Miracle-dz/UniFAR-FTUs huggingface dataset:
From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy

Researchers have been looking for insulin-stimulating factors for more than 100 years, and in the 1960ties it was definitively proven that the gastrointestinal tract releases important insulinotropic factors upon oral glucose intake, so-called incretin hormones. The first significant factor identified was the duodenal glucose-dependent insulinotropic polypeptide, GIP, which however, turned out not to stimulate insulin secretion in patients with type 2 diabetes. But resection experiments clearly indicated the presence of an additional incretin, and in 1986, an unexpected processing fragment of the recently identified glucagon precursor, proglucagon, namely truncated glucagon-like peptide 1 (GLP-1 7–36 amide), was isolated from the gut and found to both stimulate insulin secretion and inhibit glucagon secretion. The peptide also inhibited appetite and food intake. Unlike GIP, this peptide had preserved effects in patients with type 2 diabetes and it was soon documented to have powerful antidiabetic effects in clinical studies. Its utility was limited, however, because of an extremely short half-life in humans, but this problem had two solutions, both of which gave rise to important antidiabetic drugs: (1) orally active inhibitors of the enzyme dipeptidylpeptidase 4 (DPP-4 inhibitors), which was responsible for the rapid degradation; the inhibitors protect endogenous GLP-1 from degradation and thereby unfold its antidiabetic activity, and (2) long-acting injectable analogs of GLP-1 protected against DPP-4 degradation. Particularly, the latter, the GLP-1 receptor agonists, either alone or in various combinations, are so powerful that treatment allows more than 2/3 of type 2 diabetes patients to reach glycemic targets. In addition, these agents cause a weight loss which, with the most successful compounds, may exceed 10% of body weight. Most recently they have also been shown to be renoprotective and reduce cardiovascular risk and mortality.
A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix

BV-265, a BMP-2/BMP-6/activin A chimera, delivered in a composite matrix generates bone repair in nonhuman primates at lower concentrations than BMP-2. Building better bone Bone morphogenetic protein (BMP) can promote superior bone growth compared to autograft, historically considered the “gold standard” for bone repair; however, supraphysiologic concentrations of BMP are typically required. Seeherman et al. developed chimeric BMPs with improved potency and an optimized carrier matrix. Chimeras based on BMP-2 were engineered to express BMP-6 and activin A receptor binding domains, which improved binding affinity and activated BMP target genes in cells and resulted in greater bone formation in rats. Complete bone healing was observed in nonhuman primate models of open fracture using composite carrier to deliver concentrations of chimeric BMP that were lower than those approved for clinical use. This study systematically identifies an optimized BMP chimera and carrier combination with promising potential for bone healing. Bone morphogenetic protein (BMP)/carriers approved for orthopedic procedures achieve efficacy superior or equivalent to autograft bone. However, required supraphysiological BMP concentrations have been associated with potential local and systemic adverse events. Suboptimal BMP/receptor binding and rapid BMP release from approved carriers may contribute to these outcomes. To address these issues and improve efficacy, we engineered chimeras with increased receptor binding by substituting BMP-6 and activin A receptor binding domains into BMP-2 and optimized a carrier for chimera retention and tissue ingrowth. BV-265, a BMP-2/BMP-6/activin A chimera, demonstrated increased binding affinity to BMP receptors, including activin-like kinase-2 (ALK2) critical for bone formation in people. BV-265 increased BMP intracellular signaling, osteogenic activity, and expression of bone-related genes in murine and human cells to a greater extent than BMP-2 and was not inhibited by BMP antagonist noggin or gremlin. BV-265 induced larger ectopic bone nodules in rats compared to BMP-2 and was superior to BMP-2, BMP-2/6, and other chimeras in nonhuman primate bone repair models. A composite matrix (CM) containing calcium-deficient hydroxyapatite granules suspended in a macroporous, fenestrated, polymer mesh–reinforced recombinant human type I collagen matrix demonstrated improved BV-265 retention, minimal inflammation, and enhanced handling. BV-265/CM was efficacious in nonhuman primate bone repair models at concentrations ranging from 1/10 to 1/30 of the BMP-2/absorbable collagen sponge (ACS) concentration approved for clinical use. Initial toxicology studies were negative. These results support evaluations of BV-265/CM as an alternative to BMP-2/ACS in clinical trials for orthopedic conditions requiring augmented healing.
Arsenate phytoextraction abilities of one-year-old tree species and its effects on the nutritional element content in plant organs

