Miracle-dz/UniFAR-FTUs huggingface dataset:
Parallel and Distributed Thompson Sampling for Large-scale Accelerated Exploration of Chemical Space

Chemical space is so large that brute force searches for new interesting molecules are infeasible. High-throughput virtual screening via computer cluster simulations can speed up the discovery process by collecting very large amounts of data in parallel, e.g., up to hundreds or thousands of parallel measurements. Bayesian optimization (BO) can produce additional acceleration by sequentially identifying the most useful simulations or experiments to be performed next. However, current BO methods cannot scale to the large numbers of parallel measurements and the massive libraries of molecules currently used in high-throughput screening. Here, we propose a scalable solution based on a parallel and distributed implementation of Thompson sampling (PDTS). We show that, in small scale problems, PDTS performs similarly as parallel expected improvement (EI), a batch version of the most widely used BO heuristic. Additionally, in settings where parallel EI does not scale, PDTS outperforms other scalable baselines such as a greedy search, $\epsilon$-greedy approaches and a random search method. These results show that PDTS is a successful solution for large-scale parallel BO.
Pluripotency transcription factors and Metabolic reprogramming of mitochondria in tumor-initiating stem-like cells.

SIGNIFICANCE Neoplasms contain tumor-initiating stem-like cells (TICs) that drive malignant progression and tumor growth with drug resistance. TICs proliferate through self-renewal process in which the two daughter cells differ in their proliferative potential, with one retaining self-renewing phenotype and another displaying the differentiated phenotype. Recent advances: Cancer traits (hepatocellular carcinoma: HCC) are triggered by alcoholism, obesity and hepatitis B or C virus (HBV and HCV), including genetic changes, angiogenesis, defective tumor immunity, immortalization, metabolic reprogramming, excessive & prolonged inflammation, migration/invasion/metastasis, evasion of cell cycle arrest, anti-cell death and compensatory regeneration/proliferation. CRITICAL ISSUES This review describes how metabolic reprogramming in mitochondria promotes self-renewal and oncogenicity of TICs. Pluripotency transcription factors NANOG, OCT4, MYC and SOX2 contribute to cancer progression by mitochondrial reprogramming leading to the genesis of TICs and cancer. For example, oxidative phosphorylation (OXPHOS) and fatty acid metabolism are identified as major pathways contributing to pluripotency transcription factor-mediated oncogenesis. FUTURE DIRECTIONS Identification of novel metabolic pathways provides potential drug targets for neutralizing the activity of highly malignant TICs found in cancer patients.
Anti-Angiogenics: Their Value in Lung Cancer Therapy

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths. Different targeted therapies and the introduction of immunotherapy have successfully improved outcome for patients with non-small lung cancer (NSCLC). Anti-angiogenic drugs are an essential component in the treatment of NSCLC patients. The vascular endothelial growth factor (VEGF)-A antibody bevacizumab is approved for first-line treatment of advanced-stage patients in combination with platinum-based chemotherapy. Ramucirumab, a VEGF receptor antibody, and nintedanib, an anti-angiogenic multi-tyrosine kinase inhibitor, are approved for second-line treatment in combination with docetaxel. This review provides a summary of pivotal trials with anti-angiogenic drugs in NSCLC in different settings. We give an overview of how to position anti-angiogenic therapy in the current treatment algorithms and highlight future directions. The identification of predictive biomarkers for patient selection could improve the success of anti-angiogenic drugs and represents an important area of research. In addition, novel therapeutic targets including endothelial metabolomic intermediates and cellular components of the tumor microenvironment could lead to the identification of innovative new targets besides the VEGF axis.
Development of dihydrochalcone-functionalized gold nanoparticles for augmented antineoplastic activity

