Miracle-dz/UniFAR-FTUs huggingface dataset:
Working Memory and Cognitive Flexibility Mediates Visuoconstructional Abilities in Older Adults with Heterogeneous Cognitive Ability

Abstract Previous studies suggest that executive functions influence the performance on visuoconstructional tasks. This study aims to investigate whether the relationship between planning ability and the copy of complex figures is mediated by distinct components of executive functions (i.e., working memory, inhibitory control and cognitive flexibility). We included a 129 older adults with Alzheimer’s disease (n=36, AD), mild cognitive impairment (MCI, n=67), and with no evidence of cognitive impairment (controls, n=26). We evaluated the mediation effect of planning abilities, working memory, cognitive flexibility and inhibitory control on visuoconstructional tasks using a multiple mediation models. We found a significant direct effect of planning on visuoconstructional abilities and a partial mediation effect of working memory and cognitive flexibility on visuoconstructional abilities. The present results indicate that the performance on visuoconstructional task is mediated by multiple interrelated executive functions components, in particular working memory and cognitive flexibility. (JINS, 2015, 21, 392–398)
A Comprehensive Review of the Treatment of Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is an uncommon but malignant cutaneous neuroendocrine carcinoma with a high incidence of local recurrence, regional lymph node metastases, and subsequent distant metastases. The etiology of MCC remains unknown. It usually occurs in sun-exposed areas in elderly people, many of whom have a history of other synchronous or metachronous sun-associated skin lesions. The outcome for most patients with MCC is generally poor. Surgery is the mainstay of treatment. The role of adjuvant therapy has been debated. However, data from recent development support a multimodality approach, including surgical excision of primary tumor with adequate margins and sentinel lymph node dissection followed by postoperative radiotherapy in most cases, as current choice of practice with better locoregional control and disease-free survival. Patients with regional nodal involvement or advanced disease should undergo nodal dissection followed by adjuvant radiotherapy and, perhaps, systemic platinum-based chemotherapy in most cases.
Glyco-epitope Diversity: An Evolving Area of Glycomics Research and Biomarker Discovery.

Copyright: © 2014 Wang D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Although the term “glyco code” has only recently come into use [1-4], recognition of the carbohydrate signatures of microbes was documented nearly a century ago. In 1917, Dochez and Avery [5] found that when Pneumococci were grown in fluid media, there was a substance in the culture fluid that precipitated specifically with antisera to the same Pneumococcus. Heidelberger and Avery [6] showed that the substance recognized by the antibodies was a carbohydrate molecule and not a protein, as previously thought. It was later found that almost every microorganism expresses such glyco codes that are recognized by the host immune systems and are effective in stimulating specific antibody responses [7,8]. Such immunogenic carbohydrate moieties often serve as key targets for development of vaccines against infectious diseases [9-13]. Tumor glycomics research in recent years has uncovered a large panel of tumor-associated carbohydrate antigens [14,15] and evidence of immune recognition of tumor-derived aberrant carbohydrates [16-20].
The Structure of Nonlinearity for Point Feature SLAM Problems with Spherical Covariance Matrices

This paper proves that the optimization problem of one-step point feature Simultaneous Localization and Mapping (SLAM) is equivalent to a nonlinear optimization problem of a single variable when the associated uncertainties can be described using spherical covariance matrices. Furthermore, it is proven t hat this optimization problem has at most two minima. The necessary and sufficient condi tions for the existence of one or two minima are derived and the conditions can be easily checked from the observation and odometry data. It is demonstrated that more than one minimum exists only when the observation and odometry data are extremely inconsistent with each other. A numerical algorithm based on bisection is proposed to solve the one dimensional nonlinear optimization problem. It is shown that the approach extends to joining two maps, thus can be used to obtain an approximate solution to the complete SLAM problem through map joining.
Zero-Sum Ergodic Stochastic Games with Feller Transition Probabilities

We consider zero-sum stochastic games with Borel state spaces satisfying a generalized geometric ergodicity condition. The main objective of this paper is to establish a minimax theorem for a class of ergodic stochastic games with the Feller transition probability function. All previous results on ergodic stochastic games are based on a strong continuity of the transition probabilities in the actions of the players.
Amyloid oligomers: formation and toxicity of Aβ oligomers

