gebhart/patrepeval huggingface dataset:
Intrinsic Defects in Macrophage IL-12 Production Associated with Immune Dysfunction in the MRL/++ and New Zealand Black/White F1 Lupus-Prone Mice and the Leishmania major -Susceptible BALB/c Strain (1998)

We have demonstrated that macrophages (Mphi) from young, prediseased, lupus-prone MRL/++ and New Zealand Black/White F1 mice display defective production of TNF-alpha, IL-1, and IL-6, but normal production of IL-10. In an attempt to determine the potential functional implications of this phenotype for autoimmunity, we demonstrate here that endotoxin-activated Mphi from these lupus-prone mice showed dramatically reduced expression of IL-12, a cytokine essential for Th1 responses that may be defective during lupus. IL-12 production was also reduced by Mphi from the control BALB/c strain, compatible with the concept that a genetically programmed deficit in IL-12 levels may underlie the IL-4-dominated BALB/c response to infection by the parasite Leishmania major. Although both IL-12 and TNF-alpha expression defects by Mphi from lupus-prone strains are expressed rapidly after activation, treatment with each cytokine demonstrated that only TNF-alpha contributes to the subsequent dysregulation of Mphi IL-1 and IL-6 expression in these strains, and that the reduced autocrine activity of defective IL-12 or TNF-alpha levels was not causal to each other. Although the intrinsic defect in IL-12 expression by lupus-prone and BALB/c Mphi may lead to defective Th1 responses, these Mphi responded to the Th1-derived cytokine, IFN-gamma, in a normal fashion suggesting a defective role in the induction, rather than the propagation, of Th1 responses in these mice. Our finding of a conserved intrinsic defect in IL-12 production by Mphi from the two principal mouse models of multigenic lupus provides insight into how excessive humoral responses may develop, and perhaps be prevented, in systemic autoimmune disease.
Impromptu teaching and a collaborative approach. Enhancing the patient's comprehension and satisfaction. (1990)

Although multiple studies have shown that knowledgeable patients are better able to deal with health problems and are more compliant with prescribed medical regimens, health-care providers often fail to educate patients adequately. The most commonly professed barrier to patient education is time, even though nurses spend more time with patients than other members of the health-care team. This time is usually in frequent but small segments. These small segments of time can be used for impromptu teaching, an efficient means of conveying information when a patient's learning readiness and needs are high.
Autoencoder-based feature learning for cyber security applications (2017)

This paper presents a novel feature learning model for cyber security tasks. We propose to use Auto-encoders (AEs), as a generative model, to learn latent representation of different feature sets. We show how well the AE is capable of automatically learning a reasonable notion of semantic similarity among input features. Specifically, the AE accepts a feature vector, obtained from cyber security phenomena, and extracts a code vector that captures the semantic similarity between the feature vectors. This similarity is embedded in an abstract latent representation. Because the AE is trained in an unsupervised fashion, the main part of this success comes from appropriate original feature set that is used in this paper. It can also provide more discriminative features in contrast to other feature engineering approaches. Furthermore, the scheme can reduce the dimensionality of the features thereby signicantly minimising the memory requirements. We selected two different cyber security tasks: networkbased anomaly intrusion detection and Malware classication. We have analysed the proposed scheme with various classifiers using publicly available datasets for network anomaly intrusion detection and malware classifications. Several appropriate evaluation metrics show improvement compared to prior results.
Semi-Analytic Methods for the Navier-Stokes Equations (1999)

Probabilities and conditional averages in turbulence by E. S. C. Ching Spatiotemporal chaos in large systems: The scaling of complexity with size by H. S. Greenside Empirical dynamical system reduction I: Global nonlinear transformations by M. Kirby and R. Miranda Empirical dynamical system reduction II: Neural charts by D. R. Hundley, M. Kirby, and R. Miranda Asymmetries in eastward and westward jets in a model planetary atmosphere by C. Lee and P. S. Marcus Lagrangian averaging for dynamic Eddy-viscosity subgrid models for filtered Navier-Stokes equation by C. Meneveau and T. S. Lund Punctuated Hamiltonian models of structured turbulence by J. B. Weiss.
A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. (2001)

