Miracle-dz/UniFAR-FTUs huggingface dataset:
A CORDIC Arithmetic Processor Chip

A monolithic processor computes products, quotients, and several common transcendental functions. The algorithms are based on the well-known principles of "CORDIC," but recourse to a subtle novel corollary results in a scale factor of unity. Compared to older machines, the overhead burden is significantly reduced. Also, expansion of the functional repertoire beyond the circular domain, i.e., addition to the menu of hyperbolic and linear operations, is a relatively trivial matter, in terms of both hardware cost and execution time. A bulk CMOS technology with conservative layout rules is used for the sake of high reliability, low-power consumption, and good cycle speed.
Structure and Mechanism of the Rebeccamycin Sugar 4′-O-Methyltransferase RebM*

The 2.65-Å crystal structure of the rebeccamycin 4′-O-methyltransferase RebM in complex with S-adenosyl-l-homocysteine revealed RebM to adopt a typical S-adenosylmethionine-binding fold of small molecule O-methyltransferases (O-MTases) and display a weak dimerization domain unique to MTases. Using this structure as a basis, the RebM substrate binding model implicated a predominance of nonspecific hydrophobic interactions consistent with the reported ability of RebM to methylate a wide range of indolocarbazole surrogates. This model also illuminated the three putative RebM catalytic residues (His140/141 and Asp166) subsequently found to be highly conserved among sequence-related natural product O-MTases from GC-rich bacteria. Interrogation of these residues via site-directed mutagenesis in RebM demonstrated His140 and Asp166 to be most important for catalysis. This study reveals RebM to be a member of the general acid/base-dependent O-MTases and, as the first crystal structure for a sugar O-MTase, may also present a template toward the future engineering of natural product MTases for combinatorial applications.
Early Postnatal Additional High-Dose Oral Vitamin A Supplementation versus Placebo for 28 Days for Preventing Bronchopulmonary Dysplasia or Death in Extremely Low Birth Weight Infants

Background: Prematurity and the associated risk for bronchopulmonary dysplasia (BPD) remain a significant threat to extremely low birth weight (ELBW) infants. Vitamin A has been considered a therapeutic alternative in reducing the rate of BPD and mortality. Objectives: To investigate whether early postnatal, additional high-dose oral vitamin A supplementation for 28 days is more efficient in reducing BPD or death in ELBW infants than placebo treatment. Methods: This is a multicenter, double-blind RCT comparing postnatal high-dose oral vitamin A supplementation (5,000 IU vitamin A/kg/day vs. placebo) for 28 days in ELBW neonates requiring mechanical ventilation, noninvasive ventilatory support or supplemental oxygen at 24 h of age. The primary end point is the proportion of children who died before 36 weeks' gestational age or developed moderate or severe BPD. BPD is defined as the need for supplemental oxygen to maintain SaO2 of ≥92% at rest at 36 weeks' postmenstrual age (PMA). Clinical secondary end points include the following: BPD (including mild form), intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, total number of days of mechanical ventilation and oxygen supplementation, and safety and tolerability of high-dose vitamin A supplementation. Results and Conclusions: The results of the NeoVitaA trial will provide robust data with regard to the efficacy of high-dose oral vitamin A supplementation in reducing the incidence of BPD or death at 36 weeks' PMA in ELBW infants.
Generation Y: indigenous tourism interests and environmental values

Indigenous tourism is an important sector worldwide. While demand for Indigenous tourism has previously been examined, there is a paucity of research on the relationship between Generation Y’s (Gen Y) Indigenous tourism interests and their environmental values. This paper reports the results of exploratory, qualitative semi-structured interviews with 14 Gen Y members in Western Australia. The Gen Y participants in this study displayed strong egocentric environmental values, and a disconnect between stated environmental ideals and travel behaviour. They were also largely disinterested in Australian domestic Indigenous tourism, showing a strong preference to engage with international Indigenous tourism that included cultural and social components rather than nature-based.
Optimal Dynamic Upgrading in Revenue Management