Alzheimer’s disease (AD) is an age‐related, progressive degenerative disorder that is characterized by synapse and neuron loss in the brain and the accumulation of protein‐containing deposits (referred to as ‘senile plaques’) and neurofibrillary tangles. Insoluble amyloid β‐peptide (Aβ) fibrillar aggregates found in extracellular plaques have long been thought to cause the neurodegenerative cascades of AD. However, accumulating evidence suggests that prefibrillar soluble Aβ oligomers induce AD‐related synaptic dysfunction. The size of Aβ oligomers is distributed over a wide molecular weight range (from < 10 kDa to > 100 kDa), with structural polymorphism in Aβ oligomers of similar sizes. Recent studies have demonstrated that Aβ can accumulate in living cells, as well as in extracellular spaces. This review summarizes current research on Aβ oligomers, focusing on their structures and toxicity mechanism. We also discuss possible formation mechanisms of intracellular and extracellular Aβ oligomers.
Inhibition of synthesis of pyrimidine nucleotides by 2-hydroxy-3-(3,3-dichloroallyl)-1,4-naphthoquinone.

Abstract Dichloroallyl lawsone [2-hydroxy-3-(3,3-dichloroallyl)-1,4-naphthoquinone, NSC 126771] is of interest as an antitumor agent. Like certain other naphthoquinones, it is known to be a respiratory poison as a result of interference with electron transport, but it has not been shown that this action is responsible for its toxicity or antitiumor activity. Studies in cultured L1210 cells showed that dichloroallyl lawsone (a) stimulated the incorporation of [14C]uridine into macromolecules, (b) specifically decreased the pool sizes of uridine triphosphate, (c) prevented the pyrazofurin-induced accumulation of orotidine and orotic acid, and (d) exerted cytotoxicity that could be prevented or reversed almost completely by uridine. This evidence that dichloroallyl lawsone specifically inhibited biosynthesis of pyrimidine nucleotides in intact cells was confirmed by studies in homogenates; these showed that this agent inhibited the conversion of [14C]carbamylphosphate to orotate and uridine monophosphate but not its conversion to dihydroorotate and that it was without effect on the conversion of [6-14C]orotate to uridine monophosphate. That the site of inhibition was dihydroorotate dehydrogenase was confirmed in studies with isolated mitochondria from mouse liver. An enzyme from this source catalyzed the oxidation of [6-14C]dihydroorotate (apparent Km, 6.7 × 10−6m), and dichloroallyl lawsone functioned as an inhibitor uncompetitive with dihydroorotate (Ki, 2.7 × 10−8m). Addition of ubiquinone was without effect on the reaction. Dichloroallyl lawsone, however, did not inhibit dihydroorotate dehydrogenase from Zymobacterium oroticum. These results indicate that the blockade of pyrimidine biosynthesis resulting from inhibition of dihydroorotate dehydrogenase is primarily responsible for the cytotoxicity of dichloroallyl lawsone to L1210 cells. More limited studies with the structurally related quinone, lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone], indicated that it exerts similar effects on biosynthesis of pyrimidines.
Top Companies Ranking Based on Financial Ratio with AHP-TOPSIS Combined Approach and Indices of Tehran Stock Exchange A Comparative Study

This paper aims to explore the relationship between ranking of the top-50 listed companies on Tehran Stock Exchange (TSE) for the years 2009- 2011 in terms of their liquidity, operation, leverage and profitability ratios using combined AHP-TOPSIS approach and the ranking made by the stock exchange. Ranking of the companies on the stock exchange is done based on their state in terms of the above ratios and it serves as a criterion for decision making on investment. Using a questionnaire, views of experts, scholars and the capital market authorities on the effect of financial ratios were gathered and then using AHP- TOPSIS technique the companies were ranked based on these ratios. The obtained results from the Spearman Test show a weak correlation between the rankings based on AHP-TOPSIS approach and the ranking of the stock exchange. Finally, our results indicate that financial ratios of the top stock exchange selected companies are crucial factors in investment and ranking. This paper contributes to a signaled need for investigation on how and why financial statements of top listed companies cannot be regarded as a critical factor in ranking and decision making on investment.
Johnson Noise Thermometry Measurement of the Boltzmann Constant With a 200 $\Omega$ Sense Resistor

