bluuebunny/crossref_metadata_2025 huggingface dataset:
Physicians’ strategies for using family history data: having the data is not the same as using the data
Authors: Taber Peter , Ghani Parveen , Schiffman Joshua D , Kohlmann Wendy , Hess Rachel , Chidambaram Valli , Kawamoto Kensaku , Waller Rosalie G , Borbolla Damian , Del Fiol Guilherme , Weir Charlene
Published: October 2020

Objective

To identify needs in a clinical decision support tool development by exploring how primary care providers currently collect and use family health history (FHH).

Design

Survey questionnaires and semi-structured interviews were administered to a mix of primary and specialty care clinicians within the University of Utah Health system (40 surveys, 12 interviews).

Results

Three key themes emerged regarding providers’ collection and use of FHH: (1) Strategies for collecting FHH vary by level of effort; (2) Documentation practices extend beyond the electronic health record’s dedicated FHH module; and (3) Providers desire feedback from genetic services consultation and are uncertain how to refer patients to genetic services.

Conclusion

Study findings highlight the varying degrees of engagement that providers have with collecting FHH. Improving the integration of FHH into workflow, and providing decision support, as well as links and tools to help providers better utilize genetic counseling may improve patient care.
The Evolution of Amitraz and Its Metabolic Degradation Products in Human Blood over 90 Days for Use in Forensic Determination
Authors: Chen Yanmin , Zhao Qingbiao , Guo Hao
Published: October 2020

Amitraz is a pesticide that is often involved in poisoning cases. In determination process of poisoning cases, a problem often encountered is that when the evidence samples were examined, the poison had already decomposed, thus posing significant difficulty for obtaining evidences. In this study, we qualitatively and quantitatively tracked the metabolic degradation products of amitraz and ascertained that the metabolic degradation products were N,N'-bisdimethylphenylformamidine, N'-(2,4-dimethylphenyl)-N-methylformamidine (DMPF), 2,4-dimethylformamidine (DMF) and 2,4-dimethylaniline (DMA). It was found that although amitraz decomposed rather rapidly, the metabolic degradation products of amitraz persisted for quite a long time. This study demonstrates that forensic evidence in poisoning cases of amitraz can be obtained by the determination of DMPF, DMF and DMA. This study can provide insights on obtaining forensic evidences in poisoning cases.
Development of an Analytical Method for Quantitation of 2,2ʹ-Dimorpholinodiethyl Ether (DMDEE) in Rat Plasma, Amniotic Fluid and Fetal Homogenate by UPLC–MS-MS for Determination of Gestational and Lactational Transfer in Rats
Authors: Silinski Melanie A Rehder , Uenoyama Teruyo , Fernando Reshan A , Robinson Veronica G , Roberts Georgia , Cunny Helen , Hubbard Troy , Waidyanatha Suramya
Published: October 2020

2,2ʹ-Dimorpholinodiethyl ether (DMDEE) is a specialty amine catalyst used in the production of flexible foams, adhesives and coatings. The potential for occupational exposure to DMDEE is high, but toxicity data are very limited. The objective of this work was to develop a method to quantitate DMDEE in biological matrices to assess gestational and lactational transfer of DMDEE in rats following exposure of dams The method used protein precipitation, followed by removal of phospholipids and analysis of supernatant by ultra-performance liquid chromatography-tandem mass spectrometry. Rat fetuses were homogenized in water prior to protein precipitation and delipidation procedures. The method was evaluated in male Sprague Dawley rat plasma over the concentration range 5 to 1000 ng/mL. The method was linear (r ≥ 0.99), accurate (mean relative error (RE) ≤ ±11.9%) and precise (relative standard deviation (RSD) ≤ 2.7%). The mean absolute recovery was 106%. The limit of detection was 0.262 ng/mL. Standards as high as ∼100,000 ng/mL could be successfully diluted into the calibration range (mean %RE = −14.9; %RSD = 0.5). The method was evaluated in Sprague Dawley rat dam plasma, post-natal day 4 pup plasma, gestational day (GD) 18 amniotic fluid and fetal homogenate (mean %RE ≤ ±11.9; %RSD ≤ 2.3). Concentrations of DMDEE in rat dam plasma, amniotic fluid and fetal homogenate stored for at least 29 days and in pup plasma for at least 18 days at −80°C were within 87.7 to 99.5% of Day 0 concentrations, demonstrating that DMDEE is stable in these matrices. The method was used to quantitate DMDEE in rat plasma, amniotic fluid and fetus samples from a dose range finding toxicology study in which dams were dosed via gavage with DMDEE from GD 6 at doses of 0 (control), 62.5 and 250 mg/kg/day. DMDEE concentration increased with the dose in all matrices examined. The concentration in GD 18 fetuses was almost 2-fold higher than GD 18 dams demonstrating gestational transfer of DMDEE. However, the concentration in post-natal day 4 pup plasma was more than an order of magnitude lower than corresponding dam plasma suggesting less potential for transfer of DMDEE from dams to pups via lactation. There was no significant difference in concentration for male and female pup plasma.
Shocked Though the Heart and YouTube Is to Blame—The Rising Incidence of Accidental Trans-cardiac Electrocution From Do-It-Yourself Fractal Wood Art, and a Call to Action
Authors: Russo Rachel , Pumiglia Luke , Bettencourt Amanda P , Roman Jordan , Vercruysse Gary A
Published: October 2020

