gebhart/patrepeval huggingface dataset:
X-Linked Inhibitor of Apoptosis Protein (XIAP) Is a Nonredundant Modulator of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)- Mediated Apoptosis in Human Cancer Cells (2004)

Although the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to play an important role in the immunosurveillance of neoplasia, apoptotic factors that modulate the sensitivity of cancer cells to TRAIL are poorly understood. The inhibitor of apoptosis proteins (IAPs) have generated considerable interest as potential targets for cancer therapy, but the lack of a phenotype in X-linked IAP (XIAP) knockout mice has generated speculation that IAP function may be redundant. Using gene targeting technology, we show that disruption of the gene encoding XIAP in human cancer cells did not interfere with basal proliferation, but caused a remarkable sensitivity to TRAIL. These results demonstrate that XIAP is a nonredundant modulator of TRAIL-mediated apoptosis and provide a rationale for XIAP as a therapeutic target.
Successes and Failures in Achieving the Goals of the World Food Summit (2002)

At the World Food Summit (WFS) in Rome in 1996, heads of state representing 186 countries affirmed their "common and national commitment to achieving food security for all" and agreed to work toward achieving the intermediate goal of "reducing the number of undernourished people to half their present number no later than 2015." That would mean reducing the number of undernourished people from 800 million to 400 million by 2015. But recognizing the multifaceted nature of this commitment, the WFS plan of action also contains seven commitments, which, in a broad action area, are relevant for reducing the number of undernourished and eventually achieving food security for all. The seven related commitments that accompany the goal of halving the number of undernourished are often forgotten. This paper will recall the seven commitments but mainly focus on the extent to which the hunger target has been achieved, what factors might explain the successes and failures, and what lessons may be drawn from these experiences.
How much can behavioral targeting help online advertising? (2009)

Behavioral Targeting (BT) is a technique used by online advertisers to increase the effectiveness of their campaigns, and is playing an increasingly important role in the online advertising market. However, it is underexplored in academia when looking at how much BT can truly help online advertising in commercial search engines. To answer this question, in this paper we provide an empirical study on the click-through log of advertisements collected from a commercial search engine. From the comprehensively experiment results on the sponsored search log of the commercial search engine over a period of seven days, we can draw three important conclusions: (1) Users who clicked the same ad will truly have similar behaviors on the Web; (2) Click-Through Rate (CTR) of an ad can be averagely improved as high as 670% by properly segmenting users for behavioral targeted advertising in a sponsored search; (3) Using the short term user behaviors to represent users is more effective than using the long term user behaviors for BT. The statistical t-test verifies that all conclusions drawn in the paper are statistically significant. To the best of our knowledge, this work is the first empirical study for BT on the click-through log of real world ads.
Intrapulmonary Pharmacokinetics and Pharmacodynamics of Itraconazole and 14-Hydroxyitraconazole at Steady State (2004)

We determined the steady-state intrapulmonary pharmacokinetic and pharmacodynamic parameters of orally administered itraconazole (ITRA), 200 mg every 12 h (twice a day [b.i.d.]), on an empty stomach, for a total of 10 doses, in 26 healthy volunteers. Five subgroups each underwent standardized bronchoscopy and bronchoalveolar lavage (BAL) at 4, 8, 12, 16, and 24 h after administration of the last dose. ITRA and its main metabolite, 14-hydroxyitraconazole (OH-IT), were measured in plasma, BAL fluid, and alveolar cells (AC) using high-pressure liquid chromatography. Half-life and area under the concentration-time curves (AUC) in plasma, epithelial lining fluid (ELF), and AC were derived using noncompartmental analysis. ITRA and OH-IT maximum concentrations of drug (C(max)) (mean +/- standard deviation) in plasma, ELF, and AC were 2.1 +/- 0.8 and 3.3 +/- 1.0, 0.5 +/- 0.7 and 1.0 +/- 0.9, and 5.5 +/- 2.9 and 6.6 +/- 3.1 microg/ml, respectively. The ITRA and OH-IT AUC for plasma, ELF, and AC were 34.4 and 60.2, 7.4 and 18.9, and 101 and 134 microg. hr/ml. The ratio of the C(max) and the MIC at which 90% of the isolates were inhibited (MIC(90)), the AUC/MIC(90) ratio, and the percent dosing interval above MIC(90) for ITRA and OH-IT concentrations in AC were 1.1 and 3.2, 51 and 67, and 100 and 100%, respectively. Plasma, ELF, and AC concentrations of ITRA and OH-IT declined monoexponentially with half-lives of 23.1 and 37.2, 33.2 and 48.3, and 15.7 and 45.6 h, respectively. An oral dosing regimen of ITRA at 200 mg b.i.d. results in concentrations of ITRA and OH-ITRA in AC that are significantly greater than those in plasma or ELF and intrapulmonary pharmacodynamics that are favorable for the treatment of fungal respiratory infection.
Regulation of Escherichia coli fumarate reductase (frdABCD) operon expression by respiratory electron acceptors and the fnr gene product (1987)

