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Additional file 1.

Additional file 1: Table S1. Subgroup analysis of THA after fixation failure.

Recently, we have shown that manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) conjugated with exendin-4 (Ex4) act as a contrast agent that directly trace implanted mouse islet β-cells by magnetic resonance imaging (MRI). Here we further advanced this technology to track implanted porcine neonatal pancreatic cell clusters (NPCCs) containing ducts, endocrine, and exocrine cells. NPCCs from one-day-old neonatal pigs were isolated, cultured for three days, and then incubated overnight with MnMEIO-Ex4 NPs. Binding of NPCCs and MnMEIO-Ex4 NPs was confirmed with Prussian blue staining in vitro prior to the transplantation of 2000 MnMEIO-Ex4 NP-labeled NPCCs beneath the left renal capsule of six nondiabetic nude mice. The 7.0 T MRI on recipients revealed persistent hypointense areas at implantation sites for up to 54 days. The MR signal intensity of the graft on left kidney reduced 62–88% compared to the mirror areas on the contralateral kidney. Histological studies showed colocalization of insulin/iron and SOX9/iron staining in NPCC grafts, indicating that MnMEIO-Ex4 NPs were taken up by mature β-cells and pancreatic progenitors. We conclude that MnMEIO-Ex4 NPs are excellent contrast agents for detecting and long-term monitoring implanted NPCCs by MRI.

Background Previous studies showed inconsistent Results of the effects of dipeptidyl peptidase (DPP)-IV inhibitors on syngeneic mouse islet transplantation. We hypothesized that the implanted islet numbers are critical for the effects of DPP-IV inhibitors on the outcomes of transplantation. Methods One hundred and fifty or three hundred islets were syngeneically transplanted under the renal capsule of each streptozocin-diabetic C57/B6 mouse and recipients were then treated without or with LAF237 (10 mg/kg/day, po) for 6 weeks. After transplantation, recipients’ blood glucose, body weight and intraperitoneal glucose tolerance test (IPGTT) were followed-up periodically. The graft was removed for the measurement of β-cell mass at 6 weeks. Results In recipients with 150 islets, it was not significantly different between the LAF237- treated group (n = 14) and control group (n = 14) in terms of the blood glucose, body weight, glucose tolerance at 2, 4 and 6 weeks or the graft β-cell mass at 6 weeks. In contrast, in recipients with 300 islets, the LAF237-treated group (n = 24) did have a lower area under the curve of the IPGTT at 4 weeks (p = 0.0237) and 6 weeks (p = 0.0113) as well as more graft β-cell mass at 6 weeks (0.655 ± 0.008 mg vs. 0.435 ± 0.006 mg, p = 0.0463) than controls (n = 24). Conclusions Our findings revealed 6-week treatment of LAF237 improves glucose tolerance and increases graft β-cell mass in diabetic mice transplanted with a sufficient number but not marginal number of islets. These indicate that the effects of DPP-IV inhibitors are influenced by the implanted islet mass.

Additional file 4. The Version 2 questionnaire. This is the English version of Version 2 questionnaire, whose categories were based on the above-methodology chapter-mentioned statistical method.

Additional file 3. Exploratory factor analysis results. Exploratory factor analysis results of all the version 1 questionnaire questions after pre-testing.

Additional file 5. Exploratory factor analysis results. Exploratory factor analysis results of all the version 3 questionnaire questions after pre-testing.

Additional file 1. The references of our questions. Questions in our study and where it adapted from.

Additional file 2. The Version 1 questionnaire. This is the pre-testing questionnaire administered to the parturients, and the English version is only translated for the publication of this research.

