bluuebunny/crossref_metadata_2025 huggingface dataset:
Stellar X-rays and magnetic activity in 3D MHD coronal models
Authors: Zhuleku J. , Warnecke J. , Peter H.
Published: June 2021

Context. Observations suggest a power-law relation between the coronal emission in X-rays, LX, and the total (unsigned) magnetic flux at the stellar surface, Φ. The physics basis for this relation is poorly understood.

Aims. We use three-dimensional (3D) magnetohydrodynamics (MHD) numerical models of the coronae above active regions, that is, strong concentrations of magnetic field, to investigate the LX versus Φ relation and illustrate this relation with an analytical model based on simple well-established scaling relations.

Methods. In the 3D MHD model horizontal (convective) motions near the surface induce currents in the coronal magnetic field that are dissipated and heat the plasma. This self-consistently creates a corona with a temperature of 1 MK. We run a series of models that differ in terms of the (unsigned) magnetic flux at the surface by changing the (peak) magnetic field strength while keeping all other parameters fixed.

Results. In the 3D MHD models we find that the energy input into the corona, characterized by either the Poynting flux or the total volumetric heating, scales roughly quadratically with the unsigned surface flux Φ. This is expected from heating through field-line braiding. Our central result is the nonlinear scaling of the X-ray emission as LX ∝ Φ3.44. This scaling is slightly steeper than found in recent observations that give power-law indices of up to only 2 or 3. Assuming that on a real star, not only the peak magnetic field strength in the active regions changes but also their number (or surface filling factor), our results are consistent with observations.

Conclusions. Our model provides indications of what causes the steep increase in X-ray luminosity by four orders of magnitude from solar-type activity to fast rotating active stars.
Effectiveness of Fiscal and Financial Incentive Mechanism in Promoting the Development of TCM Health Industry
Authors: Huang Zhixuan , Li Jun
Published: June 2021

On the basis of field research, this paper uses AHP and fuzzy comprehensive evaluation method to study the effectiveness of financial incentive mechanism in promoting the development of Chinese medicine health industry. The results show that the effectiveness of financial incentive mechanism in Chinese medicine health industry is not enough. The government should strengthen the construction of financial incentive mechanism in Chinese medicine health industry and pay attention to the regulation of relevant policies It is necessary to set up and implement the plan, so as to realize the modernization of the health industry of traditional Chinese medicine as soon as possible.
A Study of the Development Mode of Internet Finance in China in the Context of Big Data
Authors: Dou Tingting , Liu Geng
Published: June 2021

In recent years, with the continuous development of China’s financial technology, the relationship between Internet finance and computing information technology such as big data is getting increasingly close. Based on the existing research results, following the research ideas of finding, analyzing and solving problems, this paper studied several main development modes of Internet finance in China in the context of big data, and pointed out the existing problems, so as to put forward policy suggestions to optimize China’s Internet finance on the basis of analyzing the reasons.
The impact of investor sentiment for the U.S. stock market based on Fama-French 3-factor model
Authors: Yu Sifan
Published: June 2021

Particularly, it is difficult to accurately measure investor sentiment due to the inherent complexity and dynamic change. This paper tests the impact of investors’ behavior in the U.S. equity market. By using monthly data from February 2014 to December 2018, the impacts of investor sentiment are examined. Besides, Fama-French risk factors are investigated in a new multiple factor asset pricing model. Specifically, the investor sentiment is measured by six-variable composite index. Empirical results indicate that the investor sentiment is a composition of systemic risk. In this case, the Fama-French three factor model with investor sentiment factor can fully explains the return of stocks in the USA stock market. By comparing the trend of investor sentiment and market index, investor sentiment will affect asset pricing and market volatility, i.e., verifies the effectiveness of investor sentiment index in the U.S, stock market.
Research On The Identification And Evaluation Of Supply Chain Finance Credit Risk
Authors: Liu Yinuo
Published: June 2021

Narrow financing channels and high costs have gradually become the main factors restricting the development of small and medium-sized enterprises. The break of the capital chain will restrict the development of the overall supply chain. The emergence of supply chain finance has brought good news for solving the problem of limited capital of small and medium-sized enterprises. However, affected by many factors such as the imperfection of the existing regulatory system, the inefficiency of the credit rating work of financial institutions, and the low moral standards of supply chain member companies, financial institutions bear huge credit risks. Based on the current research of supply chain financial credit risk, this paper analyzes the causes and characteristics of supply chain financial credit risk, finds out the problems and their causes in the identification and evaluation of supply chain financial credit risk, and how to identify and effectively identify and analyze the supply chain financial credit risk in a more timely and effective manner. It is expected to provide reference for financial institutions to strengthen the financial credit risk management of supply chain.
Research on Ecological Compensation in the Yellow River Basin Based on the Perspective of Game Theory
Authors: Zhao YongQi , Dong ShiHao
Published: June 2021

