cssi/SciSciGPT-SciSciNet huggingface dataset:
SMAD Signaling Is Required for Structural Integrity of the Female Reproductive Tract and Uterine Function During Early Pregnancy in Mice

Pregnancy is a complex physiological process tightly controlled by the interplay among hormones, morphogens, transcription factors, and signaling pathways. Although recent studies using genetically engineered mouse models have revealed that ligands and receptors of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) signaling pathways are essential for multiple reproductive events during pregnancy, the functional role of SMAD transcription factors, which serve as the canonical signaling platform for the TGFbeta/BMP pathways, in the oviduct and uterus is undefined. Here, we used a mouse model containing triple conditional deletion of the BMP receptor signaling Smads (Smad1 and Smad5) and Smad4, the central mediator of both TGFbeta and BMP signaling, to investigate the role of the SMADs in reproductive tract structure and function in cells from the Amhr2 lineage. Unlike the respective single- or double-knockouts, female Smad1(flox/flox) Smad5(flox/flox) Smad4(flox/flox) Amhr2(cre/+)conditional knockout (i.e., Smad1/5/4-Amhr2-cre KO) mice are sterile. We discovered that Smad1/5/4-Amhr2-cre KO females have malformed oviducts that subsequently develop oviductal diverticuli. These oviducts showed dysregulation of multiple genes essential for oviduct and smooth muscle development. In addition, uteri from Smad1/5/4-Amhr2-cre KO females exhibit multiple defects in stroma, epithelium, and smooth muscle layers and fail to assemble a closed uterine lumen upon embryo implantation, with defective uterine decidualization that led to pregnancy loss at early to mid-gestation. Taken together, our study uncovers a new role for the SMAD transcription factors in maintaining the structural and functional integrity of oviduct and uterus, required for establishment and maintenance of pregnancy.
Multilocular Cystic Renal Cell Carcinoma

Multilocular cystic renal cell carcinoma (MCRCC) appears to be a distinct subtype of renal cell carcinoma with characteristic gross and microscopic features. The authors' ten-year experience (1977-1987) included six cases of MCRCC that were followed for a minimum of two years, with neither recurrence nor metastasis observed in any of the cases. During this period, there were 855 urologic procedures for the upper urinary tract, with 256 neoplasms or cysts identified. These included 32 simple cysts, 41 transitional cell carcinomas, 133 renal cell carcinomas, 17 papillary renal cell carcinomas, and 33 miscellaneous tumors. Histologically, the MCRCCs were well-demarcated multicystic lesions containing variably sized aggregates of neoplastic clear cells showing grade 1 nuclear features and little or no mitotic activity. The cyst walls were densely fibrotic, and the lining was often devoid of epithelium. Flow-cytometric analysis performed in five of the six cases with the use of paraffin-embedded tissue showed the tumors to be diploid in all instances, with low proliferative activity. The authors believe that this tumor is a low-grade variant of renal cell carcinoma and should be studied further to determine appropriate therapy.
Literary genre, medieval studies, and the prosthesis of disability

ABSTRACTBecause ‘disability’ is a concept anachronistic to the Middle Ages, the subfield of medieval disability studies calls for complex negotiations of temporality and historicist interpretation. This essay regards medieval disability as a historicist ‘prosthesis’ and seeks to clarify what new capacities, altered interpretations, and critical insights it yields. What happens, I ask, when disability’s untimely prosthesis does not fit? The prominent medieval genre of the exemplum, or brief illustrative tale, provides my case study. Full of stereotyped and instrumental representations of impairment, exemplary stories seem to jar against the values of disability studies - but is their significance only negative? I argue that studying disability in medieval literature calls for reading with tendentious solidarity, I and show what this might look like by interpreting one of the tales of the Gesta Romanorum. Ultimately I claim that wilful and prostheticised reading practices are not deviant from the history of...
Elucidating the 30-Year-Longstanding Bioenergetic Mystery in Alkalophilic Bacteria

The decades-longstanding energetic mystery of alkalophilic bacteria as to how they are able to synthesize ATP has now, for the first time, been clearly solved using the proton-electrostatics localization hypothesis [Lee JW (2015) Proton-Electrostatic Localization: Explaining the Bioenergetic Conundrum in Alkalophilic Bacteria. Bioenergetics 4:121. doi:10.4172/2167-7662.1000121; Lee JW (2012) Proton-Electrostatics Hypothesis for Localized Proton Coupling Bioenergetics. Bioenergetics 1:104. doi:10.4172/2167-7662.1000104]. This is a major breakthrough advance in understanding proton-coupling bioenergetics over the Nobel-prize work of Peter Mitchell's chemiosmotic theory. The widespread textbook Mitchellian proton motive force (pmf) equation could significantly underestimate the true pmf value and thus must be revised. Use of our newly derived bioenergetics equation results in an overall pmf value (215∼233 mV) that is more than 4 times larger than that (44.3 mV) calculated from the Mitchellian equation for the alkalophilic bacteria growing at pH 10.5. This newly calculated pmf value is sufficient to overcome the observed phosphorylation potential ∆Gp of −478 mV to synthesize ATP in the bacteria, which can now explain the 30-year-longstanding bioenergetics conundrum. This finding may have fundamental implications not only in the science of bioenergetics but also in understanding the importance of water to life not only as a solvent and substrate but also as a proton conductor for proton coupling energy transduction. In this presentation, the results of our latest bioenergetics calculation and analysis will be presented and discussed in greater details.
Multi-Parameter Magnetic Material Characterization for High Power Medium Frequency Converters