In the past year, we have become aware of a new mechanism of severe electrical injury ascribed to fractal wood art. This type of art has become increasingly popular and deadly due to exponential popularity in the use of Youtube type video teaching. This manuscript is one of the initial descriptions of the injury mode, presentation, treatment, and outcomes from four such cases treated at our institution. Additionally, we elicit a call for action in preventing further similar unnecessary injuries and deaths.
The Larvicidal and Adulticidal Effects of Selected Plant Essential Oil Constituents on Greater Wax Moths
Authors: Sohail Mubasshir , Aqueel Muhammad Anjum , Dai Pingli , Ellis James D
Published: October 2020

Some plant essential oil constituents, such as monoterpenoids and phenylpropanoids, are promising insecticides in some situations and for certain insect pests. They vary in their toxicity, depending on the target insect. Moths (Lepidoptera) appear susceptible to these compounds, making them of promise for use against greater wax moths (Galleria mellonella Fabricius, (Lepidoptera: Pyrallidae), GWM), an important pest of western honey bee (Apis mellifera Linnaeus. (Hymenoptera: Apidae)) colonies. We determined the LC50 for GWM larvae or LD50 for GWM adults of select compounds (thymol, carvacrol, (S)-(+)-carvone, estragole, citral, linalool, (S)-(−)-limonene, and γ-terpinene). Concentrations between 8 and 2,266 µg/cm3 were mixed into the diets of GWM larvae and doses ranging between 0.08 and 70.3 mg per adult were applied topically to the abdomens of GWM adults. Lethal concentrations and doses were calculated after of 72 h of exposure. All eight compounds showed insecticidal activity against all tested stages of GWMs. Thymol (LC50 µg/cm3 (95% CI) = 21 [9–56], carvacrol = 46 [26–79], citral = 63 [30–134], and carvone = 76 [33–201]) had the highest toxicity toward GWM larvae. The hydrocarbons limonene (296 [231–377]), estragole (466 [354–611]), and γ-terpinene (729 [630–857]) had the lowest toxicity toward GWM larvae. Thymol had the highest toxicity towards GWM adults (LD50 (CI) = 0.5 [0.4–0.8] mg/adult). However, carvacrol (11.6 [10.1–13.6]), linalool (12.9 [9.3–17.8]), and limonene (15.8 [13.1–19.2]) were less toxic to GWM larvae. Our data show that select plant essential oil constituents are promising controls of GWM.
Modeling Time-Varying Tail Dependence, with Application to Systemic Risk Forecasting
Authors: Hoga Yannick
Published: October 2020

Empirical evidence for multivariate stock suggests that there are changes from asymptotic independence to asymptotic dependence and vice versa. Under asymptotic independence, the probability of joint extremes vanishes, whereas under asymptotic dependence, this probability remains positive. In this paper, we propose a dynamic model for bivariate extremes that allows for smooth transitions between regimes of asymptotic independence and asymptotic dependence. In doing so, we ignore the bulk of the distribution and only model the joint tail of interest. We propose a maximum-likelihood estimator for the model parameters and demonstrate its accuracy in simulations. An empirical application to losses on the CAC 40 and DAX 30 illustrates that our model provides a detailed description of changes in the extremal dependence structure. Furthermore, we show that our model issues adequate forecasts of systemic risk, as measured by CoVaR. Finally, we find some evidence that our CoVaR forecasts outperform those of a benchmark dynamic t-copula model.returns
Immunocompromised Seroprevalence and Course of Illness of SARS-CoV-2 in One Pediatric Quaternary Care Center
Authors: Freeman Megan Culler , Rapsinski Glenn J , Zilla Megan L , Wheeler Sarah E
Published: October 2020

Background

The burden of coronavirus disease 2019 (COVID-19) is poorly understood in pediatric patients due to frequent asymptomatic and mild presentations. Additionally, the disease prevalence in pediatric immunocompromised patients remains unknown.

Methods

This cross-sectional study tested convenience samples from pediatric patients who had clinically indicated lab work collected and an immunocompromising condition, including oncologic diagnoses, solid organ transplant (SOT), bone marrow transplant, primary immunodeficiency, and rheumatologic conditions or inflammatory bowel disease on systemic immunosuppression, for the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results

We tested sera from 485 children and observed SARS-CoV-2 seroprevalence of 1.0% (Confidence Interval [CI] 95%: 0.3%–2.4%). Two patients were positive by nasopharyngeal (NP) swab Reverse transcriptase polymerase chain reaction (RT-PCR), but only 1 seroconverted. Patients with oncologic diagnoses or SOT were most likely to be tested for COVID-19 when presenting with respiratory illness as compared with other groups.

