bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility study of the K+d → K0pp reaction for the Θ+ pentaquark
Authors: Sekihara Takayasu , Kim Hyun-Chul , Hosaka Atsushi 
Published: April 2020

Abstract
We investigate theoretically the $K^{0} p$ invariant mass spectrum of the $K^{+} d \to K^{0} p p$ reaction and scrutinize how the signal of the “$\Theta ^{+}$” pentaquark, if it exists, emerges in the $K^{0} p$ spectrum. The most prominent advantage of this reaction is that we can clearly assess whether the “$\Theta ^{+}$” exists or not as a direct-formation production without significant backgrounds, in contrast to other reactions such as photoproduction and $\pi$-induced productions. We show that while the impulse or single-step scattering process can cover the “$\Theta ^{+}$” energy region with an initial kaon momentum $k_{\rm lab} \approx 0.40 \text{ GeV} / c$ in the laboratory frame, the contributions from double-step processes may have a potential possibility to reach the “$\Theta ^{+}$” energy region with a higher kaon momentum $k_{\rm lab} \sim 1 \text{ GeV} / c$. Assuming that the full decay width of the “$\Theta ^{+}$” is around $0.5 \text{ MeV}$, we predict that the magnitude of the peak corresponding to the “$\Theta^+$” is around a few hundred $\mu \text{b}$ to $1 \text{ mb}$ with the momentum of the kaon beam $k_{\rm lab} \approx 0.40 \text{ GeV} / c$ while it is around $\lesssim 1 ~\mu \text{b}$ with $k_{\rm lab} \approx 0.85 \text{ GeV} / c$. Thus, the “$\Theta^+$” peak is more likely to be seen at $k_{\mathrm{lab}} \approx 0.40 \text{ GeV} / c$ than at $k_{\mathrm{lab}} \approx 0.85 \text{ GeV} / c$.
A Study of Microcirculation in the Foot of Dark‐Skin Africans and Light‐Skin Caucasians.
Authors: Akambase Jonas Atulebire , Kozlov Valentine Ivanovich , Akambase Joseph Atule , Poku Frank Adusei , Gurova Olga Aleksandrovna , Kokoreva Tatyana Valerevna 
Published: April 2020

The aim of this research is to study the racial differences in the microcirculation of the foot among dark‐skin Africans (DSA – 20 males) and light‐skin Caucasians (LSC – 20 males) using laser doppler flowmetry (LDF). The participants were all males between the ages of 18 to 20. The average values of the microcirculation parameters (PM) in the subjects with high (DSA) and low (LSC) degree of skin pigmentation on the first toe of the foot were [Plantar surface: Blood perfusion – 6.8±0.8 perfusion units (PU), Flux – 1.8±0.4 perfusion units (PU), Fluxmotion index – 1.3±0.19; Dorsal surface: Blood perfusion – 3.3±0.6 perfusion unit (PU), Flux – 1.8±0.4 perfusion units, Fluxmotion index – 0.6±0.1] and [Plantar surface: Blood perfusion – 7.2±0.7 perfusion units (PU), Flux – 1.9±0.2 perfusion units (PU), Fluxmotion index – 1.4±0.16; Dorsal surface: Blood perfusion – 4.7±0.6 perfusion unit (PU), Flux – 1.5±0.1 perfusion units, Fluxmotion index – 1.1±0.1], respectively. Our research reported no significant difference in the microcirculation parameters on the plantar surface of the first toe in both DSA and LSC. This indicates that both groups at the level of the microcirculatory system triggered the same type of regulatory mechanisms. On the dorsal surface of the first toe, where there is significant difference in melanin content, we recorded significant differences in the parameters of microcirculation. Thus, blood perfusion in LSC was 30% higher than in DSA. However, on the dorsal surface of the first toe, flux was 87% higher in those surveyed with less melanin (LSC) than in those surveyed with more melanin (DSA). The average Fluxmotion index on the dorsal surface of the first toe was 45% higher in those with less melanin than in those with more melanin. In conclusion, we can hypothesize that the high content of melanin in the skin shields the probing signal, leading to a decrease in Laser Doppler Flowmetry metrics.Support or Funding InformationResearch supported by the Department of Human Anatomy at RUDN University, Moscow, RussiaMeasurement of microcirculation in the foot of a light‐skin Caucasian using Laser Doppler Flowmetry (Lakk‐OP).Figure 1Measurement of microcirculation in the foot of a dark‐skin African using Laser Doppler Flowmetry (Lakk‐OP).Figure 2
Keratin 19 Promotes Cell Cycle by Regulating GSK3B‐Cyclin D3 Pathway in Breast Cancer Cells
Authors: Sharma Pooja , Chung Byung Min (Justin) 
Published: April 2020

