gebhart/patrepeval huggingface dataset:
X through the firewall, and other application relays (1993)

Organizations often impose an administrative security policy when they connect to other organizations on a public network such as the Internet. Many applications have their own notions of security, or they simply rely on the security of the underlying protocols. Using the X Window System as a case study, we describe some techniques for building application-specific relays that allow the use of applications across organizational boundaries. In particular, we focus on analyzing administrative and application-specific security policies to construct solutions that satisfy the security requirements while providing the necessary functions of the applications.
Extracting Gene Networks for Low-Dose Radiation Using Graph Theoretical Algorithms (2006)

Genes with common functions often exhibit correlated expression levels, which can be used to identify sets of interacting genes from microarray data. Microarrays typically measure expression across genomic space, creating a massive matrix of co-expression that must be mined to extract only the most relevant gene interactions. We describe a graph theoretical approach to extracting co-expressed sets of genes, based on the computation of cliques. Unlike the results of traditional clustering algorithms, cliques are not disjoint and allow genes to be assigned to multiple sets of interacting partners, consistent with biological reality. A graph is created by thresholding the correlation matrix to include only the correlations most likely to signify functional relationships. Cliques computed from the graph correspond to sets of genes for which significant edges are present between all members of the set, representing potential members of common or interacting pathways. Clique membership can be used to infer function about poorly annotated genes, based on the known functions of better-annotated genes with which they share clique membership (i.e., "guilt-by-association"). We illustrate our method by applying it to microarray data collected from the spleens of mice exposed to low-dose ionizing radiation. Differential analysis is used to identify sets of genes whose interactions are impacted by radiation exposure. The correlation graph is also queried independently of clique to extract edges that are impacted by radiation. We present several examples of multiple gene interactions that are altered by radiation exposure and thus represent potential molecular pathways that mediate the radiation response.
Reconstitution of human epidermal growth factor receptors and its deletion mutants in cultured hamster cells. (1986)

DNA sequences encoding the human epidermal growth factor (EGF) receptor and various EGF-receptor deletion mutants were transfected into chinese hamster ovary (CHO) cells devoid of endogenous EGF receptors. A functional human EGF-receptor is expressed on the surface of heterologous CHO cells with the following properties: it exhibits typical high affinity (10%; Kd = 3 X 10(-10) M) and low affinity (90%; Kd = 3 X 10(-9) M) binding sites for 125I-EGF; it is expressed as a polypeptide of 170,000 molecular weight with intrinsic protein tyrosine kinase activity. EGF stimulates the kinase activity leading to self-phosphorylation and to phosphorylation of exogenous substrate; 125I-EGF is rapidly internalized into the CHO cells by receptor mediated endocytosis and; EGF stimulates DNA synthesis in the cells expressing the human EGF-receptor. Deletion of 63 amino acids from the C-terminal end of EGF-receptor, which removes two autophosphorylation sites, abolishes the high affinity state of the receptor. Nevertheless, this receptor mutant is able to undergo endocytosis and to respond mitogenically to EGF to a similar extent as the "wild type" receptor. Further deletions from the cytoplasmic domain give rise to low affinity endocytosis-defective receptor mutants. Finally, deletion of the transmembrane domain of the human receptor yields an EGF-receptor ligand binding domain which is secreted from the cells.
Cas9–crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria (2012)

Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide adaptive immunity against viruses and plasmids in bacteria and archaea. The silencing of invading nucleic acids is executed by ribonucleoprotein complexes preloaded with small, interfering CRISPR RNAs (crRNAs) that act as guides for targeting and degradation of foreign nucleic acid. Here, we demonstrate that the Cas9-crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system introduces in vitro a double-strand break at a specific site in DNA containing a sequence complementary to crRNA. DNA cleavage is executed by Cas9, which uses two distinct active sites, RuvC and HNH, to generate site-specific nicks on opposite DNA strands. Results demonstrate that the Cas9-crRNA complex functions as an RNA-guided endonuclease with RNA-directed target sequence recognition and protein-mediated DNA cleavage. These findings pave the way for engineering of universal programmable RNA-guided DNA endonucleases.
Conformational and Experimental Studies on the Dipole Moments of Models of Comblike Polymers (1997)

