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Reproducible laboratory research relies on correctly identified reagents. We have previously described gene research papers with wrongly identified nucleotide sequence(s), including papers studying miR‐145. Manually verifying reagent identities in 36 recent miR‐145 papers found that 56% and 17% of papers described misidentified nucleotide sequences and cell lines, respectively. We also found 5 cell line identifiers in miR‐145 papers with misidentified nucleotide sequences and cell lines, and 18 cell line identifiers published elsewhere, that did not represent indexed human cell lines. These 23 identifiers were described as non‐verifiable (NV), as their identities were unclear. Studying 420 papers that mentioned 8 NV identifier(s) found 235 papers (56%) that referred to 7 identifiers (BGC‐803, BSG‐803, BSG‐823, GSE‐1, HGC‐7901, HGC‐803, and MGC‐823) as independent cell lines. We could not find any publications describing how these cell lines were established. Six cell lines were sourced from cell line repositories with externally accessible online catalogs, but these cell lines were not indexed as claimed. Some papers also stated that short tandem repeat (STR) profiles had been generated for three cell lines, yet no STR profiles could be identified. In summary, as NV cell lines represent new challenges to research integrity and reproducibility, further investigations are required to clarify their status and identities. [ABSTRACT FROM AUTHOR]

Penance is often said to be a part of the process of making amends for wrongdoing. Here I clarify the nature of penance as a remedial action, highlighting the differences between it and more familiar corrective actions such as reparation and apology, and I offer an account of how penance contributes to the expiation of wrongdoing. In doing so, I reject a popular view according to which one does penance primarily by either punishing oneself or voluntarily submitting to punishment at the hands of others. I contend that non‐punitive actions such gifts or acts of service are typically more conducive to achieving the reparative aims of penance. [ABSTRACT FROM AUTHOR]

Libertarianism about free will conjoins the thesis that free will requires indeterminism with the thesis that we have free will. Here the claim that we have experiential evidence for the libertarian position is assessed. It is argued that, on a straightforward reading, the claim is false, for our experiences as agents don't support the claim that free will requires indeterminism. However, our experiences as agents may still have a role to play in an overall case for libertarianism, insofar as they give us some (defeasible) reason to think that we have free will. This latter claim is defended against a pair of objections that have been leveled against it. [ABSTRACT FROM AUTHOR]

This study examined the factors associated with social‐communicative outcomes for children on the autism spectrum receiving early intervention in inclusive versus specialised early childhood education programmes. Fifty‐eight preschool‐aged children randomly assigned to receive the Group‐Early Start Denver Model (G‐ESDM) in either inclusive or specialised (i.e., autism‐specific) classrooms across one calendar year showed similar outcomes at group mean‐level across measures of communication and social behaviour. We examined factors moderating outcomes across settings. Novel moderation analyses revealed that higher baseline social interest and nonverbal cognitive skills were associated with increased social communication gains for children in the inclusive classrooms, but not for those in specialised settings. Children who spend more time paying attention to people and have higher cognitive skills might benefit from receiving early intervention in inclusive settings, whilst these factors might be less relevant for children educated in specialised settings. Lay Summary: This study examined the characteristics of children on the autism spectrum who benefit the most from receiving intervention in inclusive versus specialised early childhood education settings. Fifty‐eight preschool‐aged children were randomly assigned to receive an evidence‐supported intervention called the G‐ESDM in either inclusive or autism‐specific classrooms across one calendar year. Children who spent more time paying attention to people and had higher cognitive skills prior to receiving the intervention experienced more gains in inclusive settings. Conversely, these factors were unrelated to gains for children educated in specialised settings. [ABSTRACT FROM AUTHOR]

Immortalized or continuous cell lines are invaluable tools in basic and preclinical research. However, the widespread use of misidentified cell lines is a serious threat to scientific reproducibility. Based on the experiences of mandatory cell line authentication at the International Journal of Cancer (IJC), we provide an overview of the issues pertinent to misidentified cell lines and discuss available solutions. We also summarize the lessons learned, revealing that at least 5% of the human cell lines used in manuscripts considered for peer review are misidentified. About 4% of the considered manuscripts are rejected for severe cell line problems, and most are subsequently published in other journals. In order to diminish such malpractice and its consequences for the scientific record, we postulate that strict multi‐layered quality control is essential. Besides journals and publishers, we encourage scientists, research institutions, and funders to take action on the matter and revise their respective policies. Hence, we provide concrete recommendations on introducing regular authentication schemes and staff training, and discuss future steps for enhancing good cell culture practices. [ABSTRACT FROM AUTHOR]

