gebhart/patrepeval huggingface dataset:
Analysis of the promoter region of the gene encoding mouse cholesterol side-chain cleavage enzyme. (1990)

The cholesterol side-chain cleavage enzyme (SCC) catalyzes the initial and rate-limiting step in the synthesis of steroid hormones. The mouse gene encoding SCC was cloned and the nucleotide sequence of its 5'-flanking region determined. This sequence includes an AP-1 motif at -319 and two motifs, AGGTCA at -70 and AGCCTTG at -40, that match elements proposed to be important in the expression of steroid 21-hydroxylase. When transfected into mouse Y1 adrenocortical tumor cells, 1.5 kilobase pairs of 5'-flanking region of the SCC gene directed high levels of expression of a growth hormone reporter gene; treatment of the transfected Y1 cells with 8-bromo-cAMP increased this expression by 5-fold. In contrast, transfected mouse MA-10 Leydig cells showed appreciably lower expression, suggesting that SCC expression in Leydig cells requires additional elements not contained in the 5'-flanking region of the SCC gene used in these experiments. Deletion experiments showed that 424 base pairs of 5'-flanking sequences were sufficient for regulated expression in Y1 cells and mapped two regulatory regions: one from -424 to -327 and a second from -219 to -77. DNase I footprinting and gel mobility shift analyses of these 424 base pairs defined several interactions between nuclear proteins and the SCC promoter, including footprints centered over the AP-1 motif, over a sequence at -120, and over the sequences (-70 and -40) that resemble 21-hydroxylase promoter elements. Finally, site-selected mutagenesis of the potential elements at -40, -70, or -120 decreased SCC promoter activity in transfected Y1 adrenocortical cells, thus establishing their importance in SCC expression.
Targeted therapy using nanotechnology: focus on cancer (2014)

Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.
Definite characterization of porcine flow karyotype by chromosome painting after PARM-PCR (1992)

Chantier qualité spécifique "Auteurs Externes" département de Génétique animale : uniquement liaison auteur au référentiel HR-Access
Open pore biodegradable matrices formed with gas foaming (1998)

Engineering tissues utilizing biodegradable polymer matrices is a promising approach to the treatment of a number of diseases. However, processing techniques utilized to fabricate these matrices typically involve organic solvents and/or high temperatures. Here we describe a process for fabricating matrices without the use of organic solvents and/or elevated temperatures. Disks comprised of polymer [e.g., poly (D,L-lactic-co-glycolic acid)] and NaCl particles were compression molded at room temperature and subsequently allowed to equilibrate with high pressure CO2 gas (800 psi). Creation of a thermodynamic instability led to the nucleation and growth of gas pores in the polymer particles, resulting in the expansion of the polymer particles. The polymer particles fused to form a continuous matrix with entrapped salt particles. The NaCl particles subsequently were leached to yield macropores within the polymer matrix. The overall porosity and level of pore connectivity were regulated by the ratio of polymer/salt particles and the size of salt particles. Both the compressive modulus (159+/-130 kPa versus 289+/-25 kPa) and the tensile modulus (334+/-52 kPa versus 1100+/-236 kPa) of the matrices formed with this approach were significantly greater than those formed with a standard solvent casting/particulate leaching process. The utility of these matrices was demonstrated by engineering smooth muscle tissue in vitro with them. This novel process, a combination of high pressure gas foaming and particulate leaching techniques, allows one to fabricate matrices with a well controlled porosity and pore structure. This process avoids the potential negatives associated with the use of high temperatures and/or organic solvents in biomaterials processing.
A Polydimethylsiloxane (PDMS) Sponge for the Selective Absorption of Oil from Water (2011)

We present a sugar-templated polydimethylsiloxane (PDMS) sponge for the selective absorption of oil from water. The process for fabricating the PDMS sponge does not require any intricate synthesis processes or equipment and it is not environmentally hazardous, thus promoting potential in environmental applications. The proposed PDMS sponge can be elastically deformed into any shape, and it can be compressed repeatedly in air or liquids without collapsing. Therefore, absorbed oils and organic solvents can be readily removed and reused by simply squeezing the PDMS sponge, enabling excellent recyclability. Furthermore, through appropriately combining various sugar particles, the absorption capacity of the PDMS sponge is favorably optimized.
B‐Lymphocytes Activated by CD40 Ligand Induce an Antigen‐Specific Anti‐Tumour Immune Response by Direct and Indirect Activation of CD8+ T‐cells (2004)

In this report, we describe the ability of CD40-ligand (CD40L)-activated, antigen-loaded B-cells to initiate antigen-specific anti-tumour immune responses in vivo. Mice immunized by means of intravenous administration of CD40L-activated B-cells loaded with an MHC class-I-binding peptide, and challenged with a tumour cell line expressing the same class-I epitope, showed a marked delay in tumour growth, compared to non-immunized controls or to mice receiving either freshly isolated B-cells or B-cells activated with lipopolysaccharide or interleukin-4. The ability of CD40L-activated B-cells to induce antigen-specific T-cell activation appeared to be through a combination of cross-presentation of antigen from activated B-cells to resident antigen-presenting cells and direct T-cell activation by the administered B-cells themselves. Immunization with CD40L-activated B-cells may, therefore, represent a means by which to stimulate anti-tumour CD8(+) T-cell responses in vivo.
Noncovalent Association of Protein and Capsular Polysaccharide on Bacteria-Sized Latex Beads as a Model for Polysaccharide-Specific Humoral Immunity to Intact Gram-Positive Extracellular Bacteria (2013)

Intact Streptococcus pneumoniae expressing type 14 capsular polysaccharide (PPS14) and type III S. agalactiae containing a PPS14 core capsule identical to PPS14 exhibit noncovalent associations of PPS14 and bacterial protein, in contrast to soluble covalent conjugates of these respective Ags. Both bacteria and conjugates induce murine PPS14-specific IgG responses dependent on CD4⁺ T cells. Further, secondary immunization with conjugate and S. agalactiae, although not S. pneumoniae, results in a boosted response. However, in contrast to conjugate, PPS14-specific IgG responses to bacteria lack affinity maturation use the 44.1-idiotype and are dependent on marginal zone B cells. To better understand the mechanism underlying this dichotomy, we developed a minimal model of intact bacteria in which PPS14 and pneumococcal surface protein A (PspA) were stably attached to 1 μm (bacteria-sized) latex beads, but not directly linked to each other, in contrast to PPS14-PspA conjugate. Beads coated simultaneously with PPS14+[PspA], similar to conjugate, induced in mice boosted PPS14-specific IgG secondary responses, dependent on T cells and ICOS-dependent costimulation, and in which priming could be achieved with PspA alone. In contrast to conjugate, but similar to intact bacteria, the primary PPS14-specific IgG response to beads coated simultaneously with PPS14+[PspA] peaked rapidly, with the secondary response highly enriched for the 44.1-idiotype and lacking affinity maturation. These results demonstrate that noncovalent association in a particle, of polysaccharide and protein, recapitulates essential immunologic characteristics of intact bacteria that are distinct from soluble covalent conjugates of these respective Ags.
Reversible ubiquitination regulates the Smad/TGF-β signalling pathway (2006)

TGF-beta (transforming growth factor-beta) signals through serine/threonine kinase receptors and intracellular Smad transcription factors. An important regulatory step involves specific ubiquitination by Smurfs (Smad-ubiquitin regulatory factors), members of the HECT (homologous to E6-associated protein C-terminus) ubiquitin ligase family, which mediate the proteasomal degradation of Smads and/or receptors. Recently, we have defined a novel interaction between Smads and UCH37 (ubiquitin C-terminal hydrolase 37), a DUB (de-ubiquitinating enzyme) that could potentially counteract Smurf-mediated ubiquitination. We have demonstrated specific interactions between UCH37 and inhibitory Smad7, as well as weaker associations with Smad2 and Smad3. Importantly, Smad7 can act as an adaptor able to recruit UCH37 to the type I TGF-beta receptor. Consequently, UCH37 dramatically up-regulates TGF-beta-dependent gene expression by de-ubiquitinating and stabilizing the type I TGF-beta receptor. Our findings suggest that competing effects of ubiquitin ligases and DUBs in complex with Smad7 can serve to fine-tune responses to TGF-betas under various physiological and pathological conditions. Studies are currently under way using activity-based HA (haemagglutinin)-tagged ubiquitin probes to identify the full spectrum of DUBs that impact on Smad/TGF-beta signalling activity.
Report on a long-term trial of CYBEST Model 2 for prescreening for squamous cell carcinoma of the uterine cervix. (1989)

The results of a 12 year field trial, on a large patient base, of the CYBEST Model 2, an automated screening system using an image analysis method, are summarized. The cell specimens were stained by a conventional Papanicolaou method. Individual cellular atypism was determined from the sum of the nuclear area, the N/C ratio, the mean nuclear optical density, and the nuclear roundness with an ambiguity function value of 0.4295. CYBEST's final assessment as 'suspicious' or 'normal' was statistically determined from a cumulative histogram of the cellular atypism of a maximum 300 detected cells for each cell population using the Kolmogrov-Smirnov test, and those of unsatisfactory samples were automatically classed as 'rejected', which occurred in 6% of the study. A total of 84 atypical preparations including 17 histologically proven carcinoma patients were encountered during the entire test period from 1977 to 1988, and the overall false negative rate was 1.19% (1/84). Among the results on a total of 42,988 slides during the test period of the last 9 years from 1980 to 1988, the false positives occurred at a rate of 30.7% (12,383/40,307 of non-dysplastic slides) and the false negatives at approximately 2% (1/55 of dysplastic slides). These results are compared with those of other important systems.
A Highly Efficient Catalyst for Oxime Ligation and Hydrazone–Oxime Exchange Suitable for Bioconjugation (2013)