Keratin 19 (K19) is a cytoskeletal protein that is utilized as a diagnostic and prognostic marker in select human carcinomas. Despite the positive correlation between higher expression of K19 in tumor and worse patient survival, the role of K19 in breast cancer remains unclear. We previously used K19 knockout (KO) MCF7 breast cancer cells to identify that K19 is required for proper cell cycle progression. Specifically, K19 regulated expression of D‐type cyclins (cyclin D1 and cyclin D3) which promote the G1/S transition. We found that K19 interacts with cyclin D3, and a loss of K19 resulted in decreased protein stability of cyclin D3. To better understand how K19 prevents cyclin D3 degradation, we examined the cyclic adenosine 3′,5′‐monophosphate (cAMP) signaling pathway where cAMP induction causes glycogen synthase kinase GSK3B to promote cyclin D3 degradation. When cells were treated with forskolin to elevate intracellular cAMP level, cyclin D3 turnover was increased in the absence of K19, suggesting that K19 inhibits GSK3B from degrading cyclin D3. Indeed, inhibiting GSK3B activity using LiCl and GSK3B expression via siRNA rescued the cyclin D3 level in K19 KO cells. These data suggest that K19 plays an important role in GSK3B‐mediated cyclin D3 degradation. By using molecular biology tools and biochemical approaches, we are in the process of characterizing specifics of K19‐dependent regulation of cyclin D3 stability including identification of GSK3B and K19 domains responsible for their interaction. We aim to provide evidences for a novel mechanism by which a cytoskeletal protein stabilizes a cell cycle regulator and promotes proper cell cycle progression.Schematic model for the role of K19 in regulation of GSK3B‐mediated cyclin D3 degradation.(a) K19 serve as scaffold for both for GSK3B and cyclin D3, preventing GSK3B to access cyclin D3.(b) In absence of K19, GSK3B has a full access to cyclin D3 for degradation.Figure 1
Cell‐assembled Extracellular Matrix (CAM) as a Biomaterial for Building Vascular Grafts
Authors: L’Heureux Nicolas 
Published: April 2020

Sheets of human CAM, produced by cultured cells in vitro, have been rolled to produce completely biological tissue‐engineered vascular grafts (TEVGs). Despite a rapid and successful progression to clinical trials, this approach remains complex. Our novel strategy is to produce TEVG with yarns produced from CAM sheets using a textile‐based approach. This strategy is faster, more reliable, more versatile and more easily automated. CAM sheets can be cut in ribbons of various widths, which can also be twisted to make threads. Yarn (ribbons or threads) can be processed in different ways: devitalized (freezing/dehydration/freezing/rehydration cycle), decellularized (8 mM CHAPS, 1 M NaCl, 25 mM EDTA, 0.12 M NaOH) and/or gamma‐sterilized (25 kGy). We have evaluated the effect of these processing steps on the histological and mechanical properties of the yarn. We have also assessed the impact of these steps on the remodeling (histological and mechanical) of the yarn after subcutaneous implantation in a nude rat for up to 6 months. Results showed that the human CAM‐based yarn creates very little inflammatory reaction and is essentially only mildly remodeled by the host response. However, some processing steps do lead to increased reactivity and decreased performance in vivo. Woven vessels display remarkable mechanical properties without the need for synthetic scaffolding or chemical crosslinking. An allogeneic large animal model is in development to address remodeling in an allogeneic setting in an immunologically competent recipient. Because it can be produced according to specific mechanical and physical specifications, and because it can be used with standard textile assembly methods, the CAM can truly be called a “bio‐material”. More importantly, because of its native‐like structure, this material has the potential to be accepted by the host without significant immune responses and to support a long‐term “physiological” remodeling process.Support or Funding InformationNational Institute of Health Small Business Innovation Research (SBIR) program (HL105010), the Ministère de la Recherche et de l’Enseignement Supérieur, the Chaire Senior de l’Initiative d’Excellence de l’Université de Bordeaux (IdEx Bordeaux), the Agence Nationale de la Recherche (ANR‐16‐CE18‐0024‐01), the Région Nouvelle Aquitaine (2016‐1R30402), and the European Research Council (Advanced Grant # 785908).A thread and a woven vessel made from human CAM.Figure 1
Not just for patterning anymore: Hox genes function in skeletal stem cells throughout life
Authors: Wellik Deneen M. , Song Jane Y. 
Published: April 2020