In 2010, the National Institute of Standards and Technology measured the Boltzmann constant k with an electronic technique that measured the Johnson noise of a 100 Ω resistor at the triple point of water and used a voltage waveform synthesized with a quantized voltage noise source (QVNS) as a reference. In this paper, we present measurements of k using a 200 Ω sense resistor and an appropriately modified QVNS circuit and waveform. Preliminary results show agreement with the previous value within the statistical uncertainty. An analysis is presented, where the largest source of uncertainty is identified, which is the frequency dependence in the constant term a0 of the two-parameter fit.
Involvement of the amino‐terminal β‐hairpin of the Aspergillus ribotoxins on the interaction with membrances and nonspecific ribonuclease activity

Ribotoxins are a family of potent cytotoxic proteins from Aspergillus whose members display a high sequence identity (85% for about 150 amino acid residues). The three‐dimensional structures of two of these proteins, α‐sarcin and restrictocin, are known. They interact with phospholipid bilayers, according to their ability to enter cells, and cleave a specific phosphodiester bond in the large subunit of ribosome thus inhibiting protein biosynthesis. Two nonconservative sequence changes between these proteins are located at the amino‐terminal β‐hairpin of α‐sarcin, a characteristic structure that is absent in other nontoxic structurally related microbial RNases. These two residues of α‐sarcin, Lys 11 and Thr 20, have been substituted with the equivalent amino acids in restrictocin. The single mutants (K11L and T20D) and the corresponding K11L/T20D double mutant have been produced in Escherichia coli and purified to homogeneity. The spectroscopic characterization of the purified proteins reveals that the overall native structure is preserved. The ribonuclease and lipid‐perturbing activities of the three mutants and restrictocin have been evaluated and compared with those of α‐sarcin. These proteins exhibit the same ability to specifically inactivate ribosomes, although they show different activity against nonspecific substrate analogs such as poly(A). The mutant variant K11L and restrictocin display a lower phospholipid‐interacting ability correlated with a decreased cytotoxicity. The results obtained are interpreted in terms of the involvement of the amino‐terminal β‐hairpin in the interaction with both membranes and polyadenylic acid.
Genetic shift in photoperiodic response correlated with global warming

To date, all altered patterns of seasonal interactions observed in insects, birds, amphibians, and plants associated with global warming during the latter half of the 20th century are explicable as variable expressions of plastic phenotypes. Over the last 30 years, the genetically controlled photoperiodic response of the pitcher-plant mosquito, Wyeomyia smithii, has shifted toward shorter, more southern daylengths as growing seasons have become longer. This shift is detectable over a time interval as short as 5 years. Faster evolutionary response has occurred in northern populations where selection is stronger and genetic variation is greater than in southern populations. W. smithii represents an example of actual genetic differentiation of a seasonality trait that is consistent with an adaptive evolutionary response to recent global warming.
Dizygotic to monozygotic twinning ratio at The Royal Women's Hospital, Melbourn 1947–1997, compared with Australian national twinning incidence

Abstract The incidence of dizygotic (Dz) twinning can be used as an index of natural human fertility. A retrospective study was done at The Royal Women's Hospital, Australia, to see whether the dizygotic to monozygotic (Mz) twinning ratio from one hospital can accurately reflect the national incidence of Dz twinning. The yearly twinning incidence from 1947–1997 was expressed as a Dz:Mz ratio, standardised for maternal age and plotted against previously published national statistics. The proportion of mothers born in Asia (of both singleton and multiples) between 1983–1997 was analysed to see whether different racial mixes might influence twinning trends. There were 5275 twins born of known sex and maternal age between 1947–1997. The agestandardised Dz:Mz ratio increased non-significantly from 1.39 in 1947 to 2.29 in 1953 (P = 0.08), underwent a significant decline to 0.73 in 1977, then remained stable until 1997 (P > 0.05). The same trends were also apparent when the data was pooled into 2-year groups with the increase from 1947/48–1953/54 becoming highly significant (P < 0.009). These trends observed in the hospital-based data were in close agreement with those found in the national statistics, with the exception of a rise in 1977–1982 only reflected in the Australia-wide data. In 1993, 2.6% of mothers were born in Asian countries; by 1997, this had risen to 10.6%. We found that the Dz:Mz ratio from one hospital closely reflects national twinning trends. Prospective studies must account for race, and would need around 200–300 twin pairs per year to minimise fluctuations of the ratio. Twin Research (2000) 3, 12–16.
Notice of RetractionA Neuroscience lens to MIS researh: NeuroIS

