Miracle-dz/UniFAR-FTUs huggingface dataset:
The Sphingosine-1-Phosphate Modulator FTY720 Targets Multiple Myeloma via the CXCR4/CXCL12 Pathway

Purpose: To explore the functional consequences of possible cross-talk between the CXCR4/CXCL12 and the sphingosine-1-phosphate (S1P) pathways in multiple myeloma (MM) cells and to evaluate the effect of S1P targeting with the FTY720 modulator as a potential anti-MM therapeutic strategy. Experimental Design and Results: S1P targeting with FTY720 induces MM cell apoptosis. The combination of FTY720 with the SPHK1 inhibitor SKI-II results in synergistic inhibition of MM growth. CXCR4/CXCL12-enhanced expression correlates with reduced MM cell sensitivity to both FTY720 and SKI-II inhibitors, and with SPHK1 coexpression in both cell lines and primary MM bone marrow (BM) samples, suggesting regulative cross-talk between the CXCR4/CXCL12 and SPHK1 pathways in MM cells. FTY720 was found to directly target CXCR4. FTY720 profoundly reduces CXCR4 cell-surface levels and abrogates the CXCR4-mediated functions of migration toward CXCL12 and signaling pathway activation. Moreover, FTY720 cooperates with bortezomib, inducing its cytotoxic activity and abrogating the bortezomib-mediated increase in CXCR4 expression. FTY720 effectively targets bortezomib-resistant cells and increases their sensitivity to bortezomib, promoting DNA damage. Finally, in a recently developed novel xenograft model of CXCR4-dependent systemic MM with BM involvement, FTY720 treatment effectively reduces tumor burden in the BM of MM-bearing mice. FTY720 in combination with bortezomib demonstrates superior tumor growth inhibition and abrogates bortezomib-induced CXCR4 increase on MM cells. Conclusions: Altogether, our work identifies a cross-talk between the S1P and CXCR4 pathways in MM cells and provides a preclinical rationale for the therapeutic application of FTY720 in combination with bortezomib in patients with MM. Clin Cancer Res; 23(7); 1733–47. ©2016 AACR.
Positive Feedback From Male Authority Figures Boosts Women’s Math Outcomes

People often search for cues in the environment to determine whether or not they will be judged or treated negatively based on their social identities. Accordingly, feedback from gatekeepers—members of majority groups who hold authority and power in a field—may be an especially important cue for those at risk of experiencing social identity threat, such as women in math settings. Across a series of studies, women who received positive (“Good job! ”) versus objective (score only) feedback from a male (vs. female) authority figure in math reported greater confidence; belonging; self-efficacy; more favorable Science, Technology, Engineering, and Mathematics (STEM) attitudes/identification/interest; and greater implicit identification with math. Men were affected only by the type of math feedback they received, not by the source of feedback. A meta-analysis across studies confirmed results. Together, these findings suggest that positive feedback from gatekeepers is an important situational cue that can improve the outcomes of negatively stereotyped groups.
Evaluation of the fossil fish‐specific diversity in a chadian continental assemblage: Exploration of morphological continuous variation in Synodontis (Ostariophysi, Siluriformes)

In the fossil record, the quantification of continuous morphological variation has become a central issue when dealing with species identification and speciation. In this context, fossil taxa with living representatives hold great promise, because of the potential to characterise patterns of intraspecific morphological variation in extant species prior to any interpretation in the fossil record. The vast majority of catfish families fulfil this prerequisite, as most of them are represented by extant genera. However, although they constitute a major fish group in terms of distribution, and ecological and taxonomic diversity, the quantitative study of their past morphological variation has been neglected, as fossil specimens are generally identified based on the scarcest remains, that is, complete neurocrania that bear discrete characters. Consequently, a part of freshwater catfish history is unprospected and unknown. In this study, we explored the morphological continuous variation of the humeral plate shape in Synodontis catfishes using Elliptic Fourier Analysis (EFA), and compared extant members and fossil counterparts. We analysed 153 extant specimens of 11 Synodontis species present in the Chad basin, in addition to 23 fossil specimens from the Chadian fossiliferous area of Toros Menalla which is dated around 7 Ma. This highly speciose genus, which is one of the most diversified in Africa, exhibits a rich fossil record with several hundred remains mostly identified as Synodontis sp. The analysis of the outline of the humeral plate reveals that some living morphological types were already represented in the Chad Basin 7 My ago, and allows for the discovery of extinct species. Beside illuminating the complex Neogene evolutionary history of Synodontis, these results underline the interest in the ability of isolated remains to reconstruct a past dynamic history and to validate the relevance of EFA as a tool to explore specific diversity through time. J. Morphol. 277:1486–1496, 2016. © 2016 Wiley Periodicals, Inc.
Lack of viral control and development of combination antiretroviral therapy escape mutations in macaques after bone marrow transplantation

