Miracle-dz/UniFAR-FTUs huggingface dataset:
The Clinical Dementia Rating Sum of Box Score in Mild Dementia

Background: Making an early diagnosis of dementia is becoming increasingly important, but is difficult in practice. The Clinical Dementia Rating (CDR) scale is a widely used dementia staging instrument, yielding a global score and a summated score (sum of box score). This study examines the utility of the CDR sum of box score, rather than the CDR global score, in making a diagnosis of early dementia. Objective: To determine whether the CDR sum of box score is predictive of an ICD-10 diagnosis of dementia in cases with mild cognitive deficits. Methods: Clinical data recorded on our Memory Clinic database were examined for all patients seen over a 6-year period. Data were extracted from 276 first visits in which patients had scored 0.5 using the CDR global score. We examined the relationship between CDR sum of box score and consensus diagnosis of dementia using logistic regression. Results: We found that increased CDR sum of box score was significantly associated with a higher probability of being assigned an ICD-10 diagnosis of dementia (p < 0.001). The odds ratio for the coefficient of CDR sum of box was 2.3 (95% CI 1.7–3.1), indicating that the likelihood of being diagnosed as having dementia increased by a factor of 2.3 for every point increase on the CDR sum of box score. Conclusion: These findings indicate that the CDR sum of box score provides additional information to the CDR global score in mild cases. The CDR sum of box score is a helpful indicator in making/excluding a diagnosis of dementia in people with mild cognitive deficits.
mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene‐expression levels

Activation of the Akt/mammalian target of rapamycin (mTOR) pathway has been shown to be associated with resistance to endocrine therapy in estrogen receptor alpha (ERα)‐positive breast cancer patients. Utmost importance is attached to strategies aimed at overcoming treatment resistance. In this context, this work aimed to investigate whether, in breast cancer cells, the use of an mTOR inhibitor would be sufficient to reverse the resistance acquired after exposure to endocrine therapy. The ERα‐positive human breast adenocarcinoma derived‐MCF‐7 cells used in this study have acquired both cross‐resistance to hydroxy‐tamoxifen (OH‐Tam) and to fulvestrant and strong activation of the Akt/mTOR pathway. Cell proliferation tests in control cells demonstrated that the mTOR inhibitor rapamycin enhanced cell sensitivity to endocrine therapy when combined to OH‐Tam or to fulvestrant. In resistant cells, rapamycin used alone greatly inhibited cell proliferation and reversed resistance to endocrine therapy by blocking the agonist‐like activity of OH‐Tam on cell proliferation and bypassing fulvestrant resistance. Reversion of resistance by rapamycin was associated with increased ERα protein expression levels and modification of the balance of phospho‐ser167 ERα/total ERα ratio. Pangenomic DNA array experiments demonstrated that the cotreatment of resistant cells with fulvestrant and rapamycin allowed the restoration of 40% of the fulvestrant gene‐expression signature. Taken together, data presented herein strongly support the idea that mTOR inhibitor might be one of the promising therapeutic approaches for patients with ERα‐positive endocrine therapy‐resistant breast cancers. (Cancer Sci 2008; 99: 1992–2003)
A new four-level converter for low and medium voltage applications

The paper presents a new four-level voltage source converter (VSC). Compared to conventional four-level converters, this proposed converter has fewer components and can be used for a higher power density system in low and medium voltage applications. Its principles and advantages are studied in this paper. The effect of various redundant switching states on the voltages of flying capacitors is analyzed. The voltages of flying capacitors can be balanced by selecting proper redundant switching states. A carrier-based pulse width modulation (CBPWM) is used to control the proposed converter. The performance of the converter is investigated and simulated in MATLAB/Simulink as well as on a 5 kVA experimental prototype.
Microscale Distribution of Populations and Activities ofNitrosospira and Nitrospira spp. along a Macroscale Gradient in a Nitrifying Bioreactor: Quantification by In Situ Hybridization and the Use of Microsensors

