gebhart/patrepeval huggingface dataset:
The p16<SUP>INK4a</SUP>-RB pathway : molecular link between cellular senescence and tumor suppression (2004)

The p16INK4a tumor suppressor protein functions as an inhibitor of CDK4 and CDK6, the D-type cyclin-dependent kinases that initiate the phosphorylation of the retinoblastoma tumor suppressor protein, RB. Thus, p16INK4a has the capacity to arrest cells in the G1-phase of the cell cycle and its probable physiological role is in the implementation of irreversible growth arrest termed cellular senescence. Cellular senescence is a state of permanent growth arrest that can be induced by a variety of stresses such as DNA-damage and aberrant mitogenic signaling in human primary cells. In contrast to normal cells, the function of the p16INK4a gene or its downstream mediators is frequently deregulated in many types of human cancers, illustrating the importance of cellular senescence in tumor suppression. Here we discuss the molecular mechanisms that direct cellular senescence and reveal its potential for tumor suppression.
Easy Data Analysis (2000)

G raphical presentation and analysis of experimental data are parts of every working scientist's life, and the ubiquitous availability of computers has generated a panoply of programs to help in these tasks. Choosing the most appropriate package for one's needs is the key to efficient and reliable analysis.

Prism is a neat, compact, and flexible program with a “clean” interface that can be used to plot and analyze two-dimensional data sets. The software is available in Windows and Macintosh versions with very similar interfaces. The User's Guide is slightly different for the two versions, and both come with the book Analyzing Data with GraphPad Prism , which not only explains how to use Prism but also helps users to choose an analysis appropriate for their data and make sense of the results. A major strong point of the software is the extraordinary way in which the documentation and online help manage to provide instruction in the principles of data analysis.

The organization of Prism is based on “Projects” and within each project there are five components comprising Data, Graphs, Results, Layouts, and Notes. Data can be entered from the keyboard or by importing text files, although there is no extensive set of filters for other file formats. Once entered, the data can be plotted in a variety of styles. In addition to the normal parametric ( x-y ) plot, histograms and various column plot types are available. The user has considerable freedom to define the attributes of the graph (axes, symbols, legends, error bars). A button brings up a Greek or Mathematical symbols keypad.

There are a variety of options for analysis of data, including basic column operations (transformations, transpositions, baseline correction), statistical tests (t-tests, analysis of variance, survival curves), and regression (linear and nonlinear). The nonlinear regression encompasses both built-in equations and a straightforward equation editor for user-defined functions. The program's built-in functions are aimed squarely at the biological sciences with equations for one- and two-site hyperbolic binding, sigmoidal dose-response curves, and exponential growth or decay. The program's ability to fit two different equations to the same data set is very useful.

Graphs and layouts produced in Prism can be saved as PICT files (Mac) or WMF files (Windows) for easy incorporation into other programs. Prism can also export graphs or layouts in .bmp or .tiff extension formats at up to 1200 dots per inch.

Overall, Prism is an easy-to-learn and fairly flexible package. Although not as feature-laden as more heavyweight data analysis and graphing software, it does an excellent job of concentrating on ease of use, speed, and convenience. It is ideally suited to basic data plotting or analysis applications in the life sciences. The associated Web site and documentation both contain a wealth of sensible, useful advice on data analysis and curve fitting and are real bonuses.
Face detection, pose estimation, and landmark localization in the wild (2012)

We present a unified model for face detection, pose estimation, and landmark estimation in real-world, cluttered images. Our model is based on a mixtures of trees with a shared pool of parts; we model every facial landmark as a part and use global mixtures to capture topological changes due to viewpoint. We show that tree-structured models are surprisingly effective at capturing global elastic deformation, while being easy to optimize unlike dense graph structures. We present extensive results on standard face benchmarks, as well as a new “in the wild” annotated dataset, that suggests our system advances the state-of-the-art, sometimes considerably, for all three tasks. Though our model is modestly trained with hundreds of faces, it compares favorably to commercial systems trained with billions of examples (such as Google Picasa and face.com).
Regulatory T Cells Suppress CD8+ T Cell Responses Induced by Direct Priming and Cross-Priming and Moderate Immunodominance Disparities (2005)

