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Decoherence-free subspaces and subsystems (DFS) preserve quantum information by encoding it into symmetry-protected states unaffected by decoherence. An inherent DFS of a given experimental system may not exist; however, through the use of dynamical decoupling (DD), one can induce symmetries that support DFSs. Here, we provide the first experimental demonstration of DD-generated decoherence-free subsystem logical qubits. Utilizing IBM Quantum superconducting processors, we investigate two and three-qubit DFS codes comprising up to six and seven noninteracting logical qubits, respectively. Through a combination of DD and error detection, we show that DFS logical qubits can achieve up to a 23% improvement in state preservation fidelity over physical qubits subject to DD alone. This constitutes a beyond-breakeven fidelity improvement for DFS-encoded qubits. Our results showcase the potential utility of DFS codes as a pathway toward enhanced computational accuracy via logical encoding on quantum processors., (Creative Commons Attribution license.)

Aging compromises brain function leading to cognitive decline. A cyclic ketogenic diet (KD) improves memory in aged mice after long-term administration; however, short-term effects later in life and the molecular mechanisms that govern such changes remain unclear. Here, we explore the impact of a short-term KD treatment starting at elderly stage on brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings reveal that KD improves working memory and hippocampal LTP. Furthermore, the synaptosome proteome of aged mice fed a KD long-term evidence changes predominantly at the presynaptic compartment associated to the protein kinase A (PKA) signaling pathway. These findings were corroborated in vivo by western blot analysis, with high BDNF abundance and PKA substrate phosphorylation. Overall, we show that a KD modifies brain function even when it is administered later in life and recapitulates molecular features of long-term administration, including the PKA signaling pathway, thus promoting synaptic plasticity at advanced age., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Ala Wai Canal is an artificial waterway in the tourist district of Waikiki in Honolulu, HI. Originally built to collect runoff from industrial, residential, and green spaces dedicated to recreation, the Ala Wai Canal has since experienced potent levels of toxicity due to this runoff entering the watershed and making it hazardous for both marine life and humans at current concentration, including Danio rerio (zebrafish). A community of learners at educations levels from high school to postbaccalaureate from Oahu, HI was connected through the Consortium for Increasing Research and Collaborative Learning Experiences (CIRCLE) distance research program. This team conducted research with an Investigator and team from Mayo Clinic in Rochester, MN, with the Ala Wai Canal as its primary subject. Through CIRCLE, research trainees sent two 32 oz bottles of Ala Wai- acquired water to a partnered laboratory at the Mayo Clinic in which zebrafish embryos were observed at differing concentrations of the sampled water against a variety of developmental and behavioral assays. Research trainees also created atlases of developmental outcomes in zebrafish following exposure to environmental toxins and tables of potential pesticide contaminants to enable the identification of the substances linked to structural defects and enhanced stress during Ala Wai water exposure experiments.

Objectives: To assess the feasibility of identifying fetal brain structures and anatomic landmarks included in the anterior complex (AC) and posterior complex (PC), as well as the proximal hemisphere (PH)., Methods: This was a prospective observational multicenter study of healthy pregnant women evaluated by ultrasound screening at 24 to 36 + 6 weeks' gestation. Six physicians performed transabdominal ultrasound, to obtain the planes required to visualize the AC, PC, and PH. Blind analysis by an expert and non-expert operator in fetal neurosonography was used to assess the structures included in each plane view., Results: In the population studied (n=366), structure detection rates for AC were over 95 %, with an agreement of 96 % when comparing expert and non-expert examiners. Visualization of the corpus callosum crossing the midline was detected in over 97 and 96 % of cases for the AC and PC, respectively, with an agreement of over 96 %. The PH plane, particularly through the posterior access via the mastoid fontanelle, enabled visualization of the proximal anatomical structures in almost 95 % of cases. Detection of the corpus callosum through the AC and PC, both proximal/distal germinal matrix (AC) and proximal Sylvian fissure through the anterior access (PH) in the 24-25 + 6, 26-31 + 6 and 32-36 + 6 weeks' gestation groups were successful in over 96 % of cases with high level of agreement., Conclusions: Inclusion of AC, PC, and PH later in pregnancy proves feasible with a high level of agreement between both expert and non-expert operators., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