ABSTRACT The change of activity and abundance of Nitrosospiraand Nitrospira spp. along a bulk water gradient in a nitrifying fluidized bed reactor was analyzed by a combination of microsensor measurements and fluorescence in situ hybridization. Nitrifying bacteria were immobilized in bacterial aggregates that remained in fixed positions within the reactor column due to the flow regimen. Nitrification occurred in a narrow zone of 100 to 150 μm on the surface of these aggregates, the same layer that contained an extremely dense community of nitrifying bacteria. The central part of the aggregates was inactive, and significantly fewer nitrifiers were found there. Under conditions prevailing in the reactor, i.e., when ammonium was limiting, ammonium was completely oxidized to nitrate within the active layer of the aggregates, the rates decreasing with increasing reactor height. To analyze the nitrification potential, profiles were also recorded in aggregates subjected to a short-term incubation under elevated substrate concentrations. This led to a shift in activity from ammonium to nitrite oxidation along the reactor and correlated well with the distribution of the nitrifying population. Along the whole reactor, the numbers of ammonia-oxidizing bacteria decreased, while the numbers of nitrite-oxidizing bacteria increased. Finally, volumetric reaction rates were calculated from microprofiles and related to cell numbers of nitrifying bacteria in the active shell. Therefore, it was possible for the first time to estimate the cell-specific activity of Nitrosospira spp. and hitherto-uncultured Nitrospira-like bacteria in situ.
Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes

Horizontal cells mediate inhibitory feed-forward and feedback communication in the outer retina; however, mechanisms that underlie transmitter release from mammalian horizontal cells are poorly understood. Toward determining whether the molecular machinery for exocytosis is present in horizontal cells, we investigated the localization of syntaxin-4, a SNARE protein involved in targeting vesicles to the plasma membrane, in mouse, rat, and rabbit retinae using immunocytochemistry. We report robust expression of syntaxin-4 in the outer plexiform layer of all three species. Syntaxin-4 occurred in processes and tips of horizontal cells, with regularly spaced, thicker sandwich-like structures along the processes. Double labeling with syntaxin-4 and calbindin antibodies, a horizontal cell marker, demonstrated syntaxin-4 localization to horizontal cell processes; whereas, double labeling with PKC antibodies, a rod bipolar cell (RBC) marker, showed a lack of co-localization, with syntaxin-4 immunolabeling occurring just distal to RBC dendritic tips. Syntaxin-4 immunolabeling occurred within VGLUT-1-immunoreactive photoreceptor terminals and underneath synaptic ribbons, labeled by CtBP2/RIBEYE antibodies, consistent with localization in invaginating horizontal cell tips at photoreceptor triad synapses. Vertical sections of retina immunostained for syntaxin-4 and peanut agglutinin (PNA) established that the prominent patches of syntaxin-4 immunoreactivity were adjacent to the base of cone pedicles. Horizontal sections through the OPL indicate a one-to-one co-localization of syntaxin-4 densities at likely all cone pedicles, with syntaxin-4 immunoreactivity interdigitating with PNA labeling. Pre-embedding immuno-electron microscopy confirmed the subcellular localization of syntaxin-4 labeling to lateral elements at both rod and cone triad synapses. Finally, co-localization with SNAP-25, a possible binding partner of syntaxin-4, indicated co-expression of these SNARE proteins in the same subcellular compartment of the horizontal cell. Taken together, the strong expression of these two SNARE proteins in the processes and endings of horizontal cells at rod and cone terminals suggests that horizontal cell axons and dendrites are likely sites of exocytotic activity.
Delayed‐rectifier potassium currents and the control of cardiac repolarization: Noble and Tsien 40 years after

