Miracle-dz/UniFAR-FTUs huggingface dataset:
Delayed auditory feedback in the treatment of stuttering: clients as consumers.

PURPOSE To investigate the effect of repeated exposure to delayed auditory feedback (DAF) during a 3-month period outside a clinical environment and with only minimal clinical guidance on speech fluency in people who stutter. METHOD A pretest-post-test design was used with repeated exposure to DAF during 3 months as the independent variable. Nine stuttering individuals aged between 18 and 45 years served as subjects. Videotaped samples from different speech tasks were collected before and after 3 months' exposure to DAF, each time under two conditions: first during non-altered feedback (NAF) and subsequently during DAF. RESULTS Before the repeated exposure to DAF, the percentage of stuttered words was significantly higher during NAF than during DAF. After 3 months' exposure to DAF, the percentage of stuttered words during NAF had dropped to a non-significant level in comparison with the DAF condition. Comparison of the percentage of stuttered words during NAF before and after repeated exposure to DAF showed significantly less stuttering after the repeated exposure to DAF. The percentage of stuttered words during DAF was generally somewhat higher, but not significantly so, after the 3 months' repeated exposure to DAF than before the exposure to DAF. CONCLUSIONS Results confirm that DAF is an effective means of reducing stuttering even when employed as the only treatment approach outside a therapeutic environment. They also suggest that DAF continues to promote fluency when used over a longer period, but also that length of exposure and fluency enhancement are probably not in a linear relationship.
MLYCD mutation analysis: Evidence for protein mistargeting as a cause of MLYCD deficiency

Malonyl‐CoA decarboxylase (MLYCD) deficiency is an autosomal recessive disorder characterized by malonic aciduria, developmental delay, seizure disorder, hypoglycemia, and cardiomyopathy. Genomic sequencing of MLYCD in nine unrelated patients identified 16 of 18 pathogenic alleles, which are documented in the newly created Human MLYCD Allelic Variant Database (http://mlycd.hgu.mrc.ac.uk/). Fibroblast cell lines were available from eight of these patients and two previously reported patients with homozygous MLYCD mutations. Western blot analysis using antisera raised to a C‐terminal peptide detected a 66‐kDa band that was absent in six patients and substantially reduced in three patients. One patient showed an increase in protein levels with a prominent smeary 68–l83‐kDa band. Immunocytochemical analysis of MLYCD‐expressing patient cell lines showed apparent intracellular mislocalization. An extreme N‐terminal mutation c.8G>A (p.G3D) mislocalized to the plasma membrane, suggesting that a novel targeting signal may reside in a four–amino acid conserved N‐terminal motif. A 25‐base deletion between the putative mitochondrial and peroxisomal initiating codons (M1 and M40) and a point mutation ablating the second of these (c.119T>C, p.M40T) both showed punctate perinuclear staining. As none of the three mislocalizing mutations are predicted to alter the catalytic function of the peptide, it seems likely that correct subcellular localization of MLYCD is critical for it to function normally. Hum Mutat 22:288–300, 2003. © 2003 Wiley‐Liss, Inc.
Broadband 3-D Luneburg Lenses Based on Metamaterials of Radially Diverging Dielectric Rods

In this letter, we describe and study microwave Luneburg lenses using a broadband metamaterial composed of radially diverging dielectric rods. The gradual Luneburg's permittivity profile is achieved in this lens through arranging identical thin rods with a spatially variable cross section in various radial directions with a subwavelength separation. The performance of the considered metamaterial lenses was studied by full-wave numerical simulation and measurements in an anechoic chamber. The results reveal that, although anisotropy of the structure causes aperture phase errors, the structure composed of diverging dielectric rods may still operate as a cylindrical or spherical Luneburg lens. Advantageously, the considered design is attractive for mass production of large-scaled beam-steering antennas because the lens is composed of identical shaped dielectric parts.
Reduced switching loss based DC-bus voltage balancing algorithm for three-level neutral point clamped (NPC) inverter for electric vehicle applications