A human cell line of neuroblastic tissue, which was believed to have been lost to science due to its unavailability in public repositories, is revived and reclassified. In the 1970s, a triple set of neuroblastoma (NB) cell lines became available for research as MYCNamplified vs nonamplified models (CHP-126/-134 and CHP-100, respectively). Confusingly, CHP-100 was used in subsequent years as a model for NB and, since the 1990s, as a model for neuroepithelioma and later as a model for Ewing's sarcoma (ES), which inevitably led to non-reproducible results. A deposit at a bioresource center revealed that globally available stocks of CHP-100 were identical to the prominent NB cell line IMR-32 and CHP-100 was included into the list of misidentified cell lines. Now we report on the rediscovery of an authentic CHP-100 cell line and provide evidence of incorrect classification during establishment. We show that CHP-100 cells carry a t(11;22)(q24;q12) type II EWSR1-FLI1 fusion and identify it as a classic ES. Although the question of whether CHP-100 was a virtual and never existing cell line from the beginning is now clarified, the results of all relevant publications should be considered questionable. Neither the time of the cross-contamination event with IMR-32 is known nor was the final classification as a model for Ewing family of tumors available with an associated short tandem repeat profile. After a long road of errors and confusion, authentic CHP-100 is now characterized as a type II EWSR1-FLI1 fusion model 44 years after its establishment. [ABSTRACT FROM AUTHOR]

Despite an increased awareness of the problematic of cell line cross‐contamination and misidentification, it remains nowadays a major source of erroneous experimental results in biomedical research. To prevent it, researchers are expected to frequently test the authenticity of the cell lines they are working on. STR profiling was selected as the international reference method to perform cell line authentication. While the experimental protocols and manipulations for generating a STR profile are well described, the available tools and workflows to analyze such data are lacking. The Cellosaurus knowledge resource aimed to improve the situation by compiling all the publicly available STR profiles from the literature and other databases. As a result, it grew to become the largest database in terms of human STR profiles, with 6,474 distinct cell lines having an associated STR profile (release July 31, 2019). Here we present CLASTR, the Cellosaurus STR similarity search tool enabling users to compare one or more STR profiles with those available in the Cellosaurus cell line knowledge resource. It aims to help researchers in the process of cell line authentication by providing numerous functionalities. The tool is publicly accessible on the SIB ExPASy server (https://web.expasy.org/cellosaurus-str-search) and its source code is available on GitHub under the GPL‐3.0 license. What's new? Despite increased awareness, cell line cross‐contamination and misidentification remain a major source of erroneous experimental results in biomedical research. Nowadays, researchers performing experiments on cell lines are thus expected to ensure their authenticity using short‐tandem repeat (STR) profiling. The Cellosaurus, which compiles all publicly available STR profiles, has become a valuable knowledge resource for this purpose. However, the database lacked a dedicated tool allowing a similarity search for a query STR profile. Here, the authors present CLASTR, the Cellosaurus STR similarity search tool that aims to facilitate the authentication process and the detection of potentially cross‐contaminated or misidentified cell lines. [ABSTRACT FROM AUTHOR]

Rule A: if it's metaphysically necessary that p, we may validly infer that no one is even partly morally responsible for the fact that p. Our principal aim in this article is to highlight the importance of this rule and to respond to two recent challenges to it. We argue that rule A is more important to contemporary theories of moral responsibility than has previously been recognized. We then consider two recent challenges to the rule and argue that neither challenge successfully undermines the rule's initial appeal. [ABSTRACT FROM AUTHOR]

A variety of analytical approaches have indicated that melanoma cell line UCLA-SO-M14 (M14) and breast carcinoma cell line MDA-MB-435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor and instead became falsely identified (through cross-contamination or other means) as a cell line from a different donor. Initial studies concluded that MDA-MB-435 was the misidentified cell line and M14 was the authentic cell line, although contradictory evidence has been published, resulting in further confusion. To address this question, we obtained early samples of the melanoma cell line (M14), a lymphoblastoid cell line from the same donor (ML14), and donor serum preserved at the originator's institution. M14 samples were cryopreserved in December 1975, before MDA-MB-435 cells were established in culture. Through a series of molecular characterizations, including short tandem repeat (STR) profiling and cytogenetic analysis, we demonstrated that later samples of M14 and MDA-MB-435 correspond to samples of M14 frozen in 1975, to the lymphoblastoid cell line ML14, and to the melanoma donor's STR profile, sex and blood type. This work demonstrates conclusively that M14 is the authentic cell line and MDA-MB-435 is misidentified. With clear provenance information and authentication testing of early samples, it is possible to resolve debates regarding the origins of problematic cell lines that are widely used in cancer research. [ABSTRACT FROM AUTHOR]

