Miracle-dz/UniFAR-FTUs huggingface dataset:
GILA, a Replacement for the Soft‐Agar Assay that Permits High‐Throughput Drug and Genetic Screens for Cellular Transformation

For the last five decades, measuring the ability of cells to grow in soft agar has served as the gold standard assay for in vitro cellular transformation. Nevertheless, the soft agar colony formation assay is time consuming and ill‐suited for high‐throughput screens. This unit describes an equally qualitative and quantitative assay known as growth in low attachment or GILA. The GILA assay is suitable for high‐throughput pharmacological or genetic screens and allows the simultaneous examination of multiple cell lines and experimental perturbations. GILA conditions are specific and relevant to the transformed state because they depend on a property of cancer cells that is not shared by non‐transformed cells. The GILA assay enables ex vivo drug sensitivity testing of patient‐derived tumor cells to define precise treatments for individual patients. © 2016 by John Wiley & Sons, Inc.
The composition and initial evaluation of a grimace scale in ferrets after surgical implantation of a telemetry probe

Reliable recognition of pain is difficult in ferrets as many currently available parameters are non-specific, inconsistent and/or impractical. Grimace scales have successfully been applied to assess pain in different animal species and might also be applicable to ferrets. To compose a Ferret Grimace Scale (FGS), we studied the facial musculature of ferrets and compared lateral photographs of 19 ferret faces at six time points before and after intraperitoneal telemetry probe implantation. We identified the Action Units (AUs) orbital tightening, nose bulging, cheek bulging, ear changes and whisker retraction as potential indicators of pain in ferrets. To evaluate whether these AUs could reliably be used to identify photographs taken before and after surgery, the photographs were scored 0, 1 or 2 (not, moderately or obviously present) by 11 observers that were blinded to the treatment and timing of the photographs. All AU-scores assigned to the photographs taken five hours after surgery were significantly higher compared to their time-matched baseline scores. Further analysis using the weights that were obtained using a Linear Discriminant Analysis revealed that scoring orbital tightening alone was sufficient to make this distinction with high sensitivity, specificity and accuracy. Including weighted scores for nose bulging, cheek bulging and ear change did not change this. As these AUs had more missing values than orbital tightening, their descriptions should be re-evaluated. Including whisker retraction, which had a negative weight, resulted in lower accuracy and should therefore in its current form be left out of the FGS. Overall, the results of this study suggest that the FGS and the AU orbital tightening in particular could be useful in a multifactorial pain assessment protocol for ferrets. However, before applying the FGS in practice, it should be further validated by incorporating more time points before and after applying (different) painful stimuli, and different levels of analgesia.
Quantitative Assessment of the Effect of Nitric Oxide Synthase Inhibition on Tumor Vascular Activity Using Dynamic Contrast-Enhanced Computed Tomography

