Miracle-dz/UniFAR-FTUs huggingface dataset:
The BH3 α-Helical Mimic BH3-M6 Disrupts Bcl-XL, Bcl-2, and MCL-1 Protein-Protein Interactions with Bax, Bak, Bad, or Bim and Induces Apoptosis in a Bax- and Bim-dependent Manner*

A critical hallmark of cancer cell survival is evasion of apoptosis. This is commonly due to overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-XL, and Mcl-1, which bind to the BH3 α-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function. We designed a BH3 α-helical mimetic BH3-M6 that binds to Bcl-XL and Mcl-1 and prevents their binding to fluorescently labeled Bak- or Bim-BH3 peptides in vitro. Using several approaches, we demonstrate that BH3-M6 is a pan-Bcl-2 antagonist that inhibits the binding of Bcl-XL, Bcl-2, and Mcl-1 to multi-domain Bax or Bak, or BH3-only Bim or Bad in cell-free systems and in intact human cancer cells, freeing up pro-apoptotic proteins to induce apoptosis. BH3-M6 disruption of these protein-protein interactions is associated with cytochrome c release from mitochondria, caspase-3 activation and PARP cleavage. Using caspase inhibitors and Bax and Bak siRNAs, we demonstrate that BH3-M6-induced apoptosis is caspase- and Bax-, but not Bak-dependent. Furthermore, BH3-M6 disrupts Bcl-XL/Bim, Bcl-2/Bim, and Mcl-1/Bim protein-protein interactions and frees up Bim to induce apoptosis in human cancer cells that depend for tumor survival on the neutralization of Bim with Bcl-XL, Bcl-2, or Mcl-1. Finally, BH3-M6 sensitizes cells to apoptosis induced by the proteasome inhibitor CEP-1612.
QuadTIN: quadtree based triangulated irregular networks

Interactive visualization of large digital elevation models is of continuing interest in scientific visualization, GIS, and virtual reality applications. Taking advantage of the regular structure of grid digital elevation models, efficient hierarchical multiresolution triangulation and adaptive level-of-detail (LOD) rendering algorithms have been developed for interactive terrain visualization. Despite the higher triangle count, these approaches generally outperform mesh simplification methods that produce irregular triangulated network (TIN) based LOD representations. In this project we combine the advantage of a TIN based mesh simplification preprocess with high-performance quadtree based LOD triangulation and rendering at run-time. This approach, called QuadTIN, generates an efficient quadtree triangulation hierarchy over any irregular point set that may originate from irregular terrain sampling or from reducing oversampling in high-resolution grid digital elevation models.
MERLIN: MEasure the router level of the INternet

In this paper, we present a new router-level Internet mapping tool called MERLIN. MERLIN takes advantage of mrinfo, a multicast management tool that collects all IPv4 multicast enabled interfaces of a router and all its multicast links towards its neighbors. Our new probing tool fixes mrinfo technical limitations and eases the deployment of multicast probing campaign. We deploy and evaluate the performance of MERLIN at large scale. We investigate the completeness of MERLIN by providing a lower bound on the proportion of information that it may miss. We also demonstrate that the use of several vantage points is crucial to circumvent IGMP filtering in order to increase the amount of collected routers. MERLIN is a valuable tool for collecting the router-level Internet topology.
What Will Others Choose? How a Majority Vote Reward Scheme Can Improve Human Computation in a Spatial Location Identification Task

We created a spatial location identification task (SpLIT) in which workers recruited from Amazon Mechanical Turk were presented with a camera view of a location, and were asked to identify the location on a two-dimensional map. In cases where these cues were ambiguous or did not provide enough information to pinpoint the exact location, workers had to make a best guess. We tested the effects of two reward schemes. In the “ground truth” scheme, workers were rewarded if their answers were close enough to the correct locations. In the “majority vote” scheme, workers were told that they would be rewarded if their answers were similar to the majority of other workers. Results showed that the majority vote reward scheme led to consistently more accurate answers. Cluster analysis further showed that the majority vote reward scheme led to answers with higher reliability (a higher percentage of answers in the correct clusters) and precision (a smaller average distance to the cluster centers). Possible reasons for why the majority voting reward scheme was better were discussed.
Gene Selection in Arthritis Classification With Large-Scale Microarray Expression Profiles