Conclusions

Seroprevalence of antibodies to SARS-CoV-2 in immunocompromised children was similar to that of an immunocompetent pediatric population (0.6%, CI 95%: 0.3%–1.1%), suggesting an adequate antibody response. However, none of the patients who tested positive for antibodies or via NP RT-PCR had more than a mild illness course and 2 patients did not have any reported illness, suggesting that SARS-CoV-2 may not cause a worse clinical outcome in immunosuppressed children, in contrast to immunocompromised adults.
Inter-State Arbitration
Authors: Veeder V. V.
Published: October 2020

This chapter explores inter-state arbitration, which is largely influenced by two different traditions, drawn from diplomacy and commerce under public and private international law respectively. The recent history of state–state and also, in part, of investor–state arbitration is the history of the Permanent Court of Arbitration (PCA). As intended by the two Hague Conferences more than a century ago, arbitrations under treaties are still marked by the necessity for the parties’ consent, including a state’s limitation as to the categories of dispute referable to arbitration; a neutral appointing or administering authority; a settled procedure subject to party autonomy; the parties’ involvement in the appointment of the tribunal; and the absence of any appeal from an award for an error of law or fact. For inter-state arbitration and (notwithstanding the ICSID and New York Conventions) investor–state arbitration also, the recognition of the award by the losing party is usually made voluntarily. It is the parties’ arbitration, the award is the product of their consent and, accordingly, the award has a moral binding force for the parties often absent from non-consensual mechanisms.
International Arbitration
Authors: Muir-Watt Horatia
Published: October 2020

This chapter discusses international arbitration as a crucial part of the legal framework that has progressively enabled the contemporary neo-liberal orientation of global governance. As such, it presents the perspective of critical private international law. If the latter discipline constitutes a significant viewpoint in this respect, it is precisely because it provided the foundational legal tools and discourse by means of which international arbitration attained such astounding success as a cornerstone of cross-border trade and investment regimes. The specific contention here is that in sanctifying freedom of contract to an unprecedented degree, including unrestricted party choice of law and forum, it has deactivated the regulatory constraints to which private actors are subject in a domestic setting and, involuntarily thereby, sealed the ‘loss of control’ by nation-states of various crucial aspects of the global economy. The chapter then explores the grievances generally addressed to arbitration as emblematic of the privatization of global governance, understood alternatively as a confiscation of power in the hands of a happy few individuals or as the subordination of public concerns to private interests.
Cultural Heritage and International Humanitarian Law
Authors: O’Keefe Roger
Published: October 2020

The beginnings of international cultural heritage law can be traced to rules on the treatment of cultural sites and objects in war—that is, to international humanitarian law, the branch of public international law dedicated to the regulation of the conduct of what we now refer to as armed conflict. Today there exists a detailed body of conventional and customary international humanitarian law designed to protect tangible cultural heritage, both immovable and movable, from destruction and damage and from all forms of misappropriation in the course of international and non-international armed conflict. The chapter provides an account and analysis of these rules.
Intentional Destruction of Cultural Heritage
Authors: Lenzerini Federico
Published: October 2020

This chapter focuses on the practice of deliberate destruction of cultural heritage, which has represented a plague accompanying humanity throughout all phases of its history and has involved many different human communities either as perpetrators or victims. In most instances of deliberate destruction of cultural heritage, the target of perpetrators is not the heritage in itself but, rather, the communities and persons for whom the heritage is of special significance. This reveals a clear discriminatory and persecutory intent against the targeted cultural groups, or even against the international community as a whole. As such, intentional destruction of cultural heritage, in addition of being qualified as a war crime, is actually to be considered as a crime against humanity. Furthermore, it also produces notable implications in terms of human rights protection. Protection of cultural heritage against destruction is today a moral and legal imperative representing one of the priorities of the international community. In this respect, two rules of customary international law exist prohibiting intentional destruction of cultural heritage in time of war and in peacetime.
International Criminal Law and the Protection of Cultural Heritage
Authors: Frulli Micaela
Published: October 2020

This chapter looks at how international criminal law has become a crucial tool to foster the protection of cultural heritage. On the normative level, the main developments consisted in the introduction of rules criminalizing acts against cultural property in binding treaties dealing with the protection of cultural property in times of armed conflict. Then, international criminal tribunals (ICTs) paved the way for implementing individual criminal responsibility. Three different and partially divergent approaches have characterized the criminalization of acts against cultural property. The first two—civilian use and cultural value—emerged in different moments and had a strong impact on the drafting of rules criminalizing acts against cultural property in times of armed conflict. The third one, the human dimension approach, developed from the jurisprudence of ICTs and characterizes both the qualification of acts against cultural property as crimes against humanity and their role in proving the mental element of genocide.
Cultural Heritage and Disasters
Authors: Bartolini Giulio
Published: October 2020

This chapter addresses the main legal, institutional, and operative challenges to the protection of cultural and natural heritage along the temporal phases of a disaster. Recent disasters have demonstrated how cultural and natural heritage can suffer significantly from calamitous events. Despite the frequency and magnitude of disasters, the international legal framework has paid little attention to legal challenges posed by the protection of cultural and natural heritage in disaster settings, a situation compounded by the absence of in-depth scholarly analysis. The chapter then examines how international cultural heritage law (ICHL) has so far addressed this topic, also in light of the increasing cross-fertilization with inputs provided by an emerging branch, namely international disaster law (IDL). It also highlights the so-called ‘cycles of a disaster’, commonly arranged along the phases of mitigation and preparedness, relief and recovery.
Grasping the Nettle of Illicit Export, Import, and Transfer of Ownership of Cultural Objects
Authors: Shyllon Folarin
Published: October 2020