Purpose: The purpose of this study was to develop a method to quantitatively assess the effect of nitric oxide synthase (NOS) inhibition on tumor vascular activity using dynamic contrast-enhanced computed tomography (DCE-CT) and to investigate its usefulness using animal experiments. Mate-rials and Methods: The DCE-CT studies were performed in anesthetized Fisher rats bearing tumors using a 4-row multi-slice CT. The scanning started 4 s before a bolus injection of iodinated contrast agent (CA) (150 mgI/kg) from the tail vein using an automatic injector and lasted 60 s at 1-s in-tervals. The contrast enhancement (CE) images were generated by subtracting the CT images before and after the administration of CA. First, the DCE-CT studies were performed before and 15, 30, and 45 min after administration of N-nitro-L-arginine (L-NNA) (1, 3, and 10 mg/kg) or vehicle, and the relative CE values were calculated by normalizing the CE image at each time point by that obtained from the first DCE-CT study. Second, we investigated the case when L-arginine (L-ARG) (200 mg/kg) and L-NNA (1, 3, and 10 mg/kg) were administered after the first and second DCE-CT studies, respectively. Third, we investigated the case when L-NNA (1, 3, and 10 mg/kg) and L-ARG (200 mg/kg) were administered after the first and second DCE-CT studies, respectively. Finally, we investigated the case when L-NNA (1, 3, and 10 mg/kg) and L-ARG (200 mg/kg) were administered simultaneously after the first DCE-CT study. Results: The relative CE value significantly decreased after L-NNA administration in a dose-dependent manner (p-values = 0.0074 and <0.0001 for 0 vs. 3 mg/kg and 0 vs. 10 mg/kg, respectively, at 15 min, 0.0003 and <0.0001 for 0 vs. 3 mg/kg and 0 vs. 10 mg/kg, respectively, at 30 min, and 0.0367 and 0.0004 for 0 vs. 3 mg/kg and 0 vs. 10 mg/kg, respectively, at 45 min). When L-ARG was administered prior to the administration of 1 mg/kg L-NNA, the relative CE value at 45 min was significantly higher than that at 15 min. When L-ARG was administered after L-NNA administration, there was no significant difference between the relative CE values at 15 min and 45 min. These results suggest that when using L-NNA in combination with L-ARG, their effect on tumor vascular activity differs depending on the order of their administration. When L-NNA and L-ARG were administered simultaneously, there was a tendency for the relative CE value to be higher than that when only L-NNA was administered, at all injected doses of L-NNA. Conclusion: Our method using DCE-CT is useful for monitoring the effect of NOS inhibition on tumor vascular activity and for determining the optimal injected dose and timing of NOS inhibitors for anticancer therapy.
The challenge of forgetting: Neurobiological mechanisms of auditory directed forgetting

Directed forgetting (DF) is considered an adaptive mechanism to cope with unwanted memories. Understanding it is crucial to develop treatments for disorders in which thought control is an issue. With an item‐method DF paradigm in an auditory form, the underlying neurocognitive processes that support auditory DF were investigated. Subjects were asked to perform multi‐modal encoding of word‐stimuli before knowing whether to remember or forget each word. Using functional magnetic resonance imaging, we found that DF is subserved by a right frontal‐parietal‐cingulate network. Both qualitative and quantitative analyses of the activation of this network show converging evidence suggesting that DF is a complex process in which active inhibition, attentional switching, and working memory are needed to manipulate both unwanted and preferred items. These results indicate that DF is a complex inhibitory mechanism which requires the crucial involvement of brain areas outside prefrontal regions to operate over attentional and working memory processes. Hum Brain Mapp 39:249–263, 2018. © 2017 Wiley Periodicals, Inc.
Pathologic Reporting of Tall-Cell Variant of Papillary Thyroid Cancer: Have We Reached a Consensus?

BACKGROUND Tall-cell variant (TCV) is widely believed to be a more aggressive subtype of papillary thyroid carcinoma (PTC). Despite the significance of TCV with respect to risk stratification and therapeutic decision making, its diagnosis is subject to inter-observer variability. This study aimed to determine the level of agreement among expert pathologists in the identification and reporting of TCV. METHODS Seventeen surgical resections for thyroid cancer containing the diagnostic term "tall cell" in their pathology reports and 22 cases diagnosed as classical PTC were selected. Cases were digitalized, and 14 expert pathologists reviewed the scanned slides blinded to the original interpretation. Each pathologist designated each case as TCV or not and answered multiple questions about diagnostic histopathologic features of TCV. RESULTS The overall strength of agreement for identifying TCV was fair (Fleiss kappa 0.34), and the proportion of observed agreement was 0.70. Of 22 cases originally diagnosed as PTC classical variant, 15 (68%) were reclassified as TCV by at least one expert pathologist. It was noted that four different definitions for TCV were used by the participants based on various combinations of cell height to width (H:W) ratio and the percentage of tumor cells showing that specific ratio. All pathologists agreed that the diagnosis of TCV does not rely solely on a specific H:W ratio. CONCLUSIONS Pathologic reporting of TCV varies among pathologists. This disagreement is a result of the lack of unanimous diagnostic criteria and variation in individual pathologists' interpretations. These discrepancies lead to over- and under-diagnosis of TCV, which has significant implications in patient management. It is imperative to understand this variability in diagnosis TCV as it relates to risk stratification and interpretation of clinical studies related to this histologic subtype of PTC. Further studies are needed to reach consensus on the diagnostic criteria of TCV.
What good are character strengths beyond subjective well-being? The contribution of the good character on self-reported health-oriented behavior, physical fitness, and the subjective health status