The Yellow River Basin is an important ecological function zone in China, and it plays an important role in the national economic and social development pattern. However, the over-utilization of water resources has made the ecological and environmental problems in the river basin more and more serious. For this reason, the coordinated governance of the areas along the Yellow River basin has become very important. Based on the static game model, this paper conducts a comprehensive analysis of the coordinated governance of the Yellow River basin in the upstream and downstream areas, constructs a static game model of ecological compensation between the Shanxi and Henan governments under coordinated governance, and studies the feedback equilibrium strategies of the Shanxi and Henan governments. This article provides theoretical basis and suggestions for collaborative governance to achieve sustainable development. The game results show that: reducing the cost of protecting the ecological environment of the upstream basin, increasing the benefits of protecting the ecological environment, and increasing the amount of ecological compensation can promote the implementation of the ecological compensation policy between the upstream and downstream in the basin.
Synchronizing energy production and vehicle routing
Authors: Bendali Fatiha , Mole Kamga Eloise , Mailfert Jean , Quilliot Alain , Toussaint Hélène
Published: June 2021

The emergence of locally produced renewable energies induces the appearance of a new generation of local energy players, which are at the same time producers and consumers. In case of time dependent solar energy production, it raises the question of synchronizing production and consumption. We deal here with this issue, in the context of an experimental Solar Hydrogen (H2) production platform. More precisely, we try here to simultaneously schedule a H2fueled vehicle which follows a pre-computed route while being compelled to periodically refuel, and the H2production micro-plant which is required to produce related energy under time dependent production costs and productivity rates, both processes being subject to storage capacity constraints. In order to do it, we design a global dynamic programming (DP) algorithm for the resulting NP-Hard problem. This DP algorithm involves a 2D time space which links energy consumption by the vehicle and its production by the micro-plant. Since the number of states induced by this DP algorithm becomes an issue as soon as the size of the problem increases, we first propose a theoretical Polynomial Time Approximation Scheme (PTAS), next design several practical pruning devices and finally perform numerical tests in order to check their efficiency.
Thrombin: A Pivotal Player in Hemostasis and Beyond
Authors: Larsen Julie Brogaard , Hvas Anne-Mette
Published: June 2021

The serine protease thrombin, a naturally derived enzyme, plays a key role in hemostasis by converting fibrinogen to fibrin and activating coagulation factor XIII whereby the fibrin clot is stabilized. Furthermore, thrombin activates platelets through protease-activated receptors on the platelet surface. Conversely, thrombin also exerts anticoagulant effects, enhancing the protein C activity while complexed with thrombomodulin. During recent years, it has become evident that thrombin has significant effects beyond hemostasis, as it contributes also to modulation of the endothelium, promotes inflammation and angiogenesis, and plays a role in tumor progression. Yet, due to the very short half-life and almost immediate inhibition in fluid phase by antithrombin, thrombin itself remains elusive, and only indirect measurement of thrombin generation is possible. This review provides a description of structure and mechanisms of action of thrombin both in physiological and pathological processes. Furthermore, it summarizes laboratory tests that measure in vivo or ex vivo thrombin generation, and presents knowledge on the value of these biomarkers in bleeding disorders, cardiopulmonary bypass surgery, and thromboembolic risk assessment in different patient populations. Finally, this review outlines further perspectives on using thrombin generation biomarkers for research purposes and in clinical practice.
Simplified dopant-free color-tunable organic light-emitting diodes
Authors: Wang Qian , Bai Junwu , Zhao Changbin , Ali Muhammad Umair , Miao Jingsheng , Meng Hong
Published: June 2021

Organic light-emitting diodes (OLEDs) manifest a high performance that has enabled the industrial applications of this technology; nevertheless, achieving high efficiency in these devices via introducing dopants makes the fabrication process quite complicated. In this Letter, we demonstrate color-tunable organic light-emitting diodes (CT-OLEDs) with a simplified structure that incorporates a dopant-free PN heterojunction as the emitting layer. By depositing a hole transport layer, 1,1-bis[(di-4-tolylamino)phenyl] cyclohexane (TAPC) as the P-region and co-depositing DMIC-TRZ (LGH001) and 1,3,5-tri[(3-pyridyl)-phen-3-yl] benzene (TmPyPB), the electron transport layer, as the N-region to construct a PN heterojunction, our optimal CT-OLED exhibited a low turn-on voltage of 2.58 V with the maximum current and power efficiencies of 17.8 cd/A and 21.5 lm/W, respectively. We found that enhancing the hole-blocking property of the N-junction for improved charge–carrier balance and higher exciton formation is beneficial to boost the device performance. CT-OLEDs based on TAPC/TmPyPB:LGH001 as PN heterojunction achieved sunlight white emission with correlated color temperature and color rendering indexes of 7765 K and 74, respectively. Importantly, the emission of these devices can be well-tuned by simply regulating the bias voltage. Furthermore, the underlying physics of our developed CT-OLEDs is thoroughly investigated.
On the mechanism of ionization oscillations in Hall thrusters
Authors: Chapurin O. , Smolyakov A. I. , Hagelaar G. , Raitses Y.
Published: June 2021

