Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitotic Recombination in Patients with Ichthyosis Causes Reversion of Dominant Mutations in KRT10

Gaining from a Loss Mitotic recombination can cause a cell carrying heterozygous mutations in a tumor suppressor gene to lose the wild-type copy of the gene, setting the cell on the pathway to uncontrolled growth. But can mitotic recombination have beneficial effects in other settings—that is, lead to phenotypic correction of a diseased cell by facilitating loss of the disease-causing mutation? Choate et al. (p. 94, published online 26 August; see the Perspective by Davis and Candotti) now find evidence for this type of event in a rare skin disease called ichthyosis with confetti (IWC). Patients with IWC display severe scaling of the skin but have widespread patches of normal skin that reflect clonal expansion of revertant cells. The revertant cells showed loss of heterozygosity on chromosome 17q and, as a result of mitotic recombination, these cells selectively lost dominant disease-causing mutations in the keratin 10 gene (KRT10), but retained the wild-type copy of the gene. Patches of normal skin in patients with a rare skin disorder are due to cells that have lost the disease-causing mutation. Somatic loss of wild-type alleles can produce disease traits such as neoplasia. Conversely, somatic loss of disease-causing mutations can revert phenotypes; however, these events are infrequently observed. Here we show that ichthyosis with confetti, a severe, sporadic skin disease in humans, is associated with thousands of revertant clones of normal skin that arise from loss of heterozygosity on chromosome 17q via mitotic recombination. This allowed us to map and identify disease-causing mutations in the gene encoding keratin 10 (KRT10); all result in frameshifts into the same alternative reading frame, producing an arginine-rich C-terminal peptide that redirects keratin 10 from the cytokeratin filament network to the nucleolus. The high frequency of somatic reversion in ichthyosis with confetti suggests that revertant stem cell clones are under strong positive selection and/or that the rate of mitotic recombination is elevated in individuals with this disorder.
Sensitivity Analysis of TRL Calibration in Waveguide Integrated Membrane Circuits

We present a sensitivity analysis on TRL calibrated S-parameter measurements of membrane circuits in the WR-03 waveguide band (220-325 GHz). The impact of waveguide and membrane circuit misalignment, as well as waveguide dimension mismatch is investigated. The analysis is performed for the thru-reflect-line (TRL) calibration applied to E-plane split waveguide blocks carrying membrane circuits. The analysis shows a large influence of the waveguide width tolerance on transmission and reflection phase after the TRL calibration. For a 20 mm long rectangular waveguide with a ± 5 μm width tolerance a phase uncertainty as large as ± 45° for reflection and ± 30° for transmission measurements is observed.
An Imaging Comparison of 64 Cu-ATSM and 60 Cu-ATSM in Cancer of the Uterine Cervix

Tumor uptake of copper(II)-diacetyl-bis( N 4 -methylthiosemicar-bazone) (copper-ATSM), a hypoxia-targeting radiopharmaceutical, assessed by PET has been found to correlate with prognosis in several human cancers. Wide clinical utility of this tracer will require its labeling with a copper radionuclide having a longer half-life than the 60 Cu used in studies to date. The purpose of this work was to obtain the requisite preclinical data for copper-ATSM to ﬁle an investigational new drug application, followed by a crossover comparison of PET image quality and tumor uptake with 60 Cu-ATSM and 64 Cu-ATSM in women with cancer of the uterine cervix. Methods: The preclinical toxicology and pharmacology of a copper-ATSM formulation was examined using standard in vitro and in vivo assays, as well as 14-d toxicity studies in both rats and rabbits. For the clinical test–retest imaging study, 10 patients with cervical carcinoma underwent PET on separate days with 60 Cu-ATSM and 64 Cu-ATSM. Image quality was assessed qualitatively, and the tumor-to-muscle activity ratio was measured for each tracer. Results: The toxicology and pharmacology data demonstrated that the formulation has an appropriate margin of safety for clinical use. In the patient study, we found that the image quality with 64 Cu-ATSM was better than that with 60 Cu-ATSM because of lower noise. In addition, we found that the pattern and magnitude of tumor uptake of 60 Cu-ATSM and 64 Cu-ATSM on studies separated by 1–9 d were similar. Conclusion: 64 Cu-ATSM appears tobe asafe radiopharmaceutical that can be used to obtain high-quality images of tumor hypoxia in human cancers.
Mild vitamin A deficiency leads to inborn nephron deficit in the rat.

