gebhart/patrepeval huggingface dataset:
Network firewalls (1994)

Computer security is a hard problem. Security on networked computers is much harder. Firewalls (barriers between two networks), when used properly, can provide a significant increase in computer security. The authors classify firewalls into three main categories: packet filtering, circuit gateways, and application gateways. Commonly, more than one of these is used at the same time. Their examples and discussion relate to UNIX systems and programs. The majority of multiuser machines on the Internet run some version of the UNIX operating system. Most application-level gateways are implemented in UNIX. This is not to say that other operating systems are more secure; however, there are fewer of them on the Internet, and they are less popular as targets for that reason. But the principles and philosophy apply to network gateways built on other operating systems as well. Their focus is on the TCP/IP protocol suite, especially as used on the Internet.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Century changes in Connecticut, U.S.A., lakes as inferred from siliceous algal remains and their relationships to land‐use change (1999)

Scaled chrysophytes and planktonic diatoms are used to infer changes in lake water pH, specific conductivity, trophic score, and total nitrogen in 23 Connecticut waterbodies over the last 100 yr, and the changes are correlated with quantified changes in land use in the surrounding watersheds. In general, there was good agreement between the changes inferred from both organismal groups in this suite of lakes. Significant correlations were observed between chemical conditions inferred from organisms in surface sediments and present‐day land uses, especially the percentages of the watersheds that are forest or residential land cover types. Approximately 20% of the water‐bodies have significantly increased in pH since 1890, and none of the lakes have significantly declined in pH despite the fact that this region receives significant amounts of acidic deposition. These findings support previous work, indicating that the pH of Connecticut lakes has not declined over the recent past. One fourth of the lakes have significantly increased in specific conductivity, especially those situated in watersheds that have become highly residential in nature. Inferred specific conductivity has more than doubled in six of the lakes during the last century. Six of the lakes have become significantly more eutrophic, while only one lake has become more oligotrophic since 1890. The majority of the lakes situated in watersheds that have remained over ∼80% forested have not significantly changed, whereas those that have become over ∼25% residential have experienced the greatest amount of change. The potential influences of watershed‐based alkalinity generation, winter road salt use, and implications of these findings in lake management are discussed.
Characterization of Human Class-Switched Polymeric (Immunoglobulin M [IgM] and IgA) Anti-Human Immunodeficiency Virus Type 1 Antibodies 2F5 and 2G12 (2003)

We have previously generated human monoclonal anti-human immunodeficiency virus type 1 (anti-HIV-1) antibodies 2F5IgG and 2G12IgG with an exceptional cross-clade neutralizing potential. 2F5IgG and 2G12IgG passively administrated to macaques were able to confer complete protection from both intravenous and mucosal challenge with pathogenic HIV-simian immunodeficiency virus chimeric strains and have shown beneficial effects in a phase-1 clinical trial. We now class-switched 2F5 and 2G12 to the immunoglobulin M (IgM) or IgA isotype, to enforce features like avidity, complement activation, or the potential to neutralize mucosal transmission. For this purpose we expressed functional polymeric 2F5 and 2G12 antibodies in CHO cells and evaluated their anti-HIV-1 activity in vitro. The class switch had a strong impact on the protective potential of 2F5 and 2G12. 2G12IgM inhibited HIV-1 infection of peripheral blood mononuclear cell cultures up to 28-fold-more efficiently than the corresponding IgG and neutralized all of the primary isolates tested. The 2F5 and 2G12 antibodies of all isotypes were able to interact with active human serum to inhibit viral infection. Furthermore, we demonstrated that polymeric 2F5 and 2G12 antibodies but not the corresponding IgGs could interfere with HIV-1 entry across a mucosal epithelial layer in vitro. Although polymeric 2F5 antibodies had only limited potential in the standard neutralization assay, the results from the mucosal assay suggest that 2F5 and 2G12 antibodies may have a high potential to prevent natural HIV-1 transmission in vivo.
Second generation teletext and viewdata decoders (1979)