Little is known regarding the participation of CD4+ CD25+ regulatory T cells (Treg) in TCD8+ responses. In this study, we show that Treg depletion via treatment with anti-CD25 mAb (PC61) significantly enhances TCD8+ responses to influenza A virus, vaccinia virus, and SV40-transformed cells induced by either direct priming or cross-priming. PC61 did not enhance TCD8+ responses in CD4-deficient mice, providing the initial demonstration that PC61 acts on a subset of TCD4+, and not on other cells that express either CD25 or a fortuitously cross-reactive Ag. We further show that Treg selectively suppress responses to the most immunodominant TCD8+ determinants in the three systems examined. Therefore, Treg influence TCD8 immunodominance hierarchies by moderating disparities in responses to different determinants.
PoplarFT2Shortens the Juvenile Phase and Promotes Seasonal Flowering (2006)

Many woody perennials, such as poplar (Populus deltoides), are not able to form flower buds during the first several years of their life cycle. They must undergo a transition from the juvenile phase to the reproductive phase to be competent to produce flower buds. After this transition, trees begin to form flower buds in the spring of each growing season. The genetic factors that control flower initiation, ending the juvenile phase, are unknown in poplar. The factors that regulate seasonal flower bud formation are also unknown. Here, we report that poplar FLOWERING LOCUS T2 (FT2), a relative of the Arabidopsis thaliana flowering-time gene FT, controls first-time and seasonal flowering in poplar. The FT2 transcript is rare during the juvenile phase of poplar. When juvenile poplar is transformed with FT2 and transcript levels are increased, flowering is induced within 1 year. During the transition between vegetative and reproductive growth in mature trees, FT2 transcripts are abundant during reproductive growth under long days. Subsequently, floral meristems emerge on flanks of the axillary inflorescence shoots. These findings suggest that FT2 is part of the flower initiation pathway in poplar and plays an additional role in regulating seasonal flower initiation that is integrated with the poplar perennial growth habit.
Draft Genome Sequence of the Paenibacillus polymyxa Type Strain (ATCC 842 T ), a Plant Growth-Promoting Bacterium (2011)

Paenibacillus polymyxa is an endospore-forming Gram-positive soil bacterium that is well-known for its ability to promote plant growth. Here we report the draft genome sequence of P. polymyxa ATCC 842(T), the type strain of the species P. polymyxa, and the family Paenibacillaceae. The P. polymyxa genome contains a repertoire of biosynthetic genes for antibiotics and hydrolytic enzymes that account for its beneficial effects in the rhizosphere to the host plants it associates with.
DnaX Complex of Escherichia coli DNA Polymerase III Holoenzyme THE χ·ψ (1995)

An artificial operon that contains tandem holC-holD genes was used to overproduce a complex of the χ and ψ subunits of the DNA polymerase III holoenzyme. Normally insoluble by itself, ψ forms a tight soluble complex with χ. A purification procedure that yields pure, active χ·ψ complex in 100-mg quantities suitable for biophysical studies is reported. Sedimentation equilibrium studies demonstrate that χ·ψ is a 1:1 heterodimer. The presence of χ·ψ dramatically lowers the level of δ·δ′ required to reconstitute holoenzyme to levels expected in vivo. That χ·ψ accomplishes this by binding to γ or τ and increasing their affinity for δ·δ′ was demonstrated by surface plasmon resonance using a Pharmacia BIAcoreTM instrument. In the absence of δ·δ′, χ·ψ binds to either the γ or τ DnaX protein with Kd = 2 nM. An artificial operon that contains tandem holC-holD genes was used to overproduce a complex of the χ and ψ subunits of the DNA polymerase III holoenzyme. Normally insoluble by itself, ψ forms a tight soluble complex with χ. A purification procedure that yields pure, active χ·ψ complex in 100-mg quantities suitable for biophysical studies is reported. Sedimentation equilibrium studies demonstrate that χ·ψ is a 1:1 heterodimer. The presence of χ·ψ dramatically lowers the level of δ·δ′ required to reconstitute holoenzyme to levels expected in vivo. That χ·ψ accomplishes this by binding to γ or τ and increasing their affinity for δ·δ′ was demonstrated by surface plasmon resonance using a Pharmacia BIAcoreTM instrument. In the absence of δ·δ′, χ·ψ binds to either the γ or τ DnaX protein with Kd = 2 nM.
Androgen Receptor Cofactors in Prostate Cancer: Potential Therapeutic Targets of Castration-Resistant Prostate Cancer (2011)

