Mold‐casted non‐degradable, islet macro‐encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice

Islet transplantation is a potential cure for diabetic patients, however this procedure is not widely adopted due to the high rate of graft failure. Islet encapsulation within hydrogels is employed to provide a three‐dimensional microenvironment conducive to survival of transplanted islets to extend graft function. Herein, we present a novel macroencapsulation device, composed of PEG hydrogel, that combines encapsulation with lithography techniques to generate polydimethylsiloxane (PDMS) molds. PEG solutions are mixed with islets, which are then cast into PDMS molds for subsequent crosslinking. The molds can also be employed to provide complex architectures, such as microchannels that may allow vascular ingrowth through pre‐defined regions of the hydrogel. PDMS molds allowed for the formation of stable gels with encapsulation of islets, and in complex architectures. Hydrogel devices with a thickness of 600 μm containing 500 islets promoted normoglycemia within 12 days following transplantation into the epididymal fat pad, which was sustained over the two‐month period of study until removal of the device. The inclusion of microchannels, which had a similar minimum distance between islets and the hydrogel surface, similarly promoted normoglycemia. A glucose challenge test indicated hydrogel devices achieved normoglycemia 90 min post‐dextrose injections, similar to control mice with native pancreata. Histochemical staining revealed that transplanted islets, identified as insulin positive, were viable and isolated from host tissue at 8 weeks post‐transplantation, yet devices with microchannels had tissue and vascular ingrowth within the channels. Taken together, these results demonstrate a system for creating non‐degradable hydrogels with complex geometries for encapsulating islets capable of restoring normoglycemia, which may expand islet transplantation as a treatment option for diabetic patients. Biotechnol. Bioeng. 2016;113: 2485–2495. © 2016 Wiley Periodicals, Inc.Macroencapsulating PEG hydrogel devices were created without microchannels (A) or cast in PDMS molds with column‐like features (B) to create hydrogels with microchannels (C, D). Islets were successfully encapsulated in these hydrogel devices (E, F), remained viable post‐encapsulation, and transplanted into the fat pad to restore normoglycemia in diabetic mice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134144/1/bit26005_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134144/2/bit26005.pd

Numerical and Experimental Studies of a Two-Stage Pulse Tube Cryocooler Working Around 20K

The absence of cold moving parts in pulse tube cryocoolers has allowed it to has advantages of low vibration, high reliability, and low cost, which can meet requirements of many high-temperature superconducting applications. However, Stirling type pulse tube cryocoolers working around 20 K are still not commerally aviable due to low efficiency and low power density. With Comprehensive consideration of higher specific power of whole system and performance in relative lower working temperature of 20K, this paper proposes a thermally coupled two stage co-axial pulse tube cryocooler to pursue several watts cooling power around 20K.At the first stage, an ultrahigh frequency operation of 100 Hz is utilized to precoo the second stage for seeking a higher power density. At the second stage, a relative lower frequency of around 30Hz is used for improving system efficiency. Firstly, a quasi-one-dimensional numeric model based on the thermoacoustic theory is used to optimize the operating and structure parameters and some simulation results are briefly introduced. The influences of different phase shifters such as doule-inlet and room temperature displacers are also also investigated numerically. Then, in the experiments, typically a lowest no-load temperature of 13 K has been obtained and the cooling power at 20K was 2 W with an input electric power of 500 W, which mean an efficiency of 5.6% of Carnot. The influences of different operating and structure parameters such as frequency, mean pressure and precooling temperature were also investigated numerically and experimentally

A Cross-Cultural Perspective on the Preference for Potential Effect: An Individual Participant Data (IPD) Meta-Analysis Approach

A recent paper [Tormala ZL, Jia JS, Norton MI (2012). The preference for potential. Journal of personality and social psychology, 103:567-583] demonstrated that persons often prefer potential rather than achievement when evaluating others, because information regarding potential evokes greater interest and processing, resulting in more favorable evaluations. This research aimed to expand on this finding by asking two questions: (a) Is the preference for potential effect replicable in other cultures? (b) Is there any other mechanism that accounts for this preference for potential? To answer these two questions, we replicated Tormala et al.'s study in multiple cities (17 studies with 1,128 participants) in China using an individual participant data (IPD) meta-analysis approach to test our hypothesis. Our results showed that the preference for potential effect found in the US is also robust in China. Moreover, we also found a pro-youth bias behind the preference for potential effect. To be specific, persons prefer a potential-oriented applicant rather than an achievement-oriented applicant, partially because they believe that the former is younger than the latter

What a Whole Slide Image Can Tell? Subtype-guided Masked Transformer for Pathological Image Captioning