To detect and trace transplanted β-cells by magnetic resonance imaging (MRI), we conjugated manganese magnetism-engineered iron oxide (MnMEIO) nanoparticles with exendin-4 (MnMEIO-Ex4) which can specifically bind glucagon-like peptide-1 receptors on β-cells. Incubation of MIN6 β-cells and MnMEIO showed MnMEIO with iron content 5-40 μg/mL had no adverse effect on MIN6 β-cells assessed by the fluorescence of propidium iodide and insulin secretory response to glucose. Positive iron staining by Prussian blue was found in the MIN6 loaded with MnMEIO-Ex4 but not with MnMEIO. A transmission electron microscope with elementary mapping of iron and manganese demonstrated MnMEIO-Ex4 nanoparticles distributed in the cytoplasm of MIN6 β-cells. In vitro 7.0 T MR image showed loss of intensity in MIN6 β-cells loaded with MnMEIO-Ex4 but not with MnMEIO. With addition of poly-L-lysine, only MIN6 β-cells incubated with MnMEIO-Ex4 but not MnMEIO stimulated proinsulin mRNA expression and insulin secretion. On day 1, 6, 15, 22 and 29 after syngeneic transplantation of 700 C57/B6 mouse islets labeled with MnMEIO-Ex4, the islet graft under left kidney capsule could be visualized on 7.0 T MRI as persistent hypodense areas (indicated by arrows in Figure). Our results indicate MnMEIO-Ex4 nanoparticles are safe and effective for the detection and monitoring of islet grafts by MRI. Disclosure J. Juang: None. C. Shen: None. J. Wang: None. S. Wu: None. C. Chen: None. C. Kao: None. S. Lin: None. Y. Wang: None. Funding Chang Gung Memorial Hospital

Producing a large amount of annotated speech data for training ASR systems remains difficult for more than 95% of languages all over the world which are low-resourced. However, we note human babies start to learn the language by the sounds (or phonetic structures) of a small number of exemplar words, and "generalize" such knowledge to other words without hearing a large amount of data. We initiate some preliminary work in this direction. Audio Word2Vec is used to learn the phonetic structures from spoken words (signal segments), while another autoencoder is used to learn the phonetic structures from text words. The relationships among the above two can be learned jointly, or separately after the above two are well trained. This relationship can be used in speech recognition with very low resource. In the initial experiments on the TIMIT dataset, only 2.1 hours of speech data (in which 2500 spoken words were annotated and the rest unlabeled) gave a word error rate of 44.6%, and this number can be reduced to 34.2% if 4.1 hr of speech data (in which 20000 spoken words were annotated) were given. These results are not satisfactory, but a good starting point.

Recently, we demonstrated the feasibility of subcutaneous transplantation of MIN6 cells embedded in a scaffold with poly(ethylene glycol) methyl ether (mPEG)-poly(Ala) hydrogels. In this study, we further tracked these grafts using magnetic resonance (MR) and bioluminescence imaging. After being incubated overnight with chitosan-coated superparamagnetic iron oxide (CSPIO) nanoparticles and then mixed with mPEG-poly(Ala) hydrogels, MIN6 cells appeared as dark spots on MR scans. For in vivo experiments, we transfected MIN6 cells with luciferase and/or incubated them overnight with CSPIO overnight, 5 × 106 MIN6 cells embedded in mPEG-poly(Ala) hydrogels were transplanted into the subcutaneous space of each nude mouse. The graft of CSPIO-labeled MIN6 cells was visualized as a distinct hypointense area on MR images located at the implantation site before day 21. However, this area became hyperintense on MR scans for up to 64 days. In addition, positive bioluminescence images were also observed for up to 64 days after transplantation. The histology of removed grafts showed positive insulin and iron staining. These results indicate mPEG-poly(Ala) is a suitable scaffold for β-cell encapsulation and transplantation. Moreover, MR and bioluminescence imaging are useful noninvasive tools for detecting and monitoring mPEG-poly(Ala) hydrogel-embedded MIN6 cells at a subcutaneous site.