Hox genes play fundamental and highly conserved roles in vertebrates patterning of the axial and limb skeleton during embryonic development. We have shown that Hox genes continue to be regionally‐expressed through postnatal development and adult life. Hox‐expressing cells are observed only within a subset of the stromal cells defined as progenitor‐enriched mesenchymal stem/stromal cells. Using a Hoxa11‐CreERT2 allele, we show that Hox‐expressing cells lineage label into chondrocytes, osteoblasts, osteocytes and adipose cells at all stages of life, during growth, homeostasis and in response to injury. Further, lineage labeling from any stage, including during embryogenesis, results in the permanent labeling of a self‐renewing skeletal stem cell population, confirming that Hox‐expressing cells are bona fide skeletal stem cells throughout the life of the animal. However, whether Hox genes continue to function after embryonic stages has never been demonstrated. Embryonic patterning roles and perinatal lethality has prevented this question from being addressed. Using our newly generated Hoxd11 conditional allele and temporally restricted deletion only at adult stages, we show that Hox genes continue to play critical roles in skeletal maintenance and repair throughout life. Loss of Hox function leads to dramatic and progressive perturbations in skeletal integrity with loss of collagen organization, and defective osteocyte and osteoblast formation. Loss of Hox function does not lead to loss of the skeletal stem cell population, but rather an inability of early‐stage progenitors to properly differentiate into functional chondrocytes and osteoblasts. How Hox transcription factors direct these differentiation processes throughout the life of the animal is the focus of current investigations.Support or Funding InformationNIH NIAMS R01 AR 061402 and R61 AR073523Hox Skeletal LineageFigure 1
Blood level of alpha‐1 antitrypsin in the course of acute myocardial infarction patients: A possible clinical significance
Authors: Khatib Said Y. , AlGhamdi Abdulaziz , Adnan Mohammed H. , AlSaeed Asim H. , AlAhmadi Ali H. , Abdelrahman Amr 
Published: April 2020

IntroductionWide experimental evidence has proved Alpha 1 antitrypsin, which is released from the liver, to protect lung tissue from damage during inflammation. There is experimental evidence also suggests such protection is extended to myocardial tissues during myocardial ischemia/infarction.ObjectiveThe aim of the study was to determine the levels and the time course of A1AT in the plasma of myocardial infarction patients over 96 hours and compare it with healthy subject as control.MethodsBlood samples were collected from patients (n=40) arriving at emergency department at 1, 4, 24, 48 and 96 hrs after diagnosis and admission to King Salman Cardiac Center, in King Fahad Medical City in Riyadh, Saudi Arabia. Blood samples were collected in purple top tubes containing EDTA to prevent blood coagulation. Blood plasma was separated by centrifugation with in 3 hrs of collection. Plasma was decanted and stored until analyzed. Alpha 1 antitrypsin was determined in all patients’ blood samples using human Eliza kits( abcam USA). In addition control blood samples were collected from 20 healthy individuals.ResultsA1AT levels were significantly less in MI patients (1025±77 ug/ml at 96 hrs, P<001) compared to (1655±128 ug/ml) (mean ± SEM) in controls. It was very interesting to find those patients win whom the decrease in A1AT was >50 % of control values, they did not survive and passed away (deceased) (673+71 ug/ml, n=3). Also the levels of A1AT after an MI attack was comparable and not significant in hypertensive compared to non‐hypertensive or in STEMI and Non‐STEMI patients but was significantly (P<0.03) higher in non‐smokers (1457+163, n=27) compared to smokers (1153±155, n=10).ConclusionThe plasma level of A1AT is suggested to be important in providing some protection to myocardial cells during an MI attack. A1AT levels seem to drop shortly following an MI attack. The drop in the level is larger in smokers. In those patients in whom the level of A1AT drops to more about 50 % of normal values they are less likely to survive the MI attack. More studies are needed to confirm the above findings.Support or Funding InformationWe acknowledge the financial support from the research center at King Fahad Medical City, Riyadh, Saudi ArabiaFigure 1Figure 2
Activation of lysophosphatidic acid receptors regulate differentiation of hematopoietic stem cells in myeloid lineage
Authors: Lin Kuan-Hung , Chiang Jui-Chung , Yao Chao-Ling , Lee Hsinyu 
Published: April 2020