Pathological captioning of Whole Slide Images (WSIs), though is essential in computer-aided pathological diagnosis, has rarely been studied due to the limitations in datasets and model training efficacy. In this paper, we propose a new paradigm Subtype-guided Masked Transformer (SGMT) for pathological captioning based on Transformers, which treats a WSI as a sequence of sparse patches and generates an overall caption sentence from the sequence. An accompanying subtype prediction is introduced into SGMT to guide the training process and enhance the captioning accuracy. We also present an Asymmetric Masked Mechansim approach to tackle the large size constraint of pathological image captioning, where the numbers of sequencing patches in SGMT are sampled differently in the training and inferring phases, respectively. Experiments on the PatchGastricADC22 dataset demonstrate that our approach effectively adapts to the task with a transformer-based model and achieves superior performance than traditional RNN-based methods. Our codes are to be made available for further research and development

ARHI (DIRAS 3), an Imprinted Tumor Suppressor Gene, Binds to Importins, and Blocks Nuclear Translocation of Stat3

ARHI (DIRAS3) is an imprinted tumor suppressor gene whose expression is lost in the majority of breast and ovarian cancers. Unlike its homologs Ras and Rap, ARHI functions as a tumor suppressor. Our previous study showed that ARHI can interact with transcription activator Stat3 and inhibit its nuclear translocation in human breast and ovarian cancer cells. To identify proteins that interact with ARHI in nuclear translocation, we have performed proteomic analysis and identified several importins that can associate with ARHI. To further explore this novel finding, we have purified 10 GST-importin fusion proteins (importin 7, 8, 13, b1, a1, a3, a5, a6, a7 as well as mutant a1). Using a GST-pull down assay, we found that ARHI can bind strongly to most importins; however, its binding is significantly reduced with an importin a1 mutant which contains an altered nuclear localization signal (NLS) domain. In addition, an ARHI N-terminal deletion mutant (NTD) exhibits much less binding to all importins than does wild type ARHI ARHI and NTD proteins were purified and tested for their ability to inhibit nuclear importation of proteins in HeLa cells. ARHI protein inhibits interaction of Ran-importin complexes with GFP fusion proteins that contain an NLS domain and a beta-like import receptor binding domain, blocking their nuclear localization. Addition of ARHI also blocked nuclear localization of phosphorylated Stat3β. By GST-pull down assays, we found that ARHI could compete for Ran-importins binding. Thus, ARHI-induced disruption of importin binding to cargo proteins including Stat3 could serve as an important regulatory mechanism that contributes to the tumor suppressor function of ARHI

An Integrated Clinical-mRNA-lncRNA-miRNA Signature for Muscle-Invasive Bladder Cancer Prognosis

An increasing number of evidence suggests that clinical variables alone are not enough to predict the survival of patients with muscle invasive bladder cancer (MIBC), and the expression of mRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) also plays an important role in the onset of MIBC. This study aims to establish a more accurate model for predicting the overall survival of MIBC based on clinical information and genetic characteristics. In this study, the RNAs profiles and clinical variable data of patients with MIBC were downloaded from the Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis, differential expression analysis and elastic net-regulated Cox regression analysis were used to identify the clinical variables and RNAs (mRNAs, lncRNAs and miRNAs) related to the prognosis of MIBC. Prognostic models of MIBC were established by multivariate Cox regression and ridge regression analysis using the identified prognostic clinical variables and RNAs. Three clinical variables, 25 mRNAs, 3 lncRNAs and 2 miRNAs related to the prognosis of MIBC were identified, and an integrated signature, a clinical variable signature, and an mRNA-lncRNA-miRNA signature were established based on the identified clinical variables and/or RNAs. Among the three models, the integrated signature had the highest predictive accuracy (5-year the area under the curve (AUC)=0.835, 95%CI:0.776-0.894) among the three models (P 0.05). The patients in the TCGA MIBC cohort were classified into high- or low-risk groups by the integrated signature, and it was found that the patients in the low-risk group had a significantly longer overall survival time compared with the patients in the high-risk group (P 0.001). Applying published gene signatures and TCGA data, a new and more accurate integrated clinical-mRNA-lncRNA-miRNA signature for MIBC prognostic was established

Time and frequency localized pulse shape for resolution enhancement in STFT-BOTDR

Short Time Fourier Transform-Brillouin Optical Time Domain Reflectometry (STFT-BOTDR) implements STFT over the full frequency spectrum to measure the distributed temperature and strain along the optic fiber, providing new research advances in dynamic distributed sensing. The spatial and frequency resolution of the dynamic sensing is limited by the Signal to Noise Ratio (SNR) and the Time-Frequency (T-F) localization of the input pulse shape. T-F localization is fundamentally important for the communication system, which suppresses interchannel interference (ICI) and intersymbol interference (ISI) to improve the transmission quality in multi-carrier modulation (MCM). This paper demonstrates that the T-F localized input pulse shape can enhance the SNR, the spatial and frequency resolution in STFT-BOTDR. Simulation and experiments of T-F localized different pulses shapes are conducted to compare the limitation of the system resolution. The result indicates that rectangular pulse should be selected to optimize the spatial resolution, Lorentzian pulse could be chosen to optimize the frequency resolution, while Gaussian shape pulse can be used in general applications for its balanced performance in both spatial and frequency resolution. Meanwhile, T-F localization is proved to be useful in the pulse shape selection for system resolution optimization