Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Differentiability”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7

miR-675 promotes odontogenic differentiation of human dental pulp cells by epigenetic regulation of DLX3

Highlights: • miR-675 promotes the odontogenic differentiation of human dental pulp cells (hDPCs). • miR-675 regulates the odontogenic differentiation of hDPCs by epigenetic regulating DLX3. • Our findings shed light on the regulatory mechanism of dentin hypoplasia in TDO patients. In a previous study, we showed that microRNA-675 (miR-675) was significantly down-regulated in patients with tricho-dento-osseous (TDO) syndrome. One of the main features of TDO syndrome is dentin hypoplasia. Thus, we hypothesize that miR-675 plays a role in dentin development. In this study, we determined the role of miR-675 in the odontogenic differentiation of human dental pulp cells (hDPCs). Stable overexpression and knockdown of miR-675 in hDPCs were performed using recombinant lentiviruses containing U6 promoter-driven miR-675 and short hairpin-miR675 expression cassettes, respectively. Alkaline phosphatase (ALP) assay, Alizarin red staining assay, quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescent staining revealed the promotive effects of miR-675 on the odontogenic differentiation of hDPCs. Further, we found that miR-675 facilitates the odontogenic differentiation process of hDPCs by epigenetic regulation of distal-less homeobox (DLX3). Thus, for the first time, we determined that miR-675 regulates the odontogenic differentiation of hDPCs by inhibiting the DNA methyltransferase 3 beta (DNMT3B)-mediated methylation of DLX3. Our findings uncover an unanticipated regulatory role for miR-675 in the odontogenic differentiation of hDPCs by epigenetic changes in DLX3 and provide novel insight into dentin hypoplasia feature in TDO patients.

60 APPLIED LIFE SCIENCES↗

Commonly used thiol-containing antioxidants reduce cardiac differentiation and alter gene expression ratios of sarcomeric isoforms

Highlights: • β-mercaptoethanol (BME) and monothiolglycerol (MTG) reduce cardiac differentiation. • BME and MTG treatments decrease TNNI3/TNNI1 and MLC2V/MLC2A expression ratios. • BME and MTG treatments reduce beating rates and contraction/relaxation velocities. • Trolox, a strong ROS scavenger, does not inhibit cardiac differentiation. Reactive oxygen species (ROS) scavengers such as beta-mercaptoethanol (BME) and monothiol glycerol (MTG) are extensively used in stem cell research to prevent cellular oxidative stress. However, how these antioxidant supplements impact stem cell cardiac differentiation, a process regulated by redox-signaling remains unknown. In this study, we found that removal of BME from the conventional high-glucose, serum-based differentiation medium improved cardiac differentiation efficiency by 2-3 fold. BME and MTG treatments during differentiation significantly reduced mRNA expression of cardiac progenitor markers (NKX2.5 and ISL1) as well as sarcomeric markers (MLC2A, MLC2V, TNNI3, MYH6 and MYH7), suggesting reduced cardiomyogenesis by BME or MTG. Moreover, BME and MTG altered the expression ratios between the sarcomeric isoforms. In particular, TNNI3 to TNNI1 ratio and MLC2V to MLC2A ratio were significantly lower in BME or MTG treated cells than untreated cells, implying altered cardiomyocyte phenotype and maturity. Lastly, BME and MTG treatments resulted in less frequent beating, slower contraction and relaxation velocities than untreated cells. Interestingly, none of the above-mentioned effects was observed with Trolox, a non-thiol based antioxidant, despite its strong antioxidant activity. This work demonstrates that commonly used antioxidant supplements may cause considerable changes to cellular redox state and the outcome of differentiation.