Imine-based reactions are useful for a wide range of bioconjugation applications. Although aniline is known to catalyze the oxime ligation reaction under physiological conditions, it suffers from slow reaction kinetics, specifically when a ketone is being used or when hydrazone-oxime exchange is performed. Here, we report on the discovery of a new catalyst that is up to 15 times more efficient than aniline. That catalyst, m-phenylenediamine (mPDA), was initially used to analyze the kinetics of oxime ligation on aldehyde- and ketone-containing small molecules. While mPDA is only modestly more effective than aniline when used in equal concentrations (~2-fold), its much greater aqueous solubility relative to aniline allows it to be used at higher concentrations, resulting in significantly more efficient catalysis. In the context of protein labeling, it was first used to site-specifically label an aldehyde-functionalized protein through oxime ligation, and its kinetics were compared to reaction with aniline. Next, a protein was labeled with an aldehyde-containing substrate in crude cell lysate, captured with hydrazide-functionalized beads and then the kinetics of immobilized protein release via hydrazone-oxime exchange were analyzed. Our results show that mPDA can release and label 15 times more protein than aniline can in 3 h. Then, using the new catalyst, ciliary neurotrophic factor, a protein with therapeutic potential, was successfully labeled with a fluorophore in only 5 min. Finally, a protein containing the unnatural amino acid, p-acetyl phenylalanine, a ketone-containing residue, was prepared and PEGylated efficiently via oxime ligation using mPDA. This new catalyst should have a significant impact on the field of bioconjugation, where oxime ligation and hydrazone-oxime exchange are commonly employed.
Two-dimensional imaging through diffusing media using 150-fs gated electronic holography techniques (1991)

We combine 150-fs holographic gating with specifically adapted electronic holography techniques to produce transmission images of objects embedded in diffusing material. The technique captures, without the use of scanning procedures, complete two-dimensional images with 150-fs temporal resolution, thereby yielding submillimeter spatial resolution through diffusing objects several centimeters thick.
MRBAYES: Bayesian inference of phylogenetic trees (2001)

MRBAYES, including the source code, documentation, sample data files, and an executable, is available at http://brahms.biology.rochester.edu/software.html.
Automated particle classification based on digital acquisition and analysis of flow cytometric pulse waveforms (1996)

In flow cytometry, the typical use of front-end analog processing limits the pulse waveform features that can be measured to pulse integral, height, and width. Direct digitizing of the waveforms provides a means for the extraction of additional features, for example, pulse skewness and kurtosis, and Fourier properties. In this work, we have first demonstrated that the Fourier properties of the pulse can be employed usefully for discrimination between different types of cells that otherwise cannot be classified by using only time-domain features of the pulse. We then implemented and evaluated automatic procedures for cell classification based on neural networks. We established that neural networks could provide an efficient means of classification of cell types without the need for user interaction. The neural networks were also employed in an innovative manner for analysis of the digital flow cytometric data without feature extraction. The performance of the neural networks was compared with that of a more conventional means of classification, the K-means clustering algorithm. Neural networks can be realized in hardware, and this, in addition to their highly parallel architecture, makes them an important potential part of real-time analysis systems. These results are discussed in terms of the design of a real-time digital data acquisition system for flow cytometry. © 1996 Wiley-Liss, Inc.
C-Reactive Protein, Interleukin-6, and Fibrinogen as Predictors of Coronary Heart Disease (2003)

This association may reflect the underlying inflammatory reaction located in the atherosclerotic plaque or a genetic susceptibility on the part of CHD subjects to answer a proinflammatory stimulus and subsequent increase in hepatic CRP gene expression.
Differences and similarities in the A2.1‐restricted cytotoxic T cell repertoire in humans and human leukocyte antigen‐transgenic mice (1996)