Low-frequency ionization oscillations involving plasma and neutral density (breathing modes) are the most violent perturbations in Hall thrusters for electric propulsion. Because of its simplicity, the zero-dimensional (0D) predator–prey model of two nonlinearly coupled ordinary differential equations for plasma and neutral density has often been used for the characterization of such oscillations and scaling estimates. We investigate the properties of its continuum analog, the one-dimensional (1D) system of two nonlinearly coupled equations in partial derivatives (PDEs) for plasma and neutral density. This is a more general model, of which the standard 0D predator–prey model is a special limit case. We show that the 1D model is stable and does not show any oscillations for the boundary conditions relevant to Hall thrusters and the uniform ion velocity. We then propose a reduced 1D model based on two coupled PDEs for plasma and neutral densities that is unstable and exhibit oscillations if the ion velocity profile with the near-the-anode back-flow (toward the anode) region is used. Comparisons of the reduced model with the predictions of the full model that takes into account the self-consistent plasma response show that the main properties of the breathing mode are well captured. In particular, it is shown that the frequency of the breathing mode oscillations is weakly dependent on the final ion velocity but shows a strong correlation with the width of the ion back-flow region.
On the unsteady Reynolds-averaged Navier–Stokes capability of simulating turbulent boundary layers under unsteady adverse pressure gradients
Authors: Park Junshin , Ha Sanghyun , You Donghyun
Published: June 2021

Predictive capabilities of unsteady Reynolds-averaged Navier–Stokes (URANS) techniques using the k−ω shear stress transport and Spalart–Allmaras models are assessed for the simulation of turbulent boundary layers under unsteady adverse pressure gradients by comparing their results with direct numerical simulation (DNS) results. Simulations are conducted for separating and reattaching turbulent boundary layers under periodic adverse pressure gradients. Phase-wise comparisons of the velocity, the Reynolds stress, and the skin friction coefficient obtained by URANS simulations and DNS are carried out. URANS techniques are found to qualitatively well predict the formation of the separation bubble and the phase response of the shear layer height, while they predict earlier separation and a larger recirculation bubble compared with those in DNS. Phase responses of the skin friction predicted by URANS simulations are found not to be an accurate indication of flow separation and reattachment of the turbulent boundary layer. The main causes of discrepancies among DNS and URANS results in the near-wall region are attributed to the different anisotropy of the Reynolds stress, which can be characterized by a barycentric map.
Experimental realization of noncyclic geometric gates with shortcut to adiabaticity in a superconducting circuit
Authors: Qiu Luqing , Li Hao , Han Zhikun , Zheng Wen , Yang Xiaopei , Dong Yuqian , Song Shuqing , Lan Dong , Tan Xinsheng , Yu Yang
Published: June 2021

Possessing the noise-resilience feature, geometric phases have become important in robust quantum computation. Gates based on the Abelian and non-Abelian geometric phases have been experimentally demonstrated in different physical systems. However, previous proposals require cyclic evolution with a constant operation time even for small rotation angles, which set a limit to the gate operation time. Here, we experimentally realize noncyclic geometric gates, where the cyclic condition is removed and the operation time is proportional to the rotation angle. With the adiabatic process sped up by shortcut to adiabaticity, the fidelities of a noncyclic geometric gate characterized by randomized benchmarking are above 99.5%. Comparing with the dynamic scheme, we demonstrate the robustness of our gate against control instability in the experiment. Moreover, our results indicate that the noncyclic geometric gate with a smaller rotation angle corresponds to a shorter evolution time and higher fidelity. As small rotation angles are essential in the quantum algorithm, the superiority of noncyclic geometric gates makes them promising candidates in fast and robust quantum computation.
Large tunable bandgaps in the InAs/AlAs strain-compensated short-period superlattices grown by molecular beam epitaxy
Authors: Yao Jinshan , Pan Rui , Wang Wenyang , Li Chen , Chen Baile , Lu Hong , Chen Yan-Feng
Published: June 2021

To explore the bandgap tunability in strain-compensated superlattices, we have grown a series of InAs/AlAs strain-compensated short-period superlattices (SPSs) with different period lengths by molecular beam epitaxy. Although the average indium composition of the InAs/AlAs SPS samples remains the same, the bandgaps of these SPSs measured by photoluminescence show a strong dependence on the period length, ranging from 1.41 to 1.01 eV as the period length varies from 4 ML to 10 ML. This fine control on the period length can extend the cutoff wavelength of this digital-alloy-like InAlAs (lattice matched to InP) material up to 1230 nm at room temperature. Multiple transitions are observed in Fourier transform infrared spectra, which agree well with the calculation and confirm the confinement in this structure. The strain effect in tuning the band structures and the band alignments is demonstrated, showing that longer period length together with smaller conduction band offset has led to the smaller effective bandgap of the InAs/AlAs SPS.
Test structure in some pioneer multichambered Paleozoic foraminifera
Authors: Dubicka Zofia , Gajewska Maria , Kozłowski Wojciech , Mikhalevich Valeria
Published: June 2021

