Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrophoretic separation and quantitation of cardiac myosin heavy chain isoforms in eight mammalian species.

A protocol for sample preparation and gel electrophoresis is described that reliably results in the separation of the α- and β-isoforms of cardiac myosin heavy chain (MHC-α and MHC-β) in eight mammalian species. The protocol is based on a simple, nongradient denaturing gel. The magnitude of separation of MHC-α and MHC-β achieved with this protocol is sufficient for quantitative determination of the relative amounts of these two isoforms in mouse, rat, guinea pig, rabbit, canine, pig, baboon, and human myocardial samples. The sensitivity of the protocol is sufficient for the detection of MHC isoforms in samples at least as small as 1 μg. The glycerol concentration in the separating gel is an important factor for successfully separating MHC-α and MHC-β in myocardial samples from different species. The effect of sample load on MHC-α and MHC-β band resolution is illustrated. The results also indicate that inclusion of a homogenization step during sample preparation increases the amount of MHC detected on the gel for cardiac samples to a much greater extent than for skeletal muscle samples. Although the protocol described in this study is excellent for analyzing cardiac samples, it should be noted that the same protocol is not optimal for separating MHC isoforms expressed in skeletal muscle, as is illustrated.
Checkpoint inhibitors and acute myelogenous leukemia: promises and challenges

ABSTRACT Introduction: Immunity, for treatment of acute myelogenous leukemia (AML), has been leveraged historically in the form of allogeneic stem cell transplantation. Checkpoint inhibitors (CPI) as positive modulators of immune response have been recent major breakthroughs in solid tumors. Areas covered: Emerging concepts and clinical data with CPIs in acute Myeloid Leukemia – the focus of this review- will be discussed. CPIs can potentially be effective in absence of ‘actionable’ mutations and are expected to be effective against poor-risk AML. Immune inhibitory checkpoint molecules are upregulated in both de novo and relapsed AML. Similar data also suggest role of checkpoint molecules in mediating resistance particularly to hypomethylating agent (HMA) therapy, which can potentially be reversed by using checkpoint inhibitors. Expert commentary: Ongoing clinical trials in combination with HMAs are showing early promise, with doubling of response than that seen in historic controls. The optimal combinations of CPIs and the optimal space that they will fit in the continuum of AML therapies need lot of in depth work.
Variability of the conversion of beta-carotene to vitamin A in women measured by using a double-tracer study design.

BACKGROUND Blood beta-carotene and vitamin A responses to oral beta-carotene are variable in humans. Some individuals are characterized as responders and others as low- or nonresponders. A better understanding of the conditions that produce the variability is important to help design public health programs that ensure vitamin A sufficiency. OBJECTIVE Our objective was to assess variability in absorption and conversion of beta-carotene to vitamin A in vivo in humans by using a novel double-tracer ¿hexadeuterated (D(6)) beta-carotene and D(6) retinyl acetate approach. DESIGN Eleven healthy women were housed at the US Department of Agriculture Western Human Nutrition Research Center metabolic unit for 44 d, where they consumed diets adequate in vitamins and minerals except for carotenoids. After an adaptation period, the women were given 30 micromol D(6) retinyl acetate orally, followed 1 wk later with 37 micromol D(6) beta-carotene (approximately equimolar doses). Time-dependent plasma concentration curves were determined for D(6) retinol, D(6) beta-carotene, and trideuterated (D(3)) retinol (derived from D(6) beta-carotene). RESULTS Mean (+/-SE) absorption of D(6) beta-carotene was 3.3 +/- 1.3% for all subjects. The mean conversion ratio was 0.81 +/- 0.34 mol D(3) retinol to 1 mol D(6) beta-carotene for all subjects. However, only 6 of the 11 subjects had plasma D(6) beta-carotene and D(3) retinol concentrations that we could measure. The mean absorption of D(6) beta-carotene in these 6 subjects was 6.1 +/- 0.02% and their conversion ratio was 1.47 +/- 0.49 mol D(3) retinol to 1 mol D(6) beta-carotene. The remaining 5 subjects were low responders with </=0.01% absorption and a mean conversion ratio of 0.014 +/- 0.004 mol D(3) retinol to 1 mol D(6) beta-carotene. CONCLUSION Variable absorption and conversion of beta-carotene to vitamin A both contribute to the variable response to consumption of beta-carotene. Our double-tracer approach is adaptable for identifying efficient converters of carotenoid to retinoid.
Sparse Representations in Audio and Music: From Coding to Source Separation

