Miracle-dz/UniFAR-FTUs huggingface dataset:
Triptolide Inhibits MDM 2 and Induces Apoptosis in Acute Lymphoblastic Leukemia Cells through a p 53-Independent Pathway

Triptolide, a natural product derived from the Chinese plant Tripterygium wilfordii, is reported to exhibit antitumor effects in a broad range of cancers. The antitumor activity of triptolide is associated with its biologic activities, as it inhibits various proproliferative or antiapoptotic factors that are dominantly expressed in given types of cancer cells. Herein, we show that triptolide induced apoptosis in a subgroup of acute lymphoblastic leukemia (ALL) cells overexpressing the MDM2 oncoprotein by inhibiting MDM2 expression. More specifically,we found that triptolide inhibitedMDM2at the transcriptional level by suppressing itsmRNAsynthesis. This MDM2 inhibition led in turn to increased levels of p53 protein; however, p53 functionality was not activated due to the fact that triptolide-treated cells lacked induction of p21 and PUMA as well as in G1 cellcycle arrest. Triptolide-mediated downregulation of MDM2 increased inhibition of X-linked inhibitor of apoptosis protein (XIAP), its translational target, in amannerdistinct fromreactions to cellular stress andDNAdamaging agent ionizing radiation that induce XIAP due to p53-activated MDM2. These results suggest that increased inhibition of XIAP due to downregulation of MDM2 may play a critical role in triptolide-induced apoptosis in MDM2-overexpressing cancers. Mol Cancer Ther; 12(2); 184–94. 2012 AACR.
Strategic female reproductive investment in response to male attractiveness in birds

Life-history theory predicts that individuals should adjust their reproductive effort according to the expected fitness returns on investment. Because sexually selected male traits should provide honest information about male genetic or phenotypic quality, females may invest more when paired with attractive males. However, there is substantial disagreement in the literature whether such differential allocation is a general pattern. Using a comparative meta-regression approach, we show that female birds generally invest more into reproduction when paired with attractive males, both in terms of egg size and number as well as food provisioning. However, whereas females of species with bi-parental care tend to primarily increase the number of eggs when paired with attractive males, females of species with female-only care produce larger, but not more, eggs. These patterns may reflect adaptive differences in female allocation strategies arising from variation in the signal content of sexually selected male traits between systems of parental care. In contrast to reproductive effort, female allocation of immune-stimulants, anti-oxidants and androgens to the egg yolk was not consistently increased when mated to attractive males, which probably reflects the context-dependent costs and benefits of those yolk compounds to females and offspring.
Language skills, peer rejection, and the development of externalizing behavior from kindergarten to fourth grade.

BACKGROUND Children with poorer language skills are more likely to show externalizing behavior problems, as well as to become rejected by their peers. Peer rejection has also been found to affect the development of externalizing behavior. This study explored the role of peer rejection in the link between language skills and the development of externalizing behavior. METHODS Six hundred and fifteen (615) children were followed from kindergarten to grade 4. Receptive language skills were measured with the Peabody Picture Vocabulary Test in grade 2. Teachers reported externalizing behavior and peer reports of social rejection were measured annually. RESULTS Children with poorer receptive language skills showed increasing externalizing behavior, while children with better receptive language skills showed decreases in externalizing behavior. Children with poorer receptive language skills experienced peer rejection most frequently. The link between receptive language skills and the development of externalizing behavior was mediated by the development of peer rejection. Findings suggested that this mediational link applied mostly to boys. CONCLUSION Children with poorer language skills are at increased risk of becoming rejected by mainstream peers, which adds to the development of externalizing behavior.
Interaction of polymorphonuclear leukocytes with smooth and rough strains of Brucella abortus