The development and growth of prostate cancer depends on the androgen receptor and its high-affinity binding of dihydrotestosterone, which derives from testosterone. Most prostate tumors regress after therapy to prevent testosterone production by the testes, but the tumors eventually recur and cause death. A critical question is whether the androgen receptor mediates recurrent tumor growth after androgen deprivation therapy. Here we report that a majority of recurrent prostate cancers express high levels of the androgen receptor and two nuclear receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. Overexpression of these coactivators increases androgen receptor transactivation at physiological concentrations of adrenal androgen. Furthermore, we provide a molecular basis for this activation and suggest a general mechanism for recurrent prostate cancer growth.
The Israeli Economy from the Foundation of the State through the 21 st Century (review) (2012)

The Israeli Economy from the Foundation of the State through the 21st Century, by Paul Rivlin. Cambridge, UK and New York: Cambridge University Press, 2011. 308 pages. $31.99. There are many good reasons to read Paul Rivlin's account of the recent history of the Israeli economy. However, there are also many reasons to be very careful in accepting all of the analyses as established facts. The first part of the book discusses the history of the Israeli economy in terms of its broad structure. The second part focuses on individual topics in Israeli political economy. The good and the bad in the book roughly follow this division into two parts. In the first part of the book, Rivlin nicely summarizes how, between 1917 and 1948, the Jews planted the seeds of the pre-state economy under the shadow of British rule and conflict with the Arabs. The Jewish community combined a strong socialist identity with reliance on private capital for growth. The economy was dominated by agricultural collectives (Kibbutzim and Moshavim), an all-powerful federation of trade and labor unions (the Histadrut) whose headquarters in Tel Aviv was nicknamed the Kremlin, and an overbearing central government which owned all of the land. After the War of Independence in 1948, the Israeli economy continued to be controlled by the unions and the government. But the focus of the economy began to shift away from agriculture and towards basic industries such as textiles and clothing. Economic policy also changed focus, concentrating mostly on absorbing immigrants, encouraging investment by Jewish entrepreneurs from abroad, and protecting local industries (import substitution). Despite several praiseworthy but fleeting attempts to liberalize the economy (especially in the late 1970s), protectionism, union domination, and massive expenditures by the central government (including necessarily high defense outlays) continued unabated. This inevitably led to an unsustainable public debt burden, monetization, and hyperinflation. By 1985, Israel had no choice but to introduce a radical and comprehensive stabilization program which shocked the economy onto a new trajectory. The need for more free trade and establishing a modern market economy finally began to be taken more seriously. Since 1985, the struggle for economic freedom has made important but still limited inroads into the public consciousness. Israelis are just beginning to understand that enormous economic potential exists and that it is being stymied by anachronistic economic structures. …
Biophysical characterization of one-, two-, and three-tandem repeats of human mucin (muc-1) protein core. (1993)

Until recently mucin tandem repeat protein cores were believed to exist in random-coil conformations and to attain structure solely by the addition of carbohydrates to serine and threonine residues. Matsushima et al. (Proteins Struct. Funct. Genet., 7: 125-155, 1990) recently proposed a model of the secondary structure of proline rich tandem repeat proteins that has challenged this idea, especially for the case of the human polymorphic epithelial mucin encoded by the muc-1 gene. We report here results of structural analyses of the muc-1 protein core by using synthetic peptide analogues. Synthetic peptides were prepared to correspond to one-, two-, and three-tandem repeats of muc-1. Results of one- and two-dimensional 1H NMR correlation spectroscopy on these peptides confirm that the muc-1 protein core is not a random-coil secondary structure. Long-lived amide protons are protected in D2O, and increasing spectral complexity in the region of the beta-protons of Asp2 and His 15 reveals that structural changes are occurring as the number of repeats increases. The greatest changes occur when the number of repeats increases from one to two. These results are supported by the reactivity of a panel of monoclonal antibodies raised against tumor associated muc-1 with these synthetic peptides in enzyme-linked immunosorbent assay. The primary immunodominant mucin epitope, PDTRP, does not appear to attain a native conformation in the single repeat peptide (20 amino acids, starting with P), but is expressed on peptides with multiple repeats. Intrinsic viscosity measurements of the peptide containing three repeats indicate that an ordered structure present in solution is rod shaped. The circular dichroism spectrum of the same peptide is dominated by proline in the trans conformation. These results are all consistent with the prediction that the muc-1 tandem repeat polypeptide core forms a polyproline beta-turn helix.
Structure and sequence of the chicken type II procollagen gene. Characterization of the region encoding the carboxyl-terminal telopeptide and propeptide. (1984)

