gebhart/patrepeval huggingface dataset:
Immunoassay Standardization (1991)

Assays employed in the biological sciences fall into two categories, which may be respectively termed "comparative" (or "functionally-specific") and "analytical" (or "structurally-specific"). The former are intended to compare the relative effects of substances, or mixtures of substances--not necessarily of identical chemical structure--on a biological system (e.g. whole animal, tissue, cell, etc). Results are represented by units of effect (i.e. they are not units of "amount" of the substance(s) measured), and differ depending on the biological system used. Such assays cannot be "standardised" by the use of a calibrant. In contrast, analytical assays are intended to measure the number of molecules (or mass) of a single substance of unique chemical structure in a test sample, and cannot legitimately be employed to measure mixtures of substances of different structure. Results are represented by units of molecular number or mass, and should be identical for any test sample irrespective of the assay system used. Immunoassays generally fall into this category. Insofar as the antigenic substances present in standards or test samples are dissimilar and/or molecularly heterogeneous, an immunoassay is invalid, and the results it yields have no universal significance. Attempts to standardize "analytically-invalid" immunoassays inevitably fail. Many substances of biological interest (e.g. TSH)--initially defined in terms of their biological function--have subsequently been shown to be molecularly heterogenous. Problems thus arise in the standardization of immunoassays used for their measurement, reflecting the fact that the measurement of a mixture of substances of differing molecular structure (and function) is a meaningless concept. It is thus impossible to "measure TSH"; it is only possible to measure the effect TSH exerts in a particularly assay system. The only long-term solution to this problem is the development of assay systems measuring individual components of such heterogenous mixtures.
Use of bacteria as anticancer agents (2001)

Historically, bacteria were used as oncolytic agents for malignant brain tumours. Advances in bacteriology and molecular biology have widened the scope of bacterial approaches to cancer therapy and various possibilities include the use of bacteria as sensitising agents for chemotherapy, as delivery agents for anticancer drugs, and as vectors for gene therapy. Bacterial toxins can be used for tumour destruction and cancer vaccines can be based on immunotoxins of bacterial origin. The most promising approaches are the use of genetically modified bacteria for selective destruction of tumours, and bacterial gene-directed enzyme prodrug therapy. Knowledge gained from study of bacterial genomes forms an important basis of use of bacteria as anticancer agents. TAPET (Tumour Amplified Protein Expression Therapy) uses a genetically altered strain of Salmonella as a bacterial vector, or vehicle, for preferentially delivering anticancer drugs to solid tumours. Verotoxin 1 (VT1) of Escherichia coli has been used for ex vivo purging of human bone marrow of cancer cells before autologous bone marrow transplant. E. coli genes and enzymes have become part of well-known prodrug approaches to cancer in which inert prodrugs can be converted in vivo to highly active species. IL-4 fused with Pseudomonas exotoxin has been administered directly into malignant brain tumours and binds with high affinity to IL-4 receptors, which do not exist on normal brain cells, thus destroying a major part of the tumour without harming the normal brain tissue. It is in Phase I/II clinical trials in patients with glioblastoma. No ideal anticancer agent of bacterial origin that is applicable to all types of cancers has been discovered yet. The most promising approach to malignant brain tumours appears to be the use of genetically engineered bacteria that destroy the tumour selectively while sparing the normal brain tissue.
Water-soluble porphyrins as a dual-function molecular imaging platform for MRI and fluorescence zinc sensing (2007)

We report a molecular platform for dual-function fluorescence/MRI sensing of mobile zinc. Zinc-selective binding units were strategically attached to a water-soluble porphyrin template. The synthetic strategy for achieving the designed target ligand is flexible and convenient, and the key intermediates can be applied as general building blocks for the construction of other metal sensors based on a similar mechanism. The metal-free form, (DPA-C 2 ) 2 -TPPS 3 ( 1 ), where DPA is dipicolylamine and TPPS 3 is 5-phenyl-10,15,20-tris(4-sulfonatophenyl)porphine, is an excellent fluorescent sensor for zinc. It has certain superior physical properties compared with earlier-generation zinc sensors including emission in the red and near-IR regions [λ em = 645 nm (s) and 715 nm (m)], with a large Stokes shift of &gt;230 nm. The fluorescence intensity of 1 increases by &gt;10-fold upon zinc binding. The fluorescence “turn-on” is highly selective for zinc versus other divalent metal ions and is relatively pH-insensitive within the biologically relevant pH window. The manganese derivative, [(DPA-C 2 ) 2 -TPPS 3 Mn(III)] ( 2 ), switches the function of the molecule to generate an MRI contrast agent. In the presence of zinc, the relaxivity of 2 in aqueous solution is significantly altered, which makes it a promising zinc MRI sensor. Both metal-free and Mn(III)-inserted forms are efficiently taken up by live cells, and the intracellular zinc can be imaged by either fluorescence or MR, respectively. We anticipate that in vivo applications of the probes will facilitate a deeper understanding of the physiological roles of zinc and allow detection of abnormal zinc homeostasis for pathological diagnoses.
Death-induced changes to the nuclear matrix: the use of anti-nuclear matrix antibodies to study agents of apoptosis. (1993)

