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We introduce a systematically improvable family of variational wave functions for the simulation of strongly correlated fermionic systems. This family consists of Slater determinants in an augmented Hilbert space involving "hidden" additional fermionic degrees of freedom. These determinants are projected onto the physical Hilbert space through a constraint that is optimized, together with the single-particle orbitals, using a neural network parameterization. This construction draws inspiration from the success of hidden-particle representations but overcomes the limitations associated with the mean-field treatment of the constraint often used in this context. Our construction provides an extremely expressive family of wave functions, which is proved to be universal. We apply this construction to the ground-state properties of the Hubbard model on the square lattice, achieving levels of accuracy that are competitive with those of state-of-the-art variational methods.
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Gauge symmetries play a key role in physics appearing in areas such as quantum field theories of the fundamental particles and emergent degrees of freedom in quantum materials. Motivated by the desire to efficiently simulate many-body quantum systems with exact local gauge invariance, gauge equivariant neural-network quantum states are introduced, which exactly satisfy the local Hilbert space constraints necessary for the description of quantum lattice gauge theory with Z_{d} gauge group and non-Abelian Kitaev D(G) models on different geometries. Focusing on the special case of Z_{2} gauge group on a periodically identified square lattice, the equivariant architecture is analytically shown to contain the loop-gas solution as a special case. Gauge equivariant neural-network quantum states are used in combination with variational quantum Monte Carlo to obtain compact descriptions of the ground state wave function for the Z_{2} theory away from the exactly solvable limit, and to demonstrate the confining or deconfining phase transition of the Wilson loop order parameter.
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Nitric oxide, a signaling molecule, inhibits mitochondrial respiration by binding with cytochrome c oxidase, resulting in elevated production of reactive superoxide species (reactive oxygen and nitrogen) in the mitochondria and increased susceptibility to cell death. Generation of mitochondrial superoxide species can be suppressed by natural compounds such as resveratrol, a dietary polyphenol found in the skin of red fruits. In various cancer cells, resveratrol shows anti-oxidant and cancer preventive properties. Since, the effect of resveratrol on reactive superoxide species-independent apoptosis in prostate cancer cells is not well illustrated; therefore, we investigated this phenomenon in TRAMP murine prostate cancer cells. To accomplish this, TRAMP cells were incubated with resveratrol, resveratrol + DETA-NONOate, DETA-NONOate (nitric oxide donor), resveratrol + L-NMMA, or L-NMMA (nitric oxide inhibitor) for 48 h, and reactive superoxide species in the mitochondria and culture supernatant were measured. In addition, the mitochondrial membrane potential, cell viability, expression of apoptotic markers (Bax and Bcl2), γ-H2A.x, p53, and caspase-3 was determined. We found that resveratrol suppressed reactive superoxide species such as reactive oxygen species in the mitochondria and nitric oxide in culture supernatant when compared to the DETA-NONOate treatment and disrupted the mitochondrial membrane potential. Resveratrol also reduced cell viability, altered the expression of apoptotic markers (Bax and Bcl2), and increased expression of γ-H2A.x (indicative marker of DNA fragmentation) and p53 (a critical DNA damage response protein). However, there was no appreciable modulation of the caspase-3. Therefore, our data suggest that resveratrol induces superoxide species-independent apoptosis and may act as a therapeutic agent against prostate cancer.
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Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Próstata/patologia , Estilbenos/farmacologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , ResveratrolRESUMO
It is possible to couple Dirac-Born-Infeld scalars possessing generalized Galilean internal shift symmetries (Galileons) to nonlinear massive gravity in four dimensions, in such a manner that the interactions maintain the Galilean symmetry. Such a construction is of interest, because it is not possible to couple such fields to massless general relativity in the same way. We show that this theory has the primary constraint necessary to eliminate the Boulware-Deser ghost, thus preserving the attractive properties of both the Galileons and ghost-free massive gravity.
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In bone tissue engineering, the organo-ceramic composite, electrospun polycaprolactone/hydroxyapatite (PCL/HA) scaffold has the potential to support cell proliferation, migration, differentiation, and homeostasis. Here, we report the effect of PCL/HA scaffold in tissue regeneration using human mesenchymal stem cells (hMSCs). We characterized the scaffold by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscope (SEM) and assessed its biocompatibility. PCL/HA composite is superior as a scaffold compared to PCL alone. Furthermore, increasing HA content (5-10%) was more efficacious in supporting cell-scaffold attachment, expression of ECM molecules and proliferation. These results suggest that PCL/HA is useful as a scaffold for tissue regeneration.
