gebhart/patrepeval huggingface dataset:
Design of a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering (2012)

Repeat proteins have recently been of great interest as potential alternatives to immunoglobulin antibodies due to their unique structural and biophysical features. We here present the development of a binding scaffold based on variable lymphocyte receptors, which are nonimmunoglobulin antibodies composed of Leucine-rich repeat modules in jawless vertebrates, by module engineering. A template scaffold was first constructed by joining consensus repeat modules between the N- and C-capping motifs of variable lymphocyte receptors. The N-terminal domain of the template scaffold was redesigned based on the internalin-B cap by analyzing the modular similarity between the respective repeat units using a computational approach. The newly designed scaffold, termed "Repebody," showed a high level of soluble expression in bacteria, displaying high thermodynamic and pH stabilities. Ease of molecular engineering was shown by designing repebodies specific for myeloid differentiation protein-2 and hen egg lysozyme, respectively, by a rational approach. The crystal structures of designed repebodies were determined to elucidate the structural features and interaction interfaces. We demonstrate general applicability of the scaffold by selecting repebodies with different binding affinities for interleukin-6 using phage display.
Adult-onset pulmonary fibrosis caused by mutations in telomerase (2007)

Idiopathic pulmonary fibrosis (IPF) is an adult-onset, lethal, scarring lung disease of unknown etiology. Some individuals with IPF have a familial disorder that segregates as a dominant trait with incomplete penetrance. Here we used linkage to map the disease gene in two families to chromosome 5. Sequencing a candidate gene within the interval, TERT, revealed a missense mutation and a frameshift mutation that cosegregated with pulmonary disease in the two families. TERT encodes telomerase reverse transcriptase, which together with the RNA component of telomerase (TERC), is required to maintain telomere integrity. Sequencing the probands of 44 additional unrelated families and 44 sporadic cases of interstitial lung disease revealed five other mutations in TERT. A heterozygous mutation in TERC also was found in one family. Heterozygous carriers of all of the mutations in TERT or TERC had shorter telomeres than age-matched family members without the mutations. Thus, mutations in TERT or TERC that result in telomere shortening over time confer a dramatic increase in susceptibility to adult-onset IPF.
A network-centric design for relationship-based security and access control (1997)

As part of the Stanford Digital Libraries Project, we have prototyped a novel architecture for security and access control in heterogeneous, networked environments. Conceptually, this architecture recasts security issues from an “information access” metaphor into a “relationship management” framewo rk and uniformly applies a contracting model. Architecturally, it introduces a “network-centric” design that generalizes previous models of client- or server-centered control into a third, relationship-based form.
A proposal for the structure of conotoxin ‐ a potent antagonist of the nicotinic acetylcholine receptor (1985)

Conotoxin, a thirteen residue neurotoxic peptide, is demonstrated, by circular dichroism measurements, to possess a high content of alpha-helix. The location of this helix in the sequence is severely limited by the structural preferences of individual amino acids and by the positioning of the two cystine links. Comparisons are made between the reactive site of elapidae snake venom postsynaptic neurotoxins and the surface of the conotoxin molecule.
Identification of an RNA binding region within the N-terminal third of the influenza A virus nucleoprotein (1995)

The influenza A virus nucleoprotein (NP) has been examined with regard to its RNA-binding characteristics. NP, purified from virions and devoid of RNA, bound synthetic RNAs in vitro and interacted with the ribonucleotide homopolymers poly(A), poly(G), poly(U), and poly(C) in a salt-dependent manner, showing higher binding affinity for polypyrimidine homopolymers. To map the NP regions involved in RNA binding, a series of deleted forms of the NP were prepared, and these truncated polypeptides were tested for their ability to bind poly(U) and poly(C) homopolymers linked to agarose beads. Proteins containing deletions at the N terminus of the NP molecule showed reduced RNA-binding activity, indicating that this part of the protein was required to bind RNA. To identify the NP region or regions which directly interact with RNA, proteins having the maltose-binding protein fused with various NP fragments were obtained and tested for binding to radioactively labeled RNAs in three different assays: (i) nitrocellulose filter binding assays, (ii) gel shift assays, and (iii) UV light-induced cross-linking experiments. A maltose-binding protein fusion containing the N-terminal 180 amino acids of NP behaved as an RNA-binding protein in the three assays, demonstrating that the N terminus of NP can directly interact with RNA. This NP region could be further subdivided into two smaller regions (amino acids 1 to 77 and 79 to 180) that also retained RNA-binding activity.
Remote Authentication Dial In User Service (RADIUS) (1997)

This document describes a protocol for carrying authentication, authorization, and configuration information between a Network Access Server which desires to authenticate its links and a shared Authentication Server.
Maximizing DNA Loading on a Range of Gold Nanoparticle Sizes (2006)

