Bacteriocins are antimicrobial peptides, which can be considered as safe since they can be easily degraded by proteolytic enzymes of the mammalian gastrointestinal tract. Also, most bacteriocin producers belong to lactic acid bacteria (LAB), a group that occurs naturally in foods and have a long history of safe use in dairy industry. Since they pose no health risk concerns, bacteriocins, either purified or excreted by bacteriocin producing strains, are a great alternative to the use of chemical preservatives in dairy products. Bacteriocins can be applied to dairy foods on a purified/crude form or as a bacteriocin-producing LAB as a part of fermentation process or as adjuvant culture. A number of applications of bacteriocins and bacteriocin-producing LAB have been reported to successful control pathogens in milk, yogurt, and cheeses. One of the more recent trends consists in the incorporation of bacteriocins, directly as purified or semi-purified form or in incorporation of bacteriocin-producing LAB into bioactive films and coatings, applied directly onto the food surfaces and packaging. This review is focused on recent developments and applications of bacteriocins and bacteriocin-producing LAB for reducing the microbiological spoilage and improve safety of dairy products.
Intravascular ultrasound as an adjunct tool for angiographically intermediate lesions and complex coronary interventions: patient selection and perspectives

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress. com/permissions.php Journal of Vascular Diagnostics 2015:3 41–51 Journal of Vascular Diagnostics Dovepress
De Novo CNV Formation in Mouse Embryonic Stem Cells Occurs in the Absence of Xrcc4-Dependent Nonhomologous End Joining

Spontaneous copy number variant (CNV) mutations are an important factor in genomic structural variation, genomic disorders, and cancer. A major class of CNVs, termed nonrecurrent CNVs, is thought to arise by nonhomologous DNA repair mechanisms due to the presence of short microhomologies, blunt ends, or short insertions at junctions of normal and de novo pathogenic CNVs, features recapitulated in experimental systems in which CNVs are induced by exogenous replication stress. To test whether the canonical nonhomologous end joining (NHEJ) pathway of double-strand break (DSB) repair is involved in the formation of this class of CNVs, chromosome integrity was monitored in NHEJ–deficient Xrcc4 −/− mouse embryonic stem (ES) cells following treatment with low doses of aphidicolin, a DNA replicative polymerase inhibitor. Mouse ES cells exhibited replication stress-induced CNV formation in the same manner as human fibroblasts, including the existence of syntenic hotspot regions, such as in the Auts2 and Wwox loci. The frequency and location of spontaneous and aphidicolin-induced CNV formation were not altered by loss of Xrcc4, as would be expected if canonical NHEJ were the predominant pathway of CNV formation. Moreover, de novo CNV junctions displayed a typical pattern of microhomology and blunt end use that did not change in the absence of Xrcc4. A number of complex CNVs were detected in both wild-type and Xrcc4 −/− cells, including an example of a catastrophic, chromothripsis event. These results establish that nonrecurrent CNVs can be, and frequently are, formed by mechanisms other than Xrcc4-dependent NHEJ.
Channel quality aware active queue management in cellular networks

Queue management plays an important role in the performance of IP based networks and cellular networks in particular where large buffers are often deployed in order to absorb bursts resulting from the dynamic nature of the radio channel. Long standing queues building up in large buffers leads to “Bufferbloat”, degrading the performance especially for delay-sensitive applications while small buffers may lower the link utilization. This paper proposes a novel Active Queue Management (AQM) algorithm tailored to cellular networks, mainly by utilizing the Channel Quality Indicator (CQI) periodically reported by user equipment, in order to mitigate Bufferbloat and maintain acceptable levels of performance. Simulation results show that the proposed algorithm reduces the average queuing delay of packets for each user by 40% on average with TCP traffic compared with the CoDel algorithm which has recently become popular.
Cavitation in Vial Drop Subjected to Mechanical Shock

