Dead or alive: Distinguishing active from passive particles using supervised learning

A longstanding open question in the field of dense disordered matter is how precisely structure and the dynamics are related to each other. With the advent of machine learning, it has become possible to agnostically predict the dynamic propensity of a particle in a dense liquid based on its local structural environment. Thus far, however, these machine learning studies have focused almost exclusively on simple liquids composed of passive particles. Here we consider a mixture of both passive and active (i.e. self-propelled) Brownian particles, with the aim to identify the active particles from minimal local structural information. We find that the established machine learning approaches for passive systems are ineffective for our goal, implying that dynamic propensity and non-equilibrium activity carry a fundamentally different structural signature. To distinguish passive from active particles, we instead develop a pseudo-static machine learning method that uses both local structural order parameters and their averaged fluctuations as input. Our final neural network is able to detect with almost 100% accuracy which particles are active and which ones are not. Hence, our machine learning model can identify distinct dynamical single-particle properties with minimal dynamical information. Ultimately, these efforts might also find relevance in the context of biological active glasses such as confluent cell layers, where subtle changes in the microstructure can hint at pathological changes in cell dynamics

Occipital hypometabolism is a risk factor for conversion to Parkinson’s disease in isolated REM sleep behaviour disorder

Purpose: Isolated REM sleep behaviour disorder (iRBD) patients are at high risk of developing clinical syndromes of the α-synuclein spectrum. Progression markers are needed to determine the neurodegenerative changes and to predict their conversion. Brain imaging with 18F-FDG PET in iRBD is promising, but longitudinal studies are scarce. We investigated the regional brain changes in iRBD over time, related to phenoconversion.Methods: Twenty iRBD patients underwent two consecutive 18F-FDG PET brain scans and clinical assessments (3.7 ± 0.6 years apart). Seventeen patients also underwent 123I-MIBG and 123I-FP-CIT SPECT scans at baseline. Four subjects phenoconverted to Parkinson’s disease (PD) during follow-up. 18F-FDG PET scans were compared to controls with a voxel-wise single-subject procedure. The relationship between regional brain changes in metabolism and PD-related pattern scores (PDRP) was investigated.Results: Individual hypometabolism t-maps revealed three scenarios: (1) normal 18F-FDG PET scans at baseline and follow-up (N = 10); (2) normal scans at baseline but occipital or occipito-parietal hypometabolism at follow-up (N = 4); (3) occipital hypometabolism at baseline and follow-up (N = 6). All patients in the last group had pathological 123I-MIBG and 123I-FP-CIT SPECT. iRBD converters (N = 4) showed occipital hypometabolism at baseline (third scenario). At the group level, hypometabolism in the frontal and occipito-parietal regions and hypermetabolism in the cerebellum and limbic regions were progressive over time. PDRP z-scores increased over time (0.54 ± 0.36 per year). PDRP expression was driven by occipital hypometabolism and cerebellar hypermetabolism.Conclusions: Our results suggest that occipital hypometabolism at baseline in iRBD implies a short-term conversion to PD. This might help in stratification strategies for disease-modifying trials.</p

Silane-Mediated Expansion of Domains in Si-Doped κ-Ga2O3 Epitaxy and its Impact on the In-Plane Electronic Conduction

Unintentionally doped (001)-oriented orthorhombic κ-Ga2O3 epitaxial films on c-plane sapphire substrates are characterized by the presence of ≈ 10 nm wide columnar rotational domains that can severely inhibit in-plane electronic conduction. Comparing the in- and out-of-plane resistance on well-defined sample geometries, it is experimentally proved that the in-plane resistivity is at least ten times higher than the out-of-plane one. The introduction of silane during metal-organic vapor phase epitaxial growth not only allows for n-type Si extrinsic doping, but also results in the increase of more than one order of magnitude in the domain size (up to ≈ 300 nm) and mobility (highest µ ≈ 10 cm2V−1s−1, with corresponding lowest ρ ≈ 0.2 Ωcm). To qualitatively compare the mean domain dimension in κ-Ga2O3 epitaxial films, non-destructive experimental procedures are provided based on X-ray diffraction and Raman spectroscopy. The results of this study pave the way to significantly improved in-plane conduction in κ-Ga2O3 and its possible breakthrough in new generation electronics. The set of cross-linked experimental techniques and corresponding interpretation here proposed can apply to a wide range of material systems that suffer/benefit from domain-related functional properties

