Calculation of centralities in protein kinase A

Topological analysis of amino acid networks is a common method that can help to understand the roles of individual residues. The most popular approach for network construction is to create a connection between residues if they interact. These interactions are usually weighted by absolute values of correlation coefficients or mutual information. Here we argue that connections in such networks have to reflect levels of cohesion within the protein instead of a simple fact of interaction between residues. If this is correct, an indiscriminate combination of correlation and anti-correlation, as well as the all-inclusive nature of the mutual information metrics, should be detrimental for the analysis. To test our hypothesis, we studied amino acid networks of the protein kinase A created by Local Spatial Pattern alignment, a method that can detect conserved patterns formed by Cα-Cβ vectors. Our results showed that, in comparison with the traditional methods, this approach is more efficient in detecting functionally important residues. Out of four studied centrality metrics, Closeness centrality was the least efficient measure of residue importance. Eigenvector centrality proved to be ineffective as the spectral gap values of the networks were very low due to the bilobal structure of the kinase. We recommend using joint graphs of Betweenness centrality and Degree centrality to visualize different aspects of amino acid roles.

REGULATION OF REPRODUCTIVE CLONING AND INHERITABLE GENETIC MODIFICATIONS ON HUMANS - PERILS AND DEFICIENCIES

Harms arising from reproductive cloning or inheritable genetic modifications, for the time being, seem significant. This is supported by the simple fact that the first cloned monkeys were short-lived or by the fact that inheritable genetic modifications still carry a high chance of getting “off-target” results, which could result in serious health problems. Inheritable genetic modifications, in particular, have a high therapeutic potential, and it is suggested that this technology’s comprehension is shifting from an absolute ban, to concerns over safety issues. International law can prove to be facilitative when it comes to deciding which new technology should be prohibited, restricted or allowed, having in mind possible consequences and the so-called phenomenon of reproductive tourism. Legally binding regulation of both technologies has proven challenging at the universal level. However, there has been some progress in Europe on that matter. Harms arising from inheritable genetic modifications seem even higher than in the case of reproductive cloning, since they have the potential to affect the whole of humanity, including future generations. The Criminal Code of Serbia and the Constitution of the Republic of Serbia prohibit reproductive cloning. However, the prohibition of inheritable genetic modifications on humans is not regulated explicitly in the Criminal Code of Serbia, making this technology seem more acceptable or less harmful.

Where We Live, Work, and Play

This chapter focuses on place, which is one of the key factors that determines whether or not we can live a healthy life, for the simple fact that place is a ubiquitous exposure. It first provides an overview of the link between place and health, before looking at the physical spaces where we live and work, our communities and transportation networks, and the condition of our global home. COVID-19 showed that for all the segregation in our society, for all the difference between high- and low-income neighborhoods, for all the variety of spaces we navigate, there is really only one place to truly speak of—the world we share. The story of place and health is ultimately the story how we can support the long-term sustainability of our planet. Just as it is not enough to have nice homes if they are situated in dangerous neighborhoods, it is not enough to make our communities more conducive to health if we neglect the broader environmental challenges that shape the health of our fragile, indispensable world. This means, centrally, mitigating the effects of climate change by designing healthier, more sustainable cities.

Electrophoretic Deposition of Biocompatible and Bioactive Hydroxyapatite-Based Coatings on Titanium

Current trends in biomaterials science address the issue of integrating artificial materials as orthopedic or dental implants with biological materials, e.g., patients’ bone tissue. Problems arise due to the simple fact that any surface that promotes biointegration and facilitates osteointegration may also provide a good platform for the rapid growth of bacterial colonies. Infected implant surfaces easily lead to biofilm formation that poses a major healthcare concern since it could have destructive effects and ultimately endanger the patients’ life. As of late, research has centered on designing coatings that would eliminate possible infection but neglected to aid bone mineralization. Other strategies yielded surfaces that could promote osseointegration but failed to prevent microbial susceptibility. Needless to say, in order to assure prolonged implant functionality, both coating functions are indispensable and should be addressed simultaneously. This review summarizes progress in designing multifunctional implant coatings that serve as carriers of antibacterial agents with the primary intention of inhibiting bacterial growth on the implant-tissue interface, while still promoting osseointegration.

Soundfullessness

Are the predictable associations between sound and darkness, night and music, based solely on the ability of the aural sense to focus thanks to a reduction of the visible field? Even if the answer lies in a correlation between physical manifestation and physiological adaptation, the socio-cultural scaffolding that stems from this simple fact is of interest. Sites of investigation: John Oswald’s pitch black performances; Studio 303’s Noises from the Dark series; Adrian Piper’s Untitled Performance at Max’s Kansas City; Andre Lepecki’s (and by extension Fred Moten’s) ‘shared aurality’ active in the quartet of darkness/blackness/potentiality/freedom; Derek Jarman’s Blue and, especially, Akira Mizuta Lippit’s analysis of the film where sound becomes image and image becomes sound; the use of darkness at the famed 1938 International Surrealist Exhibition in Paris; the Saydnaya Military Prison; Guy Debord’s Hurlements en faveur de Sade; amongst others. Is sound necessarily of the dark, from the dark, in the dark? Eclipses and shadows, caves and caverns are moments and sites where and when sounds thrive, or at least are invoked and conjured. How does the night sound? Merleau-Ponty begins to answer the question by depicting the night as generator of a different kind of space, one that ‘has no outlines; … is pure depth without foreground or background, without surfaces and without any distance separating it from me’. The implications on sound of the inside/outside blur, the porous muddle, are that its sensorial properties have ontological consequences.