60 APPLIED LIFE SCIENCES↗

Nrf2 activation is involved in osteogenic differentiation of periodontal ligament stem cells under cyclic mechanical stretch

Highlights: • Cyclic mechanical stretch increases the nuclear accumulation of Nrf2 in PDLSCs. • T-BHQ promotes osteogenic differentiation under cyclic mechanical stretch. • Nrf2 activation may improve alveolar bone remodeling during orthodontic treatment. During orthodontic treatment, mechanical stretch serves a crucial function in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Up-regulated reactive oxygen species (ROS) level is a result of cyclic mechanical stretch in many cell types. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master regulator in various antioxidants expression. However, it is not known whether cyclic mechanical stretch could induce the ROS generation in PDLSCs and whether Nrf2 participated in this process. The present study was aimed to investigate the role of Nrf2 in PDLSCs under cyclic mechanical stretch. Our results showed that cyclic mechanical stretch increased ROS level and the nuclear accumulation of Nrf2 during osteoblast differentiation. Knocking down Nrf2 by siRNA transfection increased ROS formation and suppressed osteogenic differentiation in PDLSCs. T-BHQ, a Nrf2 activator, promoted the osteogenic differentiation in PDLSCs under cyclic mechanical stretch, and improved the microstructure of alveolar bone during orthodontic tooth movement in rats by employing micro-CT system. Taken together, Nrf2 activation was involved in osteogenic differentiation under cyclic mechanical stretch in PDLSCs. T-BHQ could promote the osteogenic differentiation in vitro and in vivo, suggesting a promising option for the remodeling of the alveolar bone during orthodontic tooth movement.

60 APPLIED LIFE SCIENCES↗

Keratin Promotes Differentiation of Keratinocytes Seeded on Collagen/Keratin Hydrogels

Keratinocytes undergo a complex process of differentiation to form the stratified stratum corneum layer of the skin. In most biomimetic skin models, a 3D hydrogel fabricated out of collagen type I is used to mimic human skin. However, native skin also contains keratin, which makes up 90% of the epidermis and is produced by the keratinocytes present. We hypothesized that the addition of keratin (KTN) in our collagen hydrogel may aid in the process of keratinocyte differentiation compared to a pure collagen hydrogel. Keratinocytes were seeded on top of a 100% collagen or 50/50 C/KTN hydrogel cultured in either calcium-free (Ca-free) or calcium+ (Ca+) media. Our study demonstrates that the addition of keratin and calcium in the media increased lysosomal activity by measuring the glucocerebrosidase (GBA) activity and lysosomal distribution length, an indication of greater keratinocyte differentiation. We also found that the presence of KTN in the hydrogel also increased the expression of involucrin, a differentiation marker, compared to a pure collagen hydrogel. We demonstrate that a combination (i.e., containing both collagen and kerateine or “C/KTN”) hydrogel was able to increase keratinocyte differentiation compared to a pure collagen hydrogel, and the addition of calcium further increased the differentiation of keratinocytes. This multi-protein hydrogel shows promise in future models or treatments to increase keratinocyte differentiation into the stratum corneum.

Zuniga, Kameel (ORCID:0000000196674007)↗

4-Coumarate:coenzyme A ligase and isoperoxidase expression in Zinnia mesophyll cells induced to differentiate into tracheary elements

When cultured in inductive medium containing adequate auxin and cytokinin, isolated mesophyll cells of Zinnia elegans L. cv Envy differentiate into tracheary elements with lignified secondary wall thickenings. Differentiation does not occur when cells are cultured in control medium, which has reduced levels of auxin and/or cytokinin. The activities of two enzymes involved in lignin synthesis, 4-coumarate:coenzyme A ligase and peroxidase, were examined. An induction-specific cationic isoperoxidase, visualized by low pH polyacrylamide gel electrophoresis, is detectable in soluble and wall fractions of cultured Zinnia cells long before tracheary elements visibly differentiate and is thus an early marker of differentiation. Compounds (such as antiauxins, anticytokinins, and tunicamycin) that inhibit or delay differentiation alter the expression of this isoperoxidase. 4-Coumarate:coenzyme A ligase activity increases dramatically only as cells differentiate. Together, these results suggest that the onset of lignification in differentiating Zinnia cells might be controlled by the availability of precursors synthesized by way of 4-coumarate:coenzyme A ligase. These precursors would then be polymerized into lignin in the cell wall by the induction-specific isoperoxidase.