Lysophosphatidic acid (LPA) is a membrane‐derived lysophospholipid that exists in plasma and platelet. It exerts its functions through activating various LPA receptors (LPARs), which belong to the family of G‐protein coupled receptors (GPCRs). Activation of LPARs has been implicated for important roles during stem cell differentiation. However, how LPA affects human hematopoietic stem cell (HSC) differentiation and underlying lineages remains elusive. In our previous studies, we have demonstrated that activation of LPA receptor 3 (LPA3) promotes erythropoiesis in human HSC and zebrafish. In the present study, pharmacological approach was adopted to further elucidate the functions of LPA receptors during red blood cell (RBC) differentiation. Treatment of LPA2 agonist GRI977143 suppressed erythropoiesis, whereas activation of LPA3 by 2S‐OMPT promoted RBC differentiation both in vitro and in vivo. Furthermore, our results demonstrated a negative role of LPA3 during platelet differentiation both in vitro and in vivo. Moreover, the expression pattern of LPA receptors correlated to the hematopoietic transcriptional factors GATA1 and GATA2 in different stages of myeloid progenitors. In addition, manipulation of these GATA factors affected the expression level of LPA2 and LPA3. By luciferase assays, we demonstrated that the promoter region of LPAR2 and LPAR3 were regulated by these GATA factors. Mutation of identified GATA‐Binding‐Sites (GBS) in the region abrogate the luciferase activities, suggested that LPA2and LPA3 are regulated by GATA factors. In addition, chromatin immunoprecipitation assays confirmed the directly interaction between GATA factors and promoter region of LPARs. Taken together, our results suggested that the expression level of LPA2 and LPA3, which may be determined by GATA factors, is a regulatory switch for the lineage commitment in myeloid progenitors. The pharmacological activation of LPA receptor subtypes represents a novel strategyfor regulating erythropoiesis.LPA receptors are expressed at different stages during myeloid differentiation. GATA switch, which is an important molecular switch in hematopoiesis, cause the difference of expressional pattern of LPA receptor in different lineage.Figure 1
Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation of Lornoxicam to Develop Personalized Drug Optimization regarding to CYP2C9 Genetic Polymorphism
Authors: CHO CHANGKEUN , LIM CHANGWOO , OH KYUNGYUL , SHIN HYOBIN , JUNG EUIHYUN , LEE CHOONGMIN , BYEON JIYOUNG , LEE SEOKYONG 
Published: April 2020

Lornoxicam is a non‐steroidal anti‐inflammatory drug (NSAID) of oxicam class that has analgesic and anti‐inflammatory effects. Lornoxicam decreases various prostaglandin synthesis via inhibition of cyclo‐oxygenase (COX). Lornoxicam is primarily metabolized to 5’‐hydroxy lornoxicam through cytochrome P450 2C9 (CYP2C9) enzyme. Polymorphism of the CYP2C9 enzyme, e.g., CYP2C9*3 and CYP2C9*13, are associated with decreased activity of CYP2C9. Consequently, the difference of CYP2C9 activity by polymorphism triggers diverse drug concentration and response despite equal dose administration. For individual drug optimization, we develop a predictable pharmacokinetic model based on physiological characteristics related to CYP2C9 activity. In our research, 13 healthy Korean male subjects were included in the pharmacokinetic study of lornoxicam. All subjects were divided into three different CYP2C9*1/*1, CYP2C9*1/*3, and CYP2C9*1/*13 groups. 8mg dose of lornoxicam was administered to individual subjects. After administration, venous blood samples were collected and analyzed by HPLC‐UV method. Pharmacokinetic parameter values were predicted using PBPK software, PK‐Sim® 8. Vmax and Km parameter values were adjusted to reflect a difference in CYP2C9 activity based on in vitro CYP2C9 kinetic studies of lornoxicam. Simulated pharmacokinetic data were compared to our clinical data for the development and verification of the lornoxicam model and assessed for validity using a 99.998% confidence interval and two‐fold error criteria. In our clinical trial, pharmacokinetic parameters, e.g., AUCinf, Cmax, Tmax, and half‐life, were considerably changed in CYP2C9*1/*3 and CYP2C9*1/*13 groups compared to CYP2C9*1/*1 group. Firstly, AUCinf, Cmax, Tmax, and half‐life values are 2730.2, 655.7, 2.2, 2.74 in CYP2C9*1/*1 group, secondly 5464, 815.3, 1.6, 4.99 in CYP2C9*1/*3, finally 5315, 935.1, 2.3, 5.19 in CYP2C9*1/*13 respectively. For predicted data for this is as follows: 3099.2, 640.9, 1.5, 2.9 in CYP2C9*1/*1, 5312.5, 748.3, 1.6, 5.2 in CYP2C9*1/*3, 5551, 782.7, 1.6, 4.17 in CYP2C9*1/*13. Based on these result, simulated values were within suitable assessment for model development. Values for verification conducted simulation in Chinese ethnic also were fit in the assessment. Therefore, the PBPK model of lornoxicam was confirmed development successfully. Unfortunately, we could not find pharmacokinetic profiles in the ethnic group except the Chinese. So, we verified the PBPK model by conducting simulation only in Chinese ethnic. Because of this limitation, we expect to be able to develop a more validated model through the verification of various ethnic in further studies.PBPK model of lornoxicam in CYP2C9*1/*1 genotypes.Figure 1PBPK model of lornoxicam in CYP2C9*1/*3 genotypes. Km and Vmax values were scaledFigure 2
Insights from 20 Years of the Molecule of the Month and PDB‐101
Authors: Zardecki Christine , Berman Helen M. , Burley Stephen K. , Goodsell David S. 
Published: April 2020

