gebhart/patrepeval huggingface dataset:
Adaptive packet filters (2002)

Adaptive packet filters (APFs) are motivated by the proliferation of distributed servers and the lack of quality-of-service (QoS) management solutions for them. APFs merge packet-filtering and server load monitoring into a novel load-sensitive packet-filtering abstraction for overload protection and QoS differentiation. They integrate well into network protocol stacks and firewalls, scale to large server farms while remaining completely transparent to the applications. Experimental results of our prototype implementation demonstrate APFs' efficacy in providing QoS differentiation and overload protection with minimal overheads.
Profiling and targeting of cellular bioenergetics: inhibition of pancreatic cancer cell proliferation (2014)

Detailed profiling of cellular bioenergetics can provide new insight into the design of therapeutic strategies for inhibiting pancreatic cancer cell metabolism and proliferation.
Sustained Notch1 signaling instructs the earliest human intrathymic precursors to adopt a γδ T-cell fate in fetal thymus organ culture (2003)

Notch1 activity is essential for the specification of T-lineage fate in hematopoietic progenitors. Once the T-cell lineage is specified, T-cell precursors in the thymus must choose between alphabeta and gammadelta lineages. However, the impact of Notch1 signaling on intrathymic pro-T cells has not been addressed directly. To approach this issue, we used retroviral vectors to express constitutively active Notch1 in human thymocyte progenitors positioned at successive developmental stages, and we followed their differentiation in fetal thymus organ culture (FTOC). Here we show that sustained Notch1 signaling impairs progression to the double-positive (DP) stage and efficiently diverts the earliest thymic progenitors from the main alphabeta T-cell pathway toward development of gammadelta T cells. The impact of Notch1 signaling on skewed gammadelta production decreases progressively along intrathymic maturation and is restricted to precursor stages upstream of the pre-T-cell receptor checkpoint. Close to and beyond that point, Notch1 is not further able to instruct gammadelta cell fate, but promotes an abnormal expansion of alphabeta-committed thymocytes. These results stress the stage-specific impact of Notch1 signaling in intrathymic differentiation and suggest that regulation of Notch1 activity at defined developmental windows is essential to control alphabeta versus gammadelta T-cell development and to avoid deregulated expansion of alphabeta-lineage cells.
Selective immunosuppression by administration of major histocompatibility complex (MHC) class II-binding peptides. I. Evidence for in vivo MHC blockade preventing T cell activation. (1992)

Draining lymph node cells (LNC) from mice immunized with hen egg white lysozyme (HEL) display at their surface antigen-MHC complexes able to stimulate, in the absence of any further antigen addition, HEL peptide-specific, class II-restricted T cell hybridomas. Chloroquine addition to these LNC cultures fails to inhibit antigen presentation, indicating that antigenic complexes of class II molecules and HEL peptides are formed in vivo. MHC class II restriction of antigen presentation by LNC from HEL-primed mice was verified by the use of anti-class II monoclonal antibodies. Coinjection of HEL and the I-Ak-binding peptide HEL 112-129 in mice of H-2k haplotype inhibits the ability of LNC to stimulate I-Ak-restricted, HEL 46-61-specific T cell hybridomas. Similar results are obtained in mice coinjected with the HEL peptides 46-61 and 112-129. Inhibition of T hybridoma activation can also be observed using as antigen-presenting cells irradiated, T cell-depleted LNC from mice coinjected with HEL 46-61 and HEL 112-129, ruling out the possible role of either specific or nonspecific suppressor T cells. Inhibition of T cell proliferation is associated with MHC-specific inhibition of antigen presentation and with occupancy by the competitor of class II binding sites, as measured by activation of peptide-specific T cell hybridomas. These results demonstrate that administration of MHC class II binding peptide competitors selectively inhibits antigen presentation to class II-restricted T cells, indicating competitive blockade of class II molecules in vivo.
Improving Spectral Results Using Row-by-Row Fourier Transform of Spatial Heterodyne Raman Spectrometer Interferogram (2016)