With the rapid availability of new magnetic materials and even more options in post-processing techniques such as field and strain annealing, full property maps of materials and final fabricated components are needed for proper system design. This is especially critical in modern wide bandgap power electronics based converters where medium switching frequencies are used to deliver high power. In these systems, the magnetic design has a significant impact in the overall losses. The magnetics constitute a majority of the losses and magnetic properties have a defining influence on the overall systems, e.g. available power flow and soft switching regions. A new lossless structural harness that allows easy testing of cores and the development of property maps is presented. The harness also enables the testing of mechanical variations such as gapping and clamping pressure on the core.
Recent strategies in cartilage repair: A systemic review of the scaffold development and tissue engineering

Osteoarthritis results in irreparable loss of articular cartilage. Due to its avascular nature and low mitotic activity, cartilage has little intrinsic capacity for repair. Cartilage loss leads to pain, physical disability, movement restriction, and morbidity. Various treatment strategies have been proposed for cartilage regeneration, but the optimum treatment is yet to be defined. Tissue engineering with engineered constructs aimed towards developing a suitable substrate may help in cartilage regeneration by providing the mechanical, biological and chemical support to the cells. The use of scaffold as a substrate to support the progenitor cells or autologous chondrocytes has given promising results. Leakage of cells, poor cell survival, poor cell differentiation, inadequate integration into the host tissue, incorrect distribution of cells, and dedifferentiation of the normal cartilage are the common problems in tissue engineering. Current research is focused on improving mechanical and biochemical properties of scaffold to make it more efficient. The aim of this review is to provide a critical discussion on existing challenges, scaffold type and properties, and an update on ongoing recent developments in the architecture and composition of scaffold to enhance the proliferation and viability of mesenchymal stem cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2343–2354, 2017.
Graph Databases for Knowledge Management

Emerging technologies let companies manage their knowledge assets with more innovative and effective methods. Due to the complex nature of knowledge management processes, it is cumbersome to design, develop, and implement a system based on relational databases. This article proposes a specific graph database application in streamlining major knowledge management processes. The author develops a property graph data model to facilitate the process model of knowledge management. In addition, this property graph data model is implemented through the Neo4j graph database system. This research provides some guidance for practitioners in seeking alternative approaches to traditional methods of knowledge management.
Socioeconomic Achievement Among Arab Immigrants in the USA: The Influence of Region of Origin and Gender

Based on the Integrated Public Use Microdata Series (IPUMS) data derived from 2001–2013 samples of the American Community Surveys, we examine the impact of region of origin and gender on socioeconomic achievement variation among Arab immigrants in the USA. Region of origin includes North Africa (Algeria, Egypt, Libya, Morocco, and Sudan), Levant (Jordan, Lebanon, Syria, and Iraq), and the Arabian Peninsula (Bahrain, Qatar, United Arab Emirates, Oman, Saudi Arabia, and Yemen). This examination is particularly important given the prevailing scholarly consensus that Arab immigrants are collectively portrayed as socioeconomically successful. Our analyses suggest two key findings. First, we find that region of origin is not a consistent predictor of earnings. While Arab immigrants from North Africa earned significantly less than those from the Levant, this was only true for males. No significant effect is found for region of origin in all other comparisons (both overall and when the analysis is restricted to males or females). Second, and by contrast, gender, net of other variables is a powerful predictor of earnings (both within regions and across regions).
How discernible is user impromptu behavior when unlocking a touch screen

Being a popular computing device, smartphone (or tablet, wearable device) system's screen unlocking mechanisms have recently come under numerous successful attacks. In an aim to deter the attacks, we explored users' spontaneous touch behavioral traits in order to identify the users which we opine could be an added layer of security. We experimented with four conventional unlocking schemes: 4 Digit Pin, 3×3 “Connect the Dots”, Glow Pad, Slide Unlock and proposed one new unlocking mechanism, “Pressure Circle”. Six high-level features have been extracted from user touch activities and we designed our own verifier to identify users. For each unlocking scheme, experimental results generated from 992 impostor attacks performed on 32 user samples, show that users can be identified with an accuracy of up to 77.3% solely by considering their touch behavior. Overall, we achieve an average accuracy of 68.8%. We argue that, this inherent behavioral biometric trait when combined with the conventional unlocking schemes, would be less susceptible to attacks.
A human-like game theory-based controller for automatic lane changing