Background Phloridzin, an antidiabetic and antineoplastic agent usually found in fruit trees, is a dihydrochalcone constituent that has a clinical/pharmaceutical significance as a sodium-glucose linked transport 2 (SGLT2) inhibitor. While the aglycone metabolite of phloridzin, phloretin, displays a reduced capacity of SGLT2 inhibition, this nutraceutical displays enhanced antineoplastic activity in comparison to phloridzin. Purpose The objective of this study was to develop gold nanoparticle (AuNP) mediated delivery of phloridzin and phloretin and explore their anticancer mechanism through conjugation of the dihydrochalcones and the AuNP cores. Methods Phloridzin and phloretin conjugated AuNPs (Phl-AuNP and Pht-AuNP) were synthesized in single-step, rapid, biofriendly processes. The synthesized AuNPs morphology was characterized via transmission electron microscopy and ultraviolet-visible spectroscopy. The presence of phloridzin or phloretin was confirmed using scanning electron microscopy-energy dispersive x-ray spectroscopy. The percentage of organic component (phloridzin/phloretin) onto AuNPs surface was characterized using thermogravimetric analysis. Assessment of the antineoplastic potency of the dihydrochalcones conjugated AuNPs against cancerous cell lines (HeLa) was accomplished through monitoring via flow cytometry. Results The functionalized AuNPs were synthesized via a single-step method that relied only upon the redox potential of the conjugate itself and required no toxic chemicals. The synthesized Phl-AuNPs were found to be in the size range of 15±5 nm, whereas the Pht-AuNP were found to be 8±3 nm, placing both conjugated AuNPs well within the size range necessary for successful pharmaceutical applications. These assays demonstrate a significant increase in the cancerous cell toxicities as a result of the conjugation of the drugs to AuNPs, as indicated by the 17.45-fold increase in the efficacy of Pht-AuNPs over pure phloretin, and the 4.49-fold increase in efficacy of Phl-AuNP over pure phloridzin. Conclusion We report a simple, biofriendly process using the reducing and capping potential of the dihydrochalcones, phloridzin and phloretin, to synthesize stable AuNPs that have promising futures as potential antineoplastic agents.
On the Posted Pricing in Crowdsourcing: Power of Bonus

In practical crowdsourcing systems such as Amazon Mechanical Turk, posted pricing is widely used due to its simplicity, where a task requester publishes a pricing rule a priori, on which workers decide whether to accept and perform the task or not, and are often paid according to the quality of their effort. One of the key ingredients of a good posted pricing lies in how to recruit more high-quality workers with less budget, for which the following two schemes are considered: (i) personalized pricing by profiling users in terms of their quality and cost, and (ii) additional bonus payment offered for more qualified task completion. Despite their potential benefits in crowdsourced pricing, it has been under-explored how much gain each or both of personalization and bonus payment actually provides to the requester. In this paper, we study four possible combinations of posted pricing made by pricing with/without personalization and bonus. We aim at analytically quantifying when and how much such two ideas contribute to the requester's utility. To this end, we first derive the optimal personalized and common pricing schemes and analyze their computational tractability. Next, we quantify the gap in the utility between with and without bonus payment in both pricing schemes. We analytically prove that the impact of bonus is negligible significantly marginal in personalized pricing, whereas crucial in common pricing. Finally, we study the notion of Price of Agnosticity that quantifies the utility gap between personalized and common pricing policies. This implies that a complex personalized pricing with privacy concerns can be replaced by a simple common pricing with bonus. We validate our analytical findings through extensive simulations and real experiments done in Amazon Mechanical Turk, and provide additional implications that are useful in designing a pricing policy.
Rural Family Physicians Are Twice as Likely to Use Telehealth as Urban Family Physicians.