Significance

Most calcareous Paleozoic foraminifera have been traditionally assigned to one high-level taxonomic rank, Fusulinata, based on one common feature, a microgranular test texture. Unfortunately, this inorganic trait has not been sufficiently documented. These results show that Paleozoic foraminifera are taxonomically diverse as observed in recent foraminifera with varied test characteristics, suggesting that different biomineralization mechanisms occurred in Paleozoic foraminifera.
Environmental drivers of annual population fluctuations in a trans-Saharan insect migrant
Authors: Hu Gao , Stefanescu Constanti , Oliver Tom H. , Roy David B. , Brereton Tom , Van Swaay Chris , Reynolds Don R. , Chapman Jason W.
Published: June 2021

Significance

The painted lady butterfly is an annual migrant to northern regions, but the size of the immigration varies by more than 100-fold in successive years. Unlike the monarch, the painted lady breeds year round, and it has long been suspected that plant-growing conditions in winter-breeding locations drive this high annual variability. However, the regions where caterpillars develop over winter remained unclear. Here, we show for the European summer population that winter plant greenness in the savanna of sub-Saharan Africa is the key driver of the size of the spring immigration. Our results show that painted ladies regularly cross the Sahara Desert and elucidate the climatic drivers of the annual population dynamics.
Uncialamycin-based antibody–drug conjugates: Unique enediyne ADCs exhibiting bystander killing effect
Authors: Nicolaou K. C. , Rigol Stephan , Pitsinos Emmanuel N. , Das Dipendu , Lu Yong , Rout Subhrajit , Schammel Alexander W. , Holte Dane , Lin Baiwei , Gu Christine , Sarvaiya Hetal , Trinidad Jose , Barbour Nicole , Valdiosera Amanda M. , Sandoval Joseph , Lee Christina , Aujay Monette , Fernando Hanan , Dhar Anukriti , Karsunky Holger , Taylor Nicole , Pysz Marybeth , Gavrilyuk Julia
Published: June 2021

Significance

A number of antibody–drug conjugates (ADCs) with varying linkers carrying an uncialamycin analogue as payload were synthesized and tested for their cytotoxicity in vitro and in PDX mouse models. Importantly, a number of these enediyne-containing ADCs were found to exhibit potent and selective in vivo and in vitro cytotoxicities and also displayed a significant bystander killing effect. The latter finding is of particular importance since the currently approved enediyne ADCs (featuring an N-acetylated calicheamicin

γ
1
I

derivative as payload) are known not to induce bystander killing, thus lacking a possibly beneficial characteristic that could potentially improve the efficacy of oncological therapies.
Combination inhibition of triple-negative breast cancer cell growth with CD36 siRNA-loaded DNA nanoprism and genistein
Authors: Wang Beinuo , Yan Ni , Wu Di , Dou Yin , Liu Zhenyu , Hu Xiaojuan , Chen Cancan
Published: June 2021

Currently, a single treatment is less effective for triple-negative breast cancer (TNBC) therapy. Additionally, there are some limitations to the use of siRNA alone as a new method to treat breast cancer, such as its effective delivery into cells. In this study, we proposed a strategy that combines a siRNA-loaded DNA nanostructure and genistein for TNBC therapy. Both CD36 siRNA-loaded self-assembled DNA nanoprisms (NP-siCD36) and genistein knocked down CD36, resulting in enhanced anticancer efficacy through phosphorylation of the p38 MAPK pathway. In vitro studies showed that combination therapy could effectively enhance cell apoptosis and reduce cell proliferation, achieving an antitumor effect in TNBC cells. The current study suggests that NP-siCD36 combined with genistein might be a promising strategy for breast cancer and treatment.
Huntington’s disease: nearly four decades of human molecular genetics
Authors: Gusella James F , Lee Jong-Min , MacDonald Marcy E
Published: June 2021

Huntington’s disease (HD) is a devastating neurogenetic disorder whose familial nature and progressive course were first described in the 19th century but for which no disease-modifying treatment is yet available. Through the active participation of HD families, this disorder has acted as a flagship for the application of human molecular genetic strategies to identify disease genes, understand pathogenesis and identify rational targets for development of therapies.
Citrullination Inhibits SERPIN Activity
Authors: Thompson Paul R.
Published: June 2021

