gebhart/patrepeval huggingface dataset:
Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. (1994)

Deletion of phenylalanine at position 508 (AF608) in the f i s t nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator (CFTR)is the most common mutation in patients with cystic fibrosis.Although retaining functional C1channel activity, this mutant is recognized as abnormal by the cellular "quality control" machinery and is retained within the endoplasmic reticulum (ER).W e have used human epithelial cells and recombinant Chinese hamster ovary cells to identify molecular interactions that may contribute to this intracellular retention.Based upon coimmunoprecipitation and cosedimentation through glycerol density gradients, newly synthesized wild-type and AFS08 mutant CFTRa associated specifically with calnexin, the calcium-binding transmembrane chaperone of the E R This association was restricted to the immature (or ERassociated) forms of the CFTR proteins.Although the bulk of wild-type and AFS08 CFTRs were present initially in complexes containing calnexin, only wild-type CFTR was able to escape from this association and exit the ER.Calnexin retains misfolded or incompletely assembled proteins in the ER and thus is likely to contribute to the mislocalization of mutant CFTR.Mutations in the gene encoding CFTR' (1-3) result in the clinical symptoms of CF due to the absence or malfunction of a regulated C1-channel in the apical membrane of secretory epithelia (for recent reviews, see Refs.4-6).The demonstration that CFTR itself forms the channel (7) has fueled intensive research into methods to alleviate CF through gene therapy (e.g.Refs.8 and 9).Alternative approaches involve attempts to overcome the functional impairment of various mutant CFTRs, especially that in which phenylalanine at position 508 is deleted from the first nucleotide-binding fold (AF508 CFTR).This mutation is found in -70% of CF chromosomes and results in a severe form of the disease (3); >90% of CF patients have at
The specific cytotoxic effects of daunomycin conjugated to antitumor antibodies. (1975)

Daunomycin was covalently bound to immunoglobulins by periodate oxidation as described in the preceding paper. Conjugates were prepared with immunoglobulins directed against either of two mouse lymphoid tumors or with nonspecific immunoglobulins. These conjugates were tested for their toxic effects on various tumor target cells as measured either by their inhibition of RNA synthesis or by their reduction of the growth of the tumor cells after transplantation. We found that the drug preferentially affected the target cells that the antibody to which it was attached could recognize. These daunomycin-antibody conjugates are therefore sufficiently toxic and selective in their effects to be potentially useful in in vivo therapeutic studies.
Response of Murine γδ T Cells to the Synthetic Polypeptide Poly-Glu50Tyr50 1 (2000)

Random heterocopolymers of glutamic acid and tyrosine (pEY) evoke strong, genetically controlled immune responses in certain mouse strains. We found that pE50Y50 also stimulated polyclonal proliferation of normal gamma delta, but not alpha beta, T cells. Proliferation of gamma delta T cells did not require prior immunization with this Ag nor the presence of alpha beta T cells, but was enhanced by IL-2. The gamma delta T cell response proceeded in the absence of accessory cells, MHC class II, beta 2-microglobulin, or TAP-1, suggesting that Ag presentation by MHC class I/II molecules and peptide processing are not required. Among normal splenocytes, as with gamma delta T cell hybridomas, the response was strongest with V gamma 1+ gamma delta T cells, and in comparison with related polypeptides, pE50Y50 provided the strongest stimulus for these cells. TCR gene transfer into a TCR-deficient alpha beta T cell showed that besides the TCR, no other components unique to gamma delta T cells are needed. Furthermore, interactions between only the T cells and pE50Y50 were sufficient to bring about the response. Thus, pE50Y50 elicited a response distinct from those of T cells to processed/presented peptides or superantigens, consistent with a mechanism of Ig-like ligand recognition of gamma delta T cells. Direct stimulation by ligands resembling pE50Y50 may thus selectively evoke contributions of gamma delta T cells to the host response.
Macrophage Migration Inhibitory Factor Promotes Tumor Invasion and Metastasis via the Rho-Dependent Pathway (2005)