The architecture of second generation hardware for teletext and viewdata decoding, System 12, is shown as an evolutionary progression of industry&apos;s experience and needs. The new architecture is described with emphasis on its application to data sources other than teletext, e.g. viewdata and cassette text. The (AI2L) technology strength which allowed such a system is also described, together with some commercial and technical reasons for its choice. Speed-power products in the order of 0.5 pJ, and delays of about 15 ns for a 5-collector gate, are achieved in production at a circuit density, and process complexity comparable to the most up-to-date m.o.s. processes in industry without the complexity of iterative design. Two of the newer devices that greatly increase system capability are described in greater detail. The remote control interface chip, SN76926, integrates System 12 to Texas Instruments Ltd.&apos;s Mistic family of t.v. peripherals, which includes a low cost, 64-channel remote control. The bus system used also allows communication with Texas Instruments microprocessors. The other circuit described in detail is the system controller, i.e. SN76924, which allows microprocessors handling data to delegate to it a large proportion of the total task of communicating with System 12. Two-way interchange of information with System 12 is so far eased as to allow very low cost, 4-bit microcomputers to cope with major data handling functions. The technical and commercial maturity of product reached by this system gives UK teletext and Prestel services a substantial leadership which should be difficult to ignore if other factors do not retard the speedy development of the market
MINIREVIEW: Differentiated Mammalian Cell Lines Immortalized by Temperature Sensitive Tumor Viruses (1989)

A major goal of cell biologists is to have an in vitro cell model that simulates in vivo conditions. This cell model should be able to propagate in culture, express specialized tissue functions, and allow fundamental biological problems to be answered by a simple manipulation of the culture conditions. Unfortunately, normal differentiated cells generally do not proliferate in culture and often cease to express their specialized functions. As a result, studies have often been carried out on aberrant tumor cell lines that are capable of growth in culture and yet retain the ability to express the tissue-specific functions. However, because of their malignant state and in the absence of normal controls, conclusions from tumor cell studies may not be relevant to normal gene regulation. In the past decade, various attempts have been made to immortalize cells from normal tissues. Cell lines retaining differentiated functions have been established by transformation with chemical carcinogens (1), oncogenes (2, 3), and tumor viruses (4-6). These cell lines retain a spectrum of tissue-specific functions and have been employed in a variety of studies. However, the results obtained from studies using these transformed cell lines, which possess only a transformed phenotype, again may not simulate in vivo gene regulation. To circumvent most of these problems and, additionally, to provide a normal control, we immortalized cells with a temperature-sensitive (ts) A mutant virus of simian virus 40 (SV40). The A gene of SV40 encodes the large tumor (T) antigen which is required for the initiation and maintenance of transformation (7). The fsA mutant virus-transformed cells are conditionally transformed and only express the transformed phenotype at the permissive temperature. At the nonpermissive temperature, these cells quickly revert to a normal nontransformed phenotype. As a result, studies using SV40 teA mutant virus-transformed cells
IS-IS Extension for BGP FRR Protection against Edge Node Failure (2012)

Consider a BGP free core scenario where traffic is tunneled between
edge routers. Suppose the edge BGP speakers PE1, PE2,..., PEn know
about a prefix P/m via the external routers CE1, CE2,..., CEm. If the
edge router PEi crashes or becomes totally disconnected from the core,
it desirable for a core router that is carrying traffic to the
failed edge router PEi to immediately restore traffic by re- routing
packets originally tunneled to PEi and destined to the prefix P/m to
one of the other edge routers that advertised P/m, say PEj, until BGP
re-converges. If the packets originally flowing to the failed edge
router PEi are labeled, then the repairing core router P router may
need to swap, push, or pop the label advertised by the failed edge
router PEi with another label before re-routing the packet through an
LSP terminating PEj so that PEj can correctly forward the packet. The
document proposes an extension to IS-IS protocol to inform core
routers about the repair edge router PEj and, for labeled packets, the
label that needs to be pushed/swapped before sending the packet into
the tunnel terminating on PEj
Cell-associated episialin is a complex containing two proteins derived from a common precursor. (1992)

