Anticooperativity in diffusion-controlled reactions with pairs of anisotropic domains: a model for the antigen-antibody encounter

The encounter between anisotropic agents in diffusion-controlled reactions is a topic of very general relevance in chemistry and biology. Here we introduce a simplified model of encounter of an isotropic molecule with a pair of partially reacting agents and apply it to the encounter reaction between an antibody and its antigen. We reduce the problem to the solution of dual series relations, which can be solved iteratively, yielding the exact solution for the encounter rate constant at any desired order of accuracy. We quantify the encounter effectiveness by means of a simple indicator and show that the two binding centers systematically behave in an anticooperative fashion. However, we demonstrate that a reduction of the binding active sites allows the composite molecule to recover binding effectiveness, in spite of the overall reduction of the rate constant. In addition, we provide a simple formula that enables one to calculate the anticooperativity as a function of the size of the binding site for any values of the separation between the two active lobes and of the antigen size. Finally, some biological implications of our results are discusse

A nonparametric Bayesian approach toward robot learning by demonstration

In the past years, many authors have considered application of machine learning methodologies to effect robot learning by demonstration. Gaussian mixture regression (GMR) is one of the most successful methodologies used for this purpose. A major limitation of GMR models concerns automatic selection of the proper number of model states, i.e., the number of model component densities. Existing methods, including likelihood- or entropy-based criteria, usually tend to yield noisy model size estimates while imposing heavy computational requirements. Recently, Dirichlet process (infinite) mixture models have emerged in the cornerstone of nonparametric Bayesian statistics as promising candidates for clustering applications where the number of clusters is unknown a priori. Under this motivation, to resolve the aforementioned issues of GMR-based methods for robot learning by demonstration, in this paper we introduce a nonparametric Bayesian formulation for the GMR model, the Dirichlet process GMR model. We derive an efficient variational Bayesian inference algorithm for the proposed model, and we experimentally investigate its efficacy as a robot learning by demonstration methodology, considering a number of demanding robot learning by demonstration scenarios

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe

Iron Age and Anglo-Saxon genomes from East England reveal British migration history

British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain

Circulating Brain-Injury Markers After Surgery for Craniosynostosis

Objective: Historically, there have been few quantitative methods for effectively evaluating outcomes after surgery for craniosynostosis. In this prospective study, we assessed a novel approach for detecting possible postsurgery brain injury in patients with craniosynostosis. Methods: We included consecutive patients operated on for sagittal (pi-plasty or craniotomy combined with springs) or metopic (frontal remodeling) synostosis at the Craniofacial Unit at Sahlgrenska University Hospital, Gothenburg, Sweden, from January 2019 to September 2020. Plasma concentrations of the brain-injury biomarkers neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau were measured immediately before induction of anesthesia, immediately before and after surgery, and on the first and the third postoperative days using single-molecule array assays. Results: Of the 74 patients included, 44 underwent craniotomy combined with springs for sagittal synostosis, 10 underwent pi-plasty for sagittal synostosis, and 20 underwent frontal remodeling for metopic synostosis. Compared with baseline, GFAP level showed a maximal significant increase at day 1 after frontal remodeling for metopic synostosis and pi-plasty (P = 0.0004 and P = 0.003, respectively). By contrast, craniotomy combined with springs for sagittal synostosis showed no increase in GFAP. For neurofilament light, we found a maximal significant increase at day 3 after surgery for all procedures, with significantly higher levels observed after frontal remodeling and pi-plasty compared with craniotomy combined with springs (P < 0.001). Conclusions: These represent the first results showing significantly increased plasma levels of brain-injury biomarkers after surgery for craniosynostosis. Furthermore, we found that more extensive cranial vault procedures resulted in higher levels of these biomarkers relative to less extensive procedures

Tiltaksanalyse for Morsa (Vansjø-Hobøl-vassdraget) - Sluttrapport

Årsliste 2001Tiltaksanalysen for Morsa (Vansjø-Hobølvassdraget) viser at vassdraget er overbelastet med næringssalter. Den totale fosfortilførselen er beregnet til ca. 19 tonn, hvorav ca. 5 tonn kommer fra naturlig bakgrunnsavrenning, 11 tonn fra jordbruket, 2 tonn fra spredt kloakkavløp (2210 separate avløpsanlegg er registrert i nedbørfeltet) og 1 tonn fra kommunalt kloakkavløp. For å nå miljømålene om at Vansjø-Storefjorden skal egne seg til drikkevann og at vassdraget for øvrig skal egne seg til bading, fritidsfiske og jordvanning må 65% av de menneskeskapte fosfortilførslene fjernes. Kvantifiserte tiltak innen jordbruket (der endret jordarbeiding er det viktigste enkelttiltaket), tiltak innen separate avløp (særlig på direkte utslipp og slamavskillere), samt utbedring av feilkoblinger på kommunale kloakkledninger vil fjerne drøyt 50% av de menneskeskapte fosfortilførslene, mens andre tiltak innen jordbruk og avløpssektoren (særlig mot overløp og lekkasjer) vil kunne gi betydelige tilleggsgevinster, som sannsynliggjør oppnåelse av målet om 65% reduksjon. Overføring av restutslipp fra to kommunale renseanlegg til andre resipienter vil fjerne < 0,5 % av tilførslene og være lite kostnadseffektivt idag. Dersom antall tilknyttede boliger tredobles i framtiden vil tiltaket kunne få en kostnadseffektivitet som er ca. 2 ganger dårligere enn tiltak innen separate avløp. Vassdragsinterne tiltak som utfisking og regulering av vannstanden har potensiale til å gi ytterligere forbedringer, men effekten er vanskelig å kvantifisere. Klimaendringer vil kunne motvirke effekten av de iverksatte tiltakene og potensielt forverre dagens tilstand i vassdraget.Hovedstyret for Morsa-prosjekte

Anti-cooperativity in diffusion-controlled reactions with pairs of anisotropic domains: a model for the antigen-antibody encounter

The encounter between anisotropic agents in diffusion-controlled reactions is a topic of very general relevance in chemistry and biology. Here we introduce a simplified model of encounter of an isotropic molecule with a pair of partially reacting agents and apply it to the encounter reaction between an antibody and its antigen. We reduce the problem to the solution of dual series relations, which can be solved iteratively, yielding the exact solution for the encounter rate constant at any desired order of accuracy. We quantify the encounter effectiveness by means of a simple indicator and show that the two binding centers systematically behave in an anti-cooperative fashion. However, we demonstrate that a reduction of the binding active sites allows the composite molecule to recover binding effectiveness, in spite of the overall reduction of the rate constant. In addition, we provide a simple formula that enables one to calculate the anti-cooperativity as a function of the size of the binding site for any values of the separation between the two active lobes and of the antigen size. Finally, some biological implications of our results are discussed

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm