Miracle-dz/UniFAR-FTUs huggingface dataset:
Aging in a dish: Age‐dependent changes of neuronal survival, protein oxidation, and creatine kinase BB expression in long‐term hippocampal cell culture

Results from different experimental systems demonstrate that increased oxidative damage plays a role in normal aging and age‐associated pathology. In the current study, long‐term cultures of hippocampal neurons were examined as a model system. It was established that neuronal survival in long‐term culture decreases according to the Gompertz law and that neuronal “aging in the dish” is associated with increased oxidative damage of cell proteins. The increase of protein carbonyl formation in aged neurons was demonstrated both by Western blot analysis for oxidized proteins and by in situ immunocytochemical method, which was developed to analyze protein oxidation in fixed cells. In aging neuronal cultures, a gradual increase in creatine kinase (CK) content but decreased activity of enzyme per immunoreactive protein was found, suggesting the accumulation of inactive CK molecules. The increase in CK content was not a result of generalized protein elevation, since analysis of β‐actin content showed a time‐dependent loss, probably reflecting decreased number of cellular processes with aging. These findings, showing “aging in a dish,” consistent with the notion that aging is associated with increased protein oxidation, provide a system for study of age‐related neurodegenerative disorders associated with oxidative stress. J. Neurosci. Res. 58:308–317, 1999. © 1999 Wiley‐Liss, Inc.
Toll-Like Receptor 2 Is Required for Inflammatory Responses to Francisella tularensis LVS

ABSTRACT Francisella tularensis, a gram-negative bacterium, is the etiologic agent of tularemia and has recently been classified as a category A bioterrorism agent. Infections with F. tularensis result in an inflammatory response that plays an important role in the pathogenesis of the disease; however, the cellular mechanisms mediating this response have not been completely elucidated. In the present study, we determined the role of Toll-like receptors (TLRs) in mediating inflammatory responses to F. tularensis LVS, and the role of NF-κB in regulating these responses. Stimulation of bone marrow-derived dendritic cells from C57BL/6 wild-type (wt) and TLR4−/− but not TLR2−/− mice, with live F. tularensis LVS elicited a dose-dependent increase in the production of tumor necrosis factor alpha. F. tularensis LVS also induced in a dose-dependent manner an up-regulation in the expression of the costimulatory molecules CD80 and CD86 and of CD40 and the major histocompatibility complex class II molecules on dendritic cells from wt and TLR4−/− but not TLR2−/− mice. TLR6, not TLR1, was shown to be involved in mediating the inflammatory response to F. tularensis LVS, indicating that the functional heterodimer is TLR2/TLR6. Stimulation of dendritic cells with F. tularensis resulted in the activation of NF-κB, which resulted in a differential effect on the production of pro- and anti-inflammatory cytokines. Taken together, our results demonstrate the role of TLR2/TLR6 in the host's inflammatory response to F. tularensis LVS in vitro and the regulatory function of NF-κB in modulating the inflammatory response.
Sequential Effects in Essay Ratings: Evidence of Assimilation Effects Using Cross-Classified Models

Writing assessments are an indispensable part of most language competency tests. In our research, we used cross-classified models to study rater effects in the real essay rating process of a large-scale, high-stakes educational examination administered in China in 2011. Generally, four cross-classified models are suggested for investigation of rater effects: (1) the existence of sequential effects, (2) the direction of the sequential effects, and (3) differences in raters by their individual characteristics. We applied these models to the data to account for possible cluster effects caused by the application of multiple rating strategies. The results of our research showed that raters demonstrated sequential effects during the rating process. In contrast to many other studies on rater effects, our study found that raters exhibited assimilation effects. The more experienced, lenient, and qualified raters were less susceptible to assimilation effects. In addition, our research demonstrated the feasibility and appropriateness of using cross-classified models in assessing rater effects for such data structures. This paper also discusses the implications for educators and practitioners who are interested in reducing sequential effects in the rating process, and suggests directions for future research.
Correlations between social-emotional feelings and anterior insula activity are independent from visceral states but influenced by culture

