gebhart/patrepeval huggingface dataset:
Lipid modification of proteins and their membrane transport (1989)

An effective method for artificial attachment of lipid anchors to water-soluble proteins has been developed. To this end, a protein molecule is modified in a system of reversed micelles by a water-insoluble reagent, e.g. fatty acid chloride. Fatty acylated proteins acquire an ability to translocate across lipid membranes and penetrate intact cells. This principle of imparting transmembrane properties to water-soluble proteins makes it possible to realize in vivo a direct transport of antibodies across the hemato-encephalic barrier into the brain and to develop a method for virus suppression by fatty acylated anti-viral antibodies capable of penetrating infected cells. The effect of a drastic increase in the biological activity of exogenous protein factors, e.g. Staphylococcus aureus enterotoxin A, as a result of their artificial fatty acylation has been discovered. The above-mentioned phenomena are discussed in relation to the in vivo data, indicating that post-translational modification of proteins by fatty acids and phospholipids is very widespread in nature and evidently plays an important role in protein transport and sorting. In this connection, lipid modification of proteins is regarded as a possible general step of protein transport in vivo.
Treatment of therapy-resistant Alopecia areata with fumaric acid esters. (2006)

FAE can be useful in the treatment of therapy-resistant Alopecia areata. This therapy approach should be validated in a multi-centre study.
Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice (2009)

siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in both hepatic and subcutaneous tumor models. This was correlated with target gene silencing following a single intravenous administration that was sufficient to cause extensive mitotic disruption and tumor cell apoptosis. Our siRNA formulations induced no measurable immune response, minimizing the potential for nonspecific effects. Additionally, RNAi-specific mRNA cleavage products were found in tumor cells, and their presence correlated with the duration of target mRNA silencing. Histological biomarkers confirmed that RNAi-mediated gene silencing effectively inhibited the target's biological activity. This report supports an RNAi-mediated mechanism of action for siRNA antitumor effects, suggesting a new methodology for targeting other key genes in cancer development with siRNA-based therapeutics.
Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin. (1994)

Transforming growth factor beta (TGF-beta) and activin bind to receptor complexes that contain two distantly related transmembrane serine/threonine kinases known as receptor types I and II. The type II receptors determine ligand binding specificity, and each interacts with a distinct repertoire of type I receptors. Here we identify a new type I receptor for activin, ActR-IB, whose kinase domain is nearly identical to that of the recently cloned TGF-beta type I receptor, T beta R-I. ActR-IB has the structural and binding properties of a type I receptor: it binds activin only in the presence of an activin type II receptor and forms a heteromeric noncovalent complex with activin type II receptors. In Mv1Lu lung epithelial cells, ActR-IB and T beta R-I signal a common set of growth-inhibitory and transcriptional responses in association with their corresponding ligands and type II receptors. The transcriptional responses include elevated expression of fibronectin and plasminogen activator inhibitor 1. Although T beta R-I and ActR-IB are nearly identical in their kinase domains (90% amino acid sequence identity), their corresponding type II receptor kinase domains are very different from each other (42% amino acid sequence identity). Therefore, signaling of a specific set of responses by TGF-beta and activin correlates with the presence of similar type I kinases in their complex. Indeed, other TGF-beta and activin type I receptors (TSR-I and ActR-I) whose kinase domains significantly diverge from those of T beta R-I and ActR-IB do not substitute as mediators of these growth-inhibitory and extracellular matrix transcriptional responses. Hence, we conclude that the type I receptor subunits are primary specifiers of signals sent by TGF-beta and activin receptor complexes.
Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors (2011)