This chapter studies the illegal import, export, and transfer of ownership of movable cultural objects. Illicit trafficking in cultural property has been going on for decades. The exponential increase in the 1960s raised concern, and this coincided with the wave of independence being granted to several African countries and Asian countries. Codes of ethics and international treaties are two important elements of the current, major international effort to prevent the damage caused by the illegal trade in cultural objects that continue to blossom. Another key element is increased globalization of cultural heritage law. Finally, the creation of national cultural heritage police units by all countries is very important.
World Cultural Heritage
Authors: Francioni Francesco
Published: October 2020

The concept of ‘world heritage’ was legally codified by the 1972 UNESCO Convention Concerning the Protection of the World Cultural and Natural Heritage (WHC). This convention occupies a special position in the ever-expanding body of international cultural heritage law. This is for three fundamental reasons. First, with its 193 States Parties, it is a truly universal treaty in force for the protection of cultural heritage. Second, it represents a major innovation by its unprecedented approach that brings together cultural properties and natural sites of exceptional importance, both subject to the same system of international cooperation for their identification, delineation, and protection. Third, this convention has contributed to the reconceptualization of ‘cultural property’, paving the way for its dynamic evolution into the more comprehensive concept of ‘cultural heritage’, understood as the inherited patrimony of culture—inclusive of the intangible heritage and living culture of relevant human communities.
Cultural Heritage and Human Rights
Authors: Donders Yvonne
Published: October 2020

This chapter studies the link between cultural heritage and human rights, considering treaties on cultural heritage and treaties on human rights. Cultural heritage is increasingly seen in international law not merely as an important product or value in itself but also in relation to the construction and preservation of cultural identities and, thereby, of the dignity of peoples, communities, and individuals. This has enhanced the human rights dimension of cultural heritage, in particular for minorities and Indigenous peoples. Several human rights—including the rights to take part in cultural life, to enjoy culture, and to freedom of expression and assembly—confirm that protection and promotion of cultural heritage is part of human rights. Strengthening and maintaining the link between cultural heritage and human rights reaffirms cultural heritage as a value for human dignity and reflects a shift from a sovereignty and State-centric approach to a people’s and peoples’ approach.
Cultural Heritage in International Investment Law
Authors: Vadi Valentina
Published: October 2020

This chapter evaluates whether the existing legal framework adequately protect cultural heritage vis-à-vis the economic interests of foreign investors. It aims to address this question by examining recent arbitrations and proposing three principal legal tools to foster a better balance between economic and cultural interests in international investment law and arbitration. This recent jurisprudence highlights that arbitral tribunals are increasingly providing consideration to cultural concerns. Yet, the interplay between the protection of cultural heritage and the promotion of foreign direct investment in international investment law and arbitration continues to pose two main problems: one ontological, concerning the essence of international investment law and international law more generally; and one epistemological, concerning the mandate of arbitral tribunals. The chapter then considers three principal avenues that can facilitate a better balance between the public and private interests in international investment law: a ‘treaty-driven approach’; a ‘judicially driven approach’; and counterclaims.
Cultural Heritage and State Succession
Authors: Jakubowski Andrzej
Published: October 2020

This chapter describes the relationship between the evolving international law regime for the protection of cultural heritage and the theory and practice of State succession. State succession in respect of cultural heritage has usually been associated with the allocation and division of movable cultural treasures following territorial transfers. Hence, much of the doctrinal effort has focused on the principles and criteria governing the passing of State cultural property and attempted to respond to the topical question of to whom cultural property belongs. The chapter then looks at the codified sources of the law on State succession. It also examines the consequences of State succession relating to distinct pre-existing legal situations: State archives and property; international cultural heritage obligations arising from treaties and customary international law; and international responsibility for cultural heritage wrongs committed prior to the date of succession.
Remedies
Authors: Novic Elisa
Published: October 2020

This chapter explores the remedies for violations of international cultural heritage law. Notwithstanding the availability of justice mechanisms, the question of repairing attacks against culture poses a set of philosophical and practical questions—namely, the definition of victimhood and adequate measures of reparation. Here, international law provides a relatively harmonized account of reparation, based on a restorative approach. As such, reparation should be adequate and proportionate to the harm suffered and may therefore consist of one or more of the five following measures: compensation, restitution, satisfaction, rehabilitation, and guarantees of non-repetition. The chapter then looks at the categories of recurrent harms against culture that have received international attention, whether from a legal or political perspective—namely, looted or stolen art; historical processes of group cultural destruction; and intentional attacks against cultural heritage.
International Cultural Heritage Law
Authors: Scovazzi Tullio
Published: October 2020

