Miracle-dz/UniFAR-FTUs huggingface dataset:
Plectin-targeted liposomes enhance the therapeutic efficacy of a PARP inhibitor in the treatment of ovarian cancer

Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise. About 10% of the patients who received Olaparib (PARP inhibitor) showed adverse side effects including neutropenia, thrombocytopenia and in some cases resulted in myelodysplastic syndrome, indicating that off-target effects were substantial in these patients. Through proteomic analysis, our lab previously identified plectin, a cytolinker protein that mislocalized onto the cell surface during malignant transformation of healthy ovarian tissue. This cancer specific phenotype allowed us to image pancreatic cancer successfully using plectin targeted peptide (PTP) conjugated to nanoparticles or displayed on capsid protein of adeno-associated virus (AAV) particles. Objective: The goal of this study was to integrate the available pharmacogenomics and proteomic data to develop effective anti-tumor therapies using a targeted drug delivery approach. Methods: Plectin expression and localization in human ovarian tumor specimens were analyzed followed by in vitro confirmation of cell surface plectin localization in healthy and ovarian cancer cell lines. PTP-conjugated liposomes were prepared and their specificity for plectin+ cells was determined in vitro and in vivo. A remote loading method was employed to encapsulate a PARP inhibitor (AZ7379) into liposomes. An ideal buffer exchange method and remote loading conditions were determined based on the amount of lipid and drug recovered at the end of a remote loading process. Finally, in vivo tumor growth studies were performed to determine the efficacy of PTP liposomes in preventing PARP activity in mice bearing OVCAR8 (high grade epithelial ovarian cancer (EOC)) tumors. Results: PTP liposomal AZ7379 delivery not only enhanced PARP inhibition but also resulted in decelerated tumor growth in mice bearing subcutaneous and intraperitoneal OVCAR8 tumors. In mice bearing subcutaneous or intraperitoneal tumors, treatment with PTP liposomes resulted in a 3- and 1.7-fold decrease in tumor volume, respectively, compared to systemic drug treatment. Conclusion: Targeted drug delivery assisted by genomic and proteomic data provides an adaptable model system that can be extended to effectively treat other cancers and diseases.
Characterization of nontypeable rotavirus strains from the United States: identification of a new rotavirus reassortant (P2A[6],G12) and rare P3[9] strains related to bovine rotaviruses.

Among 1316 rotavirus specimens collected during strain surveillance in the United States from 1996 to 1999, most strains (95%) belonged to the common types (G1 to G4 and G9), while 5% were mixed infections of common serotypes, rare strains, or not completely typeable. In this report, 2 rare (P[9],G3) and 2 partially typeable (P[6],G? ; P[9],G? ) strains from that study were further characterized. The P[6] strain was virtually indistinguishable by hybridization analysis in 10 of its 11 gene segments with recently isolated P2A[6],G9 strains (e.g., U.S.1205) from the United States, but had a distinct VP7 gene homologous (94.7% a.a. and 90.2% nt) to the cognate gene from P1B[4],G12 reference strain L26. Thus, this serotype P2A[6],G12 strain represents a previously unrecognized reassortant. Three P3[9] strains were homologous (97.8-98.2% aa) in the VP8 region of VP4 to the P3[9],G3 feline-like reference strain AU-1, but had a high level of genome homology to Italian bovine-like, P3[9],G3 and P3[9],G6 rotavirus strains. Two of the U.S. P3[9] strains were confirmed to be type G3 (97.2-98.2% VP7 aa homology with reference G3 strain AU-1), while the other was most similar to Italian bovine-like strain PA151 (P3[9],G6), sharing 99.0% a.a. homology in VP7. Cross-neutralization studies confirmed all serotype assignments and represented the first detection of these rotavirus serotypes in the United States. The NSP4 genes of all U.S. P3[9] strains and rotavirus PA151 were most closely related to the bovine and equine branch within the DS-1 lineage, consistent with an animal origin. These results demonstrate that rare strains with P and G serotypes distinct from those of experimental rotavirus vaccines circulate in the United States, making it important to understand whether current vaccine candidates protect against these strains.
Integrating education for sustainable development into a higher education institution: beginning the journey

Much of the current literature on integrating sustainability into HEIs is focussed on why HEIs should embrace sustainable development (SD) and what is still missing or hindering work and the integration of efforts. There is much less exploration of how SD has been interpreted at the individual HEI level and action taken as a result. This case study reflects on important elements of the journey Nottingham Trent University (NTU) in the UK has taken to integrate sustainability, focussing on key decisions and activity in 2009/10. In highlighting this, the authors seek to empower those looking to support and/or lead the embedding of Education for Sustainable Development (ESD), separately or as part of an integrated effort, in their own institution. Today in 2019, NTU is a global leader in integrating ESD as part of a wider SD agenda. The work which this paper presents, to understand and establish a baseline of key elements of NTU’s existing ESD activity and systems, was an important turning point. Activities undertaken to review and assess ‘where are we now? ’, primarily through an institution-wide survey in 2009/10, led to important insights and supported dialogue, as well as the connection and underpinning of core administrative elements of the NTU SD framework and systems. Further recommendations are given in the final section of this paper on other drivers that can help to embed ESD within an HEI.
DupHunter: Detecting Duplicate Pull Requests in Fork-Based Development