We consider a revenue management problem involving a two compartment aircraft flying a single leg, with no cancellations or over‐booking. We apply the practice of transforming a choice revenue management model into an independent demand model. Within this assumed independent model, there are two sets of demands, business and economy, each with multiple fare class products. A business passenger can only be accepted into business. An economy passenger can be accepted into economy or upgraded into business. We define a two‐dimensional dynamic program (DP) and show that the value function is sub‐modular and concave in seat availability in the two compartments. Thus the bid prices are non‐decreasing with respect to these state variables. We use this result to propose an exact algorithm to solve the DP. Our numerical investigation suggests that in contrast to standard backward induction, our method could be included in production revenue management systems. Further, when the economy compartment is capacity constrained, we observe a substantial monetary benefit from optimal dynamic upgrading compared to the static upgrading procedures currently used in practice.
Analyzing native membrane protein assembly in nanodiscs by combined non-covalent mass spectrometry and synthetic biology

Membrane proteins frequently assemble into higher order homo- or hetero-oligomers within their natural lipid environment. This complex formation can modulate their folding, activity as well as substrate selectivity. Non-disruptive methods avoiding critical steps, such as membrane disintegration, transfer into artificial environments or chemical modifications are therefore essential to analyze molecular mechanisms of native membrane protein assemblies. The combination of cell-free synthetic biology, nanodisc-technology and non-covalent mass spectrometry provides excellent synergies for the analysis of membrane protein oligomerization within defined membranes. We exemplify our strategy by oligomeric state characterization of various membrane proteins including ion channels, transporters and membrane-integrated enzymes assembling up to hexameric complexes. We further indicate a lipid-dependent dimer formation of MraY translocase correlating with the enzymatic activity. The detergent-free synthesis of membrane protein/nanodisc samples and the analysis by LILBID mass spectrometry provide a versatile platform for the analysis of membrane proteins in a native environment. DOI: http://dx.doi. org/10.7554/eLife.20954. 001
The Online Dissemination of Nature–Health Concepts: Lessons from Sentiment Analysis of Social Media Relating to “Nature-Deficit Disorder”

Evidence continues to grow supporting the idea that restorative environments, green exercise, and nature-based activities positively impact human health. Nature-deficit disorder, a journalistic term proposed to describe the ill effects of people’s alienation from nature, is not yet formally recognized as a medical diagnosis. However, over the past decade, the phrase has been enthusiastically taken up by some segments of the lay public. Social media, such as Twitter, with its opportunities to gather “big data” related to public opinions, offers a medium for exploring the discourse and dissemination around nature-deficit disorder and other nature–health concepts. In this paper, we report our experience of collecting more than 175,000 tweets, applying sentiment analysis to measure positive, neutral or negative feelings, and preliminarily mapping the impact on dissemination. Sentiment analysis is currently used to investigate the repercussions of events in social networks, scrutinize opinions about products and services, and understand various aspects of the communication in Web-based communities. Based on a comparison of nature-deficit-disorder “hashtags” and more generic nature hashtags, we make recommendations for the better dissemination of public health messages through changes to the framing of messages. We show the potential of Twitter to aid in better understanding the impact of the natural environment on human health and wellbeing.
Monoclonal Antibodies Allow Precipitation of Esterasic but Not Peptidasic Activities Associated with Butyrylcholinesterase

Abstract: Commercially available and affinity‐purified bu‐tyrylcholinesterases isolated from human serum were examined for their esterasic activity and their ability to hydrolyze various neuropeptides, including neurotensin, substance P, and leucine‐enkephalin. The three pools that displayed the lowest esterasic activities were shown to hydrolyze neurotensin with the same HPLC degradative pattern. By contrast, noticeable qualitative and quantitative discrepancies were observed when hydrolyses of substance P and leucineenkephalin by these three butyrylcholinesterase pools were studied. The pool that exhibited the highest esterasic activity appeared to be homogeneously constituted by 90‐ and 180‐kDa protein bands by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis analysis and was totally unable to hydrolyze these three neuropeptides. This suggested that the three other butyrylcholinesterase preparations could be contaminated by exogenous peptidases. This was confirmed by means of three distinct monoclonal antibodies directed toward human serum butyrylcholinesterase. The three IgG‐purified fractions precipitated the esterasic activity, whereas they failed to precipitate the neuropeptide‐hydrolyzing activities whatever the substrate examined. Altogether, these results demonstrate that peptidases associated with butyrylcholinesterase are contaminating enzymes that cannot be considered as intrinsic activities of this enzyme.
Auditory steady-state evoked potentials vs. compound action potentials for the measurement of suppression tuning curves in the sedated dog puppy