Objective:We have previously demonstrated robust control of simian/human immunodeficiency virus (SHIV1157-ipd3N4) viremia following administration of combination antiretroviral therapy (cART) in pigtailed macaques. Here, we sought to determine the safety of hematopoietic stem cell transplantation (HSCT) in cART-suppressed and unsuppressed animals. Design:We compared disease progression in animals challenged with SHIV 100 days post-transplant, to controls that underwent transplant following SHIV challenge and stable cART-dependent viral suppression. Methods:SHIV viral load, cART levels, and anti-SHIV antibodies were measured longitudinally from plasma/serum from each animal. Flow cytometry was used to assess T-cell subset frequencies in peripheral blood and the gastrointestinal tract. Deep sequencing was used to identify cART resistance mutations. Results:In control animals, virus challenge induced transient peak viremia, viral set point, and durable suppression by cART. Subsequent HSCT was not associated with adverse events in these animals. Post-transplant animals were challenged during acute recovery following HSCT, and displayed sustained peak viremia and cART resistance. Although post-transplant animals had comparable plasma levels of antiretroviral drugs and showed no evidence of enhanced infection of myeloid subsets in the periphery, they exhibited a drastic reduction in virus-specific antibody production and decreased T-cell counts. Conclusions:These results suggest that virus challenge prior to complete transplant recovery impairs viral control and may promote drug resistance. These findings may also have implications for scheduled treatment interruption studies in patients on cART during post-HSCT recovery: premature scheduled treatment interruption could similarly result in lack of viral control and cART resistance.
Kefir Peptides Prevent Hyperlipidemia and Obesity in High‐Fat‐Diet‐Induced Obese Rats via Lipid Metabolism Modulation

SCOPE Obesity has reached epidemic proportions worldwide. Obesity is a complex metabolic disorder that is linked to numerous serious health complications with high morbidity. The present study evaluated the effects of kefir peptides on high fat diet (HFD)-induced obesity in rats. METHODS AND RESULTS Kefir peptides markedly improved obesity, including body weight gain, inflammatory reactions and the formation of adipose tissue fat deposits around the epididymis and kidney, and adipocyte size. Treating high fat diet (HFD)-induced obese rats with kefir peptides significantly reduced the fatty acid synthase protein and increased the p-acetyl-CoA carboxylase protein to block lipogenesis in the livers. Kefir peptides also increased fatty acid oxidation by increasing the protein expressions of phosphorylated AMP-activated protein kinase, peroxisome proliferator-activated receptor-α, and hepatic carnitine palmitoyltransferase-1 in the livers. In addition, administration of kefir peptides significantly decreased the inflammatory response (TNF-α, IL-1β, and TGF-β) to modulate oxidative damage. CONCLUSION These results demonstrate that kefir peptides treatment improves obesity via inhibition of lipogenesis, modulation of oxidative damage, and stimulation of lipid oxidation. Therefore, kefir peptides may act as an anti-obesity agent to prevent body fat accumulation and obesity-related metabolic diseases.
Cholinergic modulation of the parafacial respiratory group