Cell culture is a technique that requires vigilance from the researcher. Common cell culture problems, including contamination with microorganisms or cells from other cultures, can place the reliability and reproducibility of cell culture work at risk. Here we use survey data, contributed by research scientists based in Australia and New Zealand, to assess common cell culture risks and how these risks are managed in practice. Respondents show that sharing of cell lines between laboratories continues to be widespread. Arrangements for mycoplasma and authentication testing are increasingly in place, although scientists are often uncertain how to perform authentication testing. Additional risks are identified for preparation of frozen stocks, storage and shipping. [ABSTRACT FROM AUTHOR]

Stochastic processes may be used as an efficient model for the line shapes affected by Stark effect in edge plasma conditions. We check the accuracy of this approach on the Lyman γ line of hydrogen perturbed by ions only. We also use a stochastic process to investigate the effect of plasma oscillations on a line shape. Our model assumes that Langmuir waves are a sequence of oscillating electric fields changing their amplitude and phase according to an exponential waiting time distribution. The possible effects of Langmuir waves on the Lyman α Stark profile are discussed in edge plasma conditions. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

A line shape model that accounts for low-frequency fluctuations is applied to the Balmer series of the hydrogen isotopes (atomic transitions n → 2). The plasma fluid parameters (density, temperature, etc.) are described as random variables characterized by a prescribed joint probability density function. A special emphasis is devoted to Stark broadened lines, which are sensitive to the plasma density. It is shown that fluctuations can lead to a significant increase of the line width if the fluctuation level Δ N e/〈 N e〉 (with 〈 N e〉 and Δ N e being respectively the density averaged along the line-of-sight and its RMS value) is large. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

The article focuses on the concept of compatibilism and determinism which is compatible to free action and moral responsibility. It mentions that compatibilism feature thought-experiments including a deity, devil or sophisticated behavioral engineer. It states that determinism is incompatible with various kinds of morally relevant control.

Continuous human cell lines have been used extensively as models for biomedical research. In working with these cell lines, researchers are often unaware of the risk of cross-contamination and other causes of misidentification. To reduce this risk, there is a pressing need to authenticate cell lines, comparing the sample handled in the laboratory to a previously tested sample. The American Type Culture Collection Standards Development Organization Workgroup ASN-0002 has developed a Standard for human cell line authentication, recommending short tandem repeat (STR) profiling for authentication of human cell lines. However, there are known limitations to the technique when applied to cultured samples, including possible genetic drift with passage. In our study, a dataset of 2,279 STR profiles from four cell banks was used to assess the effectiveness of the match criteria recommended within the Standard. Of these 2,279 STR profiles, 1,157 were grouped into sets of related cell lines-duplicate holdings, legitimately related samples or misidentified cell lines. Eight core STR loci plus amelogenin were used to unequivocally authenticate 98% of these related sets. Two simple match algorithms each clearly discriminated between related and unrelated samples, with separation between related samples at ≥80% match and unrelated samples at <50% match. A small degree of overlap was noted at 50-79% match, mostly from cell lines known to display variable STR profiles. These match criteria are recommended as a simple and effective way to interpret results from STR profiling of human cell lines. [ABSTRACT FROM AUTHOR]

In this article I argue that it is possible to be blameworthy for doing something that was not objectively morally wrong. If I am right, this would have implications for several debates at the intersection of metaphysics and moral philosophy. I also float a view about which actions can serve as legitimate bases for blame that allows for the possibility of blameworthiness without objective wrongdoing and also suggests an explanation for the appeal of the commonly held view that blameworthiness requires objective wrongdoing. [ABSTRACT FROM AUTHOR]

Improving the description of the far scrape-off layer (SOL) in current edge code suites such as SOLPS is the subject of current efforts, given the importance of main chamber plasma wall interactions (first wall recycling and sputtering) in the design and operation of tokamaks. One of the specific features of the far SOL is the large amplitude of turbulent fluctuations. Neutral particles (atom and molecules) are affected by these fluctuations through the rates of atomic physics processes. In accordance with experimentally measured PDF (probability density function) for both the plasma density and temperature fluctuations, n e and T e are modeled using a Beta PDF. Space and time correlations are accounted for by using an autogressive process. The effects of fluctuations on the neutral atoms penetration depth, as well as on the beryllium sputtering yield are discussed (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