Sparse representations have proved a powerful tool in the analysis and processing of audio signals and already lie at the heart of popular coding standards such as MP3 and Dolby AAC. In this paper we give an overview of a number of current and emerging applications of sparse representations in areas from audio coding, audio enhancement and music transcription to blind source separation solutions that can solve the ¿cocktail party problem. ¿ In each case we will show how the prior assumption that the audio signals are approximately sparse in some time-frequency representation allows us to address the associated signal processing task.
The Diet Quality Index-International (DQI-I) provides an effective tool for cross-national comparison of diet quality as illustrated by China and the United States.

A composite measure of diet has been preferred to an index of a single nutrient or food in the area of dietary assessment. However, the lack of such a tool for cross-national comparisons has restricted the ability to compare diet quality between countries using an overall measure of diet. In this study, we created a tool called the Diet Quality Index-International (DQI-I) for global monitoring and exploration of diet quality across countries. The major categories of the index components are variety, adequacy, moderation and overall balance. Using the tool, this research presents a cross-national comparison of diet quality between China and the United States, incorporating comparable national in-depth diet data. The mean of the DQI-I score was slightly higher in China than in the United States. By major categories of the DQI-I, dietary variety was better achieved in the U.S. diet; moderation and overall balance of intakes were better accomplished in China. The DQI-I was successful in capturing variability in intakes of food and nutrients in both countries. Some distinct patterns of poor quality diet in each country were also identified. As demonstrated in this study, the DQI-I provides an effective means of cross-national comparative work for global understanding of diet quality. Furthermore, the dietary problem areas identified by the DQI-I may be useful in guiding the development of programs to improve public health.
Assessing the validity of surrogate endpoints in the context of a controversy about the measurement of effectiveness of hepatitis C virus treatment

Surrogate endpoints are often used in clinical trials, as they allow for indirect measures of outcomes (eg, shorter trials with less participants). Improvements in surrogate endpoints (eg, reduction in low density lipoprotein cholesterol, normalisation of glycated haemoglobin) achieved with an intervention are, however, not always associated with improvements in patient-important outcomes. The common tendency in evidence-based medicine is to view results based on surrogate endpoints as less certain than results based on long term, final patient-important outcomes and rate them as ‘lower quality evidence’. However, careful appraisal of the validity of a surrogate endpoint as a measure of the final, patient-important outcome is more useful than an automatic judgement. In this guide, we use a contemporary and currently highly debated example of the surrogate endpoint ‘sustained viral response’ (ie, viral eradication considered to represent successful treatment) in patients treated for chronic hepatitis C virus. We demonstrate how the validity of a surrogate endpoint can be critically appraised to assess the quality of the evidence (ie, the certainty in estimates) and the implications for decision-making.
Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men.

