Miracle-dz/UniFAR-FTUs huggingface dataset:
SentRNA: Improving computational RNA design by incorporating a prior of human design strategies

Designing RNA sequences that fold into specific structures and perform desired biological functions is an emerging field in bioengineering with broad applications from intracellular chemical catalysis to cancer therapy via selective gene silencing. Effective RNA design requires first solving the inverse folding problem: given a target structure, propose a sequence that folds into that structure. Although significant progress has been made in developing computational algorithms for this purpose, current approaches are ineffective at designing sequences for complex targets, limiting their utility in real-world applications. However, an alternative that has shown significantly higher performance are human players of the online RNA design game EteRNA. Through many rounds of gameplay, these players have developed a collective library of "human" rules and strategies for RNA design that have proven to be more effective than current computational approaches, especially for complex targets. Here, we present an RNA design agent, SentRNA, which consists of a fully-connected neural network trained using the $eternasolves$ dataset, a set of $1.8 x 10^4$ player-submitted sequences across 724 unique targets. The agent first predicts an initial sequence for a target using the trained network, and then refines that solution if necessary using a short adaptive walk utilizing a canon of standard design moves. Through this approach, we observe SentRNA can learn and apply human-like design strategies to solve several complex targets previously unsolvable by any computational approach. We thus demonstrate that incorporating a prior of human design strategies into a computational agent can significantly boost its performance, and suggests a new paradigm for machine-based RNA design.
Convolutional neural network based automatic plaque characterization for intracoronary optical coherence tomography images

Optical coherence tomography (OCT) can provide high-resolution cross-sectional images for analyzing superficial plaques in coronary arteries. Commonly, plaque characterization using intra-coronary OCT images is performed manually by expert observers. This manual analysis is time consuming and its accuracy heavily relies on the experience of human observers. Traditional machine learning based methods, such as the least squares support vector machine and random forest methods, have been recently employed to automatically characterize plaque regions in OCT images. Several processing steps, including feature extraction, informative feature selection, and final pixel classification, are commonly used in these traditional methods. Therefore, the final classification accuracy can be jeopardized by error or inaccuracy within each of these steps. In this study, we proposed a convolutional neural network (CNN) based method to automatically characterize plaques in OCT images. Unlike traditional methods, our method uses the image as a direct input and performs classification as a single- step process. The experiments on 269 OCT images showed that the average prediction accuracy of CNN-based method was 0.866, which indicated a great promise for clinical translation.
Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management

Chronic neutrophilic leukemia (CNL) is a potentially aggressive myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of ≥ 25 x 109/L of which ≥ 80% are neutrophils, with < 10% circulating neutrophil precursors with blasts rarely observed. In addition, there is no dysplasia, nor clinical or molecular criteria for other myeloproliferative neoplasms.
Pseudomonas aeruginosa Magnesium Transporter MgtE Inhibits Type III Secretion System Gene Expression by Stimulating rsmYZ Transcription

ABSTRACT Pseudomonas aeruginosa causes numerous acute and chronic opportunistic infections in humans. One of its most formidable weapons is a type III secretion system (T3SS), which injects powerful toxins directly into host cells. The toxins lead to cell dysfunction and, ultimately, cell death. Identification of regulatory pathways that control T3SS gene expression may lead to the discovery of novel therapeutics to treat P. aeruginosa infections. In a previous study, we found that expression of the magnesium transporter gene mgtE inhibits T3SS gene transcription. MgtE-dependent inhibition appeared to interfere with the synthesis or function of the master T3SS transcriptional activator ExsA, although the exact mechanism was unclear. We now demonstrate that mgtE expression acts through the GacAS two-component system to activate rsmY and rsmZ transcription. This event ultimately leads to inhibition of exsA translation. This inhibitory effect is specific to exsA as translation of other genes in the exsCEBA operon is not inhibited by mgtE. Moreover, our data reveal that MgtE acts solely through this pathway to regulate T3SS gene transcription. Our study reveals an important mechanism that may allow P. aeruginosa to fine-tune T3SS activity in response to certain environmental stimuli. IMPORTANCE The type III secretion system (T3SS) is a critical virulence factor utilized by numerous Gram-negative bacteria, including Pseudomonas aeruginosa, to intoxicate and kill host cells. Elucidating T3SS regulatory mechanisms may uncover targets for novel anti-P. aeruginosa therapeutics and provide deeper understanding of bacterial pathogenesis. We previously found that the magnesium transporter MgtE inhibits T3SS gene transcription in P. aeruginosa. In this study, we describe the mechanism of MgtE-dependent inhibition of the T3SS. Our report also illustrates how MgtE might respond to environmental cues, such as magnesium levels, to fine-tune T3SS gene expression.
Role of interleukin-12 gene polymorphisms in the onset risk of cancer: a meta-analysis

