gebhart/patrepeval huggingface dataset:
Challenges in T cell receptor gene therapy (2012)

The function of T lymphocytes as orchestrators and effectors of the adaptive immune response is directed by the specificity of their T cell receptors (TCRs). By transferring into T cells the genes encoding antigen-specific receptors, the functional activity of large populations of T cells can be redirected against defined targets including virally infected or cancer cells. The potential of therapeutic T cells to traffic to sites of disease, to expand and to persist after a single treatment remains a major advantage over the currently available immunotherapies that use monoclonal antibodies. Here we review recent progress in the field of TCR gene therapy, outlining challenges to its successful implementation and the strategies being used to overcome them. We detail strategies used in the optimization of affinity and surface expression of the introduced TCR, the choice of T cell subpopulations for gene transfer, and the promotion of persistence of gene-modified T cells in vivo. We review the safety concerns surrounding the use of gene-modified T cells in patients, discussing emerging solutions to these problems, and describe the increasingly positive results from the use of gene-modified T cells in recent clinical trials of adoptive cellular immunotherapy. The increasing sophistication of measures to ensure the safety of engineered T cells is accompanied by an increasing number of clinical trials: these will be essential to guide the effective translation of cellular immunotherapy from the laboratory to the bedside.
Metabolism and excretion in bile of SC4453, a new semi-synthetic derivative of digoxin following an i.v. bolus injection in the guinea-pig. (1984)

After a single bolus injection of tritiated SC4453 in the guinea-pig, 36% of the dose was excreted in the bile during the first 6 hours after administration. Solvent partition has shown that 88% of the total radioactivity excreted was soluble in dichloromethane (DCM). Thin layer chromatography analysis of the DCM soluble fraction has shown that SC4453 was mainly excreted unchanged in the bile. Enzymatic hydrolysis of the water soluble fraction has shown that the main partner of conjugation was SC4453 itself. This study has demonstrated a significant enterohepatic circulation for SC4453, suppression of which modified the pharmacokinetic parameters of SC4453 in the guinea-pig. The half-life of elimination decreases from 4.2 hours to 3.22 hours and the volume of distribution (Vdarea) was equal to 2680 ml/kg versus 3692 ml/kg for normal guinea-pig.
Strategy for Increasing Drug Solubility and Efficacy through Covalent Attachment to Polyvalent DNA–Nanoparticle Conjugates (2011)

Paclitaxel, a potent chemotherapeutic utilized in a variety of cancers, can be limited in its effectiveness due to inherent insolubility in aqueous media and acquired chemoresistance within certain cells. An approach has been developed for increasing Paclitaxel solubility and effectiveness by covalent attachment to gold nanoparticles via DNA linkers. The resulting conjugates are highly soluble in aqueous buffer, exhibiting greater than a 50-fold increase in solubility over the unconjugated drug. DNA linkers are labeled with a fluorophore, which affords a convenient means of visualizing resultant conjugates within cells. Internalized conjugates demonstrate increased activity as compared with free drug across a variety of cell types, including a Paclitaxel-resistant cell line. Attachment to DNA-nanoparticle conjugates may become a general strategy for solubilizing and enhancing a wide variety of therapeutic agents in aqueous media.
Prostate-specific antigen in the early detection of prostate cancer (2007)

Throughout Canada, the United States and much of Europe, prostate-specific antigen (PSA) screening for prostate cancer has proliferated over the past 2 decades, leading to dramatic increases in detection rates of prostate cancer. Although it has unquestionably led to increased detection of cancer and a migration to lower-stage and -volume tumours, it is still unknown whether PSA screening significantly reduces mortality from prostate cancer. Often thought to be dichotomous (i.e., either normal or elevated), PSA measurements actually reflect cancer risk, with the risks of cancer and of aggressive cancer increasing with the level of PSA. The recently developed risk calculator from the Prostate Cancer Prevention Trial, which integrates family history of prostate cancer, digital rectal examination findings, PSA test result, age, ethnicity, and history of a prior prostate biopsy with a negative result, allows clinicians to assess a patient's individual risk of cancer. This risk should be examined in the context of a patient's life expectancy and comorbidity as well as his concern about the possibility of prostate cancer. The terms "normal" and "elevated" as descriptors of PSA results should be abandoned.
A dual-port 65ns 64K × 4 DRAM with a 50MHz serial output (1986)