The synthesis and radical polymerization of 2,2-bis[4-(2-hydroxyethoxy)phenyl]propyl monoacrylate are described. The values found at 50 and 60 °C for the rate constants ratio, kp/kt1/2, are similar to those reported for some acrylic polymers with short side groups at the same temperatures although conflicting results are obtained by comparison with the kinetic constants reported for other similar acrylic monomers. The experimental value of the mean-square dipole moment per repeating unit of the resulting polymer, poly{2,2-bis[4-(2-hydroxyethoxy)phenyl]propyl monoacrylate} was 7.24 D2 at 30 °C. This result is very close to the value of 7.83 D2 found, at the same temperature, for the model compound of the side group of the polymer, 2,2-bis[4-(2-hydroxyethoxy)phenyl]propyl monoacetate. Owing to the wide distribution of dipole moments associated with the side groups, the dipolar correlation coefficient of the chains was calculated by combining matricial products of the rotational isomeric state model and Monte Carlo techniques. The calculations suggest that the statistics of long side groups rather than the statistics of the main chain govern the dipolar correlation coefficient of atactic comblike polymers.
ALK a Novel Lymphoma-associated Tumor Antigen for Vaccination Strategies (2003)

The discovery of Tumor Associated Antigens (TAAs) demonstrated that tumor cells can be specifically recognized by the immune system raising the hypothesis that tumors express antigens that Cytotoxic T Lymphocytes (CTLs) can potentially attack. The identification of immunogenic epitopes led to their use as targets to mediate the specific clearance of neoplastic cells by TAA targeting strategies such as vaccination strategies. One of the critical issues in the development of efficient vaccination protocols is the identification of the appropriate TAAs. The TAA should be effective as a "tumor rejection antigen" able to induce an immune response that will affect tumor growth. A distinct pathologic entity characterized by the expression of the Anaplastic Lymphoma Kinase (ALK) protein and named "ALKoma" has recently emerged within the heterogeneous group of CD30+ Anaplastic Large Cell Lymphoma (ALCL). ALK is a receptor tyrosine kinase whose expression is normally restricted to a few scattered cells in the nervous system. Its pathological expression in lymphoma cells is due to a chromosomal translocation that leads to the formation of an ALK-derived oncogenic fusion proteins. ALK fusion proteins ectopically over-expressed and constitutively activated in lymphoid cells play a key role in the neoplastic transformation by the aberrant phosphorylation of intracellular substrates that likely contributes to the molecular pathogenesis of ALCL. The high level of ALK expression in lymphoma cells and its direct role in lymphomagenesis, combined with the fact that normal ALK is expressed at low levels in the immune privileged nervous system, makes ALK an ideal lymphoma-specific target for immunotherapy of ALK+ALCL.
Human Detection via Classification on Riemannian Manifolds (2007)

We present a new algorithm to detect humans in still images utilizing covariance matrices as object descriptors. Since these descriptors do not lie on a vector space, well known machine learning techniques are not adequate to learn the classifiers. The space of d-dimensional nonsingular covariance matrices can be represented as a connected Riemannian manifold. We present a novel approach for classifying points lying on a Riemannian manifold by incorporating the a priori information about the geometry of the space. The algorithm is tested on INRIA human database where superior detection rates are observed over the previous approaches.
Fundamental Concepts of the Angiogenic Process (2003)

The process of angiogenesis encompasses the growth and regression of capillary blood vessels. Angiogenesis is finely regulated at the molecular and genetic levels, not unlike other physiologic processes such as coagulation, glucose metabolism, and blood pressure. During the development of the field of angiogenesis research over the past three decades, fundamental concepts have been introduced along the way in an attempt where possible, to unify new data from a variety of different laboratories. I have assembled here the major concepts which underlie the angiogenic process as we currently understand it. Many of these are now taken for granted, but this was not always the case, and I have tried to show how they were developed. My goal is to provide a conceptual framework for those basic scientists or clinicians who may enter this rapidly expanding field. Each concept discussed here is accompanied by a few key references as a guide to the pertinent literature.
IscA/SufA paralogues are required for the [4Fe-4S] cluster assembly in enzymes of multiple physiological pathways inEscherichia coliunder aerobic growth conditions (2009)

IscA/SufA paralogues are the members of the iron-sulfur cluster assembly machinery in Escherichia coli. Whereas deletion of either IscA or SufA has only a mild effect on cell growth, deletion of both IscA and SufA results in a null-growth phenotype in minimal medium under aerobic growth conditions. Here we report that cell growth of the iscA/sufA double mutant (E. coli strain in which both iscA and sufA had been in-frame-deleted) can be partially restored by supplementing with BCAAs (branched-chain amino acids) and thiamin. We further demonstrate that deletion of IscA/SufA paralogues blocks the [4Fe-4S] cluster assembly in IlvD (dihydroxyacid dehydratase) of the BCAA biosynthetic pathway in E. coli cells under aerobic conditions and that addition of the iron-bound IscA/SufA efficiently promotes the [4Fe-4S] cluster assembly in IlvD and restores the enzyme activity in vitro, suggesting that IscA/SufA may act as an iron donor for the [4Fe-4S] cluster assembly under aerobic conditions. Additional studies reveal that IscA/SufA are also required for the [4Fe-4S] cluster assembly in enzyme ThiC of the thiamin-biosynthetic pathway, aconitase B of the citrate acid cycle and endonuclease III of the DNA-base-excision-repair pathway in E. coli under aerobic conditions. Nevertheless, deletion of IscA/SufA does not significantly affect the [2Fe-2S] cluster assembly in the redox transcription factor SoxR, ferredoxin and the siderophore-iron reductase FhuF. The results suggest that the biogenesis of the [4Fe-4S] clusters and the [2Fe-2S] clusters may have distinct pathways and that IscA/SufA paralogues are essential for the [4Fe-4S] cluster assembly, but are dispensable for the [2Fe-2S] cluster assembly in E. coli under aerobic conditions.
Algal biofuels: the eternal promise? (2010)

