gebhart/patrepeval huggingface dataset:
Telomere shortening and metabolic compromise underlie dystrophic cardiomyopathy (2016)

Significance We have found that long telomeres protect mice from genetic cardiac diseases analogous to those found in humans, such as Duchenne muscular dystrophy (DMD). Mice lacking dystrophin, similar to patients with DMD, exhibit only mild disease. In contrast, mice that lack dystrophin and have “humanized” telomere lengths ( mdx 4cv /mTR G2 ) fully manifest both the severe human skeletal muscle wasting and cardiac failure typical of DMD. Remarkably, telomere shortening accompanies cardiac development even after cardiomyocyte division has ceased. This chronic proliferation-independent shortening in dystrophin-deficient cardiomyocytes is associated with induction of a DNA damage response, mitochondrial dysfunction, increased oxidative stress, and metabolic failure. Our findings highlight an interplay between telomere length and mitochondrial homeostasis in the etiology of dystrophic heart failure.
Cloning, purification, and properties of a phosphotyrosine protein phosphatase from Streptomyces coelicolor A3(2) (1996)

We describe the isolation and characterization of a gene (ptpA) from Streptomyces coelicolor A3(2) that codes for a protein with a deduced M(r) of 17,690 containing significant amino acid sequence identity with mammalian and prokaryotic small, acidic phosphotyrosine protein phosphatases (PTPases). After expression of S. coelicolor ptpA in Escherichia coli with a pT7-7-based vector system, PtpA was purified to homogeneity as a fusion protein containing five extra amino acids. The purified fusion enzyme catalyzed the removal of phosphate from p-nitrophenylphosphate (PNPP), phosphotyrosine (PY), and a commercial phosphopeptide containing a single phosphotyrosine residue but did not cleave phosphoserine or phosphothreonine. The pH optima for PNPP and PY hydrolysis by PtpA were 6.0 and 6.5, respectively. The Km values for hydrolysis of PNPP and PY by PtpA were 0.75 mM (pH 6.0, 37 degrees C) and 2.7 mM (pH 6.5, 37 degrees C), respectively. Hydrolysis of PNPP by S. coelicolor PtpA were 0.75 mM (pH 6.0, 37 degrees C) and 2.7 mM (pH 6.5, 37 degrees C), respectively. Hydrolysis of PNPP by S. coelicolor PtpA was competitively inhibited by dephostatin with a Ki of 1.64 microM; the known PTPase inhibitors phenylarsine oxide, sodium vanadate, and iodoacetate also inhibited enzyme activity. Apparent homologs of ptpA were detected in other streptomycetes by Southern hybridization; the biological functions of PtpA and its putative homologs in streptomycetes are not yet known.
Glucose transporter isotypes switch in T-antigen-transformed pancreatic beta cells growing in culture and in mice. (1992)

High-level expression of the low-Km glucose transporter isoform GLUT-1 is characteristic of many cultured tumor and oncogene-transformed cells. In this study, we tested whether induction of GLUT-1 occurs in tumors in vivo. Normal mouse beta islet cells express the high-Km (approximately 20 mM) glucose transporter isoform GLUT-2 but not the low-Km (1 to 3 mM) GLUT-1. In contrast, a beta cell line derived from an insulinoma arising in a transgenic mouse harboring an insulin-promoted simian virus 40 T-antigen oncogene (beta TC3) expressed very low levels of GLUT-2 but high levels of GLUT-1. GLUT-1 protein was not detectable on the plasma membrane of islets or tumors of the transgenic mice but was induced in high amounts when the tumor-derived beta TC3 cells were grown in tissue culture. GLUT-1 expression in secondary tumors formed after injection of beta TC3 cells into mice was reduced. Thus, high-level expression of GLUT-1 in these tumor cells is characteristic of culture conditions and is not induced by the oncogenic transformation; indeed, overnight culture of normal pancreatic islets causes induction of GLUT-1. We also investigated the relationship between expression of the different glucose transporter isoforms by islet and tumor cells and induction of insulin secretion by glucose. Prehyperplastic transgenic islet cells that expressed normal levels of GLUT-2 and no detectable GLUT-1 exhibited an increased sensitivity to glucose, as evidenced by maximal insulin secretion at lower glucose concentrations, compared with that exhibited by normal islets. Further, hyperplastic islets and primary and secondary tumors expressed low levels of GLUT-2 and no detectable GLUT-1 on the plasma membrane; these cells exhibited high basal insulin secretion and responded poorly to an increase in extracellular glucose. Thus, abnormal glucose-induced secretion of insulin in prehyperplastic islets in mice was independent of changes in GLUT-2 expression and did not require induction of GLUT-1 expression.
FUNCTIONS OF LIPID RAFTS IN BIOLOGICAL MEMBRANES (1998)