A performance comparison study for two proposed DC-bus voltage balancing algorithms is carried out, with a three-level NPC based permanent magnet synchronous machine (PMSM) drive for the electric vehicle propulsion application. Both the control algorithms are able to keep the two DC-link capacitor voltage variation within a tolerance level with wider range of speed and torque variation of the load drive cycle. However, with the second proposed control strategy inverter total switching losses can be reduced considerably, compared to the first proposed strategy. Both the losses are then compared with a conventional two-level inverter, with a wider variation in switching frequency. Results show a significant reduction in total inverter losses at higher switching frequencies with three-level inverter. Both the two- and three-level inverter control strategies are developed using space-vector pulse width modulation (SV-PWM) scheme. The switching and conduction loss distribution in different switches and diodes for both the two- and three-level inverters are also studied. Finally the total voltage harmonic distortion (%THDv), percentage torque ripple (%Trip), and capacitor voltage fluctuation (%Vcaprip) are also compared. Switching losses are calculated in a PLECS environment using data sheet parameters from Infineon and control logics are developed in MATLAB/Simulink. For this study a 110 kW surface-PMSM is considered. A scaled down prototype is built in laboratory for both the inverters and tested with a 6.0 kW surface-PMSM. Both the simulation and experimental results show satisfactory performance of the proposed system.
Effects of Human Capital on Regional Growth: Evidence from US County Data

The purpose of the paper is to empirically investigate the role of human capital and labour market conditions in the growth process. To do so, cross-sectional data for 3062 counties across 50 states of the US. Firstly, findings from the empirical estimation suggest income convergence among US counties. Secondly, the stock of human capital appears to have the growth enhancing effect while education expenditures turn out to retard economic growth. Thirdly, it is found that the unemployment rate would have a negative association with regional growth whereas the net migration rate is likely to have a positive relationship with growth. Once the sample counties are divided into both the poor group and the rich group, finally, such main empirical results overall remain unchanged and statistically significant.
A 18.5-fJ/step VCO-based 0–1 MASH ΔΣ ADC with digital background calibration

A scaling-friendly and energy-efficient 0-1 MASH ΔΣ ADC is proposed in this work. An 8b SAR is used as the 1st stage for coarse quantization. A ring VCO is used as the 2nd stage for fine quantization. The proposed ADC uses digital background calibration to track VCO gain variation across PVT. A 40nm CMOS prototype achieves a Walden FoM of 18.5 fJ/conv-step while operating from 1.1V supply.
Increased Affinity and Stability of an Anti-HIV-1 Envelope Immunotoxin by Structure-based Mutagenesis*

HIV-infected cells are selectively killed by an immunotoxin in which a truncated form of Pseudomonasexotoxin A is joined to the variable region of a broadly neutralizing antibody (3B3) that recognizes the viral envelope glycoprotein (Env). To improve the efficacy of this molecule, we used three-dimensional structural information and phage selection data to design 23 single and multiple point mutations in the antibody variable region sequences that contact Env. Substituting an aromatic residue for an aspartate in the third complementarity-determining region of VH increased the potency of the immunotoxin by ∼10-fold in a cell-killing assay. Detailed analysis of one such mutant, N31H/Q100eY, revealed both a higher affinity for monomeric and cell surface Env and an increased stability against aggregation compared with the starting immunotoxin. Conversion to a disulfide-linked two-chain format further stabilized the protein. N31H/Q100eY retained the ability to bind to Env from multiple viral isolates, to inhibit Env-mediated cell fusion, and to limit spreading viral infection in peripheral blood mononuclear cells. Such site-directed mutants may increase the utility of immunotoxins for reducing or eradicating persistent HIV-1 infection in humans.
CSPred: A machine-learning-based compound model to identify the functional activities of biologically-stable toxins

Pharmaceutical industries are interested in Cysteine-stabilized peptides because they offer an array bioactive properties while being highly stable under a range of physiological conditions. However, it is widely appreciated that only a small fraction of this type of peptides have been experimentally discovered while a large number remain unidentified. However, identification of these cysteine-stabilized peptides using normal sequence alignment is challenging because of the high noise to signal ratio. Therefore, we propose a machine learning-based compound model to predict functional properties of cysteine-stabilized peptides from their primary sequence. We also offer a freely available web-server at http://watson.ecs. baylor.edu/cspred to make the model available to the scientific community.
Reference change values