On a global basis, the protection of cultural heritage falls within the mandate of UNESCO. UNESCO has the purpose of contributing to peace and security by promoting collaboration among the nations through education, science, and culture in order to further universal respect for justice, the rule of law, human rights, and fundamental freedoms. Cooperation between the UN and UNESCO has been strengthened to face the threats posed by the practice of targeting or looting cultural properties in situations of crisis aimed at exacerbating tensions and financing illegal activities. This sheds further light on the link between culture and international peace and security. The main organs of UNESCO are the General Conference, the Executive Board, and the Secretariat. The present UNESCO normative framework for culture includes several declarations and recommendations and six so-called ‘heritage conventions’, devoted to different kinds of cultural heritage.
An Interventionist’s Guide to Exotic Choice
Authors: Stern Reuben
Published: October 2020

In this paper, I use interventionist causal models to identify some novel Newcomb problems, and subsequently use these problems to refine existing interventionist treatments of causal decision theory. The new Newcomb problems that make trouble for existing interventionist treatments involve so-called ‘exotic choice’—that is, decision-making contexts where the agent has evidence about the outcome of her choice. I argue that when choice is exotic, the interventionist can adequately capture causal decision-theoretic reasoning by introducing a new interventionist approach to updating on exotic evidence. But I also argue that this new updating procedure is principled only if the interventionist trades in the typical interventionist conception of choice for an alternative Ramseyan conception. I end by arguing that the guide to exotic choice developed here may, despite its name, be useful in some everyday contexts.
Increasing the census of ultracool dwarfs in wide binary and multiple systems using Dark Energy Survey DR1 and Gaia DR2 data
Authors: dal Ponte M , Santiago B , Carnero Rosell A , Burningham B , Yanny B , Marshall J L , Bechtol K , Martini P , Li T S , De Paris L , Abbott T M C , Aguena M , Allam S , Avila S , Bertin E , Bhargava S , Brooks D , Buckley-Geer E , Kind M Carrasco , Carretero J , da Costa L N , De Vicente J , Diehl H T , Doel P , Eifler T F , Everett S , Flaugher B , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Kuropatkin N , Maia M A G , March M , Menanteau F , Miquel R , Palmese A , Paz-Chinchón F , Plazas A A , Sanchez E , Scarpine V , Serrano S , Sevilla-Noarbe I , Smith M , Suchyta E , Swanson M E C , Tarle G , Thomas D , Varga T N , Walker A R ,   DES Collaboration
Published: October 2020

We present the discovery of 255 binary and 6 multiple system candidates with wide (> 5 arcsec) separation composed by ultracool dwarfs (UCDs) companions to stars, plus nine double ultracool dwarf systems. These systems were selected based on common distance criteria. About 90 per cent of the total sample has proper motions available and 73 per cent of the systems also satisfy a common proper motion criterion. The sample of ultracool candidates was taken from the Dark Energy Survey (DES) and the candidate stellar primaries are from Gaia DR2 and DES data. We compute chance alignment probabilities in order to assess the physical nature of each pair. We find that 174 candidate pairs with Gaia DR2 primaries and 81 pairs with a DES star as a primary have chance alignment probabilities $\lt 5{{\ \rm per\ cent}}$. Only nine candidate systems composed of two UCDs were identified. The sample of candidate multiple systems is made up of five triple systems and one quadruple system. The majority of the UCDs found in binaries and multiples are of early L type and the typical wide binary fraction over the L spectral types is $2\!-\!4{{\ \rm per\ cent}}$. Our sample of candidate wide binaries with UCDs as secondaries constitutes a substantial increase over the known number of such systems, which are very useful to constrain the formation and evolution of UCDs.
Structure and kinematics of shocked gas in Sgr B2: further evidence of a cloud–cloud collision from SiO emission maps
Authors: Armijos-Abendaño J , Banda-Barragán W E , Martín-Pintado J , Dénes H , Federrath C , Requena-Torres M A
Published: October 2020

We present SiO J = 2–1 maps of the Sgr B2 molecular cloud, which show shocked gas with a turbulent substructure comprising at least three cavities at velocities of $[10,40]\, \rm km\, s^{-1}$ and an arc at velocities of $[-20,10]\, \rm km\, s^{-1}$. The spatial anticorrelation of shocked gas at low and high velocities, and the presence of bridging features in position-velocity diagrams suggest that these structures formed in a cloud–cloud collision. Some of the known compact H ii regions spatially overlap with sites of strong SiO emission at velocities of $[40,85]\, \rm km\, s^{-1}$, and are between or along the edges of SiO gas features at $[100,120]\, \rm km\, s^{-1}$, suggesting that the stars responsible for ionizing the compact H ii regions formed in compressed gas due to this collision. We find gas densities and kinetic temperatures of the order of $n_{\rm H_2}\sim 10^5\, \rm cm^{-3}$ and $\sim 30\, \rm K$, respectively, towards three positions of Sgr B2. The average values of the SiO relative abundances, integrated line intensities, and line widths are ∼10−9, $\sim 11\, \rm K\, km\, s^{-1}$, and $\sim 31\, \rm km\, s^{-1}$, respectively. These values agree with those obtained with chemical models that mimic grain sputtering by C-type shocks. A comparison of our observations with hydrodynamical simulations shows that a cloud–cloud collision that took place $\lesssim 0.5\, \rm Myr$ ago can explain the density distribution with a mean column density of $\bar{N}_{\rm H_2}\gtrsim 5\times 10^{22}\, \rm cm^{-2}$, and the morphology and kinematics of shocked gas in different velocity channels. Colliding clouds are efficient at producing internal shocks with velocities $\sim 5\!-\!50\, \rm km\, s^{-1}$. High-velocity shocks are produced during the early stages of the collision and can readily ignite star formation, while moderate- and low-velocity shocks are important over longer time-scales and can explain the widespread SiO emission in Sgr B2.
Concerning P450 Evolution: Structural Analyses Support Bacterial Origin of Sterol 14α-Demethylases
Authors: Lamb David C , Hargrove Tatiana Y , Zhao Bin , Wawrzak Zdzislaw , Goldstone Jared V , Nes William David , Kelly Steven L , Waterman Michael R , Stegeman John J , Lepesheva Galina I
Published: October 2020