Recent studies showing that detergent-resistant membrane fragments can be isolated from cells suggest that biological membranes are not always in a liquid-crystalline phase. Instead, sphingolipid and cholesterol-rich membranes such as plasma membranes appear to exist, at least partially, in the liquid-ordered phase or a phase with similar properties. Sphingolipid and cholesterol-rich domains may exist as phase-separated "rafts" in the membrane. We discuss the relationship between detergent-resistant membranes, rafts, caveolae, and low-density plasma membrane fragments. We also discuss possible functions of lipid rafts in membranes. Signal transduction through the high-affinity receptor for IgE on basophils, and possibly through related receptors on other hematopoietic cells, appears to be enhanced by association with rafts. Raft association may also aid in signaling through proteins anchored by glycosylphosphatidylinositol, particularly in hematopoietic cells and neurons. Rafts may also function in sorting and trafficking through the secretory and endocytic pathways.
The farAB‐encoded efflux pump mediates resistance of gonococci to long‐chained antibacterial fatty acids (1999)

Gonococci often infect mucosal surfaces bathed in antibacterial fatty acids (FAs). Resistance of gonococci to FAs and other antibacterial hydrophobic agents has been attributed to the mtrCDE-encoded efflux pump system and a heretofore undefined mechanism. This alternative resistance mechanism has been suggested to mediate gonococcal resistance to long-chained FAs independently of the mtr efflux pump. We have now identified this alternative FA resistance system in gonococci and report that it bears significant similarity to the emrAB-encoded efflux pump possessed by Escherichia coli and the vceAB-encoded pump of Vibrio cholerae. We termed the gonococcal version of this efflux pump farAB (fatty acid resistance) to signify its involvement in FA resistance expressed by gonococci and to distinguish it from the emrAB- or vceAB-encoded pumps that modulate bacterial susceptibility to uncoupling agents and certain antibiotics. Although the farAB system in gonococci was found to provide resistance to FAs independently of the mtrCDE-encoded efflux pump, its function was dependent on the MtrE outer membrane protein. Moreover, expression of the tandemly linked farA and farB genes was positively associated with the presence of the MtrR transcriptional regulatory protein that normally downregulates the expression of mtrCDE. Thus, the data presented herein suggest that, while the mtrCDE- and farAB-encoded systems act independently to mediate resistance of gonococci to host-derived, hydrophobic antimicrobial agents, their capacity to export these agents is dependent on the same outer membrane protein (MtrE), and their expression may be differentially controlled by the same transcriptional regulatory protein (MtrR).
Limiting Acute Renal Failure (1999)

Although the cause may be inadequate blood flow or a toxic insult to the renal tubules--or a combination thereof--iatrogenesis often underlies acute renal failure. Awareness of the procedures and treatments most likely to precipitate renal failure can help physicians to prevent the condition, or at least to detect it at the earliest opportunity.
Micro- and nanoscale structures for tissue engineering constructs (2000)

Nanotopography presents an effective physical approach for biomaterial cell manipulation mediated through material-extracellular matrix interactions. The extracellular matrix that exists in the cellular microenvironment is crucial for guiding cell behaviours, such as determination of integrin ligation and interaction with growth factors. These interactions with the extracellular matrix regulate downstream mechanotransductive pathways, such as rearrangements in the cytoskeleton and activation of signal cascades. Protein adsorption onto nanotopography strongly influences the conformation and distribution density of extracellular matrix and, therefore, subsequent cell responses. In this review, we first discuss the interactive mechanisms of protein physical adsorption on nanotopography. Secondly, we summarise advances in creating nanotopographical features to instruct desired cell behaviours. Lastly, we focus on the cellular mechanotransductive pathways initiated by nanotopography. This review provides an overview of the current state-of-the-art designs of nanotopography aiming to provide better biomedical materials for the future.
Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials (2004)