This study investigates the effects of cholinergic transmission on the expiratory oscillator, the parafacial respiratory group (pFRG) in urethane anaesthetized adult rats. Local inhibition of the acetyl cholinesterase enzyme induced activation of expiratory abdominal muscles and active expiration. Local application of the cholinomimetic carbachol elicited recruitment of late expiratory neurons, expiratory abdominal muscle activity and active expiration. This effect was antagonized by local application of the muscarinic antagonists scopolamine, J104129 and 4DAMP. We observed distinct physiological responses between the more medial chemosensitive region of the retrotrapezoid nucleus and the more lateral region of pFRG. These results support the hypothesis that pFRG is under cholinergic neuromodulation and the region surrounding the facial nucleus contains a group of neurons with distinct physiological roles.
Machine learning, social learning and the governance of self-driving cars

Self-driving cars, a quintessentially ‘smart’ technology, are not born smart. The algorithms that control their movements are learning as the technology emerges. Self-driving cars represent a high-stakes test of the powers of machine learning, as well as a test case for social learning in technology governance. Society is learning about the technology while the technology learns about society. Understanding and governing the politics of this technology means asking ‘Who is learning, what are they learning and how are they learning? ’ Focusing on the successes and failures of social learning around the much-publicized crash of a Tesla Model S in 2016, I argue that trajectories and rhetorics of machine learning in transport pose a substantial governance challenge. ‘Self-driving’ or ‘autonomous’ cars are misnamed. As with other technologies, they are shaped by assumptions about social needs, solvable problems, and economic opportunities. Governing these technologies in the public interest means improving social learning by constructively engaging with the contingencies of machine learning.
Yes, health is important, but as much for its importance via social life: The direct and indirect effects of health on subjective well‐being in chronically ill individuals

There is an increasing evidence that health-related quality of life, income, and social relationships are important to our subjective well-being (SWB). Little is known, however, about the specific indirect pathways that link health to SWB via social relationships and income. On the basis of a unique data set of 7 disease groups from 6 OECD-countries (N = 6,173), we investigate the direct and indirect effects of health on SWB by using structural equation modeling. Three alternative measures of health are used: For generic instruments (EQ-5D-5L; SF-6D), the total indirect effect was stronger (0.226; 0.249) than its direct effect (0.157; 0.205). For the visual analogue scale, the direct effect was stronger (0.322) than its total indirect effect (0.179). Most of the indirect effect of improved health on SWB transmitted through social relationships. The effect via income was small. Nevertheless, the presence of unmeasured confounders may bias the estimates. An important lesson for researchers is to include meaningful items on social relationships when measuring the benefits from improved health. An important lesson for policy makers is that social isolation appears to be more detrimental to overall well-being than ill health. Hence, the Health and Care Services should facilitate social arenas for people with chronic conditions.
Correlation between Anterior Chamber IgG/Albumin Concentrations and Laser Flare Photometry in Eyes with Endogenous Uveitis

Purpose: To assess the correlation between laser flare measurements and anterior chamber IgG/albumin concentrations in eyes with mild to severe inflammation. Materials and Methods: Seventeen eyes of 17 patients with endogenous uveitis underwent diagnostic paracentesis. IgG and albumin concentrations were determined from the samples of aqueous humor. Laser flare measurements were performed 1 h prior to paracentesis. The relationship between flare measurements and IgG/albumin concentrations was studied be plotting the data on a logarithmic scale. Results: The flare measurement was 97.5±150.0 photons ms (mean ± SD; range 4.3–528.7). The IgG concentration was 41.0±51.4 mg/dl mean ± SD; range 0.2–200). The albumin concentration was 184.6±196.2 mg/dl (mean ± SD; range 4–535). When plotted on a logarithmic scale, there was a statistically significant linear relationship between the flare measurements and the anterior chamber IgG or albumin concentrations (y = 1.14x–0.64, r = 0.87, p < 0.001 for IgG; y = 1.39x–0.1, r = 0.94, p < 0.001 for albumin). Conclusion: Laser flare photometry is an accurate technique for assessing anterior chamber inflammation. Flare measurements strongly correlate with blood-aqueous barrier breakdown.
Empirical Profiles of Alcohol and Marijuana Use, Drugged Driving, and Risk Perceptions.