V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificity is an important goal for HIV-1 vaccine development. A critical question is which immunogens and vaccine formulations might be used to trigger and drive the development of memory B cell precursors with V2/V3 conformational epitope specificity. In this paper we identified a clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer and inferred their common reverted unmutated ancestor (RUA) antibodies. While conformational epitope antibodies rarely bind recombinant Env monomers, a screen of 32 recombinant envelopes for binding to the CH01 to CH04 antibodies showed monoclonal antibody (MAb) binding to the E.A244 gp120 Env and to chronic Env AE.CM243; MAbs CH01 and CH02 also bound to transmitted/founder Env B.9021. CH01 to CH04 neutralized 38% to 49% of a panel of 91 HIV-1 tier 2 pseudoviruses, while the RUAs neutralized only 16% of HIV-1 isolates. Although the reverted unmutated ancestors showed restricted neutralizing activity, they retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. Thus, E.A244, B.9021, and AE.CM243 Envs are three potential immunogen candidates for studies aimed at defining strategies to induce V2/V3 conformational epitope-specific antibodies.
Geometrically deformed models (1991)

We propose a new approach to the problem of generating a simple topologically-closed geometric model from a point-sampled volume data set. We call such a model a Geometrically Deformed Model or GDM. A GDM is created by placing a 'seed' model in the volume data set. The model is then deformed by a relaxation process that minimizes a set of constraints that provides a measure of how well the model fits the features in the data. Constraints are associated with each vertex in the model that control local deformation, interaction between the model and the data set, and the shape and topology of the model. Once generated, a GDM can be used for visualization, shape recognition, geometric measurements, or subjected to a series of geometric operations. This technique is of special importance because of the advent of nondestructive sensing equipment (CT, MRI) that generates point samples of true three-dimensional objects.
In Vitro-Generation of Islets in Long-Term Cultures of Pluripotent Stem Cells From Adult Mouse Pancreas (1997)

Pancreatic islets of Langerhans exhibit an architecture and cellular organization ideal for rapid, yet finely controlled, responses to changes in blood glucose levels. In type I, insulin-dependent diabetes (IDD), this organization is lost as a result of the progressive autoimmune response which selectively destroys the insulin-producing pancreatic beta cells. Since beta cells are perceived as end-stage differentiated cells having limited capacity for regeneration in situ, individuals with IDD resulting from beta cell loss or dysfunction require life-long insulin therapy. Efforts to produce islet neogenesis or initiate islet growth in vitro from either fetal or adult tissue have had minimal success. We now report that pancreatic-derived, pluripotent islet-producing stem cells (IPSCs), isolated from prediabetic mice, can be grown in long-term cultures and differentiated into immature functional islet-like structures containing cells which express low levels of insulin, glucagon and/or somatostatin. When such in vitro grown islets were implanted into clinically diabetic NOD mice, the implanted mice were successfully weaned from insulin long-term (>50 days) without ill effects. The implanted mice maintained blood glucose levels just above euglycemic (180-220 mg/dl) and showed no signs of disease. Thus, this technical breakthrough provides new therapeutic approaches to diabetes as an alternative to insulin therapy.
Vitamin E Analogues: A New Class of Inducers of Apoptosis with Selective Anti-Cancer Effects (2004)

In spite of unrelenting effort, the net incidence of neoplastic diseases appears not to have been curbed. While some types of cancer have been suppressed significantly, others are either stagnating or on the increase. Therefore, the need for a cure is imperative, in particularly a drug or combination of drugs that would be selective for malignant cells, i.e. with as low secondary toxicity as possible. Recent data strongly suggest that analogues of vitamin E, epitomised by the most studied alpha-tocopheryl succinate (alpha-TOS), may meet the need for the coveted drugs with a selective anti-neoplastic effect. The reasons for this optimism are reviewed in this article.
Morphology of rabbit retinal ganglion cells projecting to the medial terminal nucleus of the accessory optic system (1986)

