gebhart/patrepeval huggingface dataset:
Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. (1987)

We investigated the peroxisomal beta-oxidation system in liver from a patient with clinical features similar to those in the cerebrohepatorenal (Zellweger) syndrome and with elevated levels in body fluids of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. The peroxisomal beta-oxidation of fatty acids, measured as the cyanide-insensitive formation of [14C]acetyl units from [14C]palmitoyl-CoA, was very low in the patient (less than 10% of the values in control subjects). Immunoblotting experiments using antibodies to peroxisomal beta-oxidation enzymes indicated that peroxisomal 3-oxoacyl-CoA thiolase (acyl-CoA:acetyl-CoA C-acyltransferase, EC 2.3.1.16) was deficient. Addition of purified rat-liver peroxisomal 3-oxoacyl-CoA thiolase to a reaction mixture containing liver homogenate from the patient restored peroxisomal beta-oxidation. We conclude that the deficiency of peroxisomal 3-oxoacyl-CoA thiolase is responsible for the very low peroxisomal beta-oxidation activity and for the accumulation of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. Furthermore, the finding that both very-long-chain fatty acids and abnormal bile acids accumulate in this patient suggests that a single peroxisomal 3-oxoacyl-CoA thiolase is involved in the oxidative chain shortening of both very-long-chain fatty acids and the coprostanoic acids.
MOLECULAR BIOLOGY OF THE LysR FAMILY OF TRANSCRIPTIONAL REGULATORS (1993)

The LysR family is composed of > 50 similar-sized, autoregulatory transcriptional regulators (LTTRs) that apparently evolved from a distant ancestor into subfamilies found in diverse prokaryotic genera. In response to different coinducers, LTTRs activate divergent transcription of linked target genes or unlinked regulons encoding extremely diverse functions. Mutational studies and amino acid sequence similarities of LTTRs identify: (a) a DNA-binding domain employing a helix-turn-helix motif (residues 1-65), (b) domains involved in coinducer recognition and/or response (residues 100-173 and 196-206), (c) a domain required for both DNA binding and coinducer response (residues 227-253). DNA footprinting studies suggest that in the absence of coinducer many LTTRs bind to regulated promoters via a 15-bp dyadic sequence with a common structure and position (near -65). Coinducer causes additional interactions of LTTRs with sequences near the -35 RNA polymerase binding site and/or DNA bending that results in transcription activation.
Etching in Microsystem Technology (1999)

Features of microtechnical etching wet chemical etching methods dry-etching methods microforming by etching of locally changed material selected recipes.
Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. (1987)

We have examined the effect of short-term and long-term growth in the absence of estrogens on the proliferation rate and estrogen and antiestrogen responsiveness of MCF-7 human breast cancer cells. The removal of phenol red, the pH indicator in tissue culture medium that is weakly estrogenic (Y. Berthois et al., Proc. Natl. Acad. Sci. USA, 83:2496-2500, 1986), immediately slows the cell proliferation rate, and MCF-7 cells grown in phenol red-free medium with charcoal dextran-treated serum for periods up to 1 mo maintain this reduced rate of cell proliferation. In these short-term phenol red-withdrawn cells, estradiol stimulates proliferation markedly and reproducibly, and antiestrogens inhibit estrogen-stimulated proliferation. Antiestrogens by themselves appear as partial agonists/antagonists; at low concentrations they stimulate proliferation weakly, but they show no stimulation at the high concentrations where they fully inhibit estrogen-stimulated proliferation. In contrast to the short-term phenol red-withdrawn cells, cells maintained for several months (5 to 6 mo) in the apparently complete absence of estrogens (no phenol red, with charcoal dextran-treated calf serum) show a markedly increased basal rate of cell proliferation; estradiol is unable to increase this rate of proliferation further, but antiestrogens are able to decrease proliferation. This change in growth pattern is associated with a 3-fold increase in cellular estrogen receptor levels. Despite their differing basal growth rates, cells grown in either the short-term (less than 1 mo) or long-term (greater than 6 mo) absence of estrogens both have progesterone receptor levels that are very low and, in both cases, estradiol increases progesterone receptor levels markedly. Thus, under long-term estrogen-free conditions, there is a dissociation between the stimulation of cell proliferation and of specific protein synthesis (progesterone receptor) by estrogen. The increase in the cell proliferation rate observed in cells grown in the long-term absence of estrogen may reflect altered regulation of growth factor production or altered sensitivity to growth factors in the medium or produced by the cells themselves. Hence, these breast cancer cells adapt significantly to long-term growth in estrogen-free conditions, an observation that may be relevant to understanding the growth of hormone-responsive human breast cancers in vivo.
Assessing disease onset and progression in the SOD1 mouse model of ALS (2003)