The emergence of numerous fork-based development platforms facilitates the development of Open-Source Software (OSS) projects. Developers across the world can fork software projects and submit their Pull Requests (PRs) to the projects. However, as the number of forks increases, numerous duplicate PRs might be submitted. These duplicate PRs may cause extra code review workload and frustrate developers working on the projects. To detect duplicate PRs, many approaches have been proposed, which analyze the similarity of different elements in PRs. However, previous approaches still suffer from unsatisfied detection accuracy due to two challenges. That is, they ignore the syntactic structural information of text elements in PRs and lack the joint reasoning between different elements of two PRs. In this study, we propose an automated duplicate PRs detector named DupHunter (Duplicate PRs Hunter), which includes a graph embedding component and a duplicate PRs detection component to address the above challenges. The graph embedding component uses a feature graph to represent a PR. It encodes the syntactic structure and semantics of text elements (e.g., the title and the description), as well as the knowledge of non-text elements (e.g., the submission time), to address the syntactic structural information challenge. The duplicate PRs detection component tackles the joint reasoning challenge using a graph matching network, which enables the information exchange and matching across different elements of two feature graphs with an attention coefficient mechanism. Experiments on 26 open-source projects show that DupHunter achieves an average F1-score@1 value of 0.650, significantly outperforming the state-of-the-art approaches by 3.2% to 48.1%. DupHunter can accurately detect duplicate PRs, with an average Precision@1 value of 0.922 and an average Recall@1 value of 0.502.
Dissipative Control of Linear Time-Delay Systems: Full State Feedback

The control and observation of autonomous linear time delay systems (LTDSs) remain a challenging problem when considering an unlimited number of pointwise and general distributed delays (DDs) with dissipative constraints. Existing solutions are hindered by theoretical limitations, numerical obstacles, or an inability to handle the complexities of DD kernels. In this paper, we present a unified framework based on the equivalent decomposition-approximation (EDA) technique that we recently developed for the analysis of general DDs. The framework can simultaneously address two separated control problems using the Krasovski\u{\i} functional (KF) approach, where all DDs can contain an unlimited number of square-integrable functions. We demonstrate in detail how the EDA technique can factorize and approximate any kernel function simultaneously without introducing conservatism. This approach also enables us to construct a complete-type KF, where its integral kernels can include any number of weakly differentiable and linearly independent functions, supported by the utilization of novel integral inequalities derived from the least-squares principle. The solution to each synthesis problem comprises two theorems accompanied by an iterative algorithm, which can be utilized as a single package to compute controller gains, eliminating the need for nonlinear solvers. We test several challenging examples, which cannot be addressed by existing methods, to demonstrate the effectiveness of our methodology. The paper also reviews some of the latest results on the analysis of LTDSs, which may serve as a useful reference for both students and experienced researchers in related fields.
Industry Internet of Things based Intelligent Driver Monitoring System

Emerging technologies making motor vehicles smarter and upgraded with humanly features. With these new technologies, made easier to develop vehicles smarter with advance safety features. Besides road safety rules, safety alert systems, awareness programs and road surveillance systems, still road accidents deaths are increasing frequently and subsequently. The analysis report shows that many of these occurred due to lack of following the safety guidelines like over-speeding, not using seat belts, wrong side driving and so on. In four-wheeled vehicles, it is enforced to buckle up the seat belts to avoid life damages, and vehicles comes up with the feature of alarm generation to ensure the same. Still people are capable of forge these alerts systems and drive without wearing seat belts. Hence, to fill up this gap, this article represents an Industry Internet of Things (IIoT) based driver monitoring system mounted with a micro-camera, which is capable of ensuring the presence of seat belts on both driver and co-driver. In case to its unavailability of safety belt microcontroller will discontinue the power supply and stop the ignition, until the seat belt is not buckled up by the users. In addition to that, system is also capable of monitor the yawning and eye movement to generate the required alerts ensuring that driver is in conscious condition to drive safely or not Collectively, generating a real time monitoring system for the safety of four wheeler users. Further, these features can br embedded along with the driverless transportation vehicles ensuring the safety for end users.
TRIMS LST: A daily 1-km all-weather land surface temperature dataset for the Chinese landmass and surrounding areas (2000-2021)