Character strengths were tested in relation to subjective (life satisfaction) and physical (self-evaluated health and physical fitness) well-being (440 adults). Health-behaviors and the mediating role of health-behaviors in explaining the relationship between character and well-being were also considered. Emotional, intellectual strengths and strengths of the heart were positively associated with life satisfaction and physical fitness. Emotional strengths correlated positively with the self-evaluation of feeling healthy. All strengths (except for modesty and religiousness) were related to health-behaviors; e.g. healthy eating and watching ones food consumption were associated with self-regulation and intellectual strengths. Health behaviors partially mediated the relation of broader strengths factors on subjective and physical well-being. The largest indirect effects were found for leading an active way of life. The study suggests that there are positive relations between character strengths and subjective but also physical well-being. Furthermore, potential mechanisms, which might account for these relations (i.e. health-behaviors) are assessed.
Are Banks Peer Disciplined? Evidence from Post-Crisis Russia

Market discipline is usually studied in the retail or the corporate deposit markets, while the interbank loan market is disregarded. Banks' abilities to exert market discipline are taken for granted, as they are expected to have the expertise to assess correctly the riskiness of other banks. However, the “crises of trust” (as one in 2004 in Russia) create some doubts as to whether efficient peer monitoring and peer discipline exist: the interbank loan market may be frozen in response to external information which is unrelated to the banks’ current reliability. This seems to be one of the reasons for the interbank loan markets being extremely fragile during periods of financial instability, undermining the smooth functioning of the whole banking system, as banks are tightly interconnected. We provide some evidence for market discipline in the Russian interbank market. We show that the only disciplinary mechanism that functions is a price-based one: more reliable banks enjoy lower interest rates. The quantitative discipline functions only for the largest borrowers. In general, decisions on credit limits are based not on changes in another bank’s riskiness but on other information like reputation, soft information or public announcements that may be even unrelated to a particular bank.
Low-Dose Atomoxetine for Maintenance Treatment of Attention-Deficit/Hyperactivity Disorder

OBJECTIVE. Data from acute studies of atomoxetine in patients with attention-deficit/hyperactivity disorder suggest that a dose of ∼1.2 mg/kg per day is required to attain a maximal symptom response. However, lower doses could be effective during maintenance treatment, which would reduce drug exposure and potential problems related to tolerability during chronic treatment. METHODS. Patients 6 to 16 years of age who had a robust response to an initial acute trial of atomoxetine were assigned randomly under double-blind conditions to continue treatment for up to 8 months with either the dose to which they had responded acutely (1.2–1.8 mg/kg per day, N = 116, continued same dose) or a lower dose (0.5 mg/kg per day, N = 113, low dose). The primary outcome measure was relapse, defined as an Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score returned to ≥90% of the original baseline value (before acute treatment) for 2 consecutive visits. Mean change in Attention-Deficit/Hyperactivity Disorder Rating Scale total score was assessed as a secondary outcome. RESULTS. At randomization, symptom severity was low and similar in both groups. At end point, relapse rates did not differ between the groups. Mean change in Attention-Deficit/Hyperactivity Disorder Rating Scale total score from the conclusion of acute treatment to end point also was not different between groups. Reports of affective lability were higher in the patients in the low-dose group. Also, increases in heart rate (compared with when atomoxetine was started) were higher in the patients in the continued same-dose group than in the low-dose group. Finally, increases in weight over the course of the trial were greater for the low-dose group than the continued same-dose group. CONCLUSIONS. For patients who experience a robust response to atomoxetine, it may be possible to retain the response during maintenance treatment with a reduced dose of atomoxetine.
Idiotype suppression. I. Influence of the dose and of the effector functions of anti‐idiotypic antibody on the production of an idiotype