Many molecular epidemiologic studies have explored the possible links between interleukin-12 (IL-12) polymorphisms and various cancers. However, results from these studies remain inconsistent. This meta-analysis is aimed to shed light on the associations between three common loci (rs568408, rs2243115, rs3212227) of IL-12 gene and overall cancer risk. Our meta-analysis finally included 33 studies comprising 10,587 cancer cases and 12,040 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the cancer risk. We observed a significant association between IL-12B rs3212227 and overall cancer risk, especially in hepatocellular carcinoma, nasopharyngeal cancer, and among Asians. IL-12A polymorphisms (rs2243115 and rs568408) were found no influence on overall cancer risk. Nevertheless, stratification analyses demonstrated that rs568408 polymorphism contributed to increasing cancer risk of Caucasians and cervical cancer. And, rs2243115 may enhance the risk of brain tumor. These findings provided evidence that IL-12 polymorphisms may play a potential role in cancer risk.
A Survey on Image Denoising

In Image Processing, the impulse noise reduction from images plays a very vital role. Image denoising is one such powerful methodology which is deployed to remove the noise through the manipulation of the image data to produce very high quality images. There are several such algorithms devised for denoising, each having their own merits and demerits. In this notion reviews the existing denoising algorithms and performs their comparative study.
Serum Lipids in Association With Type 2 Diabetes Risk and Prevalence in a Chinese Population

Context We previously reported an association between lysophosphatidylinositol (LPI) (16:1) and risk for type 2 diabetes in a Chinese population using an untargeted analysis. Objective To examine the overall associations of LPIs and their related metabolites, such as nonesterified fatty acids (NEFAs) and acylcarnitines, with incident and prevalent type 2 diabetes using a targeted approach. Design and Setting A case-control study was nested within the Singapore Chinese Health Study. Cases and controls were individually matched by age, sex, and date of blood collection. We used both liquid and gas chromatography tandem mass spectrometry to measure serum metabolite levels at baseline, including 8 LPIs, 19 NEFAs, and 34 acylcarnitines. Conditional logistic regression models were used to estimate the associations between metabolites and diabetes risk. Participants Participants included 160 incident and 144 prevalent cases with type 2 diabetes and 304 controls. Main Outcome Measure Incident and prevalent type 2 diabetes. Results On the basis of a false discovery rate <0.1, we identified 37 metabolites associated with prevalent type 2 diabetes, including 7 LPIs, 18 NEFAs, and 12 acylcarnitines, and 11 metabolites associated with incident type 2 diabetes, including 2 LPIs and 9 NEFAs. Two metabolites, LPI (16:1) and dihomo-γ-linolenic acid, showed independent associations with incident type 2 diabetes and significantly enhanced the risk prediction. Conclusions We found several LPIs and NEFAs that were associated with risk for type 2 diabetes and may improve our understanding of the pathogenesis. The findings suggest that lipid profiles could aid in diabetes risk assessment in Chinese populations.
State-Aware Concurrency Throttling

Reconfiguration of parallel applications has gained traction with the increasing emphasis on energy/performance trade-off. The ability to dynamically change the amount of resources used by an application allows reaction to changes in the environment, in the application behavior or in the user’s requirements. A popular technique consists in changing the number of threads used by the application (Dynamic Concurrency Throttling). Although this provides good control of application performance and power consumption, managing the technique can impose a significant burden on the application programmer, mainly due to state management and redistribution following the addition or removal of a thread. Nevertheless, some common state access patterns have been identified in some popular applications. By leveraging on this knowledge, we will describe how it is possible to simplify the state management procedures following a Concurrency Throttling operation.
T-2 mycotoxin: toxicological effects and decontamination strategies

