Miracle-dz/UniFAR-FTUs huggingface dataset:
MK-5108, a Highly Selective Aurora-A Kinase Inhibitor, Shows Antitumor Activity Alone and in Combination with Docetaxel

Aurora-A kinase is a one of the key regulators during mitosis progression. Aurora-A kinase is a potential target for anticancer therapies because overexpression of Aurora-A, which is frequently observed in some human cancers, results in aberrant mitosis leading to chromosomal instability and possibly tumorigenesis. MK-5108 is a novel small molecule with potent inhibitory activity against Aurora-A kinase. Although most of the Aurora-kinase inhibitors target both Aurora-A and Aurora-B, MK-5108 specifically inhibited Aurora-A kinase in a panel of protein kinase assays. Inhibition of Aurora-A by MK-5108 in cultured cells induced cell cycle arrest at the G2-M phase in flow cytometry analysis. The effect was confirmed by the accumulation of cells with expression of phosphorylated Histone H3 and inhibition of Aurora-A autophosphorylation by immunostaining assays. MK-5108 also induced phosphorylated Histone H3 in skin and xenograft tumor tissues in a nude rat xenograft model. MK-5108 inhibited growth of human tumor cell lines in culture and in different xenograft models. Furthermore, the combination of MK-5108 and docetaxel showed enhanced antitumor activities compared with control and docetaxel alone–treated animals without exacerbating the adverse effects of docetaxel. MK-5108 is currently tested in clinical trials and offers a new therapeutic approach to combat human cancers as a single agent or in combination with existing taxane therapies. Mol Cancer Ther; 9(1); 157–66
A clonal analysis of neural progenitors during axolotl spinal cord regeneration reveals evidence for both spatially restricted and multipotent progenitors

Complete regeneration of the spinal cord occurs after tail regeneration in urodele amphibians such as the axolotl. Little is known about how neural progenitor cells are recruited from the mature tail, how they populate the regenerating spinal cord, and whether the neural progenitor cells are multipotent. To address these issues we used three types of cell fate mapping. By grafting green fluorescent protein-positive (GFP+) spinal cord we show that a 500 μm region adjacent to the amputation plane generates the neural progenitors for regeneration. We further tracked single nuclear-GFP-labeled cells as they proliferated during regeneration, observing their spatial distribution, and ultimately their expression of the progenitor markers PAX7 and PAX6. Most progenitors generate descendents that expand along the anterior/posterior (A/P) axis, but remain close to the dorsal/ventral (D/V) location of the parent. A minority of clones spanned multiple D/V domains, taking up differing molecular identities, indicating that cells can execute multipotency in vivo. In parallel experiments, bulk labeling of dorsally or ventrally restricted progenitor cells revealed that ventral cells at the distal end of the regenerating spinal cord switch to dorsal cell fates. Analysis of PAX7 and PAX6 expression along the regenerating spinal cord indicated that these markers are expressed in dorsal and lateral domains all along the spinal cord except at the distal terminus. These results suggest that neural progenitor identity is destabilized or altered in the terminal vesicle region, from which clear migration of cells into the surrounding blastema is also observed.
Spectral resampling based on user-defined inter-band correlation filter : C 3 1 and C 4 grass species classification 2 3 4

13 In this paper, a user-defined inter-band correlation filter function was used to resample 14 hyperspectral data and thereby mitigate the problem of multicol linearity in classification 15 analysis. The proposed resampling technique convolves the spectr al dependence information 16 between a chosen band-centre and its shorter and longer wavelength ne ighbours. Weighting 17 threshold of inter-band correlation (WTC, Pearson’s r) was calculated, whereby r = 1 at the 18 band-centre. Various WTC ( r = 0.99, r = 0.95 and r = 0.90) were assessed, and bands with 19 coefficients beyond a chosen threshold were assigned r = 0. The resultant data were used in 20 the random forest analysis to classify C 3 and C4 grass species. The respective WTC datasets 21 yielded improved classification accuracies (kappa = 0.82, 0.79 a nd 0.76) with less correlated 22 wavebands when compared to resampled Hyperion bands (kappa = 0.76). Overa ll, the esults 23 obtained from this study suggested that resampling of hyperspectra l data should account for 24 the spectral dependence information to improve overall classific ation accuracy as well as 25 reducing the problem of multicollinearity. 26 27
Cognitive reflection vs. calculation in decision making