Following activation by depolarization, all excitable cells undergo repolarizing steps to return the transmembrane potential to the initial resting level (often called the ‘resting potential’). In comparison with other excitable cells, cardiac myocytes remain depolarized for substantially greater periods, generating the action potential ‘plateau’ (Fig. 1A). The unique cardiac action potential plateau permits sufficient transmembrane Ca2+ entry into the cell via voltage-gated Ca2+ channels to maintain the sarcoplasmic reticulum Ca2+ stores needed for effective contraction, which occurs when the sarcoplasmic reticulum releases Ca2+ in response to triggering by transmembrane Ca2+ entry initiated via cell depolarization. The plateau also keeps Na+ channels inactivated for a substantial ‘refractory period’, preventing excessively rapid beating rates during cardiac arrhythmias. Cardiac repolarization is a delicate and highly regulated process, governed by sets of ion channels, pumps and exchangers, as well as autonomic nervous system modulators (Conrath & Opthof, 2006). If the repolarization process is impaired, cardiac action potentials are prolonged (Fig. 1B). When prolongation becomes exaggerated, voltage-dependent Ca2+ currents have sufficient time to recover from the inactivation that occurs at the most depolarized levels of the action potential. The consequent reactivation of plateau Ca2+ currents causes abnormal, arrhythmia-generating ‘early afterdepolarizations’. When repolarization is excessively rapid, action potentials are abbreviated (Fig. 1C), permitting re-entrant arrhythmias (a form of ‘short-circuiting’ of cardiac electrical activity; for a detailed review see Nattel et al. 2007). Figure 1 Schematic representation of the cardiac action potential and the consequences of repolarization abnormalities
The Maize Golden2 Gene Defines a Novel Class of Transcriptional Regulators in Plants

In the C4 plant maize, three photosynthetic cell types differentiate: C4 bundle sheath, C4 mesophyll, and C3 mesophyll cells. C3 mesophyll cells represent the ground state, whereas C4 bundle sheath and C4 mesophyll cells are specialized cells that differentiate in response to light-induced positional signals. The Golden2 (G2) gene regulates plastid biogenesis in all photosynthetic cells during the C3 stages of development. However, G2 function is specifically committed to the differentiation of bundle sheath cell chloroplasts in C4 leaf blades. In this article, we report the isolation of G2-like (Glk) genes from maize and rice, providing evidence for a family of Glk genes in plants. The expression profiles of the rice Glk genes suggest that these genes may act redundantly to promote photosynthetic development in this C3 species. In maize, G2 and ZmGlk1 transcripts accumulate primarily in C4 bundle sheath and C4 mesophyll cells, respectively, suggesting a specific role for each gene in C4 differentiation. We show that G2 and ZmGLK1 both can transactivate reporter gene transcription and dimerize in yeast, which supports the idea that these proteins act as transcriptional regulators of cell-type differentiation processes.
Higher Protein Intake Is Associated with Higher Lean Mass and Quadriceps Muscle Strength in Adult Men and Women.

BACKGROUND The impact of dietary protein intake on lower extremity lean mass and strength in community-dwelling adult Americans is not fully understood. OBJECTIVES The objective was to determine the associations between total protein (TP), animal protein (AP), and plant protein (PP) intakes and lean mass of the legs and quadriceps muscle strength. We further examined whether the associations with quadriceps strength may be explained by lean mass of the legs. METHODS This cross-sectional study included men (n = 1166) and women (n = 1509) from the Framingham Offspring Cohort in Massachusetts. Protein intake in grams per day was measured in either 1995-1998 or 1998-2001. Leg lean mass and isometric quadriceps strength, both in kilograms, were measured in 1996-2001. Multilinear regression models estimated adjusted least squares means of each of the muscle measures by quartile categories of protein intake, adjusting for relevant confounders and covariates. RESULTS Mean age was 59 ± 9 y (range: 29-86 y) and TP intake was 80 ± 27 g/d in men and 76 ± 26 g/d in women. In men and women, leg lean mass was higher in participants in the highest quartiles of TP and AP intake compared with those in the lowest quartiles of intake [least squares means (kg): TP-17.6 vs. 17.1 in men, P-trend: 0.005, and 11.7 vs. 11.4 in women, P-trend: 0.006; AP-17.6 vs. 17.1 in men, P-trend: 0.002, and 11.7 vs. 11.4 in women, P-trend: 0.003]. PP intake was not associated with lean mass in either sex. In men and women, quadriceps strength was higher in participants in the highest quartile of PP intake compared with those in the lowest quartile [least squares means (kg): 22.9 vs. 21.7 in men, P-trend: 0.01, and 19.0 vs. 18.2 in women, P-trend: 0.01]; this association was no longer significant after adjustment for fruit and vegetable intake (P-trend: 0.06 in men and 0.10 in women). Although no significant association was observed for AP intake in either sex, nonsignificant protective trends were observed for TP intake (P-trend: 0.08 in men and 0.10 in women). CONCLUSIONS Our findings suggest that maintaining adequate protein intake with age may help preserve muscle mass and strength in adult men and women. Dietary protein types may differentially affect muscle mass and strength. Whether PP is a marker of dietary quality or has a direct effect on muscle strength (independent of lean mass) needs to be further clarified.
Energy spectrum and persistent current in one-dimensional rings.