Abstract The aim of the study was to evaluate the As phytoextraction potential of four tree species: Acer pseudoplatanus L. , Betula pendula Roth. , Quercus robur L. , and Ulmus laevis Pall. in light of their prospective use in the phytoremediation of arsenate [As(V)] contaminated soils. The content of nutritional elements: B, Ca, K, Mg, Na, Si, P, and S was also analyzed. The trees were grown for 1 month in hydroponic cultures (Knop medium) supplemented with As(V), (1 mM). The results showed that the highest As accumulation efficiency was characterized by B. pendula (BCF = 0.87) and Q. robur (BCF = 0.5). Betula pendula accumulated about 80% of As in its roots (TF = 0.22) whereas Q. robur accumulated more than 60% of As in its shoots (TF = 1.60). The other tree species accumulated significantly lower amounts of As, more than 60% of which collected in their shoots. As(V) phytoextraction led to a significantly lower level of P and S in the roots of all tested tree species. Betula pendula seems promising for phytostabilisation and Q. robur for phytoextraction of As(V) from contaminated soils. The obtained results confirm the accumulation and translocation of As(V), as well as the acquisition of nutritional elements by the selected tree species.
Voltage control of DC-DC Three level Boost converter using TS Fuzzy PI controller

Appropriate control contributes essentially in the design of efficient DC-DC converters. With this intention, a study deals with the synthesis of a controller for DC-DC Three-level Boost converter (TLBC), has been addressed. The studied TLBC, known as nonlinear system, has been locally modeled using transfer function models. For instance, PI controllers were designed using the local models, and then they were combined using Takagi-Sugeno fuzzy (TSF) approach to form a TSF-PI controller. Simulation tests show the flexibility of the proposed controller, its rejection capability to different disturbances, and its ability to achieve the performance specification overall the wide operating range of the system.
Decentralized Multi-Task Learning Based on Extreme Learning Machines

In multi-task learning (MTL), related tasks learn jointly to improve generalization performance. To exploit the high learning speed of extreme learning machines (ELMs), we apply the ELM framework to the MTL problem, where the output weights of ELMs for all the tasks are learned collaboratively. We first present the ELM based MTL problem in the centralized setting, which is solved by the proposed MTL-ELM algorithm. Due to the fact that many data sets of different tasks are geo-distributed, decentralized machine learning is studied. We formulate the decentralized MTL problem based on ELM as majorized multi-block optimization with coupled bi-convex objective functions. To solve the problem, we propose the DMTL-ELM algorithm, which is a hybrid Jacobian and Gauss-Seidel Proximal multi-block alternating direction method of multipliers (ADMM). Further, to reduce the computation load of DMTL-ELM, DMTL-ELM with first-order approximation (FO-DMTL-ELM) is presented. Theoretical analysis shows that the convergence to the stationary point of DMTL-ELM and FO-DMTL-ELM can be guaranteed conditionally. Through simulations, we demonstrate the convergence of proposed MTL-ELM, DMTL-ELM, and FO-DMTL-ELM algorithms, and also show that they can outperform existing MTL methods. Moreover, by adjusting the dimension of hidden feature space, there exists a trade-off between communication load and learning accuracy for DMTL-ELM.
Cerebrospinal fluid analysis by 8-color flow cytometry in children with acute lymphoblastic leukemia

Maria Gabelli , Silvia Disar o, Pamela Scarparo, Samuela Francescato, Andrea Zangrando, M. Grazia Valsecchi, M. Caterina Putti, Giuseppe Basso and Barbara Buldini Pediatric Onco-Hematology Unit, Department of Women’s and Children’s Health, University of Padova, Padova, Italy; Pediatric Research Institute “Citt a della Speranza”, Padova, Italy; Department of Pediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy; Italian Institute for Genomic Medicine, Torino, Italy
Apoptosis resistance in fibroblasts precedes progressive scarring in pulmonary fibrosis and is partially mediated by Toll-like receptor 4 activation.