Scores on the three-item Cognitive Reflection Test (CRT) have been linked with dual-system theory and normative decision making (Frederick, 2005). In particular, the CRT is thought to measure monitoring of System 1 intuitions such that, if cognitive reflection is high enough, intuitive errors will be detected and the problem will be solved. However, CRT items also require numeric ability to be answered correctly and it is unclear how much numeric ability vs. cognitive reflection contributes to better decision making. In two studies, CRT responses were used to calculate Cognitive Reflection and numeric ability; a numeracy scale was also administered. Numeric ability, measured on the CRT or the numeracy scale, accounted for the CRT's ability to predict more normative decisions (a subscale of decision-making competence, incentivized measures of impatient and risk-averse choice, and self-reported financial outcomes); Cognitive Reflection contributed no independent predictive power. Results were similar whether the two abilities were modeled (Study 1) or calculated using proportions (Studies 1 and 2). These findings demonstrate numeric ability as a robust predictor of superior decision making across multiple tasks and outcomes. They also indicate that correlations of decision performance with the CRT are insufficient evidence to implicate overriding intuitions in the decision-making biases and outcomes we examined. Numeric ability appears to be the key mechanism instead.
Assessment of smooth muscle contribution to descending thoracic aortic elastic mechanics in conscious dogs.

Early investigators found contradictory evidence that vascular smooth muscle activation reduces the elastic modulus of the arterial wall under isotonic conditions but increases it under isometric conditions, concomitant with increased pulse-wave velocity. We examined the individual contributions of aortic constituents to the elastic modulus of the aortic wall to determine if isobaric analysis produces an accurate assessment of vascular smooth muscle activation. We used a modified Maxwell model assuming an incremental elastic modulus (Einc) composed of the elastic modulus of elastin fibers (EE), the elastic modulus of collagen fibers (EC) affected by the fraction of collagen fibers (fC) recruited to support wall stress, and the elastic modulus of the vascular smooth muscle (ESM) according to the following formula: Einc = EE+EC x fC+ESM.Einc was assessed in eight conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements. Stress-strain relations in the control state and during activation of smooth muscle by continuous administration of phenylephrine (5 micrograms.kg-1 x min-1) were obtained by transient occlusions of the descending aorta and inferior vena cava. Results were as follows: EE was 4.99 +/- 1.58 x 10(6) dynes/cm2 (mean +/- SD), and EC was 965.8 +/- 399.8 x 10(6) dynes/cm2, assessed during the control state. Phenylephrine administration increased the theoretical pulse-wave velocity (Moens-Korteweg equation) from 5.25 +/- 1.03 m/s during the control state to 7.57 +/- 2.53 m/s (P < .005). Active muscle exhibited a unimodal stress-strain curve with a maximum stress of 0.949 +/- 0.57 x 10(6) dynes/cm2 at a corresponding strain value of 1.299 +/- 0.083. The maximum value observed corresponded, on the pressure-diameter curve of the active artery, to a pressure of 234.28 +/- 46.6 mm Hg and a diameter of 17.94 +/- 1.6 mm. The maximum ESM derived from the stress-strain relation of the active muscle was 8.345 +/- 7.56 x 10(6) dynes/cm2 at a strain value of 1.283 +/- 0.079. This point was located at 208.01 +/- 40.8 mm Hg and 17.73 +/- 1.41 mm on the active pressure-diameter curve. During activation of vascular smooth muscle, Einc decreased (P < .05) when plotted against internal pressure but increased (P < .05) when plotted against strain, over the operative range. (ABSTRACT TRUNCATED AT 400 WORDS)
The Uncracked Pieces in Database Cracking