NASA Discipline Plant Biology↗

Ferroelectric Field-Effect Transistor Differential Amplifier Circuit Analysis

There has been considerable research investigating the Ferroelectric Field-Effect Transistor (FeFET) in memory circuits. However, very little research has been performed in applying the FeFET to analog circuits. This paper investigates the use of FeFETs in a common analog circuit, the differential amplifier. The two input Metal-Oxide-Semiconductor (MOS) transistors in a general MOS differential amplifier circuit are replaced with FeFETs. Resistors are used in place of the other three MOS transistors. The FeFET model used in the analysis has been previously reported and was based on experimental device data. Because of the FeFET hysteresis, the FeFET differential amplifier has four different operating modes depending on whether the FeFETs are positively or negatively polarized. The FeFET differential amplifier operation in the different modes was analyzed by calculating the amplifier voltage transfer and gain characteristics shown in figures 2 through 5. Comparisons were made between the FeFET differential amplifier and the standard MOS differential amplifier. Possible applications and benefits of the FeFET differential amplifier are discussed.

Phillips, Thomas A.↗

Radar Differential Phase Signatures of Ice Orientation for the Prediction of Lightning Initiation and Cessation

The majority of lightning-related casualties typically occur during thunderstorm initiation (e.g., first flash) or dissipation (e.g., last flash). The physics of electrification and lightning production during thunderstorm initiation is fairly well understood. As such, the literature includes a number of studies presenting various radar techniques (using reflectivity and, if available, other dual-polarimetric parameters) for the anticipation of initial electrification and first lightning flash. These radar techniques have shown considerable skill at forecasting first flash. On the other hand, electrical processes and lightning production during thunderstorm dissipation are not nearly as well understood and few, if any, successful techniques have been developed to anticipate the last flash and subsequent cessation of lightning. One promising approach involves the use of dual-polarimetric radar variables to infer the presence of oriented ice crystals in lightning producing storms. In the absence of strong vertical electric fields, ice crystals fall with their largest (semi-major) axis in the horizontal associated with gravitational and aerodynamic forces. In thunderstorms, strong vertical electric fields (100-200 kV m(sup -1)) have been shown to orient small (less than 2 mm) ice crystals such that their semi-major axis is vertical (or nearly vertical). After a lightning flash, the electric field is typically relaxed and prior radar research suggests that ice crystals rapidly resume their preferred horizontal orientation. In active thunderstorms, the vertical electric field quickly recovers and the ice crystals repeat this cycle of orientation for each nearby flash. This change in ice crystal orientation from primarily horizontal to vertical during the development of strong vertical electric fields prior to a lightning flash forms the physical basis for anticipating lightning initiation and, potentially, cessation. Research has shown that radar reflectivity (Z) and other co-polar back-scattering radar measurements like differential reflectivity (Z(sub dr)) typically measured by operational dual-polarimetric radars are not sensitive to these changes in ice crystal orientation. However, prior research has demonstrated that oriented ice crystals cause significant propagation effects that can be routinely measured by most dual-polarimetric radars from X-band (3 cm) to S-band (10 cm) wavelengths using the differential propagation phase shift (often just called differential phase, phi(sub dp)) or its range derivative, the specific differential phase (K(sub dp)). Advantages of the differential phase include independence from absolute or relative power calibration, attenuation, differential attenuation and relative insensitivity to ground clutter and partial beam occultation effects (as long as the signal remains above noise). In research mode, these sorts of techniques have been used to anticipate initial cloud electrification, lightning initiation, and cessation. In this study, we develop a simplified model of ice crystal size, shape, orientation, dielectric, and associated radar scattering and propagation effects in order to simulate various idealized scenarios of ice crystals responding to a hypothetical electric field and their dual-polarimetric radar signatures leading up to lightning initiation and particularly cessation. The sensitivity of the K(sub dp) ice orientation signature to various ice properties and radar wavelength will be explored. Since K(sub dp) is proportional to frequency in the Rayleigh- Gans scattering regime, the ice orientation signatures should be more obvious at higher (lower) frequencies (wavelengths). As a result, simulations at radar wavelengths from 10 cm down to 1 cm (Ka-band) will be conducted. Resonance effects will be considered using the T-matrix method. Since most K(sub dp) Vbased observations have been shown at S-band, we will present ice orientation signatures from C-band (UAH/NASA ARMOR) and X-bd (UAH MAX) dual-polarimetric radars located in Northern Alabama. Issues related to optimal radar scanning for the detection of oriented ice will be discussed. Preliminary suggestions on how these differential phase signatures of oriented ice could contribute to lightning initiation and cessation algorithms will be presented.