BACKGROUND Vitamin A plays a critical role in fetal organogenesis, and its severe deficiency during pregnancy is known to result in malformations of several organs, including the kidney. However, the consequences of mild vitamin A deficiency (VAD) has received little attention. In the present study, we examined the effect of in utero exposure to mild VAD on renal organogenesis. METHODS A rat model of mild VAD compatible with normal gestation was developed. Plasma retinol was determined by reverse phase HPLC in mothers and fetuses. Nephron counting was performed in kidneys of fetuses and pups issued from control and VAD mothers. Metanephroi explanted from 14-day-old fetuses from both groups were cultured in the presence or absence of retinoic acid (RA), and growth and differentiation were assessed. c-ret expression was analyzed from fetuses exposed in utero to VAD or to normal vitamin A status and also in metanephroi grown in culture with or without RA using RT-PCR. RESULTS The 50% reduction in circulating vitamin A levels induced by vitamin A deprivation in pregnant rats did not affect the overall fetal development. However, the number of nephrons was reduced by 20% in 21-day-old VAD fetuses. The number of nephrons was closely correlated with circulating vitamin A level in both VAD and control fetuses. Metanephroi taken from VAD fetuses developed to a lesser extent in vitro, but their capacity to respond to exogenous retinoic acid was not altered. Finally, we found that the expression of the proto-oncogene c-ret was modulated according to the retinoid environment. CONCLUSION We conclude that vitamin A supply to the fetus is critical in determining the number of nephrons. Data available thus far on the frequency of mild VAD during pregnancy and on the long-term consequences of inborn nephron deficit highlight the clinical relevance of the present study.
Growth of Sodium Dodecyl Sulfate Micelles with Detergent Concentration

Sodium alkyl sulfate micelles are predicted to grow as a power law of the total counterion salt concentration, Yaq, in the aqueous phase as follows: NA = K~(Y~~)Y, where NA is the micelle aggregation number and ~2 and y are constants which are estimated from the critical micelle concentration and the apparent degree of counterion attachment. For sodium dodecyl sulfate, NA = 162(Y,q)1/4 is predicted and is shown to be in good agreement with aggregation numbers measured by a number of techniques over a wide range of Yaq whether this quantity is varied by changing the concentrations of the detergent, the added counterion salt, or both. Values of ~2 and y are estimated for six members of the sodium alkyl sulfate family.
[Comparison of risk factors between patients with non-allergic rhinitis and allergic rhinitis].

OBJECTIVE To investigate and describe the differences in age, sex, seasonality distribution, and related environmental factors between patients with non-allergic rhinitis (NAR) and allergic rhinitis (AR). METHODS One hundred and eleven patients with NAR and 112 patients with AR were enrolled in this study. All patients were first diagnosed in outpatient department between January and August 2010. Questionnaires were distributed to all participants to record the general information, medical history, and the factors relevant to symptom onset. Statistical analysis was performed using a SPSS13.0 software. RESULTS The proportion of patients with NAR increased with age, compared to patients with AR. The peak age was 21 - 30 years old in patients with NAR, whereas 11 - 20 years old in patients with AR. In adults more than 18 years old, the average age (years, x(-) ± s) of patients with NAR (38.6 ± 14.5) was significantly higher than those with AR (32.8 ± 13.0; t = 2.58, P = 0.024). NAR was more likely to be males before 30 years old, while after 30 years old, it likely to be female predominance. The same case occurred in AR subjects but in their 20 years old. NAR was symptomatically worse in winter (χ(2) = 27.57, P = 0.000), whereas AR worse in spring (χ(2) = 13.75, P = 0.003). The cases of NAR were significantly more than those of AR during the winter season (χ(2) = 12.34, P = 0.000). Among the disease-related environmental factors, living or working place near the traffic artery had 1.94-fold increased risk for development of NAR compared with AR; however, living or working in ground floor or sunshine time less than 2 h per day had 1.77- or 1.91-fold increased risk for development of NAR compared with NAR. Subjects with personal or family history of allergic disease had 2.14 to 4.06-fold increased risk for development of AR compared with NAR. The self-reported predisposing factors in NAR patients were mainly including temperature shift (56.3%), common cold (52.8%), climate change (32.4%), and strong odors (31.1%). However, there were no significant differences in these nonspecific triggers between NAR and AR (all P > 0.05). CONCLUSION There are significant differences in the distribution of age, sex and seasonality, personal and family history of allergic disease, and some environmental factors relevant to the onset of symptom between patients with NAR and AR.
Assessing Heart Rate Variability Using A 12 lead ECG In Patients With Alcohol Dependence Syndrome