The correlations in the energy spectrum and persistent current of electrons in one-dimensional disordered rings threaded by an Aharonov-Bohm magnetic flux are shown to be so strong that the current of any level is sufficient to cancel the sum of the contributions of all previous levels. Hence, the sign of the sum of the n lowest single-level currents alternates as a function of n. A new relation between the real part of the inverse transmission coefficient and the energy spectrum is also derived.
Depression in older people living in residential homes

There is a large body of published research relating to depression in residential homes for older people (also called long-term-care homes, and including both nursing homes and hostels) (Ames 1990; 1993; Seitz et al., 2010; Snowdon and Purandare, 2010; Snowdon, 2010). However, despite increased detection and more frequent treatment in recent years, depression remains a significant problem for many older people living in such settings. This guest editorial summarizes current knowledge about prevalence, etiology, detection and screening, treatment and outcomes of depression in residential homes and concludes with a summary of key issues requiring urgent future action.
Effects of simultaneous aortocaval occlusion on oxygen consumption in patients

The effects of simultaneous occlusion of the thoracic aorta and inferior vena cava on oxygen consumption () have not yet been reported in humans. Ten patients (all ASA II) needed such simultaneous occlusion to allow hypoxic abdominal perfusion in the treatment of pancreatic cancer. With the development of the PhysioFlex® anaesthesia machine for closed‐circuit anaesthesia, intra‐operative real‐time curves of became available. Thus, we can continuously measure , and air consumption. By placing a pulmonary artery catheter, we could also intermittently calculate during the several phases of the perfusion procedure. Immediately after the simultaneous aortocaval occlusion started, decreased by 35% (68 ml min−1 m−2) and decreased below the critical value of 330 ml min−1 m−2. At reperfusion, repayment of the oxygen debt was by a two‐stage pattern: a fast repayment stage with an increase of about 65% was followed by a slow repayment stage of 14% increase (values compared to steady state). Oxygen consumption in women was found to be significantly lower than in men (P = 0·02), with significant variation between the sexes during different stages of the procedure. The oxygen debt was not completely repaid by the end of the procedure. We conclude that the significant variation found in oxygen consumption will have consequences while performing low‐flow anaesthesia, that additional oxygen supply during the recovery period because of the initially incomplete repayment of oxygen debt may be useful and that studies on oxygen consumption must present gender‐specific data because of the gender‐dependent variation found in oxygen consumption.
A joint model for interval‐censored functional decline trajectories under informative observation

Multi‐state models are useful for modelling disease progression where the state space of the process is used to represent the discrete disease status of subjects. Often, the disease process is only observed at clinical visits, and the schedule of these visits can depend on the disease status of patients. In such situations, the frequency and timing of observations may depend on transition times that are themselves unobserved in an interval‐censored setting. There is a potential for bias if we model a disease process with informative observation times as a non‐informative observation scheme with pre‐specified examination times. In this paper, we develop a joint model for the disease and observation processes to ensure valid inference because the follow‐up process may itself contain information about the disease process. The transitions for each subject are modelled using a Markov process, where bivariate subject‐specific random effects are used to link the disease and observation models. Inference is based on a Bayesian framework, and we apply our joint model to the analysis of a large study examining functional decline trajectories of palliative care patients. Copyright © 2015 John Wiley & Sons, Ltd.
Microneedle based sampling for breast cancer tissues

We have developed a microneedle based system that is capable of extracting cell membrane lipids from real breast cancer tissues. We show that it is possible to extract phosphatidylcholine (PC) and phosphoethanolamine (PE) lipids from the cancer tissue samples with the microneedle system and analyse them with mass spectrometry (MS). PC and PE lipids act as biomarkers for breast cancer. In future such system can help surgeons in their decision making during operations or they can be used as device for tissue research at high spatial resolution.
Site‐directed mutagenesis of Asp853 in Pdr3p transcriptional activator from Saccharomyces cerevisiae