The anterior insula (AI) maps visceral states and is active during emotional experiences, a functional confluence that is central to neurobiological accounts of feelings. Yet, it is unclear how AI activity correlates with feelings during social emotions, and whether this correlation may be influenced by culture, as studies correlating real-time AI activity with visceral states and feelings have focused on Western subjects feeling physical pain or basic disgust. Given psychological evidence that social-emotional feelings are cognitively constructed within cultural frames, we asked Chinese and American participants to report their feeling strength to admiration and compassion-inducing narratives during fMRI with simultaneous electrocardiogram recording. Trial-by-trial, cardiac arousal and feeling strength correlated with ventral and dorsal AI activity bilaterally but predicted different variance, suggesting that interoception and social-emotional feeling construction are concurrent but dissociable AI functions. Further, although the variance that correlated with cardiac arousal did not show cultural effects, the variance that correlated with feelings did. Feeling strength was especially associated with ventral AI activity (the autonomic modulatory sector) in the Chinese group but with dorsal AI activity (the visceral-somatosensory/cognitive sector) in an American group not of Asian descent. This cultural group difference held after controlling for posterior insula (PI) activity and was replicated. A bi-cultural East-Asian American group showed intermediate results. The findings help elucidate how the AI supports feelings and suggest that previous reports that dorsal AI activation reflects feeling strength are culture related. More broadly, the results suggest that the brain's ability to construct conscious experiences of social emotion is less closely tied to visceral processes than neurobiological models predict and at least partly open to cultural influence and learning.
Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability

Episodic ataxia type 1 (EA1) is an autosomal dominant central nervous system potassium channelopathy characterized by brief attacks of cerebellar ataxia and continuous interictal myokymia. Point mutations in the voltage‐gated potassium channel gene KCNA1 on chromosome 12p associate with EA1. We have studied 4 families and identified three new and one previously reported heterozygous point mutations in this gene. Affected members in Family A (KCNA1 G724C) exhibit partial epilepsy and myokymia but no ataxic episodes, supporting the suggestion that there is an association between mutations of KCNA1 and epilepsy. Affected members in Family B (KCNA1 C731A) exhibit myokymia alone, suggesting a new phenotype of isolated myokymia. Family C harbors the first truncation to be reported in KCNA1 (C1249T) and exhibits remarkably drug‐resistant EA1. Affected members in Family D (KCNA1 G1210A) exhibit attacks typical of EA1. This mutation has recently been reported in an apparently unrelated family, although no functional studies were attempted. Heterologous expression of the proteins encoded by the mutant KCNA1 genes suggest that the four point mutations impair delayed‐rectifier type potassium currents by different mechanisms. Increased neuronal excitability is likely to be the common pathophysiological basis for the disease in these families. The degree and nature of the potassium channel dysfunction may be relevant to the new phenotypic observations reported in this study. Ann Neurol 2000;48:647–656
Design of Class-E $_{\rm M}$ Oscillator With Second Harmonic Injection

This paper presents the class-EM oscillator with the second-harmonic injection current, along with its design procedure, design curves, and design example. In the proposed oscillator, the output frequency of the proposed oscillator is locked with the input frequency of the injection circuit. Additionally, the switch-voltage and switch-current waveforms in the main circuit achieve the class-EM zero-voltage switching, zero-voltage-derivative switching, zero-current switching, and zero-current-derivative switching (ZVS/ZVDS/ZCS/ZCDS) conditions and the switch voltage waveform in the injection circuit satisfied the class-E ZVS/ZDS conditions. In the laboratory experiment, the oscillator achieved 92.0% power-conversion efficiency at 34.8 W output power and 1 MHz operating frequency. The experimental results agreed with the numerical predictions quantitatively, which denotes the validity of the design procedure.
HOXA5 and p53 cooperate to suppress lung cancer cell invasion and serve as good prognostic factors in non-small cell lung cancer