The liver is the current site of choice for clinical islet transplantation, but many intraportal grafts were lost in the early stage of transplantation. Other disadvantages include the difficulty of monitoring the islets and procedure-associated complications. In contrast, the subcutaneous space offers the advantages of a large space, a less invasive procedure and easy graft monitoring and removal. However, islet transplantation into an unmodified subcutaneous site has poor efficacy; possibly due to poor oxygenation and inadequate vascularization of the transplanted tissue. In this study, we tested the feasibility of subcutaneous transplantation of MIN6 beta cells embedded in temperature-sensitive poly(ethylene glycol) methyl ether (mPEG)-Ala hydrogels as scaffolds. After culturing for 14 days, the viability of MIN6 beta cells in mPEG-Ala hydrogel was comparable with those in medium, either assayed by MTT or LIVE/DEAD. Static incubation showed that both had comparable insulin secretion. For in vivo experiments, we infected MIN6 beta cells with luciferase by AAV and then transplanted 5*106 cells embedded in mPEG-Ala hydrogel into the subcutaneous space of each nude mouse’s upper back. Positive In Vivo Imaging System (IVIS) images and positive insulin staining of tissue histology were observed up to 41 days after transplantation. Meanwhile, we incubated MIN6 beta cells with chitosan-coated superparamagnetic iron oxide (CSPIO) overnight and then transplanted 5*106 MIN6 beta cells into the subcutaneous tissue of each nude mouse’s left flank. The graft of CSPIO-labeled MIN6 beta cells was visualized on Magnetic Resonance (MR) scans as distinct hypointense spots on T2-weighted images located at the transplantation site at day 6 and 20. These results indicate that subcutaneous transplantation of MIN6 beta cells embedded in temperature-sensitive mPEG-Ala hydrogels is feasible. Moreover, the IVIS and MR imaging are useful tools for detecting and monitoring beta cells at the subcutaneous site. Disclosure J. Juang: None.H. Lin: None.C. Chen: None.C. Kao: None.S. Wu: None.S. Lin: None.C. Shen: None.J. Wang: None.I. Chu: None.

Ductal epithelium is primarily detected in porcine neonatal pancreatic cell clusters (NPCCs) bearing grafts, suggesting that transplants might exhibit progenitor-like phenotypes. Here we found that soon after NPCC isolation, PDX1+/insulin− and SOX9+ pancreatic progenitor-like cells dramatically increased while dual-hormonal progenitor-like cells were routinely observed in NPCC culture. After transplantation (Tx), insulin+ cells increased and PDX1+ and SOX9+ cells gradually decreased in both non-diabetic (NDM) and streptozotocin-induced diabetic (DM) grafts over 2 months. Strikingly, a significantly higher percentage of insulin+ cells were detected in 9-day and 16-day, but not in 23-day, 30-day and 60-day grafts implying that hyperglycemia could only facilitate NPCC-derived β cells early post-Tx. A higher percentage of NPCC-derived β cells in early DM grafts was determined via an enhanced neogenic differentiation based on the detection of insulin+ cells budding out from PDX1+/SOX9+ epithelium. Interestingly, a drop in SOX9+ progenitor-like cells was detected 16 days post-Tx in DM grafts whilst PDX1+ cells do not show a significant difference until 60 days post-Tx between DM and NDM grafts, demonstrating that distinct progenitor-like populations fuel new β cells post-Tx. In conclusion, PDX1+/SOX9+ cells could be quickly activated after NPCC isolation, maintain their multipotency in culture and differentiate into new β cell post-Tx.

In this paper, we propose the joint learning attention and recurrent neural network (RNN) models for multi-label classification. While approaches based on the use of either model exist (e.g., for the task of image captioning), training such existing network architectures typically require pre-defined label sequences. For multi-label classification, it would be desirable to have a robust inference process, so that the prediction error would not propagate and thus affect the performance. Our proposed model uniquely integrates attention and Long Short Term Memory (LSTM) models, which not only addresses the above problem but also allows one to identify visual objects of interests with varying sizes without the prior knowledge of particular label ordering. More importantly, label co-occurrence information can be jointly exploited by our LSTM model. Finally, by advancing the technique of beam search, prediction of multiple labels can be efficiently achieved by our proposed network model., Accepted at 32nd AAAI Conference on Artificial Intelligence (AAAI-18)