Heavy or hazardous drinking is associated with an increased risk of cardiac morbidity and mortality and this has been attributed to abnormalities in cardiac autonomic regulation. Current study aimed to assess the role of simple indices derived from 12 lead ECG in subjects with chronic alcohol dependence. Data suggested that alcohol group had significantly lower 12 lead ECG derived RR variability compared to age and gender matched controls. Study further supports the implication of 12 lead derived RR variability indices in various clinical settings.
Divergent genes in potential inoculant Sinorhizobium strains are related to DNA replication, recombination, and repair

To serve as inoculants of legumes, nitrogen‐fixing rhizobium strains should be competitive and tolerant of diverse environments. We hybridized the genomes of symbiotically efficient and salt tolerant Sinorhizobium inoculant strains onto the Sinorhizobium meliloti Rm1021 microarray. The number of variable genes, that is, divergent or putatively multiplied genes, ranged from 503 to 1556 for S. meliloti AK23, S. meliloti STM 1064 and S. arboris HAMBI 1552. The numbers of divergent genes affiliated with the symbiosis plasmid pSymA and related to DNA replication, recombination and repair were significantly higher than expected. The variation was mainly in the accessory genome, implying that it was important in shaping the adaptability of the strains.
Kappa opioids promote the proliferation of astrocytes via Gβγ and β‐arrestin 2‐dependent MAPK‐mediated pathways

GTP binding regulatory protein (G protein)‐coupled receptors can activate MAPK pathways via G protein‐dependent and ‐independent mechanisms. However, the physiological outcomes correlated with the cellular signaling events are not as well characterized. In this study, we examine the involvement of G protein and β‐arrestin 2 pathways in kappa opioid receptor‐induced, extracellular signal‐regulated kinase 1/2 (ERK1/2)‐mediated proliferation of both immortalized and primary astrocyte cultures. As different agonists induce different cellular signaling pathways, we tested the prototypic kappa agonist, U69593 as well as the structurally distinct, non‐nitrogenous agonist, C(2)‐methoxymethyl salvinorin B (MOM‐Sal‐B). In immortalized astrocytes, U69593, activated ERK1/2 by a rapid (min) initial stimulation that was sustained over 2 h and increased proliferation. Sequestration of activated Gβγ subunits attenuated U69593 stimulation of ERK1/2 and suppressed proliferation in these cells. Furthermore, small interfering RNA silencing of β‐arrestin 2 diminished sustained ERK activation induced by U69593. In contrast, MOM‐Sal‐B induced only the early phase of ERK1/2 phosphorylation and did not affect proliferation of immortalized astrocytes. In primary astrocytes, U69593 produced the same effects as seen in immortalized astrocytes. MOM‐Sal‐B elicited sustained ERK1/2 activation which was correlated with increased primary astrocyte proliferation. Proliferative actions of both agonists were abolished by either inhibition of ERK1/2, Gβγ subunits or β‐arrestin 2, suggesting that both G protein‐dependent and ‐independent ERK pathways are required for this outcome.
Using Carnoy's Solution in Treatment of Keratocystic Odontogenic Tumor