Interventions to prevent falls in older adults are effective in reducing both the risk of falling and the monthly rate of falling. The most effective intervention was a multifactorial falls risk assessment and management programme. Exercise programmes were also effective in reducing the risk of falling.
Chronic Abacterial Prostatitis and Hyperthermia A Possible New Treatment? (1991)

A group of 45 patients with chronic abacterial prostatitis or prostatodynia underwent 6 weekly, 1-hour sessions of local deep microwave hyperthermia (42.5 +/- 0.5 degrees C) to the prostate. All patients had a long history of symptoms typical of the condition. They all failed to respond to a variety of conventional treatments administered over several years by various specialists. Each patient served as his own control before and after the hyperthermic treatment. The results of this study are encouraging: 25% showed a sustained and complete loss of symptoms and 50% had a partial response; the remaining 25% reported no improvement. These results open up new possibilities in the treatment of this condition, which has so far responded poorly to conventional therapy.
Properties and Applications of Colloidal Nonspherical Noble Metal Nanoparticles (2010)

Nanoparticles of noble metals belong to the most extensively studied colloidal systems in the field of nanoscience and nanotechnology. Due to continuing progress in the synthesis of nanoparticles with controlled morphologies, the exploration of unique morphology-dependent properties has gained momentum. Anisotropic features in nonspherical nanoparticles make them ideal candidates for enhanced chemical, catalytic, and local field related applications. Nonspherical plasmon resonant nanoparticles offer favorable properties for their use as analytical tools, or as diagnostic and therapeutic agents. This Review highlights morphology-dependent properties of nonspherical noble metal nanoparticles with a focus on localized surface plasmon resonance and local field enhancement, as well as their applications in various fields including Raman spectroscopy, fluorescence enhancement, analytics and sensing, photothermal therapy, (bio-)diagnostics, and imaging.
Engineering a leucine zipper-TRAIL homotrimer with improved cytotoxicity in tumor cells (2009)

Successful cancer therapies aim to induce selective apoptosis in neoplastic cells. The current suboptimal efficiency and selectivity drugs have therapeutic limitations and induce concomitant side effects. Recently, novel cancer therapies based on the use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have emerged. TRAIL, a key component of the natural antitumor immune response, selectively kills many tumor cell types. Earlier studies with recombinant TRAIL, however, revealed its many shortcomings including a short half-life, off-target toxicity, and existence of TRAIL-resistant tumor cells. We improved the efficacy of recombinant TRAIL by redesigning its structure and the expression and purification procedures. The result is a highly stable leucine zipper (LZ)-TRAIL chimera that is simple to produce and purify. This chimera functions as a trimer in a manner that is similar to natural TRAIL. The formulation of the recombinant LZ-TRAIL we have developed has displayed high specific activity in both cell-based assays in vitro and animal tests in vivo. Our results have shown that the half-life of LZ-TRAIL is improved and now exceeds 1 h in mice compared with a half-life of only minutes reported earlier for recombinant TRAIL. We have concluded that our LZ-TRAIL construct will serve as a foundation for a new generation of fully human LZ-TRAIL proteins suitable for use in preclinical and clinical studies and for effective combination therapies to overcome tumor resistance to TRAIL.
Serum Calcitonin Precursors in Sepsis and Systemic Inflammation1 (1998)

High serum levels of the calcitonin (CT) prohormone, procalcitonin (pro-CT), and its component peptides occur in systemic inflammation and sepsis. Using two different assays, we undertook a prospective study to determine the utility of serum precalcitonin peptides (pre-CT) as markers in this condition. Twenty-nine patients meeting criteria for the systemic inflammatory response syndrome were studied daily in two intensive care units. Sera were collected, and APACHE II scores were determined until recovery or death. All patients had markedly elevated serum pre-CT. Prognostically, peak values were the most important. The highest values portended mortality, and a lower level could be ascertained below which all patients survived. Peak pre-CT levels were significantly higher in patients with infection documented by blood cultures than in those patients with no documented infection from any source (P < 0.05). Mature CT remained normal or only moderately elevated. Compared with the serum pre-CT levels, receiver operating characteristic curve analysis revealed that the APACHE II scores, although more cumbersome, were better overall predictors of mortality. Thus, pre-CT is an important serum marker for systemic inflammatory response syndrome and is predictive of outcome. It also provides data concerning the presence of severe infection and may prove to be clinically useful for proactive patient care.
Scalable and efficient provable data possession (2008)

Storage outsourcing is a rising trend which prompts a number of interesting security issues, many of which have been extensively investigated in the past. However, Provable Data Possession (PDP) is a topic that has only recently appeared in the research literature. The main issue is how to frequently, efficiently and securely verify that a storage server is faithfully storing its client's (potentially very large) outsourced data. The storage server is assumed to be untrusted in terms of both security and reliability. (In other words, it might maliciously or accidentally erase hosted data; it might also relegate it to slow or off-line storage.) The problem is exacerbated by the client being a small computing device with limited resources. Prior work has addressed this problem using either public key cryptography or requiring the client to outsource its data in encrypted form.
2D/3D registration with the CMA-ES method (2008)

In this paper, we propose a new method for 2D/3D registration and report its experimental results. The method employs the Covariance Matrix Adaptation Evolution Strategy (CMA-ES) algorithm to search for an optimal transformation that aligns the 2D and 3D data. The similarity calculation is based on Digitally Reconstructed Radiographs (DRRs), which are dynamically generated from the 3D data using a hardware-accelerated technique - Adaptive Slice Geometry Texture Mapping (ASGTM). Three bone phantoms of different sizes and shapes were used to test our method: a long femur, a large pelvis, and a small scaphoid. A collection of experiments were performed to register CT to fluoroscope and DRRs of these phantoms using the proposed method and two prior work, i.e. our previously proposed Unscented Kalman Filter (UKF) based method and a commonly used simplex-based method. The experimental results showed that: 1) with slightly more computation overhead, the proposed method was significantly more robust to local minima than the simplex-based method; 2) while as robust as the UKF-based method in terms of capture range, the new method was not sensitive to the initial values of its exposed control parameters, and has also no special requirement about the cost function; 3) the proposed method was fast and consistently achieved the best accuracies in all compared methods.
Automated mass spectrometry: a revolutionary technology for clinical diagnostics. (2000)

For various diagnostic analyses and the studies of functional genomics, the use of an accurate and cost-effective analytic platform to analyze large numbers of samples is essential. An automated platform called MassArray (Sequenom, Inc, San Diego, CA), designed for high-throughput diagnostic analyses, has recently been validated. The platform combines miniaturized, two-dimensional chip arrays with proven high-fidelity enzymatic procedures and matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Nanoliter dispensing of samples in high-density formats of 384 or greater results in improved throughput and reduced costs. Automation prevails from the initial assay design through sample processing and data analysis, for the most part eliminating the labor component of assay development and implementation. The MassArray platform is being used in the following areas: (1) molecular diagnosis of genetic disease and infectious agents, (2) pharmacogenomics, (3) paternity and/or identity testing, and (4) agriculture (e.g., marker-assisted breeding). MALDI-TOF mass spectrometry can also be used for analyzing proteins; therefore, genotype/phenotype testing can be performed on a single platform.
A generative model for parsing natural language to meaning representations (2008)

In this paper, we present an algorithm for learning a generative model of natural language sentences together with their formal meaning representations with hierarchical structures. The model is applied to the task of mapping sentences to hierarchical representations of their underlying meaning. We introduce dynamic programming techniques for efficient training and decoding. In experiments, we demonstrate that the model, when coupled with a discriminative reranking technique, achieves state-of-the-art performance when tested on two publicly available corpora. The generative model degrades robustly when presented with instances that are different from those seen in training. This allows a notable improvement in recall compared to previous models.
Differential activation of ErbB receptors in the rat olfactory mucosa by transforming growth factor-? and epidermal growth factorin vivo (1998)

Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) are members of the EGF family of growth factors. They have a common receptor, the EGF receptor. This belongs to the tyrosine kinase group of receptors called the ErbB receptor family. Other members are ErbB-2, ErbB-3, and ErbB-4. Binding of either ligand to the receptor elicits an increase in tyrosine kinase activity, resulting in the autophosphorylation of the receptor followed by a phosphorylation cascade of other tyrosine kinase substrates including mitogen-activated protein kinase (MAPK). TGF-alpha and EGF have been shown to stimulate cell division in the olfactory epithelium in vitro and may regulate cell division in vivo. To investigate whether exogenous TGF-alpha or EGF has a functional effect on the olfactory mucosa in vivo, 12.5-50 micrograms of each growth factor was administered to rats via the carotid artery. After 2 min, olfactory mucosa and liver samples were collected, homogenized, and immunoprecipitated with antibodies to the ErbB receptors. The immunoprecipitates were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting. Using phosphotyrosine antibody, the receptors were probed for phosphorylation. Activation of MAPK was also investigated using MAPK antibody. Exogenous TGF-alpha activated EGFR, ErbB-2 and MAPK, whereas EGF activated only the EGFR. TGF-alpha was a more potent activator of EGFR than EGF. Neither ligand had an effect on ErbB-3 and ErbB-4 receptors. These effects were absent in the control animals which received the same solution without the growth factor. These results are consistent with the notion that binding of TGF-alpha to EGFR may play a role in olfactory cell division in vivo.
LAGAN and Multi-LAGAN: Efficient Tools for Large-Scale Multiple Alignment of Genomic DNA (2003)

To compare entire genomes from different species, biologists increasingly need alignment methods that are efficient enough to handle long sequences, and accurate enough to correctly align the conserved biological features between distant species. We present LAGAN, a system for rapid global alignment of two homologous genomic sequences, and Multi-LAGAN, a system for multiple global alignment of genomic sequences. We tested our systems on a data set consisting of greater than 12 Mb of high-quality sequence from 12 vertebrate species. All the sequence was derived from the genomic region orthologous to an approximately 1.5-Mb region on human chromosome 7q31.3. We found that both LAGAN and Multi-LAGAN compare favorably with other leading alignment methods in correctly aligning protein-coding exons, especially between distant homologs such as human and chicken, or human and fugu. Multi-LAGAN produced the most accurate alignments, while requiring just 75 minutes on a personal computer to obtain the multiple alignment of all 12 sequences. Multi-LAGAN is a practical method for generating multiple alignments of long genomic sequences at any evolutionary distance. Our systems are publicly available at http://lagan.stanford.edu.
NATURE: a hybrid nanotube/CMOS dynamically reconfigurable architecture (2006)

Recent progress on nanodevices, such as carbon nanotubes and nanowires, points to promising directions for future circuit design. However, nanofabrication techniques are not yet mature, making implementation of such circuits, at least on a large scale, in the near future infeasible. However, if photo-lithography could be used to implement circuits using these nanodevices, then hybrid nano/CMOS chips could be fabricated and the benefits of nanotechnology could be utilized immediately. A startup company, called Nantero, has developed and implemented a non-volatile nanotube random-access memory (NRAM) using photo-lithography that is considerably faster and denser than DRAM, has much lower power consumption than DRAM or flash, has similar speed to SRAM and is highly resistant to environmental forces (temperature, magnetism). In this paper, we propose a novel high performance reconfigurable architecture, called NATURE, that utilizes CMOS logic and NRAMs. Use of the highly-dense NRAMs allows large on-chip configuration storage, enabling fine-grain run-time reconfiguration and temporal logic folding of a circuit before being mapped to the architecture. This can significantly increase the logic density of NATURE (by over an order of magnitude for larger circuits) while remaining competitive in performance. Compared to traditional reconfigurable architectures, NATURE also allows the designer the flexibility to adjust the level of logic folding in order to improve performance or perform area-performance trade-offs. Experimental results establish its efficacy and give comparisons with today's mainstream FPGA technology which does not allow logic folding.