Abstract Lane changing is a critical task for autonomous driving, especially in heavy traffic. Numerous automatic lane-changing algorithms have been proposed. However, surrounding vehicles are usually treated as moving obstacles without considering the interaction between vehicles/drivers. This paper presents a game theory-based lane-changing model, which mimics human behavior by interacting with surrounding drivers using the turn signal and lateral moves. The aggressiveness of the surrounding vehicles/drivers is estimated based on their reactions. With this model, the controller is capable of extracting information and learning from the interaction in real time. As such, the optimal timing and acceleration for changing lanes with respect to a variety of aggressiveness in target lane vehicle behavior are found accordingly. The game theory-based controller was tested in Simulink and dSPACE. Scenarios were designed so that a vehicle controlled by a game theory-based controller could interact with vehicles controlled by both robot and human drivers. Test results show that the game theory-based controller is capable of changing lanes in a human-like manner and outperforms fixed rule-based controllers.
Genuine Progress Indicator for California: 2010–2014

Abstract In this paper, we estimate the Genuine Progress Indicator (GPI), which is a measure of sustainable economic welfare, for California for a five-year period, 2010–2014. This relatively short time period, which covers the recovery from a deep recession, allows us to examine how integration of environmental degradation, nonmarket activities, and inequality affects the GPI of California. The California GPI is only 52% of Gross State Product (GSP) – comparable to other GPI to GDP proportions – because the large negative environmental components offset the large positive social components and because many government expenditures, such as those related to defence and law enforcement, are excluded. Between 2010 and 2014, California GSP grew 9.2% and GPI grew 9.8%. We evaluate our estimation of the California GPI (CA-GPI) in two specific ways. First, we compare California’s GPI to an alternative indicator of social welfare, the Human Development Index (HDI) for California. Our comparison points out that the GPI is a more holistic measure of sustainable economic well-being, although the HDI is useful for evaluating educational attainment, life expectancy, or earnings across regions or demographic groups in the state. Second, we compare our estimation of CA-GPI to the California results from a recent GPI estimation for all fifty states for 2011, in order to evaluate how different methodological decisions and data selection affect the results. Our overall estimate is 13 percent higher, with the primary differences reflecting discrepancies in methodological assumptions or data sources in the calculation of a few key variables, including the value of time used for calculating nonmarket activities. These two estimates of CA-GPI allow us to analyze the sensitivity of two widely used approaches for calculating the GPI, and the sensitivity of using California-specific public data sources compared to national public data sources (scaled to California). The variation in the two California GPI estimations demonstrates the importance of standardizing the method and the data sources, with the goal of creating a viable alternative to the GDP for measuring economic performance. Comparison of the two GPI estimations shows how the use of region-specific data increases the accuracy of estimates, which is important for evaluating regional outcomes and trends over time. However, using data and method that prioritizes standardization is essential for cross-regional comparability, even though the trade-off is diminished regional accuracy. The paper concludes with a discussion of the uses of the GPI to evaluate policies, and suggests fruitful steps forward.
Random and Chaotic Time Series Analysis: Minimum Phase-Volume Deconvolution

Any stationary process can be decomposed into the sum of (1) a linearly deterministic term and (2) a purely random moving average. It is conjectured that the latter can in turn be decomposed into the sum of a chaotic moving average and a random one. A new technique, called minimum phase-volume (MPV) deconvolution, is proposed to estimate the corresponding models from time series data. In the instructive example provided by the one-sided Bernoulli shift the procedure leads to the symbolic dynamical representation of the original process.
c-myc transactivates the ornithine decarboxylase gene.

Several observations suggest that the c-myc proto-oncogene is a key regulator of cell growth and differentiation. First, expression of c-myc RNA and protein is tightly regulated by mitogens and are suppressed by growth inhibitory agents (Luscher and Eisenman, 1991). Second, removal of c-myc protein appears required for withdrawal from the cell cycle since enforced c-myc expression promotes cell cycle progression (Askew et al., 1991; Eilers et al., 1991; Evan et al., 1992) and inhibits terminal differentiation (Prochownik and kukowska, 1986; Coppolla and Cole, 1986). Finally, inhibiton of c-myc expression by antisense oligonucleotides or RNA prevents entry of cells into S phase and accelerates differentiation (Heikkela et al, 1987; Prowchownik et al., 1988). The precise function that c-myc provides to promote cell cycle progression is unknown. Myc family proteins have domains characteristic of known transcription factors, including a basic-helix-loop-helix-(B-HLH) motif and a leucine zipper (LZ) domain, and have therefore been proposed to function as transcription factors (Luscher and Eisenman, 1991). Furthermore, it has recently been demonstrated that c-myc functions as a sequence-specific DNA binding protein (Blackwell et al., 1990; Prendergast and Ziff, 1991; Halazonetis and kandil, 1991) and through dimerization with a novel B-HLH-LZ partner, max, myc binds with high affinity to the “E-box” motif CACGTG (Blackwood and Eisenman, 1991). In addition, regions of the amino terminus of c-myc have been shown to function as transactivation domains when fused to the DNA binding domain of the transcription factor GAL4 (kato et al., 1990).
Contested Authorship, Self-Plagiarism, and the Scholarly Record