BACKGROUND Telehealth has the potential to reduce health inequities and improve health outcomes among rural populations through increased access to physicians, specialists, and reduced travel time for patients. INTRODUCTION Although rural telehealth services have expanded in several specialized areas, little is known about the attitudes, beliefs, and uptake of telehealth use in rural American primary care. This study characterizes the differences between rural and urban family physicians (FPs), their perceptions of telehealth use, and barriers to further adoption. MATERIALS AND METHODS Nationally representative randomly sampled survey of 5,000 FPs. RESULTS Among the 31.3% of survey recipients who completed the survey, 83% practiced in urban areas and 17% in rural locations. Rural FPs were twice as likely to use telehealth as urban FPs (22% vs. 10%). Logistic regressions showed rural FPs had greater odds of reporting telehealth use to connect their patients to specialists and to care for their patients. Rural FPs were less likely to identify liability concerns as a barrier to using telehealth. DISCUSSION Telemedicine allows rural patients to see specialists without leaving their communities and permits rural FPs to take advantage of specialist expertise, expand their scope of practice, and reduce the feeling of isolation experienced by rural physicians. CONCLUSION Efforts to raise awareness of current payment policies for telehealth services, addressing the limitations of current reimbursement policies and state regulations, and creating new avenues for telehealth reimbursement and technological investments are critical to increasing primary care physician use of telehealth services.
Tropical dead zones and mass mortalities on coral reefs

Significance Oxygen-starved coastal waters are rapidly increasing in prevalence worldwide. However, little is known about the impacts of these “dead zones” in tropical ecosystems or their potential threat to coral reefs. We document the deleterious effects of such an anoxic event on coral habitat and biodiversity, and show that the risk of dead-zone events to reefs worldwide likely has been seriously underestimated. Awareness of, and research on, reef hypoxia is needed to address the threat posed by dead zones to coral reefs. Degradation of coastal water quality in the form of low dissolved oxygen levels (hypoxia) can harm biodiversity, ecosystem function, and human wellbeing. Extreme hypoxic conditions along the coast, leading to what are often referred to as “dead zones,” are known primarily from temperate regions. However, little is known about the potential threat of hypoxia in the tropics, even though the known risk factors, including eutrophication and elevated temperatures, are common. Here we document an unprecedented hypoxic event on the Caribbean coast of Panama and assess the risk of dead zones to coral reefs worldwide. The event caused coral bleaching and massive mortality of corals and other reef-associated organisms, but observed shifts in community structure combined with laboratory experiments revealed that not all coral species are equally sensitive to hypoxia. Analyses of global databases showed that coral reefs are associated with more than half of the known tropical dead zones worldwide, with >10% of all coral reefs at elevated risk for hypoxia based on local and global risk factors. Hypoxic events in the tropics and associated mortality events have likely been underreported, perhaps by an order of magnitude, because of the lack of local scientific capacity for their detection. Monitoring and management plans for coral reef resilience should incorporate the growing threat of coastal hypoxia and include support for increased detection and research capacity.
Pulsed laser cladding of pre-placed hydroxyapatite powder on titanium

This paper deals with an experimental study of pulsed laser surface pre-placed powder cladding procedure. This process aims to coat titanium alloy Ti-6Al-4V with hydroxyapatite (HA) using a Nd-YAG laser (wavelength 1.06 μm) in order to form a bioactive layer on a metallic substrate. It clearly aims to orthopaedic applications. It is shown that this process is a possible substitution to plasma spraying coating technology, at present the most current one, avoiding most of the disadvantages of this technique. Nevertheless practical problems have been encountered; seldom reported although important for engineering, this paper essentially focalises on some of them. So pollutions of the calcium coating, calcium-phosphorus ratio modification, change in coating thickness and bonding are approached from chemical-physical or biological point of view. Solutions or ways are proposed to pass over these practical problems.
Efficient Fine-Grained Classification and Part Localization Using One Compact Network

Fine-grained classification of objects such as vehicles, natural objects and other classes is an important problem in visual recognition. It is a challenging task because small and localized differences between similar looking objects indicate the specific fine-grained label. At the same time, accurate classification needs to discount spurious changes in appearance caused by occlusions, partial views and proximity to other clutter objects in scenes. A key contributor to fine-grained recognition are discriminative parts and regions of objects. Past work has often attempted to solve the problems of classification and part localization separately resulting in complex models and ad-hoc algorithms, leading to low performance in accuracy and processing time. We propose a novel multi-task deep network architecture that jointly optimizes both localization of parts and fine-grained class labels by learning from training data. The localization and classification sub-networks share most of the weights, yet have dedicated convolutional layers to capture finer level class specific information. We design our model as memory and computational efficient so that can be easily embedded in mobile applications. We demonstrate the effectiveness of our approach through experiments that achieve a new state-of-the-art 93.1% performance on the Stanford Cars-196 dataset, with a significantly smaller multi-task network (30M parameters) and significantly faster testing speed (78 FPS) compared to recent published results.
A Survey of Power-Saving Techniques on Data Centers and Content Delivery Networks