Using immunological techniques, we have shown for the first time that change in the nuclear matrix is an observable step in the cell death program. Immunometric assays detect soluble nuclear matrix proteins in the culture supernatants of cells killed by adriamycin, tumor necrosis factor and serum growth factor deprivation. Studies of cells killed by tumor necrosis factor and serum growth factor deprivation using dual immunofluorescent and 4'-6-diamidino-2-phenylindole (DAPI) staining detect many cells strongly positive for DNA that have little or no nuclear matrix protein. The staining pattern of cells killed by adriamycin is very different. There is good correspondence between the immunofluorescent and DAPI staining patterns indicating the presence of nuclear matrix proteins and DNA, although at a reduced ratio. It is concluded that the nuclear matrix changes are dependent on the agents that trigger cell death.
Activation of CB 2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: Pain inhibition by receptors not present in the CNS (2003)

We designed AM1241, a selective CB2 cannabinoid receptor agonist, and used it to test the hypothesis that CB2 receptor activation would reverse the sensory hypersensitivity observed in neuropathic pain states. AM1241 exhibits high affinity and selectivity for CB2 receptors. It also exhibits high potency in vivo. AM1241 dose-dependently reversed tactile and thermal hypersensitivity produced by ligation of the L5 and L6 spinal nerves in rats. These effects were selectively antagonized by a CB2 but not by a CB1 receptor antagonist, suggesting that they were produced by actions of AM1241 at CB2 receptors. AM1241 was also active in blocking spinal nerve ligation-induced tactile and thermal hypersensitivity in mice lacking CB1 receptors (CB1-/- mice), confirming that AM1241 reverses sensory hypersensitivity independent of actions at CB1 receptors. These findings demonstrate a mechanism leading to the inhibition of pain, one that targets receptors localized exclusively outside the CNS. Further, they suggest the potential use of CB2 receptor-selective agonists for treatment of human neuropathic pain, a condition currently without consistently effective therapies. CB2 receptor-selective agonist medications are predicted to be without the CNS side effects that limit the effectiveness of currently available medications.
Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals. (1994)

The frequency of the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been reported to be elevated in myocardial infarction and other patients. We therefore hypothesized that death rate of DD individuals should be increased in the population as a whole and this should be evident as a decrease in DD frequency with age. This hypothesis was tested in 118 Caucasian subjects who were already at high risk of cardiovascular events by having severe, early onset, familial hypertension (HT). A group of 196 age-, sex- and body mass index-matched normotensives (NTs) was used as a control. In the NT group II, ID, and DD genotype frequencies were similar for different age groups. DD frequency was 0.42 in NTs, but in HTs was 0.28, 0.26, and 0.10 for the age groups < 50, 50-59, and > or = 60 yr, respectively. Corresponding D allele frequencies were 0.52, 0.46, and 0.40 in the respective age groups of HTs, compared with 0.61 in NTs (by chi 2-analysis, P = 0.1, 0.047, and 0.0006, respectively). In HTs aged > or = 60, DD frequency was only 14% of expected. Plasma ACE activity tracked similarly with I/D genotype in HTs (P = 0.027; n = 35) as in NTs (P = 0.0001; n = 94) and Michaelis constant was identical for DD and II. Neither blood pressure, body mass index, nor sex bore any relationship with I/D genotype. In conclusion, in a group of severely HT patients not selected for cardiac pathology, there appeared to be a marked, selective decrease, in subgroups of increasing age, in frequency of the ACE DD genotype. One possibility suggested by this data might be that DD increases risk of premature death, at least in HTs who have two HT parents.
Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy. (1987)

Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p less than 0.0005) and with a relative lack of histologic honeycombing (p less than 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte contents did not correlate with the degree of clinical impairment (quantitated by a composite score based on dyspnea, radiographic abnormalities, and physiologic impairment) upon presentation. However, BALF eosinophil content correlated significantly with the severity of clinical impairment, higher eosinophil counts being associated with more severe initial clinical impairment (p less than 0.01). Neither pretreatment BALF neutrophil nor eosinophil content was related to the frequency or magnitude of subsequent clinical change in 20 patients evaluated before and after 1 yr of corticosteroid therapy. In contrast, pretreatment BALF lymphocytosis was associated with significant subsequent clinical improvement (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
Design and characterization of the anion‐sensitive coiled‐coil peptide (1997)