Rabbit retinal ganglion cells were retrogradely labeled following injection of rhodamine-labeled microspheres into the medial terminal nucleus. The small fraction of rhodamine-labeled neurons reached their peak concentration within the visual streak and then decreased with increasing eccentricity until none were encountered in the far periphery. The same rabbits also received injections of the fluorescent tracer Fast Blue into the superior colliculus. No double-labeled neurons were observed, i.e., ganglion cells projecting to the medial terminal nucleus (MTN) had no axon collaterals to the superior colliculus. In fixed retinae rhodamine-labeled ganglion cells were intracellularly injected with the fluorescent dye Lucifer Yellow to reveal their full dendritic arborization. MTN-projecting cells had medium-sized to large somata with thin and frequently branched dendrites. The large dendritic trees had a distinct morphology and were predominantly unistratified in a narrow band that presumably corresponded to the electrophysiologically determined on-sublamina of the inner plexiform layer. Dendritic field sizes were inversely related to ganglion cell density, thus providing an eccentricity-independent, constant dendritic coverage factor. Approximately five to six dendritic fields from neighboring cells cover every point of the retina. Published reports claim that the physiological class of on-direction-selective ganglion cells provides the sole retinal input to the MTN in the rabbit. In this context morphological features of MTN-projecting cells and their presumed functional correlation with on-direction-selective ganglion cells are discussed.
Hypoxia induces transcription of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase‐4 gene via hypoxia‐inducible factor‐1α activation (2004)

The PFKFB4 gene encodes isoenzyme of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB or PFK-2/FBPase-2) which originally was found in the testes. We have studied hypoxic regulation of PFKFB4 gene in prostate cancer cell line, PC-3, and several other cancer cell lines. It was shown that hypoxia significantly induced PFKFB4 mRNA levels in PC-3 as well as in HeLa, Hep3B and HepG2 cell lines. Hypoxia increased PFKFB4 protein levels also. Moreover, desferrioxamine and cobalt chloride, which are known to mimic hypoxia, also had a stimulatory effect on the expression of PFKFB4 mRNA. In order to investigate the mechanisms of hypoxic regulation of PFKFB4 gene expression, we used dimethyloxalylglycine, which has the ability to mimic effect of hypoxia by significant induction of hypoxia-inducible factor (HIF-1alpha) protein levels. Our studies showed that PFKFB4 mRNA expression in PC-3, HeLa, Hep3B and HepG2 cell lines was highly responsive to dimethyloxalylglycine, an inhibitor of HIF-1alpha hydroxylase enzymes, suggesting that the hypoxia responsiveness of this gene is regulated by HIF proteins. To better understand the hypoxic regulation of PFKFB4 gene expression, we isolated genomic DNA, which includes the promoter region of PFKFB4. Cell transfection, deletion and site-specific mutagenesis of the PFKFB4 promoter region indicates that hypoxic induction of PFKFB4 gene expression is mediated by the hypoxia-responsive element (HRE). These experiments identified a HRE 422-429 bp upstream from the translation start site. Thus, our results indicate that testis-specific form of PFKFB or PFK-2/FBPase-2 is also expressed in several cancer cell lines and that hypoxia induces transcription of PFKFB4 gene in these cell lines by HIF-1alpha dependent mechanism. HRE in 5'-promoter region of PFKFB4 gene mediates hypoxic induction of PFKFB4 gene transcription.
Heterogeneous Ribonucleoprotein M Is a Splicing Regulatory Protein That Can Enhance or Silence Splicing of Alternatively Spliced Exons (2007)