SOD1 transgenic mice are the most widely used animal model of amyotrophic lateral sclerosis (ALS). In addition to providing valuable insights into the pathogenesis of ALS, these animals are used intensively in many laboratories as an in vivo model for investigating novel therapeutic interventions towards this devastating motorneuron disease. Such pre-clinical studies require objective and reliable quantification of the clinical phenotype of individual mice, most importantly of the neuromuscular abnormalities. Here we compare four parameters of the clinical phenotype: motor signs, body weight, rotarod performance and paw grip endurance for their usefulness in monitoring the SOD1 mouse model. We found that paw grip endurance is a sensitive and inexpensive alternative to the widely used rotarod test.
Enhancing an Embedded Processor Core with a Cryptographic Unit for Performance and Security (2008)

We present a set of low-cost architectural enhancements to accelerate the execution of certain arithmetic operations common in cryptographic applications on an extensible embedded processor core. The proposed enhancements are generic in the sense that they can be beneficially applied in almost any RISC processor. We implemented the enhancements in form of a cryptographic unit (CU) that offers the programmer an extended instruction set. The CU features a 128-bit wide register file and datapath, which enables it to process 128-bit words and perform 128-bit loads/stores. We analyze the speed-up factors for some arithmetic operations and public-key cryptographic algorithms obtained through these enhancements. In addition, we evaluate the hardware overhead (i.e. silicon area) of integrating the CU into an embedded RISC processor. Our experimental results show that the proposed architectural enhancements allow for a significant performance gain for both RSA and ECC at the expense of an acceptable increase in silicon area. We also demonstrate that the proposed enhancements facilitate the protection of cryptographic algorithms against certain types of side-channel attacks and present an AES implementation hardened against cache-based attacks as a case study.
Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites (2004)

O-GalNAc-glycosylation is one of the main types of glycosylation in mammalian cells. No consensus recognition sequence for the O-glycosyltransferases is known, making prediction methods necessary to bridge the gap between the large number of known protein sequences and the small number of proteins experimentally investigated with regard to glycosylation status. From O-GLYCBASE a total of 86 mammalian proteins experimentally investigated for in vivo O-GalNAc sites were extracted. Mammalian protein homolog comparisons showed that a glycosylated serine or threonine is less likely to be precisely conserved than a nonglycosylated one. The Protein Data Bank was analyzed for structural information, and 12 glycosylated structures were obtained. All positive sites were found in coil or turn regions. A method for predicting the location for mucin-type glycosylation sites was trained using a neural network approach. The best overall network used as input amino acid composition, averaged surface accessibility predictions together with substitution matrix profile encoding of the sequence. To improve prediction on isolated (single) sites, networks were trained on isolated sites only. The final method combines predictions from the best overall network and the best isolated site network; this prediction method correctly predicted 76% of the glycosylated residues and 93% of the nonglycosylated residues. NetOGlyc 3.1 can predict sites for completely new proteins without losing its performance. The fact that the sites could be predicted from averaged properties together with the fact that glycosylation sites are not precisely conserved indicates that mucin-type glycosylation in most cases is a bulk property and not a very site-specific one. NetOGlyc 3.1 is made available at www.cbs.dtu.dk/services/netoglyc.
Molecular Pathogenesis of Ovarian Borderline Tumors: New Insights and Old Challenges (2005)

Ovarian borderline (low malignant potential) tumors are a puzzling group of neoplasms that do not fall neatly into benign or malignant categories. Their behavior is enigmatic, their pathogenesis unclear, and their clinical management controversial, especially for serous borderline tumors (SBT), the most common type of ovarian borderline tumor. Clarifying the nature of borderline tumors and their relationship to invasive carcinoma has puzzled investigators since the category was created over 30 years ago. Much of the confusion and controversy concerning these tumors is due to a lack of understanding of their pathogenesis and an absence of a model for the development of ovarian carcinoma. This review summarizes recent molecular studies of ovarian borderline tumors with special emphasis on the role of SBT in tumor progression and its relationship to ovarian serous carcinoma.
Monoclonal antibodies distinguish several differentially phosphorylated states of the two largest rat neurofilament subunits (NF-H and NF-M) and demonstrate their existence in the normal nervous system of adult rats (1987)