A graphical abstract is available for this content
Investigation of the nucleation of oxygen precipitates in Czochralski silicon at an early stage (1992)

The nucleation of oxygen precipitates in Czochralski silicon is examined in an early stage by measuring vacancy profiles with platinum diffusion. Using an analytical expression, which was deduced from the equations of the Frank–Turnbull diffusion mechanism, the vacancy profiles are calculated from measured platinum diffusion profiles. The vacancy concentration of differently treated Czochralski (CZ) material is compared to the vacancy concentration of float zone (FZ) silicon. In CZ silicon a decrease of the vacancy concentration with increasing nucleation time and platinum diffusion time is found. This decrease cannot be explained by a supersaturation of silicon self-interstitials caused by nucleation and by recombination of self-interstitials and vacancies alone. A direct consumption of vacancies during nucleation also is present. The annihilation rate of the vacancies during nucleation can be estimated to be smaller than 5×108 cm−3 s−1 at 770 °C.
Breast Cancer Stem Cells and the Epithelial-Mesenchymal Transition. (2009)

Abstract The acquisition of highly malignant traits by carcinoma cells is often associated with the activation of a transdifferentiation program termed the epithelial-mesenchymal transition (EMT). The EMT program is deployed in a variety of steps of embryonic morphogenesis, enabling the interconversion of epithelial and mesenchymal cell types. When both normal and neoplastic epithelial cells undergo an EMT, they acquire addition changes in addition to expressing characteristic mesenchymal cell markers. In particular, they acquire motility, an increased resistance to apoptosis and, in the case of carcinoma cells, invasiveness. The motility and invasiveness components associated with the EMT would appear to empower many types of cancer cells to metastasize. An interesting question is how the resulting disseminated cancer cells are able to spawn a macroscopic tumor mass at distant anatomical sites, since this clonal expansion would appear to require an ability to self-renew. Recently, we have examined the cellular products of an EMT. Contrary to our expectations, the resulting cells acquired many of the attributes of stem cells, including the expression of stem cell-associated cell-surface markers. Conversely, mammary epithelial cells that naturally express these markers also express greatly elevated levels of at least four pleiotropically acting transcription factors that have been found able to induce an EMT. More recent studies have confirmed that the product of an EMT in mouse mammary epithelial cells is a cell that has a greatly increased ability to generate an entire mammary ductal epithelial tree. Moreover, we find that cells with the attributes of stem cells exist naturally as minor subpopulations in cultured human mammary epithelial cells. These cells can differentiate spontaneously into non-stem cells and, conversely, the non-stem cells appear capable of dedifferentiating spontaneously into cells with progenitor or stem-cell phenotypes. Hence, the study of certain aspects of mammary epithelial cell biology, including the biology of mammary carcinoma stem cells, may be feasible with cultured cells. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr A1-1.
Safety Considerations in Somatic Gene Therapy of Human Disease with Retrovirus Vectors (1990)

Somatic gene therapy of human disease with retrovirus vectors is a new technology with potentially important medical benefits. Although it involves recombinant DNA technologies and modified retroviruses, proper design of the vectors and delivery systems removes most potential foreseen risks. Furthermore, even in the very remote possibility that there is a nontherapeutic biological effect of the treatment, it is unlikely to be a harmful one. Thus, once very safe retrovirus vector-helper cell systems are constructed and in use, safety considerations should not hold up further human trials of retrovirus vectors.
Silicon microring carrier-injection-based modulators/switches with tunable extinction ratios and OR-logic switching by using waveguide cross-coupling (2007)

We demonstrate silicon microring carrier-injection-based modulators/switches with waveguide cross-coupling. We tune the modulator extinction ratio by forward-biasing either the microring or cross-coupled waveguide p-i-n diode, while modulating the other. We also demonstrate OR-logic switching functionality by simultaneously applying two different electrical data streams across the microring and cross-coupled waveguide diodes. For both the modulator and the switch, we observe NRZ pattern-dependent optical waveform distortions.
Delineating the Cellular Mechanisms Associated with Skin Electroporation (2018)