BACKGROUND Dietary plant sterols (phytosterols) have been shown to lower plasma lipid concentrations in animals and humans. However, the effect of phytosterol intake from tall oil on cholesterol and phytosterol metabolism has not been assessed in subjects fed precisely controlled diets. OBJECTIVE Our objective was to examine the effects of sitostanol-containing phytosterols on plasma lipid and phytosterol concentrations and de novo cholesterol synthesis rate in the context of a controlled diet. DESIGN Thirty-two hypercholesterolemic men were fed either a diet of prepared foods alone or a diet containing 1.7 g phytosterols/d for 30 d in a parallel study design. RESULTS No overall effects of diet on total cholesterol concentrations were observed, although concentrations were lower with the phytosterol-enriched than with the control diet on day 30 (P < 0.05). LDL-cholesterol concentrations on day 30 had decreased by 8.9% (P < 0.01) and 24.4% (P < 0.001) with the control and phytosterol-enriched diets, respectively. HDL-cholesterol and triacylglycerol concentrations did not change significantly. Moreover, changes in circulating campesterol and beta-sitosterol concentrations were not significantly different between phytosterol-fed and control subjects. In addition, there were no significant differences in fractional (0.091 +/- 0.028 and 0.091 +/- 0.026 pool/d, respectively) or absolute (0.61 +/- 0.24 and 0.65 +/- 0.23 g/d, respectively) synthesis rates of cholesterol observed between control and phytosterol-fed subjects. CONCLUSION Addition of blended phytosterols to a prudent North American diet improved plasma LDL-cholesterol concentrations by mechanisms that did not result in significant changes in endogenous cholesterol synthesis in hypercholesterolemic men.
Vagal and splanchnic afferents are not necessary for the anorexia produced by peripheral IL-1β, LPS, and MDP.

We investigated the extrinsic gut neural mediation of the suppression of food intake in male Sprague-Dawley rats induced by peripheral intraperitoneal administration of 2 μg/kg interleukin-1β (IL-1β), 100 μg/kg bacterial lipopolysaccharide (LPS), and 2 mg/kg muramyl dipeptide (MDP). Food intake during the first 3 and 6 h of the dark cycle was measured in rats with subdiaphragmatic vagal deafferentation ( n = 9), celiac superior mesenteric ganglionectomy ( n = 9), combined vagotomy and ganglionectomy ( n = 9), and sham deafferentation ( n = 9). IL-1β, LPS, and MDP suppressed food intake at 3 and 6 h in all surgical groups. The results demonstrate that neither vagal nor nonvagal afferent nerves from the upper gut are necessary for the feeding-suppressive effects of intraperitoneal IL-1β, LPS, or MDP in the rat and suggest that peripheral administration of immunomodulators produces anorexia via a humoral pathway.
Six1 promotes colorectal cancer growth and metastasis by stimulating angiogenesis and recruiting tumor-associated macrophages

The homeoprotein Six1 is overexpressed in many human cancers and is associated with increased tumor progression and metastasis. Recent studies have shown that Six1 is associated with poorer overall survival in advanced-stage colorectal cancer (CRC). In the current study, we explored the functional changes and molecular events associated with Six1 overexpression in a mouse model of CRC. An orthotopic model and a splenic injection metastasis model were used to investigate the role of Six1 in CRC tumor growth and metastasis using mouse colon adenocarcinoma MC38 cells overexpressing Six1. We found that overexpression of Six1 dramatically promotes CRC tumor growth and metastasis in vivo. Six1 overexpression in MC38 increased protein levels of aldehyde dehydrogenase-1 and expanded CD44+/CD166+ populations, indicating Six1 increased features of cancer stem cells. In addition, Six1 overexpression stimulated angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF). Six1-overexpressing tumor cells recruited tumor-associated macrophages (TAM) by increasing the expression of macrophage-specific colony stimulating factor, chemokine (C-C motif) ligand 2/5 and VEGF, further facilitating CRC tumor growth and metastasis. Furthermore, we determined that Six1 activated mitogen-activated protein kinase (MAPK) signaling in CRC cells. In summary, our studies strongly suggest that Six1 overexpression promotes CRC growth and metastasis and remodels tumor stroma by stimulating angiogenesis and recruiting TAM. MAPK activation may be a pivotal event in Six1-associated tumor progression, which may provide opportunities for pharmacologic intervention.
Fabricating Microchannels in Elastomer Substrates for Stretchable Electronics