Lung cancer is the leading cause of cancer mortality worldwide and tumor metastasis is the major cause of cancer-related death. Our previous study suggested that Homeobox A5 (HOXA5) could inhibit lung cancer cell invasion via regulating cytoskeletal remodeling and involved in tumor metastasis. Recently, consensus HOX binding sites was found in the p53 gene promoter region. However, whether the HOXA5 could cooperate with p53 and contribute the inhibition of lung cancer cell invasion is still unclear. The aim of the current study is to elucidate the correlation of HOXA5 and p53 in tumor invasion and its prognostic influence in lung cancer patient specimens. Totally 71 cases of primary non-small cell lung cancer (NSCLC) were collected. The median follow-up period is 6.8 years. Immunohistochemical stain for p53 and HOXA5 were performed. Kaplan-Meier plot was done for overall survival analysis. In addition, lung cancer cell lines transfected with wild-type or mutated p53 constructs were overexpressed with HOXA5 for invasion assay. In human specimens, HOXA5 expressed mainly in the cytoplasm (54.1%) rather than nuclei (14.6%) of the NSCLC tumor part. The HOXA5 expression is higher in adenocarcinoma than in squamous cell carcinoma (P < 0.001). In addition, poor prognosis is seen in group with both non-immunoreactive for p53 and HOXA5. HOXA5 and p53 could cooperate to inhibit tumor cell invasion significantly partly by decreasing MMP2 activity in a concentration-dependent manner. Our studies provide new insights into how HOXA5 and p53 cooperate to contribute to the suppression of lung cancer cell invasion and play good prognostic roles in NSCLC.
Extreme Conservation Leads to Recovery of the Virunga Mountain Gorillas

As wildlife populations are declining, conservationists are under increasing pressure to measure the effectiveness of different management strategies. Conventional conservation measures such as law enforcement and community development projects are typically designed to minimize negative human influences upon a species and its ecosystem. In contrast, we define “extreme” conservation as efforts targeted to deliberately increase positive human influences, including veterinary care and close monitoring of individual animals. Here we compare the impact of both conservation approaches upon the population growth rate of the critically endangered Virunga mountain gorillas (Gorilla beringei beringei), which increased by 50% since their nadir in 1981, from approximately 250 to nearly 400 gorillas. Using demographic data from 1967–2008, we show an annual decline of 0.7%±0.059% for unhabituated gorillas that received intensive levels of conventional conservation approaches, versus an increase 4.1%±0.088% for habituated gorillas that also received extreme conservation measures. Each group of habituated gorillas is now continuously guarded by a separate team of field staff during daylight hours and receives veterinary treatment for snares, respiratory disease, and other life-threatening conditions. These results suggest that conventional conservation efforts prevented a severe decline of the overall population, but additional extreme measures were needed to achieve positive growth. Demographic stochasticity and socioecological factors had minimal impact on variability in the growth rates. Veterinary interventions could account for up to 40% of the difference in growth rates between habituated versus unhabituated gorillas, with the remaining difference likely arising from greater protection against poachers. Thus, by increasing protection and facilitating veterinary treatment, the daily monitoring of each habituated group contributed to most of the difference in growth rates. Our results argue for wider consideration of extreme measures and offer a startling view of the enormous resources that may be needed to conserve some endangered species.
Transverse Tripolar Spinal Cord Stimulation: Results of an International Multicenter Study

