Linking spontaneous and stimulated spine dynamics

Our brains continuously acquire and store memories through synaptic plasticity. However, spontaneous synaptic changes can also occur and pose a challenge for maintaining stable memories. Despite fluctuations in synapse size, recent studies have shown that key population-level synaptic properties remain stable over time. This raises the question of how local synaptic plasticity affects the global population-level synaptic size distribution and whether individual synapses undergoing plasticity escape the stable distribution to encode specific memories. To address this question, we (i) studied spontaneously evolving spines and (ii) induced synaptic potentiation at selected sites while observing the spine distribution pre- and post-stimulation. We designed a stochastic model to describe how the current size of a synapse affects its future size under baseline and stimulation conditions and how these local effects give rise to population-level synaptic shifts. Our study offers insights into how seemingly spontaneous synaptic fluctuations and local plasticity both contribute to population-level synaptic dynamics

NK cell receptors in anti-tumor and healthy tissue protection: Mechanisms and therapeutic advances

natural killer (NK) cells are integral to the innate immune system, renowned for their ability to target and eliminate cancer cells without the need for antigen presentation, sparing normal tissues. these cells are crucial in cancer immunosurveillance due to their diverse array of activating and inhibitory receptors that modulate their cytotoxic activity. however, the tumor microenvironment can suppress NK cell function through various mechanisms. over recent decades, research has focused on overcoming these tumor escape mechanisms. Initially, efforts concentrated on enhancing T cell activity, leading to impressive results with immunotherapeutic approaches aimed at boosting T cell responses. nevertheless, a substantial number of patients do not benefit from these treatments and continue to seek effective alternatives. In this context, NK cells present a promising avenue for developing new treatments, given their potent cytotoxic capabilities, safety profile, and activity against T cell- resistant tumors, such as those lacking HLA-I expression. recent advancements in immunotherapy include strategies to restore and amplify NK cell activity through immune checkpoint inhibitors, cytokines, adoptive NK cell therapy, and CAR-NK cell technology. this review provides a comprehensive overview of NK cell receptors, the tumor escape mechanisms that hinder NK cell function, and the evolving field of NK cell-based cancer immunotherapy, highlighting ongoing efforts to develop more effective and targeted cancer treatment strategies

The landscape of combining immune checkpoint inhibitors with novel Therapies: Secret alliances against breast cancer

this review focuses on the immune checkpoint inhibitors (ICIs) in the context of breast cancer (BC) management. these innovative treatments, by targeting proteins expressed on both tumor and immune cells, aim to overcome tumor-induced immune suppression and reactivate the immune system. the potential of this approach is the subject of numerous clinical studies. here, we explore the key studies and emerging therapies related to ICIs providing a detailed analysis of their specific and combined use in BC treatment

Anti-thymocyte globulin with CsA and MMF as GVHD prophylaxis in nonmyeloablative HLA-mismatched allogeneic HCT

Nonmyeloablative regimens are used for allogeneic hematopoietic cell transplantation (HCT) of older or medically unfit patients, but successful outcome is still hindered by graft-versus-host disease (GVHD), especially in the setting of HLA-mismatched HCT. New GVHD prophylaxis strategies are emerging, including the triple drug strategy, that improve the GVHD-free and relapse-free survival (GRFS). Because the impact of ATG in HLA-mismatched Flu-TBI-based nonmyeloablative HCT has not been investigated, we did a retrospective analysis in three Dutch centers. 67 patients were evaluable, with a median age of 56 years. Overall survival, relapse-free survival and GRFS at 4 years were 52%, 43%, and 38%, respectively. NRM findings and cumulative incidence of relapse at 4 years were 26% and 31%, respectively. At 1-year grade II-IV had occurred in 40% of the patients, and the incidence of moderate-severe chronic GVHD incidence was 16%. Acknowledging the limitations of retrospective analyses, we conclude that the use of ATG for HLA-mismatched truly nonmyeloablative Flu-TBI HCT is feasible and results in acceptable long term outcomes, especially with regards to GRFS. We consider ATG in combination with cyclosporin and mycophenolate mofetil as an alternative for the triple drug strategy that uses sirolimus for GVHD prophylaxis in this particular setting

Damage mechanism of wind turbine blade under the impact of lightning induced arcs