Taken together, these results suggest that MIF promotes tumor invasion and metastasis via the Rho-dependent pathway.
Linear birefringence of the retinal nerve fiber layer measured in vitro with a multispectral imaging micropolarimeter (2002)

The <i>Journal of Biomedical Optics</i> (JBO) is a Gold Open Access journal that publishes peer-reviewed papers on the use of novel optical systems and techniques for improved health care and biomedical research.
Increased C-type natriuretic peptide mRNA expression in the kidney of diabetic rats (1998)

To investigate the responsiveness of renal-synthesized C-type natriuretic peptide (CNP) to changes in water and electrolyte balance, we measured renal CNP mRNA levels, plasma CNP concentrations and urinary CNP excretion rates in streptozotocin-induced diabetic rats eating a normal (0.26% NaCl) or low (0.04% NaCl) salt diet. Using reverse transcription-PCR followed by Southern blot analysis, we found that renal cortical and medullary CNP mRNA levels were markedly enhanced in diabetic rats from the 14th day and remained enhanced with an accompanying elevation of urinary CNP excretion rates for the entire 60-day study period. All increases of renal CNP mRNA and urinary CNP excretion rates in diabetic rats were attenuated in low salt diet-treated diabetic rats as well as insulin-treated diabetic rats. These results demonstrate that renal CNP synthesis is enhanced in diabetic rats and the increase of renal CNP mRNA is ameliorated by salt restriction and insulin treatment. These results imply that renal-synthesized CNP is responsive to the alteration of water and electrolyte homeostasis in diabetic rats.
T‐DNA transfer in meristematic cells of maize provided with intracellular Agrobacterium (1996)

Agrobacterium has been established as a tool for gene delivery to most dicotyledonous plant species. However, it is not generally efficient in monocotyledonous plant species, especially not in Graminae . In maize, Agrobacterium ‐mediated DNA transfer has been detected but early developmental stages in the plant proved incompetent as recipients. This research tests whether the lack of competence in young immature embryos of maize could be overcome by providing Agrobacterium in the interior of the plant cell. A microinjection technique was used to target single meristematic cells and prove competence to Agrobacterium . This response is dependent on the maize plant genotype.
On the Mechanism of Interaction of Steroids with Human Glucose 6-Phosphate Dehydrogenase (1995)

Previous studies have demonstrated that certain 17- and 20-ketosteroids are potent inhibitors of the NADP-linked oxidation of glucose 6-phosphate by mammalian glucose 6-phosphate dehydrogenases. This inhibition is uncompetitive with respect to both NADP+ and glucose 6-phosphate. In order to elucidate the detailed mechanism of this rare type of inhibition, we examined the effects of steroids on human glucose 6-phosphate dehydrogenase catalyzing the reverse reaction, i.e., the reduction of the gluconolactone by NADPH. To circumvent problems associated with the known instability of 6-phospho-delta-gluconolactone, the natural product of glucose 6-phosphate oxidation, the more stable 6-phospho-gamma-gluconolactone was used. Dehydroepiandrosterone, epiandrosterone, 16 alpha-bromoepiandrosterone, and dehydroepiandrosterone sulfate all inhibited the reverse reaction uncompetitively with respect to both NADPH and the gamma-lactone. The Ki values for each of these steroids, determined by varying either coenzyme or substrate in both the forward and the reverse reactions, are very similar. These results demonstrate that steroids inhibit glucose 6-phosphate dehydrogenase by binding to the ternary enzyme-coenzyme-substrate ternary complex(es). This is the first direct demonstration that uncompetitive inhibition of a two-substrate enzyme, by compounds other than its substrates or products, can occur by binding of the inhibitor to a ternary enzyme complex.
A Miniature Mobile Robot for Navigation and Positioning on the Beating Heart (2009)