Abstract Auditory steady-state evoked potential (ASSEP) tuning curves were compared to compound action potential (CAP) tuning curves, both measured at 2 Hz, using sedated beagle puppies. The effect of two types of masker (narrowband noise and sinusoidal) on the tuning curve parameters was assessed. Whatever the masker type, CAP tuning curve parameters were qualitatively and quantitatively similar to the ASSEP ones, with a similar inter-subject variability, but with a greater incidence of upward tip displacement. Whatever the procedure, sinusoidal maskers produced sharper tuning curves than narrow-band maskers. Although these differences are not likely to have significant implications for clinical work, from a fundamental point of view, their origin requires further investigations. The same amount of time was needed to record a CAP and an ASSEP 13-point tuning curve. The data further validate the ASSEP technique, which has the advantages of having a smaller tendency to produce upward tip shifts than the CAP technique. Moreover, being non invasive, ASSEP tuning curves can be easily repeated over time in the same subject for clinical and research purposes. Sumario Se compararon las curvas de afinamiento de los potenciales evocados auditivos de estado estable (ASSEP) con las curvas de afinamiento de los potenciales compuestos de acción (CAD), ambas medidas a 2 Hz, utilizando cachorros de Beagle sedados. Se evaluó el efecto de dos tipos de enmascarador (ruido de banda estrecha y ruido sinusoidal) sobre los parámetros de la curva de afinamiento. Sin importar el tipo de enmascarador, los parámetros de la curva de afinamiento de los CAP fueron cuantitativa y cualitativamente similares a los de los ASSEP, con una variabilidad inter-sujeto similar, pero con una incidencia mayor de desplazamiento de la punta ascendente. Sin importar el procedimiento, los enmascaradores sinusoidales produjeron curvas de afinamiento más agudas que los enmascaradores de banda estrecha. Aunque estas diferencias no parece que puedan tener implicaciones significativas para el trabajo clínico, desde un punto de vista fundamental, su origen requiere de mayores investigaciones. Se requirió la misma cantidad de tiempo para registrar una curva de afinamiento de 13 puntos de CAP y de ASSEP. La información validó más aún la técnica de los ASSEP, que tiene la ventaja de mostrar una menor tendencia a producir desplazamientos de punta ascendente que la técnica de CAP. Más aún, por ser no invasivas, las curvas de afinamiento de los ASSEP pueden ser repetidas fácilmente en el tiempo, en el mismo sujeto, para propósitos clínicos y de investigación.
Complete Genome Sequence of Gordonia terrae 3612

ABSTRACT Here, we report the complete genome sequence of Gordonia terrae 3612, also known by the strain designations ATCC 25594, NRRL B-16283, and NBRC 100016. The genome sequence reveals it to be free of prophage and clustered regularly interspaced short palindromic repeats (CRISPRs), and it is an effective host for the isolation and characterization of Gordonia bacteriophages.
Caveolin-3 Null Mice Show a Loss of Caveolae, Changes in the Microdomain Distribution of the Dystrophin-Glycoprotein Complex, and T-tubule Abnormalities*