The bactericidal activity of guinea pig and human polymorphonuclear leukocytes (PMNs) against a smooth-intermediate strain (45/0) and a rough strain (45/20) of Brucella abortus has been examined. After incubation for 120 min, guinea pig PMNs incubated with either the smooth strain 45/0 or the rough strain 45/20 exhibited no bactericidal activity against the former and caused only a 34% decrease in viability of the latter. Human PMNs were more bactericidal than guinea pig PMNs to both strains; however, the killing of strain 45/20 by human PMNs was less than that observed in control experiments with S. aureus strain 502A. Both strains of B. abortus readily associated with guinea pig and human PMNs, and the bacteria were apparently ingested without stimulation of the hexose monophosphate pathway. Lysates (10 micrograms/ml, pH 5.5), prepared from guinea pig or human granules, were not particularly toxic to either strain unless supplemented with H2O2 and a halide (I- or Cl-). An oxygen-dependent killing system appeared to be lethal against both strains of B. abortus, with I- being more active than Cl- in the presence of H2O2 and granule lysate. The data suggest that degranulation after ingestion of Brucella by phagocytes does not occur due to the lack of a proper stimulus or possibly the baccilli actively inhibit the degranulation process thereby protecting the microbe from killing systems normally effective against extracellular parasites.
MITES ASSOCIATED WITH NEW WORLD PASSALID BEETLES (COLEOPTERA: PASSALIDAE)

Más de 200 especies de ácaros se han colectado asociadas a escarabajos pasólídos (Passalidae). Estos registros representan colectas de solamente una pequeña porción de los pasálidos conocidos. los ácaros están distribuidos en 21 familias y 68 géneros. Seis de estas familias ocurren solamente en asociación con pasálidos. El mayor número de ácaros asociados con pasálidos pertenece al grupo taxonómico Mesostígmata, supercohorte Trigynaspida. las especies de dos familias de ácaros viven con ios escarabajos en una relación parásita o comensal. las familias restantes tienen una asociación forética con los escarabajos, usándolos para transportarse a nuevos habítats. Especies de nueve de estas familias no son comunes en pasálidos y son probablemente pasajeros oportunistas en el escarabajo. Algunos estudios sugieren que cuando solamente la hembra se dispersa estos ácaros pueden reproducirse partenogenóticamente, pero cuando ambos sexos se dispersan la cópula se lleva a cabo después de la dispersión. Varios métodos para sujetarse al escarabajo han evolucionado entre los diferentes grupos de ácaros. la selección de sitios de transportación en los escarabajos por ios ácaros así como la selección de áreas reproductivas en el túnel del escarabajo, reduce o elimina la competencia entre los ácaros. los datos sugieren que la especificidad al huésped entre ácaro-escarabajo raramente es 1:1. Posiblemente la especificidad este relacionada con el habitat, e.g., escarabajos que viven bajo la corteza versus escarabajos que viven mée profundamente en el tronco. Acaros de 17 familias han sido colectadas de pasálidos del Nuevo Mundo. Se incluyen claves para las familias y los géneros de los ácaros asociados con pasálidos del Nuevo Mundo, así como los caracteres para el reconocimiento de las familias, el número de especies conocidas y comentarios sobre ellas. Palabras Clave: Passalidae, ácaros, asociaciones de ácaros, foresia.
TCALAS: Temporal Credential-Based Anonymous Lightweight Authentication Scheme for Internet of Drones Environment

A user (external party) is interested in accessing the real-time data from some designated drones of a particular fly zone in the Internet of Drones (IoD) deployment. However, to provide this facility, the user needs to be authenticated by an accessed remote drone and vice-versa. After successful authentication both parties can establish a secret session key for the secure communication. To handle this important problem in IoD environment, we design a novel temporal credential based anonymous lightweight user authentication mechanism for IoD environment, called TCALAS. A detailed security analysis using formal security under the broadly applied real-or-random (ROR) model, formal security verification under the broadly used software verification tool, known as automated validation of internet security protocols and applications, and also informal security analysis reveal that TCALAS has the capability to resist various known attacks against passive/active adversary. In addition, a detailed comparative study has been conducted for TCALAS and other related schemes, and the study also reveals that TCALAS provides better security and functionality features, and lower costs in both computation and communication as compared to existing schemes.
Adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes: a mechanism for methotrexate-induced nodulosis in rheumatoid arthritis.