How to reduce power consumption within individual data centers has attracted major research efforts in the past decade, as their energy bills have contributed significantly to the overall operating costs. In recent years, increasing research efforts have also been devoted to the design of practical power-saving techniques in content delivery networks (CDNs), as they involve thousands of globally distributed data centers with content server clusters. In this paper, we present a comprehensive survey on existing research works aiming to save power in data centers and content delivery networks that share high degree of commonalities in different aspects. We firstly highlight the necessities of saving power in these two types of networks, followed by the identification of four major power-saving strategies that have been widely exploited in the literature. Furthermore, we present a high-level overview of the literature by categorizing existing approaches with respect to their scopes and research directions. These schemes are later analyzed with respect to their strategies, advantages and limitations. In the end, we summarize several key aspects that are considered to be crucial in effective power-saving schemes. We also highlight a number of our envisaged open research directions in the relevant areas that are of significance and hence require further elaborations.
Toll-like receptor 5 agonist CBLB502 induces radioprotective effects in vitro

CBLB502 derived from Salmonella flagellin is a novel agonist of Toll-like receptor 5 (TLR5). It has been shown that CBLB502 can exert high radioprotective efficacy on mice and primates from both GI and hematopoietic syndromes during whole-body irradiation with low toxicity and immunogenicity. However, no effective system has been used to investigate the protective effect of CBLB502 against irradiation and the related mechanism in vitro. In this study, we investigated the radioprotective properties of CBLB502 in HEK293-N-T cells constitutively expressing human TLR5 and NF-κB-dependent luciferase. HEK293-N-T cells were treated with different doses of CBLB502 prior to 60Co-γ ray irradiation. After irradiation, cell viability was real-time measured for 4 days by using the real-time cell analysis system. We found that CBLB502 was capable of efficiently maintaining the survival rate of irradiated HEK293-N-T cells. Then apoptotic cell death and cell cycle were detected by flow cytometry. The results showed that CBLB502 pre-treatment could reduce the apoptosis and promote the recovery of irradiated HEK293-N-T cells from G2-phase arrest in a dose-dependent manner. Our data indicated that CBLB502 has a direct radioprotective effect in vitro via anti-apoptosis and promotes cell cycle recovery. The method developed here could be an effective in vitro system to screen other TLR5-target radioprotectants like CBLB502.
Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis

Cystic Fibrosis (CF) is one of the most common life shortening conditions in Caucasians. CF is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene which result in reduced or altered CFTR functionality. Several microRNAs (miRNAs) downregulate the expression of CFTR, thus causing or exacerbating the symptoms of CF. In this context, the design of anti-miRNA agents represents a valid functional tool, but its translation to the clinic might lead to unpredictable side effects because of the interference with the expression of other genes regulated by the same miRNAs. Herein, for the first time, is proposed the use of peptide nucleic acids (PNAs) to protect specific sequences in the 3’UTR (untranslated region) of the CFTR messenger RNA (mRNA) by action of miRNAs. Two PNAs (7 and 13 bases long) carrying the tetrapeptide Gly-SerP-SerP-Gly at their C-end, fully complementary to the 3’UTR sequence recognized by miR-509-3p, have been synthesized and the structural features of target PNA/RNA heteroduplexes have been investigated by spectroscopic and molecular dynamics studies. The co-transfection of the pLuc-CFTR-3´UTR vector with different combinations of PNAs, miR-509-3p, and controls in A549 cells demonstrated the ability of the longer PNA to rescue the luciferase activity by up to 70% of the control, thus supporting the use of suitable PNAs to counteract the reduction in the CFTR expression.
Research Progress of Au-and Ag-based Mid-temperature Brazing Filler Alloys for Electronic Industry

