Search

The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). The neural basis of this altered auditory processing in Cntnap2 knock-out rats is currently unknown. Auditory brainstem recordings previously revealed no differences between the genotypes. The next step is to investigate brainstem structures outside of the primary auditory pathway that mediate ASR and PPI, which are the pontine reticular nucleus (PnC) and pedunculopontine tegmentum (PPTg), respectively. Multi-unit responses from the PnC and PPTg in vivo of the same rats revealed sex-specific effects of loss of CASPR2 expression on PnC activity, but no effects on PPTg activity. Female Cntnap2

Pathogenic autoreactive antibodies that may be associated with life-threatening Coronavirus disease 2019 (COVID-19) remain to be identified. Here we show that self-assembled genome-scale libraries of full-length proteins covalently coupled to unique DNA barcodes for analysis by sequencing can be used for the unbiased identification of autoreactive antibodies in plasma samples. By screening 11,076 DNA-barcoded proteins expressed from a sequence-verified human ORFeome library, the method, which we named MIPSA (for molecular indexing of proteins by self-assembly), allowed us to detect circulating neutralizing type-I and type-III interferon (IFN) autoantibodies in plasma samples from 55 patients with life-threatening COVID-19. In addition to identifying neutralizing type-I IFN-α and IFN-ω autoantibodies and other previously known autoreactive antibodies in the patient samples, MIPSA enabled the detection of as yet unidentified neutralizing type-III anti-IFN-λ3 autoantibodies that were not seen in ten healthy plasma samples or in convalescent plasma from ten non-hospitalized individuals with COVID-19. The low cost and simple workflow of MIPSA will facilitate unbiased high-throughput analyses of protein–antibody, protein–protein and protein-small-molecule interactions. Pathogenic autoreactive antibodies associated with severe COVID-19 can be identified via self-assembled genome-scale libraries of full-length proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing.

Deficits in social communication and language development belong to the earliest diagnostic criteria of autism spectrum disorders. Of the many risk factors for autism spectrum disorder, the contactin-associated protein-like 2 gene, CNTNAP2, is thought to be important for language development. The present study used a rat model to investigate the potential compounding effects of autism spectrum disorder risk gene mutation and environmental challenges, including breeding conditions or maternal immune activation during pregnancy, on early vocal communication in the offspring. Maternal isolation-induced ultrasonic vocalizations from Cntnap2 wildtype and knockout rats at selected postnatal days were analyzed for their acoustic, temporal and syntax characteristics. Cntnap2 knockout pups from heterozygous breeding showed normal numbers and largely similar temporal structures of ultrasonic vocalizations to wildtype controls, whereas both parameters were affected in homozygously bred knockouts. Homozygous breeding further exacerbated altered pitch and transitioning between call types found in Cntnap2 knockout pups from heterozygous breeding. In contrast, the effect of maternal immune activation on the offspring's vocal communication was confined to call type syntax, but left ultrasonic vocalization acoustic and temporal organization intact. Our results support the "double-hit hypothesis" of autism spectrum disorder risk gene-environment interactions and emphasize that complex features of vocal communication are a useful tool for identifying early autistic-like features in rodent models.

The startle response consists of whole-body muscle contractions, eye-blink, accelerated heart rate, and freezing in response to a strong, sudden stimulus. It is evolutionarily preserved and can be observed in any animal that can perceive sensory signals, indicating the important protective function of startle. Startle response measurements and its alterations have become a valuable tool for exploring sensorimotor processes and sensory gating, especially in the context of pathologies of psychiatric disorders. The last reviews on the neural substrates underlying acoustic startle were published around 20 years ago. Advancements in methods and techniques have since allowed new insights into acoustic startle mechanisms. This review is focused on the neural circuitry that drives the primary acoustic startle response in mammals. However, there have also been very successful efforts to identify the acoustic startle pathway in other vertebrates and invertebrates in the past decades, so at the end we briefly summarize these studies and comment on the similarities and differences between species.