We have investigated the variables that influence DNA coverage on gold nanoparticles. The effects of salt concentration, spacer composition, nanoparticle size, and degree of sonication have been evaluated. Maximum loading was obtained by salt aging the nanoparticles to approximately 0.7 M NaCl in the presence of DNA containing a poly(ethylene glycol) spacer. In addition, DNA loading was substantially increased by sonicating the nanoparticles during the surface loading process. Last, nanoparticles up to 250 nm in diameter were found have approximately 2 orders of magnitude higher DNA loading than smaller (13-30 nm) nanoparticles, a consequence of their larger surface area. Stable large particles are attractive for a variety of biodiagnostic assays.
Low threshold GaInAsP/InP buried-heterostructure lasers with a chemically etched and mass-transported mirror (1984)

The mass-transport technique has been used to improve chemically etched mirrors on GaInAsP/InP double heterostructure wafers. Vertical and flat mirror facets have been obtained. Buried-heterostructure lasers fabricated with one such mirror and the other mirror cleaved show high device yield with threshold currents as low as 6 mA and differential quantum efficiency as high as 33%.
Cubilin Is Essential for Albumin Reabsorption in the Renal Proximal Tubule (2010)

Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubule. This process involves two interacting receptors, megalin and cubilin, which form a complex with amnionless. Whether these proteins function in parallel or as part of an integrated system is not well understood. Here, we report the renal effects of genetic ablation of cubilin, with or without concomitant ablation of megalin, using a conditional Cre-loxP system. We observed that proximal tubule cells did not localize amnionless to the plasma membrane in the absence of cubilin, indicating a mutual dependency of cubilin and amnionless to form a functional membrane receptor complex. The cubilin-amnionless complex mediated internalization of intrinsic factor-vitamin B12 complexes, but megalin considerably increased the uptake. Furthermore, cubilin-deficient mice exhibited markedly decreased uptake of albumin by proximal tubule cells and resultant albuminuria. Inactivation of both megalin and cubilin did not increase albuminuria, indicating that the main role of megalin in albumin reabsorption is to drive the internalization of cubilin-albumin complexes. In contrast, cubulin deficiency did not affect urinary tubular uptake or excretion of vitamin D-binding protein (DBP), which binds cubilin and megalin. In addition, we observed cubilin-independent reabsorption of the "specific" cubilin ligands transferrin, CC16, and apoA-I, suggesting a role for megalin and perhaps other receptors in their reabsorption. In summary, with regard to albumin, cubilin is essential for its reabsorption by proximal tubule cells, and megalin drives internalization of cubilin-albumin complexes. These genetic models will allow further analysis of protein trafficking in the progression of proteinuric renal diseases.
Synthesis of Lipid A Derivatives and Their Interactions with Polymyxin B and Polymyxin B Nonapeptide (2003)

Lipid A is the causative agent of Gram-negative sepsis, a leading cause of mortality among hospitalized patients. Compounds that bind lipid A can limit its detrimental effects. Polymyxin B, a cationic peptide antibiotic, is one of the simplest molecules capable of selectively binding lipid A and may serve as a model for further development of lipid A binding agents. However, association of polymyxin B with lipid A is not fully understood, primarily due to the low solubility of lipid A in water and inhomogeneity of lipid A preparations. To better understand lipid A-polymyxin B interaction, pure lipid A derivatives were prepared with incrementally varied lipid chain lengths. These compounds proved to be more soluble in water than lipid A, with higher aggregation concentrations. Isothermal titration calorimetric studies of these lipid A derivatives with polymyxin B and polymyxin B nonapeptide indicate that binding stoichiometries (peptide to lipid A derivative) are less than 1 and that affinities of these binding partners correlate with the aggregation states of the lipid A derivatives. These studies also suggest that cooperative ionic interactions dominate association of polymyxin B and polymyxin B nonapeptide with lipid A.
Experiences from development of home health care applications based on emerging Java technology. (2001)

Home health care is an expanding area within the health care system. The idea of moving parts of the health care process from expensive specialised hospital care to primary health care and home health care might be attractive in a cost perspective. The introduction of home health care applications must be based on a rigorous analysis of necessary requirements to secure a safe and reliable health care. This article reports early experiences from the development of a home health care application based on emerging Java technologies such as the OSGi platform. A pilot application for follow-up of diabetes patients is presented and discussed in relation to a list of general requirements on home health care applications.
Identification and properties of the catalytic domain of mammalian DNA polymerase .beta. (1990)