The prevalence of quantum crosstalk in current quantum devices poses challenges for achieving high-fidelity quantum logic operations and reliable quantum processing. Through quantum control theory, we develop an analytical condition for achieving crosstalk-robust single-qubit control of multiqubit systems. We examine the effects of quantum crosstalk via a cumulant expansion and develop a condition to suppress the leading order contributions to the dynamics. The efficacy of the condition is illustrated in the domains of quantum state preservation and noise characterization through the development of crosstalk-robust dynamical decoupling and quantum noise spectroscopy (QNS) protocols. Using the IBM Quantum Experience, crosstalk-robust state preservation is demonstrated on 27 qubits, where up to a 3.5× improvement in coherence decay is observed for single-qubit product and multipartite entangled states. Through the use of noise injection, we demonstrate crosstalk-robust dephasing QNS on a seven qubit processor, where a 10^{4} improvement in reconstruction accuracy over alternative protocols is found. Together, these experiments highlight the significant impact the crosstalk suppression condition can have on improving multiqubit characterization and control on current quantum devices.

Antecedentes: En Chile el parto prematuro es la principal causa de morbilidad y mortalidad perinatal. Objetivo: Evaluar la utilidad clínica de la longitud cervical y la detección de fibronectina, en la predicción de parto prematuro. Método: Estudio observacional prospectivo, de corte transversal en 86 pacientes que consultaron por síntomas de parto prematuro (SPP), con membranas indemnes y edad gestacional entre las 22 y 34 semanas. El grupo estudio formado por gestantes con parto prematuro dentro de los 7 días. Al ingreso se tomó muestra cervical para fibronectina y se midió longitud cervical mediante ultrasonografía transvaginal. Resultados: De las 86 gestantes estudiadas, en 13 (15%) se produjo el parto dentro de los 7 días. La curva ROC mostró un área bajo la curva para longitud cervical de 0,475 y sensibilidad 31% (4/13), especificidad 96% (70/73), valor predictivo positivo 57% (4/7) y valor predictivo negativo 89% (70/79), riesgo relativo positivo 5,0 y riesgo relativo negativo 0,47 (p=0,014). El área bajo la curva para fibronectina fue 0,92 con una sensibilidad 77% (10/13), especificidad 90% (66/73), valor predictivo positivo (10/17) 59% y valor predictivo negativo 96% (66/69), riesgo relativo positivo 13,48 y riesgo relativo negativo 0,43 (pBackground: In Chile the preterm labor is the main cause of perinatal morbidity and mortality. Objective: To evalúate the clinical utility of the cervical length and fibronectin determination in predicting preterm delivery. Method: A prospective observational and transactional study was made, in 86 patients with preterm labor symptoms and gestational age between 22 and 34 weeks. The study group included patients with labor and delivery within a week of admission. From each patient a cervico-vaginal specimen was obtained to measure fibronectin and transvaginal ultrasonographic evaluation of the uterine cervix. Results: From 86 patients admitted to the study, thirteen had preterm labor (15%). The ROC curve showed an área under curve for cervical length of 0.475 and sensitivity 31 % (4/13), specificity 96% (70/73), positive predictive valué 57%(4/13), negative predictive valué 88% (70/79), positive relative risk was 5.0, and the negative relative risk 0.47 (p=0.014); for fibronectin was 0.92 and sensitivity 77% (10/13), specificity 90% (66/73), positive predictive valué 59% (10/17), negative predictive valué 96% (66/69), positive relative riskof 13.48, negative relative risk 0.43 (p=0.014). Conclusión: In patients with premature labor symptoms, the cervical lengths none shortened and negative fibronectin result were associated with a low risk of having a preterm labor. Positive fibronectin was a better predictor of premature birth in a week of admission and the cervical length was the best in ruling out the occurrence of a premature birth