The Au-and Ag-based brozing filler alloys become more and more important for applications in electronic industry due to characteristics of their low vapor pressure,perfect wet ability,higher strength of welded joints and excellent corrosion resistance etc.The Au-and Ag-based brazing filler alloys with fusion temperature in 400~600℃ used for the electronic packaging are still the research hot spot.But the workability of them is generally not well,it has brought some limitations for the production and the application.The paper summarizes the research progress of the Au-and Ag-based mid-temperature brazing filler alloys used in electronic packaging at present.Simultaneously,the characteristic and workability of them were discussed.
An Ecological Investigation of the Emotional Context Surrounding Nonsuicidal Self‐Injurious Thoughts and Behaviors in Adolescents and Young Adults

Ecological momentary assessment (EMA) methodology was used to examine the emotional context of nonsuicidal self-injury (NSSI). Forty-seven adolescents and young adults used a novel smartphone app to monitor their emotional experiences, NSSI thoughts, and NSSI behaviors for 2 weeks. Momentary changes in both negative and positive emotions predicted greater intensity of NSSI thoughts at the subsequent assessment, while only increases in negative emotion predicted NSSI behaviors. Immediately following NSSI behaviors participants reported reduced high-arousal negative emotions and increased low-arousal positive emotions, suggesting that NSSI may be an efficient and effective method of regulating emotion. Findings highlight the importance of addressing emotion regulation in NSSI interventions.
Autumn Leaves: Curing the Window Plague in IDEs

Navigating large software systems is difficult as the various artifacts are distributed in a huge space, while the relationships between different artifacts often remain hidden and obscure. As a consequence, developers using a modern interactive development environment (IDE) are forced to open views on numerous source artifacts to reveal these hidden relationships, leading to a crowded workspace with many opened windows or tabs. Developers often lose the overview in such a cluttered workspace as IDEs provide little support to get rid of unused windows. AutumnLeaves automatically selects windows unlikely for future use to be closed or grayed out while important ones are displayed more prominently. This reduces the number of windows opened at a time and adds structure to the developer’s workspace. We validate AutumnLeaves with a benchmark evaluation using recorded navigation data of various developers to determine the prediction quality of the employed algorithms.
MEMS-compatible processes for fabricating nanostructures and their applications

During the past decades, many different nanostructures have been successfully synthesized and developed. Due to their nanoscale dimensions, the nanostructures (i.e., nanostructured film, nanotubes, quantum dots) usually exhibit unique optical, electronic, or mechanical properties, which differ from those of the same bulk material. This dissertation focuses on the development and applications of two types of nanostructures: high aspect ratio (HAR) silicon nanostructures and anodic aluminum oxide (AAO) nanopores. (i) High aspect ratio (HAR) silicon nanostructures, including nanopillars, nanoforest and nanotubes, have attracted enormous attention in the fields of energy harvesting and storage, biomedical sensing, drug delivery, and template-based nanofabrication. Recently, several technologies, such as e-beam lithography and AAO template-based process, have been developed to synthesize HAR nanostructures such as silicon nanotubes. However, these technologies are expensive and usually complicated. In this effort, silicon nanopillars fabrication using nanospheres lithography (NSL) and nanoforest formation through a maskless Bosch process have been successfully developed. Nanomaterial grafted-nanopillar antireflection surface and a nanoforest-based SERS substrate have been demonstrated. Furthermore, a new simple process for fabricating silicon nanotubes at room temperature based on the Bosch process has been developed successfully, offering a unique platform for many potential exciting applications. (ii) Among many different applications, anodic aluminum oxide (AAO) nanopores have been utilized as nanopore thin film interferometers for biochemical sensing. Using a two-step anodization process, AAO nanopores are usually fabricated from a piece of high purity Al foil.