cDNA for the epithelial sialomucin episialin encodes a transmembrane molecule with a large extracellular domain, which mainly consists of repeats of 20 amino acids. Here we confirm the existence of a previously proposed proteolytic cleavage of episialin that occurs in the endoplasmic reticulum (Hilkens, J., and Buijs, F. (1988) J. Biol. Chem. 263, 4215-4222) and show that a similar cleavage takes place in in vitro translation systems. Using in vitro translation of truncated mRNAs, we map the cleavage site to a region located between 71 and 53 amino acids upstream of the transmembrane domain. Analysis of a mutant, in which this region has been deleted, indicates that the cleavage sites used in vitro and in vivo are identical or in close proximity. Both cleavage products remain associated although they are not linked through disulfide bonds. Therefore, the subunit derived from the N terminus, which represents the actual mucin-like domain, remains indirectly anchored to the cell membrane as a result of its interaction with the C-terminal subunit.
PLANT PROTEIN SERINE/THREONINE KINASES: Classification and Functions (1999)

The first plant protein kinase sequences were reported as recently as 1989, but by mid-1998 there were more than 500, including 175 in Arabidopsis thaliana alone. Despite this impressive pace of discovery, progress in understanding the detailed functions of protein kinases in plants has been slower. Protein serine/threonine kinases from A. thaliana can be divided into around a dozen major groups based on their sequence relationships. For each of these groups, studies on animal and fungal homologs are briefly reviewed, and direct studies of their physiological functions in plants are then discussed in more detail. The network of protein-serine/threonine kinases in plant cells appears to act as a "central processor unit" (cpu), accepting input information from receptors that sense environmental conditions, phytohormones, and other external factors, and converting it into appropriate outputs such as changes in metabolism, gene expression, and cell growth and division.
Trading spaces: Rap, Rac, and Rho as architects of transendothelial migration (2004)

Understanding the complex series of events involved in cell-cell interactions during leukocyte transendothelial migration is a prerequisite for designing novel therapies to treat clinical conditions in which an inappropriate inflammatory response leads to disease. A discussion is provided of recent developments in the molecular regulation of leukocyte recruitment.
Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells (2005)

Immunization with Plasmodium sporozoites that have been attenuated by gamma-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and humoral immune responses invoked by infected hepatocytes cells that contain long-lived, partially developed parasites. Here we analyzed sporozoites of Plasmodium berghei that are deficient in P36p (p36p(-)), a member of the P48/45 family of surface proteins. P36p plays no role in the ability of sporozoites to infect and traverse hepatocytes, but p36p(-) sporozoites abort during development within the hepatocyte. Immunization with p36p(-) sporozoites results in a protective immunity against subsequent challenge with infectious wild-type sporozoites, another example of a specifically genetically attenuated sporozoite (GAS) conferring protective immunity. Comparison of biological characteristics of p36p(-) sporozoites with radiation-attenuated sporozoites demonstrates that liver cells infected with p36p(-) sporozoites disappear rapidly as a result of apoptosis of host cells that may potentiate the immune response. Such knowledge of the biological characteristics of GAS and their evoked immune responses are essential for further investigation of the utility of an optimized GAS-based malaria vaccine.
Epidemiology of Type 2 Diabetes – Global Burden of Disease and Forecasted Trends (2019)

The rising burden of type 2 diabetes is a major concern in healthcare worldwide. This research aimed to analyze the global epidemiology of type 2 diabetes. We analyzed the incidence, prevalence, and burden of suffering of diabetes mellitus based on epidemiological data from the Global Burden of Disease (GBD) current dataset from the Institute of Health Metrics, Seattle. Global and regional trends from 1990 to 2017 of type 2 diabetes for all ages were compiled. Forecast estimates were obtained using the SPSS Time Series Modeler. In 2017, approximately 462 million individuals were affected by type 2 diabetes corresponding to 6.28% of the world's population (4.4% of those aged 15-49 years, 15% of those aged 50-69, and 22% of those aged 70+), or a prevalence rate of 6059 cases per 100,000. Over 1 million deaths per year can be attributed to diabetes alone, making it the ninth leading cause of mortality. The burden of diabetes mellitus is rising globally, and at a much faster rate in developed regions, such as Western Europe. The gender distribution is equal, and the incidence peaks at around 55 years of age. Global prevalence of type 2 diabetes is projected to increase to 7079 individuals per 100,000 by 2030, reflecting a continued rise across all regions of the world. There are concerning trends of rising prevalence in lower-income countries. Urgent public health and clinical preventive measures are warranted.
Molecular regulation of tumor cell vasculogenic mimicry by tyrosine phosphorylation: role of epithelial cell kinase (Eck/EphA2). (2001)