Land surface temperature (LST) is a key variable within the Earth’s climate system and a necessary input parameter required by numerous land-atmosphere models. It can be directly retrieved from satellite thermal infrared (TIR) observations, 10 but cloud contamination results in many spatial missing. To investigate the temporal and spatial variations of LST in China, long-term, high-quality, and spatio-temporally continuous LST datasets (i.e., all-weather LST) are urgently needed. Fusing satellite TIR LST and reanalysis datasets is a viable route to obtain long time-series all-weather LST. Among satellite TIR LSTs, the MODIS LST is the most commonly used and a few all-weather LST products generated in this way have been reported recently. However, the publicly reported all-weather LSTs are not available during the temporal gaps of MODIS 15 between 2000 and 2002. In this context, we report a daily 1-km all-weather LST dataset for the Chinese landmass and surrounding areas – TRIMS LST. Different from other products, the TRIMS LST begins on the first day of the new millennium (i.e., January 1, 2000). The TRIMS LST was generated based on the Enhanced Reanalysis and Thermal infrared remote sensing Merging (E-RTM) method. Specifically, the original RTM method was used to generate the TRIMS LST outside the temporal gaps. Two newly developed approaches, including the Random-Forest based Spatio-Temporal Merging (RFSTM) approach 20 and Time-Sequential LST based Reconstruction (TSETR) approach, were used to produce Terra/MODIS-based and Aqua/MODIS-based TRIMS LSTs during the temporal gaps, respectively. Thorough evaluation of the TRIMS LST was conducted. A comparison with the GLDAS and ERA5-Land LSTs demonstrates that TRIMS LST has similar spatial patterns but higher image quality, more spatial details, and no evident spatial discontinuities. Further comparison with MODIS and AATSR LSTs shows that TRIMS LSTs agree well with them, with mean bias deviation (MBD) between -0.40 K and 0.30 K 25 and standard deviation of bias (STD) between 1.17 K and 1.50 K. Validation based on ground measured LST at 19 ground sites showed that the mean bias error (MBE) of the TRIMS LST ranged from -2.26 K to 1.73 K and the root mean square error (RMSE) was 0.80 K to 3.68 K, with no significant difference between the clear-sky and cloudy conditions. The TRIMS LST has already been used by scientific communities in various applications such as soil moisture downscaling, evapotranspiration estimation, and urban heat island (UHI) modelling. The TRIMS LST is freely and conveniently available at
VALIDITY OF BASIC PHYSICS MODULE OF CAC MODEL TO IMPROVE HIGHER ORDER THINKING SKILLS OF COLLEGE STUDENTS.

Agus Kadarmanto 1 , Indrawati 2 , Yushardi 3 and Sutarto 4 . 1. Student of Magister Sains of Education, Jember University. 2. Sains Education Departmen, University of Jember. Manuscript Info Abstract . Manuscript History
Messy Genetic Algorithms Revisited: Studies in Mixed Size and Scale

Genetic algorithms have been finding increasing application to difficult search and optimization problems in science and engineering. As more demands are placed on the methodology, the remaining challenges to the technique have become increasingly apparent, and that they have remained largely unanswered has become less than acceptable to a user base seeking to cash in on the method's oft-repeated promises of robustness. Foremost among these challenges is the so-called linkage problem. In difficult problems-so-called deceptive problems-if needed bits or features are not coded tightly on the artificial chromosome, simple genetic algorithms will be forced to bypass global optima and instead be misled toward less acceptable local optima. Standard suggestions to circumvent this problem through inversion or other reordering operators have not been successful, and it has been suggested that many of these operators are too slow to be of timely use. These difficulties led to the invention of so-called messy genetic algorithms that were introduced in a previous paper. Simply stated, messy genetic algorithms tackle the linkage problem by finding tightly coded building blocks initially and then juxtaposing them to find globally optimal structures. In the original study, a 3D-bit, order-three deceptive problem was solved to global optimality, but a number of challenges were posed for the messy methodology. Specifically, nonuniform building block scale and size were highlighted as difficulties that must be overcome if mGAs were to become a technique of general applicability. These challenges have been overcome, and this paper presents theoretical and computational results using mGAs on problems of varying building block size and scale. The problem of nonuniform building block scale is tackled with a technique called genic selective crowding, and the problem of nonuniform building-block size is handled with null bits and tie breaking. Together, these techniques appear to overcome these difficult hurdles, yielding convergence to global optima in problems of bounded deception. Furthermore, this desirable convergence is performed with remarkable efficiency. Theoretical computations are presented that show that mGAs converge in time that grows only as a polynomial function of the number of decision variables on a serial machine and as a logarithmic function of the number of decision variables on a parallel machine with a polynomial number of processors. The paper also suggests a number of extensions and continuations of this work, including the trial of messy floating point codes, messy permutations, and messy classifiers (rules). Although additional basic work is both needed and recommended, the compelling convergence and efficiency demonstrated by mGAs recommends them for immediate application in some of the many tough, blind combinatorial optimization problems of science and engineering that have gone unsolved for want of more tractable solution techniques.
Long-term Air Pollution Exposure, Genome-wide DNA Methylation and Lung Function in the LifeLines Cohort Study