The DNA sequence of two overlapping cDNA clones and a genomic lambda clone covering the region coding for 288 amino acids at the COOH terminus of the chicken type II procollagen gene is reported. This region consists of 4 exons coding for the last 15 amino acids of the triple helical domain and 273 amino acids which correspond to the COOH-terminal telopeptide and COOH-terminal propeptide. The sequence, base composition, and codon usage of this region of the type II procollagen gene show particularly high similarity to those of the chicken alpha 1(I) procollagen gene and differ from those of the alpha 2(I) and alpha 1(III) gene sequences. Two DNA tracts of low sequence similarity were observed. One of these regions spans the telopeptide and COOH-terminal propeptidase cleavage site, although 4-5 amino acids at the actual cleavage site are conserved compared with the alpha 1(I) and alpha 2(I) genes. A region of unusually high nucleotide sequence conservation is present in exon 2 (amino acids 171c - 186c ) consisting of approximately 45 nucleotides with only one or two base substitutions compared with the other procollagen genes. Within this conserved sequence is a site for carbohydrate attachment. The 3' nontranslated sequence of the type II procollagen mRNA is longer than that of either the alpha 1(I) or alpha 2(I) mRNA and contains several unusual long tracts consisting primarily of one or two bases. Although the canonical site for polyadenylation is not present, two related sequences, AACAAA and ATATAAA , are present 32 and 41 bases preceding the end of the major RNA species. The exon/intron structure of the type II procollagen gene is similar to that of other collagen genes which have been described. This DNA sequence provides the first extensive report of the amino acid sequence of chicken type II procollagen.
T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes. (1992)

Two members of the RBTN gene family, RBTN1/Ttg-1 and RBTN2/Ttg-2, were found by their association with T-cell tumour-specific chromosomal translocations and are thought to be involved in the aetiology of such T-cell tumours. Here a transgenic mouse model is described in which T-cell tumours are induced by the presence of RBTN1 and RBTN2 transgenes that direct expression in thymus-derived cells. The latency period for lymphoid tumour appearance is variable, and tumours occur in a small proportion of transgenic animals that develop T-cell acute lymphoblastic malignancies. No significant increase in the rate of tumour development was observed in RBTN1 transgenic mice infected with Moloney murine leukaemia virus, nor did tumours arise in mice bearing a construct in which RBTN1 was expressed from the insulin transcriptional promoter. These data, which provide formal proof of the oncogenic activity of these genes, suggest that aberrant expression of transcription factor genes, such as RBTN1 and RBTN2, functions in tumour aetiology by disturbing some aspect of T-cell differentiation.
Non-chromatographic Purification of Recombinant Elastin-like Polypeptides and their Fusions with Peptides and Proteins from <em>Escherichia coli</em> (2014)