HLA-A2.1-binding peptides (n = 38) were screened for immunogenicity with human peripheral blood mononuclear cells in cytotoxic T lymphocyte (CTL) induction experiments in vitro and with splenocytes from HLA-A2.1/Kb transgenic mice following immunization in vivo. These data were compiled and analyzed to determine the level of overlap between the A2.1-restricted CTL repertoire of A2.1/Kb-transgenic mice and A2.1+ humans. In both humans and mice, a major histocompatibility complex affinity threshold of approximately 500 nM appears to determine the capacity of a peptide to elicit a CTL response. Good concordance between the human data in vitro and mouse data in vivo was observed with 85% of the high-binding peptides, 58% of the intermediate binders, and 83% of the low/negative binders. Although some peptides immunogenic for mouse CTL but not for humans (and vice versa) could be identified, the data as a whole suggest an extensive overlap between T cell receptor repertoires of mouse and human CTL and support the use of HLA-transgenic mice for the identification of potential human CTL epitopes.
The Cost of Protein Production (2015)

The economy of protein production is central to cell physiology, being intimately linked with cell division rate and cell size. Attempts to model cellular physiology are limited by the scarcity of experimental data defining the molecular processes limiting protein expression. Here, we distinguish the relative contribution of gene transcription and protein translation to the slower proliferation of budding yeast producing excess levels of unneeded proteins. In contrast to widely held assumptions, rapidly growing cells are not universally limited by ribosome content. Rather, transcription dominates cost under some conditions (e.g., low phosphate), translation in others (e.g., low nitrogen), and both in other conditions (e.g., rich media). Furthermore, cells adapted to enforced protein production by becoming larger and increasing their endogenous protein levels, suggesting limited competition for common resources. We propose that rapidly growing cells do not exhaust their resources to maximize growth but maintain sufficient reserves to accommodate changing requirements.
Randomized, Double-Blind, Placebo-Controlled Trial Using Lidocaine Patch 5% in Traumatic Rib Fractures (2009)

The lidocaine patch 5% does not significantly improve pain control in polytrauma patients with traumatic rib fractures.
Settlement of Ulva Zoospores on Patterned Fluorinated and PEGylated Monolayer Surfaces (2007)

Various designs for coatings that resist the attachment of marine organisms are based on the concept of "ambiguous" surfaces that present both hydrophobic and hydrophilic functionalities as surface domains. In order to facilitate the optimal design of such surfaces, information is needed on the scale of the domains that the settling stages of marine organisms are able to distinguish. Previous experiments showed that Ulva zoospores settle (attach) in high numbers onto fluorinated monolayers compared to PEGylated monolayers. The main aim of the present study was to determine, when zoospores of the green alga Ulva are presented with a choice of fluorinated or PEGylated surfaces, what the minimum dimensions of the two types of surface are that zoospores can detect and consequently settle on. Silicon wafers were chemically modified to produce a pattern of squares containing alternating fluorinated and PEGylated stripes of different widths on either a uniform fluorinated or PEGylated background. Each 1 cm x 1 cm square contained stripes with widths of 500, 200, 100, 50, 20, 5, or 2 microm as well as an unpatterned square with a chemistry opposite that of the background. Spores were selective in choosing where to settle, settling at higher densities on fluorinated stripes compared to PEGylated stripes. However, the magnitude of response, and the consequences for settlement on patterned areas overall, was dependent on both the width of the stripes and the chemistry of the background. The data are discussed in relation to the ability of spores to "choose" favorable sites for settlement and the implications for the development of novel antifouling coatings.
Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion (2006)

Lenalidomide can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients who have the myelodysplastic syndrome with the 5q31 deletion. (ClinicalTrials.gov number, NCT00065156 [ClinicalTrials.gov].).
Dynamic, Structural, And Regulatory Aspects Of Lambda-Site-Specific Recombination (1989)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Active Message Applications Programming Interface (1996)

High-performance network hardware is advancing, with multi-gigabit link bandwidths and sub-microsec and switch latencies. Network-interface hardware also continues to evolve, although the design space remains large and diverse. One critical abstraction, a simple, portable, and general-purpose communications interface, is required to make effective use of these increasingly high-performance networks and their capable interfaces. Without a new interface, the software overheads of existing ones will dominate communication costs, and many applications may not benefit from the advancements in network hardware. This document specifies a new active message communications interface for these networks. Its primitives, in essence an instruction set for communications, map efficiently onto underlying network hardware and compose effectively into higher-level protocols and applications. For high-performance implementations, the interface enables direct application-network interface interactions. In the common case, for applications exhibiting locality in communication, these interactions bypass the operating system. To enable the construction of large-scale, general-purpose systems, the interface supports the protected multiprogramming of many users onto finite network resources. This document also describes a prototype system that uses the virtual-memory facilities of the Solaris operating system to implement virtual networks that sup port protected, network multiprogramming. The system caches the active communication endpoints in network-interface memory and demand-pages them between the host and network-interface memories.