Abstract Reference change values (RCV) provide objective tools for assessment of the significance of differences in serial results from an individual. The concept is simple and the calculation easy, since all laboratories know their analytical imprecision (CVA) and estimates of within-subject biological variation (CVI) are available for a large number of quantities. Generally, CVI are constant over time, geography, methodology and in health and chronic stable disease. The formula is RCV=21/2 · Z · (CVA2 + CVI2)1/2, where Z is the number of standard deviations appropriate to the probability. Correct interpretation of the semantics describing the clinical use of RCV is vital for selection of the Z-score. Many quantities of clinically importance exist for which good estimates of RCV are unavailable. Derivation of CVI may be difficult for such quantities: flair and imagination are required in selecting populations with chronic but stable disease on whom CVI can be determined. RCV can be used for delta-checking and auto-verification and laboratory information management systems (LIMS) can be adapted to do this. Recently, log-normal transformation to obtain unidirectional RCV has been used. Gaps in knowledge of RCV still require filling since the need for measures of change is clearly expressed in guidelines.
Curvature-driven lipid sorting needs proximity to a demixing point and is aided by proteins

Sorting of lipids and proteins is a key process allowing eukaryotic cells to execute efficient and accurate intracellular transport and to maintain membrane homeostasis. It occurs during the formation of highly curved transport intermediates that shuttle between cell compartments. Protein sorting is reasonably well described, but lipid sorting is much less understood. Lipid sorting has been proposed to be mediated by a physical mechanism based on the coupling between membrane composition and high curvature of the transport intermediates. To test this hypothesis, we have performed a combination of fluorescence and force measurements on membrane tubes of controlled diameters pulled from giant unilamellar vesicles. A model based on membrane elasticity and nonideal solution theory has also been developed to explain our results. We quantitatively show, using 2 independent approaches, that a difference in lipid composition can build up between a curved and a noncurved membrane. Importantly, and consistent with our theory, lipid sorting occurs only if the system is close to a demixing point. Remarkably, this process is amplified when even a low fraction of lipids is clustered upon cholera toxin binding. This can be explained by the reduction of the entropic penalty of lipid sorting when some lipids are bound together by the toxin. Our results show that curvature-induced lipid sorting results from the collective behavior of lipids and is even amplified in the presence of lipid-clustering proteins. In addition, they suggest a generic mechanism by which proteins can facilitate lipid segregation in vivo.
Adaptive Filtering Under a Variable Kernel Width Maximum Correntropy Criterion

The maximum correntropy criterion (MCC) algorithm with constant kernel width leads to a tradeoff problem in terms of convergence rate and steady-state misalignment. Thus, this brief proposes a variable kernel width (VKW) MCC algorithm to overcome this problem. The optimal kernel width of the proposed VKW-MCC algorithm is calculated at each iteration by maximizing <inline-formula> <tex-math notation="LaTeX">${{\rm exp}(-e_{k}^{2}/2\sigma _{k}^{2})}$ </tex-math></inline-formula> with respect to the kernel width <inline-formula> <tex-math notation="LaTeX">${ \sigma _{k}}$ </tex-math></inline-formula>, wherein the kernel width is a function of the error, to make the error with greatest attenuation along the direction of the gradient ascent. Simulations in the contexts of system identification and echo cancellation have demonstrated that the proposed VKW-MCC algorithm yields a superior performance.
Immunohistochemical Analysis of MUC5B Apomucin Expression in Breast Cancer and Non-malignant Breast Tissues