The Protein Arginine Deiminases (PADs) hydrolyze arginine residues to form citrulline. This post‐translational modification, termed citrullination, is upregulated in numerous cancers and autoimmune disorders including Rheumatoid Arthritis (RA), lupus, and Alzheimer's disease. While these enzymes are important regulators of gene transcription, the full spectrum of biological activities is relatively underexplored. Recently, the Thompson group reported the development of a suite of probes to detect and isolate citrullinated proteins. These probes are premised on the chemo‐selective reaction of citrulline with phenylglyoxals under acidic conditions. Herein, I will discuss our development of these probes and their use to uncover the RA citrullinome. Specifically, these probes were used to identify the citrullinated proteins present in RA serum, RA synovial fluid, and RA synovial tissue. The proteins identified from these analyses include >150 proteins that were previously not known to be citrullinated. Moreover, these proteins include numerous metabolic enzymes and serine protease inhibitors (SERPINs). Citrullination inactivates the activity of a subset of these proteins, including nicotinamide N‐methyltransferase and numerous P1‐arginine containing SERPINs (e.g., C1 inhibitor, anti‐thrombin, and anti‐plasmin). The ability to inhibit SERPIN activity is highly significant because it suggests PAD release within the RA synovium leads to SERPIN citrullination with a consequent increase in protease activity, thereby activating multiple processes including tissue remodeling, altered blood coagulation, and the activation of the complement cascade.

Support or Funding Information

This work was supported in part by NIH grant GM109767 to P.R.T.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Loss of mitochondrial phosphate carrier in skeletal muscle: dissociation of muscle dysfunction from lower ADP phosphorylating potential
Authors: Seifert Erin L. , Anderson‐Pullinger Lauren , Sharpadskaya Yana
Published: June 2021

Many mutations in the mitochondrial genome and in nuclear genes that encode mitochondrial proteins hamper oxidative phosphorylation (oxphos) and lead to tissue dysfunction. Yet, whether an energy deficit is necessarily a direct cause of tissue dysfunction is not clear. We addressed this question in mice in which the mitochondrial phosphate carrier, PiC, was depleted from skeletal muscle (skm) by tamoxifen‐induced excision of nuclear gene SLC25A3 encoding PiC (Cre+). Three weeks after tamoxifen injections, PiC protein in skm was <5% of levels found in control (Ctrl) wild‐type mice (tamoxifen‐treated). Oxphos, measured in mitochondria isolated from skm, was greatly suppressed to <2%, 35% or 50% of Ctrl, depending on substrate, with essentially no oxphos when succinate (+rotenone) was supplied and the highest residual oxphos when fatty acid substrate and malate were supplied; the residual oxphos may be driven by alternate Pi uptake on the dicarboxylate carrier. Residual oxphos was similar at 3 and 9 wks of PiC depletion, suggesting that the oxphos defect was stable for this interval. Furthermore, subunits of the oxphos machinery were robustly upregulated (50–70% rise) at both time points. Nonetheless, treadmill running capacity worsened during this time. Time‐to‐exhaustion was ~50 mins in Cre+ mice with PiC absent for 3 wks, but ~25 mins when PiC was absent for 9 wks, whereas Ctrl mice ran for the scheduled 80 mins. Thus, deteriorating treadmill running in Cre+ mice seems unrelated to suppressed oxphos per se. Stress signaling via transcription factor ATF4 as well as elevated mTORC1 signaling have been associated with oxphos defects caused by mitochondrial DNA depletion in cell models and in mouse skm. These models have also suggested a causal relationship between persistent mTORC1 activation/stress signaling and cell dysfunction. Yet we found little evidence for stress signaling via ATF4 (or ATF2, ATF3, or ATF5) after 3 or 9 wks of PiC depletion, and evidence for only mild mTORC1 activation after 9 wks of PiC loss. Overall, these observations suggest that skm dysfunction is not related to an oxphos deficit in a simple way. Rather, the oxphos deficit may drive adaptive mechanisms that either become exhausted or turn maladaptive when ongoing over a longer term, or trigger additional processes that are deleterious for muscle function. Furthermore, the model presented here suggests that a mechanism other than stress signaling through ATFs is responsible for tissue dysfunction in the context of a severe oxphos defect.

Support or Funding Information

Funding: R01 GM123771 to ELS

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glycocalyx engineering with tunable synthetic glycopolypeptides
Authors: Kramer Jessica
Published: June 2021

All cells are coated with an array of glycoproteins, glycolipids, and polysaccharides that collectively form the glycocalyx. In bulk, the glycocalyx functions to hydrate, lubricate, and shield the cell from injury and infection. The glycocalyx also has biochemical functions and plays roles in essential process from adhesion and fertilization to infection and immunity. Glycoproteins are challenging to study at the molecular levels due to complex and heterogeneous glycosylation patterns that dynamically vary. These patterns are metabolically controlled and resist manipulation by traditional biochemical and genetic methods. Synthetic glycopolymers have emerged as useful tools to probe glycan based biological interactions. Glycosylated polypeptides are particularly attractive polymers since they can display glycans in their native form, take on natural secondary structures that are important for function, and are biodegradable.