Aim: The aim of this study was to assess the treatment of keratocystic odontogenic tumor using enucleation and Carnoy's solution with peripheral ostectomy. Materials and Methods: Twenty-nine patients (14 females and 15 males) with age range from 12 to 62 years were included in this study and followed up for 7 years; all the patients were treated in the Department of Oral and Maxillofacial Surgery of the Specialized Surgeries Teaching Hospital (Al-Shaheed Ghazi Al-Hariri Hospital-Medical City, Baghdad, Iraq). Enucleation followed by peripheral ostectomy and the application of Carnoy's solution is the standardized method of treatment. Results: This study showed (32.7%) unilocular radiolucency for the lesions (19.9%) as multilocular radiolucency. Furthermore, it showed that the recurrence rate by this method was 0% with a minimum neurosensory disturbance. Conclusion: The complications and morbidity originating from the application of Carnoy's solution occurred less frequently and were less serious than those associated with resection while the recurrence rate is 0% which is equal to the recurrence rate of resection.
Pulmonary lymphoepithelioma-like carcinoma: a Surveillance, Epidemiology, and End Results database analysis.

BACKGROUND Pulmonary lymphoepithelioma-like carcinoma (LELC) is one of the rare histological non-small cell lung cancers. Only a few case reports have been published. The knowledge of its characteristics and prognosis in western population is limited. Based on the data of the Surveillance, Epidemiology, and End Results database (SEER), an analysis was performed to fill the gap of our knowledge. METHODS Characteristics, treatment and outcomes of all pulmonary LELC patients was extracted both from the SEER database from 1973 to 2011 using SEER*Stat 8.2. 1 statistical analysis was performed using SPSS 16.0 and GraphPad Prism 5. RESULTS A total of 62 patients with pulmonary LELC are identified and analyzed. The median age at diagnosis is 65. Among them, the majority was male (64.4%). Early stage patients account for the largest proportion (67.8%). The median survival of all LELC patients is 107 months [95% confidence interval (CI), 67-147]. The 1, 3 and 5 years survival rates of LELC are 85.6%, 74.5% and 55.2%. In the comparisons incorporating with other types of large cell lung cancer (LCC), adenocarcinoma (AD) and squamous cell lung cancer (SQ), the overall survival (OS) of LELC is superior to others. Most of the early stage (localized and regional) LELC patients (37/45, 82.2%) received surgical resection as the primary treatment. Patients older than 65 years predicted a worse prognosis. CONCLUSIONS Pulmonary LELC is a rare pathological type of lung cancer. In this cohort, most LELC cases were male and in early stage. Majority of early stage LELC patients have received surgical resection. Patients older than 65 years had worse survival. Unfortunately, no other prognostic factor has been identified in our study. In addition, we observed that LELC had an ideal prognosis comparing to other types of LCC, AD and SQ. In order to understand pulmonary LELC more thoroughly, more cases are required.
A Reply to Commentaries on “How the Object of Affect Guides its Impact”

Commentaries focused on the emotional appraisal part of our article. Cunningham and Van Bavel argued for distinguishing core disgust from moral disgust, and we describe how the theory might accommodate their proposal. They also suggested that temporal and other comparisons could account for emotional variety. We concur, but see such comparisons as inherent in the different emotional objects. Winkielman emphasized unconscious affect, but we suggest its power flows from the absence of situational constraints on its meaning. He characterized our appraisal model as coldly cognitive rather than embodied, but the complaint is misdirected, as the model addresses emotional structure, not emotional process. Indeed, embodied accounts will still require structural accounts to determine why one emotion rather than another is elicited.
The Effect of Market Leadership in Business Process Innovation: The Case(s) of E-Business Adoption