Robotic assistance enhances conventional endoscopy; yet, limitations have hindered its mainstream adoption for cardiac surgery. HeartLander is a miniature mobile robot that addresses several of these limitations by providing precise and stable access over the surface of the beating heart in a less-invasive manner. The robot adheres to the heart and navigates to any desired target in a semiautonomous fashion. The initial therapies considered for HeartLander generally require precise navigation to multiple surface targets for treatment. To balance speed and precision, we decompose any general target acquisition into navigation to the target region followed by fine positioning to each target. In closed-chest, beating-heart animal studies, we demonstrated navigation to targets located around the circumference of the heart, as well as acquisition of target patterns on the anterior and posterior surfaces with an average error of 1.7 mm. The average drift encountered during station-keeping was 0.7 mm. These preclinical results demonstrate the feasibility of precise semiautonomous delivery of therapy to the surface of the beating heart using HeartLander.
Preparation and Storage of High-Titer Lactic Streptococcus Bacteriophages (1974)

Various techniques were employed for preparation of high-titer bacteriophage lysates of Streptococcus lactis, S. cremoris, and S. diacetilactis strains. Infection of a 4-h host culture in litmus milk at 30 C yielded the highest titers (2 x 10 to 4 x 10 plaque-forming units/ml) for most phages. Host infection in lactose-containing broth produced similar virus numbers only when 0.1 M tris(hydroxymethyl)aminomethane buffer stabilized the pH. The pH at the time of infection as well as the inoculum phage titer were critical in obtaining high titers. Optimum conditions for infection in broth were coupled with a polyethylene glycol concentration procedure to routinely produce milligram quantities of phage from 1 liter of lysate. Neutralization of whey lysates, as a means of storage, offered no survival advantage over unneutralized samples. Storage of phage lysates in a 15% glycerol whey solution at -22 C yielded a high rate of survival in most cases, even with repeated freezing and thawing, over a period of 24 months.
Specific amino-acid residues in the N-terminus and TM3 implicated in channel function and oligomerization compatibility of connexin43 (2003)

To identify signals that convey connexin oligomerization compatibility, we have aligned amino-acid sequences of alpha and beta group connexins (Cx) and compared the physico-chemical properties of each homologous amino-acid residue. Four positions were identified that consistently differed between alpha and beta-type connexins; two are located in the N-terminal domain (P1 and P2, corresponding to residues 12 and 13 of the Cx43 sequence), and two in the third trans-membrane-spanning domain TM3 (P3 and P4, corresponding to residues 152 and 153 of the Cx43 sequence). Replacement of each of these residues in Cx43 (an alpha-type connexin) with the corresponding residues of Cx32 (a beta-type connexin) resulted in the assembly of all variants into gap junctions; however, only the P4 variant was functional, as indicated by lucifer yellow dye transfer assays. The other three variants exerted a moderate to severe dose-dependent, dominant-negative effect on co-expressed wild-type (wt) Cx43 channel activity. Moreover, a significant dose-dependent, trans-dominant inhibition of channel activity was observed when either one of the N-terminal variants was co-expressed with wt Cx32. Assembly analyses indicated that dominant and trans-dominant inhibitory effects appeared to be based on the oligomerization of wt and variant connexins into mixed connexons. Interestingly, the identified N-terminal amino acids coincide with the position of naturally occurring, disease-causing missense mutations of several beta-connexin genes (Cx26, Cx30, Cx31, Cx32). Our results demonstrate that three of the identified discriminative amino-acid residues (positions 12, 13 and 152) are crucial for Cx43 channel function and suggest that the N-terminal amino-acid residues at position 12/13 are involved in the oligomerization compatibility of alpha and beta connexins.
Tumorigenic conversion of immortal human keratinocytes through stromal cell activation (1998)