A new panel of greater than 300 monoclonal antibodies (mAbs) was prepared to the high, middle, and low Mr rat neurofilament (NF) subunits (NF-H, NF-M and NF-L, respectively). NF proteins were purified both from native, i.e., phosphorylated rat NFs and from enzymatically dephosphorylated rat NFs. The resulting mAbs were used to biochemically and immunochemically distinguish and characterize distinct and differentially phosphorylated isoforms of NF subunits. By immunoblot, all mAbs specific for NF-L and some mAbs specific for NF-M detected their specific NF subunit regardless of whether or not the NFs had been treated with alkaline phosphatase, and such antibodies were termed "phosphate-independent" or P[ind] mAbs. The other mAbs were specific for NF-M, NF-H, or for both NF-M and NF-H, and they recognized epitopes in the COOH termini of these subunits. Significantly, the latter mAbs could discriminate different isoforms of NF-M and NF-H, depending on the phosphorylation state of each variant. Such mAbs were assigned to one of 4 distinct categories on the basis of their performance in immunoblots of progressively dephosphorylated rat NF samples and by immunohistochemistry of various adult rat nervous tissues: (1) P[-] mAbs preferentially stained neuronal perikarya and dendrites, and they recognized only extensively dephosphorylated (and nonphosphorylated) NF-H; (2) P[+] mAbs stained axons more strongly than perikarya, and primarily blotted phosphorylated, but not nonphosphorylated, forms of NF-H and NF-M; (3) P[++] mAbs stained axons almost to the exclusion of perikarya, and in blots recognized only the extensively phosphorylated forms of NF-H and NF-M (i.e., subunits subjected to limited enzymatic dephosphorylation); (4) P[ ] mAbs also predominantly stained axons, but the briefest alkaline phosphatase treatment abolished the NF-M and NF-H immunobands produced by these mAbs. Two-dimensional gel analysis and immunoblotting of total proteins from adult rat dorsal root ganglion verified mAb specificity in situ, and showed that differentially phosphorylated isoforms of NF-M and NF-H occur in vivo. This provided additional evidence that mAbs can detect all 4 phosphorylation-dependent endogenous isoelectric variants of NF-H and NF-M.(ABSTRACT TRUNCATED AT 400 WORDS)
Acceptable sampling times at plateau for drug analysis. (1981)

1 Two methods of estimating the average plasma drug concentration at plateau Cav are considered. 2 Given an acceptable error in the estimate of Cav, a range of sampling times, rather than a single time, during the dosing interval, can be calculated. This range depends on the variability of the half-life within the patient population, the dosing interval, the error in assay measurement and the therapeutic index of the drug. 3 When the minimum plasma drug concentration is monitored, an estimate of the individual's half-life is needed, unless the dosing interval is short. Then the population half-life may be used to obtain a reasonable estimate of Cav.
Biological properties of chimeric domain-deleted anticarcinoma immunoglobulins. (1995)

CC49 is a second-generation monoclonal antibody (MAb) that has high affinity for the tumor-associated pancarcinoma antigen tumor-associated glycoprotein-72. In clinical trials using gamma scanning, radiolabeled CC49 has facilitated the detection of more than 90% of carcinomas. We report here the development of a constant heavy-chain 2 (CH2) domain-deleted chimeric (c) CC49 MAb by transfecting an expression construct consisting of the CC49 murine variable region and a CH2 domain-deleted human IgG1 constant region into cCC49 kappa producing SP2/0 murine myeloma cells. As determined by SDS-PAGE, the intact cCC49 delta CH2 has a molecular weight of 153,000 and, under reducing conditions, molecular weights of 43,000 and 27,000. The plasma clearance and tumor-targeting properties of cCC49 delta CH2 were evaluated and compared with those of mouse/human chimeric forms cCC49 delta CH1 and intact cCC49. Previous studies have shown that the in vitro antigen-binding properties of cCC49 delta CH1 are similar to those of cCC49. Biodistribution studies reported here, using 131I-labeled cCC49 delta CH1 and 125I-labeled cCC49 in athymic mice bearing human colon carcinoma xenografts, demonstrated that both cMAbs localized to the tumor and cleared from the normal tissues similarly. However, in comparison with 125I-labeled cCC49, 131I-labeled cCC49 delta CH2 localized to tumors earlier and had a significantly lower percentage of the injected dose of cMAb/g (%ID/g) in normal tissues than cCC49. Immunoscintigraphy of 131I-labeled cCC49 delta CH2 and 125I-labeled cCC49 in athymic mice bearing human tumor xenografts demonstrated a clear image of the tumor by 24 h after i.v. administration of the delta CH2 cMAb versus the 72 h required for cCC49. Biodistribution studies using 177Lu-conjugated cCC49 delta CH1 and cCC49 showed no significant difference between the radiolocalization indices (% ID/g in tumor divided by % ID/g in normal tissue). 177Lu-conjugated cCC49 delta CH2, however, had lower % ID/g values in tumor xenografts and lower radiolocalization indices than either 177Lu-conjugated cCC49 delta CH1 or 177Lu-conjugated cCC49. Pharmacokinetic studies in non-tumor-bearing athymic mice using cCC49 delta CH1 and cCC49 revealed no significant difference between these cMAbs. However, the plasma clearance of cCC49 delta CH2 in non-tumor-bearing mice was significantly faster than that of cCC49. These results were similar when the cMAbs were labeled with either iodine or lutetium. In nonhuman primates, 131I-labeled cCC49 delta CH2 cleared significantly faster than 125I-labeled cCC49. The similar plasma clearance and tumor localization of cCC49 and cCC49 delta CH1 suggest that these two cMAbs may be used in similar clinical settings. However, because of the unique pharmacokinetics and tumor targeting of cCC49 delta CH2 versus cCC49 or cCC49 delta CH1, this chimeric immunoglobulin form may be useful in clinical settings that require efficient tumor targeting and rapid serum and whole-body clearance.
Usage statistics collection and management in the ELINOR electronic library (1995)