We have developed a chemical route to synthesize glycopolypeptides via polymerization of amino acid N‐carboxyanhydrides. These glycopolypeptide are readily tunable in terms of molecular weight, composition, and glycan density and pattern. Our glycopolypeptides are also dual end‐functionalized with chemical handles that allow for conjugation to probes and biological targets. We have focused on preparing synthetic versions of cell‐surface human mucins and pathogenic glycopolypeptides associated with fungi and bacteria. Our results indicate that glycan pattern and protein‐linkage type have profound effects on conformation. We have also devised methods to engineer the glycocalyx by display these synthetic glycopolypeptides on the cell‐surface to probe and modulate biological outcomes. Overall, these are exciting new materials to systematically examine the role of glycosylation in protein conformation and bioactivity.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Predictors of success on the MCAT for post‐baccalaureate pre‐medicine students
Authors: Dobrydneva Yuliya , Schwartz Lisa
Published: June 2021

Students who aspire to enter medical school have to take the MCAT (Medical College Admission Test). In 2015, the MCAT was redesigned, covering a new set of foundational concepts. Also in 2015, a 12‐month post‐baccalaureate pre‐medicine certificate program at the GWU School of Medicine and Health Sciences was launched to address the changes to the new MCAT. The program prepares students for medical school coursework, such as biochemistry, histology, physiology and pharmacology. The objectives of post‐bac courses are closely aligned with MCAT objectives. The GW post‐bac pre‐med program is intended for career changers who typically majored in the social sciences or humanities, and thus have little or no science background (“scientifically naïve”). Therefore, in our admissions process, we need to identify predictors of future success in heavily scientific courses for students who have minimal prior exposure to sciences. We have analyzed data of the first and second cohorts of students to determine what predictors appeared to be positively or negatively associated with MCAT performance. Variables include past standardizes test scores (ACT, SAT), undergraduate GPA, performance in post‐bac courses (physics, chemistry, biology, organic chemistry and biochemistry) and demographics data correlated with MCAT overall and sub‐sections performance. The analysis will be expanded in the future to include non‐parametric statistics measures to more precisely define predictors of success.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of oxidative liver injury by the probiotic Lactobacillus rhamnosus GG
Authors: Saeedi Bejan Jon , Robinson Brian , Owens Joshua , Liu Ken , Luo Liping , Darby Trevor , Jones Dean , Jones Rheinallt , Neish Andrew
Published: June 2021

The gut microbiome is composed of a diverse and dynamic community of microorganisms colonizing the intestinal lumen and mucosa. Using germ‐free model organisms, recent research has established the importance of these communities in influencing key metabolic, endocrine, and immunologic processes in the host. The majority of this research has focused on its effects on the intestine, the tissue with which the microbiome is in the most intimate contact. Recent studies, however, have revealed that these physiologic effects are significantly more far‐reaching, with roles in hepatic, cardiovascular, and even neurological health. As the primary metabolic and detoxification hub, the liver is a critical checkpoint between the digestive functions of the gut and the rest of the body. Therefore, it is likely that liver health and homeostasis may be affected through alterations in the gut microbiota. This possibility presents an opportunity for therapeutic intervention in hepatic disease by modulating the bacterial communities in the lumen of the intestine. This can be accomplished through the oral administration of probiotics, a group of beneficial bacteria that can influence the health of the host. Previous work by our group demonstrated a key role for the widely‐studied probiotic Lactobacillus rhamnosus GG (LGG) in protection against oxidative liver injury to the intestinal epithelium. It accomplishes this through activation of Nrf2, a basic leucine zipper transcription factor and master regulator of cellular antioxidant and xenobiotic responses. Here, we extend these findings by investigating the ability of LGG to augment this pathway in the liver. We performed daily administration of LGG by oral gavage to conventional mice. In these mice we observe increased hepatic Nrf2 activity relative to vehicle control as determined by increased Nrf2 stabilization, nuclear localization, and target transcription. Induction of the Nrf2 pathway has been shown to protect the liver from xenobiotic and oxidative stress. Indeed, LGG fed animals were protected against a challenge with acetaminophen, a potent inducer of hepatic oxidative stress. These data provide important mechanistic insights into the role of the microbiome and probiotics in regulating systemic host homeostasis.