As flexible devices and machines become more ubiquitous, there is a growing need for similarly deformable electronics. Soft polymers continue to be widely used as stretchable and flexible substrates for soft electronics, and in particular, soft sensing. These soft sensors generally consist of a highly elastic substrate with embedded microchannels filled with a conductive fluid. Deforming the substrate deforms the embedded microchannels and induces a change in the electrical resistance through the conductive fluid. Microchannels, thus, are the foundation of flexible electronic devices and sensors. These microchannels have been fabricated using various methods, where the manufacturing method greatly impacts device functionality. In this paper, comparisons are made between the following methods of microchannel manufacturing: cast molding, 3D printing of the elastomer substrate itself, and laser ablation. Further processing of the microchannels into flexible electronics is also presented for all three methods. Lastly, recommended ranges of microchannel sizes and their associated reproducibility and accuracy measures for each manufacturing method are presented.
Self-Organized Nanostructure Modified Microelectrode for Sensitive Electrochemical Glutamate Detection in Stem Cells-Derived Brain Organoids

Neurons release neurotransmitters such as glutamate to communicate with each other and to coordinate brain functioning. As increased glutamate release is indicative of neuronal maturation and activity, a system that can measure glutamate levels over time within the same tissue and/or culture system is highly advantageous for neurodevelopmental investigation. To address such challenges, we develop for the first time a convenient method to realize functionalized borosilicate glass capillaries with nanostructured texture as an electrochemical biosensor to detect glutamate release from cerebral organoids generated from human embryonic stem cells (hESC) that mimic various brain regions. The biosensor shows a clear catalytic activity toward the oxidation of glutamate with a sensitivity of 93 ± 9.5 nA·µM−1·cm−2. It was found that the enzyme-modified microelectrodes can detect glutamate in a wide linear range from 5 µM to 0.5 mM with a limit of detection (LOD) down to 5.6 ± 0.2 µM. Measurements were performed within the organoids at different time points and consistent results were obtained. This data demonstrates the reliability of the biosensor as well as its usefulness in measuring glutamate levels across time within the same culture system.
Concordance between physiological arousal and emotion expression during fear in young children with autism spectrum disorders

This study aimed to measure emotional expression and physiological arousal in response to fear in 21 children with autism spectrum disorders (43–75 months) and 45 typically developing children (41–81 months). Expressions of facial and bodily fear and heart rate arousal were simultaneously measured in response to a remote controlled robot (Laboratory Temperament Assessment Battery). Heart rate analyses revealed a main effect of task from baseline to fear (p < 0.001, η p 2 ), no interaction effect and no effect for group. In addition, children with autism spectrum disorder showed intact facial and bodily expressions of fearful affect compared to typically developing children. With regard to the relationship between expression and arousal, the results provided evidence for concordance between expression and arousal in typically developing children (r = 0.45, n = 45, p < 0.01). For children with autism spectrum disorder, no significant correlation was found (r = 0.20, n = 21, p = 0.38). A moderation analysis revealed no significant interaction between expression and arousal for children with and without autism spectrum disorder (F(1, 62) = 1.23, p = 0.27, η p 2 ), which might be the result of limited power. The current results give reason to further study concordance between expression and arousal in early autism spectrum disorder. Discordance might significantly impact social functioning and is an important topic in light of both early identification and treatment.
IDENTIFICATION AND EXPERIMENTAL INVESTIGATION ON THERMAL INTERFACE RESISTANCE FOR CRYOCOOLER COOLED HIGH-T_c SUPERCONDUCTOR

The application of high-T-c superconductor magnetic system was promoted by the development of high-T-c superconductor material and low temperature technology. Reducing thermal interface resistance is one of the key technologies for a cryocooler cooled high-T-c superconductor system. The principle and experimental apparatus of measuring thermal interface resistance is introduced, and the parameter identification method is presented to analyse the measured data of the thermal interface resistance across Bi-2223 and AlN contact. It is shown that heat flow direction and the process of increasing and decreasing temperature did not affect the thermal interface resistance, however, thermal interface resistance decreases with the increasing contact pressure and interface temperature within the contact pressure range from 0.15 to 0.55MPa. The thermal interface resistance is decreased from 0.02868 to 0.01109m2·K·W{-1} when the contact pressure is increased from 0.23 to 0.55MPa and the temperature maintains 55K, which means the thermal interface resistance is decreased 61.3%. It is reasonable to increase the contact pressure within the permitted stress range to reduce thermal interface resistance. The results of this study is of great importance for the application of cryocooler cooled high-T-c superconductor system.
Using density rather than mass to express the concentration of gastrointestinal tract constituents.