Se analizan las cordocentesis efectuadas en el Servicio en un lapso de 11 años. Se realizaron 30 procedimientos. Quince en 5 pacientes RhD (-) severamente sensibilizadas, siendo sometidas a transfusiones intrauterinas 4 de ellas y obteniéndose la sobrevida de 4 fetos, 2 de ellos hidrópicos al momento de su ingreso. Además, se realizaron cordocentesis con fines diagnósticos en 9 pacientes con fetos hidrópicos y 2 con fetos malformados. Se encontró 3 fetos con anemia y dos fetos con infección a citomegalovirus en 8 pacientes con fetos hidrópicos. En otras 4 pacientes, dos con fetos hidrópicos y dos con fetos malformados se realizó además estudio genético y se encontró triploidia en un feto hidrópico. Se concluye que la cordocentesis es un excelente procedimiento diagnóstico y terapéuticoThirty cordocentesis that were made in our hospital in a period of eleven years are analyzed. Fifteen procedures were made in 5 pregnant patients, complicated by severe red cell isoimmunization. Three fetus were hydropic at the first scan. Intravascular fetal blood transfusions were performed in these patients, and 4 fetus survival after birth. Fetal blood sampling has been used in the prenatal dianosis of cytomegalovirus in two cases and anaemia in there cases, in eight patients with nonimmunological fetal hydrops. Karyotyping were performed in another four patients with nonimmunological fetal hydrops or a fetal malformation, and in one case was identified a triploidia. It is concludes that cordocentesis is an excellent diagnostic and therapeutic procedure

Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-box binding protein 1 (XBP1). To artificially enforce the adaptive capacity of the UPR in the AD brain, we developed strategies to express the active form of XBP1 in the brain. Overexpression of XBP1 in the nervous system using transgenic mice reduced the load of amyloid deposits and preserved synaptic and cognitive function. Moreover, local delivery of XBP1 into the hippocampus of an 5xFAD mice using adeno-associated vectors improved different AD features. XBP1 expression corrected a large proportion of the proteomic alterations observed in the AD model, restoring the levels of several synaptic proteins and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of targeting UPR-dependent gene expression programs as a strategy to ameliorate AD features and sustain synaptic function., Competing Interests: Declaration of interests The authors declare that no conflicts of interest exist., (Copyright © 2023. Published by Elsevier Inc.)

Age is the main risk factor for the development of neurodegenerative diseases. In the aged brain, axonal degeneration is an early pathological event, preceding neuronal dysfunction, and cognitive disabilities in humans, primates, rodents, and invertebrates. Necroptosis mediates degeneration of injured axons, but whether necroptosis triggers neurodegeneration and cognitive impairment along aging is unknown. Here, we show that the loss of the necroptotic effector Mlkl was sufficient to delay age-associated axonal degeneration and neuroinflammation, protecting against decreased synaptic transmission and memory decline in aged mice. Moreover, short-term pharmacologic inhibition of necroptosis targeting RIPK3 in aged mice, reverted structural and functional hippocampal impairment, both at the electrophysiological and behavioral level. Finally, a quantitative proteomic analysis revealed that necroptosis inhibition leads to an overall improvement of the aged hippocampal proteome, including a subclass of molecular biofunctions associated with brain rejuvenation, such as long-term potentiation and synaptic plasticity. Our results demonstrate that necroptosis contributes to age-dependent brain degeneration, disturbing hippocampal neuronal connectivity, and cognitive function. Therefore, necroptosis inhibition constitutes a potential geroprotective strategy to treat age-related disabilities associated with memory impairment and cognitive decline., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Recessive gene mutations underlie many developmental disorders and often lead to disabling neurological problems. Here, we report identification of a homozygous c.170G>A (p.Cys57Tyr or C57Y) mutation in the gene coding for protein disulfide isomerase A3 (PDIA3, also known as ERp57), an enzyme that catalyzes formation of disulfide bonds in the endoplasmic reticulum, to be associated with syndromic intellectual disability. Experiments in zebrafish embryos show that PDIA3 C57Y expression is pathogenic and causes developmental defects such as axonal disorganization as well as skeletal abnormalities. Expression of PDIA3 C57Y in the mouse hippocampus results in impaired synaptic plasticity and memory consolidation. Proteomic and functional analyses reveal that PDIA3 C57Y expression leads to dysregulation of cell adhesion and actin cytoskeleton dynamics, associated with altered integrin biogenesis and reduced neuritogenesis. Biochemical studies show that PDIA3 C57Y has decreased catalytic activity and forms disulfide-crosslinked aggregates that abnormally interact with chaperones in the endoplasmic reticulum. Thus, rare disease gene variant can provide insight into how perturbations of neuronal proteostasis can affect the function of the nervous system., (© 2021 MRC Laboratory of Molecular Biology. Published under the terms of the CC BY 4.0 license.)