As a model for analyzing the role of charge repulsion in proteins and its shielding by the solvent, we designed a peptide of 27 amino acid residues that formed a homodimeric coiled-coil. The interface between the coils consisted of hydrophobic Leu and Val residues, and 10 Lys residues per monomer were incorporated into the positions exposed to solvent. During the preparation of a disulfide-linked dimer in which the two peptides were linked in parallel by the two disulfide bonds located at the N and C terminals, a cyclic monomer with an intramolecular disulfide bond was also obtained. On the basis of CD and 1H-NMR, the conformational stabilities of these isomers and several reference peptides were examined. Whereas all these peptides were unfolded in the absence of salt at pH 4.7 and 20 degrees C, the addition of NaClO4 cooperatively stabilized the alpha-helical conformation. The crosslinking of the peptides by disulfide bonds significantly decreased the midpoint salt concentration of the transition. The 1H-NMR spectra in the presence of NaClO4 suggested that, whereas the disulfide-bonded dimer assumed a native-like conformation, the cyclic monomer assumed a molten globule-like conformation with disordered side chains. However, the cyclic monomer exhibited cooperative transitions against temperature and Gdn-HCl that were only slightly less cooperative than those of the disulfide-bonded parallel dimer. These results indicate that the charge repulsion critically destabilizes the native-like state as well as the molten globule-like state, and that the solvent-dependent charge repulsion may be useful for controlling the conformation of designed peptides.
Design and Implementation of Probability-Based Scoring Function for Peptide Mass Fingerprinting Protein Identification (2006)

Protein identification through high-throughput mass spectrum data is an important domain in proteomics. Peptide Mass Fingerprinting (PMF) is one of the major methods for protein identification using the mass-spec technology. We developed a software package called "ProteinDecision" for PMF protein identification, together with a user-friendly graphical interface. "ProteinDecision" can handle the issues of selecting peaks from mass spectrum, transforming database format, displaying the top ranks of identification result, and detailed information for each ranking. We used a novel scoring function by considering the distribution of matching a mass-to-charge and peak intensity in a database based on the MOWSE table. Our new scoring function is assessed better than existing ones by comparing the computational results using experimental PMF data. A standalone version of "ProteinDecision" is freely available upon request.
Cofermentation of Glucose, Xylose, and Arabinose by Genomic DNA-lntegrated Xylose/Arabinose Fermenting Strain of Zymomonas mobilis AX101 (2002)

Cofermentation of glucose, xylose, and arabinose is critical for complete bioconversion of lignocellulosic biomass, such as agricultural residues and herbaceous energy crops, to ethanol. We have previously developed a plasmid-bearing strain of Zymomonas mobilis (206C[pZB301]) capable of cofermenting glucose, xylose, and arabinose to ethanol. To enhance its genetic stability, several genomic DNA-integrated strains of Z. mobilis have been developed through the insertion of all seven genes necessay for xylose and arabinose fermentation into the Zymomonas genome. From all the integrants developed, four were selected for further evaluation. The integrants were tested for stability by repeated transfer in a nonselective medium (containing only glucose). Based on the stability test, one of the integrants (AX101) was selected for further evaluation. A series of batch and continuous fermentations was designed to evaluate the cofermentation of glucose, xylose, and L-arabinose with the strain AX101. The pH range of study was 4.5, 5.0, and 5.5 at 30 degrees C. The cofermentation process yield was about 84%, which is about the same as that of plasmid-bearing strain 206C(pZB301). Although cofermentation of all three sugars was achieved, there was a preferential order of sugar utilization: glucose first, then xylose, and arabinose last.
Dynamic location area management and performance analysis (2002)

A dynamic location area scheme is proposed for cellular networks, in which the size of location areas of a user is dynamically determined according to its current incoming call arrival rate and mobility as the signaling traffic in radio channels reaches the minimum. The protocols and algorithms of the proposed scheme are presented, and its performance is compared with that of the conventional system.
Cholera toxin discriminates between T helper 1 and 2 cells in T cell receptor-mediated activation: role of cAMP in T cell proliferation. (1990)

CD4+ T helper (Th) clones can be divided into interleukin 2 (IL-2)-secreting Th1 and IL-4-secreting Th2 cells. We show in the present report that these two Th subsets have different activation requirements for lymphokine production and proliferation: namely, cholera toxin (CT) as well as forskolin inhibit T cell receptor (TCR)-mediated IL-2 production and proliferation in Th1 cells, while the same reagents fail to block IL-4 production and proliferation in Th2 cells. In addition, CT and forskolin differentially influence the proto-oncogene mRNA expression in Th1 vs. Th2 cells after stimulation with Con A. Since both reagents lead to elevated levels of intracellular cAMP, it is likely that Th1 and Th2 cells differ in their sensitivity to an increase in cAMP. Our results indicate that the two Th subsets use different transmission signal pathways upon TCR-mediated activation.
Effect of soft‐segment chemistry on polyurethane biostability during in vitro fatigue loading (2004)