Carey, L.D.↗

Constant-Differential-Pressure Two-Fluid Accumulator

A two-fluid accumulator has been designed, built, and demonstrated to provide an acceptably close approximation to constant differential static pressure between two fluids over the full ranges of (1) accumulator stroke, (2) rates of flow of the fluids, and (3) common static pressure applied to the fluids. Prior differential- pressure two-fluid accumulators are generally not capable of maintaining acceptably close approximations to constant differential pressures. The inadequacies of a typical prior differential-pressure two-fluid accumulator can be summarized as follows: The static differential pressure is governed by the intrinsic spring rate (essentially, the stiffness) of an accumulator tank. The spring rate can be tailored through selection of the tank-wall thickness, selection of the number and/or shape of accumulator convolutions, and/or selection of accumulator material(s). Reliance on the intrinsic spring rate of the tank results in three severe limitations: (1) The spring rate and the expulsion efficiency tend to be inversely proportional to each other: that is to say, as the stiffness (and thus the differential pressure) is increased, the range of motion of the accumulator is reduced. (2) As the applied common static pressure increases, the differential pressure tends to decrease. An additional disadvantage, which may or may not be considered limiting, depending on the specific application, is that an increase in stiffness entails an increase in weight. (3) The additional weight required by a low expulsion efficiency accumulator eliminates the advantage given to such gas storage systems. The high expulsion efficiency provided by this two-fluid accumulator allows for a lightweight, tightly packaged system, which can be used in conjunction with a fuel cell-based system.

Piecuch, Benjamin↗

Special Component Designs for Differential-Amplifier MMICs

Special designs of two types of electronic components transistors and transmission lines have been conceived to optimize the performances of these components as parts of waveguide-embedded differential-amplifier monolithic microwave integrated circuits (MMICs) of the type described in the immediately preceding article. These designs address the following two issues, the combination of which is unique to these particular MMICs: Each MMIC includes a differential double-strip transmission line that typically has an impedance between 60 and 100 W. However, for purposes of matching of impedances, transmission lines having lower impedances are also needed. The transistors in each MMIC are, more specifically, one or more pair(s) of InP-based high-electron-mobility transistors (HEMTs). Heretofore, it has been common practice to fabricate each such pair as a single device configured in the side-to-side electrode sequence source/gate/drain/gate/source. This configuration enables low-inductance source grounding from the sides of the device. However, this configuration is not suitable for differential operation, in which it is necessary to drive the gates differentially and to feed the output from the drain electrodes differentially. The special transmission-line design provides for three conductors, instead of two, in places where lower impedance is needed. The third conductor is a metal strip placed underneath the differential double-strip transmission line. The third conductor increases the capacitance per unit length of the transmission line by such an amount as to reduce the impedance to between 5 and 15 W. In the special HEMT-pair design, the side-to-side electrode sequence is changed to drain/gate/source/gate/ drain. In addition, the size of the source is reduced significantly, relative to corresponding sizes in prior designs. This reduction is justified by the fact that, by virtue of the differential configuration, the device has an internal virtual ground, and therefore there is no need for a low-resistance contact between the source and the radio-frequency circuitry. The source contact is needed only for DC biasing. These designs were implemented in a single-stage-amplifier MMIC. In a test at a frequency of 305 GHz, the amplifier embedded in a waveguide exhibited a gain of 0 dB; after correcting for the loss in the waveguide, the amplifier was found to afford a gain of 0.9 dB. In a test at 220 GHz, the overall gain of the amplifier- and-waveguide assembly was found to be 3.5 dB.