Elastin-like polypeptides are repetitive biopolymers that exhibit a lower critical solution temperature phase transition behavior, existing as soluble unimers below a characteristic transition temperature and aggregating into micron-scale coacervates above their transition temperature. The design of elastin-like polypeptides at the genetic level permits precise control of their sequence and length, which dictates their thermal properties. Elastin-like polypeptides are used in a variety of applications including biosensing, tissue engineering, and drug delivery, where the transition temperature and biopolymer architecture of the ELP can be tuned for the specific application of interest. Furthermore, the lower critical solution temperature phase transition behavior of elastin-like polypeptides allows their purification by their thermal response, such that their selective coacervation and resolubilization allows the removal of both soluble and insoluble contaminants following expression in Escherichia coli. This approach can be used for the purification of elastin-like polypeptides alone or as a purification tool for peptide or protein fusions where recombinant peptides or proteins genetically appended to elastin-like polypeptide tags can be purified without chromatography. This protocol describes the purification of elastin-like polypeptides and their peptide or protein fusions and discusses basic characterization techniques to assess the thermal behavior of pure elastin-like polypeptide products.
Structural Basis for Bisphosphonate-mediated Inhibition of Isoprenoid Biosynthesis (2004)

Farnesyl pyrophosphate synthetase (FPPS) synthesizes farnesyl pyrophosphate through successive condensations of isopentyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. Nitrogen-containing bisphosphonate drugs used to treat osteoclast-mediated bone resorption and tumor-induced hypercalcemia are potent inhibitors of the enzyme. Here we present crystal structures of substrate and bisphosphonate complexes of FPPS. The structures reveal how enzyme conformational changes organize conserved active site residues to exploit metal-induced ionization and substrate positioning for catalysis. The structures further demonstrate how nitrogen-containing bisphosphonates mimic a carbocation intermediate to inhibit the enzyme. Together, these FPPS complexes provide a structural template for the design of novel inhibitors that may prove useful for the treatment of osteoporosis and other clinical indications including cancer.
Engineered protein inhibitors of proteases. (2006)

The control of proteolysis in an organism is achieved under normal circumstances through a balance of protease production, degradation and inactivation, via interaction with an endogenous inhibitor. When one of these mechanisms for control of proteolysis fails, it can result in the onset or progression of disease. Control of aberrant proteolysis is, therefore, a potetntial point of therapeutic intervention, and can be achieved either through the replacement of an absent endogenous inhibitor or by dosing with an inhibitor that is specific for a protease that is being over produced. Engineered protein inhibitors of proteases offer the potential to overcome the difficulties involved in identifying specific inhibitors via small-molecule-based approaches.
Review: tauopathy in the retina and optic nerve: does it shadow pathological changes in the brain? (2012)

Tau protein's versatility lies in its functions within the central nervous system, including protein scaffolding and intracellular signaling. Tauopathy has been one of the most extensively studied neuropathologies among the neurodegenerative diseases. Because the retina and optic nerve are parts of the central nervous system, we hypothesize that tauopathy also plays a role in various eye diseases. However, little is known about tauopathy in the retina and optic nerve. Here, we summarize the findings from histopathological studies on animal models and human specimens with distinct neurodegenerative diseases. Similar pathological changes of tau protein can be found in Alzheimer's disease, frontotemporal lobe dementia, and glaucoma. In view of the important roles of tauopathy in the brain, it is hoped that this review can stimulate research on eye diseases of the retina and optic nerve.
Intermedilysin, a novel cytotoxin specific for human cells secreted by Streptococcus intermedius UNS46 isolated from a human liver abscess (1996)

A novel cytotoxin (intermedilysin) specific for human cells was identified as a cytolytic factor of Streptococcus intermedius UNS46 isolated from a human liver abscess. Intermedilysin caused human cell death with membrane blebs. Intermedilysin was purified from UNS46 culture medium by means of gel filtration and hydrophobic chromatography. The purified toxin was resolved into major and minor bands of 54 and 53 kDa, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These proteins reacted with an antibody against intermedilysin. Five internal peptide fragments of intermedilysin were sequenced and found to have 42 to 71% homology with the thiol-activated cytotoxin pneumolysin. However, the action of intermedilysin differed from that of thiol-activated cytotoxins, especially in terms of a lack of activation by dithiothreitol and resistance to treatments with N-ethylmaleimide and 5,5'-dithio-bis-(2-nitrobenzoic acid), although cholesterol inhibited the toxin activity. Intermedilysin was potently hemolytic on human erythrocytes but was 100-fold less effective on chimpanzee and cynomolgus monkey erythrocytes. Intermedilysin was not hemolytic in nine other animal species tested. Since human erythrocytes treated with trypsin were far less sensitive to intermedilysin than were the intact cells, a cell membrane protein(s) may participate in the intermedilysin action. These data demonstrated that intermedilysin is distinguishable from all known bacterial cytolysins.
Thematic review series: Lipid Posttranslational Modifications. Fighting parasitic disease by blocking protein farnesylation (2005)

