Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancement of Odor Avoidance Regulated by Dopamine Signaling in Caenorhabditis elegans

The enhancement of sensory responses after prior exposure to a stimulus is a fundamental mechanism of neural function in animals. Its molecular basis, however, has not been studied in as much depth as the reduction of sensory responses, such as adaptation or habituation. We report here that the avoidance behavior of the nematode Caenorhabditis elegans in response to repellent odors (2-nonanone or 1-octanol) is enhanced rather than reduced after preexposure to the odors. This enhancement effect of preexposure was maintained for at least 1 h after the conditioning. The enhancement of 2-nonanone avoidance was not dependent on the presence or absence of food during conditioning, which generally functions as a strong positive or negative unconditioned stimulus in the animals. These results suggest that the enhancement is acquired as a type of nonassociative learning. In addition, genetic and pharmacological analyses revealed that the enhancement of 2-nonanone avoidance requires dopamine signaling via D2-like dopamine receptor DOP-3, which functions in a pair of RIC interneurons to regulate the enhancement. Because dopamine signaling has been tightly linked with food-related information to modulate various behaviors of C. elegans, it may play different role in the regulation of the enhancement of 2-nonanone avoidance. Thus, our data suggest a new genetic and pharmacological paradigm for nonassociative enhancement of neural responses that is regulated by dopamine signaling.
NUP98–HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice

Here we describe hemopoietic chimeras serving as a mouse model for NUP98–HOXA9‐induced leukemia, which reproduced several of the phenotypes observed in human disease. Mice transplanted with bone marrow cells expressing NUP98–HOXA9 through retroviral transduction acquire a myeloproliferative disease (MPD) and eventually succumb to acute myeloid leukemia (AML). The NUP98 portion of the fusion protein was shown to be responsible for transforming a clinically silent pre‐leukemic phase observed for Hoxa9 into a chronic, stem cell‐derived MPD. The co‐expression of NUP98–HOXA9 and Meis1 accelerated the transformation of MPD to AML, identifying a genetic interaction previously observed for Hoxa9 and Meis1. Our findings demonstrate the presence of overlapping yet distinct molecular mechanisms for MPD versus AML, illustrating the complexity of leukemic transformation.
Simulation Model and Mechanism of Burr Formation

Burrs formation is a very complicated process in metal cutting and its formation mechanism has not yet been fully revealed. A finite element model based on material failure mode is proposed in this study to simulate the burr forming process. According to workpiece materials deformation and mechanical properties from the simulation results, burrs formation mechanism is analyzed. To reveal the changes law of burr formation, experiments with different materials and different cutting conditions are carried out on refitted milling machine. Main factors that influence the burr formation process are analyzed. Also, the effectiveness of the FEM is verified through experimental results.
Inhibition of phorbol ester-induced mouse skin tumor promotion and COX-2 expression by celecoxib: C/EBP as a potential molecular target.

PURPOSE Inflammation acts as a driving force for the development of cancer. Multiple lines of evidence suggest that nonsteroidal anti-inflammatory drugs, especially those that specifically target cyclooxygenase-2 (COX-2), are effective in preventing certain cancers. The present study was aimed at investigating the antitumor promoting potential of celecoxib in chemically induced mouse skin tumorigenesis, as well as elucidating the underlying molecular mechanisms. MATERIALS AND METHODS To study the antitumor promoting effects of celecoxib, we used the classical two-stage mouse skin tumorigenesis model that involves initiation with a single application of 7,12-dimethylbenz [alpha]anthracene (DMBA) followed by promotion with repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of celecoxib on the expression of COX-2, vascular endothelial growth factor (VEGF), p65 and the different isoforms of CCAAT/enhancer binding protein (C/EBP) were examined by performing Western blot analysis. Electrophoretic mobility gel shift assay was used to examine the effects of celecoxib on the TPA-induced DNA binding activities of various transcription factors. RESULTS Our study revealed that topical application of celecoxib (10micromol) significantly reduced the multiplicity of papillomas in DMBA-initiated and TPA-promoted mouse skin. Pretreatment with celecoxib also diminished the expression of COX-2 and VEGF in the mouse skin papillomas. Pretreatment with celecoxib attenuated DNA binding of transcription factor (C/EBP) in the TPA-stimulated mouse skin. Moreover, celecoxib suppressed the TPA-induced nuclear expression of C/EBPdelta, but not C/EBPbeta, in mouse skin in vivo. CONCLUSION Our study demonstrates the inhibitory effects of celecoxib on mouse skin tumor promotion, which was associated with a decreased expression of COX-2 and VEGF, as well as inhibition of C/EBP activation.
Control of a 19 level cascaded H-bridge multilevel converter photovoltaic system