Kangaslahti, Pekka↗

Impedance Discontinuity Reduction Between High-Speed Differential Connectors and PCB Interfaces

High-speed serial communication (i.e., Gigabit Ethernet) requires differential transmission and controlled impedances. Impedance control is essential throughout cabling, connector, and circuit board construction. An impedance discontinuity arises at the interface of a high-speed quadrax and twinax connectors and the attached printed circuit board (PCB). This discontinuity usually is lower impedance since the relative dielectric constant of the board is higher (i.e., polyimide approx. = 4) than the connector (Teflon approx. = 2.25). The discontinuity can be observed in transmit or receive eye diagrams, and can reduce the effective link margin of serial data networks. High-speed serial data network transmission improvements can be made at the connector-to-board interfaces as well as improving differential via hole impedances. The impedance discontinuity was improved by 10 percent by drilling a 20-mil (approx. = 0.5-mm) hole in between the pin of a differential connector spaced 55 mils (approx. = 1.4 mm) apart as it is attached to the PCB. The effective dielectric constant of the board can be lowered by drilling holes into the board material between the differential lines in a quadrax or twinax connector attachment points. The differential impedance is inversely proportional to the square root of the relative dielectric constant. This increases the differential impedance and thus reduces the above described impedance discontinuity. The differential via hole impedance can also be increased in the same manner. This technique can be extended to multiple smaller drilled holes as well as tapered holes (i.e., big in the middle followed by smaller ones diagonally).

Navidi, Sal↗

Differential equations for cosmological correlators

Cosmological fluctuations retain a memory of the physics that generated them in their spatial correlations. The strength of correlations varies smoothly as a function of external kinematics, which is encoded in differential equations satisfied by cosmological correlation functions. In this work, we provide a broader perspective on the origin and structure of these differential equations. As a concrete example, we study conformally coupled scalar fields in a power-law cosmology. The wavefunction coefficients in this model have integral representations, with the integrands being the product of the corresponding flat-space results and “twist factors” that depend on the cosmological evolution. Similar twisted integrals arise for loop amplitudes in dimensional regularization, and their recent study has led to the discovery of rich mathematical structures and powerful new tools for computing multi-loop Feynman integrals in quantum field theory. The integrals of interest in cosmology are also part of a finite-dimensional basis of master integrals, which satisfy a system of first-order differential equations. We develop a formalism to derive these differential equations for arbitrary tree graphs. The results can be represented in graphical form by associating the singularities of the differential equations with a set of graph tubings. Upon differentiation, these tubings grow in a local and predictive fashion. In fact, a few remarkably simple rules allow us to predict — by hand — the equations for all tree graphs. While the rules of this “kinematic flow” are defined purely in terms of data on the boundary of the spacetime, they reflect the physics of bulk time evolution. We also study the analogous structures in tr ϕ 3 theory, and see some glimpses of hidden structure in the sum over planar graphs. This suggests that there is an autonomous combinatorial or geometric construction from which cosmological correlations, and the associated spacetime, emerge.