Rat DNA polymerase beta (beta-pol) is a 39-kDa protein organized in two tightly folded domains, 8-kDa N-terminal and 31-kDa C-terminal domains, connected by a short protease-sensitive region. The 8-kDa domain contributes template binding to the intact protein, and we now report that the 31-kDa C-terminal domain contributes catalytic activity. Our results show that this domain as a purified proteolytic fragment conducts DNA synthesis under appropriate conditions but the kcat is lower and primer extension properties are different from those of the intact enzyme. A proteolytic truncation of the 31-kDa catalytic domain fragment, to remove a 60-residue segment from the NH2-terminal end, results in nearly complete loss of activity, suggesting the importance of this segment. Overall, these results indicate that the domains of beta-pol have distinct functional roles, template binding and nucleotidyltransferase, respectively; yet, the intact protein is more active for each function than the isolated individual domain fragment.
Photoreactive Bicyclic Amino Acids as Substrates for Mutant Escherichia coli Phenylalanyl-tRNA Synthetases (2004)

Unnatural amino acids carrying reactive groups that can be selectively activated under non-invasive biologically benign conditions are of interest in protein engineering as biological tools for the analysis of protein-protein and protein-nucleic acids interactions. The double ring system phenylalanine analogues benzofuranylalanine and benzotriazolylalanine were synthesized, and their photolability was tested by UV irradiation at 254, 320, and 365 nm. Although both showed photo reactivity, benzofuranylalanine appeared as the most promising compound because this amino acid was activated by UVA (long wavelength) irradiation. These amino acids were also tested for in vitro charging of tRNA(Phe) and for protein mutagenesis via the phenylalanyl-tRNA synthetase variant alphaA294G that is able to facilitate in vivo protein synthesis using a range of para-substituted phenylalanine analogues. The results demonstrate that benzofuranylalanine, but not benzotriazolylalanine, is a substrate for phenylalanine tRNA synthetase alphaA294G, and matrix-assisted laser desorption ionization time-of-flight analysis showed it to be incorporated into a model protein with high efficiency. The in vivo incorporation into a target protein of a bicyclic phenylalanine analogue, as described here, demonstrates the applicability of phenylalanine tRNA synthetase variants in expanding the scope of protein engineering.
Microscopy cell counting with fully convolutional regression networks (2015)

This paper concerns automated cell counting in microscopy images. The approach we take is to adapt Convolutional Neural Networks (CNNs) to regress a cell spatial density map across the image. This is applicable to situations where traditional single-cell segmentation based methods do not work well due to cell clumping or overlap. We make the following contributions: (i) we develop and compare architectures for two Fully Convolutional Regression Networks (FCRNs) for this task; (ii) since the networks are fully convolutional, they can predict a density map for an input image of arbitrary size, and we exploit this to improve efficiency at training time by training end-to-end on image patches; and (iii) we show that FCRNs trained entirely on synthetic data are able to give excellent predictions on real microscopy images without fine-tuning, and that the performance can be further improved by fine-tuning on the real images. We set a new state-of-the-art performance for cell counting on the standard synthetic image benchmarks and, as a side benefit, show the potential of the FCRNs for providing cell detections for overlapping cells.
Probiotic Bifidobacterium breve Induces IL-10-Producing Tr1 Cells in the Colon (2012)

Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.
Personal computers and intelligent systems (1992)

Keynote: New Science and New Art (P. McCorduck). Expanding the Power of the Personal Computer. PC Technology - Invited Paper: The Electronic Frontier: Where Personal Computing Goes From Here (E. Dyson). User Interfaces - Invited Papers: Microsoft Windows For Pen Computing (P. Singh, L. Weil) Computers, Communication and Collaboration: Revolution, Evolution and False Starts (G. Sidhu) (plus 4 other papers). Office Automation - Invited Papers: Distributed Intelligent Agents (S.J. Rosenschein) Trends in PC Database Technology (R.E. Shostak) (plus 2 other papers). Multimedia and Networking - Invited Papers: Global Systems Integration with Hypermedia (P. Maier) ISDN for Multimedia Workstations (R. Wildhack) (plus 3 other papers). Enhancing the Intelligence in Information Systems. Knowledge-Based Systems in the Transformation of Societies and Organizations - Invited Papers: Reflections on Effective Application of Information Technology in Organizations, From the Perspective of the Management in the 90's Program (R. Benjamin, M.S. Morton) Building the Intelligent Island (J. Motiwalla, M. Yap) (plus 3 other papers). The Design of Knowledge-Based Systems to Support Organizational Functions and to Aid the Work of Information Systems Professionals - Invited Paper: Knowledge Base Management Systems Using Description Logics and Their Role in Software Information Systems (A. Borgida, P. Devanbu) (plus 5 other papers). Making Sure the System is Intelligent: Knowledge-Based Systems Validation - Invited Paper: The Formalization of Knowledge-Based Systems Validation and Verification: Promises and Pitfalls (E. Hollnagel) (plus 3 other papers). Intelligence in Information Systems: Applications and Experiences (5 papers). Cooperative Research Programs (4 papers). Encouraging Academic/Practitioner Collaboration (5 papers).
REVIEW STUDY ON PHARMACOLOGICAL IMPORTANCE AND TRADITIONAL USES OF ARTOCARPUS HIRSUTUS LAM (2016)