Experienced neurosurgeons at eight spinal cord stimulation centers in the United States, Canada, and Europe participated in a study from 1997 to 2000 investigating the safety, performance, and efficacy of a Transverse Tripolar Stimulation (TTS) system invented at the University of Twente, the Netherlands. This device was proposed to improve the ability of spinal cord stimulation to adequately overlap paresthesia to perceived areas of pain. Fifty‐six patients with chronic, intractable neuropathic pain of the trunk and/or limbs more than three months’ duration (average 105 months) were enrolled with follow‐up periods at 4, 12, 26, and 52 weeks. All patients had a new paddle‐type lead implanted with four electrodes, three of them aligned in a row perpendicular to the cord. Fifteen of these patients did not undergo permanent implantation. Of the 41 patients internalized, 20 patients chose conventional programming using an implanted pulse generator to drive four electrodes, while 21 patients chose a tripole stimulation system, which used radiofrequency power and signal transmission and an implanted dual‐channel receiver to drive three electrodes using simultaneous pulses of independently variable amplitude. On average, the visual analog scale scores dropped more for patients with TTS systems (32%) than for conventional polarity systems (16%). Conventional polarity systems were using higher frequencies on average, while usage range was similar. Most impressive was the well‐controlled “steering” of the paresthesias according to the dermatomal topography of the dorsal columns when using the TTS‐balanced pulse driver. The most common complication was lead migration. While the transverse stimulation system produced acceptable outcomes for overall pain relief, an analysis of individual pain patterns suggests that it behaves like spinal cord stimulation in general with the best control of extremity neuropathic pain. This transverse tripole lead and driving system introduced the concept of electrical field steering by selective recruitment of axonal nerve fiber tracts in the dorsal columns.
3D printing of textile-based structures by Fused Deposition Modelling (FDM) with different polymer materials

3D printing is a form of additive manufacturing, i.e. creating objects by sequential layering, for pre-production or production. After creating a 3D model with a CAD program, a printable file is used to create a layer design which is printed afterwards. While often more expensive than traditional techniques like injection moulding, 3D printing can significantly enhance production times of small parts produced in small numbers, additionally allowing for large flexibility and the possibility to create parts that would be impossible to produce with conventional techniques. The Fused Deposition Modelling technique uses a plastic filament which is pushed through a heated extrusion nozzle melting the material. Depending on the material, different challenges occur in the production process, and the produced part shows different mechanical properties. The article describes some standard and novel materials and their influence on the resulting parts.
A Laboratory and Statistical Evaluation of Factors Affecting Rutting

This research identifies the most significant factors from those factors evaluated which affect rut potential of Hot-Mix Asphalt (HMA). Mixture rut potential is determined using an Asphalt Pavement Analyzer (APA) in the laboratory. The experimental program employed in this study consists of three sets of tests and each set represents a matrix whose elements are rut factors. In Set A, seven factors, each at two levels, are examined using a mixture of limestone aggregates designed in accordance with Superpave method. The test results are analyzed statistically. The analysis results presented using Set A show that binder's performance grade (PG), specimen type, test temperature and moisture in test specimen affect a mixture's rutting performance significantly. Wheel load, asphalt content and hose pressure at the selected levels in Set A are shown to be less significant. In Set B six factors, aggregate gradation, temperature, moisture, asphalt content, load and hose pressure, are investigated using one Hveem designed mixture with gravel aggregates. Gradation, temperature, asphalt content and moisture are found to be significant. The levels of asphalt content selected for Set B to be one at optimum and the other at one percent more than the optimum asphalt content. Similar results are found for the test Set C with five factors, temperature, gradation, moisture, load and hose pressure. A predicted rut depth and its range under the influence of the significant factors studied in Set A are also determined and verified by additional experiments. The paper developed and described a detail statistical procedure to analyze a designed experimental program to interpret test results without the need for a full factorial approach.
Analysis of association of TaqI VDR gene polymorphism with the chronic periodontitis in Dravidian ethnicity