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Aging in thermal active glasses

It is well established that glassy materials can undergo out-of-equilibrium aging, i.e., their properties gradually change over time. There is rapidly growing evidence that dense active and living systems also exhibit many features of glassy behavior, but it is still largely unknown if and how physical aging is manifested in such non-Hamiltonian glassy materials. Here we show, by means of computer simulations, that the aging dynamics of active thermal glasses is governed by a complex interplay of different relaxation mechanisms. Notably, we identify a time-dependent competition between thermal and active effects, which gives rise to an explicitly age-dependent effective temperature. As a consequence, the often-invoked mapping between an active system and a passive one with a unique, higher effective temperature rigorously breaks down upon aging. Moreover, unlike passive aging phenomenology, we find that the degree of dynamic heterogeneity in active aging systems is relatively small and remarkably constant with age. We attribute these differences to activity-enhanced cage breaking, which modifies both the quantitative and qualitative nature of the aging process in active glassy matter

GEO.Cool : Kühlung mit oberflächennaher Geothermie - Möglichkeiten, Grenzen, Innovation -

Das Verbundprojekt GEO.Cool von Partnern im Landesforschungszentrum Geothermie (LFZG) hat zum Ziel, Möglichkeiten sowie Grenzen der Kühlung mit oberflächennaher Geothermie in interdisziplinärer Arbeit zu erheben und daraus Impulse für Innovationen in diesem Bereich zu gewinnen. Das Vorhaben ist in die folgenden sechs Arbeitspakete (AP) gegliedert: AP 1: Bedarfe und Systemaspekte AP 2: Systemtechnik und Planung von Anlagen zur Kühlung mit oberflächennaher Ge-othermie AP 3: Analyse von Best-Practice-Beispielen AP 4: Thermisches und hydrogeologisches Verhalten des Untergrunds AP 5: Genehmigungspraxis und Grenzwerte AP 6: Synopse, Innovationspotenzial und Transfer. Das Projekt hat eine Laufzeit vom 23.01.2017 bis zum 30.09.2019 (Förderzeitraum für alle Arbeitspakete und Projektpartner)

GEO.Cool : Kühlung mit oberflächennaher Geothermie - Möglichkeiten, Grenzen, Innovation -

In dem durchgeführten Verbundvorhaben arbeiteten zum einen die Fachgebiete Geologie/Geothermie sowie Anlagen- und Systemtechnik von geothermischer Kältegewinnung und Kältenutzung der Projektpartner interdisziplinär zusammen, um den aktuellen Wissensstand der Kühlung mittels oberflächennaher Geothermie fachübergreifend zu erfassen, zu bewerten und Schnittstellenprobleme zu bearbeiten. Aus dieser interdisziplinären Betrachtungsweise wurden ganzheitliche Hinweise zur Optimierung des geothermischen Kühlpotenzials sowie Anstöße für technische und planerische Innovationen für die Praxis entwickelt und in diese transferiert. Zu folgenden Zielen wurden Beiträge erarbeitet: - Steigerung der Energieeffizienz der Kühlung und Kältebereitstellung - Nutzung regenerativer Energien zur Kühlung und Kältebereitstellung - Begrenzung der thermischen Belastung des Untergrunds und des Grundwassers - Minimierung der Schäden und Risiken durch den Eingriff in den Untergrun

p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages.: p16INK4a function in macrophages

International audienceThe CDKN2A locus, which contains the tumor suppressor gene p16(INK4a), is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role. Monocytes can polarize toward classically (CAMϕ) or alternatively (AAMϕ) activated macrophages. However, the molecular mechanisms underlying the acquisition of these phenotypes are not well defined. Here, we show that p16(INK4a) deficiency (p16(-/-)) modulates the macrophage phenotype. Transcriptome analysis revealed that p16(-/-) BM-derived macrophages (BMDMs) exhibit a phenotype resembling IL-4-induced macrophage polarization. In line with this observation, p16(-/-) BMDMs displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. Furthermore, mice transplanted with p16(-/-) BM displayed higher hepatic AAMϕ marker expression levels on Schistosoma mansoni infection, an in vivo model of AAMϕ phenotype skewing. Surprisingly, p16(-/-) BMDMs did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and lipopolysaccharide (LPS)-induced IKKα,β phosphorylation. This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. These findings identify p16(INK4a) as a modulator of macrophage activation and polarization via the JAK2-STAT1 pathway with possible roles in inflammatory diseases