Database cracking has been an area of active research in recent years. The core idea of database cracking is to create indexes adaptively and incrementally as a side-product of query processing. Several works have proposed different cracking techniques for different aspects including updates, tuple-reconstruction, convergence, concurrency-control, and robustness. However, there is a lack of any comparative study of these different methods by an independent group. In this paper, we conduct an experimental study on database cracking. Our goal is to critically review several aspects, identify the potential, and propose promising directions in database cracking. With this study, we hope to expand the scope of database cracking and possibly leverage cracking in database engines other than MonetDB. We repeat several prior database cracking works including the core cracking algorithms as well as three other works on convergence (hybrid cracking), tuple-reconstruction (sideways cracking), and robustness (stochastic cracking) respectively. We evaluate these works and show possible directions to do even better. We further test cracking under a variety of experimental settings, including high selectivity queries, low selectivity queries, and multiple query access patterns. Finally, we compare cracking against different sorting algorithms as well as against different main-memory optimised indexes, including the recently proposed Adaptive Radix Tree (ART). Our results show that: (i) the previously proposed cracking algorithms are repeatable, (ii) there is still enough room to significantly improve the previously proposed cracking algorithms, (iii) cracking depends heavily on query selectivity, (iv) cracking needs to catch up with modern indexing trends, and (v) different indexing algorithms have different indexing signatures.
Role of CD73 in renal sympathetic neurotransmission in the mouse kidney

Adenosine formed during renal sympathetic nerve stimulation (RSNS) enhances, by activating A1 receptors, the postjunctional effects of released norepinephrine and participates in renal sympathetic neurotransmission. Because in many cell types CD73 (ecto‐5′‐nucleotidase) is important for the conversion of 5′‐AMP to adenosine, we investigated whether CD73 is necessary for normal renal sympathetic neurotransmission. In isolated kidneys from CD73 wild‐type mice (CD73+/+; n = 17) perfused at a constant rate with Tyrode's solution, RSNS increased perfusion pressure by 17 ± 4, 36 ± 8, and 44 ± 10 mm Hg at 3, 5, and 7 Hz, respectively. Similar responses were elicited from kidneys isolated from CD73 knockout mice (CD73−/−; n = 13; 28 ± 11, 43 ± 10, and 44 ± 10 mm Hg at 3, 5, and 7 Hz, respectively); and a high concentration (100 μmol/L) of α,β‐methyleneadenosine 5′‐diphosphate (CD73 inhibitor) did not alter responses to RSNS in C57BL/6 mouse kidneys (n = 5; 21 ± 5, 36 ± 8, and 43 ± 9 at 3, 5, and 7 Hz, respectively). Measurements of renal venous adenosine and inosine (adenosine metabolite) by liquid chromatography‐tandem mass spectrometry demonstrated that the metabolism of exogenous 5′‐AMP to adenosine and inosine was similar in CD73−/− versus CD73+/+ kidneys. A1 receptor mRNA expression was increased in CD73−/− kidneys, and 2‐chloro‐N6‐cyclopentyladenosine (0.1 μmol/L; A1 receptor agonist) enhanced renovascular responses to norepinephrine more in CD73−/− versus CD73+/+ kidneys. We conclude that CD73 is not essential for renal sympathetic neurotransmission because in the absence of renal CD73 other enzymes metabolize 5′‐AMP to adenosine and because of compensatory upregulation of postjunctional coincident signaling between norepinephrine and adenosine.
Prevalence of enteropathogens in normal feces from healthy children at an infant day care in Brazil.

INTRODUCTION The diarrhea associated with gastroenteritis is a major cause of morbidity and mortality worldwide, affecting mainly infants. The characterization of both viral and bacterial agents associated with gastroenteritis can establish policies for surveillance, prevention and treatment of infections. Group A rotaviruses are the major infectious agent associated with dehydration in children, followed by pathotypes of Escherichia coli. There are three main types of clinical infections caused by E. coli strains that have acquired virulence genes: (i) enteric and diarrheal diseases, (ii) urinary tract infections, and (iii) sepsis and meningitis. METHODOLOGY In this study, the objective was to identify the presence of rotavirus and diarrhogenic E. coli in the feces of children 4 to 14 months of age who displayed no gastroenteritis symptoms and stayed all day in a day-care center. We analyzed 188 samples using PAGE and PCR to identify rotaviruses and E. coli virulence genes, respectively. RESULTS Thirty-six samples (19.1%) were positive for at least one pathotype of E. coli. Nineteen were identified to be of the EPEC group and fifteen of the EAEC group. Rotaviruses were not identified. CONCLUSIONS As EPEC and EAEC are potential pathogens for children less than one year of age or immunocompromised individuals, our results show the importance of appropriate monitoring by public health agencies. In the situation that we have studied, children can be considered asymptomatic carriers of these pathogens and can transmit them to other susceptible children.
Metabolic syndrome-related conditions among people with and without gout: prevalence and resource use*