Parameters that influence the effect of passively administered anti‐idiotypic antibody on the expression of idiotype‐positive and of idiotype‐negative antibodies were investigated in adult A/J mice immunized with Group A streptococci. The results suggest: 1. idiotype‐positive antibodies are eliminated from the spectrum of humoral antibodies as a consequence of the elimination of the idiotype‐forming cell precursors. 2. The heterogeneity of the idiotype‐negative compensatory response of individual suppressed mice is as restricted as that of the idiotype‐positive normal response. The isoelectric spectra of idiotype‐negative antibodies are individually specific, whereas the isoelectric spectra of idiotype‐positive antibodies are individually specific, whereas the isoelectric spectra of idiotype‐positive antibodies are shared between individual mice. 3. Suppression is transient in mice treated with low and with high doses of anti‐idiotypic antibody, but is maintained in mice treated with intermediate doses. 4. Suppression is mediated by complement and macrophage fixing (guinea pig IgG2) anti‐idiotypic antibody only. IgG1 anti‐idiotypic antibody appears to have an enhancing effect on the production of the idiotype. The results are discussed with respect to possible regulatory functions of idiotype‐anti‐idiotype interactions in the immune response.
Prediction of functional outcome and tissue loss in acute cortical infarction.

OBJECTIVE To compare the acute Allen's Prognostic Score, Canadian Neurological Score, and subacute Barthel Index as predictors of outcome functional status and infarct size at 3 months in patients with acute cortical infarction. DESIGN A prospective study of acute stroke predictors and outcome measurements in a cohort of sequential hospitalized patients. PATIENTS Fifty-one patients with acute cortical infarction and without previous disability assessed 24 hours after onset with Allen's Prognostic Score and the Canadian Neurological Score and at 7 days with the Barthel Index. MAIN OUTCOME MEASURES Mortality, Barthel Index, and volumetric measurement of infarct size on computed tomography 3 months after stroke. RESULTS There were seven deaths. The outcome Barthel Index was measured in all 44 survivors, of whom 29 had computed tomography at the time outcome was determined. In a multivariate analysis, functional outcome was best predicted by Allen's Prognostic Score, a score of less than -15 having a sensitivity of 82% and specificity of 97% in predicting a poor outcome (Barthel Index, < or = 12 or death). Volumetric tissue loss was predicted only by Allen's Prognostic Score (r = .62, P < .001). CONCLUSIONS Allen's Prognostic Score is a robust predictor of both functional outcome and tissue loss in acute cortical infarction and has a potentially important role in the analysis of the results of acute stroke intervention trials.
Determinants of Discharge Destination for Stroke Patients

&NA; Discharge to community is an important outcome measure for rehabilitation facilities. Studies consistently find that stroke patients with higher scores on the Functional Independence Measure™ (FIM) are more likely to be discharged to the community. Other variables, including age, gender, and living status, also have shown a relationship to discharge destination for stroke patients. This study explored the differences between stroke patients who were discharged to the community and those who were discharged to a nursing home after a stay on an acute inpatient rehabilitation unit. Results indicated that older patients and those with lower admission FIM scores are more likely to be discharged to nursing homes, but many patients who fit this profile are discharged to the community. The main destination determinant was how well a patient's need for care matched informal caregiving resources. These findings indicate a need for additional focused assessment of available care giving resources.
The location of new foreign-owned manufacturing plants in the United States and Seventh Federal Reserve District