This chapter considers recent cases of contested authorship in two articles involving an American philosophy professor. The examination of these unusual publishing circumstances, which include allegations of self-plagiarism, places in high relief the requirements of genuine authorship, the complexity of some self-plagiarism claims, and the challenges of requesting corrections of the scholarly record. Differing standards of evidence are often proposed in considering whether to retract a published article for authorship violations, and the chapter evaluates these standards in light of potential benefits to the larger research community. Researchers, editors, and publishers sometimes conflate standards from legal, moral, and scientific domains, and a lack of clarity about the applicable standard can significantly delay a proper correction of the scholarly record.
White button mushrooms and prostate cancer prevention

5174 A series of in vitro and in vivo experiments have been carried out to demonstrate that white button mushrooms can be a chemopreventing agent against prostate cancer. A 20% methanol extract of white button mushrooms has been found to contain phytochemicals that suppress steroid 5alpha-reductase and aromatase. Steroid 5alpha-reductase converts testosterone to dihydrotestosterone (DHT) and has been shown to play an important role in the development of prostate cancer and benign prostate hyperplasia. The use of steroid 5alpha-reductase inhibitors has been found to decrease the incidence of prostate cancer. Aromatase is the enzyme that converts androgen to estrogen. This enzyme is expressed in prostate cancer cells and has been suggested to play a role in androgen-independent prostate cancer. Cell culture experiments involving cells treated with mushroom extract for ten days, have been carried out. Through these experiments, we have revealed that white button mushroom extract has the ability to suppress the growth of hormone resistant prostate cancer cells such as PC-3 and DU145 as well as hormone dependent LNCaP cells in a dose dependent manner. The mushroom extract was found not to affect the proliferation of normal prostate epithelial cells. We have also carried out in vivo chemoprevention studies using prostate cancer cell-implanted male athymic nude mouse models. There were two groups of mice gavaged with two different concentrations of mushroom extract and also a pair-fed control group that was gavaged with water. From this in vivo study, we demonstrated that our mushroom extract decreased tumor size in a dose dependent manner. Pathology results indicated that there was significant increase in apoptosis compared to the control as well as decrease in cell proliferation. Therefore, our findings on white button mushrooms indicate that the intake of mushrooms could reduce the incidence of prostate cancer. An effective chemopreventive agent should not significantly alter quality of life, and is ideally inexpensive, safe and well tolerated. This prevention method should be readily available and affordable to the general population including underserved populations (*These authors contributed equally to this work).
Safety of tirofiban and dual antiplatelet therapy in treating intracranial aneurysms

Background Endovascular treatment of intracranial aneurysms usually involves stent-assisted coiling (SAC) and flow diverters. Glycoprotein IIb/IIIa inhibitors such as tirofiban and dual antiplatelet therapy (DAPT) are required to prevent thromboembolic complications afterwards. We sought to determine the safety of tirofiban and DAPT in these cases. Methods We conducted a retrospective analysis of our database for patients with intracranial aneurysms who underwent SAC or flow diversion. The tirofiban-DAPT protocol used is described. Data regarding duration of infusion, placement of external ventricular devices (EVDs), complications, haemoglobin levels and platelet count before and 24 hours after antiplatelet therapy were collected and analysed. Results One-hundred and forty-one patients with 148 aneurysms/procedures were included. 110 aneurysms were treated acutely and 38 electively. Minor and major haemorrhagic events were recognised in 20% (30/148) aneurysms. Only 5 (3.4%) intracerebral haemorrhages were symptomatic: 3 cortical/SAH and 2 EVD-related. The average blood volume in symptomatic haemorrhages was 24.8 cc versus 5.42 cc in asymptomatic haemorrhages (p=0.002). The rate of EVD-related haemorrhages was 15.7% (19/121) and only 2 (1.7%) were symptomatic. Most haemorrhagic events occurred in ruptured aneurysms (90.1%, p=0.01). No significant change in platelet count or haemoglobin levels before and 24 hours after administration of tirofiban and DAPT was documented. Concomitant administration of heparin did not increase haemorrhagic events. Conclusion The use of the GP IIb/IIIa inhibitors tirofiban and DAPT in this series was safe. Tirofiban and DAPT did not affect platelet count or haemoglobin levels and did not increase rate of symptomatic haemorrhages or thromboembolic complications.
iPSC model of CHRFAM7A effect on α7 nicotinic acetylcholine receptor function in the human context.