OBJECTIVE The present study sought to inform models of risk for drugged driving through empirically identifying patterns of marijuana use, alcohol use, and related driving behaviors. Perceived dangerousness and consequences of drugged driving were evaluated as putative influences on risk patterns. METHOD We used latent profile analysis of survey responses from 897 college students to identify patterns of substance use and drugged driving. We tested the hypotheses that low perceived danger and low perceived likelihood of negative consequences of drugged driving would identify individuals with higher-risk patterns. RESULTS Findings from the latent profile analysis indicated that a four-profile model provided the best model fit. Low-level engagers had low rates of substance use and drugged driving. Alcohol-centric engagers had higher rates of alcohol use but low rates of marijuana/simultaneous use and low rates of driving after substance use. Concurrent engagers had higher rates of marijuana and alcohol use, simultaneous use, and related driving behaviors, but marijuana-centric/simultaneous engagers had the highest rates of marijuana use, co-use, and related driving behaviors. Those with higher perceived danger of driving while high were more likely to be in the low-level, alcohol-centric, or concurrent engagers' profiles; individuals with higher perceived likelihood of consequences of driving while high were more likely to be in the low-level engagers group. CONCLUSIONS Findings suggested that college students' perceived dangerousness of driving after using marijuana had greater influence on drugged driving behaviors than alcohol-related driving risk perceptions. These results support targeting marijuana-impaired driving risk perceptions in young adult intervention programs.
Localization of subthalamic nucleus from microelectrode recordings with k-means clustering

OF THE THESIS Localization of Subthalamic Nucleus From Microelectrode Recordings with K-Means Clustering by FAN YANG Thesis Director: Prof. Konstantinos Michmizos Background: Microelectrode recordings (MERs) of the neural activities are a useful tool for subthalamic nucleus localization (STN) in the process of deep brain stimulation (DBS) surgery for neurological and neuropsychiatric disorders, like Parkinson’s disease. Currently, the localization of STN relies on manual demarcation performed by a neurophysiologist. It is also difficult to give an exact detection of the STN borders, especially the one between the STN and the substantia nigra pars reticulata (SNr). As a result, investigators are looking for a multi-feature machine learning method for accurate automated STN localization. We used K-means clustering and a novel set of features that are based on a combination of spike-based and spike independent metrics to address these shortcomings. Methods: We extracted 18 computational features from 31 bandpass filtered (0.5 kHz 8 kHz) MERs of 20 patients who underwent DBS implantation surgery. 12 of these 18 features were spike-based and the other 6 were spike independent. Square root transformation was performed on those positively skewed features. All features were standardized and normalized to scale [0, 1]. We additionally integrated a depth vector into the original feature matrix. The newly formed feature matrix was fed into the k-means clustering algorithm. K was chosen to be 4 because the trajectories, under
Performance of an anaerobic membrane bioreactor in which granular sludge and dynamic filtration are integrated

Abstract To alleviate the fouling of a filter, simple substrates, dynamic filtration, and granular sludge were applied in an anaerobic membrane bioreactor (AnMBR). The results showed that under a transmembrane pressure < 20 kPa, the filter flux ranged between 15 and 20 l (m−2 h)−1 for a period of 30 days. The flux was higher than the typical flux of AnMBRs with conventional membranes and most current dynamic filters. In addition, the low cost of the filter avoided the need for a higher flux. Moreover, a stable granular sludge bed, which consumed all volatile fatty acids, was maintained. A compact fouling/filtration layer formed on the filter, which contributed to low effluent chemical oxygen demand concentrations and turbidity. In addition, substrate scarcity in the filtration zone resulted in the evolution of diverse bacteria on the filter.
The Results of Trabeculectomy with and without Mitomycin C in Young Patients

