Empirical studies, often in the form of controlled experiments, have been widely adopted in software engineering research as a way to evaluate the merits of new software engineering tools. However, ...controlled experiments involving
human participants
actually
using
new tools are still rare, and when they are conducted, some have serious validity concerns. Recent research has also shown that many software engineering researchers view this form of tool evaluation as too risky and too difficult to conduct, as they might ultimately lead to inconclusive or negative results. In this paper, we aim both to help researchers minimize the risks of this form of tool evaluation, and to increase their quality, by offering practical methodological guidance on designing and running controlled experiments with developers. Our guidance fills gaps in the empirical literature by explaining, from a practical perspective, options in the recruitment and selection of human participants, informed consent, experimental procedures, demographic measurements, group assignment, training, the selecting and design of tasks, the measurement of common outcome variables such as success and time on task, and study debriefing. Throughout, we situate this guidance in the results of a new systematic review of the tool evaluations that were published in over 1,700 software engineering papers published from 2001 to 2011.
Pedigrees provide the genealogical relationships among individuals at a fine resolution and serve an important function in many areas of genetic studies. One such use of pedigree information is in ...the estimation of the short-term effective population size Formula: see text, which is of great relevance in fields such as conservation genetics. Despite the usefulness of pedigrees, however, they are often an unknown parameter and must be inferred from genetic data. In this study, we present a Bayesian method to jointly estimate pedigrees and Formula: see text from genetic markers using Markov Chain Monte Carlo. Our method supports analysis of a large number of markers and individuals within a single generation with the use of a composite likelihood, which significantly increases computational efficiency. We show, on simulated data, that our method is able to jointly estimate relationships up to first cousins and Formula: see text with high accuracy. We also apply the method on a real dataset of house sparrows to reconstruct their previously unreported pedigree.
Pedigrees contain information about the genealogical relationships among individuals and are of fundamental importance in many areas of genetic studies. However, pedigrees are often unknown and must ...be inferred from genetic data. Despite the importance of pedigree inference, existing methods are limited to inferring only close relationships or analyzing a small number of individuals or loci. We present a simulated annealing method for estimating pedigrees in large samples of otherwise seemingly unrelated individuals using genome-wide SNP data. The method supports complex pedigree structures such as polygamous families, multi-generational families, and pedigrees in which many of the member individuals are missing. Computational speed is greatly enhanced by the use of a composite likelihood function which approximates the full likelihood. We validate our method on simulated data and show that it can infer distant relatives more accurately than existing methods. Furthermore, we illustrate the utility of the method on a sample of Greenlandic Inuit.
Background In patients with suspected cardiac sarcoidosis, late gadolinium enhancement on cardiovascular magnetic resonance imaging and/or
F-fluorodeoxyglucose uptake on positron emission tomography ...are often used to reach a clinical diagnosis of cardiac sarcoidosis. On the basis of data from the imaging literature of clinical cardiac sarcoidosis, no specific features of myocardial involvement are regarded as pathognomonic for cardiac sarcoidosis. Thus, a diagnosis of cardiac sarcoidosis is challenging to make. There has been no systematic analysis of histologically diagnosed cardiac sarcoidosis for patterns of myocardial involvement. We hypothesized that certain patterns of myocardial involvement are more frequent in histologically diagnosed cardiac sarcoidosis. Methods and Results We performed a systematic review and meta-analysis of gross pathological images from the published literature of patients with histologically diagnosed cardiac sarcoidosis who underwent autopsy or cardiac transplantation. Thirty-three eligible articles provided images of 49 unique hearts. Analysis of these hearts revealed certain features of myocardial involvement in >90% of cases: left ventricular (LV) subepicardial, LV multifocal, septal, and right ventricular free wall involvement. In contrast, other patterns were seen in 0% to 6% of cases: absence of gross LV myocardial involvement, isolated LV midmyocardial involvement, isolated LV subendocardial involvement, isolated LV transmural involvement, absence of septal involvement, or isolated involvement of only one LV level. Conclusions In this systematic review and meta-analysis of histologically diagnosed cardiac sarcoidosis, we identified certain features of myocardial involvement that occurred frequently and others that occurred rarely or never. These patterns could aid the interpretation of cardiovascular magnetic resonance imaging and positron emission tomography imaging and improve the diagnosis and the prognostication of patients with suspected cardiac sarcoidosis.
Present-day hunter-gatherers (HGs) live in multilevel social groups essential to sustain a population structure characterized by limited levels of within-band relatedness and inbreeding. When these ...wider social networks evolved among HGs is unknown. To investigate whether the contemporary HG strategy was already present in the Upper Paleolithic, we used complete genome sequences from Sunghir, a site dated to ~34,000 years before the present, containing multiple anatomically modern human individuals. We show that individuals at Sunghir derive from a population of small effective size, with limited kinship and levels of inbreeding similar to HG populations. Our findings suggest that Upper Paleolithic social organization was similar to that of living HGs, with limited relatedness within residential groups embedded in a larger mating network.