Androgens, acting through the androgen receptor (AR), are responsible for many male reproductive and nonreproductive functions. Moreover, aberrant androgen/AR signaling plays a critical role in androgen-dependent prostate cancer (PCa) as well as castration-resistant prostate cancer (CRPC). The formation of a productive AR transcriptional complex requires AR cofactors that interact functionally and structurally with the AR. Since the discovery of the first such cofactor in 1995, an ever increasing number of proteins have been identified as AR coactivators or corepressors. The expression and function of several AR cofactors have been investigated in PCa, and a clear link between AR cofactors and the development and progression of PCa has been identified. Recently, AR splice variants in CRPC were reported, which display significant constitutive activity in the absence of ligand. Then, this discovery revolutionized the concept of AR cofactors in CRPC. The current review aims to provide an overview of AR cofactor proteins in the context of PCa. In addition, we discuss the potential of AR cofactors as novel therapeutic targets for PCa, particularly for CRPC.
Differentially detected coherent population trapping resonances excited by orthogonally polarized laser fields (2006)

We demonstrate the excitation and low-noise differential detection of a coherent population trapping (CPT) resonance with two modulated optical fields with orthogonal circular polarizations. When a microwave phase delay of lambda/4 is introduced in the optical path of one of the fields, the difference in the power transmitted through the cell in each polarization shows a narrow, dispersive resonance. The differential detection allows a high degree of suppression of laser-induced noise and will enable nearly shot-noise-limited operation of atomic frequency references and magnetometers based on CPT.
Morphometric Analysis of Cell Types in the Ovine Corpus Luteum throughout the Estrous Cycle1 (1986)

The cellular composition of ovine corpora lutea obtained during the early (Day 4), mid (Days 8 and 12), and late (Day 16) stages of the estrous cycle was determined by morphometric analysis. Individual corpora lutea were collected via midventral laparotomy from a total of 19 ewes. A center slice from each corpus luteum was processed for electron microscopy and subsequent morphometric analysis of the numbers and sizes of steroidogenic and nonsteroidogenic cells. Luteal weight progressively increased throughout the estrous cycle (p less than 0.05). Corpora lutea collected on Day 16 were assigned to one of two subgroups on the basis of gross appearance and weight: nonregressed (NR, 542 +/- 25 mg) or regressed (R, 260 +/- 2 mg). There were no significant changes in the proportion of the corpus luteum occupied by small luteal cells (19 +/- 2%) or large luteal cells (36 +/- 1%) throughout the estrous cycle. The total number of steroidogenic cells per corpus luteum increased from 21.8 +/- 3.7 (X 10(6)) on Day 4 to 61.7 +/- 5.4 (X 10(6)) on Day 8 (p less than 0.05) and remained elevated thereafter. The number of small luteal cells was 10.0 +/- 2.7 (X 10(6)), 39.7 +/- 1.4 (X 10(6)), 46.1 +/- 5.8 (X 10(6)), 49.0 +/- 13.7 (X 10(6)), and 29.9 +/- 8.6 (X 10(6)) on Days 4, 8, 12, 16 (NR), and 16 (R), respectively (p less than 0.05, Day 4 vs. Days 8, 12, 16 NR). In contrast, the number of large luteal cells was 11.8 +/- 1.5 (X 10(6)) on Day 4 and did not vary significantly during the remainder of the estrous cycle. The numbers of nonsteroidogenic cell types increased (p less than 0.05) from Day 4 to Day 16 (NR) but were decreased in regressed corpora lutea (Day 16 R). Regression was characterized by a 50% decrease (p less than 0.05) in the total number of cells per corpus luteum from 243 +/- 57 ( X 10(6)) on Day 16 (NR) to 125 +/- 14 ( X 10(6)) on Day 16 (R) (p less than 0.05). Small luteal cells remained constant in volume throughout the entire estrous cycle (2520 +/- 270 microns 3), whereas large luteal cells increased in size from 5300 +/- 800 microns 3 on Day 4 to 16,900 +/- 3300 microns 3 on Day 16 (NR) (p less than 0.05). In summary, small luteal cells increased in number but not size throughout the estrous cycle, whereas large luteal cells increased in size but not number.
Statistical Analyses of Next Generation Sequence Data: A Partial Overview (2010)

