Despite their partial ionic nature, many layered diatomic crystals avoid internal electric polarization by forming a centrosymmetric lattice at their optimal van-der-Waals stacking. Here, we report a ...stable ferroelectric order emerging at the interface between two naturally-grown flakes of hexagonal-boron-nitride, which are stacked together in a metastable non-centrosymmetric parallel orientation. We observe alternating domains of inverted normal polarization, caused by a lateral shift of one lattice site between the domains. Reversible polarization switching coupled to lateral sliding is achieved by scanning a biased tip above the surface. Our calculations trace the origin of the phenomenon to a subtle interplay between charge redistribution and ionic displacement, and provide intuitive insights to explore the interfacial polarization and its unique "slidetronics" switching mechanism.
Due to the high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson disease (PD), routine cognitive screening is important for the optimal management of patients with PD. The ...Montreal Cognitive Assessment (MoCA) is more sensitive than the commonly used Mini-Mental State Examination (MMSE) in detecting MCI and dementia in patients without PD, but its validity in PD has not been established.
A representative sample of 132 patients with PD at 2 movement disorders centers was administered the MoCA, MMSE, and a neuropsychological battery with operationalized criteria for deficits. MCI and PD dementia (PDD) criteria were applied by an investigator blinded to the MoCA and MMSE results. The discriminant validity of the MoCA and MMSE as screening and diagnostic instruments was ascertained.
Approximately one third of the sample met diagnostic criteria for a cognitive disorder (12.9% PDD and 17.4% MCI). Mean (SD) MoCA and MMSE scores were 25.0 (3.8) and 28.1 (2.0). The overall discriminant validity for detection of any cognitive disorder was similar for the MoCA and the MMSE (receiver operating characteristic area under the curve 95% confidence interval): MoCA (0.79 0.72, 0.87) and MMSE (0.76 0.67, 0.85), but as a screening instrument the MoCA (optimal cutoff point = 26/27, 64% correctly diagnosed, lack of ceiling effect) was superior to the MMSE (optimal cutoff point = 29/30, 54% correctly diagnosed, presence of ceiling effect).
The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, has adequate psychometric properties as a screening instrument for the detection of mild cognitive impairment or dementia in Parkinson disease. However, a positive screen using either instrument requires additional assessment due to suboptimal specificity at the recommended screening cutoff point.
Amplification of the ERBB2 gene, which encodes human epidermal growth factor receptor 2 (HER2), causes the overexpression of a major proliferative driver for a subset of breast and gastric cancers. ...Treatments for patients with HER2-positive cancer include the monoclonal antibody trastuzumab and, in the case of metastatic breast cancer, the tyrosine kinase inhibitor lapatinib. Despite significant improvement in patient outcome as a result of these therapies, challenges remain. This Review focuses on proposed mechanisms of action and resistance in the context of potential new therapeutic options. Therapeutic approaches currently in development likely will yield additional clinically meaningful improvements for patients with HER2-positive cancer.
T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. Here we integrated large-scale profiling data of alterations in gene expression, allelic copy number ...(CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identify novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor/cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM toward a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.
Xenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute ...rejection. To avoid this, pigs have been bred with a knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue.
We transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection.
The xenograft in both recipients began to make urine within moments after reperfusion. Over the 54-hour study, the kinetic eGFR increased from 23 ml per minute per 1.73 m
of body-surface area before transplantation to 62 ml per minute per 1.73 m
after transplantation in Recipient 1 and from 55 to 109 ml per minute per 1.73 m
in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys.
Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.).
Coherent control of quantum states has been demonstrated in a variety of superconducting devices. In all of these devices, the variables that are manipulated are collective electromagnetic degrees of ...freedom: charge, superconducting phase, or flux. Here we demonstrate the coherent manipulation of a quantum system based on Andreev bound states, which are microscopic quasi-particle states inherent to superconducting weak links. Using a circuit quantum electrodynamics setup, we performed single-shot readout of this Andreev qubit. We determined its excited-state lifetime and coherence time to be in the microsecond range. Quantum jumps and parity switchings were observed in continuous measurements. In addition to having possible quantum information applications, such Andreev qubits are a test-bed for the physics of single elementary excitations in superconductors.
A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 ...clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved.
Nitrogen Metabolism in the Rumen Bach, A.; Calsamiglia, S.; Stern, M.D.
Journal of dairy science
88, Številka:
13 Electronic Supplement 1
Journal Article
Recenzirano
Odprti dostop
Protein metabolism in the rumen is the result of metabolic activity of ruminal microorganisms. The structure of the protein is a key factor in determining its susceptibility to microbial proteases ...and, thus, its degradability. Ruminal protein degradation is affected by pH and the predominant species of microbial population. Ruminal proteolytic activity decreases as pH decreases with high-forage dairy cattle-type rations, but not in high-concentrate beef-type rations. Accumulation of amino acid (AA) N after feeding suggests that AA uptake by rumen microorganisms could be the limiting factor of protein degradation in the rumen. In addition, there are several AA, such as Phe, Leu, and Ile, that are synthesized by rumen microorganisms with greater difficulty than other AA. The most common assessment of efficiency of microbial protein synthesis (EMPS) is determination of grams of microbial N per unit of rumen available energy, typically expressed as true organic matter or carbohydrates fermented. However, EMPS is unable to estimate the efficiency at which bacteria capture available N in the rumen. An alternative and complementary measure of microbial protein synthesis is the efficiency of N use (ENU). In contrast to EMPS, ENU is a good measurement for describing efficiency of N capture by ruminal microbes. Using EMPS and ENU, it was concluded that optimum bacterial growth in the rumen occurs when EMPS is 29g of bacterial N/kg of fermented organic matter, and ENU is 69%, implying that bacteria would require about 1.31×rumen-available N per unit of bacterial N. Because the distribution of N within bacterial cells changes with rate of fermentation, AA N, rather than total bacterial N should be used to express microbial protein synthesis.
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