Cosmological models↗

Dihydromyricetin sensitizes human acute myeloid leukemia cells to retinoic acid-induced myeloid differentiation by activating STAT1

The success of all-trans retinoic acid (ATRA) in differentiation therapy for patients with acute promyelocytic leukemia (APL) highly encourages researches to apply a new combination therapy based on ATRA. Therefore, research strategies to further sensitize cells to retinoids are urgently needed. In this study, we showed that Dihydromyricetin (DMY), a 2,3-dihydroflavonol compound, exhibited a strong synergy with ATRA to promote APL NB4 cell differentiation. We observed that DMY sensitized the NB4 cells to ATRA-induced cell growth inhibition, CD11b expression, NBT reduction and myeloid regulator expression. PML-RARα might not be essential for DMY-enhanced differentiation when combined with ATRA, while the enhanced differentiation was dependent on the activation of p38-STAT1 signaling pathway. Taken together, our study is the first to evaluate the synergy of DMY and ATRA in NB4 cell differentiation and to assess new opportunities for the combination of DMY and ATRA as a promising approach for future differentiation therapy.

60 APPLIED LIFE SCIENCES↗

Promoting hepatogenic differentiation of human mesenchymal stem cells using a novel laminin-containing gelatin cryogel scaffold

Highlights: • The gelatin cryogel was optimized for stability in cell culture medium during stem cell differentiation. • The optimized gelatin cryogel improved with the laminin, the main component of basal lamina. • The novel scaffold with laminin efficiently enhanced differentiation of mesenchymal stem cells toward hepatocyte lineage. Liver transplantation is the only definitive treatment currently available for acute and chronic liver failure. However, this approach has been restricted by complications including rejection and infection. Tissue engineering approaches using stem cell-derived functional hepatic cells offer a potential alternative. Using biologically compatible scaffolds is an important complementary key to achieve optimal construct for hepatic replacement. In the present study, to optimize the differentiation of human adipose-derived mesenchymal stem cells (ADMSCs) toward hepatocyte-like cells, a previously described gelatin cryogel was optimized and improved by laminin, the major component of basal lamina. The ADMSCs seeded on the scaffold displayed increased attachment in the presence of laminin and the MTT assay showed good compatibility for cell proliferation. The differentiation of stem cells were evaluated using glycogen staining, urea secretion measurement, hepatocyte specific cell surface analysis and gene expression analysis. The results of tests indicated that laminin protein and gelatin cryogel 3D scaffold, each on its own, enhanced hepatogenic differentiation of ADMSCs. However, when laminin immobilized on the gelatin cryogel surface, the differentiation was promoted significantly and the resulting cells showed striking similarity to HepG2 in terms of expressing studied hepatocyte markers.

60 APPLIED LIFE SCIENCES↗

Adenylate cyclase 7 regulated by miR-192 promotes ATRA-induced differentiation of acute promyelocytic leukemia cells

Highlights: • AC7 affects cAMP production in APL cells. • Knockdown of AC7 inhibits ATRA-induced differentiation of APL cells. • MiR-192 directly targets 3′ UTR of AC7 mRNA and inhibits its expression. • MiR-192 knockdown promotes ATRA-induced differentiation of APL cells by up-regulating AC7. • AC7 and miR-192 expression levels are associated with the relapse of APL patients. Adenylate cyclase 7 (AC7) has been reported to participate in various biological processes during cancer progression. However, the roles of AC7 in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells are still unknown. In this study, firstly, our results showed that AC7 affected intracellular cAMP level and influenced ATRA-induced differentiation of APL cells. Secondly, we revealed that miR-192 could directly target AC7 expression and knockdown of miR-192 promoted ATRA-induced APL cell differentiation by regulating AC7 expression. Furthermore, we found that AC7 expression was lower in patients with relapsed APL than that in patients with newly diagnosed APL, while miR-192 expression was relatively higher in patients with relapsed APL. Taken together, our results show that miR-192-mediated AC7 could play important roles in differentiation of APL cells, AC7 and miR-192 might be new biomarkers and therapeutic targets for patients with relapsed APL.