A DRAM featuring 256×4 serial output at 50MHz and row / column redundancy will be described. Using a cell-plate driver the entire matrix amy be written in 256 flash-write cycles.
Water- and Excreta-Related Diseases: Unitary Environmental Classification (1999)

A unitary environmental classification of water- and excreta-related communicable diseases is presented, which comprises seven categories: Feco-oral waterborne and water-washed diseases; non-feco-oral water-washed (skin and eye) diseases; geohelminthiases; taeniases; water-based diseases (bacterial and fungal, as well as helminthic); insect-vector diseases; and rodent-vector diseases. The global burden of some of these diseases in 1990 is reviewed. Water- and excreta-related diseases were responsible for 2,700,000 deaths in that year (5.3% of all deaths) and for the loss of 93,200,000 disability-adjusted life years (6.8% of all DALYs). Almost all these deaths and loss of DALYs occurred in developing countries (99.9 and 99.8%, respectively).
Analysis of type 5 adenovirus transformation with a cloned rat embryo cell line (CREF). (1982)

A recently isolated cloned cell line of Fischer rat embryo fibroblasts (CREF) can be transformed at high frequency by adenovirus serotype 5 (Ad5). The CREF cells display a near diploid karyotype, do not crisscross at confluency, can be maintained at confluency for greater than 7 wk at 36 degrees C, and do not form macroscopic colonies when seeded in agar. Transformed cells are identified by their altered morphology and the presence of adenovirus DNA sequences in the transformants, which can be demonstrated by lysing cells directly on nitrocellulose filters and hybridizing with 32P-labeled Ad5 DNA (spot hybridization). The frequency of transformation at 36 degrees C is approximately equal to 2 x 10(-4) with wild-type Ad5 and approximately equal to 2 x 10(-3) with the temperature-sensitive mutant H5ts125. Southern blot hybridization analysis indicates that five out of six wild-type Ad5- and six out of six H5ts125-transformed CREF clones isolated at 36 degrees C contain the complete integrated Ad5 genome. Preliminary characterization of four transformed clones (two wild-type and two H5ts125) indicates that, even though transformation was done in CREF cells (a clonal cell line), they differ in their biological properties, such as saturation density and anchorage dependence.
Vandermonde frequency division multiplexing for cognitive radio (2008)

We consider a cognitive radio scenario where a primary and a secondary user wish to communicate with their corresponding receivers simultaneously over frequency selective channels. Under realistic assumptions that the primary user is ignorant of the secondary userpsilas presence and that the secondary transmitter has no side information about the primarypsilas message, we propose a Vandermonde precoder that cancels the interference from the secondary user by exploiting the redundancy of the cyclic prefix and the frequency selectivity of the channel. Our numerical examples show that VFDM, with an appropriate design of the input covariance, enables the secondary user to achieve a non-negligible rate while generating zero interference to the primary user.
TCR-like Biomolecules Target Peptide/MHC Class I Complexes on the Surface of Infected and Cancerous Cells (2011)

The human leukocyte antigen (HLA; also called major histocompatibility, or MHC) class I system presents peptides that distinguish healthy from diseased cells. Therefore, the discovery of peptide/MHC class I markers can provide highly specific targets for immunotherapy. Over the course of almost two decades, various strategies have been used, with mixed success, to produce antibodies that have recognition specificity for unique peptide/MHC class I complexes that mark infected and cancerous cells. Using these antibody reagents, novel peptide/MHC class I targets have been directly validated on diseased cells and new insight has been gained into the mechanisms of antigen presentation. More recently, these antibodies have shown promise for clinical applications such as therapeutic targeting of cancerous and infected cells and diagnosis and imaging of diseased cells. In this review, the authors comprehensively describe the methods used to identify disease-specific peptide/MHC class I epitopes and generate antibodies to these markers. Finally, they offer several examples that illustrate the promise of using these antibodies as anti-cancer agents.
Magnesium and potassium deprivation and supplementation in animals and man: aspects in view of intestinal absorption. (1984)