A deregulation of several MUC genes (MUC1, MUC2, MUC3, MUC5AC, and MUC6) was previously demonstrated in breast carcinomas. Considering that recently we found the “non-mammary” MUC5B mRNA in primary breast tumors (Berois et al. 2003), we undertook the present study to evaluate the expression profile of MUC5B protein product in breast tissues, using LUM5B-2 antisera raised against sequences within the non-glycosylated regions of this apomucin. Expression of MUC5B by breast cancer cells was confirmed by immunocytochemistry, in situ hybridization, and Western blot on MCF-7 cancer cells. Using an immunohistochemical procedure, MUC5B apomucin was detected in 34/42 (81%) primary breast tumors, in 13/14 (92.8%) samples of non-malignant breast diseases, in 8/19 (42.1%) samples of normal-appearing breast epithelia adjacent to cancer, and in 0/5 normal control breast samples. The staining pattern of MUC5B was very different when comparing breast cancer cells (cytoplasmic) and non-malignant breast cells (predominantly apical and in the secretory material). We analyzed MUC5B mRNA expression using RT-PCR in bone marrow aspirates from 22/42 patients with breast cancer to compare with MUC5B protein expression in the primary tumors. Good correlation was observed because the six MUC5B-positive bone marrow samples also displayed MUC5B expression in the tumor. Our results show, for the first time at the protein level, that MUC5B apomucin is upregulated in breast cancer. Its characterization could provide new insights about the glycobiology of breast cancer cells.
Multiobjective Shape Optimization of Segmented Pole Permanent-Magnet Synchronous Machines With Improved Torque Characteristics

Magnet segmentation is an effective and simple technique for cogging torque reduction in high power permanent-magnet (PM) synchronous machines; however, it deteriorates air gap flux density and decreases the output torque. Therefore, a multiobjective optimization framework is necessary for cogging torque minimization, and to diminish its adverse effect on the output torque in segmented-pole permanent-magnet synchronous machines (PMSMs). This can be fulfilled by proper selection of widths and displacements of the magnet segments. Finite-element analysis (FEA) is an accurate method for this purpose. However, it is very time consuming where finding optimal configuration needs a lot of simulations. Thus, an analytical based design optimization is very useful and eases the design process. In this paper, a novel semianalytical model for cogging torque computation in PMSMs is proposed. Based on the proposed model, a multiobjective optimization framework is developed. The particle swarm optimization (PSO) method is applied to find the optimum machine design. To show the effectiveness of the proposed method, two prototype segmented magnet PMSMs with two and three PM blocks per pole are optimized respectively. Performance characteristics are compared to the initial machine design and segmented PMSMs with design parameters chosen according to previous analytical models and initial uniform pole machines using FEA.
S-layer proteins as supporting scaffoldings for functional lipid membranes

A great challenge is the coupling of very sensitive microelectronic devices to wet biological systems in the generation of biomimetic sensors. Lipid membranes on solid supports (electrodes or semiconductors) may become the matrix of future bioelectronic devices probing and controlling biomolecular processes for scientific and technical applications. A sufficient electrical isolation between the coupling region and the surrounding electrolyte is mandatory. An attached lipid membrane with integral natural or designed proteins may be the material of choice if the biological components are kept in a proper environment. To retain the fluidity and stability of the lipid membrane and to provide an ion reservoir and space for bulky integral proteins, a separating layer composed of crystalline arrays of monomolecular proteinaceous subunits, termed S-layer, can be self-assembled on metal or semiconductor surfaces. In this way S-layer-supported lipid membranes are biomimetic structures mimicking the supramolecular principle of archeal cell envelopes. These composite architectures may ascend toward exciting new key devices, particularly in fields of membrane protein-based biosensors or lab-on-a-chip technology.
Combination Therapy With Nitric Oxide and Molecular Hydrogen in a Murine Model of Acute Lung Injury