The fumarate reductase enzyme complex, encoded by the frdABCD operon, allows Escherichia coli to utilize fumarate as a terminal electron acceptor for anaerobic oxidative phosphorylation. To analyze the expression of fumarate reductase, protein and operon fusions were constructed between the frdA and the lacZ genes and introduced onto the E. coli chromosome at the lambda attachment site. Expression of beta-galactosidase from either fusion was increased 10-fold during anaerobic versus aerobic cell growth, increased an additional 1.5-fold by the presence of fumarate, the substrate, and decreased 23-fold by nitrate, a preferred electron acceptor. The addition of trimethylamine-N-oxide as an electron acceptor did not significantly alter frdA'-'lacZ expression. Control of frd operon expression is therefore exerted at the transcriptional level in response to the availability of the electron acceptors oxygen, fumarate, and nitrate. Anaerobic induction of frdA'-'lacZ expression was impaired in an fnr mutant and was restored when the fnr+ gene was provided in trans, thus establishing that the fnr gene product, Fnr, is responsible for the anaerobic activation of frd operon expression. Nitrate repression of frdA'-'lacZ expression was observed under either aerobic or anaerobic cell growth conditions in both wild-type and fnr mutant strains, demonstrating that the mechanism for nitrate repression is independent of nitrate respiration and oxygen control imparted by Fnr. Studies performed with a fnr'-'lacZ protein fusion confirmed that the fnr gene is expressed both aerobically and anaerobically. A model is proposed for the regulation of frdABCD operon expression in response to the availability of the alternate terminal electron acceptors oxygen, nitrate, and fumarate.
A multimarker model to predict outcome in tamoxifen-treated breast cancer patients. (2006)

Our data show the predictive value of BCL2, ERBB2, MYC, and TP53 in addition to the standard hormone receptors and clinicopathologic features, and they show the importance of conditional interpretation of certain molecular markers. Our multimarker predictive model performed significantly better than standard guidelines.
Bone induction in implants of decalcified bone and dentine. (1975)

The fate of decalcified bone and dentine implanted in muscle and beneath the kidney capsule has been studied in young rats. Quantitatively speaking there was a great deal of variation, but in general the implants became surrounded and invaded by young vascular connective tissue; then tunnels were eroded and cavities enlarged by multi-nucleated giant cells; then the matrix around erosion chambers became recalcified; and finally new bone was induced on the eroded recalcified surfaces. Erosion was much more extensive, and bone was much more readily induced in the intramuscular than in the subcapsular implants. It is concluded that the presence of an eroded, recalcified surface is a pre-requisite for bone induction under these conditions.
Coding for maximum likelihood detection on a magnetic recording channel (1990)

In the construction of modulation codes, a natural selection process occurs which chooses from a set of sequences which satisfy an underlying system constraint to produce a practical code. A method of selection which increases detectability on a magnetic recording channel using maximum likelihood sequence estimation is analyzed. It is shown that significant coding gains are achievable through the judicious selection of code sequences. In other cases, despite moderate costs in terms of decreased code rate, system reliability is improved.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Nanooncology: The future of cancer diagnosis and therapy (2013)