This work describes a method of applying the Fourier transform to the two-dimensional Fizeau fringe patterns generated by the spatial heterodyne Raman spectrometer (SHRS), a dispersive interferometer, to correct the effects of certain types of optical alignment errors. In the SHRS, certain types of optical misalignments result in wavelength-dependent and wavelength-independent rotations of the fringe pattern on the detector. We describe here a simple correction technique that can be used in post-processing, by applying the Fourier transform in a row-by-row manner. This allows the user to be more forgiving of fringe alignment and allows for a reduction in the mechanical complexity of the SHRS.
Apyrases (Nucleoside Triphosphate-Diphosphohydrolases) Play a Key Role in Growth Control in Arabidopsis (2007)

Expression of two Arabidopsis (Arabidopsis thaliana) apyrase (nucleoside triphosphate-diphosphohydrolase) genes with high similarity, APY1 and APY2, was analyzed during seedling development and under different light treatments using beta-glucuronidase fusion constructs with the promoters of both genes. As evaluated by beta-glucuronidase staining and independently confirmed by other methods, the highest expression of both apyrases was in rapidly growing tissues and/or tissues that accumulate high auxin levels. Red-light treatment of etiolated seedlings suppressed the protein and message level of both apyrases at least as rapidly as it inhibited hypocotyl growth. Adult apy1 and apy2 single mutants had near-normal growth, but apy1apy2 double-knockout plants were dwarf, due primarily to reduced cell elongation. Pollen tubes and etiolated hypocotyls overexpressing an apyrase had faster growth rates than wild-type plants. Growing pollen tubes released ATP into the growth medium and suppression of apyrase activity by antiapyrase antibodies or by inhibitors simultaneously increased medium ATP levels and inhibited pollen tube growth. These results imply that APY1 and APY2, like their homologs in animals, act to reduce the concentration of extracellular nucleotides, and that this function is important for the regulation of growth in Arabidopsis.
Developing Agreement Between Very Short Flow and Longer Flow Test Wheat Mills (2000)

ABSTRACT Variations in soft wheat moisture content and kernel texture greatly affected the flour yield produced by a small (short flow) microtest mill (Quadrumat Jr.). An algorithm was developed that adjusted Quadrumat Jr. flour yield to 15% wheat moisture content, precluding the need to temper the wheat before milling. Another algorithm was developed to adjust Quadrumat flour yield relative to a constant softness equivalent (measurement of kernel texture) obtained during the micromilling procedure. Predicting the flour yield of the longer flow Allis‐Chalmers mill from Quadrumat Jr. unadjusted flour yield ( R 2 = 0.55) was compared with predicting Allis‐Chalmers flour yield from the Quadrumat Jr. adjusted flour yield ( R 2 = 0.90) across five diverse confirmation data sets. An algorithm to adjust flour yield for softness equivalent was individually developed for soft and hard wheats. Representative micromilling flour yield and softness equivalent data could be produced using as little as 10 g of untempered wheat and ≈3 min of operator time.
Autologous fibroblast implantation. Feasibility and potential problems in gene replacement therapy. (1990)

Autologous implants of genetically modified fibroblasts may be an ideal approach to gene replacement therapy. However, primary fibroblasts have limited life span and their use for gene therapy is questionable. We have developed a rat model to evaluate the feasibility of this approach. Primary fibroblasts initiated from rat skin biopsies were transfected with plasmid DNA. The transkaryotic fibroblasts were implanted into the original rat donors. A plasmid-encoded gene product, human growth hormone, was detected in the donor rats' circulation but less than 1% of the expected amount was recovered. Implantation at intraperitoneal, intramuscular or subcutaneous sites were effective in delivering the novel gene product. Fluctuating levels of human growth hormone were detected for over 6 months but their determination was rendered unreliable due to interference by extremely high titers of antibodies developed against the human growth hormone. In some cases, the antibody titer continued rising for more than 6 months, indicative of the continued presence of the antigen. One of the recipients developed two intra-abdominal fibrosarcomas that were shown to be derived from the implanted cells. In conclusion, this model demonstrates that autologous fibroblast implantation is a feasible approach to delivering novel gene products lasting for several months. Strong and prolonged immuno-reaction against the gene product will occur if the recipient's immune system is naive to the replacement product, as would occur in patients with CRM- mutations. The potential for neoplastic development from the implanted fibroblasts should prompt further evaluation of the long-term safety in gene replacement therapy.
Immunization delivered by lentiviral vectors for cancer and infectious diseases (2010)