The α7 nicotinic acetylcholine receptor (α7nAChR) has been a promising target for diseases affecting cognition and higher cortical functions; however, the effect observed in animal models failed to translate into human clinical trials identifying a translational gap. CHRFAM7A is a human-specific fusion gene with properties that enable incorporation into the α7nAChR and, being human specific, CHRFAM7A effect was not accounted for in preclinical studies. We hypothesized that CHRFAM7A may account for this translational gap and understanding its function may offer novel insights when exploring α7nAChR as a drug target. CHRFAM7A is present in different copy number variations (CNV) in the human genome with high frequency. To study the functional consequences of the presence of the CHRFAM7A, two induced pluripotent stem cell (iPSC) lines (0 copy and 1 copy direct) were developed. The 0 copy line was rescued with CHRFAM7A transfection to control for genetic heterogeneity. As readouts for genotype–phenotype correlation, α7nAChR synaptic transmission and amyloid beta 1–42 (Aβ1–42) uptake were tested. Synaptic transmission in the presence of CHRFAM7A demonstrated that PNU-modulated desensitization of α7nAChR currents increased as a function of CHRFAM7A dosage. CHRFAM7A mitigated the dose response of Aβ1–42 uptake suggesting a protective effect beyond physiological concentrations. Furthermore, in the presence of CHRFAM7A Aβ1–42 uptake activated neuronal interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) without activating the canonical inflammasome pathway. Lead optimization may identify more potent molecules when the screen has a model harboring CHRFAM7A. Incorporating pharmacogenetics into clinical trials may enhance signals in efficacy measures.
Five-Factor Model antagonism

Abstract Antagonism is one of the fundamental domains of personality. Antagonism includes such maladaptive traits as being suspicious, mistrustful, deceptive, manipulative, exploitative, self-centered, selfish, oppositional, aggressive, brutal, cruel, arrogant, conceited, and callous, as well as such adaptive traits as being cautious, skeptical, cunning, competitive, shrewd, strong, and savvy. The purpose of the current chapter is to describe the origins of its identification, alternative models, and the presence of adaptive as well as maladaptive attributes.
Embolotherapy for Neuroendocrine Tumors

The most frequent solid organ involved in metastatic neuroendocrine tumors (NET) is the liver. Hepatic metastases occur during the lifetime of 46% to 93% of patients with NETs. Intra-arterial embolotherapies are palliative and should be used for patients with unresectable disease not amenable to resection or ablation. The most widely accepted indications for liver embololization for NET metastases are progression of unresectable hepatic metastases threatening liver function and palliation of hormone-related symptoms uncontrolled by somatostatin analogues. This article will discuss patient selection and administration of all embolotherapies currently used for palliation of neuroendocrine liver metastases.
Seeing Is Believing: Nuclear Imaging of HIV Persistence

A major obstacle to HIV eradication is the presence of infected cells that persist despite suppressive antiretroviral therapy (ART). HIV largely resides outside of the peripheral circulation, and thus, numerous anatomical and lymphoid compartments that have the capacity to harbor HIV are inaccessible to routine sampling. As a result, there is a limited understanding of the tissue burden of HIV infection or anatomical distribution of HIV transcriptional and translational activity. Novel, non-invasive, in vivo methods are urgently needed to address this fundamental gap in knowledge. In this review, we discuss past and current nuclear imaging approaches that have been applied to HIV infection with an emphasis on current strategies to implement positron emission tomography (PET)-based imaging to directly visualize and characterize whole-body HIV burden. These imaging approaches have various limitations, such as the potential for limited PET sensitivity and specificity in the setting of ART suppression or low viral burden. However, recent advances in high-sensitivity, total-body PET imaging platforms and development of new radiotracer technologies that may enhance anatomical penetration of target-specific tracer molecules are discussed. Potential strategies to image non-viral markers of HIV tissue burden or focal immune perturbation are also addressed. Overall, emerging nuclear imaging techniques and platforms may play an important role in the development of novel therapeutic and HIV reservoir eradication strategies.
Inception-inspired LSTM for Next-frame Video Prediction.

The problem of video frame prediction has received much interest due to its relevance to many computer vision applications such as autonomous vehicles or robotics. Supervised methods for video frame prediction rely on labeled data, which may not always be available. In this paper, we provide a novel unsupervised deep-learning method called Inception-based LSTM for video frame prediction. The general idea of inception networks is to implement wider networks instead of deeper networks. This network design was shown to improve the performance of image classification. The proposed method is evaluated on both Inception-v1 and Inception-v2 structures. The proposed Inception LSTM methods are compared with convolutional LSTM when applied using PredNet predictive coding framework for both the KITTI and KTH data sets. We observed that the Inception based LSTM outperforms the convolutional LSTM. Also, Inception LSTM has better prediction performance compared to Inception v2 LSTM. However, Inception v2 LSTM has a lower computational cost compared to Inception LSTM.
Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice

We report that mouse hypothalamic stem/progenitor cells produce multiple pancreatic, gastrointestinal and hypothalamic peptides in addition to exosomes. Through cell sorting and selection according to insulin promoter activity, we generated a subpopulation(s) of these cells which formed 3D spherical structure with combined features of hypothalamic neurospheres and pancreatic islets. Through testing streptozotocin-induced pancreatic islet disruption and fatal diabetes, we found that peripheral implantation of these spheres in mice led to remarkable improvements in general health and survival in addition to a moderate antidiabetic effect, and notably these pro-survival versus metabolic effects were dissociable to a significant extent. Mechanistically, secretion of exosomes by these spheres was essential for enhancing survival while production of insulin was important for the antidiabetic effect. In summary, hypothalamic neural stem/progenitor cells comprise subpopulations with multifaceted secretion, and their derived hypothalamic islets can be implanted peripherally to enhance general health and survival together with an antidiabetic benefit.
Implicit shock tracking using an optimization-based high-order discontinuous Galerkin method