In recent years, there has been an unprecedented expansion in the field of nanomedicine with the development of new nanoparticles for the diagnosis and treatment of cancer. Nanoparticles have unique biological properties given their small size and large surface area-to-volume ratio, which allows them to bind, absorb, and carry compounds such as small molecule drugs, DNA, RNA, proteins, and probes with high efficiency. Their tunable size, shape, and surface characteristics also enable them to have high stability, high carrier capacity, the ability to incorporate both hydrophilic and hydrophobic substances and compatibility with different administration routes, thereby making them highly attractive in many aspects of oncology. This review article will discuss how nanoparticles are able to function as carriers for chemotherapeutic drugs to increase their therapeutic index; how they can function as therapeutic agents in photodynamic, gene, and thermal therapy; and how nanoparticles can be used as molecular imaging agents to detect and monitor cancer progression.
Skeletal Muscle Kallikrein: Potential Role in Metabolic Regulation (1996)

Skeletal muscle glucose metabolism appears to be regulated by locally derived factors as well as by systemically circulating hormones. Local factors may be particularly important during exercise, when substrate demand can increase rapidly. Numerous studies in perfused limbs suggest that the kallikrein-kinin system may participate in the regulation of substrate delivery and utilization by skeletal muscle. Evidence also suggests that kinins mediate the increase in insulin sensitivity after administration of converting enzyme inhibitors. Tissue kallikrein has been isolated and purified from rat skeletal muscles, and its level is highest in muscle with high oxidative activity. In other tissues, kallikrein synthesis is under the influence of insulin. It has not been possible to demonstrate effects of kallikrein or kinins on glucose metabolism in isolated skeletal muscle or cardiocytes. Therefore modulation of glucose metabolism by kallikrein or kinins may only be observed in intact perfused tissues or organs.
Bacterial Blight of Soybean: Regulation of a Pathogen Gene Determining Host Cultivar Specificity (1989)

Soybean cultivars resistant to Pseudomonas syringae pathovar glycinea (Psg), the causal agent of bacterial blight, exhibit a hypersensitive (necrosis) reaction (HR) to infection. Psg strains carrying the avrB gene elicit the HR in soybean cultivars carrying the resistance gene Rpg1. Psg expressing avrB at a high level and capable of eliciting the HR in the absence of de novo bacterial RNA synthesis have been obtained in in vitro culture. Nutritional signals and regions within the Psg hrp gene cluster, an approximately 20-kilobase genomic region also necessary for pathogenicity, control avrB transcription.
Isolation and culture of umbilical vein mesenchymal stem cells (2003)

Bone marrow contains a population of stem cells that can support hematopoiesis and can differentiate into different cell lines including adipocytes, osteocytes, chondrocytes, myocytes, astrocytes, and tenocytes. These cells have been denoted mesenchymal stem cells. In the present study we isolated a cell population derived from the endothelium and subendothelium of the umbilical cord vein which possesses morphological, immunophenotypical and cell differentiation characteristics similar to those of mesenchymal stem cells isolated from bone marrow. The cells were isolated from three umbilical cords after treatment of the umbilical vein lumen with collagenase. The cell population isolated consisted of adherent cells with fibroblastoid morphology which, when properly stimulated, gave origin to adipocytes and osteocytes in culture. Immunophenotypically, this cell population was found to be positive for the CD29, CD13, CD44, CD49e, CD54, CD90 and HLA-class 1 markers and negative for CD45, CD14, glycophorin A, HLA-DR, CD51/61, CD106, and CD49d. The characteristics described are the same as those presented by bone marrow mesenchymal stem cells. Taken together, these findings indicate that the umbilical cord obtained from term deliveries is an important source of mesenchymal stem cells that could be used in cell therapy protocols.
Inhibition of porcine pepsin by two substrate analogs containing statine. The effect of histidine at the P2 subsite on the inhibition of aspartic proteinases (1988)