Alzheimer's disease (AD) is a major adult-onset neurodegenerative condition with no available treatment. Compelling reports point amyloid-β (Aβ) as the main etiologic agent that triggers AD. Although there is extensive evidence of detrimental crosstalk between Aβ and microglia that contributes to neuroinflammation in AD, the exact mechanism leading to neuron death remains unknown. Using postmortem human AD brain tissue, we show that Aβ pathology is associated with the necroptosis effector pMLKL. Moreover, we found that the burden of Aβ oligomers (Aβo) correlates with the expression of key markers of necroptosis activation. Additionally, inhibition of necroptosis by pharmacological or genetic means, reduce neurodegeneration and memory impairment triggered by Aβo in mice. Since microglial activation is emerging as a central driver for AD pathogenesis, we then tested the contribution of microglia to the mechanism of Aβo-mediated necroptosis activation in neurons. Using an in vitro model, we show that conditioned medium from Aβo-stimulated microglia elicited necroptosis in neurons through activation of TNF-α signaling, triggering extensive neurodegeneration. Notably, necroptosis inhibition provided significant neuronal protection. Together, these findings suggest that Aβo-mediated microglia stimulation in AD contributes to necroptosis activation in neurons and neurodegeneration. As necroptosis is a druggable degenerative mechanism, our findings might have important therapeutic implications to prevent the progression of AD., (© 2022. The Author(s).)

The 2019 coronavirus disease (COVID-19) is now a global pandemic. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative pathogen of COVID-19. Here, we study an in-host model that highlights the effector T cell response to SARS-CoV-2. The stability of a unique positive equilibrium point, with viral load V * , suggests that the virus may replicate fast enough to overcome T cell response and cause infection. This overcoming is the bifurcation point, near which the orders of magnitude for V * can be sensitive to numerical changes in the parameter values. Our work offers a mathematical insight into how SARS-CoV-2 causes the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2020 Elsevier B.V. All rights reserved.)

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1 H -3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7 ( a - o ) and (2-{4-[3-(1 H -3-indolyl)-propyl]-1-piperazinyl}-acetylamine)- N -(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13 ( a - l ) were synthesized and evaluated as novel multitarget ligands towards dopamine D 2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying K i values from 5 to 10 nM. Compounds 7k , K i = 5.63 ± 0.82 nM, and 13c , K i = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D 2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D 2 receptor in the nanomolar range ( 7n : K i = 307 ± 6 nM and 7m : K i = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D 2 receptor (D 2 /SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q 2 = 0.625, 0.523 for CoMFA and CoMSIA and r 2 ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).

Zebrafish is becoming a popular animal model in neuropharmacology and drug discovery, mainly due to its ease of handling and low costs involved in maintenance and experimental work. This animal displays a series of complex behaviours that makes it useful for assessing the effects of psychoactive drugs. Here, adult zebrafish were used for assessment of the anxiolytic and anti-addictive properties of UFR2709, a nicotinic receptor (nAChR) antagonist, using two behavioural paradigms to test for addiction, the novel tank diving test to assess anxiety and the conditioned place preference (CPP). Furthermore, the expression of nAChR subunits α4 and α7 was measured in the zebrafish brain. The results show that UFR2709 exhibits an anxiolytic effect on zebrafish and blocks the effect evoked by nicotine on CPP. Moreover, UFR2709 significantly decreased the expression of α4 nicotinic receptor subunit. This indicates that UFR2709 might be a useful drug for the treatment of nicotine addiction.

Objective: To assess the feasibility of identifying structures included in anterior complex (AC) and posterior complex (PC), as well as a series of anatomic landmarks that could help to demonstrate the integrity of the cerebral proximal hemisphere (PH)., Methods: This was a prospective observational multicenter study of healthy pregnant women attending routine ultrasound screening at 20 + 0 to 33 + 6 weeks' gestation. Six physicians performed transabdominal (TA) ultrasound, in order to obtain the planes required to visualize the AC, PC, and PH. Blind analysis by a nonexpert and two experts in fetal neurosonography was used to assess the structures included in each plane view., Results: In the population studied (n = 747), detection of the structure rates for AC, PC, and proximal hemisphere was of 94%, 93%, and 96%, respectively, with an agreement of 97%, 94%, and 98% when comparing an expert and a nonexpert in fetal brain examiner. Detection of structures in the proximal hemisphere was significantly higher when observed through the proximal hemisphere plane rather than the transventricular plane., Conclusion: Our results suggest that inclusion of AC and PC complexes visualization, as well as real-time access to the proximal hemisphere, is feasible and could improve the prenatal detection of fetal cerebral anomalies., (© 2020 John Wiley & Sons, Ltd.)

Brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric acetylcholine-gated cation channels, have been suggested as molecular targets for the treatment of alcohol abuse and dependence. Here, we examined the effect of the competitive nAChR antagonist UFR2709 on the alcohol consumption of high-alcohol-drinking UChB rats. UChB rats were given free access to ethanol for 24-h periods in a two-bottle free choice paradigm and their ethanol and water intake were measured. The animals were i.p. injected daily for 17 days with a 10, 5, 2.5, or 1 mg/kg dose of UFR2709. Potential confounding motor effects of UFR2709 were assessed by examining the locomotor activity of animals administered the highest dose of UR2709 tested (10 mg/kg i.p.). UFR2709 reduced ethanol consumption and ethanol preference and increased water consumption in a dose-dependent manner. The most effective dose of UFR2709 was 2.5 mg/kg, which induced a 56% reduction in alcohol consumption. Administration of UFR2709 did not affect the weight or locomotor activity of the rats, suggesting that its effects on alcohol consumption and preference were mediated by specific nAChRs., (Copyright © 2019 Quiroz, Sotomayor-Zárate, González-Gutierrez, Vizcarra, Moraga, Bermudez, Reyes-Parada, Quintanilla, Lagos, Rivera-Meza and Iturriaga-Vásquez.)

The effect of meal on blood glucose concentration is a key issue in diabetes mellitus because its estimation could be very useful in therapy decisions. In the case of type 1 diabetes mellitus (T1DM), the therapy based on automatic insulin delivery requires a closed-loop control system to maintain euglycaemia even in the postprandial state. Thus, the mathematical modelling of glucose metabolism is relevant to predict the metabolic state of a patient. Moreover, the eating habits are characteristic of each person, so it is of interest that the mathematical models of meal intake allow to personalise the glycaemic state of the patient using therapy historical data, that is, daily measurements of glucose and records of carbohydrate intake and insulin supply. Thus, here, a model of glucose metabolism that includes the effects of meal is analysed in order to establish criteria for data-based personalisation. The analysis includes the sensitivity and identifiability of the parameters, and the parameter estimation problem was resolved via two algorithms: particle swarm optimisation and evonorm. The results show that the mathematical model can be a useful tool to estimate the glycaemic status of a patient and personalise it according to her/his historical data.

Alcohol abuse is a worldwide health problem with high economic costs to health systems. Emerging evidence suggests that modulation of brain nicotinic acetylcholine receptors (nAChRs) may be a therapeutic target for alcohol dependence. In this work, we assess the effectiveness of four doses of erysodine (1.5, 2.0, 4.0 or 8.0 mg/kg/day, i.p.), a competitive antagonist of nAChRs, on voluntary ethanol consumption behavior in alcohol-preferring UChB rats, administered during three consecutive days. Results show that erysodine administration produces a dose-dependent reduction in ethanol consumption respect to saline injection (control group). The highest doses of erysodine (4 and 8 mg/kg) reduce (45 and 66%, respectively) the ethanol intake during treatment period and first day of post-treatment compared to control group. While, the lowest doses of erysodine (1.5 and 2 mg/kg) only reduce ethanol intake during one day of treatment period. These effective reductions in ethanol intake were 23 and 29% for 1.5 and 2 mg/kg erysodine, respectively. Locomotor activity induced by a high dose of erysodine (10 mg/kg) was similar to those observed with saline injection in control rats, showing that the reduction in ethanol intake was not produced by hypolocomotor effect induced by erysodine. This is the first report showing that erysodine reduces ethanol intake in UChB rats in a dose-dependent manner. Our results highlight the role of nAChRs in the reward effects of ethanol and its modulation as a potentially effective pharmacological alternative for alcohol dependence treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)