Mycotoxins are highly diverse secondary metabolites produced in nature by a wide variety of fungus which causes food contamination, resulting in mycotoxicosis in animals and humans. In particular, trichothecenes mycotoxin produced by genus fusarium is agriculturally more important worldwide due to the potential health hazards they pose. It is mainly metabolized and eliminated after ingestion, yielding more than 20 metabolites with the hydroxy trichothecenes-2 toxin being the major metabolite. Trichothecene is hazardously intoxicating due to their additional potential to be topically absorbed, and their metabolites affect the gastrointestinal tract, skin, kidney, liver, and immune and hematopoietic progenitor cellular systems. Sensitivity to this type of toxin varying from dairy cattle to pigs, with the most sensitive endpoints being neural, reproductive, immunological and hematological effects. The mechanism of action mainly consists of the inhibition of protein synthesis and oxidative damage to cells followed by the disruption of nucleic acid synthesis and ensuing apoptosis. In this review, the possible hazards, historical significance, toxicokinetics, and the genotoxic and cytotoxic effects along with regulatory guidelines and recommendations pertaining to the trichothecene mycotoxin are discussed. Furthermore, various techniques utilized for toxin determination, pathophysiology, prophylaxis and treatment using herbal antioxidant compounds and regulatory guidelines and recommendations are reviewed. The prospects of the trichothecene as potential hazardous agents, decontamination strategies and future perspectives along with plausible therapeutic uses are comprehensively described.
Complexity and algorithms for composite retrieval

Online search has become a daily activity and a source of a variety of valuable information, from the finest granularity such as finding the address of a specific restaurant, to more complex tasks like looking for accessories compatible with an iPhone or planning a trip. The latter typically involves running multiple search queries to gather information about different places, reading online reviews to find out about hotels, and checking geographic proximity of places to visit. We refer to this information seeking activity as composite retrieval and propose to organize results into item bundles that together constitute an improved exploratory experience over ranked lists. As a first step towards composite retrieval definition, we need to formalize intuitive desirable properties of item bundles. We distinguish between properties of each bundle in the answer and properties of the answer as a whole. Consider the case of a user selecting the restaurants to try during a visit to a new city. The user has a limited budget which might be either financial, or simply the number of nights spent in the city. The user prefers suggested restaurants to serve different cuisines. The validity of a bundle of restaurants is given by the budget constraint and the complementarity of the restaurants in the bundle w.r. t. the cuisine they serve. Other restaurant attributes could be used for defining valid bundles. For example, instead of cuisines, different dress codes could be required to every restaurant in a single bundle. Moreover, in order to provide meaningful bundles, restaurants forming each bundle must be compatible, e.g., close geographically, or liked by similar reviewers. The degree of compatibility of the items forming a bundle defines the quality of the bundle. Intuitively, in the case geographic distance is used, the closer restaurants are from each other, the higher the quality of the bundle they belong to. Similarly, when common reviewers are used as the
Brain Potentials Reflect Behavioral Differences in True and False Recognition

People often falsely recognize nonstudied lures that are semantically similar to previously studied words. Behavioral research suggests that such false recognition is based on high semantic overlap between studied items and lures that yield a feeling of familiarity, whereas true recognition is more often associated with the recollection of details. Despite this behavioral evidence for differences between true and false recognition, research measuring brain activity (PET, fMRI, ERP) has not clearly differentiated corresponding differences in brain activity. A median split was used to separate subjects into Good and Poor performers based on their discrimination of studied targets from similar lures. Only Good performers showed late (1000-1500 msec), right frontal event-related brain potentials (ERPs) that were more positive for targets and lures compared with new items. The right frontal differences are interpreted as reflecting postretrieval evaluation processes that were more likely to be engaged by Good than Poor performers. Both Good and Poor performers showed a parietal ERP old/new effect (400-800 msec), but only Poor performers showed a parietal old/lure difference. These results are consistent with the view that the parietal and frontal ERP old/new effects reflect dissociable processes related to recollection.
Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation

In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds) has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young’s modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall designs could be further explored. In addition, creating a more precise prediction by investigating sets of in between hinge thicknesses and comparing the folding times before fracture, will be the subject of future work.
miR-3147 serves as an oncomiR in vulvar squamous cell cancer via Smad4 suppression