Next generation sequencing has revolutionized the status of biological research. For a long time, the gold standard of DNA sequencing was considered to be the Sanger method. However, in 2005, commercial launching of next generation sequencing has made it possible to generate massively parallel and high resolution DNA sequence data. Its usefulness in various genomic applications such as genome-wide detection of SNPs, DNA methylation profiling, mRNA expression profiling, whole-genome re-sequencing and so on are now well recognized. There are several platforms for generating next generation sequencing (NGS) data which we briefly discuss in this mini overview. With new technologies come new challenges for the data analysts. This mini review attempts to present a collection of selected topics in the current development of statistical methods dealing with these novel data types. We believe that knowing the advances and bottlenecks of this technology will help the researchers to benchmark the analytical tools dealing with these data and will pave the path for its proper application into clinical diagnostics.
Atomically Controlled Processing for Group IV Semiconductors by Chemical Vapor Deposition (2006)

One of the main requirements for Si-based ultrasmall devices is atomic-order control of process technology. Here we show the concept of atomically controlled processing for group IV semiconductors based on atomic-order surface reaction control. By ultraclean low-pressure chemical vapor deposition using SiH4 and GeH4 gases, high-quality low-temperature epitaxial growth of Si, Ge, and Si1-xGex with atomically flat surfaces and interfaces on Si(100) is achieved, and atomic-order surface reaction processes on group IV semiconductor surface are formulated based on a Langmuir-type surface adsorption and reaction scheme. In in-situ doped Si1-xGex epitaxial growth on the (100) surface in a SiH4–GeH4–dopant (PH3, or B2H6 or SiH3CH3)–H2 gas mixture, the deposition rate, the Ge fraction and the dopant concentration are explained quantitatively assuming that the reactant gas adsorption/reaction depends on the surface site material and that the dopant incorporation in the grown film is determined by Henry's law. Self-limiting formation of 1–3 atomic layers of group IV or related atoms in the thermal adsorption and reaction of hydride gases on Si(100) and Ge(100) is generalized based on the Langmuir-type model. Si or SiGe epitaxial growth over N, P or B layer already-formed on Si(100) or SiGe(100) surface is achieved. Furthermore, the capability of atomically controlled processing for advanced devices is demonstrated. These results open the way to atomically controlled technology for ultralarge-scale integrations.
Bioinspired, mechanical, deterministic fractal model for hierarchical suture joints (2012)

Many biological systems possess hierarchical and fractal-like interfaces and joint structures that bear and transmit loads, absorb energy, and accommodate growth, respiration, and/or locomotion. In this paper, an elastic deterministic fractal composite mechanical model was formulated to quantitatively investigate the role of structural hierarchy on the stiffness, strength, and failure of suture joints. From this model, it was revealed that the number of hierarchies (N) can be used to tailor and to amplify mechanical properties nonlinearly and with high sensitivity over a wide range of values (orders of magnitude) for a given volume and weight. Additionally, increasing hierarchy was found to result in mechanical interlocking of higher-order teeth, which creates additional load resistance capability, thereby preventing catastrophic failure in major teeth and providing flaw tolerance. Hence, this paper shows that the diversity of hierarchical and fractal-like interfaces and joints found in nature have definitive functional consequences and is an effective geometric-structural strategy to achieve different properties with limited material options in nature when other structural geometries and parameters are biologically challenging or inaccessible. This paper also indicates the use of hierarchy as a design strategy to increase design space and provides predictive capabilities to guide the mechanical design of synthetic flaw-tolerant bioinspired interfaces and joints.
Late intraphagosomal hydrogen ion concentration favors the in vitro antimicrobial capacity of a 37-kilodalton cationic granule protein of human neutrophil granulocytes (1986)