This experiment had two objectives: to develop an analytical technique to measure the density of digesta and fecal samples; to determine whether this measurement is physiologically relevant. To address the latter question, rats were provided with one of five high-fiber diets or a fiber-free control diet, and density determinations were made on samples from the cecum, proximal and distal colon, and from a passed fecal pellet. The density of colonic contents varied with the fiber component of the diet. The fiber-free control diet produced the densest stool at all sites studied (P less than 0.01), whereas wheat bran produced the least dense stool at every site (P less than 0.01). There were also density differences among bowel positions within diet treatments: the stool from those animals consuming the fiber-free, guar and pectin diets became denser as it moved distally; wheat bran, on the other hand, produced the opposite effect--the more distal the stool traveled, the less dense it became. Since the density of colonic contents varied with respect to both diet and anatomical site, these data suggest that the traditional technique of expressing the concentration of a constituent of interest (e.g., bile acid, volatile fatty acid) per gram of digesta or fecal matter may not always be appropriate. This is particularly true if exposure of the intestinal mucosal cells to a substance in the digesta or fecal stream is of interest, since density, rather than mass, reflects the diluting potential of the diet.
Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women.

BACKGROUND Metabolic studies suggest that saturated fatty acids differ in their effects on blood lipids. OBJECTIVE The objective was to examine the associations between intakes of individual saturated fatty acids and their food sources in relation to the risk of coronary heart disease (CHD). DESIGN This was a prospective cohort study of 80082 women in the Nurses' Health Study aged 34-59 y. Subjects had no known cardiovascular disease, cancer, hypercholesterolemia, or diabetes, and completed validated food-frequency questionnaires in 1980. RESULTS During 14 y of follow-up, we documented 939 incident cases of major CHD events. In multivariate analyses in which age, smoking, and other covariates were controlled for, intakes of short- to medium-chain saturated fatty acids (4:0-10:0) were not significantly associated with the risk of CHD. In contrast, intakes of longer-chain saturated fatty acids (12:0-18:0) were each separately associated with a small increase in risk. The multivariate RR for a 1% energy increase from stearic acid was 1.19 (95% CI: 1.02, 1.37). The ratio of polyunsaturated to saturated fat was strongly and inversely associated with CHD risk (multivariate RR for a comparison of the highest with the lowest deciles: 0.58; 95% CI: 0.41, 0.83; P for trend < 0.0001). Conversely, higher ratios of red meat to poultry and fish consumption and of high-fat to low-fat dairy consumption were associated with significantly greater risk. CONCLUSION A distinction between stearic acid and other saturated fats does not appear to be important in dietary advice to reduce CHD risk, in part because of the high correlation between stearic acid and other saturated fatty acids in typical diets.
Do response modality effects support multiprocessor models of divided attention?

Some studies have suggested that dual-task interference is greatly reduced when tasks requiring very different types of responses (e.g., manual and vocal) are combined. However, in those studies, the order of stimuli varied unpredictably. In Experiments 1 and 2, variable stimulus order greatly inflated interference between two manual tasks, whereas interference between a manual and a vocal task was only slightly exacerbated. However, central interference (the psychological refractory period) persisted even with the manual/vocal combination. Selection of 2 manual responses with unknown stimulus order may require a special strategy to preclude intertask intrusion errors. Experiment 3 demonstrated that such errors could be provoked with speed stress. Together, these results reconcile response modality effects with the response selection bottleneck model for dual-task interference (once it is suitably amended).