OBJECTIVE To determine why methotrexate (MTX) exacerbates rheumatoid nodules in some patients, despite the effective suppression of synovial inflammation. METHODS Phorbol myristate acetate (PMA)-induced differentiation of monocytes into multinucleated giant cells was used as an in vitro model to study the effects of adenosine on nodulosis. RESULTS MTX at 200-2,000 nM or the adenosine A1 agonist N5-cyclopentyl adenosine (CPA) (10(-12) to 10(-9) M) or the A2 antagonist 3,7-dimethyl-1-propargylxanthine markedly enhanced giant cell formation, whereas the adenosine A1 antagonist 8-cyclopentyl-dipropylxanthine completely reversed these effects. PMA, CPA, and MTX induced adenosine release by cultured monocytes at concentrations consistent with those associated with predominantly A1 effects. Furthermore, surface expression of A1 receptors was found to remain unchanged on the differentiating cells throughout the culture period. CONCLUSION Agents that inhibit adenosine A1 receptors might be useful in the treatment of MTX-induced rheumatoid nodulosis, while still potentiating the A2-mediated antiinflammatory effects of MTX on synovitis.
Look who's talking: Exploring instructors' contributions to Massive Open Online Courses

Previous research on xMOOC pedagogy has established that learner interactions in discussion forums play a fundamental role in learning. However, little is known about the extent to which MOOC instructors engage with learner conversations and the impact this has on learner engagement. Adopting a novel design, this study went beyond self‐reported methods, and combined transcript analysis and in‐depth interviews to examine the dynamics of learner‐instructor interactions and to revisit the use of the Community of Inquiry framework (CoI) in MOOC context. The findings revealed that the majority of instructors’ contributions to learner conversations are social, followed by teaching and cognitive contributions. While all contribution types decreased over the duration of the MOOC, the relative importance of each type did not necessarily change. Furthermore, the analysis showed that learners engaged with 42% of instructor contributions by responding to or liking them or both. Considering the application of the CoI to massive and open online learning contexts, this study demonstrates that while the framework can unfold educational transactions in MOOCs, reoperationalisation and reconceptualisation of some indicators along with the introduction of new indicators are essential. The implications of this for theory and practice are discussed.
Th17 and Regulatory T cells in Women with Recurrent Pregnancy Loss

The immune system of pregnant women is tightly controlled to defend against microbial infections and at the same time, to accept an embryo or the fetus, which are expressing semi‐allogenic paternal antigens. Furthermore, inflammation‐like processes are crucial for tissue growth, remodeling, and differentiation of the decidua during pregnancy. Dysregulation of elaborate immune control may lead reproductive failure, such as implantation failure, recurrent pregnancy loss (RPL), preterm birth, intrauterine fetal growth restriction, and preeclampsia. Until recent years, a balance between Th1 and Th2 cells was believed to be the key immune regulatory mechanism of T‐cell immunology especially during pregnancy. Since the identification of regulatory T cells was made, the mechanism of immune regulation has become a major issue in immunologic research. Also, the recent identification of Th17 cells has drawn our attention to a new immune effector. The balance between Th17 and regulatory T cells may explain more about the pathophysiology of reproductive failure. This review will discuss relevant human literature on regulatory T and Th17 cells in normal reproductive physiology and in women with RPL and infertility.
Phenology of farmland floral resources reveals seasonal gaps in nectar availability for bumblebees

1.Floral resources are known to be important in regulating wild pollinator populations and are therefore an important component of agri‐environment and restoration schemes which aim to support pollinators and their associated services. However, the phenology of floral resources is often overlooked in these schemes — a factor which may be limiting their success. 2.Our study characterizes and quantifies the phenology of nectar resources at the whole‐farm scale on replicate farms in Southwestern UK throughout the flowering season. We quantify the corresponding nectar demands of a subset of common wild pollinators (bumblebees) to compare nectar supply and pollinator demand throughout the year, thereby identifying periods of supply‐demand deficit. 3.We record strong seasonal fluctuations in farmland nectar supplies, with two main peaks of nectar production (May and July) and a considerable “June Gap” in between. March and August/September are also periods of low nectar availability. 4.Comparing the phenology of nectar supply with the phenology of bumblebee nectar demand reveals “hunger gaps” during March and much of August/September when supply is unlikely to meet demand. 5.Permanent pasture and woodland produced the greatest share of farmland nectar because of their large area; however, linear features such as hedgerows and field margins provided the greatest nectar per unit area. Fifty percent of total nectar was supplied by just three species (Allium ursinum, Cirsium arvense and Trifolium repens), but some less productive species (e.g. Hedera helix and Taraxacum agg.) were important in ensuring phenological continuity of nectar supply. 6.Synthesis and applications. By comparing the phenology of farmland nectar supply with the phenology of pollinator demand, we demonstrate that the timing of nectar supply may be as important as total nectar production in limiting farmland pollinator populations. Considering phenology in the design of agri‐environment or restoration schemes is therefore likely to improve their suitability for pollinators. Plant species which flower during periods of resource deficit (early spring and late summer) should be prioritized in schemes which aim to conserve or restore pollinator populations. Maintaining a range of semi‐natural habitats with complementary flowering phenologies (e.g. woodland, hedgerows and field margins) will ensure a more continuous supply of nectar on farmland, thereby supporting pollinators for their entire flight season.
Single Event Transient Hardness of a New Complementary (npn $+$ pnp) SiGe HBT Technology on Thick-Film SOI