We described previously (W.M. Shafer, L.E. Martin, and J.K. Spitznagel, Infect. Immun. 45:29-35, 1984) the presence of a 37-kilodalton cationic antimicrobial protein (37K CAP) in extracts of granules prepared from human polymorphonuclear granulocytes (PMN). In this investigation, we prepared 37K CAP from PMN granule extracts by sequential ion-exchange and molecular-sieve chromatography and examined its antimicrobial activity against a number of gram-negative and gram-positive bacteria. At concentrations of 5 micrograms/ml or lower, 37K CAP exerted selective antimicrobial activity against gram-negative bacteria. These bacteria included Acinetobacter lwoffii, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Pseudomonas cepacia, Salmonella typhi, Salmonella typhimurium, and Shigella sonnei. However, at 5 micrograms of 37K CAP per ml, Proteus mirabilis, Proteus vulgaris, and Serratia marcescens resisted this antimicrobial activity. The bactericidal activity of 37K CAP was greatest in acidic (pH 5.5) as opposed to alkaline (pH 7.5) media. The level of S. typhimurium resistance to 37K CAP correlated with the presence of O antigen in the lipopolysaccharide. In the absence of O antigen repeat units, resistance was proportional to the length of the core oligosaccharide. These results suggest that 37K CAP may contribute significantly to the ability of PMN to kill gram-negative bacteria by nonoxidative means, particularly as the maturing phagolysosome becomes acidified.
Synthesis and Biological Characterization of Arylomycin B Antibiotics (2011)

Antibiotics are virtually always isolated as families of related compounds, but the evolutionary forces underlying the observed diversity are generally poorly understood, and it is not even clear whether they are all expected to be biologically active. The arylomycin class of antibiotics is comprised of three related families that are differentiated by nitration, glycosylation, and hydroxylation of a conserved core scaffold. Previously, we reported the total synthesis of an A series member, arylomycin A2, as well as the A series derivative arylomycin C16 and showed that both are active against a broader spectrum of bacteria than previously appreciated. We now report the total synthesis of a B series analogue, arylomycin B-C16, and its aromatic amine derivative. While the aromatic amine loses activity against all bacteria tested, the B series compound shows activities that are similar to the A series compounds, except that it also gains activity against the important pathogen Streptococcus agalactiae.
Cytoplasmic Metadherin (MTDH) Provides Survival Advantage under Conditions of Stress by Acting as RNA-binding Protein (2011)

Overexpression of metadherin (MTDH) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in prostate tumors, and this localization correlates with poor prognosis. Herein, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized to the cytoplasm in endometrial cancer cells, and the N-terminal region of MTDH was required to maintain cytoplasmic localization. Next, we identified novel binding partners for cytoplasmic MTDH, including RNA-binding proteins and components of the RNA-induced silencing complex. Nucleic acids were required for the association of MTDH with these cytoplasmic proteins. Furthermore, MTDH interacted with and regulated protein expression of multiple mRNAs, such as PDCD10 and KDM6A. Depletion of cytoplasmic MTDH was associated with increased stress granule formation, reduced survival in response to chemotherapy and the tyrosine kinase inhibitor BIBF1120, Rad51 nuclear accumulation, and cell cycle arrest at G(2)/M. Finally, in vivo tumor formation was abrogated with knockdown of cytoplasmic MTDH. Taken together, our data identify a novel function for cytoplasmic MTDH as an RNA-binding protein. Our findings implicate cytoplasmic MTDH in cell survival and broad drug resistance via association with RNA and RNA-binding proteins.