Sterol biosynthesis, primarily associated with eukaryotic kingdoms of life, occurs as an abbreviated pathway in the bacterium Methylococcus capsulatus. Sterol 14α-demethylation is an essential step in this pathway and is catalyzed by cytochrome P450 51 (CYP51). In M. capsulatus, the enzyme consists of the P450 domain naturally fused to a ferredoxin domain at the C-terminus (CYP51fx). The structure of M. capsulatus CYP51fx was solved to 2.7 Å resolution and is the first structure of a bacterial sterol biosynthetic enzyme. The structure contained one P450 molecule per asymmetric unit with no electron density seen for ferredoxin. We connect this with the requirement of P450 substrate binding in order to activate productive ferredoxin binding. Further, the structure of the P450 domain with bound detergent (which replaced the substrate upon crystallization) was solved to 2.4 Å resolution. Comparison of these two structures to the CYP51s from human, fungi, and protozoa reveals strict conservation of the overall protein architecture. However, the structure of an “orphan” P450 from nonsterol-producing Mycobacterium tuberculosis that also has CYP51 activity reveals marked differences, suggesting that loss of function in vivo might have led to alterations in the structural constraints. Our results are consistent with the idea that eukaryotic and bacterial CYP51s evolved from a common cenancestor and that early eukaryotes may have recruited CYP51 from a bacterial source. The idea is supported by bioinformatic analysis, revealing the presence of CYP51 genes in >1,000 bacteria from nine different phyla, >50 of them being natural CYP51fx fusion proteins.
Contrast-FEL—A Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches
Authors: Kosakovsky Pond Sergei L , Wisotsky Sadie R , Escalante Ananias , Magalis Brittany Rife , Weaver Steven
Published: October 2020

A number of evolutionary hypotheses can be tested by comparing selective pressures among sets of branches in a phylogenetic tree. When the question of interest is to identify specific sites within genes that may be evolving differently, a common approach is to perform separate analyses on subsets of sequences and compare parameter estimates in a post hoc fashion. This approach is statistically suboptimal and not always applicable. Here, we develop a simple extension of a popular fixed effects likelihood method in the context of codon-based evolutionary phylogenetic maximum likelihood testing, Contrast-FEL. It is suitable for identifying individual alignment sites where any among the K≥2 sets of branches in a phylogenetic tree have detectably different ω ratios, indicative of different selective regimes. Using extensive simulations, we show that Contrast-FEL delivers good power, exceeding 90% for sufficiently large differences, while maintaining tight control over false positive rates, when the model is correctly specified. We conclude by applying Contrast-FEL to data from five previously published studies spanning a diverse range of organisms and focusing on different evolutionary questions.
Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development
Authors: Yang Yenan , Zhu Xiaoli , Jia Xiang , Hou Wanwan , Zhou Guoqiang , Ma Zhangjing , Yu Bin , Pi Yan , Zhang Xumin , Wang Jingqiang , Wang Gang
Published: October 2020

Msh homeobox (Msx) is a subclass of homeobox transcriptional regulators that control cell lineage development, including the early stage of vertebrate limb development, although the underlying mechanisms are not clear. Here, we demonstrate that Msx1 promotes the proliferation of myoblasts and mesenchymal stem cells (MSCs) by enhancing mitogen-activated protein kinase (MAPK) signaling. Msx1 directly binds to and upregulates the expression of fibroblast growth factor 9 (Fgf9) and Fgf18. Accordingly, knockdown or antibody neutralization of Fgf9/18 inhibits Msx1-activated extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Mechanistically, we determined that the phosphorylation of Msx1 at Ser136 is critical for enhancing Fgf9 and Fgf18 expression and cell proliferation, and cyclin-dependent kinase 1 (CDK1) is apparently responsible for Ser136 phosphorylation. Furthermore, mesenchymal deletion of Msx1/2 results in decreased Fgf9 and Fgf18 expression and Erk1/2 phosphorylation, which leads to serious defects in limb development in mice. Collectively, our findings established an important function of the Msx1-Fgf-MAPK signaling axis in promoting cell proliferation, thus providing a new mechanistic insight into limb development.
KinaseMD: kinase mutations and drug response database
Authors: Hu Ruifeng , Xu Haodong , Jia Peilin , Zhao Zhongming
Published: October 2020