The tool and theory of Cognitive Neuroscience has been used in sociology, economics, marketing, psychology disciplines recent years. “NeuroIS” was first declared by Dimoka in 2007. From then to now, the study of NeuoIS had been published in the top MIS journal such as MIS Q, ISR, as well as in the top International Conference such as ICIS and AMCIS. This paper described the clear track of NeuroIS over the period of 2007 to 2010. The significant of Neuroscience in MIS is analyzed. Finally, how to conduct a Neuroimaging study is explained with Dimoka's first fMRI study on TAM.
Radiation dose measurements during kilovoltage-cone beam computed tomography imaging in radiotherapy.

OBJECTIVE The use of image guidance during radiotherapy for accurate localization and setup has become the standard care of practice in radiotherapy. This mostly involves the use of kilovoltage-cone beam computed tomography (kV-CBCT) for verification of patient setup on the first few days and on a weekly basis. Some protocols require this to be performed daily and also before and after the treatment. Though the radiation due to this kV-CBCT is small, the repeated use could deliver a dose that could increase the probability of the stochastic effect. The main purpose of this work is to measure radiation dose during image guidance with kV-CBCT. MATERIALS AND METHODS In this work, we have attempted to measure the dose during kV-CBCT for different sites both on a humanoid phantom and on patients undergoing image-guided radiotherapy with MOSFETs calibrated against an ion chamber. RESULTS The dose measurement on patients during kV-CBCT resulted in mean doses of 0.19 and 0.3 cGy to the ipsilateral and contralateral eyes, 0.625 and 1.097 cGy to the surface of the ipsilateral and contralateral breasts, and 3.01 cGy to the surface of the pelvis. CONCLUSION Radiation dose to the eye, breast, and the surface of the pelvis have been arrived at during CBCT. The doses measured on patients agreed closely with those measured on humanoid phantom and with published values.
MicroRNA-21 Targets the Tumor Suppressor Gene Tropomyosin 1 (TPM1)*

MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that mir-21 is overexpressed in tumor tissues compared with the matched normal tissues. Moreover, suppression of mir-21 by antisense oligonucleotides inhibits tumor cell growth both in vitro and in vivo. However, it remains largely unclear as to how mir-21 affects tumor growth, because our understanding of mir-21 targets is limited. In this study, we performed two-dimensional differentiation in-gel electrophoresis of tumors treated with anti-mir-21 and identified the tumor suppressor tropomyosin 1 (TPM1) as a potential mir-21 target. In agreement with this, there is a putative mir-21 binding site at the 3′-untranslated region (3′-UTR) of TPM1 variants V1 and V5. Thus, we cloned the 3′-UTR of TPM1 into a luciferase reporter and found that although mir-21 down-regulated the luciferase activity, anti-mir-21 up-regulated it. Moreover, deletion of the mir-21 binding site abolished the effect of mir-21 on the luciferase activity, suggesting that this mir-21 binding site is critical. Western blot with the cloned TPM1-V1 plus the 3′-UTR indicated that TPM1 protein level was also regulated by mir-21, whereas real-time quantitative reverse transcription-PCR revealed no difference at the mRNA level, suggesting translational regulation. Finally, overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchorage-independent growth. Thus, down-regulation of TPM1 by mir-21 may explain, at least in part, why suppression of mir-21 can inhibit tumor growth, further supporting the notion that mir-21 functions as an oncogene.
Postoperative Sensitization and Pain After Cesarean Delivery and the Effects of Single IM Doses of Tramadol and Diclofenac Alone and in Combination