The increasing level of understanding of the lentivirus biology has been instrumental in shaping the design strategy of creating therapeutic lentiviral delivery vectors. As a result, lentiviral vectors have become one of the most powerful gene transfer vehicles. They are widely used for therapeutic purposes as well as in studies of basic biology, due to their unique characteristics. Lentiviral vectors have been successfully employed to mediate durable and efficient antigen expression and presentation in dendritic cells both in vitro and in vivo, leading to the activation of cellular immunity and humoral responses. This capability makes the lentiviral vector an ideal choice for immunizations that target a wide range of cancers and infectious diseases. Further advances into optimizing the vector system and understanding the relationship between the immune system and diseases pathogenesis will only augment the potential benefits and utility of lentiviral vaccines for human health.
Novel Degradable Poly(Ethylene Glycol) Hydrogels for Controlled Release of Protein (1998)

Hydrogels have become increasingly important in the biomedical field. This paper describes synthesis and characterization of two types of novel degradable poly(ethylene glycol) (PEG) hydrogels with potential utility as delivery carriers for bioactive drugs. The simplest gel is prepared by one-step polycondensation of difunctional PEG acid and branched PEG "polyol". The second type of the novel degradable PEG hydrogel was prepared in a two-step process, in which an ester-containing, amine-reactive PEG derivative was synthesized and then reacted with a branched PEG amine to form the gel. The two-step gels are formed in very mild conditions, and therefore fragile drugs such as proteins can be loaded during gel formation. Because most proteins have free amino groups in the sequence, these proteins can be covalently linked to the hydrogel network. This covalent attachment provides a new way to achieve long-term controlled release of proteins. These hydrogels have a wide range of degradation rates. Upon hydrolysis, these PEG hydrogels will degrade into low molecular weight PEG derivatives, which can be easily cleared by the body.
Intercalators. 1. Nature of Stacking Interactions between Intercalators (Ethidium, Daunomycin, Ellipticine, and 4‘,6-Diaminide-2-phenylindole) and DNA Base Pairs. Ab Initio Quantum Chemical, Density Functional Theory, and Empirical Potential Study (2002)

Properties of isolated intercalators (ethidium (E), daunomycin (D), ellipticine (EL), and 4,6'-diaminide-2-phenylindole (DAPI)) and their stacking interactions with adenine...thymine (AT) and guanine...cytosine (GC) nucleic acid base pairs were investigated by means of a nonempirical correlated ab initio method. All intercalators exhibit large charge delocalization, and none of them (including the DAPI dication) exhibits a site with dominant charge. All intercalators have large polarizability and are good electron acceptors, while base pairs are good electron donors. MP2/6-31G*(0.25) stabilization energies of intercalator...base pair complexes are large (E...AT, 22.4 kcal/mol; D...GC, 17.8 kcal/mol; EL...GC, 18.2 kcal/mol; DAPI...GC, 21.1 kcal/mol) and are well reproduced by modified AMBER potential (van der Waals radii of intercalator atoms are enlarged and their energy depths are increased). Standard AMBER potential underestimates binding, especially for DAPI-containing complexes. Because the DAPI dication is the best electron acceptor (among all intercalators studied), this difference is explained by the importance of the charge-transfer term, which is not included in the AMBER potential. For the neutral EL molecule, the standard AMBER force field provides correct results. The Hartree-Fock and DFT/B3LYP methods, not covering the dispersion energy, fail completely to reveal any energy minimum at the potential energy curve of the E...AT complex, and these methods thus cannot be recommended for a study of intercalation process. On the other hand, an approximate version of the DFT method, which was extended to cover London dispersion energy, yields for all complexes very good stabilization energies that are well comparable with referenced ab initio data. Besides the vertical dependence of the interaction, an energy twist dependence of the interaction energy was also investigated by a reference correlated ab initio method and empirical potentials. It is concluded that, despite the cationic (E +1, D +1, DAPI +2) or polar (EL) character of the intercalators investigated, it is the dispersion energy which predominantly contributes to the stability of intercalator...base pair complexes. Any procedure which does not cover dispersion energy is thus not suitable for studying the process of intercalation.
Characterization of Absolute Lymphocyte Count Profiles in MS Patients Treated with Delayed-Release Dimethyl Fumarate: Considerations for Patient Management (P2.099) (2016)