ABSTRACT Objective: A cohort of employees with gout were compared to those without to evaluate the differences in prevalence of disorders associated with metabolic syndrome (both those considered underlying and those associated with end-stage morbidity and mortality) as well as the cost of annual medical services (AMS) required for treatment of these conditions. Methods: Employees with gout were identified by International Classification of Diseases‑9 (ICD‑9) code during the calendar years of 2001–2004 and compared to propensity-score matched employees without gout using the Human Capital Management Services Research Reference Database. T‑tests were then used to compare prevalence and average AMS of comorbid disorders defined from Agency for Healthcare and Research Quality (AHRQ) diagnostic categories. Results: ‘Hyperlipidemia’, ‘essential hypertension’, and ‘diabetes mellitus without complications’ ranked in the top 10 categories of mean number of AMS for employees with gout using AHRQ specific categories; the values were higher than found for those without gout (all p < 0.0001). ‘Essential hypertension’, ‘hyperlipidemia’, ‘diabetes mellitus without complications’, and ‘coronary atherosclerosis’ showed an approximate 2:1 prevalence ratio for employees with gout over those without ( p ≤ 0.05). Main study limitations include the small number of subjects with gout, retrospective study design, and possible miscoding and/or non-coding of individuals with the studied disorders. Conclusion: These results support the continued need for patients with gout and their clinicians to be aware of the possibility of the increased risk of associated metabolic syndrome and related comorbidities in these individuals, emphasizing the need for prevention when possible and treatment when necessary.
Functional symptoms and signs in neurology: assessment and diagnosis

It’s a Tuesday morning at 11.30 am. You are already 45 minutes behind. A 35 year old woman is referred to your neurology clinic with a nine month history of fatigue, dizziness, back pain, left sided weakness, and reduced mobility. Her general practitioner documents a hysterectomy at the age of 25, subsequent division of adhesions for abdominal pain, irritable bowel syndrome, and asthma. She is no longer able to work as a care assistant and rarely leaves the house. Her GP has found some asymmetrical weakness in her legs and wonders if she may have developed multiple sclerosis. She looks unhappy but becomes angry when you ask her whether she is depressed. On examination you note intermittency of effort and clear inconsistency between her ability to walk and examination on the bed. She has already had extensive normal investigations. The patient and her husband want you to “do something”. As you start explaining that there’s no evidence of anything serious and that you think it’s a psychological problem, the consultation goes from bad to worse…. In this article we summarise an approach to the assessment and diagnosis of functional symptoms in neurology, paying attention to those symptoms that are particularly “neurological”, such as paralysis and epileptic-like attacks. In the second of the two articles we describe our approach to the management of functional symptoms bearing in mind the time constraints experienced by a typical neurologist. We also address difficult questions such as: “What causes functional symptoms? ”, “Are they real? ”, and “Is there anything that can be done? ” We emphasise the need for a transparent and collaborative approach. As we will explain this depends on giving up a purely “psychological” view of functional symptoms in favour of a biopsychosocial view of causation in which dysfunction of the nervous system is the …
Pronunciation and Acoustic Model Adaptation for Improving Multilingual Speech Recognition