Figure S1. High-confidence piRNA candidate identification pipeline. Figure S2. Examination of germ cell isolation efficiency using immunocytochemistry. Figure S3. Expression of potential spermatogonial stem cell (SSC) markers and genes encoding PIWI/piRNA pathway components in embryonic germ cells. Figure S4. Scheme for assessing ping-pong cycle piRNAs. Figure S5. Genomic association for piRNA candidates at each stage at a specific piRNA length. Figure S6. PiRNA distribution at the associated transcripts that reciprocally expressed compare to the quantity of mapped piRNAs (EDIL3, ANGPTL2, and PIP5K1B). Figure S7. PiRNA cluster analysis results. Figure S8. Schematic presentation of merging piRNAs from multiple stages. Figure S9. Venn diagram of number of transposable elements (TEs) and genes targeted by piRNAs from stage-enriched piRNA clusters. Figure S10. Stage-enriched piRNA clusters may contribute to stage-dependent regulatory roles. Figure S11. Ontology analysis of gene sets targeted by piRNAs from stage-enriched piRNA clusters under Enrichr: GO Biological Process 2015 category. Figure S12. Expression analysis via RT-qPCR on piRNA targeted genes associated with neural development. Table S1. Bioinformatic filtering results from high-confidence piRNA identification pipeline. Table S2. Number of piRNAs (in piRPM) mapped to TEs embedded in the transcripts that are differentially associated between E11G and E14G piRNAs. Table S3. Number of clusterable piRNAs before and piRNA cluster boundaries after adjustment. Table S4. Genes and TEs targeted by stage-enriched piRNA cluster-derived piRNAs. Table S5. Number of piRNAs (in piRPM) mapped to TEs embedded in the transcripts that are highly associated with piRNAs enriched in embryonic (E11 and E14) gonadal piRNA clusters (EG-piRC). Table S6. RT-qPCR primer sets. (DOCX 3433 kb)

Automatic speech recognition (ASR) has been widely researched with supervised approaches, while many low-resourced languages lack audio-text aligned data, and supervised methods cannot be applied on them. In this work, we propose a framework to achieve unsupervised ASR on a read English speech dataset, where audio and text are unaligned. In the first stage, each word-level audio segment in the utterances is represented by a vector representation extracted by a sequence-of-sequence autoencoder, in which phonetic information and speaker information are disentangled. Secondly, semantic embeddings of audio segments are trained from the vector representations using a skip-gram model. Last but not the least, an unsupervised method is utilized to transform semantic embeddings of audio segments to text embedding space, and finally the transformed embeddings are mapped to words. With the above framework, we are towards unsupervised ASR trained by unaligned text and speech only., Comment: Code is released: https://github.com/grtzsohalf/Towards-Unsupervised-ASR

Except for the attachment of solder ball on soldering pads, flux is generally used to remove oxidation and clean the pad surface to be soldered for good wetting and form reliable joints. The upcoming concerns about fluxes are the residues on the solder balls and leading to voids after heating. For several years, a new reflow system, known as fluxless reflow system, claiming that flux is needless during reflow has been developed. In this new system, the functions of flux are replaced by formic acid or hydrogen in the form of gas, thus the residues and voiding issue can be mitigated. In the case of ball attachment in fluxless reflow system, it is critically significant to keep solder balls on the exact pads during the reflow process. Therefore, this paper will discuss the details about the applicability of a novel temporary adhesive in fluxless reflow system from the points of view of fundamental characteristics, including viscosity measurement by viscometer, wettability by measuring wetting angle, and residues from thermal analysis by thermogravimetric analyzer (TGA). As a result, low viscosity and wetting angle on a variety of pads showed applicable to be good wetting on copper pads in a jetting or spraying way. The characterization of ultra-low residues (

Solder paste is widely used to connect surface mount devices to printed circuit boards [1]. As the components become smaller and thinner, solderability and voiding are more challenging [2]. It has been reported that a majority of assembly defects occur in the reason of quality decay of solder paste, resulting in solder paste dried-out and short shelf life. The chemical reactions between flux and solder powders, which are believed in detecting metal ions concentration in flux by inductively coupled plasma-mass spectrometer (ICP), are very critical and relevant to the quality of solder paste. Hence, a new coating technology on solder powders is introduced to eliminate this issue. In the first part of this research, a new coating solution with polymer compositions inside is developed [3]. Thermal characteristics were analyzed by thermogravimetric analyzer (TGA) to find out the optima temperature for solution activating, forming a coating layer on solder powders. The coating efficiency was found related to the ratio of coating solution and solder powders, and carried out to observe the powders surface by Focused Ion Beam (FIB). The study on effects of coating technology on solderability was performed in the second part of the research. It is realized that viscosity and rheological properties of solder paste in the condition of long-time storage are more stable for the solder paste with coating technology. On the other hand, dried-out issue was observed in the case of normal solder paste without coating. Besides, solderability and voiding were also improved by coating technology. Therefore, based on the innovation of this study, coating technology can be applied in a variety of metal surface to offer a layer to prevent from interference.

Variables and corresponding ICD-9-CM, management code or drug code, and case classification code. (DOCX 14Â kb)

Additional file 1: Table S1. Compositions of experimental diets. Figure S1. The effect of HFHF diet on the triglyceride accumulations in the skeletal muscle and hepatic tissues. Figure S2. Liver histology of Lee-Sung pigs at the end of the dietary intervention.