OBJECTIVE: Provide practical considerations for management of delayed-release dimethyl fumarate (DMF)-treated multiple sclerosis (MS) patients by characterizing absolute lymphocyte count (ALC) profiles. BACKGROUND: DMF label includes a recommendation to consider treatment interruption in patients with ALCs <500/mm3 persisting ≥6 months to minimize risk of subsequently developing severe, prolonged lymphopenia. DESIGN/METHODS: An integrated analysis of the Phase 2b and Phase 3 (DEFINE/CONFIRM, ENDORSE) DMF studies was conducted; the analysis population comprised 2,470 patients with any post-baseline ALC. ALCs were assessed at weeks 4, 8, 12, and every 12 weeks thereafter. The data cut-off was 15 April 2015. RESULTS: Mean ALCs decreased by approximately 30[percnt] during the first year of treatment, then plateaued, remaining above lower limit of normal (LLN; 910/mm3). Among patients treated for ≥6 months (N=2098), 2.5[percnt] (n=53) experienced ALCs <500/mm3 persisting ≥6 months; subsequent ALCs of these patients generally remained <500/mm3. The incidence of ALCs <500/mm3 persisting ≥6 months was 0.9[percnt] (12/1311) in patients <40 years of age, 3.5[percnt] (28/809) in patients 40-49 years of age, and 4.4[percnt] (13/297) in patients ≥50 years of age. ALCs remained ≥LLN in 84[percnt] of patients during the first 6 months and 76[percnt] of patients during the first year; of these patients, 0.3[percnt] and 0.1[percnt], respectively, subsequently developed ALCs <500/mm3 persisting ≥6 months at any time. Aside from PML in the setting of severe, prolonged lymphopenia, there was no overall increased risk for serious infections, including other opportunistic infections, with DMF. CONCLUSIONS: ALC profiles are well characterized and generally stable over time. Lymphocyte monitoring provides an effective means for early identification of patients at risk for subsequently developing severe and prolonged lymphopenia. The overall benefit-risk of DMF remains favorable. Additional data will be presented. Study Supported by: Biogen
Functionalised staple linkages for modulating the cellular activity of stapled peptides (2014)

A divergent synthetic strategy for generating helical p53 peptides bearing functionalised staple linkages, allowing for efficient optimisation of cellular activity.
Design and demonstration of an intracortical probe technology with tunable modulus (2016)

Intracortical probe technology, consisting of arrays of microelectrodes, offers a means of recording the bioelectrical activity from neural tissue. A major limitation of existing intracortical probe technology pertains to limited lifetime of 6 months to a year of recording after implantation. A major contributor to device failure is widely believed to be the interfacial mechanical mismatch of conventional stiff intracortical devices and the surrounding brain tissue. We describe the design, development, and demonstration of a novel functional intracortical probe technology that has a tunable Young's modulus from ∼2 GPa to ∼50 MPa. This technology leverages advances in dynamically softening materials, specifically thiol-ene/acrylate thermoset polymers, which exhibit minimal swelling of < 3% weight upon softening in vitro. We demonstrate that a shape memory polymer-based multichannel intracortical probe can be fabricated, that the mechanical properties are stable for at least 2 months and that the device is capable of single unit recordings for durations up to 77 days in vivo. This novel technology, which is amenable to processes suitable for manufacturing via standard semiconductor fabrication techniques, offers the capability of softening in vivo to reduce the tissue-device modulus mismatch to ultimately improve long term viability of neural recordings. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 159-168, 2017.
Biphasic effect of Max on Myc cotransformation activity and dependence on amino- and carboxy-terminal Max functions. (1992)