The stromal microenvironment plays a crucial role in tumor development and progression. One of the most potent activators of stromal cells is the platelet-derived growth factor (PDGF). To investigate the role of PDGF in epithelial tumor development we stably transfected immortal nontumorigenic human keratinocytes with the PDGF-B cDNA. Transfected HaCaT cells overexpressed PDGF-B but remained negative for the PDGF receptors alpha and beta (mRNA). Thus, they did not exhibit autocrine growth stimulation in vitro, but proliferation of cocultured fibroblasts was enhanced and this effect was inhibited by a neutralizing antibody to PDGF-BB. After subcutaneous injection into nude mice the transfected cells maintained high PDGF expression and formed progressively enlarging, rapidly proliferating cysts, classified as benign tumors. During early tumor development (up to 2 months), PDGF-B transfectants induced marked mesenchymal cell proliferation and angiogenesis, yet this effect vanished at later stages (2-6 months) concomitantly with increased epithelial cell proliferation and enhanced tumor growth. These results demonstrate that an activated stromal environment can promote tumorigenic conversion of nontumorigenic keratinocytes by inducing sustained epithelial hyperproliferation. This effect is apparently caused by a dual action of PDGF-BB: (i) PDGF-BB can promote tumor growth by inducing angiogenesis and stroma formation, and (ii) PDGF-activated stromal cells maintain elevated keratinocyte proliferation via a paracrine mechanism. Thus, PDGF, a major factor activated in wound healing, may play an important role as an endogenous promoter in epithelial tumor formation.
On Some Fundamental Properties of P2P Push/Pull Protocols (2008)

The peer-to-peer communication paradigm is changing the way the Internet works, and the perspective network and service providers are looking at the telecommunication business. P2P applications and networks are taking foot by the day, and new systems are proposed continuously with ever novel features and better performances. In spite of attention and success, however, there is still a lack of fundamental analysis and understanding of the elementary properties of these systems. In this paper we consider a class of P2P protocols suitable both for content delivery (file-based communications) and for high-bandwidth media streaming like video and TV, and explore its fundamental properties. The class considered is known as mesh-based swarming push-pull systems or interleave protocols. They split the content in pieces and alternate continuously two phases: One where the peer pushes a piece to another peer to percolate information in the system, and the other when it pulls a piece trying to retrieve missing information. We compare synchronous and asynchronous models and explore the impact of protocols parameters, such as the dimension of the active neighborhood, trying to identify the efficiency of these very simple protocols in different scenarios, gaining insight to design the next protocol generation with performance and efficiency in mind.
Oxyfunctionalization of Non-Natural Targets by Dioxiranes. 6. On the Selective Hydroxylation of Cubane (2009)

By using methyl(trifluoromethyl)dioxirane (TFDO), the direct mono- and bishydroxylation of cubane could be achieved in high yield under remarkably mild conditions. Comparison of the rates of dioxirane O-insertion with those of standard reference compounds, such as adamantane and cyclopropane, as well as ab initio computations provide useful hints concerning the mechanism of these transformations.
Synthesis of high specific activity tritium-labeled [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties (1994)

all-trans-Retinoic acid is known to bind to the retinoic acid receptors (RARs) resulting in an increase in their transcriptional activity. In contrast, recently identified 9-cis-retinoic acid (9-cis-RA), which is an additional endogenous RA isomer, is capable of binding to both RARs and retinoid X receptors (RXRs). These distinct properties have raised questions as to the biological role governed by these two retinoic acid isomers and the set of target genes that they regulate. Herein, we report the synthesis of high specific activity [3H]-9-cis-RA and its application to study the ligand-binding properties of the various retinoid receptor subtypes. We examined the binding properties of RARs and RXRs for a series of synthetic retinoids and compared the ligand-binding properties of these arotinoid analogs with their ability to regulate gene expression via the retinoid receptors in a cotransfection assay. The utilization of the [3H]-9-cis-RA competitive binding assay and the cotransfection assay has made it possible to rapidly identify important structural features of retinoids leading to increased selectivity for either the RAR or RXR receptor subtypes.
Development of a parallel code for modeling plasma based accelerators (2003)