Mutations in kinases are abundant and critical to study signaling pathways and regulatory roles in human disease, especially in cancer. Somatic mutations in kinase genes can affect drug treatment, both sensitivity and resistance, to clinically used kinase inhibitors. Here, we present a newly constructed database, KinaseMD (kinase mutations and drug response), to structurally and functionally annotate kinase mutations. KinaseMD integrates 679 374 somatic mutations, 251 522 network-rewiring events, and 390 460 drug response records curated from various sources for 547 kinases. We uniquely annotate the mutations and kinase inhibitor response in four types of protein substructures (gatekeeper, A-loop, G-loop and αC-helix) that are linked to kinase inhibitor resistance in literature. In addition, we annotate functional mutations that may rewire kinase regulatory network and report four phosphorylation signals (gain, loss, up-regulation and down-regulation). Overall, KinaseMD provides the most updated information on mutations, unique annotations of drug response especially drug resistance and functional sites of kinases. KinaseMD is accessible at https://bioinfo.uth.edu/kmd/, having functions for searching, browsing and downloading data. To our knowledge, there has been no systematic annotation of these structural mutations linking to kinase inhibitor response. In summary, KinaseMD is a centralized database for kinase mutations and drug response.
ConjuPepDB: a database of peptide–drug conjugates
Authors: Balogh Balázs , Ivánczi Márton , Nizami Bilal , Beke-Somfai Tamás , Mándity István M
Published: October 2020

Peptide–drug conjugates are organic molecules composed of (i) a small drug molecule, (ii) a peptide and (iii) a linker. The drug molecule is mandatory for the biological action, however, its efficacy can be enhanced by targeted delivery, which often also reduces unwanted side effects. For site-specificity the peptide part is mainly responsible. The linker attaches chemically the drug to the peptide, but it could also be biodegradable which ensures controlled liberation of the small drug. Despite the importance of the field, there is no public comprehensive database on these species. Herein we describe ConjuPepBD, a freely available, fully annotated and manually curated database of peptide drug conjugates. ConjuPepDB contains basic information about the entries, e.g. CAS number. Furthermore, it also implies their biomedical application and the type of chemical conjugation employed. It covers more than 1600 conjugates from ∼230 publications. The web-interface is user-friendly, intuitive, and useable on several devices, e.g. phones, tablets, PCs. The webpage allows the user to search for content using numerous criteria, chemical structure and a help page is also provided. Besides giving quick insight for newcomers, ConjuPepDB is hoped to be also helpful for researchers from various related fields. The database is accessible at: https://conjupepdb.ttk.hu/.
Potential benefits of dietary seaweeds as protection against COVID-19
Authors: Tamama Kenichi
Published: October 2020

The coronavirus disease 2019 (COVID-19) pandemic in Japan is not as disastrous as it is in other Western countries, possibly because of certain lifestyle factors. One such factor might be the seaweed-rich diet commonly consumed in Japan. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which binds to angiotensin-converting enzyme 2 (ACE2) on the cell surface and downregulates ACE2, likely elevating the ratio of angiotensin-converting enzyme (ACE) to ACE2. The overreaction of the immune system, combined with the cytokine storm and ACE dominance, is purported to cause the condition of COVID-19 patients to deteriorate rapidly. Dietary seaweeds contain numerous components, including ACE inhibitory peptides, soluble dietary fibers (eg, fucoidan, porphyran), omega-3 fatty acids, fucoxanthin, fucosterol, vitamins D3 and B12, and phlorotannins. These components exert antioxidant, anti-inflammatory, and antiviral effects directly as well as indirectly through prebiotic effects. It is possible that ACE inhibitory components could minimize the ACE dominance caused by SARS-CoV-2 infection. Thus, dietary seaweeds might confer protection against COVID-19 through multiple mechanisms. Overconsumption of seaweeds should be avoided, however, as seaweeds contain high levels of iodine.
Introduction to Israeli Politics and Society
Authors: Hazan Reuven Y. , Dowty Alan , Hofnung Menachem , Rahat Gideon
Published: October 2020

Few countries receive as much attention as Israel and are at the same time as misunderstood. The Oxford Handbook of Israeli Politics and Society brings together the leading Israeli and international figures in order to offer the most wide-ranging treatment available of an intriguing country. This chapter tackles the issue of Israeli exceptionalism, arguing against those who shy away from assessing Israel in a comparative perspective—whether for reasons of complexity or because of a political agenda. Israel is indeed different, for many reasons, but it possesses enough similarities in its democratic political institutions and social makeup that to truly understand the country, scholars need to employ a comparative analytical perspective. The chapter argues that Israeli politics and society are comparable, that comparison will improve the ability to assess Israel, and that Israel can contribute to theory building and testing in comparative politics. The chapter then outlines the sections and summarizes the main features of each chapter in this handbook.
Religion, Society, and Politics in Israel
Authors: Cohen Asher
Published: October 2020