It is not clear for the damage mechanism of the blade structure under the effect of the lightning strike arc. In this paper, the damage characteristics of blades under the effect of an lightning arc are obtained by the impulse large current experiment. Based on the actual blade structure, a magnetohydrodynamics model is built to be suitable for multifield coupling of the heat-magnetic-airflow and we obtain the temporal and spatial variation of the temperature and pressure. The experimental results show that the blade tends to crack from the position of the trailing edge near the arc attachment point and the crack extends in the direction of the blade root and tip. The length of carbonization damage caused by the high temperature of the arc is much smaller than the crack length due to the airflow impact. When the down-conductor is placed on the main beam, carbonization damage distributes in the area between the left web and the trailing edge. When placed on the right web, it distributes between the right web and the trailing edge. In the finite element simulation, the temperature of the arc ignited point increases to the peak value and then decreases rapidly and then, it increases to the maximum and tends to stabilize. The high temperature inside the blade region diffuses from the boundary between the pressure surface and the right web to the trailing edge. The pressure of the trailing edge increases to the maximum and then oscillates to decrease. The airflow inside the blade continuously oscillates between the right web and the trailing edge. It is recommended to improve the toughness of the epoxy resin adhesive and set the down-conductor on the main beam

Notes on bordered Floer homology

This is a survey of bordered Heegaard Floer homology, an extension of the Heegaard Floer invariant HF-hat to 3-manifolds with boundary. Emphasis is placed on how bordered Heegaard Floer homology can be used for computations.Comment: 73 pages, 29 figures. Based on lectures at the Contact and Symplectic Topology Summer School in Budapest, July 2012. v2: Fixed many small typo

Pretransplantation MRD in Older Patients With AML After Treatment With Decitabine or Conventional Chemotherapy

The predictive value of measurable residual disease (MRD) for survival in acute myeloid leukemia (AML) has been firmly established in younger patients treated with intensive chemotherapy. The value of MRD after treatment with decitabine in older patients is unknown. This retrospective analysis included patients ≥60 years of age with AML who received an allogeneic hematopoietic cell transplantation (alloHCT) after treatment with decitabine or intensive chemotherapy. Of the 133 consecutively transplanted patients, 109 had available pretransplantation MRD analyses (by flowcytometry [threshold 0.1%]). Forty patients received decitabine treatment (10-day schedule), and 69 patients received intensive chemotherapy (7 + 3 regimen). Patients who received decitabine were older (median 67 versus 64 years) and more often had MRD (70% versus 38%). OS after alloHCT was comparable in both groups. In the chemotherapy group, MRD-positive patients had a significantly higher relapse probability (subdistribution hazard ratio [sHR] 4.81; P= .0031) and risk of death (HR 2.8; P= .02) compared to MRD-negative patients. In the decitabine group there was no significant association between the presence of MRD and relapse (sHR 0.85; P= .83) or death (HR 0.72; P= .60). Pretransplantation MRD in patients receiving decitabine treatment does not have similar predictive value for relapse or survival in older AML patients receiving an alloHCT, compared to patients receiving intensive chemotherapy

Quantum coherent control of highly multipartite continuous-variable entangled states by tailoring parametric interactions

The generation of continuous-variable multipartite entangled states is important for several protocols of quantum information processing and communication, such as one-way quantum computation or controlled dense coding. In this article we theoretically show that multimode optical parametric oscillators can produce a great variety of such states by an appropriate control of the parametric interaction, what we accomplish by tailoring either the spatio-temporal shape of the pump, or the geometry of the nonlinear medium. Specific examples involving currently available optical parametric oscillators are given, hence showing that our ideas are within reach of present technology.Comment: 14 pages, 5 figure

Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target

Solitary and cnoidal wave scattering by a submerged horizontal plate in shallow water

Solitary and cnoidal wave transformation over a submerged, fixed, horizontal rigid plate is studied by use of the nonlinear, shallow-water Level I Green-Naghdi (GN) equations. Reflection and transmission coefficients are defined for cnoidal and solitary waves to quantify the nonlinear wave scattering. Results of the GN equations are compared with the laboratory experiments and other theoretical solutions for linear and nonlinear waves in intermediate and deep waters. The GN equations are then used to study the nonlinear wave scattering by a plate in shallow water. It is shown that in deep and intermediate depths, the wave-scattering varies nonlinearly by both the wavelength over the plate length ratio, and the submergence depth. In shallow water, however, and for long-waves, only the submergence depth appear to play a significant role on wave scattering. It is possible to define the plate submergence depth and length such that certain wave conditions are optimized above, below, or downwave of the plate for different applications. A submerged plate in shallow water can be used as a means to attenuate energy, such as in wave breakers, or used for energy focusing, and in wave energy devices