Abstract A novel framework for resolving discontinuous solutions of conservation laws, e.g., contact lines, shock waves, and interfaces, using implicit tracking and a high-order discontinuous Galerkin (DG) discretization was introduced in [39] . Central to the framework is an optimization problem whose solution is a discontinuity-aligned mesh and the corresponding high-order approximation to the flow that does not require explicit meshing of the unknown discontinuity surface. The method was shown to deliver highly accurate solutions on coarse, high-order discretizations without nonlinear stabilization and recover optimal convergence rates O ( h p + 1 ) even for problems with discontinuous solutions. This work extends the implicit tracking framework such that robustness is improved and convergence accelerated. In particular, we introduce an improved formulation of the central optimization problem and an associated sequential quadratic programming (SQP) solver. The new error-based objective function penalizes violation of the DG residual in an enriched test space and is shown to have excellent tracking properties. The SQP solver simultaneously converges the nodal coordinates of the mesh and DG solution to their optimal values and is equipped with a number of features to ensure robust, fast convergence: Levenberg-Marquardt approximation of the Hessian with weighted elliptic regularization, backtracking line search based on the l 1 merit function, and rigorous convergence criteria. We use the proposed method to solve a range of inviscid conservation laws of varying difficulty. We show the method is able to deliver accurate solutions on coarse, high-order meshes and the SQP solver is robust and usually able to drive the first-order optimality system to tight tolerances.
Computational stabilization of T cell receptors allows pairing with antibodies to form bispecifics

Recombinant T cell receptors (TCRs) can be used to redirect naive T cells to eliminate virally infected or cancerous cells; however, they are plagued by low stability and uneven expression. Here, we use molecular modeling to identify mutations in the TCR constant domains (Cα/Cβ) that increase the unfolding temperature of Cα/Cβ by 20 °C, improve the expression of four separate α/β TCRs by 3- to 10-fold, and improve the assembly and stability of TCRs with poor intrinsic stability. The stabilizing mutations rescue the expression of TCRs destabilized through variable domain mutation. The improved stability and folding of the TCRs reduces glycosylation, perhaps through conformational stabilization that restricts access to N-linked glycosylation enzymes. The Cα/Cβ mutations enables antibody-like expression and assembly of well-behaved bispecific molecules that combine an anti-CD3 antibody with the stabilized TCR. These TCR/CD3 bispecifics can redirect T cells to kill tumor cells with target HLA/peptide on their surfaces in vitro.
Correlation between Indoor Environmental Data and Biometric Parameters for the Impact Assessment of a Living Wall in a ZEB Lab

Users’ satisfaction in indoor spaces plays a key role in building design. In recent years, scientific research has focused more and more on the effects produced by the presence of greenery solutions in indoor environments. In this study, the Internet of Things (IoT) concept is used to define an effective solution to monitor indoor environmental parameters, along with the biometric data of users involved in an experimental campaign conducted in a Zero Energy Building laboratory where a living wall has been installed. The growing interest in the key theory of the IoT allows for the development of promising frameworks used to create datasets usually managed with Machine Learning (ML) approaches. Following this tendency, the dataset derived by the proposed infield research has been managed with different ML algorithms in order to identify the most suitable model and influential variables, among the environmental and biometric ones, that can be used to identify the plant configuration. The obtained results highlight how the eXtreme Gradient Boosting (XGBoost)-based model can obtain the best average accuracy score to predict the plant configuration considering both a selection of environmental parameters and biometric data as input values. Moreover, the XGBoost model has been used to identify the users with the highest accuracy considering a combination of picked biometric and environmental features. Finally, a new Green View Factor index has been introduced to characterize how greenery has an impact on the indoor space and it can be used to compare different studies where green elements have been used.
Copper‐Catalyzed Deaminative Difluoromethylation

The difluoromethyl group (CF2 H) is considered to be a lipophilic and metabolically stable bioisostere of an amino (NH2 ) group. Therefore, methods that can rapidly convert an NH2 group into a CF2 H group would be of great value to medicinal chemistry. We report herein an efficient Cu-catalyzed approach for the conversion of alkyl pyridinium salts, which can be readily synthesized from the corresponding alkyl amines, to their alkyl difluoromethane analogues. This method tolerates a broad range of functional groups and can be applied to the late-stage modification of complex amino-containing pharmaceuticals.
A theory of contrastive causal explanation and its implications concerning the explanatoriness of deterministic and probabilistic hypotheses

