Transfer of optogenetic vectors into the brain of neonatal animals to study neuron functions during subsequent periods of development

Optogenetics, that is, the control of cell activity using light-sensitive ion channels opsins with light of a specific wavelength, is increasingly being used to study activities and functions of neurons. Expression of opsins in the cell membrane, followed by the acquisition by the cell of the sensitivity to light is achieved by means of viral vectors, often created on the basis of lentiviral or adeno-associated (AAV) viruses bearing the nucleotide sequence encoding the photo-channel proteins. Inclusion of the cell-specific promoter of interest into the transgene-expression cassette allows opsin to be produced only in the target cells. The aim of this work was to briefly describe the optogenetic method, as well as to analyze the possibility to use administration of viral vectors into the brain of neonatal animals to study the function of neurons in vivo during subsequent periods of development. In this analysis, 3-day-old rat pups received intracerebroventricular injections of optovector (pAAV-CAMKIIa-ChR2h134-YFP), coding for a photo channel, which activates neurons, and the yellow fluorescent marker protein under the CAMKIIa promoter specific for glutamatergic neurons under cold anesthesia. The peak expression of the transferred gene is usually achieved at week 3–5 after the transfer of the vector, which is what was also observed in our experiments. Stimulation of the hippocampal neurons with blue light in the 20-day-old animals, to which opto-vector was transferred at the 3rd day of life, increased the discharge activity of these neurons. This light stimulation increased expression of the recognized marker of neuronal activation protein c-Fos in these photosensitive cells too. The same experiments with older animals, 60 days after the neonatal opto-channel gene transfer, revealed no noticeable expression of this channel or photoactivation of target neurons of the hippocampus. Thus, neonatal administration of a viral vector carrying an opto-channel gene is suitable for the study of brain neurons in rats of juvenile age, and requires additional control for gene expression during subsequent periods of development

Multi-Scalar-Singlet Extension of the Standard Model - the Case for Dark Matter and an Invisible Higgs Boson

We consider a simple extension of the Standard Model by the addition of N real scalar gauge singlets \vp that are candidates for Dark Matter. By collecting theoretical and experimental constraints we determine the space of allowed parameters of the model. The possibility of ameliorating the little hierarchy problem within the multi-singlet model is discussed. The Spergel-Steinhardt solution of the Dark Matter density cusp problem is revisited. It is shown that fitting the recent CRESST-II data for Dark Matter nucleus scattering implies that the standard Higgs boson decays predominantly into pairs of Dark Matter scalars. It that case discovery of the Higgs boson at LHC and Tevatron is impossible. The most likely mass of the dark scalars is in the range 15 GeV \lsim \mvp \lsim 50 GeV with BR(h \to \vp\vp) up to 96%.Comment: 18 pages, 15 figure

Events in the affective city: Affect, attention and alignment in two ordinary urban events

In a representational regime, planned urban events are used by urban planners to render urban projects visible and acceptable. As a corollary of the focus of urban studies on their representational dimension and in spite of a burgeoning literature on the notion of affective urbanism, the experiential character of events remains surprisingly unexplored. This paper argues that an ordinary regime of events is mobilised by city-makers to act on the embodied, affective experience of the city and on the ways urban dwellers know and act upon the city. By analysing planned urban events in their embodied, experiential dimension, we focus on the ways in which, through the design of ephemeral material dispositives, urbanists attempt to encourage citizens to incorporate ways of knowing and acting on space and on the modalities of knowing and acting that are at play. We stage an encounter between critical event studies and Ingoldian approaches to affect and attention, examining two urban events in a Swiss canton. We show how intense encounters with urban matter are staged in an attempt to modulate affects, guide attention, and produce alignment with a specific political project, asking urban dwellers either to embody a project still in the making or to cultivate expectations regarding an already-written future

Hypernuclear event detection in the nuclear emulsion with Monte Carlo simulation and machine learning

This study developed a novel method for detecting hypernuclear events recorded in nuclear emulsion sheets using machine learning techniques. The artificial neural network-based object detection model was trained on surrogate images created through Monte Carlo simulations and image-style transformations using generative adversarial networks. The performance of the proposed model was evaluated using $\alpha$-decay events obtained from the J-PARC E07 emulsion data. The model achieved approximately twice the detection efficiency of conventional image processing and reduced the time spent on manual visual inspection by approximately 1/17. The established method was successfully applied to the detection of hypernuclear events. This approach is a state-of-the-art tool for discovering rare events recorded in nuclear emulsion sheets without any real data for training.Comment: 32 pages, 13 figure

The Universal One-Loop Effective Action

We present the universal one-loop effective action for all operators of dimension up to six obtained by integrating out massive, non-degenerate multiplets. Our general expression may be applied to loops of heavy fermions or bosons, and has been checked against partial results available in the literature. The broad applicability of this approach simplifies one-loop matching from an ultraviolet model to a lower-energy effective field theory (EFT), a procedure which is now reduced to the evaluation of a combination of matrices in our universal expression, without any loop integrals to evaluate. We illustrate the relationship of our results to the Standard Model (SM) EFT, using as an example the supersymmetric stop and sbottom squark Lagrangian and extracting from our universal expression the Wilson coefficients of dimension-six operators composed of SM fields.Comment: 30 pages, v2 contains additional comments and corrects typos, version accepted for publication in JHE