ObjectiveTo describe the population, heart failure (HF) diagnosis rate, and 1-year hospitalisation and mortality of patients with suspected HF and elevated N-terminal pro B-type natriuretic peptide (NTproBNP) investigated according to UK National Institute for Health and Care Excellence (NICE) guidelines.MethodsNICE recommends patients with suspected HF, based on clinical presentation and elevated NTproBNP, are referred for specialist assessment and echocardiography. Patients should be seen within 2 weeks when NTproBNP is >2000 pg/mL (2-week pathway: 2WP) or within 6 weeks when NTproBNP is 400–2000 pg/mL (6-week pathway: 6WP). This is a retrospective, multicentre, observational study of consecutive patients with suspected HF referred from primary care between 2014 and 2016 to dedicated secondary care HF clinics based on the NICE 2WP and 6WP. Data were obtained from hospital records and episode statistics. Mortality and hospitalisation rates were calculated 1 year from NTproBNP measurement.Results1271 patients (median age 80; IQR 73–85) were assessed, 680 (53%) of whom were female. 667 (53%) were referred on the 2WP and 604 (47%) on the 6WP. 698 (55%) were diagnosed with HF (369 HF with reduced ejection fraction) and 566 (45%) as not HF (NHF). 1-year mortality was 10% (n=129) and hospitalisation was 33% (n=413). Patients on the 2WP had higher mortality and hospitalisation rates than those on the 6WP, 14% vs 6% (pConclusionsOutcomes using the NICE approach of short waiting time targets for specialist assessment of patients with suspected HF and raised NTproBNP are not known. The model identifies an elderly population a high proportion of whom have HF. Irrespective of diagnosis, patients have high rates of adverse outcomes. These contemporary real-world data provide a platform for discussions with patients and shaping HF services.

Funding Acknowledgements Type of funding sources: None. Background Adenosine stress perfusion has been shown to be of minimal incremental benefit in distinguishing between ischaemic and non-ischaemic aetiology of severe left ventricular systolic dysfunction (LVSD) over and above that obtained from Cardiac Magnetic Resonance (CMR) with Late Gadolinium Enhancement (LGE). Stress CMR has, however, been shown to be effective in risk-stratifying LVSD patients, with ischaemia being an independent predictor of cardiovascular death or myocardial infarction (MI) and associated with higher rates of further intervention. Purpose Evaluate real world data from a single tertiary UK cardiac MRI centre to determine the characteristics and long-term clinical outcomes of patients with LVSD referred for stress CMR. Methods As part of an ongoing registry, all consenting patients with Ejection Fraction (EF) ≤40% and a completed adenosine stress perfusion CMR between January 2015 and December 2019 were included with prospective baseline data collection. All-cause mortality and cardiac hospitalisation, coronary angiography/revascularisation was determined from electronic hospital records. Outcomes were compared between the inducible ischaemia vs. no ischaemia groups, and LGE present vs. no LGE groups using chi square. Results The sample included 86 patients. The mean EF was 32 ± 6%. Median follow up was 3.8 years (range 41-2222 days). The indications for CMR were: 30 (35%) assess ischaemia, 35 (41%) assess LVSD aetiology and 21 (24%) LVSD assess viability. Inducible ischemia was present in 30 (35%) patients and absent in 56 (65%). Patient characteristics and outcomes are shown in Table 1. Baseline characteristics were similar between the groups but there was a higher rate of hypertension and ischaemic heart disease in the ischaemia group. There was a non-significant difference in combined mortality and cardiac hospitalisation rates between the groups (40% vs. 27% p = 0.20). LGE was present in 69 (80%) patients (28 with ischaemia; 41 without) and absent in 17 (20%, 2 with ischaemia, 15 without). The event rate was 23 (33%) vs. 4 (24%) between LGE vs. No LGE groups (p = 0.44). Of the 15 patients (17%) with no LGE or ischaemia; 2 died and 1 was hospitalised, there were no MI"s and no Percutaneous Coronary Intervention (PCI). The lack of statistical difference in event rates between ischaemia and no ischaemia groups may be due to our relatively small sample size or could reflect the effectiveness of contemporary disease modifying treatment for Heart Failure with reduced EF. Conclusion This real-world data supports published findings that in patients with LVSD and no LGE on CMR, ischaemia is very uncommon and stress CMR is unlikely to increase diagnostic yield. Conversely, if stress CMR is performed and ischaemia is absent, incidence of subsequent angiography and revascularisation is very low, which is reassuring in clinical practice. In those patients without ischaemia and LGE, likelihood of MI is low.

Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis but a prosperous outer environment. During the 40 years of reform and opening-up policy, Chinese scientists contributed significantly in the field of medical genetics, garnering considerable attention worldwide. In this review, we highlight the significant findings and/or results discovered by Chinese scientists in monogenic diseases, complex diseases, cancer, genetic diagnosis, as well as gene manipulation and gene therapy. Due to these achievements, China is widely recognized to be at the forefront of medical genetics research and development. However, the significant progress and development that has been achieved could not have been accomplished without sufficient funding and a well-constructed logistics network. The successful implementation of translational and precise medicine sourced from medical genetics will depend on an open ethics policy and intellectual property protection, along with strong support at the national industry level.

Unbiased antibody profiling can identify the targets of an immune reaction. A number of likely pathogenic autoreactive antibodies have been associated with life-threatening SARS-CoV-2 infection; yet, many additional autoantibodies likely remain unknown. Here we present Molecular Indexing of Proteins by Self Assembly (MIPSA), a technique that produces ORFeome-scale libraries of proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing. We used MIPSA to profile circulating autoantibodies from 55 patients with severe COVID-19 against 11,076 DNA-barcoded proteins of the human ORFeome library. MIPSA identified previously known autoreactivities, and also detected undescribed neutralizing interferon lambda 3 (IFN-λ3) autoantibodies. At-risk individuals with anti- IFN-λ3 antibodies may benefit from interferon supplementation therapies, such as those currently undergoing clinical evaluation., Graphical Abstract, One-Sentence Summary Molecular Indexing of Proteins by Self Assembly (MIPSA) identifies neutralizing IFNL3 autoantibodies in patients with severe COVID-19.

Synthetic bioconjugation at cysteine (Cys) residues in peptides and proteins has emerged as a powerful tool in chemistry. Soft nucleophilicity of the sulfur in Cys renders an exquisite chemoselectivity with which various functional groups can be placed onto this residue under benign conditions. While a variety of reactions have been successful at producing Cys-based bioconjugates, the majority of these feature sulfur-carbon bonds. We report Cys-borylation, wherein a benchtop stable Pt(II)-based organometallic reagent can be used to transfer a boron-rich cluster onto a sulfur moiety in unprotected peptides forging a boron-sulfur bond. Discovered Cysborylation proceeds at room temperature and is tolerant to a variety of functional groups present in complex polypeptides. The resultant bioconjugates show no additional toxicity compared to their Cys aryl-based congeners. Finally, we demonstrate how the developed Cys-borylation can enhance the proteolytic stability of the produced peptide bioconjugates while maintaining the binding affinity to a protein target.

Background Myositis, or idiopathic inflammatory myopathy (IIM), is a group disorders of unknown etiology characterized by the inflammation of skeletal muscle. The role of T cells and their antigenic targets in IIM initiation and progression is poorly understood. T cell receptor (TCR) repertoire sequencing is a powerful approach for characterizing complex T cell responses. However, current TCR sequencing methodologies are complex, expensive, or both, greatly limiting the scale of feasible studies. Methods Here we present Framework Region 3 AmplifiKation sequencing (“FR3AK-seq”), a simplified multiplex PCR-based approach for the ultra-efficient and quantitative analysis of TCR complementarity determining region 3 (CDR3) repertoires. By using minimal primer sets targeting a conserved region immediately upstream of CDR3, undistorted amplicons are analyzed via short read, single-end sequencing. We also introduce the novel algorithm Inferring Sequences via Efficiency Projection and Primer Incorporation (“ISEPPI”) for linking CDR3s to their associated variable genes. Findings We find that FR3AK-seq is sensitive and quantitative, performing comparably to two different industry standards. FR3AK-seq and ISEPPI were used to efficiently and inexpensively characterize the T cell infiltrates of surgical muscle biopsies obtained from 145 patients with IIM and controls. A cluster of closely related TCRs was identified in samples from patients with sporadic inclusion body myositis (IBM). Interpretation The ease and minimal cost of FR3AK-seq removes critical barriers to routine, large-scale TCR CDR3 repertoire analyses, thereby democratizing the quantitative assessment of human TCR repertoires in disease-relevant target tissues. Importantly, discovery of closely related TCRs in muscle from patients with IBM provides evidence for a shared antigen-driven T cell response in this disease of unknown pathogenesis. Funding This work was supported by NIH grant U24AI118633 and a Prostate Cancer Foundation Young Investigator Award.