Splicing of fibroblast growth factor receptor 2 (FGFR2) alternative exons IIIb and IIIc is regulated by the auxiliary RNA cis-element ISE/ISS-3 that promotes splicing of exon IIIb and silencing of exon IIIc. Using RNA affinity chromatography, we have identified heterogeneous nuclear ribonucleoprotein M (hnRNP M) as a splicing regulatory factor that binds to ISE/ISS-3 in a sequence-specific manner. Overexpression of hnRNP M promoted exon IIIc skipping in a cell line that normally includes it, and association of hnRNP M with ISE/ISS-3 was shown to contribute to this splicing regulatory function. Thus hnRNP M, along with other members of the hnRNP family of RNA-binding proteins, plays a combinatorial role in regulation of FGFR2 alternative splicing. We also determined that hnRNP M can affect the splicing of several other alternatively spliced exons. This activity of hnRNP M included the ability not only to induce exon skipping but also to promote exon inclusion. This is the first report demonstrating a role for this abundant hnRNP family member in alternative splicing in mammals and suggests that this protein may broadly contribute to the fidelity of splice site recognition and alternative splicing regulation.
Relation of Serum Lipoprotein Levels and Systolic Blood Pressure to Early Atherosclerosis (1986)

We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.
Effect of capping layer material on tunnel magnetoresistance in CoFeB-MgO-CoFeB magnetic tunnel junctions (2005)

The effect of capping layer (CL) material on tunnel magnetoresistance (TMR) and magnetic properties in CoFeB/MgO/CoFeB magnetic tunnel junctions has been studied. The use of CL materials such as Ta, Ru, PtMn, Mg and IrMn yielded high MR ratio of more than 100%. The use of ferromagnetic materials, on the other hand, such as NiFe, CoFe or Fe decreased the MR ratio, as well as using Al, Cu, NiFeCr or Ir. The dependence of coercivity on CL materials for the same samples are also studied. It was speculated from the results that the degradation of the TMR and the magnetic properties when particular capping layer materials were used, is due to the formation of a reactive layer between the free layer and the capping layer.
A Functional Interaction between the Survival Motor Neuron Complex and RNA Polymerase II (2001)

The survival motor neuron (SMN) protein, the protein product of the spinal muscular atrophy (SMA) disease gene, plays a role in the assembly and regeneration of small nuclear ribonucleoproteins (snRNPs) and spliceosomes. By nanoelectrospray mass spectrometry, we identified RNA helicase A (RHA) as an SMN complex-associated protein. RHA is a DEAH box RNA helicase which binds RNA polymerase II (pol II) and reportedly functions in transcription. SMN interacts with RHA in vitro, and this interaction is impaired in mutant SMNs found in SMA patients. Coimmunoprecipitation demonstrated that the SMN complex is associated with pol II, snRNPs, and RHA in vivo. In vitro experiments suggest that RHA mediates the association of SMN with the COOH-terminal domain of pol II. Moreover, transfection of cells with a dominant negative mutant of SMN, SMNDeltaN27, causes accumulation of pol II, snRNPs, and RHA in nuclear structures that contain the known markers of gems and coiled bodies, and inhibits RNA pol I and pol II transcription in vivo. These findings indicate a functional as well as physical association of the SMN complex with pol II and suggest a role for the SMN complex in the assembly of the pol II transcription/processing machinery.
Relación entre métodos de medida de la fibrosidad en espárragos blancos frescos y en conserva (1997)

The force to cut white asparagus spears was measured by the shear press, at four distances from the tip. The fibrous unit percentage was determined in peeled canned asparagus by the Wilder fiberometer. The correlation between methods to measure fibrousness in fresh and canned asparagus was analysed. Freshly harvested and stored asparagus, et 20 °C during 48 horas, were used at three dates of harvest season, in the first assay. Freshly harvested asparagus and stored asparagus at 20 °C during 48 hours and at 6 and 2 °C during 8 days, were used in the second assay. The forces to cut spears at 13 and 10 cm from the tip, were highly correlated to fibrous units percentages of canned asparagus but not the forces at 16 and 19 cm.
Thermal Activation of CaO-Based Sorbent and Self-Reactivation during CO2 Capture Looping Cycles (2008)