Caveolin-3, a muscle-specific caveolin-related protein, is the principal structural protein of caveolae membrane domains in striated muscle cells. Recently, we identified a novel autosomal dominant form of limb-girdle muscular dystrophy (LGMD-1C) in humans that is due to mutations within the coding sequence of the human caveolin-3 gene (3p25). These LGMD-1C mutations lead to an ∼95% reduction in caveolin-3 protein expression, i.e. a caveolin-3 deficiency. Here, we created a caveolin-3 null (CAV3 −/−) mouse model, using standard homologous recombination techniques, to mimic a caveolin-3 deficiency. We show that these mice lack caveolin-3 protein expression and sarcolemmal caveolae membranes. In addition, analysis of skeletal muscle tissue from these caveolin-3 null mice reveals: (i) mild myopathic changes; (ii) an exclusion of the dystrophin-glycoprotein complex from lipid raft domains; and (iii) abnormalities in the organization of the T-tubule system, with dilated and longitudinally oriented T-tubules. These results have clear mechanistic implications for understanding the pathogenesis of LGMD-1C at a molecular level.
Possible causes of chromosome instability: comparison of chromosomal abnormalities in cancer cell lines with mutations in BRCA1, BRCA2, CHK2 and BUB1

A large proportion of epithelial cancers show the chromosome-instability phenotype, in which they have many chromosome abnormalities. This is thought to be the result of mutations that disrupt chromosome maintenance, but the causative mutations are not known. We identified cell lines known to have mutations that might cause chromosome instability, and examined their karyotypes. Two cell lines, the breast cancer line HCC1937 and the pancreatic cancer line CAPAN-1, that have mutations respectively in BRCA1 and BRCA2, had very abnormal karyotypes, with many structural and numerical chromosome changes and substantial variation between metaphases. However, two colorectal cancer lines with mutations in BUB1, a spindle checkpoint protein involved in chromosome segregation, had rather simple near-tetraploid karyotypes, with minimal loss or gain of chromosomes other than the endoreduplication event, and minimal structural change. Apart from tetraploidy, these karyotypes were typical of colorectal lines considered to be chromosomally stable. Two lines derived from the same tumour, DLD-1 and HCT-15, with bi-allelic mutation of CHK2, had karyotypes that were typical of near-diploid colorectal lines considered chromosomally stable. The karyotypes observed supported the proposed role for BRCA1 and BRCA2 mutations in chromosomal instability, but showed that the tested mutations in BUB1 and CHK2 did not result in karyotypes that would have been predicted if they were sufficient for chromosomal instability.
Evaluation of pulmonary function within a cohort of flavorings workers

Abstract Objectives: We present a re-analysis of a recent Health Hazard Evaluation (HHE) that was performed by the US National Institute for Occupational Safety and Health (NIOSH) regarding the pulmonary status of workers at a flavorings manufacturing facility. This facility has used acetaldehyde, acetoin, benzaldehyde, butyric acid, diacetyl and many other flavoring chemicals for many years. Methods: Ten years of spirometry testing and job descriptions data on 112 workers were analyzed by the authors and by NIOSH. Using NIOSH’s exposure assessment criteria, we compared the prevalence of restrictive findings (as determined by spirometry testing) in production workers to an internal control group that had reduced or no potential for exposure to flavoring chemicals. NIOSH used multiple linear regression to evaluate changes in pulmonary function by the exposure group. After our review of the NIOSH findings, we evaluated associations between longitudinal changes in pulmonary health and workplace exposures through the use of generalized estimating equations. We then compared our results to those obtained by NIOSH. Results: We found that the prevalence of pulmonary restriction was similar in production workers and internal controls. We found no relationship between the magnitude of exposure to flavorings chemicals and observed decrements in pulmonary function. Our findings were contrary to those reported by NIOSH, most likely because of how we accounted for the longitudinal nature of the spirometric data. Conclusion: Many years of exposures to flavoring chemicals in this workplace, including diacetyl, were not found to produce an increased risk of abnormal spirometric findings.
TRIM13 (RFP2) downregulation decreases tumour cell growth in multiple myeloma through inhibition of NF Kappa B pathway and proteasome activity

