The nature of the low energy band of the Fenna-Matthews-Olson complex: vibronic signatures

Based entirely upon actual experimental observations on electron-phonon coupling, we develop a theoretical framework to show that the lowest energy band of the Fenna- Matthews-Olson (FMO) complex exhibits observable features due to the quantum nature of the vibrational manifolds present in its chromophores. The study of linear spectra provides us with the basis to understand the dynamical features arising from the vibronic structure in non-linear spectra in a progressive fashion, starting from a microscopic model to finally performing an inhomogenous average. We show that the discreteness of the vibronic structure can be witnessed by probing the diagonal peaks of the non-linear spectra by means of a relative phase shift in the waiting time resolved signal. Moreover, we demonstrate the photon-echo and non-rephasing paths are sensitive to different harmonics in the vibrational manifold when static disorder is taken into account. Supported by analytical and numerical calculations, we show that nondiagonal resonances in the 2D spectra in the waiting time, further capture the discreteness of vibrations through a modulation of the amplitude without any effect in the signal intrinsic frequency. This fact generates a signal that is highly sensitive to correlations in the static disorder of the excitonic energy albeit protected against dephasing due to inhomogeneities of the vibrational ensemble.Comment: 14 pages, 6 figure

Band selection and disentanglement using maximally-localized Wannier functions: the cases of Co impurities in bulk copper and the Cu (111) surface

We have adapted the maximally-localized Wannier function approach of [I. Souza, N. Marzari and D. Vanderbilt, Phys. Rev. B 65, 035109 (2002)] to the density functional theory based Siesta method [J. M. Soler et al., J. Phys.: Cond. Mat. 14, 2745 (2002)] and applied it to the study of Co substitutional impurities in bulk copper as well as to the Cu (111) surface. In the Co impurity case, we have reduced the problem to the Co d-electrons and the Cu sp-band, permitting us to obtain an Anderson-like Hamiltonian from well defined density functional parameters in a fully orthonormal basis set. In order to test the quality of the Wannier approach to surfaces, we have studied the electronic structure of the Cu (111) surface by again transforming the density functional problem into the Wannier representation. An excellent description of the Shockley surface state is attained, permitting us to be confident in the application of this method to future studies of magnetic adsorbates in the presence of an extended surface state

Vibronic origin of long-lived coherence in an artificial molecular light harvester

Natural and artificial light harvesting processes have recently gained new interest. Signatures of long lasting coherence in spectroscopic signals of biological systems have been repeatedly observed, albeit their origin is a matter of ongoing debate, as it is unclear how the loss of coherence due to interaction with the noisy environments in such systems is averted. Here we report experimental and theoretical verification of coherent exciton-vibrational (vibronic) coupling as the origin of long-lasting coherence in an artificial light harvester, a molecular J-aggregate. In this macroscopically aligned tubular system, polarization controlled 2D spectroscopy delivers an uncongested and specific optical response as an ideal foundation for an in-depth theoretical description. We derive analytical expressions that show under which general conditions vibronic coupling leads to prolonged excited-state coherence

Synthetic lethal interaction of cetuximab with MEK1/2 inhibition in NRAS-mutant metastatic colorectal cancer

KRAS mutations are an established predictor of lack of response to EGFR-targeted therapies in patients with metastatic colorectal cancer (mCRC). However, little is known about the role of the rarer NRAS mutations as a mechanism of primary resistance to the anti-EGFR monoclonal antibody cetuximab in wild-type KRAS mCRC. Using isogenic mCRC cells with a heterozygous knock-in of the NRAS activating mutation Q61K, we aimed to elucidate the mechanism(s) by which mutant NRAS blocks cetuximab from inhibiting mCRC growth. NRASQ61K/+ cells were refractory to cetuximab-induced growth inhibition. Pathway-oriented proteome profiling revealed that cetuximab-unresponsive ERK1/2 phosphorylation was the sole biomarker distinguishing cetuximab-refractory NRASQ61K/+ from cetuximab-sensitive NRAS+/+ cells. We therefore employed four representative MEK1/2 inhibitors (binimetinib, trametinib, selumetinib, and pimasertib) to evaluate the therapeutic value of MEK/ERK signaling in cetuximab-refractory NRAS mutation-induced mCRC. Co-treatment with an ineffective dose of cetuximab augmented, up to more than 1,300-fold, the cytotoxic effects of pimasertib against NRASQ61K/+ cells. Simultaneous combination of MEK1/2 inhibitors with cetuximab resulted in extremely high and dose-dependent synthetic lethal effects, which were executed, at least in part, by exacerbated apoptotic cell death. Dynamic monitoring of real-time cell growth rates confirmed that cetuximab synergistically sensitized NRASQ61K/+ cellsto MEK1/2 inhibition. Our discovery of a synthetic lethal interaction of cetuximab in combination with MEK1/2 inhibition for the NRAS mutant subgroup of mCRC underscores the importance of therapeutic intervention both in the MEK-ERK and EGFR pathways to achieve maximal therapeutic efficacy against NRAS-mutant mCRC tumors