Advances in computational speed and memory make it now possible to do full scale 2D and 3D PIC simulations of laser and beam plasma interactions. However, the increased complexity of these codes and interactions make it necessary to apply modern programming approaches like object oriented frameworks to the development of these codes. We report here on our progress in developing the object oriented parallel PIC code OSIRIS that is implemented in Fortran 90. In its current state, the code can be used for 1D, 2D, and 3D simulations in Cartesian coordinates and for 2D simulations in cylindrically symmetric coordinates. We will present benchmarks of simulations done with this code for a proposed plasma wake field accelerator experiment.
Micro-dystrophin and follistatin co-delivery restores muscle function in aged DMD model (2013)

Pharmacologic strategies have provided modest improvement in the devastating muscle-wasting disease, Duchenne muscular dystrophy (DMD). Pre-clinical gene therapy studies have shown promise in the mdx mouse model; however, studies conducted after disease onset fall short of fully correcting muscle strength or protecting against contraction-induced injury. Here we examine the treatment effect on muscle physiology in aged dystrophic mice with significant disease pathology by combining two promising therapies: micro-dystrophin gene replacement and muscle enhancement with follistatin, a potent myostatin inhibitor. Individual treatments with micro-dystrophin and follistatin demonstrated marked improvement in mdx mice but were insufficient to fully restore muscle strength and response to injury to wild-type levels. Strikingly, when combined, micro-dystrophin/follistatin treatment restored force generation and conferred resistance to contraction-induced injury in aged mdx mice. Pre-clinical studies with miniature dystrophins have failed to demonstrate full correction of the physiological defects seen in mdx mice. Importantly, the addition of a muscle enhancement strategy with delivery of follistatin in combination with micro-dystrophin gene therapy completely restored resistance to eccentric contraction-induced injury and improved force. Eccentric contraction-induced injury is a pre-clinical parameter relevant to the exercise induced injury that occurs in DMD patients, and herein, we demonstrate compelling evidence for the therapeutic potential of micro-dystrophin/follistatin combinatorial therapy.
A flexible heterogeneous video processor system for television applications (1999)

A new video processing architecture for high-end TV applications is presented, featuring a flexible heterogeneous multi-processor architecture, executing video tasks in parallel and independently. The signal flow graph and the processors are programmable, enabling an optimal picture quality for different TV display modes. The concept is verified by an experimental chip design. The architecture allows several video streams to be processed and displayed in parallel and in a programmable way, with an individual signal quality.
Direct antenna modulation - a promise for ultra-wideband (UWB) transmitting (2004)

A novel antenna design concept is proposed based on antenna's nonlinear transient responses. The essential idea is to integrate RF switches into a resonant antenna such as a patch antenna. Driven by modulating signals, the switches are able to shut off and turn on the antenna's radiation slots directly. It is observed that narrow pulses can be generated and radiated this way. Thus, the patch antenna's bandpass phenomenon, which limits the antenna's bandwidth, can be overcomed. The experimental results show that a patch antenna with a resonate frequency 2.4 G and a 30 MHz bandwidth can transmit a digital modulated signal with beyond 400 MHz bandwidth.
Nod‐like proteins in inflammation and disease (2007)

The field of innate immunity has undergone an enormous upheaval during the last decade. The discovery of different groups of proteins, called pattern recognition molecules (PRMs), which detect microbial components, so-called pathogen-associated molecular patterns (PAMPs) and trigger protective responses, had a huge impact on the understanding of innate immune responses. Among the PRMs, the intracellular Nod-like receptors (NLRs) have recently been identified as key mediators of inflammatory and immune responses. The NLR family is divided into subfamilies on the basis of their different signal transduction domains, and recent studies have highlighted the role of certain NLRs, including Nod1, Nod2, Nalp3, Ipaf and Naip5, in the detection of intracellular microbes and possibly 'danger signals'. In this review, we summarize the current knowledge on the function of these proteins in immunity and inflammation, with a focus on their participation in different disease pathologies.