This paper empirically investigates how market leadership influences firm propensity to adopt new business process innovations. Using a unique data set spanning roughly 35,000 plants in 86 U.S. manufacturing industries, I study the adoption of frontier e-business practices during the early diffusion of the commercial internet. Theory predicts that firms with greater market share will be more likely to adopt innovations that build on their existing strengths, while they will resist more radical technological advances. While prior work primarily focuses on product innovation, I extend the logic into the business process setting to find that leaders were far more likely to adopt the incremental innovation of internet-based e-buying. However, they were commensurately less likely to adopt the more strategically sensitive and complex practice of e-selling. This pattern is remarkably robust, holding across a wide range of industries and controlling for factors such as productivity and related technological capabilities. The results are explicated by a framework I develop for understanding the drivers of this behavior and making it possible to classify business process innovations as radical or not. While greater market share promotes adoption of all types of business process innovations, this effect is outweighed by additional co-invention and coordination costs whenever a technological advance address strategically sensitive and complex business processes that must also span the firm boundary.
Profiling-Based Indoor Localization Schemes

In this paper, we consider the indoor localization problem, i.e., identifying the Cartesian coordinates of an object or a person under the roof. To solve this problem we consider an RF-based localization method called profiling, a two-step process, where a radio map of the monitored area is first constructed by collecting signal strength from known locations. An unknown location is then predicted using this radio map as a reference. In this paper, we first propose a K nearest neighbor (KNN) profiling-based localization method dubbed LEMON (location estimation by mining oversampled neighborhoods). It is based on a low-cost, low-power wireless devices and ensures good accuracy compared to the state-of-the-art. We then propose a variant of LEMON called combinatorial localization which exhaustively searches for the best possible set of nearest neighbors. We further define a Bayesian network model for the same localization problem. The performance of these methods is evaluated through extensive experiments in various indoor areas. We found an interesting outcome that the simple KNN-based approach can offer better localization accuracy compared to other complex localization methods. Thus we further enhance the performance of the KNN-based approach using multiple RF channels.
The Influence of the Hatching Factor on the Water Uptake of the Second Stage Larva of the Potato Cyst Nematode Heterodera Rostochiensis

1. Larvae-containing eggs of the potato cyst nematode were soaked in root diffusate in artificial tap water or in artificial tap water alone. In one experiment, the eggs were still contained in intact cysts; in another experiment they were in a halved cyst. 2. Eggs were ruptured after 0–5 days treatment and the water content of the liberated larvae immediately estimated by interference microscopy. 3. Larvae from treated eggs from both the halved and intact cysts had a higher water content than controls. 4. Larvae liberated from treated eggs from the halved cyst reached their maximum water content after 24 h treatment; those from intact cysts attained the same value after 2 days. The delay, for the intact cyst, is in keeping with the hatching response for intact cysts and supports the view that the results for water content are due to the activity of the hatching factor. 5. Reasons are advanced for the view that the hatching factor may work via a neurosecretory mechanism.
Inexperience and experience with online stores: the importance of TAM and trust

An e-vendor's website inseparably embodies an interaction with the vendor and an interaction with the IT website interface. Accordingly, research has shown two sets of unrelated usage antecedents by customers: (1) customer trust in the e-vendor and (2) customer assessments of the IT itself, specifically the perceived usefulness and perceived ease-of-use of the website as depicted in the technology acceptance model (TAM). Research suggests, however, that the degree and impact of trust, perceived usefulness, and perceived ease of use change with experience. Using existing, validated scales, this study describes a free-simulation experiment that compares the degree and relative importance of customer trust in an e-vendor vis-a-vis TAM constructs of the website, between potential (i.e., new) customers and repeat (i.e., experienced) ones. The study found that repeat customers trusted the e-vendor more, perceived the website to be more useful and easier to use, and were more inclined to purchase from it. The data also show that while repeat customers' purchase intentions were influenced by both their trust in the e-vendor and their perception that the website was useful, potential customers were not influenced by perceived usefulness, but only by their trust in the e-vendor. Implications of this apparent trust-barrier and guidelines for practice are discussed.