Background: Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not fully clear. Differential DNA methylation may explain this association. Objectives: Our main aim was to study the association between long-term air pollution exposure and DNA methylation. Methods: We performed a genome-wide methylation study using robust linear regression models in 1,017 subjects from the LifeLines cohort study to analyze the association between exposure to nitrogen dioxide (NO2) and particulate matter (PM2.5, fine particulate matter with aerodynamic diameter ≤2.5μm; PM10, particulate matter with aerodynamic diameter ≤10μm) and PM2.5absorbance, indicator of elemental carbon content (estimated with land-use-regression models) with DNA methylation in whole blood (Illumina® HumanMethylation450K BeadChip). Replication of the top hits was attempted in two independent samples from the population-based Cooperative Health Research in the Region of Augsburg studies (KORA). Results: Depending on the p-value threshold used, we found significant associations between NO2 exposure and DNA methylation for seven CpG sites (Bonferroni corrected threshold p<1.19×10−7) or for 4,980 CpG sites (False Discovery Rate<0.05). The top associated CpG site was annotated to the PSMB9 gene (i.e., cg04908668). None of the seven Bonferroni significant CpG-sites were significantly replicated in the two KORA-cohorts. No associations were found for PM exposure. Conclusions: Long-term NO2 exposure was genome-wide significantly associated with DNA methylation in the identification cohort but not in the replication cohort. Future studies are needed to further elucidate the potential mechanisms underlying NO2-exposure–related respiratory disease. https://doi.org/10.1289/EHP2045
Affective Response and the Analyst's Freedom in Work with Traumatized Adolescents

Clinical work with adolescents who come to us after traumatic experiences involves a total availability of the therapist as a human being, a readiness to accompany patients along the painful path of psychic change and to suffer for them and with them, even to immerse oneself concretely in the emotional catastrophe that once overwhelmed them. The analyst who works not simply in an office but also in public institutions (such as a hospital or juvenile court) knows very well that emotionally absent and indifferent—if not actively negligent and abusive—parents (who are always too absorbed by their own suffering to listen to children’s needs) plough a furrow in their sons’ and daughters’ psychic worlds. This injury, often compounded by complacency or denial, will inevitably remain open and, in successive periods of life or particularly critical moments (such as adolescence), give rise to severe neurotic symptoms, narcissistic pathologies, or even to psychic death, to suicide of the self. These seem to be—and are—up-to-date words, but the concepts belong to Ferenczi, who found that trauma “is far more rarely the result of a constitutional hypersensibility in children (causing them to react neurotically even to a commonplace and unavoidable painful experience) than of really improper, unintelligent, tactless, or actually cruel treatment”
Anaesthetic, cardiovascular and respiratory effects of a new steroidal agent CT 1341: a comparison with other intravenous anaesthetic drugs in the unrestrained cat

1 . The anaesthetic, cardiovascular, respiratory and adverse effects produced by the intravenous injection of CT 1341, thiopentone, methohexitone, pentobarbitone, propanidid and ketamine have been compared in unrestrained cats prepared with chronically implanted venous and arterial cannulae. Aortic blood pressure and heart rates were monitored before, during and after loss of consciousness. 2 . CT 1341 produced rapid induction of anaesthesia followed by moderately rapid recovery, was active over a wide range of doses and caused minimal respiratory depression and few adverse effects. It caused an initial short‐lasting tachycardia and fall in aortic blood pressure succeeded by a secondary depressor response. 3 . The safety margin was narrower with the barbiturate drugs than with CT 1341, and large doses induced apnoea and respiratory depression. Small doses of methohexitone elicited excitatory effects and large doses caused severe respiratory and circulatory depression, and recovery from anaesthesia was protracted. 4 . Propanidid induced short‐lasting light anaesthesia. The safety margin was narrowest with this drug and induction was associated with adverse circulatory, respiratory and other effects. 5 . Ketamine was active over a wide range of doses but exhibited qualitatively different properties from the other anaesthetics. Induction was slower after small doses and these produced circulatory stimulation, catatonia and bizarre behavioural effects. Large doses caused respiratory and circulatory depression and recovery was protracted. 6 . It is concluded that CT 1341 has a wider therapeutic latitude, produces less respiratory depression and has other advantages over the currently used intravenous anaesthetics.