gebhart/patrepeval huggingface dataset:
Fatty acid metabolism in hepatocytes isolated from rats adapted to high-fat diets containing long- or medium-chain triacylglycerols (1988)

Fatty acid oxidation and synthesis were studied in isolated hepatocytes from adult rats adapted for 44 days on low-fat, high-carbohydrate (LF), diet or high-fat diets, composed of long-chain (LCT) or medium-chain (MCT) triacylglycerols. The rates of [1-14C]octanoate oxidation were almost similar in each group studied, whereas the oxidation of [1-14C]oleate was 50% lower in the LF group than in animals adapted to high-fat diets. The rates of oleate oxidation are inversely correlated with the rates of lipogenesis. However, it seems unlikely that [malonyl-CoA] itself represents the sole mechanism involved in the regulation of oleate oxidation during long-term LCT or MCT feeding, since: (1) despite a 3-fold higher concentration of malonyl-CoA in MCT-fed rats than in LCT-fed ones, the rates of oleate oxidation are similar; (2) when malonyl-CoA concentration is increased after stimulation of lipogenesis (by adding lactate + pyruvate) in MCT-fed rats, to a level comparable with that of the LF group, the rate of oleate oxidation remains 55% higher than that measured under similar conditions in the LF-fed rats; (3) in the LF group, the 90% decrease in malonyl-CoA concentration [by 5-(tetradecyloxy)-2-furoic acid] is not associated with a stimulation of oleate oxidation. By contrast, the sensitivity of carnitine palmitoyltransferase I (CPT I) to malonyl-CoA is markedly decreased in the LCT- and MCT-fed rats, by 90% and 70% respectively. The relevance of this decrease in the sensitivity of CPT I is discussed.
A conditional rescue system reveals essential functions for the ecdysone receptor (EcR) gene during molting and metamorphosis in Drosophila (2000)

In Drosophila, pulses of the steroid hormone ecdysone trigger larval molting and metamorphosis and coordinate aspects of embryonic development and adult reproduction. At each of these developmental stages, the ecdysone signal is thought to act through a heteromeric receptor composed of the EcR and USP nuclear receptor proteins. Mutations that inactivate all EcR protein isoforms (EcR-A, EcR-B1, and EcR-B2) are embryonic lethal, hindering analysis of EcR function during later development. Using transgenes in which a heat shock promoter drives expression of an EcR cDNA, we have employed temperature-dependent rescue of EcR null mutants to determine EcR requirements at later stages of development. Our results show that EcR is required for hatching, at each larval molt, and for the initiation of metamorphosis. In EcR mutants arrested prior to metamorphosis, expression of ecdysone-responsive genes is blocked and normal ecdysone responses of both imaginal and larval tissues are blocked at an early stage. These results show that EcR mediates ecdysone signaling at multiple developmental stages and implicate EcR in the reorganization of imaginal and larval tissues at the onset of metamorphosis.
Nascent chains: folding and chaperone interaction during elongation on ribosomes (1995)

Monoclonal antibodies that detect folding intermediates in vitro were used to monitor the appearance of folded polypeptide chains during their synthesis on the ribosomes. Nascent immunoreactive chains of the bacteriophage P22 tail-spike protein and of the Escherichia coli beta 2 subunit of tryptophan-synthase were thus identified, suggesting that they can fold on the ribosomes. Moreover, the immunoreactivity of ribosome-bound tryptophan-synthase beta-chains of intermediate lengths was shown to appear with no detectable delay compared to their synthesis. This suggested that beta-chains start folding during their elongation on the ribosomes. However, newly synthesized incomplete beta-chains were shown to interact with chaperones while still bound to the ribosome. Because of the peculiar properties of the epitope recognized by the anti-tryptophan-synthase monoclonal antibody used, it could not be concluded whether the immunoreactivity of the nascent beta-chains resulted from their ability to fold cotranslationally or from their association with chaperones which might maintain them in an unfolded, immunoreactive state.
Binding and interstitial penetration of liposomes within avascular tumor spheroids (2004)