A mindfulness and compassion-based program applied to pregnant women and their partners to decrease depression symptoms during pregnancy and postpartum: Study protocol for a randomized controlled trial

Background: Pregnancy and the postpartum period are times of great change for women and their partners, often bringing substantial challenges and stress. Approximately 10%-20% of women suffer from mood disorders such as depression in the perinatal period. There are risks involved in using psychopharmacological interventions to treat perinatal depression. Mindfulness and compassion-based educational programs could be efficacious and cost-effective options for the prevention and treatment of perinatal mood disorders. The aim of this study is to assess the efficacy of an adapted Mindfulness-Based Childbirth and Parenting (MBCP) program that includes compassion training for pregnant women in primary care (PC) settings in the Spanish National Health System to decrease perinatal depression. Methods: A multicenter randomized controlled trial (RCT) will be conducted. Participants will be pregnant women (n = 122) and their partners who wish to participate. They will be enrolled and assessed in PC settings and randomly assigned to either: (1) an adapted MBCP educational program tailored to the Spanish National Health System + treatment as usual (TAU); or (2) TAU only. The main outcome to be assessed will be depression, evaluated with the Edinburgh Postnatal Depression Scale (EPDS). Secondary outcomes will include self-reported measures of perceived stress, affects, mindfulness, self-compassion, maternal self-efficacy, and use of health and social services. Patients will be assessed at four timepoints: baseline; post-treatment; and at three and six months after childbirth. Intention-to-treat and per-protocol analyses will be carried out using linear regression mixed models. Effect sizes will be estimated using Cohen''s d. Discussion: Perinatal depression is a significant health problem. An effective and low-cost childbirth education program that incorporates mindfulness and compassion practices may be a beneficial preventive complementary healthcare modality for expectant women and their partners. This study will be the first multicenter RCT in Spanish PC settings using adapted MBCP and compassion practices to reduce symptoms of depression during pregnancy and the postpartum period

Economic impact of third-wave cognitive behavioral therapies: a systematic review and quality assessment of economic evaluations in randomized controlled trials

The term third-wave cognitive behavioral therapy (CBT) encompasses new forms of CBT that both extend and innovate within CBT. Most third-wave therapies have been subject to randomized controlled trials (RCTs) focused on clinical effectiveness; however, the number and quality of economic evaluations in these RCTs has been unknown and may be few. Evidence about efficiency of these therapies may help support decisions on efficient allocation of resources in health policies. The main aim of this study was to systematically review the economic impact of third-wave therapies in the treatment of patients with physical or mental conditions. We conducted a systematic literature search in PubMed, PsycINFO, EMBASE, and CINALH to identify economic evaluations of third-wave therapies. Quality and Risk of Bias (RoB) assessment of economic evaluations was also made using the Drummond 35-item checklist and the Cochrane Collaboration’s tool for assessing risk of bias, respectively. Eleven RCTs were included in this systematic review. Mindfulness-Based Cognitive Therapy (MBCT), Mindfulness-Based Stress Reduction (MBSR), Acceptance and Commitment Therapy (ACT), Dialectical Behavior Therapy (DBT), and extended Behaviour Activation (eBA) showed acceptable cost-effectiveness and cost-utility ratios. No study employed a time horizon of more than 3 years. Quality and RoB assessments highlight some limitations that temper the findings. There is some evidence that MBCT, MBSR, ACT, DBT, and eBA are efficient from a societal or a third-party payer perspective. No economic analysis was found for many third-wave therapies. Therefore, more economic evaluations with high methodological quality are needed

Resistencia de Fasciola hepatica al Triclabendazol: primer reporte en ovinos de la provincia de Santa Cruz, Patagonia Argentina