The use of large-scale microarray expression profiling to identify predictors of disease class has become of major interest. Beyond their impact in the clinical setting (i.e. improving diagnosis and treatment), these markers are also likely to provide clues on the molecular mechanisms underlining the diseases. In this paper we describe a new method for the identification of multiple gene predictors of disease class. The method is applied to the classification of two forms of arthritis that have a similar clinical endpoint but different underlying molecular mechanisms: rheumatoid arthritis (RA) and osteoarthritis (OA). We aim at both the classification of samples and the location of genes characterizing the different classes. We achieve both goals simultaneously by combining a binary probit model for classification with Bayesian variable selection methods to identify important genes.We find very small sets of genes that lead to good classification results. Some of the selected genes are clearly correlated with known aspects of the biology of arthritis and, in some cases, reflect already known differences between RA and OA.
Integrated Membrane Protein Analysis of Mature and Embryonic Stem Cell-derived Smooth Muscle Cells Using a Novel Combination of CyDye/Biotin Labeling *S

Cultivated vascular smooth muscle cells (SMCs) were surface-labeled with CyDyes followed by biotinylation. After enrichment on avidin columns, proteins were separated on large format gradient gels by SDS-PAGE. A comparison between CyDye-tagged and non-tagged gel bands revealed a substantial increase of protein identifications from membrane, membrane-associated, and extracellular matrix proteins with a corresponding reduction in co-purified intracellular proteins. Notably the majority of identified proteins were involved in cellular adhesion processes. To demonstrate the quantitative potential of this platform, we performed a comparison between mature and embryonic stem cell-derived smooth muscle cells (esSMCs) and identified the membrane proteins E-cadherin, integrin α6, and CD98 (4F2) to be significantly up-regulated in esSMCs suggesting that SMCs derived from embryonic stem cells maintain characteristics of their embryonic stem cell origin. This was subsequently confirmed by RT-PCR: despite expressing a panel of smooth muscle markers (calponin, Sm22, and aortic smooth muscle actin), esSMCs remained positive for markers of stem cell pluripotency (Oct4, Nanog, and Rex1). In summary, we describe a novel strategy for the profiling of cell membrane proteins. The procedure combines DIGE technology with biotin/avidin labeling to discriminate membrane and membrane-associated proteins from intracellular contaminants by fluorescence tagging and permits semiquantitative differential expression analysis of membrane proteins.
Association of Tumor Necrosis Factor and Manganese Superoxide Dismutase Polymorphisms in Patients with Non-Alcoholic Steatohepatitis from Northeast Mexico

Background and Aims: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic steatohepatitis (NASH). The aim of this study was to determine if the G-238A (allele TNFA) and G-308A (allele TNF2) tumor necrosis factor-alpha (TNF-￻ ) and Ala9Val manganese superoxide dismutase (MnSOD) polymorphisms were associated with NASH in a case-control study of subjects from Northeast Mexico. Methods: We analyzed DNA samples from 68 patients with NASH (50 women and 18 men; mean age ± SD, 33.9 ± 10.8 years; BMI 43.9 ± 7.2 kg/m 2 ) and 100 healthy subjects (44 women and 56 men; mean age ± SD, 27.8 ± 10.8 years; BMI 23 ± 1.6 kg/m 2 ). The diagnosis was based on liver biopsy reviewed by two pathologists blinded to clinical data. The polymorphisms were evaluated using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequency of G-238A TNF-￻ and Ala9Val MnSOD polymorphisms in NASH patients was significantly higher in comparison with control subjects (OR = 3.06, 95% CI 1.29-7.33, p = 0.0047 and OR = 6.28, 95% CI 2.95-13.55, p = 0.001, respectively). In contrast, the G-308A TNF-￻ polymorphism did not show a statistical difference between either group (OR = 1.04, 95% CI 0.45-2.38, p = NS). Analyzed populations were in Hardy-Weinberg equilibrium. Conclusions: Our results suggest that G-238A TNF-￻ and Ala9Val MnSOD polymorphisms, which are molecules involved in inflammation and cellular oxidative stress, could be associated with NASH. These data may contribute to understanding the genetic susceptibility to NASH.
Graph sparsification by effective resistances