The results of primary trabeculectomy with and without mitomycin C (MMC) were evaluated in young glaucoma patients. The patients, 15–40 years of age, were divided into two main groups and two subgroups. In group IA, primary Cairns type trabeculectomy was performed in 24 eyes of 24 patients with juvenile glaucoma; in group IB, trabeculectomy + MMC 0.4 mg/ml in 3 min was done in 20 eyes of 20 patients with juvenile glaucoma; in group IIA, primary trabeculectomy was performed in 20 eyes of 20 patients with developmental glaucoma, and in group IIB, trabeculectomy + MMC 0.4 mg/ml in 3 min was performed in 16 eyes of 16 patients with developmental glaucoma. The success rate of the surgery was 75% in group IA, 90% in group IB, 50% in group IIA, and 75% in group IIB. There was no statistically significant difference among the groups in terms of success rates of trabeculectomies (p > 0.05).
Hall Thrusters With Permanent Magnets: Current Solutions and Perspectives

We present a focused review of selected design solutions for the permanent magnet-based magnetic circuitry of Hall-type thrusters, with the emphasis on their relevance to miniaturized devices potentially suitable for application in CubeSats and other types of small satellites. Coaxial, cylindrical, and cusped designs of Hall-type thrusters are considered. The issues related to the influence of magnetic configurations on channel wear are also addressed. This paper also outlines a state of the art in the high-temperature permanent magnets and offers some perspective views onto the further development of miniaturized Hall-type thrusters. Several nontrivial design solutions are considered, and schematics of the potentially promising ones for the reduction of wear and damage were examined. Overall, this paper demonstrates the usability and several significant advantages of Hall thrusters with permanent magnetic system.
Microwave radiation enhances teratogenic effect of cytosine arabinoside in mice.

Impregnated Swiss mice were irradiated 2 h daily on days 1-18 of gestation in nonthermal (1 or 10 mW/cm2) or thermogenic (40 mW/cm2) 2,450-MHz microwave (MW) fields. On the 19th day of pregnancy all dams were killed to check the number of resorptions. Living fetuses were isolated, weighed and checked for the presence of macroscopically visible malformations of skeleton and cleft palate (CP) and/or lip (CLP). Some of the pregnant mice in each group were injected intraperitoneally on the 9th day of gestation with 10 mg/kg of cytosine arabinoside (ara-C), a well-known teratogen resulting under the above conditions in the appearance of about 15% (42 of 354) of resorbed implantation points and the development of CP or CLP in about 30% (96 of 312) of fetuses. Exposure to nonthermal MW fields during pregnancy did not lead to resorptions or detectable malformations; however, the body mass of 19-day fetuses was significantly lower than in sham-irradiated controls. MW hyperthermia (40 mW/cm2) applied during pregnancy led to an increased number of resorptions - about 25% (37 of 157) compared to 2% (6 of 306) in controls. Significant enhancement of the teratogenic potency of ara-C was observed after combined exposure to both ara-C and MWs during pregnancy. In dams treated with ara-C alone about 20% (62 of 358) resorptions and about 30% (91 of 296) fetuses with CL or CLP were found; additional exposure in MW fields (10 mW/cm2), not resulting per se in resorptions or detectable malformations, increased the numbers to 45% (213 of 448) of resorptions and to 70% (167 of 235) fetuses with CL or CLP. +
Design and manufacturing rules for maximizing the performance of polycrystalline piezoelectric bending actuators

Increasing the energy and power density of piezoelectric actuators is very important for any weight-sensitive application, and is especially crucial for enabling autonomy in micro/milli-scale robots and devices utilizing this technology. This is achieved by maximizing the mechanical flexural strength and electrical dielectric strength through the use of laser-induced melting or polishing, insulating edge coating, and crack-arresting features, combined with features for rigid ground attachments to maximize force output. Manufacturing techniques have also been developed to enable mass customization, in which sheets of material are pre-stacked to form a laminate from which nearly arbitrary planar actuator designs can be fabricated using only laser cutting. These techniques have led to a 70% increase in energy density and an increase in mean lifetime of at least 15× compared to prior manufacturing methods. In addition, measurements have revealed a doubling of the piezoelectric coefficient when operating at the high fields necessary to achieve maximal energy densities, along with an increase in the Young’s modulus at the high compressive strains encountered—these two effects help to explain the higher performance of our actuators as compared to that predicted by linear models.