In Ras cotransformation assays, Max exhibited a biphasic effect on Myc transformation activity. Cotransfection of low levels of Max expression plasmid stimulated Myc transformation activity, but cotransfection of high levels suppressed it. Mutations in the functionally undefined Max amino- and carboxy-terminal regions outside of the B/HLH/LZ motif partly separated these activities, suggesting various modes of Max regulation. We demonstrate that the Max protein is a nuclear protein in vivo and identify a carboxy-terminal region similar to nuclear localization signals whose integrity is necessary for efficient localization. Two mutants that delete amino- or carboxy-terminal consensus signals for casein kinase II (CKII) exhibited altered gel mobility and DNA-binding potential in vitro and showed modified transforming potential in the Ras cotransformation assay, suggesting that CKII or a CKII-related enzyme may regulate Max function in vivo. Our data suggest that both the ratio of Myc/Max hetero-oligomers to Max homo-oligomers and Max-specific regulation can contribute to determining the biological activity of Myc in vivo.
The Role of Radical Cystectomy in the Management of High Grade Superficial Bladder Cancer (PA, P1PIS and P2) (1990)

Between January 1979 and 1987, 411 consecutive patients were considered candidates for bilateral pelvic iliac lymph node dissection and radical cystectomy for the management of bladder cancer. From this group 160 were identified as having pathological stage P2 or less disease, including 11 who also had positive nodes. The 5-year actuarial survival rate for the respective stages at 95% confidence limits was 100% for stage P0/A, 80% for stage P1, 78% for stage P1 with stage PIS, 85% for pure stage PIS, 76% for stage P2 and 87% for stage P2 with stage PIS. Additionally, we identified a group of patients with stage P2 transitional cell carcinoma who were at significant risk for development of metastatic disease. Of 46 patients with stage P2 transitional cell carcinoma 18 had vascular space invasion resulting in 6 of 18 cancer-related deaths (33%). Our study demonstrates that radical cystectomy has been highly effective in curing patients with high grade superficial disease, including those with superficially invasive disease associated with nodal metastases.
Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1 (2002)

The toxic effect of cholera toxin (CT) on target cells is caused by its A1 chain. This polypeptide is released from the holotoxin and unfolded in the lumen of the ER by the action of protein disulfide isomerase (PDI), before being retrotranslocated into the cytosol. The polypeptide is initially unfolded by binding to the reduced form of PDI. We show that upon oxidation of the COOH-terminal disulfide bond in PDI by the enzyme Ero1, the A1 chain is released. Both yeast Ero1 and the mammalian Ero1alpha isoform are active in this reaction. Ero1 has a preference for the PDI-toxin complex. We further show that the complex is transferred to a protein at the lumenal side of the ER membrane, where the unfolded toxin is released from PDI by the action of Ero1. Taken together, our results identify Ero1 as the enzyme mediating the release of unfolded CT from PDI and characterize an additional step in retrotranslocation of the toxin.
Hands-on interaction with virtual environments (1989)

In this paper we describe the evolution of a whole-hand interface to our virtual-environment graphical system. We present a set of abstractions that can be used to implement device-independent interfaces for hand measurement devices. Some of these abstractions correspond to known logical device abstractions, while others take further advantage of the richness of expression in the human hand. We describe these abstractions in the context of their use in our development of virtual environments.
Increased ERK and JNK activation and decreased ERK/JNK ratio are associated with long-term organ damage in patients with systemic lupus erythematosus (2014)

These results demonstrate that early activation of ERK and JNK along with decreased overall ERK expression and reduced ERK/JNK ratio may predict the severity of long-term organ damage in SLE patients.
Cancer services in England: challenges and opportunities (2003)

Following on from last month’s description of cancer services in Scotland, Isabel White outlines the systems in place in England which underpin cancer care