Multilevel Cascaded H-Bridge (CHB) converters have attractive features for the implementation of large scale photovoltaic systems. They can be directly connected to high voltages and the multilevel voltage synthesis reduces the harmonic distortion introduced. In addition, they have individual DC links ideal for connecting photovoltaic arrays. Existing high performance voltage balancing techniques can also be adapted to integrate Maximum Power Point Tracking (MPPT). This paper considers a 19 level three-phase CHB converter with photovoltaic arrays supplying power. The structure and control of the system is presented, which shows that the DC link voltages can be individually controlled according to MPPT demands, negating the need for DC/DC converters. The system also maintains balanced output currents for power transfer to the grid. Simulation and experimental results are presented that validate the operation of the system.
Mesoscopic fluctuations of the critical current in a superconductor-normal-conductor-superconductor.

Mesoscopic fluctuations are observed for the critical current in a superconductor\char22{}normal-conductor\char22{}superconductor junction using the inversion layer of $p$-type InAs as the normal conductor. As a function of the gate voltage (i.e., the Fermi energy) the critical current and the conductance exhibit mesoscopic fluctuations in both the weak and the strong localization regimes. The magnitude and the typical period of the fluctuations are discussed and compared to theoretical predictions.
A Calibration Algorithm for Mutual Coupling Errors of Array Sensors Based on the Nonlinear Constraint

A new calibration approach needing one calibration source is presented to estimate the mutual coupling coefficients of uniform circular array. Firstly, the data collection is done by placing one assistant source in different direction. Then the cost function is present by using the signal subspace vector and noise subspace vector of data covariance matrix. Under the nonlinear constraint, the union DOA estimation of assistant source and the mutual coupling coefficients of uniform circular array are given by iterative operation. The algorithm does not need know the direction of assistant source. Simulations show validity of the algorithm
Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair.

Acute myelogenous leukemias (AMLs) are genetically heterogeneous and characterized by chromosomal rearrangements that produce fusion proteins with aberrant transcriptional regulatory activities. Expression of AML fusion proteins in transgenic mice increases the risk of myeloid leukemias, suggesting that they induce a preleukemic state. The underlying molecular and biological mechanisms are, however, unknown. To address this issue, we performed a systematic analysis of fusion protein transcriptional targets. We expressed AML1/ETO, PML/RAR, and PLZF/RAR in U937 hemopoietic precursor cells and measured global gene expression using oligonucleotide chips. We identified 1,555 genes regulated concordantly by at least two fusion proteins that were further validated in patient samples and finally classified according to available functional information. Strikingly, we found that AML fusion proteins induce genes involved in the maintenance of the stem cell phenotype and repress DNA repair genes, mainly of the base excision repair pathway. Functional studies confirmed that ectopic expression of fusion proteins constitutively activates pathways leading to increased stem cell renewal (e.g., the Jagged1/Notch pathway) and provokes accumulation of DNA damage. We propose that expansion of the stem cell compartment and induction of a mutator phenotype are relevant features underlying the leukemic potential of AML-associated fusion proteins.
Functional reactive types