We present a nearly-linear time algorithm that produces high-quality sparsifiers of weighted graphs. Given as input a weighted graph G=(V,E,w) and a parameter ε>0, we produce a weighted subgraph H=(V,~E,~w) of G such that |~E|=O(n log n/ε2) and for all vectors x in RV. (1-ε) ∑uv ∈ E (x(u)-x(v))2wuv≤ ∑uv in ~E(x(u)-x(v))2~wuv ≤ (1+ε)∑uv ∈ E(x(u)-x(v))2wuv. This improves upon the sparsifiers constructed by Spielman and Teng, which had O(n logc n) edges for some large constant c, and upon those of Benczur and Karger, which only satisfied (1) for x in {0,1}V. We conjecture the existence of sparsifiers with O(n) edges, noting that these would generalize the notion of expander graphs, which are constant-degree sparsifiers for the complete graph. A key ingredient in our algorithm is a subroutine of independent interest: a nearly-linear time algorithm that builds a data structure from which we can query the approximate effective resistance between any two vertices in a graph in O(log n) time.
An Improvement of Ionospheric Phase Correction by Multiple-Aperture Interferometry

Recently a multiple-aperture interferometry (MAI)-based azimuth shift method has been proposed to correct the ionospheric phase on synthetic aperture radar (SAR) interferograms. This method needs to determine integral constants required for azimuth integration. The exact estimation of the integral constants plays a key role in this MAI-based method. In this paper, we propose an efficient method for improving the performance of integral constant estimation, which functions by simultaneously removing the ionospheric and orbital phase artifacts from the interferometric SAR interferogram. We validate the performance improvement of the proposed method using two Advanced Land Observation Satellite Phase Array L-band SAR (ALOS PALSAR) interferometric pairs. The proposed method is compared with a MAI-based method, which does not work well due to azimuth integration errors. The proposed method successfully corrects the ionospheric and orbital phase artifacts. In addition, we compare the performances of the previous and proposed methods using the in situ Global Positioning System velocities. The root-mean-square error (RMSE) in line-of sight velocity from the previous method is about 7.0 mm/yr, whereas the RMSE from the proposed method is about 4.3 mm/yr. An RMSE reduction of about 38.6% is achieved when using the proposed method. These results indicate: 1) that the proposed method successfully estimates and corrects the ionosphere and orbital phase distortions; and 2) that the proposed method is superior to the previous method.
Regulated expression on human macrophages of endoglin, an Arg‐Gly‐Asp‐containing surface antigen

Endoglin is an endothelial homodimeric membrane antigen containing the tripeptide arginine‐glycine‐aspartic acid (RGD), which is a recognition motif for adhesion receptors of the integrin family. We have investigated the expression of endoglin by monocyte/macrophage cells from different tissue compartments and at different stages of cell differentiation. Although endoglin is absent from peripheral blood monocytes, it is expressed by in vitro differentiated monocytes as determined by flow cytometry using the endoglin‐specific monoclonal antibody 44G4 and 8E11. Furthermore, Northern blot analyses revealed a correlation between the presence of endoglin mRNA and the surface expression of the antigen by in vitro differentiated monocytes. Immunostaining of frozen tissue sections with the 8E11 monoclonal antibody demonstrated the presence of endoglin not only in the endothelium of all the tissues studied, but also on the interstitial macrophages present in the red pulp of the spleen. Using as a model of macrophage differentiation monocytic cell lines treated with phorbol esters, we found that the reactivity of the 8E11 monoclonal antibody is greatly increased on U‐937 and HL‐60 cells during their PMA‐induced differentiation. These findings clearly demonstrate for the first time the regulated expression of the putative adhesion molecule endoglin by macrophages.
Complexity of CEBPA Dysregulation in Human Acute Myeloid Leukemia