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Materiais Biomiméticos , Osso e Ossos/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Regeneração Óssea , Varredura Diferencial de Calorimetria , Durapatita , Matriz Extracelular , Humanos , Células-Tronco Mesenquimais/citologia , Microscopia Eletrônica de Varredura , Poliésteres , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Found in the skins of red fruits, including grapes, resveratrol (RES) is a polyphenolic compound with cancer chemopreventive activity. Because of this activity, it has gained interest for scientific investigations. RES inhibits tumor growth and progression by targeting mitochondria-dependent or -independent pathways. However, further investigations are needed to explore the underlying mechanisms.The present study is focused on examining the role of RES-induced, mitochondria-mediated, caspase-independent apoptosis of prostate cancer cells, namely transgenic adenocarcinoma of mouse prostate (TRAMP) cells. These cells were exposed to RES for various times, and cell killing, cell morphology, mitochondrial membrane potential (Δψm), expression of Bax and Bcl2 proteins, the role of caspase-3, and DNA fragmentation were analyzed.TRAMP cells exposed to RES showed decreased cell viability, altered cell morphology, and disrupted Δψm, which led to aberrant expression of Bax and Bcl2 proteins. Furthermore, since the caspase-3 inhibitor, z-VAD-fmk (benzyloxycarbonyl-valine-alanine-aspartic acid-fluoromethyl ketone), had no appreciable impact on RES-induced cell killing, the killing was evidently caspase-independent. In addition, RES treatment of TRAMP-C1, TRAMP-C2, and TRAMP-C3 cells caused an appreciable breakage of genomic DNA into low-molecular-weight fragments.These findings show that, in inhibition of proliferation of TRAMP cells, RES induces mitochondria-mediated, caspase-independent apoptosis. Therefore, RES may be utilized as a therapeutic agent to control the proliferation and growth of cancer cells.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Mitocôndrias/efeitos dos fármacos , Neoplasias da Próstata/patologia , Estilbenos/farmacologia , Animais , Inibidores de Caspase/farmacologia , Caspases/química , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Resveratrol , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In all organisms, heat-shock proteins (HSPs) provide an ancient defense system. These proteins act as molecular chaperones by assisting proper folding and refolding of misfolded proteins and aid in the elimination of old and damaged cells. HSPs include Hsp100, Hsp90, Hsp70, Hsp40, and small HSPs. Through its substrate-binding domains, Hsp70 interacts with wide spectrum of molecules, ranging from unfolded to natively folded and aggregated proteins, and provides cytoprotective role against various cellular stresses. Under pathophysiological conditions, the high expression of Hsp70 allows cells to survive with lethal injuries. Increased Hsp70, by interacting at several points on apoptotic signaling pathways, leads to inhibition of apoptosis. Elevated expression of Hsp70 in cancer cells may be responsible for tumorigenesis and for tumor progression by providing resistance to chemotherapy. In contrast, inhibition or knockdown of Hsp70 reduces the size of tumors and can cause their complete regression. Moreover, extracellular Hsp70 acts as an immunogen that participates in cross presentation of MHC-I molecules. The goals of this review are to examine the roles of Hsp70 in cancer and to present strategies targeting Hsp70 in the development of cancer therapeutics.
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Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Proteínas de Choque Térmico HSP70/imunologia , Neoplasias/terapia , Animais , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico HSP70/genética , Humanos , Terapia de Alvo Molecular , Neoplasias/genética , Neoplasias/imunologiaAssuntos
Dor Abdominal/etiologia , Enfisema/complicações , Gastropatias/complicações , Estômago/patologia , Dor Abdominal/diagnóstico , Adulto , Angiografia , Diagnóstico Diferencial , Enfisema/diagnóstico , Gastroscopia , Humanos , Masculino , Gastropatias/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Many teams from each of the different military services, as well as numerous civilian agencies, were involved in providing care to the victims, survivors, and family members of the September 11th attacks. However, the different teams initially had difficulties with communication and command and control issues. This article describes the perspective from Health Affairs on coordination of those efforts.
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Comunicação , Sistemas de Comunicação entre Serviços de Emergência/organização & administração , Serviços de Saúde Mental/organização & administração , Medicina Militar/organização & administração , Terrorismo/psicologia , United States Government Agencies , Aeronaves , Planejamento em Desastres , Humanos , Estados Unidos , VirginiaRESUMO
In this article, we review the literature on posttraumatic stress disorder (PTSD) and PTSD-like symptoms that can occur along with mild traumatic brain injury (TBI) and concussion, with specific reference to concussive injuries in the military. We address four major areas: (1) clinical aspects of TBI and PTSD, including diagnostic criteria, incidence, predictive factors, and course; (2) biological overlap between PTSD and TBI; (3) comorbidity between PTSD and other mental disorders that can occur after mild TBI; and (4) current treatments for PTSD, with specific considerations related to treatment for patients with mild TBI or concussive injuries.