The effect of soft-segment chemistry on biostability of polyurethane elastomers was studied with a diaphragm-type film specimen under conditions of static and dynamic loading. During testing, the films were exposed to an H(2)O(2)/CoCl(2) solution, which simulated the oxidative component of the in vivo environment. Films treated for up to 24 days were evaluated by IR spectroscopy and by optical and scanning electron microscopy. Biostability of a poly(ether urethane) (PEU), which is known to undergo oxidative degradation, was compared with biostability of a poly(carbonate urethane) (PCU), which is thought to be more resistant to oxidation than PEU. Materials similar to PEU and PCU, in which the polyether or polycarbonate soft segment was partially replaced with poly(dimethylsiloxane) (PDMS), were also tested with the expectation that PDMS would improve soft-segment biostability. Oxidative degradation of the polyether soft segment of PEU was manifest chemically as chain scission and cross-linking and physically as surface pitting. Biaxial fatigue accelerated chemical degradation of PEU and eventually caused brittle stress cracking. In comparison, the polycarbonate soft segment was more stable to oxidation; there was minimal chemical or physical degradation of PCU, even in biaxial fatigue. Partial substitution of the polyether soft segment with PDMS enhanced oxidative stability of PEU. Although both strategies for modifying soft-segment chemistry improved the resistance to oxidative degradation, the outstanding mechanical properties of PEU were compromised to some extent.
WebStickers (2000)

In the WebStickers system, where barcode stickers may be attached to physical objects making them act as bookmarks to the worldwide web in a convenient way to the user. Using readily available technology, i.e., standard barcode readers and adhesive stickers, WebStickers enable users to take advantage of their physical environment when organizing and sharing bookmarks. Starting from a user-centered rather than technology-driven point of view, we discuss how the affordances of physical tokens, as well as the context they are placed in, can act as useful cues for users. Since many objects already have barcodes printed on them, they can be used with the WebStickers system without physical modification. In addition, WebStickers meets proposed design criteria for information workspaces.
An Efficient Random Jitter Measurement Technique Using Fast Comparator Sampling (2005)

This paper describes a random jitter measurement technique using simple algorithms and comparator sampling. The approach facilitates using automated test equipment (ATE) to validate devices with multiple, high-speed serial interfaces. The approach combines partial measurements based on individual data edge regions, in contrast to more common approaches that effectively first accumulate data from multiple edge regions. Random jitter is measured accurately even in the presence of deterministic and low-frequency periodic jitter, up to a cutoff frequency.
Short Channel Characteristics of Gallium–Indium–Zinc–Oxide Thin Film Transistors for Three-Dimensional Stacking Memory (2008)

Amorphous gallium-indium-zinc-oxide (GIZO) thin film transistors with short channels of 50 nm were successfully fabricated by e-beam lithographic patterning. The GIZO thin film transistors showed a high mobility of 8.2 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> /Vldrs with on-to-off current ratios up to 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> . Excellent short channel characteristics were also obtained with a small shift of the threshold voltages and no degradation of subthreshold slopes as V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DS</sub> increased, even with short channel lengths of less than 100 nm. These promising results indicate that the GIZO thin film transistors could be a candidate for selection transistors in 3-D cross point stacking memory.
Highly Efficient Iridium‐Catalyzed Oxidation of Organosilanes to Silanols. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Validating the genomic signature of pediatric septic shock (2008)

We previously generated genome-wide expression data (microarray) from children with septic shock having the potential to lead the field into novel areas of investigation. Herein we seek to validate our data through a bioinformatic approach centered on a validation patient cohort. Forty-two children with a clinical diagnosis of septic shock and 15 normal controls served as the training data set, while 30 separate children with septic shock and 14 separate normal controls served as the test data set. Class prediction modeling using the training data set and the previously reported genome-wide expression signature of pediatric septic shock correctly identified 95-100% of controls and septic shock patients in the test data set, depending on the class prediction algorithm and the gene selection method. Subjecting the test data set to an identical filtering strategy as that used for the training data set, demonstrated 75% concordance between the two gene lists. Subjecting the test data set to a purely statistical filtering strategy, with highly stringent correction for multiple comparisons, demonstrated <50% concordance with the previous gene filtering strategy. However, functional analysis of this statistics-based gene list demonstrated similar functional annotations and signaling pathways as that seen in the training data set. In particular, we validated that pediatric septic shock is characterized by large-scale repression of genes related to zinc homeostasis and lymphocyte function. These data demonstrate that the previously reported genome-wide expression signature of pediatric septic shock is applicable to a validation cohort of patients.