The incidence of vulvar squamous cell carcinoma (VSCC) has increased annually over the last decade. MicroRNAs (miRNAs/miRs) serve an important role in tumor progression and development. Our previous microarray studies have revealed that miR-3147 was overexpressed in VSCC. However, its function and underlying mechanism in VSCC remain unknown. In the present study, it was confirmed by reverse transcription-quantitative polymerase chain reaction that the expression of miR-3147 was markedly upregulated in VSCC tissues. The increased expression of miR-3147 was positively associated with the depth of invasion. The overexpression of miR-3147 resulted in the promotion of vulvar cancer cell proliferation, migration, invasion, G1/S progression and invasion-associated gene expression. miR-3147 may participate in the process of epithelial-mesenchymal transition and reduce the expressions of downstream target genes in the transforming growth factor-β/Smad signaling pathway in A431 cells. The knockdown of Smad4 by small interfering RNA promoted malignant behaviours in A431 cells. In addition, miR-3147 regulated Smad4 by directly binding to its 3′ untranslated region. In conclusion, the results indicated that miR-3147 may serve an oncogenic role in VSCC by targeting Smad4. miR-3147 may represent a novel potential therapeutic target marker for VSCC.
High-resolution mitochondrial DNA analysis sheds light on human diversity, cultural interactions, and population mobility in Northwestern Amazonia.

OBJECTIVES Northwestern Amazonia (NWA) is a center of high linguistic and cultural diversity. Several language families and linguistic isolates occur in this region, as well as different subsistence patterns, with some groups being foragers and others agriculturalists. In addition, speakers of Eastern Tukanoan languages are known for practicing linguistic exogamy, a marriage system in which partners are taken from different language groups. In this study, we use high-resolution mitochondrial DNA sequencing to investigate the impact of this linguistic and cultural diversity on the genetic relationships and population structure of NWA groups. METHODS We collected saliva samples from individuals representing 40 different NWA ethnolinguistic groups and sequenced 439 complete mitochondrial genomes to an average coverage of 1,030×. RESULTS The mtDNA data revealed that NWA populations have high genetic diversity with extensive sharing of haplotypes among groups. Moreover, groups who practice linguistic exogamy have higher genetic diversity, while the foraging Nukak have lower genetic diversity. We also find that rivers play a more important role than either geography or language affiliation in structuring the genetic relationships of populations. DISCUSSION Contrary to the view of NWA as a pristine area inhabited by small human populations living in isolation, our data support a view of high diversity and contact among different ethnolinguistic groups, with movement along rivers probably facilitating this contact. Additionally, we provide evidence for the impact of cultural practices, such as linguistic exogamy, on patterns of genetic variation. Overall, this study provides new data and insights into a remote and little-studied region of the world.
HomeStyles, A Web-Based Childhood Obesity Prevention Program for Families With Preschool Children: Protocol for a Randomized Controlled Trial

Background The home environment is where young children spend most of their time, and is critically important to supporting behaviors that promote health and prevent obesity. However, the home environment and lifestyle patterns remain understudied, and few interventions have investigated parent-led makeovers designed to create home environments that are supportive of optimal child health and healthy child weights. Objective The aim of the HomeStyles randomized controlled trial (RCT) is to determine whether the Web-based HomeStyles intervention enables and motivates parents to shape the weight-related aspects of their home environments and lifestyle behavioral practices (diet, exercise, and sleep) to be more supportive of their preschool children’s optimal health and weight. Methods A rigorous RCT utilizing an experimental group and an attention control group, receiving a bona fide contemporaneous treatment equal in nonspecific treatment effects and differing only in subject matter content, will test the effect of HomeStyles on a diverse sample of families with preschool children. This intervention is based on social cognitive theory and uses a social ecological framework, and will assess: intrapersonal characteristics (dietary intake, physical activity level, and sleep) of parents and children; family interpersonal or social characteristics related to diet, physical activity, media use, and parental values and self-efficacy for obesity-preventive practices; and home environment food availability, physical activity space and supports in and near the home, and media availability and controls in the home. Results Enrollment for this study has been completed and statistical data analyses are currently underway. Conclusions This paper describes the HomeStyles intervention with regards to: rationale, the intervention’s logic model, sample eligibility criteria and recruitment, experimental group and attention control intervention content, study design, instruments, data management, and planned analyses.