Support or Funding Information

NIH RO1AI64462

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Biological Scaffolds that Mimic Function and Structure of Basement Membranes
Authors: Ogle Roy Clinton
Published: June 2021

Biological scaffolds mimicking basement membranes are valuable tools to study biological processes like cellular differentiation and phenotypic maintenance in vitro. Such artificial basement membranes also hold great promise for engineering tissues and organs and promoting regenerative processes. Basement membrane‐like sheets were fabricated by electrospinning of nanofibers with fiber size, geometry, and the porosity of authentic basement membranes. Nanofibers were electrospun from pure murine laminin 111, murine reconstituted basement membrane (containing laminin, type IV collagen and perlecan) and human cardiac muscle basement membrane enriched in laminins 411 and 511). These proteins and complex extracts were blended with polymers such as polycaprolactone to create hybrid nanofibers with mechanical properties determined by the degradable polymer and biological properties derived from laminin. Importantly, the protein and hybrid nanofibers, unlike others reported, required no chemical crosslinking, which often disrupts biological activity, to maintain structure. These biological scaffolds were compared to films of pure laminin 111 and the mouse and human basement membrane extracts for their ability to maintain the pluripotent state of induced pluripotent stem cells and embryonic stem cells in defined media. All cell lines examined attached more rapidly and to a greater extent on the nanofibrous basement membrane scaffolds, and antibody and enzymatic staining for a variety of markers of pluripotency showed they resisted the tendency to differentiate in vitro for weeks when maintained on these substrates. Next we examined the ability of the scaffolds to promote attachment and differentiation of mesenchymal stem and PC12 cells to a neuron‐like phenotype. The basement membrane like scaffolds promoted neuronal precursor attachment and differentiation to neuron‐like cells in serum free media without the addition of cAMP or nerve growth factor, suggesting a possible biomimetic effect on differentiation from the scaffold. Together these initial studies illustrate methods to create substrates that mimic native basement membranes in structure and function‐‐these scaffolds may take our in vitro models a bit closer to the in vivo situation.

Support or Funding Information

Research generously supported by: Virginia Biosciences Health Research Corporation Grant, Nanofabrication of Tissue Scaffolds

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Porcine Lung in Biomedical Research
Authors: Meyerholz David
Published: June 2021

In biomedical research, animal models are frequently necessary for the study of human diseases. Choosing an animal model requires knowledge of several factors that may influence the relevance of the model compared to humans. In particular, anatomy is a relevant feature when choosing animal models. The lungs are essential for survival, but human lungs are not identical to animal lungs and these variations in anatomy can have significance for the study of diseases. In the lungs, large airways are divided into trachea and bronchi that extend into small airways (i.e. bronchioles) and then the respiratory acini (composed of respiratory bronchioles, alveolar ducts and alveoli). The pig lung is similar in overall size and development to humans. In humans, the tracheal cartilage is “C”‐shaped with the open side of the “C” along the posterior border, but in pigs the edges of the cartilage are longer and extend in overlapping fashion along the posterior (or “dorsal”) border. In both species, bronchi begin at the extrapulmonary tracheal bifurcation and extend into the lungs; however, pig bronchi may extend deeper into the lungs (i.e. to approach the pleural border) than humans, thus causing bronchioles of pigs to be less extensive than in humans. Additionally, human bronchi exhibit dichotomous branching (relatively synchronous) whereas pig bronchi exhibit monopodial branching (asynchronous with one main airway and smaller off‐branches). The respiratory acinus has similar organization between species, but humans have a slightly more prominent respiratory bronchiole. How can anatomical differences in lung affect disease? As one example, cystic fibrosis (CF) is a condition caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Shortly after the discovery of the gene in 1989, CFTR‐deficient mice were generated, but they failed to develop spontaneous CF lung disease. Possible factors for a failure of mice to develop disease included anatomic differences such as lack of intrapulmonary bronchi (i.e. with airway glands and cartilage) and intrapulmonary airways that were equivalent to bronchioles in humans. In 2008, CF pigs were generated and these developed spontaneous CF lung disease like humans. To address the phenotypic differences between these three species, airways were studied and ATP12A, an apical transporter prominent in large but not small airways, was identified as a possible reason for CF disease pigs and human lungs. The presence of ATP12A in bronchi is important for acidification of airways surface liquid in CF and these acidic secretions promote sticky mucus, reduced efficacy of host defenses, and defective mucociliary clearance leading to recurrent/chronic infection and inflammation. In summary, anatomic factors should be considered when developing and trouble‐shooting animal models of human disease.

Support or Funding Information

NIH and CFF.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mechanoresponsive skeletal stem cells acquire primitive neural crest identity during distraction osteogenesis
Authors: Longaker Michael
Published: June 2021

The cellular mode of regeneration in response to mandibular distraction is of great interest, as this represents a successful clinical strategy to elicit the endogenous regenerative potential of postnatal tissue. Much like regeneration of distal digit tip in mice, mandibular distraction enacts the integrated outgrowth of multiple tissues within 2–3 months, reaching a form that is similar to normal mandible in form and function. Our previous studies in the mouse digit tip have reported a lineage restriction of stem/progenitor cells as an evolutionarily conserved paradigm in which de‐differentiation of resident cells into multipotent progenitors does not occur in post‐natal repair and regeneration. Here we provide evidence, for the first time, that controlled mechanical advancement of the lower jaw activates FAK signaling events which unlock gene regulatory programs normally active in cranial neural crest cells during facial morphogenesis, leading to an enhanced regenerative potential of tissue‐resident SSCs in the adult mandible.