En el presente informe técnico se describen los principales resultados de los estudios de eficacia fasciolicida de antiparasitarios realizados en un establecimiento cercano a Los Antiguos, Santa Cruz, a partir de los cuales se confirmó la existencia de una cepa de F. hepatica resistente a triclabendazol. Los trabajos descriptos fueron realizados por el Grupo de Salud Animal de la EEA INTA Bariloche, las Agencia de Extensión Rural INTA San Julián y Los Antiguos, la EEA INTA Esquel, y el Laboratorio de Farmacología del Centro de Investigación Veterinaria de Tandil (CIVETAN). El trabajo completo se encuentra publicado en la revista Veterinary Parasitology: Regional Studies and Reports. 45. 100927.https://www.sciencedirect.com/science/article/abs/pii/S2405939023000977EEA Santa CruzFil: Larroza, Marcela Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área Producción Animal. Grupo Sanidad Animal; Argentina.Fil: Aguilar, Marcelo Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz. Agencia de Extensión Rural San Julián; Argentina.Fil: Soler, Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área Producción Animal. Grupo Sanidad Animal; Argentina.Fil: Mora, Julio Cesar. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz. Agencia de Extensión Rural Los Antiguos; Argentina.Fil: Roa, Martin Angel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz. Agencia de Extensión Rural Los Antiguos; Argentina.Fil: Cabrera, Francisco Raúl. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área de producción Animal. Grupo de Sanidad Animal; Argentina.Fil: Martinez Stanziola, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Centro Regional Patagonia Sur. Estación Experimental Agroforestal Esquel (EEAf Esquel). Campo Anexo Trevelin; Argentina.Fil: Ceballos, Laura. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina.Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.Fil: Alvarez, Luís. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina.Fil: Alvarez, Luís. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina

Cost-utility of group acceptance and commitment therapy for fibromyalgia versus recommended drugs: an economic analysis alongside a 6-month randomised controlled trial conducted in Spain (EFFIGACT study)

The aim of this study was to analyse the cost-utility of a group-based form of Acceptance and Commitment Therapy (GACT) in patients with fibromyalgia (FM) compared to patients receiving recommended pharmacological treatment (RPT) or on a waiting list (WL). The data were derived from a previously published study, an RCT that focused on clinical outcomes. Health economic outcomes included health-related quality of life and healthcare use at baseline and at 6-month follow-up using the EuroQol (EQ-5D-3L) and the Client Service Receipt Inventory (CSRI), respectively. Analyses included Quality-Adjusted Life Years (QALYs), direct and indirect cost differences, and incremental cost-effectiveness ratios (ICERs). A total of 156 FM patients were randomized (51 GACT, 52 RPT, 53 WL). GACT was related to significantly less direct costs over the 6 month study period compared to both control arms (GACT €824.2 ± 1,062.7 vs. RPT €1,730.7 ± 1,656.8 vs WL €2,462.7 ± 2,822.0). Lower direct costs for GACT in comparison to RPT were due to lower costs from primary care visits and FM-related medications. The ICERs were dominant in the completers’ analysis and remained robust in the sensitivity analyses. In conclusion, ACT appears to be a cost-effective treatment in comparison to RPT in patients with FM

Stiff monatomic gold wires with a spinning zigzag geometry

Using first principles density functional calculations, gold monatomic wires are found to exhibit a zigzag shape which remains under tension, becoming linear just before breaking. At room temperature they are found to spin, what explains the extremely long apparent interatomic distances shown by electron microscopy.The zigzag structure is stable if the tension is relieved, the wire holding its chainlike shape even as a free-standing cluster. This unexpected metallic-wire stiffness stems from the transverse quantization in the wire, as shown in a simple free electron model.Comment: 4 pages, latex, 5 figures, submitted to PR

The Balloon-Borne Large Aperture Submillimeter Telescope Observatory

The BLAST Observatory is a proposed superpressure balloon-borne polarimeter designed for a future ultra-long duration balloon campaign from Wanaka, New Zealand. To maximize scientific output while staying within the stringent superpressure weight envelope, BLAST will feature new 1.8m off-axis optical system contained within a lightweight monocoque structure gondola. The payload will incorporate a 300L $^4$He cryogenic receiver which will cool 8,274 microwave kinetic inductance detectors (MKIDs) to 100mK through the use of an adiabatic demagnetization refrigerator (ADR) in combination with a $^3$He sorption refrigerator all backed by a liquid helium pumped pot operating at 2K. The detector readout utilizes a new Xilinx RFSOC-based system which will run the next-generation of the BLAST-TNG KIDPy software. With this instrument we aim to answer outstanding questions about dust dynamics as well as provide community access to the polarized submillimeter sky made possible by high-altitude observing unrestricted by atmospheric transmission. The BLAST Observatory is designed for a minimum 31-day flight of which 70$\%$ will be dedicated to observations for BLAST scientific goals and the remaining 30$\%$ will be open to proposals from the wider astronomical community through a shared-risk proposals program.Comment: Presented at SPIE Ground-based and Airborne Telescopes VIII, December 13-18, 202