During embryogenesis, blood vessels are formed initially by the process of vasculogenesis, the in situ differentiation of mesenchymal cells into endothelial cells, which form a primitive, patterned vasculogenic network. This is followed by angiogenesis, the sprouting of new vessels from preexisting vasculature, to yield a more refined microcirculation. However, we and our collaborators have recently described a process termed "vasculogenic mimicry," which consists of the formation of patterned, tubular networks by aggressive melanoma tumor cells (in three-dimensional cultures in vitro), that mimics endothelial-formed vasculogenic networks and correlates with poor clinical prognosis in patients. Previous microarray analysis from our laboratory comparing the highly aggressive versus the poorly aggressive melanoma cells revealed a significant increased expression of tyrosine kinases associated with the aggressive melanoma phenotype. Because of the important role of protein tyrosine kinases in phosphorylating various signal transduction proteins that are critical for many cellular processes (e.g., cell adhesion, migration, and invasion), we examined whether protein tyrosine kinases are involved in melanoma vasculogenic mimicry. Immunofluorescence analysis of aggressive melanoma cells forming tubular networks in vitro showed that tyrosine phosphorylation activity colocalized specifically within areas of tubular network formation. A phosphotyrosine profile of the aggressive melanoma cells capable of forming tubular networks indicated differences in tyrosine phosphorylated proteins compared with the poorly aggressive melanoma cells (incapable of forming tubular networks). Most notably, we identified epithelial cell kinase (EphA2) as being one receptor tyrosine kinase expressed and phosphorylated exclusively in the aggressive metastatic melanoma cells. Furthermore, general inhibitors of protein tyrosine kinases hindered tube formation, and transient knockout of EphA2 abrogated the ability of tumor cells to form tubular structures. These results suggest that protein tyrosine kinases, particularly EphA2, are involved in the formation of tubular networks by aggressive melanoma tumor cells in vitro, which may represent a novel therapeutic target for further clinical investigation.
HLA‐C heavy chains free of ß2‐microglobulin: distribution in normal tissues and neoplastic lesions of non‐lymphoid origin and interferon‐γ responsiveness (1997)

Lacking monospecific antibodies to HLA-C, the expression and synthesis of these molecules have been difficult to evaluate. Using biochemical and flow cytometry approaches, the present report demonstrates that the reactivity of the murine monoclonal antibody L31 is restricted to naturally occurring HLA-C (HLA-Cw1 through -Cw8), HLA-B8 and HLA-B51 heavy chains not associated with beta2-microglobin (beta2m). This is due to two properties of HLA-C heavy chains: (a) they share the L31 epitope which distinguishes them from all the HLA-A and most HLA-B molecules; (b) they accumulate intracellularly, in a beta2m-free form, in much greater amounts than most L31-reacting HLA-B heavy chains. On the basis of this restricted reactivity, a representative panel of normal and neoplastic human tissues and cells derived from HLA-B8- B51- individuals was selected and employed to assess the tissue distribution, surface expression and IFN-gamma responsiveness of beta2m-free HLA-C heavy chains. At variance from antibody W6/32 to beta2m-associated heavy chains, L31 stains normal and neoplastic tissues with a ground-glass pattern and weakly binds to the surface of viable cells, even after treatment with interferon gamma (IFN-gamma). Thus, beta2m-free HLA-C heavy chains are, for the most part, located intracellularly. In spite of their distinct cellular localization, L31- and W6/32-reacting molecules have an overlapping tissue distribution, undergo concordant changes upon transformation and are upregulated in their synthesis by IFN-gamma to a similar extent. These observations demonstrate a coordinate regulation of HLA-C with HLA-A and -B molecules. In addition, they indicate that the assembly of HLA-C is impaired in most body districts and IFN-gamma is unable to completely reverse this impairment. The present results are consistent with a low surface expression of HLA-C and with a privileged role of these molecules in signaling class I loss to cytotoxic effectors in pathological conditions.
Acquired Immune Dysfunction in Rabbits Experimentally Infected with an Infectious Molecular Clone of the Bovine Immunodeficiency Virus (BIV127) (1995)