Organic rechargeable batteries have attracted extensive attention as a potential alternative for the current lithium-ion batteries. However, most of the reports are limited to organic macromolecules or modified small organic molecules which exhibit low reversible capacity, poor rate capability, and very limited cycle life. Herein, a small organic compound, maleic acid, is adopted as the anode for lithium ion batteries without any modification. It exhibits an ultrahigh reversible capacity of ca. 1500 mAh g–1 at 46.2 mA g–1 current density. Even at a high current density of 46.2 A g–1, the electrode still delivers a capacity of 570.8 mAh g–1. When cycled at 2.31 A g–1, a capacity retention of 98.1% is obtained after 500 cycles. The excellent performance of the maleic acid organic anode is ascribed to its small volume effect and unique lithium-ion storage mechanisms. This new type of organic anode material may have a great opportunity for large-scale energy-storage systems with high-power properties.

Introduction Chronic heart failure (HF) represents a substantial and growing public health and financial burden and has a poor prognosis. National Institute for Health and Care Excellence (NICE) guidelines and quality standards recommend timely specialist assessment for patients with suspected HF and raised natriuretic peptides. However, data on the outpatient population assessed, diagnostic rates of HF and outcomes for patients on this pathway are not known. This is in contrast to patients hospitalised with acute HF who are well described in the UK. Our aim is to describe real world data from a large patient cohort with suspected HF investigated according to NICE protocols. Methods All patients with suspected HF and elevated NTproBNP referred to a dedicated HF clinic between January 2014 – December 2016 were included. Patients underwent specialist assessment, echocardiography and diagnosis in a one-stop clinic within 2 weeks (NTproBNP>2000pg/ml) or 6 weeks (NTproBNP 400–2000pg/ml) in accordance with NICE guidelines. Patient baseline characteristics and co-morbidities were recorded prospectively. 1 year all-cause hospitalisation (1 or more admissions) and mortality rates were retrospectively calculated from the date of NTproBNP measurement using hospital coding data and electronic patient records. Outcomes were compared between those referred on the 2 and 6 week pathways; and between those diagnosed with Heart Failure (HF) vs. Not Heart Failure (NHF) after specialist assessment. Results Out of 1042 consecutive patients referred, 1013 had NTproBNP measured and were included. 544 (54%) were on the 2-week and 469 (46%) on the 6-week pathway. 543 (54%) were diagnosed with HF; 300 (55%) with Heart Failure with reduced Ejection Fraction (HFrEF) and 243 (45%) with Heart Failure with preserved Ejection Fraction (HFpEF). 454 (45%) were diagnosed as NHF. A diagnosis of HF was made in 383 (70%) in the 2-week and 160 (34%) in the 6-week pathway (p For the entire population the 1-year hospitalisation rate was 324/1013 (32%) and mortality 112/1013 (11%). There were significantly higher rates of both mortality (88 [16%] vs 24 [5%] p Conclusion The prognosis is relatively poor for outpatients with suspected chronic HF and raised natriuretic peptides, with high rates of adverse outcomes observed despite specialist investigation in accordance within NICE timeframes. This is regardless of the final diagnosis, as mortality is comparable between HF and NHF groups. The proportion of patients diagnosed with HF in the 2-week pathway was high. As expected, patients referred via the 2-week pathway had significantly higher rates of both mortality and hospitalisation. This study provides valuable real world data and insight into an important population, which will help inform discussions with patients and shape chronic HF services. Conflict of Interest None

Immune receptor repertoire (IRR) sequencing is increasingly employed to characterize adaptive immune responses. However, current IRR sequencing methodologies are complex, expensive, or both, thereby limiting routine utilization. Here we present Framework Region 3 AmplifiKation sequencing ("FR3AK-seq"), a simplified multiplex PCR-based approach for the ultra-efficient analysis of IRRs. By using minimal primer sets that target a conserved region adjacent to the hypervariable VDJ sequence, undistorted amplicon can be analyzed via short read, single-end sequencing. We find that FR3AK-seq is sensitive and quantitative, with a per sample cost of ~50-fold below the current industry standard. Inference of V-allele usage from FR3AK-seq data is demonstrated using a novel algorithm: Inferring Sequences via Efficiency Projection and Primer Incorporation ("ISEPPI"). FR3AK-seq and ISEPPI were utilized to quickly and inexpensively characterize the T cell infiltrates of 146 muscle biopsies obtained from patients with idiopathic inflammatory myopathies (IIMs) and controls. A cluster of related T cell receptors were identified in samples from patients with sporadic inclusion body myositis, suggesting the presence of an unknown shared antigen. The ease and cost of FR3AK-seq analysis removes the current barriers to routine, large-scale IRR analyses.