Artocarpushirsutus Lam. an endemic species of southern Western Ghats commonly called as ‘wild jack’ is less explored for its medicinal potentials. It forms one of the major keystone species of Western Ghats . However, there is documentation of its medicinal properties in the third volume of HortusMalabaricus, a book on the natural plant wealth of Asia. Wild jack is a tropical evergreen tree that is native to  India  ( Karnataka ,  Kerala ,  Maharashtra  and  Tamil Nadu ), where it prefers moist, deciduous to partially evergreen woodlands. The Artocarpushirsutus grows in altitudes ranging from sea level to an elevation of 1000 m in places with an annual rainfall of 1500 mm or more. Fruits are edible. Wood yellowish brown, moderately hard, durable, seasons and polishes well, does not wrap or crack, not eaten by white ants, valuable for construction work (beams, rafters, door and window frames), panelling, flooring, furniture, cooperage, agricultural implements and boat building. It can also be used for tea boxes. Infusion of bark applied to cure pimples and cracks on the skin. Powdered bark used to heal sores; dry leaves useful in treating buboes and hydrocele; unripe fruit astringent, ripe fruit appetizer, cooling, aphrodisiac, and useful in vitiated condition of vata and pitta, and anorexia.
Hyperspectral data analysis and supervised feature reduction via projection pursuit (1999)

As the number of spectral bands of high-spectral resolution data increases, the ability to detect more detailed classes should also increase, and the classification accuracy should increase as well. Often the number of labelled samples used for supervised classification techniques is limited, thus limiting the precision with which class characteristics can be estimated. As the number of spectral bands becomes large, the limitation on performance imposed by the limited number of training samples can become severe. A number of techniques for case-specific feature extraction have been developed to reduce dimensionality without loss of class separability. Most of these techniques require the estimation of statistics at full dimensionality in order to extract relevant features for classification. If the number of training samples is not adequately large, the estimation of parameters in high-dimensional data will not be accurate enough. As a result, the estimated features may not be as effective as they could be. This suggests the need for reducing the dimensionality via a preprocessing method that takes into consideration high-dimensional feature-space properties. Such reduction should enable the estimation of feature-extraction parameters to be more accurate. Using a technique referred to as projection pursuit (PP), such an algorithm has been developed. This technique is able to bypass many of the problems of the limitation of small numbers of training samples by making the computations in a lower-dimensional space, and optimizing a function called the projection index. A current limitation of this method is that, as the number of dimensions increases, it is likely that a local maximum of the projection index will be found that does not enable one to fully exploit hyperspectral-data capabilities.
Shh Signaling and Pancreatic Cancer: Implications for Therapy? (2007)

Hedgehog signaling has been implicated in the development of several human cancers, including small cell lung carcinomas, medulloblastomas, basal cell carcinomas, and digestive tract tumors. Elevated levels of pathway components are observed in pancreatic ductal adenocarcinoma (PDAC) precursor lesions, and these levels increase further as lesions progress to more advanced stages. Yet the mechanisms by which hedgehog signaling contributes to pancreatic tumorigenesis were poorly understood. We recently published results showing that activated hedgehog signaling enhances the proliferation and survival of pancreatic duct epithelial cells, the presumptive target cells for PDAC development. We also demonstrated that sonic hedgehog (Shh) expression, in cooperation with loss of the Trp53 and Ink4a/Arf tumor suppressor loci, was sufficient to initiate the formation of early pancreatic lesions. Furthermore, Shh signaling enhanced K-Ras-mediated pancreatic tumorigenesis and reduced the dependence of tumor cells on the sustained activation of Ras-stimulated signaling pathways. Here we discuss the significance of these findings and the implications for therapy.
Class Diagrams with Equated Association Chains (2013)

We investigate properties of class diagrams with multiplicity constraints - as they appear e.g. in model-based engineering or database design - augmented by equational constraints on association chains. Constraints are typically used to generate additional code that throws an exception when a constraint is violated during run-time. Our aim is different: We develop methods to check already at modelling time whether all constraints can be satisfied, to provide suitable user feedback, and to compute optimal instances of the model. In this paper we extend our approach by a family of constraints that has proven relevant in practice, namely equations between chains of associations. Such equational constraints are necessary if we want to specify that the objects reachable via one chain of associations should in fact be the same as reachable via another one.