In this paper, we address the importance of pronunciation and acoustic model adaptation in multilingual speech recognition. When aiming at modeling several languages simultaneously, the degree of speaker and language variability is even greater than when concentrating on only one language. To compensate the pronunciation variability across various speaker, bi-lingual pronunciation modeling is proposed. Once the appropriate pronunciation has been found, the unused transcription is removed in order to prevent the expansion of the vocabulary size. To further compensate the mismatches between the multilingual acoustic models and the speaker's pronunciation, MAP on-line acoustic model adaptation is applied. Experimental results with 12 languages indicate the efficiency of the joint use of these techniques. Compared with the non-adapted multilingual system, the bi-lingual pronunciation modeling and on-line acoustic model adaptation produced the average cross-language error rate reduction of 67.6% in the clean, and 55.4% in the noisy operating conditions.
Lactate Dehydrogenase Isoenzyme-1 in Serum for Detectionof Pen-Operative Myocardial Infarctionafter Cardiac Surgery

We prospectively studied changes in serum lactate dehydrogenase isoenzyme-1 (LD-1, EC 1.1.1.27) in 99 consecutive patients after either coronary artery bypass grafting (CABG, n = 61), isolated cardiac-valve replacement (n = 24), or the two procedures combined (n = 14); 86 of these had no clinical evidence of pen-operative myocardial infarction (Mi). Blood was sampled immediately after surgery and at 6-h intervals for up to 42 h thereafter. LD-1 was isolated by using the LD M-subunit antiserum. Samples from the non-MI patients were used to establish the reference intervals for LD-1. By 24 h after surgery, mean serum LD-1 values were higher (P <0.001) in non-MI patients who underwent isolated valve replacement (222 ± 74 U/L) or combined CABG and valve replacement (266 ± 58 U/L) than in 50 non-MI patients who underwent CABG alone (134 ± 42 U/L). Separate reference intervals were determined for CABG and other patients at each sampling time. By 24 h after operation, LD-1 exceeded these reference intervals in the 10 CABG and two combined-procedure patients in whom other evidence of Ml was present. Measurement of LD-1 24 to 42 h after cardiac surgery appears to be a useful test for the diagnosis of penoperative MI.
RNS2, a conserved member of the RNase T2 family, is necessary for ribosomal RNA decay in plants

RNase T2 enzymes are conserved in most eukaryotic genomes, and expression patterns and phylogenetic analyses suggest that they may carry out an important housekeeping role. However, the nature of this role has been elusive. Here we show that RNS2, an intracellular RNase T2 from Arabidopsis thaliana, is essential for normal ribosomal RNA recycling. This enzyme is the main endoribonuclease activity in plant cells and localizes to the endoplasmic reticulum (ER), ER-derived structures, and vacuoles. Mutants lacking RNS2 activity accumulate RNA intracellularly, and rRNA in these mutants has a longer half-life. Normal rRNA turnover seems essential to maintain cell homeostasis because rns2 mutants display constitutive autophagy. We propose that RNS2 is part of a process that degrades rRNA to recycle its components. This process appears to be conserved in all eukaryotes.
Variant U1 snRNAs are implicated in human pluripotent stem cell maintenance and neuromuscular disease

The U1 small nuclear (sn)RNA (U1) is a multifunctional ncRNA, known for its pivotal role in pre-mRNA splicing and regulation of RNA 3′ end processing events. We recently demonstrated that a new class of human U1-like snRNAs, the variant (v)U1 snRNAs (vU1s), also participate in pre-mRNA processing events. In this study, we show that several human vU1 genes are specifically upregulated in stem cells and participate in the regulation of cell fate decisions. Significantly, ectopic expression of vU1 genes in human skin fibroblasts leads to increases in levels of key pluripotent stem cell mRNA markers, including NANOG and SOX2. These results reveal an important role for vU1s in the control of key regulatory networks orchestrating the transitions between stem cell maintenance and differentiation. Moreover, vU1 expression varies inversely with U1 expression during differentiation and cell re-programming and this pattern of expression is specifically de-regulated in iPSC-derived motor neurons from Spinal Muscular Atrophy (SMA) type 1 patient's. Accordingly, we suggest that an imbalance in the vU1/U1 ratio, rather than an overall reduction in Uridyl-rich (U)-snRNAs, may contribute to the specific neuromuscular disease phenotype associated with SMA.