Product or Production: On the accumulative Aspect of Rock Art at Nämforsen, Northern Sweden

In this article the accumulative aspect of rock art is dis- cussed. In light of the simple fact that we are seeing rock art panels in their final form, questions concerning the interrelation between figures deriving from differ- ent time periods are addressed. The author’s aim is to draw attention to the long continuity of rock art sites and show how greater awareness of this aspect will af- fect the way we comprehend this material in general. The continuity of rock art sites is exemplified by means of a case study of Nämforsen, located in the province of Ångermanland, northern Sweden.

Dyeing to live – a case of clozapine in disguise, and physicians' courage

Objective… in which clozapine tablets were dyed pink, to work around a delusion preventing treatment, and physicians tolerated and monitored an alarming early response to the drug.Patient56-year-old female with severe enduring Bipolar I Disorder, current episode manic with psychosis, already an inpatient for six months. When first seen by us, polypharmacy was evident including haloperidol 25 mg daily. Thorough trials of mood stablisers and second generation antipsychotics in various combinations had all failed. She had never had a clozapine trial.MSEDishevelled middle-aged woman of European descent. Restless; shuffling gait; speech pressured, rapid and whispering, often to the point of unintelligibility. Affect labile: anxious and distressed, suspicious, angry, elevated and demanding. Thought form tangential+++ content paranoid persecutory themes, preoccupied with sexual trauma and delusional belief that yellow medication whether solid or liquid was poisonous. Risks of vulnerability, falls, aggression, neuroleptic malignant syndrome (NMS) and protracted psychotic mania requiring long term hospitalisation.PlanChange to clozapine.ProblemAll formulations are yellow.SolutionTeam discussion, ethical analysis, clozapine tablets dyed with red vegetable dye.Ethical analysisPotential benefit to patient great; current medications not effective and NMS possibly developing; she was fully informed about clozapine with no attempt made to hide the identity of the now crimson tablets.OutcomePatient accepted the clozapine. Temperature, C reactive protein (CRP) and troponin were all normal at baseline but all rose above normal in week 1 of initiation. They peaked in week 3 and by week 4 were dropping, normalising completely within a few weeks. She was transferred to a medical ward for monitoring during weeks 2 and 3 of titration. There were no electrocardiogram changes, no chest pain, no signs of bowel obstruction and no evidence of agranulocytosis. Clinically, she remained well throughout except for the rise in temperature. Once the yellow medicine delusion receded she accepted undyed yellow tablets; the result was discharge home with her best mental state and level of functioning in 15 years.Significance of this caseThere are no cases in the literature that we could find where tablets had been dyed, or where clozapine had been persisted with when such rises in temperature, CRP and troponin occurred. This case illustrates both. The risks in our view were outweighed by the simple fact that clozapine was her only hope of a life worth living.

How do non-geneticist physicians deal with genetic tests? A qualitative analysis

Genetic testing is accepted to be a common practice in many medical specialties. These genetic tests raise issues such as respect for basic rights, how to handle results and uncertainty and how to balance concerns for medical confidentiality with the rights of third parties. Physicians need help to deal with the rapid development of genomic medicine as most of them have received no specific training on the medical, ethical, and social issues involved. Analyzing how these professionals integrate genetic testing into the patient-provider relationship is essential to paving the way for a better use of genomics by all. We conducted a qualitative study comprising a series of focus groups with 21 neurologists and endocrinologists about their genetic testing practices in the western part of France. The interviews were transcribed and analyzed for major themes. We identified an automated care management procedure of genetic testing that affects patient autonomy. The simple fact of having a written consent cannot justify a genetic test given the stakes associated with the results. We also suggest orienting practices toward a systemic approach using a multidisciplinary team or network to provide resources for dealing with uncertainties in interpreting results or situations that require additional technical or clinical skills and, if necessary, to allow for joint consultations with both a geneticist and a non-geneticist medical specialist.

The Amish and COVID-19: A Media Survey

The Amish are a frequent topic of media coverage. The simple fact of Amish involvement often elevates a mundane story to a newsworthy one. Accordingly, the Amish received extensive coverage with regard to the COVID-19 pandemic. In this paper, I survey media output on the Amish and COVID-19 for the period of March to November 2020, drawing on conventional media stories covered on the Amish America website in addition to many others. I identify and analyze several common themes of Amish COVID coverage, including Amish attitudes toward the pandemic, negative reporting, and Amish responses to both the virus and the restrictions put in place to combat the pandemic.

How skeptics could be convinced (not persuaded) to get vaccinated against COVID-19

Central to the SARS-CoV-2 pandemic strategy, COVID-19 vaccination depends on the population’s uptake decisions. Because at least 60% of the population needs to be vaccinated, but fewer, for example, in Germany are expected to do so, it is important to know how to convince those who are undecided or skeptical. According to the health care standard of enabling citizens to make informed decisions based on balanced information (boosting) – instead of persuasion or seduction (nudging) – a comparison of benefits and harms of having or not having the vaccination would be required to inform these groups. With the help of a representative survey, we investigated the contribution of fact boxes, an established intervention format for informed intentions. Study 1 shows the development of knowledge and evaluation of COVID-19 vaccinations by German citizens between Nov 2020 and Feb 2021. Study 2 reveals objective information needs and subjective information requirements of those laypeople at the end of Nov. Study 3 shows that the fact box format is effective for risk communication about COVID-19. Based on these insights, a fact box on the efficacy and safety of mRNA-vaccines was implemented with the help of a national health authority. Study 4 shows that fact boxes increase vaccination knowledge and positive evaluations of the benefit-harm ratio of vaccination in skeptics and undecideds. Our results demonstrate that simple fact boxes can be an effective boost of informed decision making among undecided and skeptical people, and that informed decisions can lead to more positive vaccination evaluations of the public.