Protein farnesylation is a form of posttranslational modification that occurs in most, if not all, eukaryotic cells. Inhibitors of protein farnesyltransferase (PFTIs) have been developed as anticancer chemotherapeutic agents. Using the knowledge gained from the development of PFTIs for the treatment of cancer, researchers are currently investigating the use of PFTIs for the treatment of eukaryotic pathogens. This "piggy-back" approach not only accelerates the development of a chemotherapeutic agent for protozoan pathogens but is also a means of mitigating the costs associated with de novo drug design. PFTIs have already been shown to be efficacious in the treatment of eukaryotic pathogens in animal models, including both Trypanosoma brucei, the causative agent of African sleeping sickness, and Plasmodium falciparum, one of the causative agents of malaria. Here, current evidence and progress are summarized that support the targeting of protein farnesyltransferase for the treatment of parasitic diseases.
Energy cost and muscular activity required for propulsion during walking (2003)

We reasoned that with an optimal aiding horizontal force, the reduction in metabolic rate would reflect the cost of generating propulsive forces during normal walking. Furthermore, the reductions in ankle extensor electromyographic (EMG) activity would indicate the propulsive muscle actions. We applied horizontal forces at the waist, ranging from 15% body weight aiding to 15% body weight impeding, while subjects walked at 1.25 m/s. With an aiding horizontal force of 10% body weight, 1) the net metabolic cost of walking decreased to a minimum of 53% of normal walking, 2) the mean EMG of the medial gastrocnemius (MG) during the propulsive phase decreased to 59% of the normal walking magnitude, and yet 3) the mean EMG of the soleus (Sol) did not decrease significantly. Our data indicate that generating horizontal propulsive forces constitutes nearly half of the metabolic cost of normal walking. Additionally, it appears that the MG plays an important role in forward propulsion, whereas the Sol does not.
Staphylococcal protein A consists of five IgG-binding domains (1986)

A genetic approach is described to clarify the IgG-binding properties of the N-terminal portion of staphylococcal protein A (region E). Several gene fragments, encoding region E or B or protein A, have been cloned and expressed in Escherichia coli. The gene products were purified by IgG-affinity chromatography and subjected to structural and functional analyses. Both fragments can be efficiently purified using this method, suggesting that region B as well as region E has Fc-binding activity. In addition, gene fusions were assembled giving fragments EB and EE, which both showed a divalent Fc-binding. These results demonstrate that protein A consists of five IgG-binding domains. The implications of these findings for the structure of protein-A--immunoglobulin-G complexes are discussed.
Integrated Laser Doppler Blood Flowmeter Designed to Enable Wafer-Level Packaging (2010)

The authors propose a new sensor structure for an integrated laser Doppler blood flowmeter that consists of two silicon cavities with a PD and laser diode inside each cavity. A silicon lid formed with a converging microlens completes the package. This structure, which was achieved using micromachining techniques, features reduced optical power loss in the sensor, resulting in its small size and significantly low power consumption. Measurements using a model tissue blood flow system confirmed that the new sensor had high linearity and a wide dynamic range for measuring tissue blood flow.
Dementia with Lewy bodies (2000)

Dementia with Lewy bodies (DLB) is the second most common type of degenerative dementia after Alzheimer's disease (AD). A clinical diagnosis is made on the basis of probabilities considering symptoms, investigations and neuropsychological tests. It has pathological and clinical features common to both AD and Parkinson's disease. Despite this a distinctive picture is emerging that strongly points toward a diagnosis of DLB.