Inhalation of environmental toxicants such as cigarette smoke, metal or wood dust, silica, or asbestos is associated with increased risk for idiopathic pulmonary fibrosis (IPF). IPF involves progressive scarring of lung tissue, which interferes with normal respiration and is ultimately fatal; however, the complex cellular mechanisms of IPF pathogenesis remain unclear. Fibroblast apoptosis is essential in normal wound healing but is dysregulated in IPF. Recent studies suggest that Toll-like receptor 4 (TLR4) is key in the onset of IPF. Here, radiation-induced PF was used as a model for IPF because it very closely mimics the progressive and intractable nature of IPF. Female C57BL/6J (C57) and C57BL/6J TLR4-/- mice were exposed to a single dose of 13 Gy whole-thorax ionizing radiation. Although both strains showed similar levels of immediate radiation-induced damage, C57 mice exhibited more extensive fibrosis at 22 wk post-irradiation (PI) than TLR4-/- mice. Isolated C57 primary mouse lung fibroblasts (1° MLFs) showed decreased apoptosis susceptibility as early as 8 wk PI, a phenotype that persisted for the remainder of the radiation response. TLR4-/- 1° MLFs did not exhibit significant apoptosis resistance at any point. Systemic release of HMGB1, a TLR4 agonist, during the pneumonitis phase of the radiation response may act through TLR4 to contribute to fibroblast apoptosis resistance and thus interfere with wound resolution. These findings demonstrate that apoptosis resistance occurs earlier in PF pathogenesis than previously assumed, and that TLR4 signaling is a key mediator in this process.
Modelling the effect of chlorination/chloramination on induction of viable but non-culturable (VBNC) Escherichia coli

ABSTRACT Many bacteria, including Escherichia coli, are known to enter into a viable but non-culturable (VBNC) state when exposed to harsh environmental stresses. The VBNC cells introduced by chlorination/chloramination have raised increasing concern about biological safety of drinking water. A quantitative relationship between chlorination/chloramination and number of VBNC cells has not been found. In this study, a mathematical model was developed to quantify the effect of chlorination/chloramination on induction of viable but non-culturable (VBNC) Escherichia coli. the model was generated based on a first order kinetics of chlorination/chloramination using the data collected from laboratory disinfection experiments. The disinfection rates of culturable cells (kc ) and viable cells (kv ) were dose-dependent, and they were also modelled in different initial concentrations by regression analysis to overcome the shortcoming of dose-dependent. In general, the kc and kv values for chlorination (kc , 2.59–29.89 h−1; kv , 19.52–26.74 h−1) was 2–58 times greater than that for chloramination (kc , 0.5446–10.81 h−1; kv , 0.3398–14.57 h−1), suggesting that chlorine was more effective than chloramine in reducing the number of culturable and VBNC cells at same dose of disinfectant. Ultimately, the generated models, which could describe the dynamics of VBNC cells formation in chlorination/chloramination, can provide practical guidance in drinking water treatment and it can also be applied to risk assessment of drinking water management systems. GRAPHICAL ABSTRACT
Pathological evaluation of the visceral pleura in the radical pleurectomy/decortication for malignant pleural mesothelioma patients.