We report heavy-ion microbeam and total dose data for a new complementary (npn + pnp) SiGe on thick-film SOI technology. Measured transient waveforms from heavy-ion strikes indicate a significantly shortened single-event-induced transient current, while maintaining the total dose robustness associated with SiGe devices. Heavy-ion broad-beam data confirm a reduced single event upset (SEU) cross-section in a high-speed shift register circuit.
2018 Chinese Guidelines for Prevention and Treatment of Hypertension—A report of the Revision Committee of Chinese Guidelines for Prevention and Treatment of Hypertension

Revision Committee Members Chair: Li–Sheng LIU* Deputy Chairs: Zhao–Su WU, Ji–Guang WANG, Wen WANG Members (Listed in alphabetic order by last name in Chinese Pinyin) Yu–Jing BAO, Jun CAI, Lu–Yuan CHEN, Wei–Wei CHEN, Shao–Li CHU, Ying–Qing FENG, Ping–Jin GAO, Ting–Rui GUAN, Zi–Hong GUO, Qi HUA, Jun HUANG, Yong HUO, Wei–Ping JIA, Xiong–Jing JIANG, Yi–Nong JIANG, Li LI, Li–Huan LI, Nan–Fang LI, Wei LI, Xiao–Ying LI, Xue–Wang LI, Yan LI, Yong LI, Jin–Xiu LIN, Li–Sheng LIU, Xin–Zheng LU, Ji–Xiang MA, Jie MI, Jian-Jun MU, Chang–Yu PAN, Gang SUN, Ning–Ling SUN, Ying–Xian SUN, Jun TAO, Hao WANG, Ji–Guang WANG, Wen WANG, Wen–Zhi WANG, Yong–Jun WANG, Yu WANG, Zeng–Wu WANG, Hai–Ying WU, Zhao–Su WU, Liang–Di XIE, Zhang–Rong XU, Xiao–Wei YAN, Yan–Min YANG, Chong–Hua YAO, Zheng–Pei ZENG, Jian ZHANG, Wei–Zhong ZHANG, Xin–Hua ZHANG, Xin–Jun ZHANG, Yu–Qing ZHANG, Ding–Liang ZHU, Jun ZHU, Zhi–Ming ZHU
Privacy-preserving Online Human Behaviour Anomaly Detection Based on Body Movements and Objects Positions

Human behaviour anomaly detection is crucial for modern artifi-cial intelligence systems. However, privacy protection plays a great role in the realization. In this paper, an online privacy-preserving anomaly detector is presented. The proposed method is able to discriminate on human subject body movements, postures and interactions with the surrounding objects, preserving subject privacy in all the tuning, training and testing stages. ActionXPose, Single Shot MultiBox Detector and Support Vector Machine are exploited for the proposed semi-supervised anomaly detector. The method successfully detects abnormal human behaviours, including unexpected body movements and misplaced objects. A new dataset ISLD-A is also proposed1, providing suitable benchmark for performance evaluation2.
Fecal Microbial Composition of Ulcerative Colitis and Crohn’s Disease Patients in Remission and Subsequent Exacerbation