Two new inhibitors, 4 and 5, of the aspartic proteinase porcine pepsin were synthesized. These compounds, which span the P4-P'3 binding subsites of the enzyme, were derived by replacing the Nph-Phe dipeptidyl unit of a good pepsin substrate, H2N-Phe-Gly-His-Nph-Phe-Ala-Phe-OMe (3), with statine [(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, Sta]. Hexapeptide 5, H2N-Phe-Gly-Val-(S,S)-Sta-Ala-Phe-OMe, is an extremely potent inhibitor of pepsin with a Ki value less than 1 nM. This result is consistent with the proposal that statine functions as a bioisosteric replacement for a substrate dipeptidyl unit. Compound 4, which contains His at P2, is 2 orders of magnitude less active than the valine analogue 5 (Ki = 150 nM). The factor for the decrease in binding to pepsin effected by replacement of Val by His at P2 parallels the ratio of protonated vs unprotonated imidazole group in peptide 4 at pH 4, according to the Henderson-Hasselbach equation. This result suggests that a positively charged side chain at P2 is undesirable for maximum pepsin inhibition. Kinetic constants for several known inhibitors of pepsin and renin are presented that demonstrate that the effect of His incorporation at P2 on pepsin inhibition depends upon the peptide sequence and that the effect is considerably different for renin inhibitors. We further suggest that the high selectivity of potent renin inhibitors known to be only weak pepsin and cathepsin D inhibitors is due in part to the extent of histidine protonation at P2 arising from pH differences in the inhibition kinetics assay of renin (neutral conditions) compared to other aspartic proteinases (acid pH 2-4).
Primary vaginal malignant melanoma (2021)

This patient showed a good response to immunotherapy. With this treatment method, the prognosis is better for advanced-stage women, especially those who cannot endure the surgery. Local lesion resection and inguinal lymph node dissection combined with immunotherapy are recommended. The case reported here may help treat similar clinical cases.
Physicochemical, pharmacological and pharmacokinetic study of a new GABAergic compound, calcium acetylhomotaurinate. (1988)

It has been shown that calcium acetylhomotaurinate (Ca AOTA; Meram Patent, France) decreased voluntary ethanol intake in rats (1); this was antagonized by bicuculline. Homotaurine did not have this effect. We thought this was due to a different blood-brain barrier crossing ability for the two drugs. The present study was, therefore, planned to confirm blood-barrier crossing by Ca AOTA and to study the drug's physicochemical and pharmacokinetic characteristics. Both in vitro and in vivo (i.p.) administration of Ca AOTA increased the accumulation of [3H] GABA in rat striatal synaptosomal preparations. The chemical study confirmed Ca AOTA's great stability in biological and hydrophilic media, excluding a "homotaurine-dispensing" effect. The molecule was totally dissociated in such media, but the absence of any detectable acid form at any pH indicates that ion pairs are formed to cross barriers, and/or that a carrier system is used. The pharmacokinetic study showed short half-lives (5 and 30 min for the distribution and elimination phases) and small distribution volumes. However, the elimination phase distribution volume was dose-dependent, a further argument for a carrier transport system. From the present study it appears that Ca AOTA is an extremely stable drug, totally dissociated in hydrophilic media, which acts centrally as a GABA agonist after crossing the blood-brain barrier. It is not a precursor of homotaurine and presumably crosses barriers with the help of a transporter.
A batteryless 19&#x03BC;W MICS/ISM-band energy harvesting body area sensor node SoC (2012)

Recent advances in ultra-low power chip design techniques, many originally targeting wireless sensor networks, will enable a new generation of body-worn devices for health monitoring. We utilize the state-of-the-art in low power RF transmitters, low voltage boost circuits, subthreshold processing, biosignal front-ends, dynamic power management, and energy harvesting to realize an integrated reconfigurable wireless body-area-sensor node (BASN) SoC capable of autonomous power management for battery-free operation.
Construction and Immunological Characterization of a Novel Nontoxic Protective Pneumolysin Mutant for Use in Future Pneumococcal Vaccines (2005)

Pneumolysin, the pore-forming toxin produced by Streptococcus pneumoniae, may have an application as an immunogenic carrier protein in future pneumococcal conjugate vaccines. Most of the 90 S. pneumoniae serotypes identified produce pneumolysin; therefore, this protein may confer non-serotype-specific protection against pneumococcal infections such as pneumonia, meningitis, and otitis media. However, as pneumolysin is highly toxic, a nontoxic form of pneumolysin would be a more desirable starting point in terms of vaccine production. Previous pneumolysin mutants have reduced activity but retain residual toxicity. We have found a single amino acid deletion that blocks pore formation, resulting in a form of pneumolysin that is unable to form large oligomeric ring structures. This mutant is nontoxic at concentrations greater than 1,000 times that of the native toxin. We have demonstrated that this mutant is as immunogenic as native pneumolysin without the associated effects such as production of the inflammatory mediators interleukin-6 and cytokine-induced neutrophil chemoattractant KC, damage to lung integrity, and hypothermia in mice. Vaccination with this mutant protects mice from challenge with S. pneumoniae. Incorporation of this mutant pneumolysin into current pneumococcal vaccines may increase their efficacy.
Phase I Pharmacokinetic/Pharmacodynamic Study of EKB-569, an Irreversible Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Combination with Irinotecan, 5-Fluorouracil, and Leucovorin (FOLFIRI) in First-Line Treatment of Patients with Metastatic Colorectal Cancer (2008)