The origin of contemporary Europeans remains contentious. We obtained a genome sequence from Kostenki 14 in European Russia dating from 38,700 to 36,200 years ago, one of the oldest fossils of ...anatomically modern humans from Europe. We find that Kostenki 14 shares a close ancestry with the 24,000-year-old Mal'ta boy from central Siberia, European Mesolithic hunter-gatherers, some contemporary western Siberians, and many Europeans, but not eastern Asians. Additionally, the Kostenki 14 genome shows evidence of shared ancestry with a population basal to all Eurasians that also relates to later European Neolithic farmers. We find that Kostenki 14 contains more Neandertal DNA that is contained in longer tracts than present Europeans. Our findings reveal the timing of divergence of western Eurasians and East Asians to be more than 36,200 years ago and that European genomic structure today dates back to the Upper Paleolithic and derives from a metapopulation that at times stretched from Europe to central Asia.
Mutations in calreticulin (CALR) are phenotypic drivers in the pathogenesis of myeloproliferative neoplasms. Mechanistic studies have demonstrated that mutant CALR binds to the thrombopoietin ...receptor MPL, and that the positive electrostatic charge of the mutant CALR C terminus is required for mutant CALR-mediated activation of JAK-STAT signaling. Here we demonstrate that although binding between mutant CALR and MPL is required for mutant CALR to transform hematopoietic cells; binding alone is insufficient for cytokine independent growth. We further show that the threshold of positive charge in the mutant CALR C terminus influences both binding of mutant CALR to MPL and activation of MPL signaling. We find that mutant CALR binds to the extracellular domain of MPL and that 3 tyrosine residues within the intracellular domain of MPL are required to activate signaling. With respect to mutant CALR function, we show that its lectin-dependent function is required for binding to MPL and for cytokine independent growth, whereas its chaperone and polypeptide-binding functionalities are dispensable. Together, our findings provide additional insights into the mechanism of the pathogenic mutant CALR-MPL interaction in myeloproliferative neoplasms.
•The binding of mutant calreticulin to MPL can be uncoupled from MPL activation.•The lectin activity but not the chaperone functionality of mutant CALR is required for cytokine-independent growth.
Explicit programming strategies LaToza, Thomas D.; Arab, Maryam; Loksa, Dastyni ...
Empirical software engineering : an international journal,
07/2020, Letnik:
25, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Software developers solve a diverse and wide range of problems. While software engineering research often focuses on tools to support this problem solving, the strategies that developers use to solve ...problems are at least as important. In this paper, we offer a novel approach for enabling developers to follow explicit programming strategies that describe how an expert tackles a common programming problem. We define explicit programming strategies, grounding our definition in prior work both within software engineering and in other professions which have adopted more explicit procedures for problem solving. We then present a novel notation called Roboto and a novel strategy tracker tool that explicitly represent programming strategies and frame executing strategies as a collaborative effort between human abilities to make decisions and computer abilities to structure process and persist information. In a formative evaluation, 28 software developers of varying expertise completed a design task and a debugging task. We found that, compared to developers who are free to choose their own strategies, developers given explicit strategies experienced their work as more organized, systematic, and predictable, but also more constrained. Developers using explicit strategies were objectively more successful at the design and debugging tasks. We discuss the implications of Roboto and these findings, envisioning a thriving ecosystem of explicit strategies that accelerate and improve developers’ programming problem solving.
Somatic mutations in calreticulin (CALR) are present in approximately 40% of patients with myeloproliferative neoplasms (MPN), but the mechanism by which mutant CALR is oncogenic remains unclear. ...Here, we demonstrate that expression of mutant CALR alone is sufficient to engender MPN in mice and recapitulates the disease phenotype of patients with CALR-mutant MPN. We further show that the thrombopoietin receptor MPL is required for mutant CALR-driven transformation through JAK-STAT pathway activation, thus rendering mutant CALR-transformed hematopoietic cells sensitive to JAK2 inhibition. Finally, we demonstrate that the oncogenicity of mutant CALR is dependent on the positive electrostatic charge of the C-terminus of the mutant protein, which is necessary for physical interaction between mutant CALR and MPL. Together, our findings elucidate a novel paradigm of cancer pathogenesis and reveal how CALR mutations induce MPN.
The mechanism by which CALR mutations induce MPN remains unknown. In this report, we show that the positive charge of the CALR mutant C-terminus is necessary to transform hematopoietic cells by enabling binding between mutant CALR and the thrombopoietin receptor MPL.
Background and Context: Current introductory instruction fails to identify, structure, and sequence the many skills involved in programming.
Objective: We proposed a theory which identifies four ...distinct skills that novices learn incrementally. These skills are tracing, writing syntax, comprehending templates (reusable abstractions of programming knowledge), and writing code with templates. We theorized that explicit instruction of these skills decreases cognitive demand.
Method: We conducted an exploratory mixed-methods study and compared students' exercise completion rates, error rates, ability to explain code, and engagement when learning to program. We compared material that reflects this theory to more traditional material that does not distinguish between skills.
Findings: Teaching skills incrementally resulted in improved completion rate on practice exercises, and decreased error rate and improved understanding of the post-test.
Implications: By structuring programming skills such that they can be taught explicitly and incrementally, we can inform instructional design and improve future research on understanding how novice programmers develop understanding.
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