The liposomal delivery of cancer therapeutics, including gene therapy vectors, is an area of intense study. Poor penetration of liposomes into interstitial tumor spaces remains a problem, however. In this work, the penetration of different liposomal formulations into prostate carcinoma spheroids was examined. Spheroid penetration was assessed by confocal microscopy of fluorescently labeled liposomes. The impact of liposomal surface charge, mean diameter, lipid bilayer fluidity and fusogenicity on spheroid penetration was examined. A variety of different liposome systems relevant to clinical or preclinical protocols have been studied, including classical zwitterionic (DMPC:chol) and sterically stabilized liposomes (DMPC:chol:DOPE-PEG2000), both used clinically, and cationic liposomes (DMPC:DOPE:DC-chol and DOTAP), forming the basis of the vast majority of nonviral gene transfer vectors tested in various cancer trials. Surface interactions between strongly cationic vesicles and the tumor cells led to an electrostatically derived binding-site barrier effect, inhibiting further association of the delivery systems with the tumor spheroids (DMPC:DC-chol). However, inclusion of the fusogenic lipid DOPE and use of a cationic lipid of lower surface charge density (DOTAP instead of DC-chol) led to improvements in the observed intratumoral distribution characteristics. Sterically stabilized liposomes did not interact with the tumor spheroids, whereas small unilamellar classical liposomes exhibit extensive distribution deeper into the tumor volume. Engineering liposomal delivery systems with a relatively low charge molar ratio and enhanced fusogenicity, or electrostatically neutral liposomes with fluid bilayers, offered enhanced intratumoral penetration. This study shows that a delicate balance exists between the strong affinity of delivery systems for the tumor cells and the efficient penetration and distribution within the tumor mass, similar to previous work studying targeted delivery by ligand-receptor interactions of monoclonal antibodies. Structure-function relationships from the interaction of different liposome systems with 3-dimensional tumor spheroids can lead to construction of delivery systems able to target efficiently and penetrate deeper within the tumor interstitium and act as a screening tool for a variety of therapeutics against cancer.
UCB system description for the WMT 2007 shared task (2007)

For the WMT 2007 shared task, the UC Berkeley team employed three techniques of interest. First, we used monolingual syntactic paraphrases to provide syntactic variety to the source training set sentences. Second, we trained two language models: a small in-domain model and a large out-of-domain model. Finally, we made use of results from prior research that shows that cognate pairs can improve word alignments. We contributed runs translating English to Spanish, French, and German using various combinations of these techniques.
Lipids are major components of human immunodeficiency virus (HIV): Modification of HIV lipid composition, membrane organization, and protein conformation by AL‐721® (1988)

Abstract The lipid composition of human immunodeficiency virus (HIV) was investigated. Several strains of HIV were found to contain considerable amounts of lipid. The major lipid constituents were cholesterol and phospholipid with a molar ratio close to one. This lipid composition and membrane apparent microviscosity, as determined by diphenylhexatriene fluorescent polarization, indicate that the HIV envelope is an extremely rigid membrane. A previous in vitro study and two recent clinical reports have indicated that AL‐721®, a lipid mixture designed to alter membrane lipid composition and organization by extraction of membrane cholesterol, has anti‐HIV activity. We found that AL‐721® modifies the lipid composition of HIV, reducing the cholesterol content and the cholesterol to phospholipid molar ratio. Both DPH fluorescent probe and endogenous protein fluorescent studies suggest that AL‐721® alters HIV envelope organization and/or apparent microviscosity. Membrane perturbation of HIV by AL‐721® may represent a new approach to AIDS therapy.
Traumatic quadriplegia: follow-up study of self-care skills. (1980)