Introduction Natriuretic peptides, including NTproBNP, are elevated in heart failure (HF) and correlate with prognosis. They also predict the development of HF and are associated with an adverse outcome in patients without overt HF. NICE CG108 mandates that patients with potential HF and elevated natriuretic peptides are evaluated with echocardiography and specialist assessment. There are few data on how outcomes compare based on whether the final diagnosis is HF or not after assessment. Furthermore, the incidence of subsequent HF in patients where the diagnosis is initially rejected is unknown. Methods All patients with possible HF and raised NTproBNP referred to a single centre specialist HF clinic in a 1 year period from March 2014 were identified. Patients were seen within 2 (NTproBNP >2000 pg/ml) or 6 (NTproBNP 400­2000 pg/ml) weeks of referral in line with NICE CG108. Hospital coding data and electronic patient records were used to identify all-cause unplanned hospital admissions and mortality over a minimum follow up period of 2 years. Event rates were compared between patients with a final diagnosis of HF and those without (no heart failure-NHF). We also recorded how many NHF patients went on to develop HF. Results 235 patients were seen and form the study population. Mean follow up was 29±4 months. 133 (56%) patients were diagnosed with HF; 63 (47%) with HF with Reduced Ejection Fraction (HFREF) and 70 (53%) with HF with Preserved Ejection Fraction (HFPEF). 102 (43%) were diagnosed as NHF. Comorbidities in the NHF group are shown in table 2. Patients in the two groups were similar in age. HF patients had much higher NTproBNP levels and higher rates of AF and diabetes (table 1). Despite this, there were no differences in either mortality (HF 23% and NHF 22%; p=0.75) or hospitalisations (HF 41% and NHF 40%; p=0.95) between the groups; figure 1. 7 (7%) of NHF patients were subsequently diagnosed with HF. Negative predictive value of a NHF diagnosis was 93%. Conclusions Patients with suspected HF and raised natriuretic peptides are at high risk of adverse outcomes regardless of the final diagnosis after specialist evaluation. Much higher NTproBNP levels and higher rates of diabetes and AF in the HF group did not translate into a worse prognosis. This may be due to the fact that patients with a HF (in particular HFREF) diagnosis were considered for evidence based therapies. The adverse outcome in the NHF group is not explained by unrecognised HF at assessment as subsequent presentations with HF were uncommon. These findings should be taken into consideration when framing our discussions with all patients with elevated NTproBNP regarding their prognosis.