Summary of clinical characteristics of dogs with HSA or HA, and IRS of KIT expression profile. (DOCX 17 kb)

Biomolecular motors are tiny engines that transport materials at the microscopic level within biological cells. In recent years, Elston and Peskin et al have investigated the effect of the elastic properties of the tether that connects the motor to its cargo at the speed of the motor. In this paper we extend their work and present a tether in the form of symmetric linear potential. Our results show that when the driving mechanism is an imperfect Brownian ratchet, the average speed decreases as the stiffness of the tether increases in the limit of large motor diffusion coefficient, which is similar to the results of Elston and Peskin. However, a threshold for the stiffness of the tether connecting the motor to its cargo is found in our model. Only when the tether is stiffer than the threshold can the motor and its cargo function co-operatively, otherwise, the motor and its cargo depart from each other. This result is more realistic than that of the spring model of Elston and Peskin.

We introduce an agent-based model of epithelial cell morphogenesis to explore the complex interplay between apoptosis, proliferation, and polarization. By varying the activity levels of these mechanisms we derived phenotypic transition maps of normal and aberrant morphogenesis. These maps identify homeostatic ranges and morphologic stability conditions. The agent-based model was parameterized and validated using novel high-content image analysis of mammary acini morphogenesis in vitro with focus on time-dependent cell densities, proliferation and death rates, as well as acini morphologies. Model simulations reveal apoptosis being necessary and sufficient for initiating lumen formation, but cell polarization being the pivotal mechanism for maintaining physiological epithelium morphology and acini sphericity. Furthermore, simulations highlight that acinus growth arrest in normal acini can be achieved by controlling the fraction of proliferating cells. Interestingly, our simulations reveal a synergism between polarization and apoptosis in enhancing growth arrest. After validating the model with experimental data from a normal human breast line (MCF10A), the system was challenged to predict the growth of MCF10A where AKT-1 was overexpressed, leading to reduced apoptosis. As previously reported, this led to non growth-arrested acini, with very large sizes and partially filled lumen. However, surprisingly, image analysis revealed a much lower nuclear density than observed for normal acini. The growth kinetics indicates that these acini grew faster than the cells comprising it. The in silico model could not replicate this behavior, contradicting the classic paradigm that ductal carcinoma in situ is only the result of high proliferation and low apoptosis. Our simulations suggest that overexpression of AKT-1 must also perturb cell-cell and cell-ECM communication, reminding us that extracellular context can dictate cellular behavior.

An asymptotic solution of the concentration and interface morphology for a deep cellular crystal in directional solidification is obtained by using the matched asymptotic expansion method and multiple variable expansion method, and the effect of anisotropic surface tension on deep cellular crystal growth is studied. Results show that the anisotropic surface tension has a significant effect on the concentration and interface shape of deep cellular crystal growth in directional solidification. As the anisotropic surface tension parameter increases, the concentration near the front part of deep cellular crystal decays and the interface shrinks; when as the concentration near the root increases and the curvature of the interface near the root increases or the curvature radius decreases; and the amplitude of the deep cellular crystal increases. The concentration and interface shape of the deep cellular crystal in directional solidification can be calculated with the results obtained in this paper.

A new regional thunderstorm model, coupled with two primary non-inductive electrification mechanisms, namely Takahashi (1978) and Saunders (1991) schemes, is developed based on the newest version of RAMS V6.0. Based on the simulation on a thunderstorm in its early stage which occurred in Beijing, the results show that the total charge distribution is tripolar in both schemes when the electric field reaches breakdown value. The results are in agreement with some observations and results of other model. However, the evolution processes and shapes of cloud charge distribution in the two schemes are different. The result of Takahashi's (1978) scheme produces a tripolar charge distribution in the cloud before the first lightning. The Saunders' (1991) scheme produces a transform from inverted dipole distribution to tripolar charge distribution. This is because they used different experimental conditions: different factors lead to different results. The results from both schemes show that the positive charge carrier at a low level of thunderstorm is rain droplet, the aggregates and graupels are located in high level of thunderstorm, and the charge center distribution of graupels is similar to the distribution of total charge in thunderstorm cloud.