ABSTRACT Acute lung injury (ALI) is still a leading cause of morbidity and mortality in critically ill patients. Inhaled nitric oxide (NO) has been reported to ameliorate ALI. However, reactive nitrogen species produced by NO can cause lung injury. Because hydrogen gas (H2) is reported to eliminate peroxynitrite, it is expected to reduce the adverse effects of NO. Moreover, we have found that H2 inhalation can attenuate lung injury. Therefore, we hypothesized that combination therapy with NO and H2 might afford more potent therapeutic strategies for ALI. In the present study, a mouse model of ALI was induced by intratracheal administration of lipopolysaccharide (LPS). The animals were treated with inhaled NO (20 ppm), H2 (2%), or NO + H2, starting 5 min after LPS administration for 3 h. We found that LPS-challenged mice exhibited significant lung injury characterized by the deterioration of histopathology and histologic scores, wet-to-dry weight ratio, and oxygenation index (ratio of oxygen tension to inspired oxygen fraction [Pao2/Fio2]), as well as total protein in the bronchoalveolar lavage fluid (BALF), which was attenuated by NO or H2 treatment alone. Combination therapy with NO and H2 had a more beneficial effect with significant interaction between the two. While the nitrotyrosine level in lung tissue was prominent after NO inhalation alone, it was significantly eliminated after breathing a mixture of NO with H2. Furthermore, NO or H2 treatment alone markedly attenuated LPS-induced lung neutrophil recruitment and inflammation, as evidenced by downregulation of lung myeloperoxidase activity, total cells, and polymorphonuclear neutrophils in BALF, as well as proinflammatory cytokines (tumor necrosis factor &agr;, interleukins 1&bgr; and 6, and high-mobility group box 1) and chemokines (keratinocyte-derived chemokine, macrophage inflammatory proteins 1&agr; and 2, and monocyte chemoattractant protein 1) in BALF. Combination therapy with NO and H2 had a more beneficial effect against lung inflammatory response. Moreover, combination therapy with NO and H2 could more effectively inhibit LPS-induced pulmonary early and late nuclear factor &kgr;B activation as well as pulmonary cell apoptosis. In addition, combination treatment with inhaled NO and H2 could also significantly attenuate lung injury in polymicrobial sepsis. Combination therapy with subthreshold concentrations of NO and H2 still had a significantly beneficial effect against lung injury induced by LPS and polymicrobial sepsis. Collectively, these results demonstrate that combination therapy with NO and H2 provides enhanced therapeutic efficacy for ALI.
Directed Differentiation of Human‐Induced Pluripotent Stem Cells Generates Active Motor Neurons

The potential for directed differentiation of human‐induced pluripotent stem (iPS) cells to functional postmitotic neuronal phenotypes is unknown. Following methods shown to be effective at generating motor neurons from human embryonic stem cells (hESCs), we found that once specified to a neural lineage, human iPS cells could be differentiated to form motor neurons with a similar efficiency as hESCs. Human iPS‐derived cells appeared to follow a normal developmental progression associated with motor neuron formation and possessed prototypical electrophysiological properties. This is the first demonstration that human iPS‐derived cells are able to generate electrically active motor neurons. These findings demonstrate the feasibility of using iPS‐derived motor neuron progenitors and motor neurons in regenerative medicine applications and in vitro modeling of motor neuron diseases. STEM CELLS 2009;27:806–811
Recruitment and Reasons for Non-Participation in a Family-Coping-Orientated Palliative Home Care Trial (FamCope)

Cancer patients and their family caregivers need support to cope with physical, psychosocial, and existential problems early in the palliative care trajectory. Many interventions target patient symptomatology, with health care professionals acting as problem-solvers. Family coping, however, is a new research area within palliative care. The FamCope intervention was developed to test if a nurse-led family-coping-orientated palliative home care intervention would help families cope with physical and psychosocial problems at home—together as a family and in interaction with health care professionals. However, an unexpectedly high number of families declined participation in the trial. We describe and discuss the recruitment strategy and patient reported reasons for non-participation to add to the knowledge about what impedes recruitment and to identify the factors that influence willingness to participate in research aimed at family coping early in the palliative care trajectory. Patients with advanced cancer and their closest relative were recruited from medical, surgical, and oncological departments. Reasons for non-participation were registered and characteristics of participants and non-participants were compared to evaluate differences between subgroups of non-participants based on reasons not to participate and reasons to participate in the trial. A total of 65.9% of the families declined participation. Two main categories for declining participation emerged: first, that the “burden of illness is too great” and, second, that it was “too soon” to receive this kind of support. Men were more likely to participate than women. Patients in the “too soon” group had similar characteristics to participants in the trial. Timing of interventions and readiness of patients and their relatives seems to affect willingness to receive a family-coping-orientated care approach and impeded recruitment to this trial. Our findings can be used in further research and in clinical practice in order to construct interventions and target relevant populations for early family-coping-orientated palliative care.