Functional Reactive Programming (FRP) is an approach to streaming data with a pure functional semantics as time-indexed values. In previous work, we showed that Linear-time Temporal Logic (LTL) can be used as a type system for discrete-time FRP, and that functional reactive primitives perform two roles: as combinators for building streams of data, and as proof rules for constructive LTL. In this paper, we add a third role, by showing that FRP combinators can be used to define streams of types, and that these functional reactive types can be viewed both as a constructive temporal logic, and as the types for functional reactive programs. As an application of functional reactive types, we show that past-time LTL (pLTL) can be extended with FRP to get a logic pLTL+FRP. This logic is expressed as streams of boolean expressions, and so bounded satisfiability of pLTL can be translated to Satisfiability Modulo Theory (SMT). Thus, pLTL+FRP can be used as a constraint language for problems which mix properties of data with temporal properties.
Repair Site Integrity after Arthroscopic Transosseous-Equivalent Suture-Bridge Rotator Cuff Repair

Background Successful healing after arthroscopic rotator cuff repair remains a challenge. Earlier studies have shown a relatively high rate of failure. New surgical techniques may improve healing potential. The purpose of this study was to provide an objective evaluation of repair site integrity after arthroscopic transosseous-equivalent suture-bridge rotator cuff repair. Hypothesis Rotator cuff tears repaired using the transosseous-equivalent suture-bridge technique will show a higher intact rate on postoperative magnetic resonance imaging (MRI) evaluation. Study Design Case series; Level of evidence, 4. Methods The first 25 patients who underwent arthroscopic rotator cuff repair using the transosseous-equivalent suture-bridge technique underwent MRI evaluation of the postoperative shoulder. Minimum follow-up was 1 year. Demographic, clinical, and surgical factors, including tear size, were evaluated. Results Postoperative MRI demonstrated intact surgical repair sites in 22 of 25 patients (88%). Tears limited to the supraspinatus tendon were intact in 16 of 18 patients (89%). Tears of the supraspinatus involving part or all of the infraspinatus showed an 86% intact rate (6 of 7 patients). Of these tears, 3 were considered massive (complete 2-tendon or greater). These demonstrated an intact cuff on MRI. Conclusions The transosseous-equivalent suture-bridge technique demonstrates a high healing rate on imaging studies at 1 year. Of the first 25 patients repaired with the technique, 88% had an intact rotator cuff repair on MRI evaluation. This indicates excellent cuff healing, as judged by the intact repair sites, compared with most standard arthroscopic rotator cuff repair series. In this early report of the technique, a persistent tear could not be correlated with age or initial tear size; however, this may be due to the relatively small sample size.
Endothelial Nitric Oxide Synthase Uncoupling Impairs Endothelial Progenitor Cell Mobilization and Function in Diabetes

Uncoupling of the endothelial nitric oxide synthase (eNOS) resulting in superoxide anion (O2−) formation instead of nitric oxide (NO) causes diabetic endothelial dysfunction. eNOS regulates mobilization and function of endothelial progenitor cells (EPCs), key regulators of vascular repair. We postulate a role of eNOS uncoupling for reduced number and function of EPC in diabetes. EPC levels in diabetic patients were significantly reduced compared with those of control subjects. EPCs from diabetic patients produced excessive O2− and showed impaired migratory capacity compared with nondiabetic control subjects. NOS inhibition with NG-nitro-l-arginine attenuated O2− production and normalized functional capacity of EPCs from diabetic patients. Glucose-mediated EPC dysfunction was protein kinase C dependent, associated with reduced intracellular BH4 (tetrahydrobiopterin) concentrations, and reversible after exogenous BH4 treatment. Activation of NADPH oxidases played an additional but minor role in glucose-mediated EPC dysfunction. In rats with streptozotocin-induced diabetes, circulating EPCs were reduced to 39 ± 5% of controls and associated with uncoupled eNOS in bone marrow. Our results identify uncoupling of eNOS in diabetic bone marrow, glucose-treated EPCs, and EPCs from diabetic patients resulting in eNOS-mediated O2− production. Subsequent reduction of EPC levels and impairment of EPC function likely contributes to the pathogenesis of vascular disease in diabetes.
Early Lung Cancer Diagnosis by Biosensors

Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted.
Cognitive development after the Fontan operation.