Background Radical pleurectomy/decortication (P/D) is applied as a surgical treatment of resectable malignant pleural mesothelioma (MPM). Although P/D removed visceral pleura, dissection plain was not histologically explored previously. We examined a pathological evaluation of surgically removed visceral pleura in P/D. Methods Twenty-five patients with MPM who underwent P/D at the Tokyo Medical and Dental University Hospital between April 2010 and April 2018 were studied. The 25 cases included 20 with epithelioid tumors, 4 with a biphasic tumor and 1 with desmoplastic tumors. Nine, 1, 11 and 4 patients had mesotheliomas of stages I, II, III and IV, respectively. We analyzed the site of the visceral pleural lesions using the HE & Elastica van Gieson (EVG) staining. The tumor involvement of the pleura and the surgical dissection plane were defined using the depth criteria, D0-3. We added survival analyses according to the depth criteria. Results Ninety-nine lesions in total 45 lobes: 20 upper right, 14 middle, 20 lower, 22 upper left, and 23 lower were examined. Based on the depth D 0-3 criteria, there were 21 type D0, 18 type D1, 22 type D2 and 38 type D3 lesions. The growth of tumor cells in the pleura was partially diffuse or nodular in all cases. While 38 lesions which invaded the lung parenchyma were excised, another 61 lesions that reached within the pleura were dissected from lung parenchyma. Type D2&3 showed poor survivals than type D0&1. Conclusions The lung parenchyma was always the dissection plane in P/D, regardless of tumor involvement in the visceral pleura. The depth criteria would help us in classifying pleural invasion histologically and possibly predicting the prognosis.
CMBPR: Category-Aided Multi-Channel Bayesian Personalized Ranking for Short Video Recommendation

Due to the viewing convenience for social media users’ fragmented time, the short video has become a new carrier for users’ network demands on information spread, news reading, social contact, entertainment, and leisure. Therefore, short video recommendation is one of the most important research topics in social media. Current short video recommendation algorithms mainly focus on detecting user’s social attributes, developing cross-domain information and so on, few researchers combine video category information and multi-behavior information together. This paper proposes a content-based recommendation algorithm Category-aided Multi-channel Bayesian Personalized Ranking (CMBPR) for short video recommendation, which integrates users’ rich preference information by considering the difference among both different video categories and different user interactions. The experimental results demonstrate the effectiveness of the CMBPR video recommendation algorithm, which achieves a significantly higher recommendation accuracy than the traditional video recommendation algorithms and solves the influence of the “Long Tail” effect.
Low Non-structural Carbon Accumulation in Spring Reduces Growth and Increases Mortality in Conifers Defoliated by Spruce Budworm

Spruce budworm (Choristoneura fumiferana) outbreaks are important disturbance events in the boreal forests of northeastern North America, causing major growth loss and widespread tree mortality. The physiological mechanisms leading to tree mortality remain poorly understood and two important functional traits, tree-ring width and concentration of stored carbohydrate, can serve as indicators of tree vitality during defoliation. This study aims to test the hypothesis that storage starch is an indicator of tree vitality by (1) exploring the link among reductions in storage, growth and mortality, and (2) identifying starch or sugar threshold to predict the risk of mortality. We use balsam fir and black spruce, two main host species of spruce budworm. We sampled 81 trees across seven experimental sites in eastern Quebec, Canada, and assessed defoliation intensity, tree-ring growth, and tree vitality. Soluble sugar and starch concentrations in needles, twigs, and roots were measured from spring to autumn. Under conditions of increased defoliation, carbon allocation to reserves and radial growth decreased in a similar manner for both species. Starch concentration within twigs and needles in May and June was the best indicator of carbon status in defoliated trees. We observed the highest reductions in growth two to three years prior to mortality concurrently with reductions in starch in May and June. When starch concentrations were lower than 28 mg·g-1dw in needles, the probability of balsam fir mortality exceeded 50%. At this level of starch, reserves and newly produced carbon are insufficient to support tree growth and vitality.
Development and Validation of a Method for the Analysis of Zinc Oxide in Cosmetic Matrices by Flame Atomic Absorption Spectroscopy