Multiple myeloma (MM) is an incurable neoplasm caused by proliferation of malignant plasma cells in the bone marrow (BM). MM is characterized frequently by a complete or partial deletion of chromosome 13q14, seen in more than 50% of patients at diagnosis. Within this deleted region the tripartite motif containing 13 (TRIM13, also termed RFP2) gene product has been proposed to be a tumour suppressor gene (TSG). Here, we show that low expression levels of TRIM13 in MM are associated with chromosome 13q deletion and poor clinical outcome. We present a functional analysis of TRIM13 using a loss‐of‐function approach, and demonstrate that TRIM13 downregulation decreases tumour cell survival as well as cell cycle progression and proliferation of MM cells. In addition, we provide evidence for the involvement of TRIM13 downregulation in inhibiting the NF kappa B pathway and the activity of the 20S proteasome. Although this data does not support a role of TRIM13 as a TSG, it substantiates important roles of TRIM13 in MM tumour survival and proliferation, underscoring its potential role as a novel target for therapeutic intervention.
Three-Dimensional Computed Tomography-Based Specimen-Specific Kinematic Model for Ex Vivo Assessment of Lumbar Neuroforaminal Space

Study Design. Cadaveric study to accurately measure lumbar neuroforaminal area and height throughout the flexion-extension range of motion (ROM). Objective. Create a new computed tomography (CT)-based specimen-specific model technique to provide insight on the effects of kinematics on lumbar neuroforamen morphology during flexion-extension ROM. Summary of Background Data. Nerve root compression is a key factor in symptomatic progression of degenerative disc disease because these changes directly affect neuroforaminal area. Traditional techniques to evaluate the neuroforamen suffer from poor accuracy, have inherent limitations, and fail to provide data throughout the ROM. Methods. Six cadaveric specimens (L1-sacrum) were instrumented with radiopaque spheres and CT scanned. 3-Dimensional reconstructions were made of each vertebra and the sphere locations determined. During kinematic testing, the spheres were located in relation to optoelectronic targets attached to each vertebra. The result was a 3-dimensional representation of the specimen's CT reconstruction moving in response to experimental data. Bony contours of the L2–L3 and L4–L5 neuroforamen were digitized producing continuous neuroforaminal area and height data throughout the ROM. Results. Neuroforaminal area and height linearly increased in flexion and decreased in extension. There was significant correlation between flexion-extension motion and percent change in area (L2–L3: 3.1%/deg, R2 = 0.94, L4–L5: 2.5%/deg, R2 = 0.90) and neuroforaminal height (L2–L3: 2.1%/deg, R2 = 0.95, L4–L5: 1.6%/deg, R2 = 0.93). Regression analysis showed that the ratio between neuroforaminal height and area is at least 1:1.5 such that a 100% increase in height is associated with an area increase of more than 150%. Conclusion. This is the first study to measure lumbar neuroforaminal area and height throughout flexion-extension ROM. The CT-based specimen-specific model technique can accurately evaluate the effect of kinematics on morphological features of the spine. The demonstrated increase in neuroforaminal dimension in flexion is consistent with treatment modalities used in clinical therapies to relieve radicular symptoms. Level of Evidence: N/A
Integrin-like Allosteric Properties of the Catch Bond-forming FimH Adhesin of Escherichia coli*

FimH is the adhesive subunit of type 1 fimbriae of the Escherichia coli that is composed of a mannose-binding lectin domain and a fimbria-incorporating pilin domain. FimH is able to interact with mannosylated surface via a shear-enhanced catch bond mechanism. We show that the FimH lectin domain possesses a ligand-induced binding site (LIBS), a type of allosterically regulated epitopes characterized in integrins. Analogous to integrins, in FimH the LIBS epitope becomes exposed in the presence of the ligand (or “activating” mutations) and is located far from the ligand-binding site, close to the interdomain interface. Also, the antibody binding to the LIBS shifts adhesin from the low to high affinity state. Binding of streptavidin to the biotinylated residue within the LIBS also locks FimH in the high affinity state, suggesting that the allosteric perturbations in FimH are sustained by the interdomain wedging. In the presence of antibodies, the strength of bacterial adhesion to mannose is increased similar to the increase observed under shear force, suggesting the same allosteric mechanism, a shift in the interdomain configuration. Thus, an integrin-like allosteric link between the binding pocket and the interdomain conformation can serve as the basis for the catch bond property of FimH and, possibly, other adhesive proteins.