This chapter focuses on four main aspects of relations among religion, society, and the state. The first section describes religion–state relations in Israel in comparison to the models prevalent in Western democracies. The second section categorizes the components of Jewish society in Israel by attitude toward tradition and religion. The third section focuses on the political system, with a look at the distribution of political parties based on religion and state and on models of accommodational and crisis politics. The fourth section examines two key disputes involving relations among religion, society, and the state: the public nature of the Jewish Sabbath as an expression of the struggle over the public space and the question of the boundaries of the Jewish collective, known in Israel as “who is a Jew.” After seventy years of existence, Israel still wrestles with a wide range of unresolved issues pertaining to religion, society, and state, reflecting an inability to reach stable and consensual solutions.
The Jewish Ethnic Divide and Ethnic Politics in Israel
Authors: Smooha Sammy
Published: October 2020

Ethnic differences are commonly reflected in governing elites, public policies, political parties, voting, and intergroup conflicts. This is true of Jews in Israel despite the strong assimilationist ideology and lack of legitimacy of ethnicity and ethnic politics. Notwithstanding increasing assimilation, decreasing ethnic inequalities, and diminishing discrimination, Jews in Israel are still markedly divided by ethnicity, social class, religious observance, subculture, geographic concentration, and collective memory. The political divide between the Right and the Center-Left is grounded in both class and ethnicity. The bases of the right-wing parties are non-dominant and low-socioeconomic-status Jews, Mizrahim, Russian immigrants, the National Religious, the ultra-Orthodox, and offspring of the Revisionists, who are more nationalistic and less liberal than the economically better off and Ashkenazi supporters of the Center-Left. The political Right represents its supporters’ illiberal views well and grants them a feeling of being at home in Israel and some preferential treatment as Jews. The demographic predominance of its supporters gives the Right a lead in vying for power, makes Israel more Jewish than democratic, and reduces the chances of peacemaking with the Palestinians.
Gender in Israel
Authors: Itzkovitch-Malka Reut
Published: October 2020

This chapter traces, identifies, and characterizes the main features of the gender division in Israeli society and politics. It addresses questions relevant to the status of women, as well as the LGBTQ community, and assesses the magnitude of gender inequality in the various societal, cultural, and political arenas. While substantial progress has been made in improving the status of women in Israel, there is still a long road ahead before Israel can achieve true gender equality. In order for such equality to become a reality, genuine change is in order: a focus on the substantive outputs of the Knesset and the government; an emphasis on gender mainstreaming practices; and widespread feminist activity in formal politics, meant to inject critical feminist views into the political system and alter existing gender relations.
Conceptualizing Palestinian Politics in Israel in the Shadow of the Arab Spring
Authors: Jamal Amal
Published: October 2020

This chapter examines the debates about the conceptualization and practices of resistance in Palestinian society in Israel. It does so in light of two important developments that have had major repercussions for this homeland minority: the social and political upheavals in the Arab Spring states on the one hand and the growing nationalist extremism in Israel, culminating in the passing of the nation-state law in 2018 and the delegitimization of the Joint List in the 2019–2020 elections, on the other. Examining the debates taking place about resistance helps us understand how political subjects active in this community define themselves and others and the meaning and implications of such definitions. Furthermore, it assists in demonstrating how Palestinians in Israel utilize the opportunities inherent in their institutional environment and the tools provided by that environment to facilitate an alternative political ethos that will guarantee it full civil equality and human dignity.
Public Opinion in Israel
Authors: Hermann Tamar
Published: October 2020

In Israel, as in many other countries, the impact of public opinion on national policymaking has increased dramatically over the last few decades. In fact, public opinion has practically developed into one of the prime political inputs in Israel. This chapter argues that this increased impact, which could have contributed to improving the Israeli democracy, is in fact often undermined by the increasing overlapping of the main cleavages within Israel: between the political Right and Left, between Jews and Arabs, and between religious and secular Israelis. This extreme overlapping has severely eroded the national consensus and accelerated the emergence of deep disagreements in public opinion over strategic issues, such as the nature of the state (Jewish? Democratic?), the main challenges facing the nation (including the best way of dealing with the protracted Israeli–Palestinian conflict), and the desired collective future.
The Judicial Branch in Israel
Authors: Hofnung Menachem , Wattad Mohammed S.
Published: October 2020

The contemporary perception of Israel’s judiciary as an independent branch does not coincide with Israel’s first government’s perception after establishing the first Supreme Court. To a great extent the executive branch deemed the court its long arm. Until the mid-1950s judges were appointed by the government, and questions of conflicts of interest and political affiliation—in the wide sense of the term—were not compelling. However, since the 1990s the court’s power of judicial review and the legitimacy of its decisions have become issues of heated public debate. Consequently, the process of appointing justices to the court has become subject to very strict public and political scrutiny. This chapter asks whether the Israeli judiciary truly constitutes a third independent branch of government. This is relevant considering the continuous attempts to change the existing balance of power, aiming to limit the court’s capacity to apply universal judicial doctrines and legal standards to executive and legislative decisions.