The transcription factor CCAAT enhancer binding protein alpha (CEBPA) is crucial for normal development of granulocytes. Various mechanisms have been identified how CEBPA function is dysregulated in patients with acute myeloid leukemia (AML). In particular, dominant-negative mutations located either at the N- or the C terminus of the CEBPA gene are observed in roughly 10% of AML patients, either in the combination on separate alleles or as sole mutation. Clinically significant complexity exists among AML with CEBPA mutations, and patients with double CEBPA mutations seem to have a more favorable course of the disease than patients with a single mutation. In addition, myeloid precursor cells of healthy carriers with a single germ-line CEBPA mutation evolve to overt AML by acquiring a second sporadic CEBPA mutation. This review summarizes recent reports on dysregulation of CEBPA function at various levels in human AML and therapeutic concepts targeting correction of CEBPA activity. The currently available data are persuasive evidence that impaired CEBPA function contributes directly to the development of AML, whereas restoring CEBPA function represents a promising target for novel therapeutic strategies in AML. (Clin Cancer Res 2009;15(17):5303–7)
Evaluation of a screening program on reduction of gastric cancer mortality in Japan: preliminary results from a cohort study.

BACKGROUND Systematic population-based screening for gastric cancer is widely spread in Japan. However, the case-control study method has been the main method used to evaluate the effectiveness of the screen ing to reduce gastric cancer mortality in Japan. METHODS This article presents a population-based cohort study. A questionnaire about lifestyles and dietary habits was distributed to 36,990 residents in a city of Japan. The response rate to the questionnaire was 92.0%. After ineligible responders had been excluded, 24,134 subjects were classified into screened and un screened groups according to their self-reports of participation in the screening the previous year. We followed them up for 40 months and linked resident death records in the city. We compared mortality from gastric cancer and all other causes between the groups by us ing the Cox proportional hazard model. RESULTS The follow-up period was 78,156.6 person-years from September 1992 to December 1995. The multivariate relative risks for gastric cancer death of the screened group in comparison with the unscreened group were 0.72 (95% CI 0.31-1.66) among males and 1.46 (95% CI 0.43-4.90) among females. CONCLUSION Although our data are preliminary, we were unable to demonstrate a large contribution of the present screening program to decreasing gastric cancer mortality. Further follow-up is needed to in crease the precision.
A virtual photon energy fluence model for Monte Carlo dose calculation.

The presented virtual energy fluence (VEF) model of the patient-independent part of the medical linear accelerator heads, consists of two Gaussian-shaped photon sources and one uniform electron source. The planar photon sources are located close to the bremsstrahlung target (primary source) and to the flattening filter (secondary source), respectively. The electron contamination source is located in the plane defining the lower end of the filter. The standard deviations or widths and the relative weights of each source are free parameters. Five other parameters correct for fluence variations, i.e., the horn or central depression effect. If these parameters and the field widths in the X and Y directions are given, the corresponding energy fluence distribution can be calculated analytically and compared to measured dose distributions in air. This provides a method of fitting the free parameters using the measurements for various square and rectangular fields and a fixed number of monitor units. The next step in generating the whole set of base data is to calculate monoenergetic central axis depth dose distributions in water which are used to derive the energy spectrum by deconvolving the measured depth dose curves. This spectrum is also corrected to take the off-axis softening into account. The VEF model is implemented together with geometry modules for the patient specific part of the treatment head (jaws, multileaf collimator) into the XVMC dose calculation engine. The implementation into other Monte Carlo codes is possible based on the information in this paper. Experiments are performed to verify the model by comparing measured and calculated dose distributions and output factors in water. It is demonstrated that open photon beams of linear accelerators from two different vendors are accurately simulated using the VEF model. The commissioning procedure of the VEF model is clinically feasible because it is based on standard measurements in air and water. It is also useful for IMRT applications because a full Monte Carlo simulation of the treatment head would be too time-consuming for many small fields.
Osteoporosis: association of recent fractures with quantitative US findings.