States of K and Mg deficiency, deprivation or depletion, are difficult to detect by determining serum concentrations, since both cations are concentrated intracellularly. The intestinal absorption of K is rather quick and complete; the uptake of Mg probably comprises two mechanisms and proceeds continuously, although incomplete. The resulting different pharmakokinetic behavior must be kept in mind when K and Mg are supplemented by the oral route. Favorable effects of oral K and Mg supplementation are reviewed, and the fact is stressed that the body cannot retain K, unless the Mg status is adequate. Therefore, K should be supplemented together with Mg. Drugs like amiloride not only spare K, but at the same time prevent renal losses of other important electrolytes, especially of chloride and Mg.
The Harvest Smart PRePTM system versus the Friadent‐Schütze platelet‐rich plasma kit (2003)

An important reason to improve methods for isolating platelet-rich plasma (PRP) is the potential use of autogenous platelet growth factors. In addition to the Curasan PRP kit (Curasan, Kleinostheim, Germany) and the platelet concentrated collection system (PCCSTM) system, two new methods for the preparation of PRP by the surgeon are now available. This study compared the suitability of these new methods for the preparation of PRP. Whole blood was drawn from 54 healthy donors (33 men and 21 women) aged 23-79 years (38.0 +/- 17.7 years). PRP was prepared from each donor's blood using both the Smart PRePTM system (Harvest Technologies Corporation, Munich, Germany) and the Friadent-Schütze method (PRP kit; Friadent-Schütze, Vienna, Austria). The platelet count in donor whole blood was 276 810 +/- 59 440 /microl. Platelet counts differed significantly between the Smart PRP preparation (1227 890 +/- 312 440 platelets/microl) and the Friadent-Schütze PRP preparation (1440 500 +/- 501 700 platelets/microl) (sign test, P < 0.001). The Smart PRePTM system had a significantly higher collection efficiency (63.4 +/- 7.9%) than the Friadent-Schütze kit (49.6 +/- 13.6%) (sign test, P < 0.001). The leukocyte contents in the two platelet concentrates were similar (Smart PRePTM, 19 261 +/- 8082 platelets/microl; Friadent-Schütze, 21 691 +/- 16 430). Transforming growth factor (TGF)-beta1 and platelet-derived growth factor (PDGF)-AB were higher in the Friadent-Schütze PRP (TGF-beta1, 196.8 +/- 109.6 ng/ml; PDGF-AB, 251.6 +/- 115.4 ng/ml) than in the Smart PRePTM (TGF-beta1, 77.2 +/- 54.8 ng/ml; PDGF-AB, 208 +/- 85.2 ng/ml). The sign test indicated significant differences between the two methods in the concentrations of TGF-beta1 (P < 0.001) and PDGF-AB (P < 0.01). Insulin-like growth factor (IGF)-1 levels in the two PRP preparations were similar (Friadent-Schütze PRP, 72.8 +/- 22.3 ng/ml; Smart PRePTM, 91.4 +/- 21.3 ng/ml). The Smart PRePTM system was superior with respect to ease of handling and preparation time. It also had a significantly higher platelet collection efficiency than the Friadent-Schütze PRePTM kit. The Friadent-Schütze PRP kit offers a slight advantage in the resulting PRP platelet concentration. However, this is easily compensated for in the Smart PRePTM system by reducing the volume of the resulting PRP.
Parameterized object sensitivity for points-to analysis for Java (2005)