The RD of EKB-569 is 25 mg/day when combined with FOLFIRI and results in complete EGFR inhibition. Chemotherapy alone interferes with pharmacodynamic markers, an observation to be taken into account in future studies of targeted agents with chemotherapy.
A Complete Mapping of the Proteins in the Small Ribosomal Subunit of Escherichia coli (1987)

The relative positions of the centers of mass of the 21 proteins of the 30S ribosomal subunit from Escherichia coli have been determined by triangulation using neutron scattering data. The resulting map of the quaternary structure of the small ribosomal subunit is presented, and comparisons are made with structural data from other sources.
Reconstruction of 3D stacked‐up structures by rat small hepatocytes on microporous membranes (2005)

The three-dimensional (3D) culture of hepatocytes is essential for the reconstruction of functional hepatic tissues in vitro. In the present experiment, we developed a 3D-culture method in order to reconstruct hepatic cordlike structures by stacking up two-dimensional (2D) tissues composed of rat small hepatocytes (SHs), which are hepatic progenitor cells. Pairs of membranes were prepared and the cells were separately cultured on each membrane. After the SH colonies had developed, one membrane was inverted on top of the other to form an SH bilayer. Thereafter, we investigated whether the stacked cells were organized into differentiated tissues. In the 3D stacked-up structures, bile canaliculi (BC) started to form and gradually developed into anastomosing networks. Transmission electron microscopy revealed that the SHs of the upper and lower layers adhered to one another, and that BC formed between them. Bile canalicular proteins localized on the lumina of the tubular structures. Furthermore, the cells within the structures exhibited mRNA transcription of the hepatic-differentiation markers and maintained a relatively high level of albumin secretion. We conclude that highly differentiated 3D tissues, including functional BC, can be reconstructed by stacking up layers of SHs. This 3D stacked-up culture is useful for the reconstruction of tissue-engineered livers.
Monoclonal antibody analysis of a unique macrophage procoagulant activity induced by murine hepatitis virus strain 3 infection (1991)

A panel of 24 IgG2ak monoclonal antibodies was produced against murine hepatitis virus strain 3 (MHV-3)-induced procoagulant activity (PCA) from murine macrophages. The antibodies were specific and did not react in an enzyme-linked immunosorbent assay with purified MHV-3; lipopolysaccharide-induced PCA; crude mouse, human, or rabbit tissue factor, or unstimulated murine macrophages. Sixteen of 24 monoclonal antibodies inhibited functional PCA expression in a one-stage clotting assay. More detailed studies on one monoclonal antibody, 3D4.3, demonstrated that it inhibited prothrombin cleavage at concentrations of greater than or equal to 0.1 microgram/ml, and by Western blot this antibody reacted with proteins of a molecular mass of 140, 74, and 70 kDa on nonreduced gels and 74 and 70 kDa on reduced gels distinct from tissue factor known to have a molecular mass of 47 kDa. Induction of PCA was dependent on both host RNA and protein synthesis. Immunofluorescence studies showed specific binding to MHV-3-stimulated PCA-positive macrophage membranes. Both numbers of positive macrophages and intensity of staining correlated with multiplicity of infection. These monoclonal antibodies will be useful in isolation and characterization of the unique viral-induced PCA as well as in determining its biologic role in MHV infection and other diseases in which the prothrombinase has been implicated.
Practical blind demodulators for high-order QAM signals (1998)

This paper examines the problem of demodulating time dispersed digitally modulated signals with particular emphasis on two aspects: the all-digital implementation of such demodulators and the use of "blind" algorithms for initializing the demodulator in the absence of explicit training by the transmitter. The factors impacting the architecture of blind demodulators are discussed, followed by a description of several practical implementations.