to the Midwest Economy. " Linda M. Aguilar, Jack L. Hervey, and Thomas H. Klier served as workshop conveners. The workshop was the sixth of a series held at the Federal Reserve Bank of Chicago as part of the 1996–97 project "Assessing the Midwest Economy. " Inquiries should be directed to the Public Information Center, Federal Reserve Bank of Chicago, P.O. Box 834, Chicago, Illinois 60690-0834, or telephone (312) 322-5111. The Federal Reserve Bank of Chicago's Web site can be accessed at http://www.frbchi. org. The Location of New Foreign-Owned Manufacturing Plants in the United States and Seventh Federal Reserve District
CONCEPTUAL REVIEW OF FIRMS BUSINESS STRATEGY FINANCIAL FLEXIBILITY AND PROFITABILITY OF STYLE INVESTING IN THE ECONOMIC ENVIRONMENT

In this study, we're looking at this as a concept somewhat familiar with the economic environment we start edges and investment styles. Therefore, we first attempt a comprehensive definition of business strategies and are flexible. While the precise definition of the relationship they have with each of our investments and the profitability of existing styles. This study examines how firms’ financial flexibility affects the profitability of three of the most commonly used style investing strategies. They are the value-growth trading strategy (going long on stocks with high Book-toMarket ratio and short on stocks with low Book-to-Market ratio), the momentum trading strategy (going long on stocks that have performed well and short on stocks that have performed poorly recently), and the accruals based trading strategy. The results suggest that the understanding of corporate investment decisions can help improve the understanding of securities markets and portfolio investment strategies. There are a few lessons that investors can learn from the findings of this thesis. Value-growth investors should focus on value and growth firms with high investment irreversibility gap. Momentum investors should pursue the trading strategy among firms with high financial constraints and during economic upturns. They could also benefit from forming their portfolio from past winners and past losers with high investment gaps. Accruals based investors would benefit from pursuing the strategy among firms with high investment and financing flexibility and during economic upturns.
A proposal for laser cooling antihydrogen atoms

We present a scheme for laser cooling applicable to an extremely dilute sample of magnetically trapped antihydrogen atoms (). Exploiting and controlling the dynamical coupling between the 's motional degrees of freedom in a magnetic trap, three-dimensional cooling can be achieved from Doppler cooling in one dimension using the 1s1/2 − 2p3/2 transition. The lack of three-dimensional access to the trapped and the nearly separable nature of the trapping potential leads to difficulties in cooling. Using realistic models for the spatial variation of the magnetic fields, we find that it should be possible to cool the 's to ∼20 mK even with these constraints.
Comparative motif discovery combined with comparative transcriptomics yields accurate targetome and enhancer predictions

The identification of transcription factor binding sites, enhancers, and transcriptional target genes often relies on the integration of gene expression profiling and computational cis-regulatory sequence analysis. Methods for the prediction of cis-regulatory elements can take advantage of comparative genomics to increase signal-to-noise levels. However, gene expression data are usually derived from only one species. Here we investigate tissue-specific cross-species gene expression profiling by high-throughput sequencing, combined with cross-species motif discovery. First, we compared different methods for expression level quantification and cross-species integration using Tag-seq data. Using the optimal pipeline, we derived a set of genes with conserved expression during retinal determination across Drosophila melanogaster, Drosophila yakuba, and Drosophila virilis. These genes are enriched for binding sites of eye-related transcription factors including the zinc-finger Glass, a master regulator of photoreceptor differentiation. Validation of predicted Glass targets using RNA-seq in homozygous glass mutants confirms that the majority of our predictions are expressed downstream from Glass. Finally, we tested nine candidate enhancers by in vivo reporter assays and found eight of them to drive GFP in the eye disc, of which seven colocalize with the Glass protein, namely, scrt, chp, dpr10, CG6329, retn, Lim3, and dmrt99B. In conclusion, we show for the first time the combined use of cross-species expression profiling with cross-species motif discovery as a method to define a core developmental program, and we augment the candidate Glass targetome from a single known target gene, lozenge, to at least 62 conserved transcriptional targets.