For 20 years, Molecule of the Month articles have highlighted the functional stories of the 3D structures found in the Protein Data Bank (PDB). The PDB is the primary archive of atomic structures of biological molecules, currently providing open access to more than 150,000 structures studied by researchers around the world. The wealth of knowledge embodied in this resource is remarkable, with structures that allow exploration of nearly any biomolecular topic, from basic science of genetic mechanisms, to the mechanisms of photosynthesis, to central biomedical topics like cancer therapy, and the fight against infectious disease. The central motivation behind the Molecule of the Month is to provide a user‐friendly introduction to this rich body of data, charting a path for users to get started with finding and exploring the many available structures.Molecule of the Month articles and images are freely available at the education portal PDB‐101 (http://pdb101.rcsb.org/), offering an ongoing resource for molecular biology educators and students around the world. Features are used to develop additional PDB‐101 materials, from posters to interactive animations.PDB‐101 usage, trends, and impact are described.Support or Funding InformationPDB‐101 and the RCSB PDB are funded by the National Science Foundation (DBI‐1832184), the US Department of Energy (DE‐SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.Image of Measles Virus Proteins from the March 2019 Molecule of the Month. The article has been viewed more than 13,000 times to date.Figure 1
Synthetic Anatomy: arts based learning to explore the possibilities of form and function
Authors: Wingate Richard James , Williams Darren , Sagoo Mandeep , Wilson Leigh Jane 
Published: April 2020

We have developed an interdisciplinary module for students in their second year of undergraduate education which imports, into anatomy, the techniques and perspectives of success & assessment practices of art school. The module brings together biomedical engineers and anatomy students to speculate on and design imagined bodies that probe the boundaries of clinical, evolutionary and developmental anatomy. The students produce a technical and critical reflective portfolio and participate in a small, collaborative group project to 3D print imagined anatomy. Teaching and assessment emphasise the freedom to take risks and learn from failed avenues of investigation. A key emphasis is on structural exploration and experimentation coupled with reflection rather than literature review or writing per se. Technical teaching on 3D prints is accompanied by class workshops that explore the dimensions of documentation, the language of visual presentation and value of reflection. Workshops are led by visiting artists and we have applied the technique of the “crit”, which is a widely used form of group reflection in art and architecture schools, as a means of delivering a high degree of rigour into the science classroom. Projects are completed by mixed teams of engineering and anatomy students. There is no exam but a final “show” of projects is assessed on outcomes that are in part designed by the class at the start of the module. For learning outcomes and assessment, in addition to applying a technical and cognitive taxonomy we have introduced elements of Bloom’s less well‐known, affective taxonomy to authentically assess student commitment, pride, value and engagement. We have found that students are highly satisfied with their learning experience regardless of assessed outcome and show an extraordinary commitment to the course. Our emerging conclusion is that by paying attention to the material craft of science and exploring and reflecting on its community of practice, we can design and deliver modules that are a more valid preparation for higher level research both in terms of skills and passion for this subject.Support or Funding InformationKings College London Cultural InstituteStudent project work from the Synthetic Anatomy moduleFigure 1