Carl Hempel (1965) argued that probabilistic hypotheses are limited in what they can explain. He contended that a hypothesis cannot explain why E is true if the hypothesis says that E has a probability less than 0.5. Wesley Salmon (1971, 1984, 1990, 1998) and Richard Jeffrey (1969) argued to the contrary, contending that P can explain why E is true even when P says that E’s probability is very low. This debate concerned noncontrastive explananda. Here, a view of contrastive causal explanation is described and defended. It provides a new limit on what probabilistic hypotheses can explain; the limitation is that P cannot explain why E is true rather than A if P assign E a probability that is less than or equal to the probability that P assigns to A. The view entails that a true deterministic theory and a true probabilistic theory that apply to the same explanandum partition are such that the deterministic theory explains all the true contrastive propositions constructable from that partition, whereas the probabilistic theory often fails to do so.
Next-Generation Sequencing Suggests Complex, Heterogeneous Pathogenesis In Peripheral T-Cell Lymphoma Unspecified

Peripheral T-cell lymphoma (PTCL) makes up about 12 percent of non-Hodgkin lymphoma, comprising 18 diseases that are poorly understood and carry a generally worse prognosis than B-lymphomas. PTCL not otherwise specified (PTCL-NOS), a diagnosis of exclusion, is most common, making up 25-30 percent. Gene-expression studies suggest a heterogeneous origin of this diagnosis, with overlap to other PTCL types, but the genetic factors underlying its pathogenesis are undefined. Current therapy for PTCL-NOS is empiric and ultimately ineffective for most patients. Identification of specific therapeutic targets is therefore a high priority. We have sought better understanding of pathogenesis through next-generation sequencing of PTCL-NOS tumor DNA. Whole-exome sequencing revealed candidate genes but low availability of fresh-frozen samples limited our ability to draw conclusions by this method alone. We therefore sequenced the coding regions of 237 candidate genes in a collection formalin-fixed paraffin-embedded samples. We used Nimblegen Sequence Capture for PCR amplification of exons and Illumina hiSeq for raw sequence generation. Results were aligned to hg19 and compared to dbSNP and the 1,000 genomes data to exclude germline variants. Analysis, including comparison to the COSMIC database of cancer-specific mutations, revealed high-confidence mutations affecting more than 60 known cancer-related genes in 25 PTCL-NOS cases. Recurrent mutations pointed to frequent activation of three key signaling pathways: NF-kB ( TNFAIP3 ), WNT/B-Catenin ( APC, CHD8, CELSR2 ), and NOTCH ( NOTCH1, FBXW7 ). Recurrent deregulation of epigenetic processes was indicated by mutations in genes affecting histone acetylation ( EP300, CREBBP ), histone methylation ( MLL2, KDM6A ), and DNA methylation ( TET2, DNMT3A ). In addition, components of core tumor suppressor pathways showed evidence of frequent inactivation ( TP53, ATM, RB1, CUL9 , PRKDC ). In all, 22 of 25 cases had mutations in at least one of these 17 recurrently mutated genes. Multiple additional candidate disease mechanisms also were suggested by lower-confidence mutations but require confirmation studies, which are under way. In sum, analysis of the coding region of PTCL-NOS tumor DNA suggests a complex and heterogeneous pathogenesis, in line with gene-expression profiling. This work provides an opportunity to better sub-classify entities within the diagnosis of PTCL-NOS and identify specific therapeutic targets and their associated biomarkers. Disclosures: Horwitz: Seattle Genetics, Inc.: Consultancy, Research Funding; Millennium: Consultancy, Research Funding.
Integrating Event Camera Sensor Emulator

Event cameras are biologically-inspired sensors that upend the framed, synchronous nature of traditional cameras. Singh et al. proposed a novel sensor design wherein incident light values may be measured directly through continuous integration, with individual pixels' light sensitivity being adjustable in real time, allowing for extremely high frame rate and high dynamic range video capture. Arguing the potential usefulness of this sensor, this paper introduces a system for simulating the sensor's event outputs and pixel firing rate control from 3D-rendered input images.
Combined Impacts of Uncertainty in Precipitation and AirTemperature on Simulated Mountain System Recharge from anIntegrated Hydrologic Model

Abstract. Mountainous regions act as the water towers of the world by producing streamflow and groundwater recharge, a function that is particularly important in semiarid regions. Quantifying rates of mountain system recharge is difficult, and hydrologic models offer a method to estimate recharge over large scales. These recharge estimates are prone to uncertainty from various sources including model structure and parameters. The quality of meteorological forcing datasets, particularly in mountainous regions, is a large source of uncertainty that is often neglected in groundwater investigations. In this contribution, we quantify the impact of uncertainty in both precipitation and air temperature forcing datasets on the simulated groundwater recharge in the mountainous watershed of the Kaweah River in California, USA. We make use of the integrated surface water – groundwater model, ParFlow.CLM and several gridded datasets commonly used in hydrologic studies, downscaled NLDAS-2, PRISM, Daymet, Gridmet, and TopoWx. Simulations indicate that across all forcing datasets, mountain front recharge is an important component of the water budget in the mountainous watershed accounting for 25–46 % of the annual precipitation, and ~90 % of the total mountain system recharge to the adjacent Central Valley aquifer. The uncertainty in gridded air temperature or precipitation datasets, when assessed individually, results in similar ranges of uncertainty in the simulated water budget. Variations in simulated recharge to changes in precipitation (elasticities) and air temperature (sensitivities) are larger than 1 % change in recharge per 1 % change in precipitation or 1-degree C change in temperature. The total volume of snowmelt is the primary factor creating the high water budget sensitivity; and snowmelt volume is influenced by both precipitation and air temperature forcings. The combined effect of uncertainty in air temperature and precipitation on recharge is additive, and results in uncertainty levels roughly equal to the sum of the individual uncertainties. Mountain system recharge pathways including mountain block recharge, mountain aquifer recharge, and mountain front recharge are less sensitive to changes in air temperature than changes in precipitation. Mountain front and mountain block recharge are more sensitive to changes in precipitation than other recharge pathways. The magnitude of uncertainty in the simulated water budget reflects the importance of developing high qualify meteorological forcing datasets in mountainous regions.
Edge Computing Enabled Cognitive Portable Ground Penetrating Radar