Introduction T cell convergence refers to the phenomenon whereby antigen-driven selection enriches for T cell receptors having a shared antigen specificity but different amino acid or nucleotide sequence. T cell recruitment and expansion within the tumor microenvironment (TME) may be directed by responses to tumor neoantigen, suggesting that elevated T cell convergence could be a general feature of the tumor infiltrating T cell repertoire. Here we evaluate evidence for T cell convergence within tumor biopsy research samples from a set of 85 subjects with melanoma. Methods Total RNA from 85 tumor biopsy research samples (non-FFPE) was extracted for use in long-amplicon TCRB chain sequencing (mean amplicon length of 330bp covering CDR1, 2 and 3) via the Ion AmpliSeq Immune Repertoire Assay Plus, TCRB. To evaluate T cell convergence within each biopsy, we searched for instances where TCRB chains were identical in amino acid space (shared variable gene identity and CDR3 amino acid sequence) but had distinct nucleotide sequences owing to N-addition and exonucleotide chewback within the V-D and D-J junctions of the CDR3. To provide context, we evaluated evidence for T cell convergence with T cell repertoires derived from healthy donor peripheral blood leukocytes (PBL). Results Sequencing of melanoma biopsies yielded an average of 6029 clones per sample. 11 of 85 samples yielded fewer than 100 clones and were eliminated from downstream analysis. Convergent T cell receptors were identified in 68/74 (92%) of tumor infiltrating T cell repertoires having greater than 100 detected clones. The frequency of convergent rearrangements was approximately 50-fold greater in the melanoma-infiltrating T cell repertoire than healthy PBL samples (p Conclusions These data suggest that T cell convergence may be a common feature of the melanoma infiltrating T cell repertoire. Convergence was more frequently observed within the TME than T cell repertoires derived from healthy PBL, consistent with elevated antigen-driven T cell selection within the TME. The extent to which convergence is a feature of the TME in other cancers is not yet known. T cell receptor convergence may be driven by T cell responses to tumor neoantigen within the TME. In such case, in silico identification of convergent T cell receptors by long-amplicon sequencing may serve as an approach for rapid identification of antigen-specific T cell receptors for future therapeutic use. For research use only. Citation Format: Timothy J. Looney, Sean Glenn, Sarabjot Pabla, Jeff Conroy, Carl Morrison, Alice Zheng, Lauren Miller, Elizabeth Linch, Denise Topacio, Geoff Lowman, Fiona Hyland, Mark Anderson. Evidence for antigen-driven TCRB chain convergence in the tumor infiltrating T cell repertoire of 85 research subjects with melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4668.

Perhaps surprisingly, no practical performance models exist for popular (and complex) client applications such as Adobe's Designer suite, Microsoft's Office suite and Visual Studio, Mozilla, Halo 3, etc. There is currently no tool that automatically answers program developers', IT administrators' and end-users' simple what-if questions like "what happens to the performance of my favorite application X if I upgrade from Windows Vista to Windows 7?". This paper describes directions we are taking for constructing practical, versatile performance models to address this problem. The directions we have taken have two paths. The first path involves instrumenting applications better to export their state and associated metrics. This application-specific monitoring is always on and interesting data is collected from real, "in-the-wild" deployments. The second path involves statistical modeling techniques. The models we are experimenting with require no modifications to the OS or applications beyond the above instrumentation, and no explicit a priori model on how an OS or application should behave. We are in the process of learning from models we have constructed for several Microsoft products, including the Office suite, Visual Studio and Media Player. This paper presents preliminary findings from a large user deployment (several hundred thousand user sessions) of these applications that show the coverage and limitations of such models. Early indications from this work point towards future modeling strategies based on large amounts of data collected in the field. We present our thoughts on what this could imply for the SIGMETRICS community.

There are a lot of applications that run on modern mobile operating systems. Inevitably, some of these applications fail in the hands of users. Diagnosing a failure to identify the culprit, or merely reproducing that failure in the lab is difficult. To get insight into this problem, we interviewed developers of five mobile applications and analyzed hundreds of trouble tickets. We find that support for diagnosing unexpected application behavior is lacking across major mobile platforms. Even when developers implement heavy-weight logging during controlled trials, they do not discover many dependencies that are then stressed in the wild. They are also not well-equipped to understand how to monitor the large number of dependencies without impacting the phone's limited resources such as CPU and battery. Based on these findings, we argue for three fundamental changes to failure reporting on mobile phones. The first is spatial spreading, which exploits the large number of phones in the field by spreading the monitoring work across them. The second is statistical inference, which builds a conditional distribution model between application behavior and its dependencies in the presence of partial information. The third is adaptive sampling, which dynamically varies what each phone monitors, to adapt to both the varying population of phones and what is being learned about each failure. We propose a system called MobiBug that combines these three techniques to simplify the task of diagnosing mobile applications.

The study of social networks has gained new importance with the recent rise of large on-line communities. Most current approaches focus on deterministic (descriptive) models and are usually restricted to a preset number of people. Moreover, the dynamic aspect is often treated as an addendum to the static model. Taking inspiration from real-life friendship formation patterns, we propose a new generative model of evolving social networks that allows for birth and death of social links and addition of new people. Each person has a distribution over social interaction spheres, which we term "contexts." We study the robustness of our model by examining statistical properties of simulated networks relative to well known properties of real social networks. We discuss the shortcomings of this model and problems that arise during learning. Several extensions are proposed.