The immune responses elicited following delivery of DNA vaccines to the skin has previously been shown to be significantly enhanced by the addition of electroporation (EP) to the treatment protocol. Principally, EP increases the transfection of plasmid DNA (pDNA) into the resident skin cells. In addition to increasing the levels of in vivo transfection, the physical insult induced by EP is associated with activation of innate pathways which are believed to mediate an adjuvant effect, further enhancing DNA vaccine responses. We investigated the possible mechanisms associated with this adjuvant effect, primarily focusing on the cell death pathways associated with the skin EP procedure independent of pDNA delivery. Using the minimally invasive CELLECTRA<sup>®</sup>-3P intradermal electroporation device that penetrates the epidermal and dermal layers of the skin, we have investigated apoptotic and necrotic cell death in relation to the vicinity of the electrode needles and electric field generated. Employing the well-established terminal deoxynucleotidyl transferase nick-end labeling assay, we detected apoptosis beginning as early as one hour after EP and peaking at the 4 h time point. The majority of the apoptotic events were detected in the epidermal region directly adjacent to the electrode needle. Using a novel propidium iodide in vivo necrotic cell death assay, we detected necrotic events concentrated in the epidermal region adjacent to the electrode. Furthermore, we detected upregulation of calreticulin expression on skin cells after EP, thus labeling these cells for uptake by dendritic cells and macrophages. These results allow us to delineate the cell death mechanisms occurring in the skin following intradermal EP independently of pDNA delivery. We believe these events contribute to the adjuvant effect observed following electroporation at the skin treatment site.
Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones (2010)

Nature frequently utilizes opposing factors to create a stable activator gradient to robustly control pattern formation. This study employs a biomimicry approach, by delivery of both angiogenic and antiangiogenic factors from spatially restricted zones of a synthetic polymer to achieve temporally stable and spatially restricted angiogenic zones in vivo. The simultaneous release of the two spatially separated agents leads to a spatially sharp angiogenic region that is sustained over 3 wk. Further, the contradictory action of the two agents leads to a stable level of proangiogenic stimulation in this region, in spite of significant variations in the individual release rates over time. The resulting spatially restrictive and temporally sustained profiles of active signaling allow the creation of a spatially heterogeneous and functional vasculature.
The Human T-Box Mesodermal Transcription Factor Brachyury Is a Candidate Target for T-Cell–Mediated Cancer Immunotherapy (2007)

To our knowledge, this is the first demonstration that (a) a T-box transcription factor and (b) a molecule implicated in mesodermal development, i.e., EMT, can be a potential target for human T-cell-mediated cancer immunotherapy.
Local Production of Pharmaceuticals : Industrial Policy and Access to Medicines, An Overview of Key Concepts, Issues and Opportunities for Future Research (2005)

Local production of pharmaceuticals in developing countries may be seen as helping to stimulate industrial policy and/or as stimulating pharmaceutical access to needed medicines. However, if a developing country with manufacturing facilities is able to finish off bulk active ingredients sourced from developed or other countries at high costs, such manufacture may have no impact whatever on patient access to needed medicines. There has been some critical thinking in the past regarding whether or not small developing countries should make their own pharmaceuticals, but no recent comprehensive summary of the issues and policy options. This paper summarizes the issues surrounding local production from a policy and public health viewpoint. It provides four brief country-level case studies, and reviews the evidence supporting the industrial policy assumptions underlying the goal of local production. In brief, in many parts of the world, producing medicines domestically makes little economic sense. If many countries begin local production, the result may be less access to medicines, since economies of scale may be lost if there are production facilities in many countries. The document concludes by providing a research agenda specifically designed to test assumptions about local production of pharmaceuticals.
Progress with Nonhuman Primate Embryonic Stem Cells1 (2004)

Embryonic stem cells hold potential in the fields of regenerative medicine, developmental biology, tissue regeneration, disease pathogenicity, and drug discovery. Embryonic stem (ES) cell lines are now available in primates, including man, rhesus, and cynomologous monkeys. Monkey ES cells serve as invaluable clinically relevant models for studies that can't be conducted in humans because of practical or ethical limitations, or in rodents because of differences in physiology and anatomy. Here, we review the current status of nonhuman primate research with ES cells, beginning with a description of their isolation, characterization, and availability. Substantial limitations still plague the use of primate ES cells, such as their required growth on feeder layers, poor cloning efficiency, and restricted availability. The ability to produce homogenous populations of both undifferentiated as well as differentiated phenotypes is an important challenge, and genetic approaches to achieving these objectives are discussed. Finally, safety, efficiency, and feasibility issues relating to the transplantation of ES-derived cells are considered.