With distributed communication, computation, and storage resources close to end users, edge computing has great potentials to support delay-sensitive industrial applications involving intelligent edge devices. Cognitive portable ground penetrating radars (GPRs) are expected to achieve high-quality sensing performance in a variety of industrial environments by operating intelligently and adaptively under varying sensing conditions. Although edge computing makes it very promising to develop cognitive portable GPRs, both strict performance requirement and trade-offs between communication and computation pose significant challenges. This paper presents an edge computing framework for cognitive portable GPRs. Specifically, the system architecture of an EC-enabled cognitive portable GPR is developed. Based on the identification of various involved computation tasks, an offloading policy was proposed to determine whether computation tasks should be executed locally or offloaded to the edge server. Experimental results show the efficacy of the proposed methods. The framework also provides insight into the design of cognitive Internet of things (IoT) supported by edge computing.
Design thinking to create user-centered icu-ward handoffs at three academic hospitals

RATIONALE: Patient transfers from the intensive care unit (ICU) to the hospital ward are a vulnerable time for patients recovering from critical illness. Our prior work showed that ICU-ward transfers vary widely across sites. Previously, we used Human-Centered Design-an iterative, collaborative process for user-focused solutions-to develop a prototype structured ICU-ward transfer communication tool for clinicians at three academic Internal Medicine residency programs. We describe here an iterative approach to rapid prototyping and updating of this novel tool for integration into the electronic health record (EHR), based on structured focus groups using Design Thinking methodology. METHODS: In spring 2020, we conducted voluntary focus groups of PGY-2 and PGY-3 Internal Medicine Residents to co-create new iterations of an ICUward transfer tool created through prior focus groups. Each site conducted 2 focus groups with 4-10 participants per session. All focus groups were conducted via videoconference due to the COVID-19 pandemic. We used participant feedback to iteratively modify the ICU-ward transfer tool towards an ideal state. With participants' consent, we recorded and anonymously transcribed the focus group discussions conducted over the Zoom platform. We performed qualitative inquiry on transcripts for coding and thematic content analysis. Coding was performed independently by two coders (LS, BG) using both a theory-driven (deductive) and data-driven (inductive) approach;disparate coding was reconciled via in-depth discussion between coders. RESULTS: Focus groups identified several main themes around the role, content, and workflows related to an ideal ICU-wards handoff tool: (1) how the tool can best serve the needs of ICU and wards teams;(2) that the ICU-ward handoff process must balance thoroughness and usability;and (3) that design and implementation must consider user experience and training in best practices. Under these themes, participants identified specific attributes of an ideal handoff tool (Table 1), which coalesced around 3 main goals: (1) to synthesize key details and communicate the ICU team's thought process (summarized in Table 1A);(2) to integrate the new tool into the EHR within a customizable note template that minimizes click burden and redundancy (1B);and (3) to serve as a standardized outline to reduce errors of omission in written and verbal handoffs processes (1C). CONCLUSIONS: Participants valued organization of handoff information, EHR integration and user experience, and standardization and adaptability of workflows when modifying a framework based on prior resident user input to create a more user-friendly ICU-ward transfer tool using a Design Thinking Methodology.
Breaching Confidentiality to Protect the Public: Evolving Standards of Medical Confidentiality for Military Detainees

Confidentiality is a core value in medicine and public health yet, like other core values, it is not absolute. Medical ethics has typically allowed for breaches of confidentiality when there is a credible threat of significant harm to an identifiable third party. Medical ethics has been less explicit in spelling out criteria for allowing breaches of confidentiality to protect populations, instead tending to defer these decisions to the law. But recently, issues in military detention settings have raised the profile of decisions to breach medical confidentiality in efforts to protect the broader population. National and international ethics documents say little about the confidentiality of detainee medical records. But initial decisions to use detainee medical records to help craft coercive interrogations led to widespread condemnation, and might have contributed to detainee health problems, such as a large number of suicide attempts several of which have been successful. More recent military guidance seems to reflect lessons learned from these problems and does more to protect detainee records. For the public health system, this experience is a reminder of the importance of confidentiality in creating trustworthy, and effective, means to protect the public's health.