In this study to assess the extent of use of the self-care skills learned during rehabilitation and of the orthotic devices provided to support function once community living was resumed, 35 persons with traumatic cervical cord injury were tested in the home environment 1 to 4 years after discharge from the hospital. Of this group, 20 had a functional spinal cord level of C6 or C7 and 15 of C4 or C5. The results indicated that the level of self-care achieved during rehabilitation was maintained by the majority of persons at follow-up. The areas most sensitive to change were toileting and bathing, desk skills, grooming, transfers and upper and lower extremity dressing for those with C6 or C7 functional spinal cord levels, and grooming, written communication and desk skills for those with C4 or C5 levels. The majority continued to use at least some of the prescribed upper extremity orthotics and assistive devices. Neither hand surgery nor equipment use was clearly related to functional status. The ratchet hand splint was well accepted by the C4-5 group. Changes in performance are discussed in terms of a restructuring of personal priorities, the availability of interpersonal support, and architectural and attitudinal barriers within the community.
A case for NUMA-aware contention management on multicore systems (2011)

On multicore systems, contention for shared resources occurs when memory-intensive threads are co-scheduled on cores that share parts of the memory hierarchy, such as last-level caches and memory controllers. Previous work investigated how contention could be addressed via scheduling. A contention-aware scheduler separates competing threads onto separate memory hierarchy domains to eliminate resource sharing and, as a consequence, to mitigate contention. However, all previous work on contention-aware scheduling assumed that the underlying system is UMA (uniform memory access latencies, single memory controller). Modern multicore systems, however, are NUMA, which means that they feature non-uniform memory access latencies and multiple memory controllers. We discovered that state-of-the-art contention management algorithms fail to be effective on NUMA systems and may even hurt performance relative to a default OS scheduler. In this paper we investigate the causes for this behavior and design the first contention-aware algorithm for NUMA systems. 1
Confining root programs with domain and type enforcement (DTE) (1996)

The pervasive use of the root privilege is a central problem for UNIX security because an attacker who subverts a single root program gains complete control over a computing system. Domain and type enforcement (DTE) is a strong, configurable operating system access control technology that can minimize the damage root programs can cause if subverted. DTE does this by preventing groups of root programs from accessing critical files in inappropriate access modes. This paper illustrates how a DTE-enhanced UNIX prototype, driven by simple, machine-interpretable DTE policies, can provide strong protection against specific classes of attacks by malicious programs that gain root privilege. We present a sequence of policy components that protect system binaries against Rootkit, a widely-used hacker toolkit, and protect password, system log, user, and device special files against other root-based attacks. Tradeoffs among DTE policy complexity, scope of protection, and other factors are discussed.
Promoter elements required for phloem‐specific gene expression from the RTBV promoter in rice (1997)

Previous studies indicated that a DNA fragment comprising nucleotides (nt) -164 to +45 of the RTBV promoter is sufficient to drive phloem-specific expression of a reporter gene in transgenic rice plants. In addition, two potential cis elements, Box I (nt -3 to +5) and Box II (nt -53 to -39) were identified by DNA-protein interaction assays. In this study, the results of further in vivo studies involving mutagenesis of selected DNA sequences and analysis of expression of a reporter gene in transgenic rice plants revealed that, in addition to Box I and Box II, other elements are required for phloem-specific gene expression, among which are a direct repeat (ASL Box, nt -98 to -79) and a GATA motif (nt -143 to -135). All the these elements bind rice nuclear factors specifically, and mutations of the elements were identified that resulted in loss-of-competition in electrophoretic mobility shift assays. A DNA fragment comprising nt -164 to -32, which contains Box II, the ASL Box and the GATA motif, conferred phloem-specific reporter gene expression independent of Box I when fused to a heterologous CaMV 35S minimal promoter and introduced to transgenic rice plants. Studies that introduced point mutations suggested that in the context of the -103 to +45 promoter fragment, Box II and the ASL Box act synergistically to confer tissue-specific gene expression. Similar studies in the -164 to +45 promoter fragment indicated that the -164 to -103 region, which includes the GATA motif, contains sequences that are functionally redundant with those in the -103 to -32 region, including the ASL Box and Box II. It is concluded that these regions act additively to direct phloem-specific gene expression.
A NATIONAL ACADEMIC PRODUCTION STUDY ABOUT KNOWLEDGEMANAGEMENT THROUGH HABERMAS KNOWLEDGE THEORY (2008)