Support or Funding Information

NIH R01 DE026730, Hagey Laboratory for Pediatric Regenerative Medicine, The Gunn/Olivier Fund, Stinehart/Reed award

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Consider the Lung as a Sensory Organ
Authors: Sun Xin
Published: June 2021

At resting, an average person inhales/exhales 5–8 litters of air. This air may vary in oxygen content, carry allergen, pollutants or pathogens. To address how the lung senses and responds to these signals, we focused on pulmonary neuroendocrine cells (PNECs). PNECs are rare airway epithelial cells that are preferentially localized to airway branch point junctions. They are innervated by nerves, and can produce potent neuropeptides, neurotransmitters and amines. Our data suggest that proper aggregation of PNECs into neuroepithelial bodies is essential for their normal function. Disruption of PNEC clustering led to increased PNEC products and heightened baseline immune signature. We are currently testing the hypothesis that these cells serve as key nodes that mediate lung, environment, immune and nervous system interactions.

Support or Funding Information

NHLBI HL119946

NHLBI HL122406

NICHD P01HD068250

NIHOD OT2OD023857

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Targeting protein‐protein interactions in chaperone complexes to normalize proteostasis
Authors: Gestwicki Jason E.
Published: June 2021

The ~300 molecular chaperones in mammals are thought to work together to maintain protein homeostasis (proteostasis). Often, this process is carried out by groups of chaperones that physically interact with each other and with their client proteins. Thus, chaperones can be thought of as a network that is held together by either stable or transient protein‐protein interactions (PPIs). This chaperone network protects unfolded clients and shepards them through folding, function and turnover. Our goal is to understand the logic of chaperone‐mediated protein quality control decisions. Our approach is to: (a) study the PPIs between chaperones and clients and (b) create drug‐like small molecules that perturb these PPIs. In turn, we can use these molecules to probe the role of specific PPIs in quality control.

Towards this goal, we have mapped the interactions of a model client, tau, with chaperone subnetworks and identified chaperones that bind directly to this client. Interestingly, we found that a subset of these chaperones had strong anti‐aggregation and anti‐prion activity. Leveraging this knowledge, we created high throughput screening (HTS) platforms to activate the specific anti‐aggregation sub‐network. Following a medicinal chemistry campaign, the lead molecules promoted turnover of tau in multiple disease models, consistent with the model. Together, these ongoing studies have illuminated the logic of protein quality control and provided a set of chemical tools for addressing chaperone function in other systems.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Use of Voluntary 3‐D Technology and Upper‐Class Peer‐Mentoring to Enhance Anatomy Performance of Under‐Represented Minority Students in Physical Therapy
Authors: Ortiz Alexis , Bickley Christina , Kliefoth Maria
Published: June 2021

Under‐represented minority students have the greater attrition rate in health‐related graduate programs. Several strategies such as 3D enhanced educational strategies and peer‐tutoring have proven to be effective in improving student learning outcomes.

PURPOSE

The purpose of this study was to estimate the association between the voluntary use of 3D enhanced studying materials and peer‐tutoring in the grades of under‐represented minority students during practical and written anatomy exams and final overall grade in a first‐year anatomy course at a school of physical therapy.

METHODS

3D narrated dissection animation videos were available through an educational computerized platform. The times the video was accessed per student (hits) was measured. Hours attended to peer‐mentoring and tutoring was also measured. Each of three practical and written exams were averaged and the final grade for the course was also calculated. Descriptive statistics were calculated for all variables of interest. Multiple linear regressions were performed with hits and mentorship hours as predictors and grades as outcomes.

RESULTS

Average practical, written, and final grade were 80.45 ± 8.80, 80.94 ± 9.14, and 80.69 ± 8.73, respectively. Average 3D materials were 16.82 ± 4.95/hits per student while average hours of peer‐tutoring were 16.82 ± 4.95. The regression models with greater association to grades were those with both, hits and peer‐tutoring combined. The association between hits of 3D enhanced material and peer‐tutoring to practice exam grades was not statistically significant (r = 0.29, p = 0.57). The association between predictors and written exam was r = 0.27, p = 0.62, while the association with final grade was r = 0.29, p = 0.57.

CONCLUSION

Although the use of 3D enhanced anatomy studying materials and peer‐tutoring have proven effective in improving student learning outcomes and grades it appears these improvements are when such programs are mandatory. Our study demonstrated that when such services are voluntary students don't utilize them enough to have an impact on grading criteria for both, practical and written examination in anatomy in a physical therapy curriculum.

Support or Funding Information

This work was supported in whole or in part by a grant from the Texas Higher Education Coordinating Board (THECB). The opinions and conclusions expressed in this document are those of the author(s) and do not necessarily represent the opinions or policy of the THECB.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.