37 research outputs found

    Introductory Notes to Algebraic Statistics

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    These are the notes of a short course on algebraic statistics, a new discipline across the fields of statistical modeling and computational commutativa algebra. The basics of the theory are provided together with brief reference to applications to design of experiments, to exponential and graphical models, and to computational biology

    C-Terminal Binding Protein 2 Is a Novel Tumor Suppressor Targeting the Myc-Irf4 axis in Multiple Myeloma

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    Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered undruggable, as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy

    A brief cognitive-behavioral psycho-education (B-CBE) program for managing stress and anxiety of main family caregivers of patients in the intensive care unit

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    © 2016 by the authors; licensee MDPI, Basel, Switzerland. Having a loved one in the intensive care unit (ICU) is a stressful event, which may cause a high level of anxiety to the family members. This could threaten their wellbeing and ability to support the patients in, or after discharge from, the ICU. To investigate the outcomes of a brief cognitive-behavioral psycho-education program (B-CBE) to manage stress and anxiety of the main family caregivers (MFCs), a pragmatic quasi-experimental study involving 45 participants (treatment group: 24; control group: 21) was conducted in an ICU. The Depression and Anxiety Stress Scale and the Critical Care Family Need Inventory were used to evaluate the primary outcomes on stress and anxiety, and satisfaction with family needs. The treatment group reported significantly better improvement in the information satisfaction score compared to the control group (p < 0.05; η 2 = 0.09). Overall main effects were observed on the stress (p < 0.01; η 2 = 0.20), anxiety (p < 0.01; η 2 = 0.18), depression (p < 0.05; η 2 = 0.13), support satisfaction (p < 0.05; η 2 = 0.13), and comfort satisfaction (p < 0.05; η 2 = 0.11) scores. The experience of this study suggest that MFCs are in great need of additional support like B-CBE to manage their stress and anxiety. Given the brevity of B-CBE, it is practical for critical care nurses to deliver and MFCs to take within the industrious context of an ICU. More studies are needed to investigate these types of brief psychological interventions.published_or_final_versio

    Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study

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    BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group

    Volar Dislocation of the Metacarpophalangeal Joint of the Ring Finger Complicated with Chondrolysis: A Case Report and Review of the Literature

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    Volar dislocation of the metacarpophalangeal joint is rare injury. In the literature consulted only seven cases of isolated volar dislocation of the metacarpophalangeal joint of the ring finger have been published. Chondrolysis associated with the metacarpophalangeal joint dislocation has not been reported in the English literature. In this paper, an unusual case of volar dislocation of the metacarpophalangeal joint is presented and a review of the literature is described

    A study of the EB-type eclipsing binary GR Tauri with mass transfer

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    In this paper, new CCD BV light curves of the EB-type eclipsing binary GR Tau, which were obtained in 1999, are analyzed by means of the Wilson-Devinney program. The photometric solution of this system is obtained, and its absolute parameters are also derived. Our study has demonstrated that GR Tau is a near-contact binary system with an almost-contact semidetached configuration in which the primary fills its Roche lobe, and both components are main-sequence stars. The asymmetric shape of the light curves can be explained by a hot spot on the surface of the secondary, which is created by the mass transfer from the primary to the secondary. GR Tau belongs to the V1010 Oph subclass of near-contact binaries, and is a good example of a system in the broken-contact phase predicted by the TRO theory

    The association between tibial torsion, knee flexion excursion and foot progression during gait in people with knee osteoarthritis: a cross-sectional study

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    Abstract Background Lower limb malalignment is associated with gait kinematics, but there is limited information on the relationship between gait kinematics and tibial torsion in individuals with knee osteoarthritis (OA). This study aimed to investigate possible associations between tibial torsion and early stance kinematics during gait in people with mild and moderate medial knee OA. Methods Forty-seven participants (age: 62.1 ± 6.0 years; female/male: 37/10) diagnosed with medial knee OA were recruited from a regional hospital. Thirty of them had mild and seventeen had moderate knee OA. Lower limb alignment including tibial torsion and valgus/varus alignment were assessed by an EOS biplaner X-ray system with participants in weight-bearing position. Lower limb kinematics during gait was captured using the Vicon motion analysis system. The associations were estimated by partial Pearson correlation coefficient test. Results Our results indicated that external tibial torsion was related to early stance knee flexion excursion in participants with moderate knee OA (r = -0.58, p = 0.048), but not in participants with mild knee OA (r = 0.34, p = 0.102). External tibial torsion was associated with external foot progression angle (r = 0.48, p = 0.001), and knee varus/valgus alignment was associated with knee flexion excursion (r = -0.39, p = 0.010) in all participants. Conclusions Both horizontal and frontal lower limb alignments were associated with knee flexion excursion at early stance of gait cycle in participants with medial knee OA. The distal rotational profile of lower limb would likely affect knee motion in sagittal plane. It implies that people with moderate knee OA could possibly benefit from correction of rotational alignment of lower limb

    The refined physical properties of transiting exoplanetary system WASP-11/HAT-P-10

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    The transiting exoplanetary system WASP-11/HAT-P-10 was observed using the CCD camera at Yunnan Observatories, China from 2008 to 2011, and four new transit light curves were obtained. Combined with published radial velocity measurements, the new transit light curves are analyzed along with available photometric data from the literature using the Markov Chain Monte Carlo technique, and the refined physical parameters of the system are derived, which are compatible with the results of two discovery groups, respectively. The planet mass is Mp =0.526 ± 0.019 MJ , which is the same as West et al.'s value, and more accurately, the planet radius Rp =0.999+0.029-0.018 RJ is identical to the value of Bakos et al.The new result confirms that the planet orbit is circular. By collecting 19 available mid-transit epochs with higher precision, we make anorbital period analysis for WASP-11b/HAT-P-10b, and derive a new valuefor its orbital period, P = 3.72247669 days. Through an (O – C)study based on these mid-transit epochs, no obvious transit timingvariation signal can be found for this system during 2008-2012.</p

    The refined physical parameters of transiting exoplanet system HAT-P-24

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    The transiting exoplanet system HAT-P-24 was observed by using CCD cameras at Yunnan Observatory and Hokoon Astronomical Centre, China in 2010 and 2012. In order to enhance the signal to noise ratio of transit events, the observed data are corrected for systematic errors according to Collier Cameron et al.'s coarse de-correlation and Tamuz et al.'s SYSREM algorithms. Three new complete transit light curves are analyzed by means of the Markov chain Monte Carlo technique, and the new physical parameters of the system are derived. They are consistent with the old ones from the discovered paper except for a new larger radius Rp = 1.364 RJ of HAT-P-24b, which confirms its inflated nature. By combining the five available epochs of mid-transit derived from complete transit light curves, the orbital period of HAT-P-24b is refined to P = 3.3552479 d and no obvious transit timing variation signal can be found from these five transit events during 2010–2012.</p
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