BACKGROUND Patients with a single ventricle have multiple risk factors for central nervous system injury, both before and after the Fontan procedure. METHODS AND RESULTS A geographically selected cohort was invited to undergo standardized testing, including age-appropriate measures of intelligence quotient (IQ) and achievement tests. Historical information was obtained by chart review and patient questionnaires. Of the 222 eligible patients, 133 (59.9%) participated. Median age at testing was 11.1 years (range, 3. 7 to 41.0 years), 6.0 years (range, 1.6 to 19.6 years) after surgery. Mean full-scale IQ was 95.7+/-17.4 (P<0.006 versus normal); 10 patients (7.8%) had full-scale IQ scores <70 (P=0.001). After adjustment for socioeconomic status, lower IQ was associated with the use of circulatory arrest before the Fontan operation (P=0.002), the anatomic diagnoses of hypoplastic left heart syndrome (P<0.001) and "other complex" (P=0.05), and prior placement of a pulmonary artery band (P=0.04). Mean composite achievement score was 91.6+/-15. 4 (P<0.001 versus normal); 14 patients (10.8%) scored <70 (P<0.001). After adjustment for socioeconomic status, independent risk factors for low achievement scores included the diagnoses of hypoplastic left heart syndrome (P=0.004) and "other complex" (P=0.003) or prior use of circulatory arrest (P=0.03), as well as a reoperation with cardiopulmonary bypass within 30 days of the Fontan (P=0.01). CONCLUSIONS Most individual patients palliated with the Fontan procedure in the 1970s and 1980s have cognitive outcome and academic function within the normal range, but the performance of the cohort is lower than that of the general population.
IPBES: Opportunities and Challenges for SCB and Other Learned Societies

The global nature of the biodiversity crisis, and the failures of prior international agreements to reverse it, has led to the formation of a new Intergovernmental SciencePolicy Platform on Biodiversity and Ecosystem Services (IPBES) as a means to bridge the gap between biodiversity science and policy (www.ipbes.net). The IPBES offers an important opportunity for the Society for Conservation Biology (SCB) and other learned societies to provide decision makers with objective, peer-reviewed information and to participate in forming policies that affect biodiversity. The SCB and its members have participated in related consultations and plenary sessions that led to the establishment of IPBES, and will undoubtedly contribute further, but additional challenges lay ahead in making IPBES a successful endeavor.
Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER) Workflow for Research and Clinical Brain PET Applications

Objective There is a need for tools enabling efficient evaluation of amyloid- and tau-PET images suited for both clinical and research settings. The purpose of this study was to assess and validate a semi-automated imaging workflow, called Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER). We tested BLAzER using two different segmentation platforms, FreeSurfer (FS) and Neuroreader (NR), for regional brain PET quantification in images from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Methods 127 amyloid-PET and 55 tau-PET studies along with corresponding volumetric MRI were obtained from ADNI. The BLAzER workflow utilizes segmentation of MR images by FS or NR, then visualizes and quantifies regional brain PET data using FDA-cleared software (MIM), enabling quality control to ensure optimal registration and detect segmentation errors. Results BLAzER analysis required only ∼5 min plus segmentation time. BLAzER using FS segmentation showed strong agreement with ADNI for global amyloid-PET standardized uptake value ratios (SUVRs) (r = 0.9922, p < 0.001) and regional tau-PET SUVRs across all Braak staging regions (r > 0.97, p < 0.001) with high inter-operator reproducibility for both (ICC > 0.97) and nearly identical dichotomization as amyloid-positive or -negative (2 discrepant cases out of 127). Comparing FS vs. NR segmentation with BLAzER, the global SUVRs were strongly correlated for global amyloid-PET (r = 0.9841, p < 0.001), but were systematically higher (4% on average) with NR, likely due to more inclusion of white matter, which has high florbetapir binding. Conclusions BLAzER provides an efficient workflow for regional brain PET quantification. FDA-cleared components and the ability to visualize registration reduce barriers between research and clinical applications.
Risk of selected gastrointestinal toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis

We performed a systematic review and meta-analysis of the risk of gastrointestinal (GI) toxicities associated with MEK inhibitors. Eligible studies included randomized Phase II and III trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib), describing events of stomatitis, diarrhea and vomiting. Our search strategy yielded 250 potentially relevant citations from Pubmed/Medline, Google scholar and CENTRAL Cochrane registry. After exclusion of ineligible studies, a total of 16 clinical trials were considered eligible for the meta-analysis. The relative risks of all-grade stomatitis, diarrhea and vomiting were 2.03 (95% CI 1.41–2.96; p = 0.002), 1.92 (95% CI 1.48–2.50; p < 0.00001) and 1.35 (95% CI 1.06–1.71; p = 0.01). Subgroup analyses according to agent used (trametinib vs Selumetinib), the regimen used (monotherapy vs combination) and the cancer treated (melanoma vs nonmelanoma) did not reveal any significant difference between the subgroups. Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of stomatitis, diarrhea and vomiting compared to control. Clinicians should be aware of this risk and perform regular assessment.
An Analytical Model for Bandwidth Enhancement of Air-Coupled Unsealed Helmholtz Structural CMUTs

Capacitive micromachined ultrasonic transducers (CMUTs) were reported to own high potential in air-coupled ultrasonic applications such as noncontact nondestructive examination and gas flow measurement. The unsealed CMUTs which utilized the squeeze film effect were reported to overcome the narrow output pressure bandwidth of the conventional sealed CMUTs in air operation. This kind of unsealed CMUTs can also be regarded as Helmholtz resonators. In this work, we present the air-coupled unsealed Helmholtz structural CMUTs which utilize both the squeeze film effect and the Helmholtz resonant effect to enhance the output pressure bandwidth. Based on the mechanism of vibration coupling between membrane and air pistons in membrane holes, we propose an analytical model to aid the design process of this kind of CMUTs. We also use finite element method (FEM) to investigate this kind of CMUTs for our analytical model validation. The FEM results show that the significant bandwidth enhancement can be achieved when the Helmholtz resonant frequency is designed close to the fundamental resonant frequency of the CMUT membrane. Compared with the conventional sealed CMUT cell, the 4-hole unsealed Helmholtz structural CMUT cell improves both the 3-dB fractional bandwidth and SPL-bandwidth product around 35 times. Furthermore, it is found that, with more holes under the same hole area ratio or with a smaller ratio of the cavity height to the viscous boundary layer thickness, the Helmholtz resonant effect becomes weaker and thus the output pressure bandwidth decreases.
Mutations in DNA Replication Genes Reduce Yeast Life Span

ABSTRACT Surprisingly, the contribution of defects in DNA replication to the determination of yeast life span has never been directly investigated. We show that a replicative yeast helicase/nuclease, encoded by DNA2 and a member of the same helicase subfamily as the RecQ helicases, is required for normal life span. All of the phenotypes of old wild-type cells, for example, extended cell cycle time, age-related transcriptional silencing defects, and nucleolar reorganization, occur after fewer generations in dna2 mutants than in the wild type. In addition, the life span of dna2 mutants is extended by expression of an additional copy of SIR2 or by deletion of FOB1, which also increase wild-type life span. The ribosomal DNA locus and the nucleolus seem to be particularly sensitive to defects in dna2 mutants, although in dna2 mutants extrachromosomal ribosomal circles do not accumulate during the aging of a mother cell. Several other replication mutations, such as rad27Δ, encoding the FEN-1 nuclease involved in several aspects of genomic stability, also show premature aging. We propose that replication fork failure due to spontaneous, endogenous DNA damage and attendant genomic instability may contribute to replicative senescence. This may imply that the genomic instability, segmental premature aging symptoms, and cancer predisposition associated with the human RecQ helicase diseases, such as Werner, Bloom, and Rothmund-Thomson syndromes, are also related to replicative stress.