The goal of points-to analysis for Java is to determine the set of objects pointed to by a reference variable or a reference object field. We present object sensitivity , a new form of context sensitivity for flow-insensitive points-to analysis for Java. The key idea of our approach is to analyze a method separately for each of the object names that represent run-time objects on which this method may be invoked. To ensure flexibility and practicality, we propose a parameterization framework that allows analysis designers to control the tradeoffs between cost and precision in the object-sensitive analysis. Side-effect analysis determines the memory locations that may be modified by the execution of a program statement. Def-use analysis identifies pairs of statements that set the value of a memory location and subsequently use that value. The information computed by such analyses has a wide variety of uses in compilers and software tools. This work proposes new versions of these analyses that are based on object-sensitive points-to analysis.We have implemented two instantiations of our parameterized object-sensitive points-to analysis. On a set of 23 Java programs, our experiments show that these analyses have comparable cost to a context-insensitive points-to analysis for Java which is based on Andersen's analysis for C. Our results also show that object sensitivity significantly improves the precision of side-effect analysis and call graph construction, compared to (1) context-insensitive analysis, and (2) context-sensitive points-to analysis that models context using the invoking call site. These experiments demonstrate that object-sensitive analyses can achieve substantial precision improvement, while at the same time remaining efficient and practical.
The Thermal Conductivity of Silica Aerogel in the Phonon, the Fracton and the Particle-Mode Regime (1991)

Thermal conductivity data for a homologous series of base-catalyzed silica aerogels confirm that the different length scale regions in the aerogel structure are reflected in the dynamic behaviour, and we determine the contributions from long-wavelength phonons, fractons and particle modes, respectively. In the fracton regime a linear temperature dependence of the thermal conductivity is found as predicted theoretically. Further we observe that the thermal conductivity is proportional to the specific heat in the regime where the thermal properties are dominated by particle modes. From the proportionality constant we deduce a measure of the network connectivity.
Local Targeting of Malignant Gliomas by the Diffusible Peptidic Vector 1,4,7,10-Tetraazacyclododecane-1-Glutaric Acid-4,7,10-Triacetic Acid-Substance P (2006)

Targeted radiotherapy using diffusible peptidic vectors represents an innovative strategy for local control of malignant gliomas, which will be further assessed as a neoadjuvant approach.
Optimizing digital speech coders by exploiting masking properties of the human ear (1979)

In any speech coding system that adds noise to the speech signal, the primary goal should not be to reduce the noise power as much as possible, but to make the noise inaudible or to minimize its subjective loudness. ’’Hiding’’ the noise under the signal spectrum is feasible because of human auditory masking: sounds whose spectrum falls near the masking threshold of another sound are either completely masked by the other sound or reduced in loudness. In speech coding applications, the ’’other sound’’ is, of course, the speech signal itself. In this paper we report new results of masking and loudness reduction of noise and describe the design principles of speech coding systems exploiting auditory masking.
E-mail bombs and countermeasures: cyber attacks on availability and brand integrity (1998)

The simplicity of SMTP mail can be combined with the robustness of the sendmail MTA program and misused in numerous ways to create extraordinary and powerful e-mail bombs. These e-mail bombs can be launched in many different attack scenarios which can easily flood and shut down chains of SMTP mail servers. Sendmail-based SMTP mail relays also can be used covertly to distribute messages and files that could be very damaging to the integrity and brands of victims. This article discusses mail-bombing techniques, automated attack tools, and countermeasures. Also discussed is an actual Internet-based attack that was launched in 1997 on the Langley AFB SMTP e-mail infrastructure. The authors also present an analysis of the cyber attack, graphs illustrating the attack volume, and a statistical e-mail bomb early warning system.
Brain nitric oxide synthase is a biopterin‐ and flavin‐containing multi‐functional oxido‐reductase (1991)

Brain nitric oxide synthase is a Ca2+/calmodulin-regulated enzyme which converts L-arginine into NO. Enzymatic activity of this enzyme essentially depends on NADPH and is stimulated by tetrahydrobiopterin (H4biopterin). We found that purified NO synthase contains enzyme-bound H4biopterin, explaining the enzymatic activity observed in the absence of added cofactor. Together with the finding that H4biopterin was effective at substoichiometrical concentrations, these results indicate that NO synthase essentially depends on H4biopterin as a cofactor which is recycled during enzymatic NO formation. We found that the purified enzyme also contains FAD, FMN and non-heme iron in equimolar amounts and exhibits striking activities, including a Ca2+/calmodulin-dependent NADPH oxidase activity, leading to the formation of hydrogen peroxide at suboptimal concentrations of L-arginine or H4biopterin.
Bifidobacterium animalis (Mitsuoka) comb. nov. and the "minimum" and "subtile" Groups of New Bifidobacteria Found in Sewage (1974)