The PDR3 gene encodes one of the main transcriptional activators involved in the control of multidrug resistance in the yeast Saccharomyces cerevisiae. Recently, it has been demonstrated that a specific D853Y mutation results in the loss of transactivation activity of Pdr3p and its conversion to multicopy suppressor of multidrug resistance. In this study, the Asp853 in Pdr3p was replaced by eight different amino acids and the function of mutated proteins was analysed. Different levels of complementation of cycloheximide hypersensitivity and expression of autoregulated PDR3 and its PDR5 target in the pdr1Δpdr3Δ mutant strain, ranging from that of the wild‐type to loss‐of‐function alleles, were observed in pdr3 mutants containing Pro, Glu, Arg, Asn, Ser, Leu, Phe, Ile or Tyr instead of Asp853 in Pdr3p. The introduction of the D853Y mutation into gain‐of‐function Pdr3p suppressed the transcription of the PDR3 and PDR5 genes and reduced both the rhodamine 6G efflux rate and the drug resistance level in corresponding double mutants. The results indicate that, while Pdr3p can tolerate several substitutions of Asp853, the occurrence of a hydrophobic amino acid at this position has an adverse effect on its function. Copyright © 2010 John Wiley & Sons, Ltd.
NONLINEAR BEHAVIOR OF HUMAN RESPIRATORY MOVEMENT DURING DIFFERENT SLEEP STAGES

To investigate the nonlinear properties of respiratory movement during different sleep stages, we applied an algorithm proposed by Grassberger and Procaccia to calculate the correlation dimension in rapid eye movement and non-rapid eye movement sleep. We also tested for nonlinearity in respiratory movement by comparing the correlation dimension for the original data with that for surrogate data. The study population included eight healthy volunteers. We recorded respiratory movement and the sleep electroencephalogram for 8 h. The correlation dimension for respiratory movement was 3.28 ± 0.19 (mean ± SD) during rapid eye movement sleep, 2.31 ± 0.21 during light sleep (stage I) and 1.64 ± 0.25 during deep slow-wave sleep (stage IV). Thus, the correlation dimension differed significantly by sleep stage (p < 0.001): it was least during stage IV sleep and greatest during REM. The correlation dimension for the original data also differed from that for surrogate data, confirming nonlinearity in original data. The results suggest that the nonlinear dynamics of respiratory movement in sleep changes with sleep stage, presumably due to the information processing by the cerebral cortex. The increased correlation dimension for respiratory movement in REM sleep may be related to increased cortical information processing associated with dreaming. (Chronobiology International, 18(1), 71–83, 2001)
A systematic method to compose over complete dictionaries for the processing of partial discharge signals

On-site measurement of partial discharges (PD) can provide valuable information about electrical equipment insulation degradation. Classical signal processing techniques have been used for PD signal denoising, but few approaches evaluate or present effective methods to attenuate impulsive and amplitude modulated (AM) noises, which are commonly found in on-site measurements. In this paper, a PD denoising method based on an over complete wavelet dictionary and Basis Pursuit Denoising (BPD) is presented. We describe the overall denoising algorithm and propose a methodology to compose the over complete dictionaries, starting from candidate wavelet families. The procedure starts by identifying the best families, followed by a method to define the number of families and their best combination. We show that the procedure gives better results when compared to a random choice of families, and present several processing cases based on simulated and measured signals.
Three-Level Tracking Method for Animating a 3D Humanoid Character

— With a rapid growth in 3D graphics technology over the last few years, people are desired to see more flexible reacting motions of a biped in animations. In particular, it is impossible to anticipate all reacting motions of a biped while facing a perturbation. In this paper, we propose a three-level tracking method for animating a 3D humanoid character. First, we take the laws of physics into account to attach physical attributes, such as mass, gravity, friction, collision, contact, and torque, to bones and joints of a character. The next step is to employ PD controller to follow a reference motion as closely as possible. Once the character cannot tolerate a strong perturbation to prevent itself from falling down, we are capable of tracking a desirable falling-down action to avoid any falling condition inaccuracy. From the experimental results, we demonstrate the effectiveness and flexibility of the proposed method in comparison with conventional data-driven approaches.