Combining different analgesic mechanisms can reduce postoperative pain. We investigated postoperative pain and sensory sensitization in a double-blinded, placebo-controlled, randomized, single-dose comparison of the monoaminergic and &mgr;-opioid agonist tramadol, 100 mg, and diclofenac 75 mg given IM in combination or alone in 120 patients who had elective cesarean delivery. The time to first postoperative demand for rescue analgesia, pain, tramadol pharmacokinetics, and electrical sensory thresholds at or distant from the incision were studied. The median time to first rescue (interquartile range) was 197 min (70–1000 min) with tramadol plus diclofenac, 48 min (25–90 min) with tramadol plus placebo, 113 min (35–270 min) with diclofenac plus placebo, and 55 min (30–100 min) with double placebo (tramadol plus diclofenac versus all other groups, P < 0.05). Pain intensity decreased markedly over time in all groups, and time and drug effects were significant (analysis of variance; P < 0.00001). Side effects were similarly minimal with all treatments. Pain thresholds at or distant from the incision increased significantly after surgery only with tramadol plus diclofenac. Preoperative sensory thresholds correlated with postoperative sensory changes (r > 0.53; P < 0.0001). The pharmacokinetics of tramadol and O-desmethyltramadol were unchanged by diclofenac. The combination of tramadol and diclofenac resulted in improved analgesia compared with monotherapy. Only the analgesic combination prevented both primary and secondary hyperalgesia. Preoperative sensory thresholds may allow prediction of postoperative sensitization.
Differential Effect of Troglitazone on the Human Bile Acid Transporters, MRP2 and BSEP, in the PXB Hepatic Chimeric Mouse

The aims of this study were to assess the utility of the PXB mouse model of a chimeric human/mouse liver in studying human-specific effects of an important human hepatotoxic drug, the PPARγ agonist, troglitazone. When given orally by gavage for 7 days, at dose levels of 300 and 600 ppm, troglitazone induced specific changes in the human hepatocytes of the chimeric liver without an effect on the murine hepatic portions. The human hepatocytes, in the vehicle-treated PXB mouse, showed an accumulation of electron-dense lipid droplets that appeared as clear vacuoles under the light microscope in H&E-stained sections. Following dosing with troglitazone, there was a loss of the large lipid droplets in the human hepatocytes, a decrease in the amount of lipid as observed in frozen sections of liver stained by Oil-red-O, and a decrease in the expression of two bile acid transporters, BSEP and MRP2. None of these changes were observed in the murine remnants of the chimeric liver. No changes were observed in the expression of three CYPs, CYP 3A2, CYP 1A1, and CYP 2B1, in either the human or murine hepatocytes, even though the baseline expression of the enzymes differed significantly between the two hepatocyte species with the mouse hepatocytes consistently showing increased expression of the protein of all three enzymes. This study has shown that the human hepatocytes, in the PXB chimeric mouse liver, retain an essentially normal phenotype in the mouse liver and, the albeit limited CYP enzymes studied show a more human, rather than a murine, expression pattern. In line with this conclusion, the study has shown a differential response of the human versus the mouse hepatocytes, and the effects observed are highly suggestive of a differential handling of the compound by the two hepatocyte species although the exact reasons are not as yet clear. The PXB chimeric mouse system therefore holds the clear potential to explore human hepatic–specific features, such as metabolism, prior to dosing human subjects, and as such should have considerable utility in drug discovery and development.
The reaction of fumarase with iodoacetate and 4-bromocrotonate.

Abstract The reaction of fumarase with several alkylating agents has been examined. The structural similarity between these compounds and the natural substrates for the enzyme, fumarate and malate, suggested that reaction might occur with structures in the active sites. Of all the compounds tested, only iodoacetate and 4-bromocrotonate inactivated fumarase by modification of structures other than the thiol groups. Because the thiol groups appear to fulfill a structural role in the enzyme, it is possible that iodoacetate and bromocrotonate react specifically with fumarase. The enzyme is inactivated to an extent of 80 to 90% when only 3 to 6 eq of each compound have reacted with the enzyme. Inactivation by each compound is reduced markedly by substrates and competitive inhibitors, and extensive structural changes do not occur after inactivation. S-Carboxymethylmethionine and 3-carboxymethylhistidine are the major derivatives found after inactivation with iodoacetate. The distribution of these carboxymethyl derivatives among the tryptic peptides of iodoacetate-inactivated fumarase has been examined. From 80 to 85% of the S-carboxymethylmethionine and 3-carboxymethylhistidine present in the modified enzyme have been recovered in three unique peptides.