PURPOSE To study the association of quantitative ultrasound (US) parameters and bone mineral density (BMD) in patients with and patients without recent fractures. MATERIALS AND METHODS The authors studied 4,698 women (69 years or older) who had sustained 1,363 new fractures, including 106 hip fractures, during the 7 years prior to the study. Broadband ultrasound attenuation (BUA) and other velocity parameters were measured by means of quantitative US of the calcaneus. BMD was measured at the spine, hip, and calcaneus. RESULTS The standardized age-adjusted odds ratio for all fractures was 1.5 (95% confidence interval [CI] = 1.4, 1.7) for BUA and up to 1.6 (95% CI = 1.5, 1.7) for BMD. For hip fractures, the odds ratio was 1.9 (95% CI = 1.5, 2.4) for BUA and up to 2.6 (95% CI = 2.0,3.4) for BMD. Sensitivity and specificity with BUA, velocity parameters, and BMD were comparable. Results of multivariate analysis showed that both BUA and BMD were independently associated with fractures and that combined measurements improved sensitivity and specificity. CONCLUSION Quantitative US parameters are strongly associated with risk of fracture and partly independent of BMD. This simple, low-cost, portable, and radiation-free approach may complement bone densitometry in assessing risk of osteoporotic fracture.
Levator Ani Muscle Anatomy Evaluated by Origin-Insertion Pairs

OBJECTIVE: To examine the published literature and suggest a resolution to the confusion that exists in levator ani muscle descriptions and terminology. DATA SOURCES: A MEDLINE search was performed using the keyword “levator ani,” limited to human studies in women. References found in these articles were reviewed to identify research reported before 1966 and articles not included in the search. STUDY SELECTION: Studies were accepted if they contained direct observations of female specimens. Only those that contained specific descriptions or illustrations of the muscle origins and insertions in more than 5 female specimens were included. Review of 265 human studies yielded 9 qualifying articles, and reference tracing disclosed 3 additional reports. TABULATION, INTEGRATION, AND RESULTS: The literature review identified 5 origin-insertion pairs consistently described in studies directly examining the levator ani muscle in women, but 16 terms were used by authors for these 5 components of the muscle. Labeled illustrations often provided more precise information than was provided in the text. Terms were reviewed for inconsistencies of usage and appropriateness of term choice. The terms puboperineal, pubovaginal, and puboanal (for components of the pubovisceral [“pubococcygeal”] muscle), along with puborectal and iliococcygeal, are sufficient to describe the divisions of the levator ani muscle. CONCLUSION: Although there was great diversity and conflict in terms chosen among the original articles, the number of origin and insertion pairs was relatively consistent among authors and confusion can be avoided by standardizing terminology. LEVEL OF EVIDENCE: III
Gender differences in college students' self-report of personality

The BASC-SRP-COL is a standardized self-report measure that is specifically designed to measure college students’ perceived levels of positive and negative aspects of personality. As college student mental health problems become more prevalent, it is important to have valid and reliable tools for assessment with this population. After reviewing the research, relevant diagnostic trends, and results found in the BASC-SRP-COL normative sample, it was hypothesized that gender differences would be found in a sample of college students who completed the BASC-SRP-COL. Participants for the proposed study were undergraduate students attending one of two colleges in either North Carolina or Georgia. Gender differences in clinical scales and adaptive scales were examined. For clinical scales, it was hypothesized that males would score higher on the Alcohol Abuse scale, the Atypicality scale, and the Sensation Seeking scale; that females would score higher on the Anxiety and Somatization scales; and that no significant gender differences would be identified on the Attention Problems scale, the Depression scale, the Hyperactivity scale, the Locus of Control scale, the School Maladjustment scale, the Sense of Inadequacy scale, and the Social Stress scale. For the adaptive scales, it was hypothesized that males would score higher on the Self-Esteem scale; females would score higher on the Interpersonal Relations scale and the Relations with Parents scale; and no significant gender differences would be determined on the Self-Reliance scale. A one-way between-groups MANOVA was conducted to investigate gender differences on the BASC-SRP-COL rating scale. Results confirmed that college males were more likely to report higher self-esteem and were more likely to engage in behaviors related to alcohol abuse and sensation seeking. Additionally, college females were more likely to report higher levels of anxiety and somatization. Finally, no significant gender differences were found on the remaining scales. Results were compared with those of the BASC-SRP-COL normative study and with other research. Suggestions for future research and recommendations for college prevention programs were discussed.