Background Limited studies have examined the intestinal microbiota composition in relation to changes in disease course of IBD over time. We aimed to study prospectively the fecal microbiota in IBD patients developing an exacerbation during follow-up. Design Fecal samples from 10 Crohn’s disease (CD) and 9 ulcerative colitis (UC) patients during remission and subsequent exacerbation were included. Active disease was determined by colonoscopy and/or fecal calprotectine levels. Exclusion criteria were pregnancy, antibiotic use, enema use and/or medication changes between consecutive samples. The microbial composition was assessed by 16S rDNA pyrosequencing. Results After quality control, 6,194–11,030 sequences per sample were available for analysis. Patient-specific shifts in bacterial composition and diversity were observed during exacerbation compared to remission, but overarching shifts within UC or CD were not observed. Changes in the bacterial community composition between remission and exacerbation as assessed by Bray-Curtis dissimilarity, were significantly larger in CD versus UC patients (0.59 vs. 0.42, respectively; p = 0.025). Thiopurine use was found to be a significant cause of clustering as shown by Principal Coordinate Analysis and was associated with decreases in bacterial richness (Choa1 501.2 vs. 847.6 in non-users; p<0.001) and diversity (Shannon index: 5.13 vs. 6.78, respectively; p<0.01). Conclusion Shifts in microbial composition in IBD patients with changing disease activity over time seem to be patient-specific, and are more pronounced in CD than in UC patients. Furthermore, thiopurine use was found to be associated with the microbial composition and diversity, and should be considered when studying the intestinal microbiota in relation to disease course.
Intersexual differences in inhibitory influence of trans-resveratrol on activity of cytochrome P450 2D2 in rats.

OBJECTIVES Differences in the metabolism between males and females have been seen over time. Hormonal regulation of cytochrome P450 activity is understood to be involved. Trans-resveratrol (RES) is an estrogenically active plant polyphenol with many protective biological activities including neuroprotection. The present report studied the influence of sex and RES on variances in rat's cytochrome P450 2D2 hepatic metabolic activity. METHODS AND DESIGN Isolated perfused rat liver was used for determination of cytochrome P450 2D2 activity. Wistar albino rats of both sexes were treated with RES at the dose of 5 mg/kg/day for 10 days prior to liver isolation. Levels of marker substance dextromethorphan (DEM) and its 2D2 specific metabolite dextrorphan (DEX) were measured during perfusion. The metabolic ratios (DEM/DEX) and the levels of DEM and DEX in perfusate were compared. RESULTS In the controls, the activity of CYP2D2 was found to be higher in male rats compared to females. RES produced inhibition of CYP2D2, expressed by significant changes of both DEM and DEX levels in males and significant increase of only DEM levels in females. There were no gender changes in DEX levels in RES treated animals whilst DEM levels were significantly increased during the whole perfusion in females. CONCLUSION The results confirmed gender differences in the metabolic activity of CYP450 2D2 with a higher rate in male rats. RES acted as an inhibitor, however again with greater impact in males than in females. This metabolic divergence could be a cause for different sensitivity or even toxicity of drugs metabolized by the CYP450 2D2.
Role of Prostacyclin in the Cardiovascular Response to Thromboxane A2

Thromboxane (Tx) A2 is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA2 formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI2) is a vasodilator that inhibits platelet function. Here we show that injury-induced vascular proliferation and platelet activation are enhanced in mice that are genetically deficient in the PGI2receptor (IP) but are depressed in mice genetically deficient in the TxA2 receptor (TP) or treated with a TP antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors. Thus, PGI2 modulates platelet-vascular interactions in vivo and specifically limits the response to TxA2. This interplay may help explain the adverse cardiovascular effects associated with selective COX-2 inhibitors, which, unlike aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), inhibit PGI2 but not TxA2.
Reduced enzyme activities in inherited ataxia

Our group and colleagues have reported partial diminution in activities of the enzyme lipoamide dehydrogenase (LAD) in peripheral tissues of some patients with recessively inherited ataxia [l, 31. This result extended findings of low activities of the pyruvate and the a-ketoglutarate dehydrogenase complexes (PDH and KGDH) [l] and is a possible explanation for the decreased oxidation of [2-*4C]pyruvate to 14C02 in tissues of some of the same patients. Others have not been able to find these changes in their patients [2, 41, though a recent report can be interpreted as confirming our findings with respect to PDH [5]. We have therefore undertaken a “blind” study with samples from two previous patients. Technical personnel were different from those involved in prior work. The