Twenty-two strains of bifidobacteria from the feces of chickens, rats, and rabbits, and from sewage, formed a single deoxyribonucleic acid (DNA) homology group displaying complete homology with Bifidobacterium longum subsp. animalis Mitsuoka biotype a strain R 101-8 (=ATCC 25527). The DNA relatedness of this group of strains to the known species of the genus Bifidobacterium ranged from 5 to 40%. Therefore, we propose that B. longum Reuter subsp. animalis Mitsuoka biotype a should be elevated to species rank as Bifidobacterium animalis (Mitsuoka) comb. nov. The type strain is ATCC 25527. Also, a small number of strains isolated from sewage are suggested as probably being distinctive bifidobacteria and are placed in two new groups designated “ minimum” and “subtile” The reference strains for these groups are F392 (=ATCC 27538) and F395 (=ATCC 27537), respectively.
Crystallographic analysis of human hemoglobin elucidates the structural basis of the potent and dual antisickling activity of pyridyl derivatives of vanillin (2011)

Vanillin has previously been studied clinically as an antisickling agent to treat sickle-cell disease. In vitro investigations with pyridyl derivatives of vanillin, including INN-312 and INN-298, showed as much as a 90-fold increase in antisickling activity compared with vanillin. The compounds preferentially bind to and modify sickle hemoglobin (Hb S) to increase the affinity of Hb for oxygen. INN-312 also led to a considerable increase in the solubility of deoxygenated Hb S under completely deoxygenated conditions. Crystallographic studies of normal human Hb with INN-312 and INN-298 showed that the compounds form Schiff-base adducts with the N-terminus of the α-subunits to constrain the liganded (or relaxed-state) Hb conformation relative to the unliganded (or tense-state) Hb conformation. Interestingly, while INN-298 binds and directs its meta-positioned pyridine-methoxy moiety (relative to the aldehyde moiety) further down the central water cavity of the protein, that of INN-312, which is ortho to the aldehyde, extends towards the surface of the protein. These studies suggest that these compounds may act to prevent sickling of SS cells by increasing the fraction of the soluble high-affinity Hb S and/or by stereospecific inhibition of deoxygenated Hb S polymerization.
Towards estimation error guarantees for distinct values (2000)

We consider the problem of estimating the number of distinct values in a column of a table. For large tables without an index on the column, random sampling appears to be the only scalable approach for estimating the number of distinct values. We establish a powerful negative result stating that no estimator can guarantee small error across all input distributions, unless it examines a large fraction of the input data. In fact, any estimator must incur a significant error on at least some of a natural class of distributions. We then provide a new estimator which is provably optimal, in that its error is guaranteed to essentially match our negative result. A drawback of this estimator is that while its worst-case error is reasonable, it does not necessarily give the best possible error bound on any given distribution. Therefore, we develop heuristic estimators that are optimized for a class of typical input distributions. While these estimators lack strong guarantees on distribution-independent worst-case error, our extensive empirical comparison indicate their effectiveness both on real data sets and on synthetic data sets.
MDM2 interacts with MDMX through their RING finger domains (1999)

The N-terminus of MDM2 proto-oncoprotein interacts with p53 and down modulates p53 activity by inhibiting transcriptional activity and promoting p53 degradation. MDMX is structurally related to MDM2 and also binds to p53. However, the function of MDMX has not been clarified yet. We found that MDM2 hetero-oligomerized with MDMX through their C-terminal RING finger domains. Yeast two-hybrid analysis revealed that the hetero-oligomerization between MDMX and MDM2 was more stable than the homo-oligomerization of each protein. MDM2 has been shown to be degraded by the ubiquitin-proteasome pathway, while MDMX was a stable protein. Interaction of MDMX with MDM2 through the C-terminal RING finger domains resulted in inhibiting degradation of MDM2. These data indicate that MDMX functions as a regulator of MDM2.