AIM: The aim of this study is to analyze the association of TaqI vitamin D receptor (VDR) gene polymorphism with the chronic periodontitis (CP) in Dravidian ethnicity. MATERIALS AND METHODS: A total of 120 subjects were recruited for this study, which included 60 CP and 60 healthy controls. TaqI VDR gene polymorphism was analyzed using specific primers and amplified by polymerase chain reaction (PCR) and visualized under 2% agarose gel. RESULTS: Our study results showed that Tt and tt genotype had a higher frequency of occurrence in CP compared with controls. Similarly, t allele was found to be associated with CP. CONCLUSION: Our study concludes that TaqI VDR gene polymorphism is associated with CP in Dravidian ethnicity.
Stimulus-Induced and State-Dependent Sustained Gamma Activity Is Tightly Coupled to the Hemodynamic Response in Humans

A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive investigation of stimulus–response processing through noninvasive imaging, it is, however, a crucial issue whether both kinds of gamma modulation elicit a hemodynamic response. Here, we show that, in the human visual cortex, stimulus strength and internal state modulate sustained gamma activity and hemodynamic response in close correspondence. When participants reported velocity changes of gratings varying in contrast, gamma activity (35–70 Hz) increased systematically with contrast. For stimuli of constant contrast, the amplitude of gamma activity before the behaviorally relevant velocity change was inversely correlated to the behavioral response latency. This indicates that gamma activity also reflects an overall attentive state. For both sources of variance, gamma activity was tightly coupled to the hemodynamic response measured through optical topography. Because of the close relationship between high-frequency neuronal activity and the hemodynamic signal, we conclude that both stimulus-induced and state-dependent gamma activity trigger a metabolic demand and are amenable to vascular-based imaging.
Size differences of Arctic marine protists between two climate periods—using the paleoecological record to assess the importance of within‐species trait variation

Abstract Mean body size decreases with increasing temperature in a variety of organisms. This size–temperature relationship has generally been tested through space but rarely through time. We analyzed the sedimentary archive of dinoflagellate cysts in a sediment record taken from the West Greenland shelf and show that mean cell size decreased at both intra‐ and interspecific scales in a period of relatively warm temperatures, compared with a period of relatively cold temperatures. We further show that intraspecific changes accounted for more than 70% of the change in community mean size, whereas shifts in species composition only accounted for about 30% of the observed change. Literature values on size ranges and midpoints for individual taxa were in several cases not representative for the measured sizes, although changes in community mean size, calculated from literature values, did capture the direction of change. While the results show that intraspecific variation is necessary to accurately estimate the magnitude of change in protist community mean size, it may be possible to investigate general patterns, that is relative size differences, using interspecific‐level estimates.
Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects.

BACKGROUND Information regarding the safety of selective serotonin-reuptake inhibitors (SSRIs) in human pregnancy is sparse. Concern has been raised about the risk of congenital heart defects associated with the use of SSRIs in pregnancy. METHODS We obtained data on 9622 case infants with major birth defects and 4092 control infants born from 1997 through 2002 from the National Birth Defects Prevention Study. Case infants were ascertained through birth-defects surveillance systems in eight U.S. states; controls were selected randomly from the same geographic areas. Mothers completed a standardized telephone interview regarding exposure to potential risk factors, including medications, before and during pregnancy. Exposure to SSRIs was defined as treatment with any SSRI from 1 month before to 3 months after conception. Birth defects were assigned to 26 categories and subcategories. RESULTS There were no significant associations between maternal use of SSRIs overall during early pregnancy and congenital heart defects or most other categories or subcategories of birth defects. Maternal SSRI use was associated with anencephaly (214 infants, 9 exposed; adjusted odds ratio, 2.4; 95% confidence interval [CI], 1.1 to 5.1), craniosynostosis (432 infants, 24 exposed; adjusted odds ratio, 2.5; 95% CI, 1.5 to 4.0), and omphalocele (181 infants, 11 exposed; adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.7). CONCLUSIONS Maternal use of SSRIs during early pregnancy was not associated with significantly increased risks of congenital heart defects or of most other categories of birth defects. Associations were observed between SSRI use and three types of birth defects, but the absolute risks were small, and these observations require confirmation by other studies.