The radiation due to atomic lines in the tokamak edge and divertor can be strongly coupled to the plasma dynamics. Self-consistent (charged particle - atom - photon) simulations carried out for ITER conditions with the transport code B2-EIRENE have indicated modifications of the effective ionization rate induced by photon absorption effects. Up to now, all of the investigations done so far were made assuming a plasma background whose typical spatial variation scales are much larger than the radiation transport scale. In this paper, we examine the validity of this approximation within an effective transport model, relying on a statistical parameterization of the turbulent fluctuations. The model is inspired from the quasilinear theory used for plasma turbulence and assumes a small ratio lturb/ lmfp between the turbulence correlation length and the photon mean free path. We apply the model to calculations of the penetration of a radiation pencil in an optically thick turbulent plasma. The validity of this model for intermediate lturb/ lmfp is next discussed through comparison to a 'model-coefficient' approach, widely used in problems involving linear stochastic differential equations and suitable for arbitrary turbulence correlation length (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

High resolution spectra emitted by C3+ ions and measured along vertical chords in the divertor of the JT-60U tokamak in presence of an X-point MARFE are compared to synthetic profiles calculated taking into account Doppler and Stark effects but not the Zeeman effect because the latter was suppressed experimentally thanks to a linear polarizer transmitting only the component parallel to the toroidal magnetic field. For each viewing chord, the electron density is obtained using equal ion and electron temperatures determined from C IV line intensities observed with a large band visible spectrometer. In complement to the electron temperature distribution obtained previously from line intensities and collisional-radiative modeling, a spatial distribution of the electron density is obtained here for the JT-60U detached divertor with an X-point MARFE. For spectra measured along the most central viewing chords with respect to the MARFE (intensity peak of the strong radiation), it is suggested from the spectral fitting that the emission comes from two plasma layers whose parameters have been obtained (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Vesicovaginal fistula secondary to obstructed labor continues to be an all-too-common occurrence in underdeveloped nations throughout Africa and Asia. Vesicovaginal fistula remains largely an overlooked problem in developing nations as it affects the most marginalized members of society: young, poor, illiterate women who live in remote areas. The formation of obstetric fistula is a result of complex interactions of social, biologic, and economic influences. The key underlying causes of fistula are the combination of a lack of functional emergency obstetric care, poverty, illiteracy, and low status of women. In order to prevent fistula, some strategies include creation of governmental policy aimed toward reducing maternal mortality/morbidity and increasing availability of skilled obstetric care, as well as attempts to increase awareness about its prevention and treatment among policymakers, service providers, and communities. Whereas prevention will require the widespread development of infrastructure within these developing countries, treatment of fistula is an act which can be done 'in the now.' Treatment and subsequent reintegration of fistula patients requires a team of specialists including surgeons, nurses, midwives, and social workers, which is largely unavailable in developing countries. However, there is increasing support for training of fistula surgeons through standardized programs as well as establishment of rehabilitation centers in many nations. The eradication of fistula is dependent upon building programs that target both prevention and treatment. © 2011 Mount Sinai School of Medicine [ABSTRACT FROM AUTHOR]

Background and Purpose: Members of the calcin family, presently including imperatoxin A, maurocalcin, opicalcins and hemicalcin, are basic, 33-mer peptide activators of ryanodine receptors (RyRs), the calcium channels of the sarcoplasmic reticulum (SR) that provide the majority of calcium for muscle contraction. Here we describe hadrucalcin, a novel member of this family.Experimental Approach: Hadrucalcin was isolated from the venom of Hadrurus gertschi. Amino acid sequence and mass were determined by Edman degradation and mass spectrometry respectively. A cDNA library was constructed to generate clones for DNA sequence determination. Biological activity of native toxin was confirmed with [(3)H]ryanodine binding, by using SR vesicles from cardiac and skeletal muscle, and with single skeletal (RyR1) and cardiac (RyR2) channels reconstituted in lipid bilayers. Hadrucalcin was applied to intact ventricular myocytes to investigate effects on calcium transients. The secondary structure of hadrucalcin was computer-modelled by using atomic coordinates from maurocalcin, a structurally similar peptide.Key Results: Hadrucalcin is distinguished from previously described congeners by two additional amino acids in its primary sequence and the lack of prominent amphipathicity. Hadrucalcin activated RyRs with high affinity (EC(50)= 37 nmol.L(-1)), induced a long-lasting subconductance state on RyR1 and RyR2, and rapidly (lag time approximately 2 s) penetrated ventricular cardiomyocytes, eliciting discharge of internal calcium stores and spontaneous contractions.Conclusions and Implications: Hadrucalcin is a cell-permeant, powerful activator of RyRs, which has translational potential for targeted delivery of drugs to RyR as novel therapeutic intervention in arrhythmogenic disease. [ABSTRACT FROM AUTHOR]