Cavitation is a phenomenon that occurs when the local pressure falls down below the critical pressure. Previous work from the Randolph lab demonstrated that protein aggregates can form when a vial of therapeutic solution is dropped onto a hard surface. The process by which this occurs is most likely shock induced cavitation. During this process, hot spots can be created with temperatures and pressures reaching thousands of Kelvin and hundreds of atmospheres, respectively, leading to degradation of protein therapeutics. This work will extend previous efforts by exploring differences generated by change in vial materials, solutions, drop methods and fill volumes. Also this phenomenon will be computationally modeled by ANSYS program to investigate the created low pressure regions in solution inside the vial after the impact, and validated with the data in experiments. To accomplish the task of the experiments, water, histidine buffer, and a limited number of runs were performed with monoclonal antibody (mAb1). Video was collected under variable conditions: vials consisting of glass and plastic materials, fill volume, drop height, drop method and impact angle. Cavitation intensity was observed using a Phantom 7 high-speed camera recording. The results indicate that reducing the potential energy transmitted from the dropped vial to the solution cause the solution to be less likely to cavitate, and the intensity of cavitation would significantly vary by changing the abovementioned parameters.
Cholesterol: An evergreen molecule in biology

Cholesterol, an essential component of higher eukaryotic membranes, was discovered more than two centuries ago. The development and progress of cholesterol research in the last 200 years has been truly fascinating, with elements of surprise, serendipity and intrigue. In this review, we trace this journey the way we see it, and follow it up with the role of membrane cholesterol in crucial areas of contemporary research (transbilayer domains, regulation of GPCR function and role in the entry of intracellular pathogens into host cells), with considerable footprint from our work. We believe that cholesterol will continue to surprise and fascinate future researchers, thereby justifying its evergreen nature.
Effect of Steam Pressure on Chemical and Structural Properties of Kenaf Fibers during Steam Explosion Process

The chemical and structural properties of kenaf fibers that were treated at different steam pressures during the steam explosion process were investigated. With increased steam pressure, a higher percentage of cellulose and acid-insoluble lignin and a lower content of hemicellulose and pectin were obtained. This result was further confirmed by Fourier transform infrared (FTIR) spectroscopy. X-ray diffraction (XRD) studies revealed that the steam-exploded kenaf fibers were more crystalline than the raw kenaf fibers, and that excessive steam pressure above 3 MPa damaged the cellulose crystalline structure. Scanning electron microscopy (SEM) analysis showed a change in the surface morphology of the treated kenaf fibers. The lower content of gums and the effective defibrillation of steam-exploded kenaf fibers demonstrated the potential of steam explosion treatment in applications of kenaf fibers.
A naive Bayes algorithm for tissue origin diagnosis (TOD‐Bayes) of synchronous multifocal tumors in the hepatobiliary and pancreatic system

Synchronous multifocal tumors are common in the hepatobiliary and pancreatic system but because of similarities in their histological features, oncologists have difficulty in identifying their precise tissue clonal origin through routine histopathological methods. To address this problem and assist in more precise diagnosis, we developed a computational approach for tissue origin diagnosis based on naive Bayes algorithm (TOD‐Bayes) using ubiquitous RNA‐Seq data. Massive tissue‐specific RNA‐Seq data sets were first obtained from The Cancer Genome Atlas (TCGA) and ∼1,000 feature genes were used to train and validate the TOD‐Bayes algorithm. The accuracy of the model was >95% based on tenfold cross validation by the data from TCGA. A total of 18 clinical cancer samples (including six negative controls) with definitive tissue origin were subsequently used for external validation and 17 of the 18 samples were classified correctly in our study (94.4%). Furthermore, we included as cases studies seven tumor samples, taken from two individuals who suffered from synchronous multifocal tumors across tissues, where the efforts to make a definitive primary cancer diagnosis by traditional diagnostic methods had failed. Using our TOD‐Bayes analysis, the two clinical test cases were successfully diagnosed as pancreatic cancer (PC) and cholangiocarcinoma (CC), respectively, in agreement with their clinical outcomes. Based on our findings, we believe that the TOD‐Bayes algorithm is a powerful novel methodology to accurately identify the tissue origin of synchronous multifocal tumors of unknown primary cancers using RNA‐Seq data and an important step toward more precision‐based medicine in cancer diagnosis and treatment.
Electronic Spectra and Their Relation to the ( π,π) Collective Mode in High- Tc Superconductors

The photoemission line shape near (pi, 0) in Bi(2)Sr(2)CaCu(2)O(8+delta) below T(c) is characterized by a sharp peak, followed at higher energy by a dip and hump. We study the evolution of this line shape as a function of momentum, temperature, and doping. We find the hump scales with the peak and persists above T(c) in the pseudogap state. We present strong evidence that the peak-dip-hump structure arises from the interaction of electrons with a collective mode of wave vector (pi, pi). The inferred mode energy and its doping dependence agree well with a magnetic resonance observed by neutron scattering.