60 APPLIED LIFE SCIENCES↗

WeakIdent: Weak formulation for identifying differential equation using narrow-fit and trimming

Data-driven identification of differential equations is an interesting but challenging problem, especially when the given data are corrupted by noise. When the governing differential equation is a linear combination of various differential terms, the identification problem can be formulated as solving a linear system, with the feature matrix consisting of linear and nonlinear terms multiplied by a coefficient vector. This product is equal to the time derivative term, and thus generates dynamical behaviors. The goal is to identify the correct terms that form the equation to capture the dynamics of the given data. We propose a general and robust framework to recover differential equations using a weak formulation with two new mechanisms, narrow-fit and trimming, for both ordinary and partial differential equations (ODEs and PDEs). The weak formulation facilitates an efficient and robust way to handle noise, and two new mechanisms, narrow-fit and trimming, improve the coefficient support and value recoveries respectively. For each sparsity level, Subspace Pursuit is utilized to find an initial set of support from the large dictionary. Then, we focus on highly dynamic regions (rows of the feature matrix), and error normalize the feature matrix in the narrow-fit step. The support is further updated via trimming the terms that contribute the least. Finally, the support set of features with the smallest Cross-Validation error is chosen as the result. A comprehensive set of numerical experiments are presented for both systems of ODEs and PDEs with various noise levels. The proposed method gives a robust recovery of the coefficients, and a significant denoising effect which can handle up to 100% noise-to-signal ratio for some equations. We compare the proposed method with several state-of-the-art algorithms for the recovery of differential equations.

97 MATHEMATICS AND COMPUTING↗

Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival

Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24 h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. - Highlights: • Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes. • Hepatocyte nuclear factor 4A (HNF4A) plays a role in hepatic differentiation. • HNF4A improved hepatic differentiation of IHH. • Transplantation of HNF4A-overexpressing IHH could improve liver function.

60 APPLIED LIFE SCIENCES↗

Automatic Differentiation for Adjoint Stencil Loops

Stencil loops are a common motif in computations including convolutional neural networks, structured-mesh solvers for partial differential equations, and image processing. Stencil loops are easy to parallelise, and their fast execution is aided by compilers, libraries, and domain-specific languages. Reverse-mode automatic differentiation, also known as algorithmic differentiation, autodiff, adjoint differentiation, or back-propagation, is sometimes used to obtain gradients of programs that contain stencil loops. Unfortunately, conventional automatic differentiation results in a memory access pattern that is not stencil-like and not easily parallelisable. In this paper we present a novel combination of automatic differentiation and loop transformations that preserves the structure and memory access pattern of stencil loops, while computing fully consistent derivatives. The generated loops can be parallelised and optimised for performance in the same way and using the same tools as the original computation. We have implemented this new technique in the Python tool PerforAD, which we release with this paper along with test cases derived from seismic imaging and computational fluid dynamics applications.

Automatic Differentiation↗

Source-to-Source Automatic Differentiation of OpenMP Parallel Loops

This article presents our work toward correct and efficient automatic differentiation of OpenMP parallel worksharing loops in forward and reverse mode. Automatic differentiation is a method to obtain gradients of numerical programs, which are crucial in optimization, uncertainty quantification, and machine learning. The computational cost to compute gradients is a common bottleneck in practice. For applications that are parallelized for multicore CPUs or GPUs using OpenMP, one also wishes to compute the gradients in parallel. Here, we propose a framework to reason about the correctness of the generated derivative code, from which we justify our OpenMP extension to the differentiation model. We implement this model in the automatic differentiation tool Tapenade and present test cases that are differentiated following our extended differentiation procedure. Performance of the generated derivative programs in forward and reverse mode is better than sequential, although our reverse mode often scales worse than the input programs.

97 MATHEMATICS AND COMPUTING↗