To investigate the effect of bovine immunodeficiency virus (BIV) infection on the rabbit immune system, we studied the proliferative responses of peripheral blood lymphocytes (PBLs) of rabbits experimentally inoculated with BIV. All BIV127-inoculated rabbits seroconverted after 6 weeks and remained seropositive over a prolonged period of time. Assays for specific lymphocyte reactivity to concanavalin A (Con A) were performed monthly for over 1 year. One-hundred percent of infected rabbits developed abnormally low T cell responses, as measured by Con A stimulation. By 3 months postinoculation, the PBL response to Con A was diminished and remained depressed for 6 months. All animals were clinically asymptomatic within 14 months of BIV inoculation. By 15 and 16 months postinoculation, two of three infected rabbits exhibited recurrent lowering of the T cell responsiveness including a decrease in absolute PBL counts. One of these animals died unexpectedly. Our results further confirmed that a functional impairment of lymphocytes was induced early in the course of BIV infection, prior to clinical disease. These findings suggested that BIV infection may mimic asymptomatic infection of human immunodeficiency virus (HIV) and provided further evidence of the importance of BIV-induced disease in rabbits as a relevant model for the study of AIDS.
Structural Insights into Adeno-Associated Virus Serotype 5 (2013)

The adeno-associated viruses (AAVs) display differential cell binding, transduction, and antigenic characteristics specified by their capsid viral protein (VP) composition. Toward structure-function annotation, the crystal structure of AAV5, one of the most sequence diverse AAV serotypes, was determined to 3.45-Å resolution. The AAV5 VP and capsid conserve topological features previously described for other AAVs but uniquely differ in the surface-exposed HI loop between βH and βI of the core β-barrel motif and have pronounced conformational differences in two of the AAV surface variable regions (VRs), VR-IV and VR-VII. The HI loop is structurally conserved in other AAVs despite amino acid differences but is smaller in AAV5 due to an amino acid deletion. This HI loop is adjacent to VR-VII, which is largest in AAV5. The VR-IV, which forms the larger outermost finger-like loop contributing to the protrusions surrounding the icosahedral 3-fold axes of the AAVs, is shorter in AAV5, creating a smoother capsid surface topology. The HI loop plays a role in AAV capsid assembly and genome packaging, and VR-IV and VR-VII are associated with transduction and antigenic differences, respectively, between the AAVs. A comparison of interior capsid surface charge and volume of AAV5 to AAV2 and AAV4 showed a higher propensity of acidic residues but similar volumes, consistent with comparable DNA packaging capacities. This structure provided a three-dimensional (3D) template for functional annotation of the AAV5 capsid with respect to regions that confer assembly efficiency, dictate cellular transduction phenotypes, and control antigenicity.
Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging (2016)

Adult hippocampal neurogenesis may play a role in major depression and antidepressant therapy. Establishment of in vivo imaging for hippocampal neurogenic activity may be useful to diagnose depression and monitor the therapeutic efficacy of antidepressants. Positron emission tomography (PET) imaging has been studied to allow visualization of neurogenic activity; however, PET imaging has not been widely used due to the lower accumulation of the PET tracer in the neurogenic regions. Here, we succeeded in establishing highly quantitative PET imaging for neurogenic activity in adult brain with an inhibitor for drug transporter. This enhanced PET imaging allowed evaluation of the decline of neurogenic activity in the hippocampus of rats with depression and the recovery of neurogenic activity by antidepressant treatment.