Mutation in triangulated categories and rigid Cohen-Macaulay modules

We introduce the notion of mutation of $n$-cluster tilting subcategories in a triangulated category with Auslander-Reiten-Serre duality. Using this idea, we are able to obtain the complete classifications of rigid Cohen-Macaulay modules over certain Veronese subrings.Comment: 52 pages. To appear in Invent. Mat

Quantification of C1 esterase inhibitor in human serum by enzyme-linked immunosorbent assay: Correlation with turbidimetric immunoassay

C1 inhibitor of serine proteases (C1-INH) performs a regulatory function in the complement system and vascular permeability. Deficiency of C1-INH leads to various forms of angioedema, including hereditary angioedema (HAE). The cause of HAE is a genetically determined violation of the synthesis of C1-INH. A decrease in the level of C1-INH to 50% relative to the norm leads to an increase in the production of bradykinin, which is the basis for the diagnosis of HAE. The development of affordable ELISA for the quantitative determination of C1-INH is a popular direction for clinicians. During the development of a new kit for quantitative determination of C1-INH, two mouse monoclonal antibodies (mAb) with different epitope specificities were obtained. On their basis, a sandwich-type ELISA was developed. The specificity of the obtained mAb's was confirmed using the medical device “Berinert”. To prepare calibrators, C1-INH was affinity purified from human blood plasma using a sorbent with immobilized mAbs. The identity of the C1-INH protein was confirmed by PAGE electrophoresis, immunoblotting, and mass spectrometry on MALDI-TOF/TOF UltrafleXtreme mass spectrometer. To assess the quality indicators of developed reagents kit, studies were carried out in accordance with GOST R 51352-2013 and TU 21.20.23-041-01967164-2022. Values of quality indicators: accuracy — 93.53%; measurement linearity interval — 22.00-176.07 ng/mL. Using the developed ELISA test system, we examined 28 blood sera from healthy donors and 7 blood sera from patients with confirmed HAE. In the same samples, the content of C1-INH was determined by turbidimetric method, using the "Diagnostic reagents for in vitro immunochemical studies of specific blood proteins. Model: C1-esterase inhibitor (C1 EsteraseInhibitor)" (Aptec, Belgium). The correlation coefficient was 0.94 (p < 0.05). It was found that the diagnostic sensitivity and specificity of the developed ELISA is 100%. As a result of the study, an original ELISA test system for the quantitative determination of C1-INH was developed "Reagent kit for enzyme-linked immunosorbent assay of human C1-inhibitor (C1-inh PS)"

Precision of the PET activity range during irradiation with ¹⁰C, ¹¹C, and ¹²C beams

Objective. Beams of stable ions have been a well-established tool for radiotherapy for many decades. In the case of ion beam therapy with stable 12C ions, the positron emitters 10,11C are produced via projectile and target fragmentation, and their decays enable visualization of the beam via positron emission tomography (PET). However, the PET activity peak matches the Bragg peak only roughly and PET counting statistics is low. These issues can be mitigated by using a short-lived positron emitter as a therapeutic beam. Approach. An experiment studying the precision of the measurement of ranges of positron-emitting carbon isotopes by means of PET has been performed at the FRS fragment-separator facility of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany. The PET scanner used in the experiment is a dual-panel version of a Siemens Biograph mCT PET scanner. Main results. High-quality in-beam PET images and activity distributions have been measured from the in-flight produced positron emitting isotopes 11C and 10C implanted into homogeneous PMMA phantoms. Taking advantage of the high statistics obtained in this experiment, we investigated the time evolution of the uncertainty of the range determined by means of PET during the course of irradiation, and show that the uncertainty improves with the inverse square root of the number of PET counts. The uncertainty is thus fully determined by the PET counting statistics. During the delivery of 1.6 × 107 ions in 4 spills for a total duration of 19.2 s, the PET activity range uncertainty for 10C, 11C and 12C is 0.04 mm, 0.7 mm and 1.3 mm, respectively. The gain in precision related to the PET counting statistics is thus much larger when going from 11C to 10C than when going from 12C to 11C. The much better precision for 10C is due to its much shorter half-life, which, contrary to the case of 11C, also enables to include the in-spill data in the image formation. Significance. Our results can be used to estimate the contribution from PET counting statistics to the precision of range determination in a particular carbon therapy situation, taking into account the irradiation scenario, the required dose and the PET scanner characteristics.</p

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Algorithmic deformation of matrix factorisations

Branes and defects in topological Landau-Ginzburg models are described by matrix factorisations. We revisit the problem of deforming them and discuss various deformation methods as well as their relations. We have implemented these algorithms and apply them to several examples. Apart from explicit results in concrete cases, this leads to a novel way to generate new matrix factorisations via nilpotent substitutions, and to criteria whether boundary obstructions can be lifted by bulk deformations.Comment: 30 page