The purpose of this study is to challenge the academic
					production on Knowledge Management (KM) recently published by the
					Brazilian academy. A total of 6,096 articles published in the
					Proceedings of the National Meeting of Postgraduate Management
					Programs, named ENAPAD, from 1997 to 2007, were compiled. Habermas'
					knowledge theory is of great relevance for the critical debate on
					the area of knowledge management (KM) when three types of
					knowledge: technical, practical and emancipatory. Through the
					documental research it was possible to identify the absolute
					predominance of the technical interest as a characteristic of the
					instrumental reason directed to constant prediction and control in
					the area of KM. Approximately 75% of these empirical studies
					neither touch the question of power relations and knowledge nor
					human consciousness emancipation towards a critical reflection of
					oppressive practices or political and ideological social
					approaches.
Combined Action of Influenza Virus and Staphylococcus aureus Panton–Valentine Leukocidin Provokes Severe Lung Epithelium Damage (2012)

Staphylococcus aureus necrotizing pneumonia is a life-threatening disease that is frequently preceded by influenza infection. The S. aureus toxin Panton-Valentine leukocidin (PVL) is most likely causative for necrotizing diseases, but the precise pathogenic mechanisms of PVL and a possible contribution of influenza virus remain to be elucidated. In this study, we present a model that explains how influenza virus and PVL act together to cause necrotizing pneumonia: an influenza infection activates the lung epithelium to produce chemoattractants for neutrophils. Upon superinfection with PVL-expressing S. aureus, the recruited neutrophils are rapidly killed by PVL, resulting in uncontrolled release of neutrophil proteases that damage the airway epithelium. The host counteracts this pathogen strategy by generating PVL-neutralizing antibodies and by neutralizing the released proteases via protease inhibitors present in the serum. These findings explain why necrotizing infections mainly develop in serum-free spaces (eg, pulmonary alveoli) and open options for new therapeutic approaches.
Secretion of active anti-Ras single-chain Fv antibody by the yeasts Yarrowia lipolytica and Kluyveromyces lactis (2002)

Yarrowia lipolytica and Kluyveromyces lactis secretion vectors were constructed and assessed for the expression of heterologous proteins. An anti-Ras single-chain antibody fragment (scFv) coding sequence was fused in-frame to different pre- or prepro-regions, or downstream from a reporter secretory gene (Arxula adeninivorans glucoamylase), separated by a Kex2 protease (Kex2p)-like processing sequence. Both organisms are able to secrete soluble scFv, with yields depending on the nature of the expression cassette, up to levels ranging from 10 to 20 mg l(-1). N-terminal sequence analysis of the purified scFv showed that fusions are correctly processed to the mature scFv by a signal peptidase or a Kex2p-type endoprotease present in Y. lipolytica and K. lactis. The scFv protein also retains the capacity to bind to a glutathioneS-transferase (GST)-Harvey-Ras(Val12) fusion, indicating that the antibody is functional. These results indicate that the yeasts Y. lipolytica and K. lactis have potential for industrial production of soluble and active scFv.
Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis (2003)

Forty patients with severe sepsis or septic shock recently received C1 inhibitor. In the present study we studied the effect of C1 inhibitor therapy on circulating elastase-alpha(1)-antitrypsin complex (EA) and lactoferrin (LF) levels in these patients to gain further insight about agonists involved in the activation of neutrophils in human sepsis. Elevated levels of EA and LF were found in 65 and 85% of the septic patients, respectively. Patients with elevated EA levels had higher organ dysfunction scores, higher levels of cytokines, and higher levels of complement activation products than patients with normal EA levels. C1 inhibitor therapy reduced EA as well as complement activation and IL-8 release in the patients with elevated EA on admission. We conclude that neutrophil activation in human sepsis correlates with the severity of organ dysfunction and involves complement and interleukin-8 as agonists. The effect of C1 inhibitor therapy on neutrophils may provide an explanation for the beneficial, although mild, effects of this treatment on organ dysfunction in sepsis.
Biological and pharmacological characterisation of three models of human ovarian carcinoma established in nude mice: use of the CA125 tumour marker to predict antitumour activity. (1999)