A fast and simple method for the extraction and Flame Atomic Absorption Spectroscopy (FAAS) quantification of ZnO in different cosmetic matrices, including lipsticks, water-in-oil foundations, and oil-in-water creams, was developed and validated, according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the United States Pharmacopeial Convention guidelines. The sample preparation consisted of an ultrasound-assisted ethanolic extraction of ZnO followed by digestion with 1 M nitric acid (HNO3). Samples were analyzed by Flame Atomic Absorption Spectroscopy (FAAS). Specificity, linearity, the limit of detection (LOD), the limit of quantification (LOQ), sensitivity, precision, and accuracy parameters were studied. The robustness of the method was evaluated with a five-variable Youden–Steiner model. The method was specific for ZnO, and the extraction procedure did not affect the stability of the signal compared to the background. The method was linear in the range 0.2–1.0 mg/L with LOD/LOQ values equal to 0.0156 (mg·L−1)/0.0473 (mg·L−1), 0.0098 (mg·L−1)/0.0297 (mg·L−1), 0.0113 (mg·L−1)/0.0341 (mg·L−1), and 0.0131 (mg·L−1)/0.0397 (mg·L−1), respectively, for raw material, lipstick, liquid foundation, and emulsion matrices. Regarding precision, the %RSD values were below 3.0% for repeatability and intermediate precision. Global reproducibility RSD was below 8.0% for all matrices. The percentage of recovery was not statistically different from 100% in all cases. The final concentration was found to be a critical variable for all matrices except for the raw material. The variables associated with the extraction step (ethanol volume, bath temperature, and extraction time) were critical in the extraction of liquid foundations and cream emulsions. The method reduces the number and concentration of mineral acids spent on the digestion of ZnO, and its application is extendable to raw materials. This development is an adequate tool for routine analysis and cosmetic quality control of chemically different products that contain ZnO as ultraviolet radiation (UV) filter, to guarantee regulatory compliance and ensure the safety and efficacy of products delivered to consumers.
Pregnancy Induces an Earlier Chronotype in Both Mice and Women

Daily rhythms generated by endogenous circadian mechanisms and synchronized to the light-dark cycle have been implicated in the timing of birth in a wide variety of species. Although chronodisruption (e.g., shift work or clock gene mutations) is associated with poor reproductive outcomes, little is known about circadian timing during pregnancy. This study tested whether daily rhythms change during full-term pregnancies in mice and women. We compared running wheel activity continuously in both nonpregnant (n = 14) and pregnant (n = 13) 12- to 24-week-old C57BL/6NJ mice. We also monitored wrist actigraphy in women (N = 39) for 2 weeks before conception and then throughout pregnancy and measured daily times of sleep onset. We found that on the third day of pregnancy, mice shift their activity to an earlier time compared with nonpregnant dams. Their time of daily activity onset was maximally advanced by almost 4 h around day 7 of pregnancy and then shifted back to the nonpregnant state approximately 1 week before delivery. Mice also showed reduced levels of locomotor activity during their last week of pregnancy. Similarly, in women, the timing of sleep onset was earlier during the first and second trimesters (gestational weeks 4-13 and 14-27) than before pregnancy and returned to the prepregnant state during the third trimester (weeks 28 until delivery). Women also showed reduced levels of locomotor activity throughout pregnancy. These results indicate that pregnancy induces changes in daily rhythms, altering both time of onset and amount of activity. These changes are conserved between mice and women.
THE PURDUE UNIVERSITY GRADUATE SCHOOL STATEMENT OF COMMITTEE APPROVAL

Fan Ziwei M.S., Purdue University, May 2018. Ensemble Methods for Top-N Recommendation. Major Professor: Xia Ning. As the amount of information grows, the desire to efficiently filter out unnecessary information and retain relevant or interested information for people is increasing. To extract the information that will be of interest to people efficiently, we can utilize recommender systems. Recommender systems are information filtering systems that predict the preference of a user to an item. Based on historical data of users, recommender systems are able to make relevant recommendations to users. Due to its usefulness, Recommender systems have been widely used in many applications, including e-commerce and healthcare information systems. However, existing recommender systems suffer from several issues, including data sparsity and user/item heterogeneity. In this thesis, a hybrid dynamic and multi-collaborative filtering based recommendation technique has been developed to recommend search terms for physicians when physicians review a large number of patients’ information. Besides, a local sparse linear method ensemble has been developed to tackle the issues of data sparsity and user/item heterogeneity. In health information technology systems, most physicians suffer from information overload when they review patient information. A novel hybrid dynamic and multicollaborative filtering method has been developed to improve information retrieval from electronic health records. We tackle the problem of recommending the next search term to a physician while the physician is searching for information about a patient. In this method, I have combined first-order Markov Chain and multicollaborative filtering methods. For multi-collaborative filtering methods, I have de-