In this study, the thermal activation of different types of CaO-based sorbents was examined. Pretreatments were performed at different temperatures (800--1300 degrees C) and different durations (6--48 h) using four Canadian limestones. Sieved fractions of the limestones, powders obtained by grinding, and hydroxides produced following multiple carbonation/calcination cycles achieved in a tube furnace were examined. Pretreated samples were evaluated using two types of thermogravimetric reactors/ analyzers. The most important result was that thermal pretreatment could improve sorbent performance. In comparison to the original, pretreated sorbents showed better conversions over a longer series of CO2 cycles. Moreover, in some cases, sorbent activity actually increased with cycle number, and this effectwas especially pronounced for powdered samples preheated at 1000 degrees C. In these experiments, the increase of conversion with cycle number (designated as self-reactivation) after 30 cycles produced samples that were approximately 50% carbonated for the four sorbents examined here, and there appeared to be the potential for additional increase. These results were explained with the newly proposed pore--skeleton model. This model suggests, in addition to changes in the porous structure of the sorbent, that changes in the pore--skeleton produced during pretreatment strongly influence subsequent carbonation/ calcination cycles.
Cisplatin, epirubicin, and vindesine with or without lonidamine in the treatment of inoperable nonsmall cell lung carcinoma: A multicenter randomized clinical trial (1996)

The mild acute toxicity of the PEV regimen and the acceptable and nonoverlapping additional side effects of LND render our experimental therapy worthy of consideration for the management of NSCLC patients with poor performance status or low tolerance to more aggressive therapeutic approaches.
Bufferbloat: Dark Buffers in the Internet (2011)

Today’s networks are suffering from unnecessary latency and poor system performance. The culprit is bufferbloat, the existence of excessively large and frequently full buffers inside the network. Large buffers have been inserted all over the Internet without sufficient thought or testing. They damage or defeat the fundamental congestion-avoidance algorithms of the Internet’s most common transport protocol. Long delays from bufferbloat are frequently attributed incorrectly to network congestion, and this misinterpretation of the problem leads to the wrong solutions being proposed.
Learning Local Image Descriptors (2007)

In this paper we study interest point descriptors for image matching and 3D reconstruction. We examine the building blocks of descriptor algorithms and evaluate numerous combinations of components. Various published descriptors such as SIFT, GLOH, and Spin images can be cast into our framework. For each candidate algorithm we learn good choices for parameters using a training set consisting of patches from a multi-image 3D reconstruction where accurate ground-truth matches are known. The best descriptors were those with log polar histogramming regions and feature vectors constructed from rectified outputs of steerable quadrature filters. At a 95% detection rate these gave one third of the incorrect matches produced by SIFT.
p-Aminobenzoate biosynthesis in Escherichia coli. Purification of aminodeoxychorismate lyase and cloning of pabC (1991)

p-Aminobenzoate, a component of the vitamin folate, is one of seven compounds derived from the aromatic precursor chorismate in Escherichia coli. Historically the gene products of pabA and pabB were assumed to be sufficient for de novo p-aminobenzoate biosynthesis. Recent studies, however, have shown that these proteins, as nonidentical subunits of a single enzyme, act on chorismate to form a diffusible intermediate, most likely 4-amino-4-deoxychorismate. This intermediate is then converted to p-aminodeoxychorismate lyase (Nichols, B. P., Seibold, A. S., and Doktor, S. Z. (1989) J. Biol. Chem. 264, 8597-8601). Here we describe partial characterization of the intermediate and the purification of aminodeoxychorismate lyase 4100-fold to near homogeneity. Further purification of this enzyme by high pressure liquid chromatography permitted isolation of a pure sample that yielded N-terminal sequence. A 64-fold redundant oligonucleotide probe was used to identify a lambda clone containing the gene encoding aminodeoxychorismate lyase. The aminodeoxychorismate lyase gene, designated pabC, was mapped to 25 min on the E. coli chromosome and lies on a 7.5-kilobase pair EcoRI fragment. A strain harboring a pACYC184 recombinant containing pabC overproduced aminodeoxychorismate lyase activity 77-fold.