In an attempt to improve the relevance of human tumour xenografts to the clinical situation, we have established 3 models of human ovarian carcinoma (IGROV1, A2780 and NIH:OVCAR-3) in nude mice in which progressive peritoneal carcinomatosis resulted in the death of tumour-bearing animals (median survival times: 32, 40 and 64 days, respectively). Histological analyses revealed both common and different characteristics in growth patterns and dissemination profiles. In each case, three stages of the disease were defined (early, intermediate and late). The antitumour activities of adriamycin, cisplatin, cyclophosphamide and paclitaxel were then compared when administered at the early stage where small multifocal tumour nodules were detectable in the peritoneal cavity of the animals. Significant antitumour activities of cisplatin and particularly paclitaxel were noted in terms of increase in survival time of the treated mice (T/C values for IGROV1, A2780 and NIH:OVCAR-3 respectively: 152%, 167%, and 187% for cisplatin and 211%, 179% and >283% for paclitaxel), paclitaxel being curative against the NIH:OVCAR-3 xenograft. These results reflect the high efficacy of these two drugs in the clinic in the treatment of ovarian carcinoma. The clinically used CA125 tumour marker, not detectable in healthy mice, was measured in the serum of mice bearing IGROV1 and NIH:OVCAR-3 tumours. CA125 serum levels increased as a function of time and were well correlated to disease progression. Moreover, treatment with cisplatin and paclitaxel led to significant decreases in these levels of between 58% and 100%. This human serum marker could be used to predict early on the efficacy of chemotherapy in these two models. In conclusion, the three experimental ovarian carcinomas possess several important characteristics of the human disease and may thus be used as a screen to select new antitumour drugs potentially active in this pathology.
Angiogenesis in the Infarcted Myocardium (2012)

Optimization of proangiogenic therapies might include stimulation of both angiogenesis and vessel maturation and/or the use of additional sources of stem/progenitor cells, such as cardiac progenitor cells. Experimental unraveling of the mechanisms of angiogenesis, vessel maturation, and endothelial cell/cardiomyocyte cross talk in the ischemic heart, analysis of emerging pathways, as well as a better understanding of how cardiovascular risk factors impact endogenous and therapeutically stimulated angiogenesis, would undoubtedly pave the way for the development of novel and hopefully efficient angiogenesis targeting therapeutics for the treatment of acute MI.
Structure and function of laminin: anatomy of a multidomain glycoprotein (1990)

Laminin is a large (900 kDa) mosaic protein composed of many distinct domains with different structures and functions. Globular and rodlike domains are arranged in an extended four-armed, cruciform shape that is well suited for mediating between distant sites on cells and other components of the extracellular matrix. The alpha-helical coiled-coil domain of the long arm is involved in the specific assembly of the three chains (A, B1, B2, and possible variants) of laminin and is the only domain composed of multiple chains. It is terminated by a large globular domain composed of five homologous subdomains formed by the COOH-terminal part of the A chain. Sites for receptor-mediated cell attachment and promotion of neurite outgrowth reside in the terminal region of the long arm. A second cell attachment site, a cell signaling site with mitogenic action, binding sites for the closely associated glycoprotein nidogen/entactin, and regions involved in calcium-dependent aggregation are localized in the short arms. These domains, which to a large extent are composed of Cys-rich repeats with limited homology to EGF, are the most highly conserved regions in laminins of different origin. At present, most structural and functional data have been collected for a laminin expressed by a mouse tumor, which can be readily isolated in native form and dissected into functional fragments by limited proteolysis. Increasing information on laminins from different species and tissues demonstrates considerable variations of structure. Isoforms of laminin assembled from different chains are focally and transiently expressed and may serve distinct functions at early stages of development even before being laid down as major components of basement membranes.