Usage statistics collection and management in an electronic library environment is concerned with tracking, managing, analysing and reporting information resource usages by the electronic library users for various management purposes, such as copyright management and usage pattern monitor ing. Usage statistics data are summaries of resource usage events. Conventional data modelling methods which focus on 'reality' or 'situation' cannot be applied directly to usage statistics data. Finding a suitable database structure to store the usage statistics data so that queries on usage statistics can be supported efficiently is thus a major problematic issue in designing a usage statistics management subsystem. Another major concern for electronic library systems with out built-in usage statistics collection facilities, such as in the case of ELINOR, or for systems with such a facility but where the collected information is not detailed enough to match the requirements, is how to get hold of the relevant resource usage events which are generated as a by-product of resource uses. This paper presents the modelling, analy sis, design and the architecture of the usage statistics col lection and management subsystem of the ELINOR electronic library. Principles in general, as well as practical implementation issues, are discussed.
HEXA: Compact Data Structures for Faster Packet Processing (2007)

Data structures representing directed graphs with edges labeled by symbols from a finite alphabet are used to implement packet processing algorithms used in a variety of network applications. In this paper we present a novel approach to represent such data structures, which significantly reduces the amount of memory required. This approach called history-based encoding, execution and addressing (HEXA) challenges the conventional assumption that graph data structures must store pointers of lceillog <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> nrceil bits to identify successor nodes. We show how the data structures can be organized so that implicit information can be used to locate successors, significantly reducing the amount of information that must be stored explicitly. We demonstrate that the binary tries used for IP route lookup can be implemented using just two bytes per stored prefix (roughly half the space required by Eatherton's tree bitmap data structure) and that string matching can be implemented using 20-30% of the space required by conventional data representations. Compact representations are useful, because they allow the performance-critical part of packet processing algorithms to be implemented using fast, on-chip memory, eliminating the need to retrieve information from much slower off-chip memory. This can yield both substantially higher performance and lower power utilization. While enabling a compact representation, HEXA does not add significant complexity to the graph traversal and update, thus maintaining a high performance.
One pot radiofluorination of a new potential PSMA ligand [Al18F]NOTA‐DUPA‐Pep (2012)

Up to now, many radiolabeled ligands targeting prostate‐specific membrane antigen (PSMA) have been synthesized. To carry out radiofluorinations, there have been several approaches mainly involving two steps of radiosynthesis. However, in case of labelings with high activities, one radiosynthetic step (‘one pot synthesis’) is highly desirable. As an alternative, radiofluorinations of peptides coupled to the NOTA complex via Al 18 F appear to be very promising, both in terms of feasible labelling procedure and stability in vivo . Therefore, in the present study, we synthesized a new PSMA‐ligand, that is, NOTA‐DUPA‐Pep, labeled with Al 18 F and examined the reaction kinetics in dependence on temperature, time, concentration of precursor, and AlCl 3 solution. Highest radiochemical yields of 83 ± 1.1% were obtained at 105 °C after 15 min of reaction time. At the end of synthesis, [Al 18 F]NOTA‐DUPA‐Pep was prepared with a radiochemical purity of ≥98% with an overall yield of 79 ± 0.7% ( n = 3) (decay uncorrected) within 55 min. Copyright © 2012 John Wiley &amp; Sons, Ltd.
Roles of Calcium, Serum, Plasma, and Folic Acid in the Control of Proliferation of Normal and Rous Sarcoma Virus-Infected Chicken Fibroblasts (1973)

In a culture medium of pH 7.4 and a folic acid concentration of 100 mug/liter that contains 5% heat-inactivated chicken plasma rather than serum, the rate of proliferation of normal chicken fibroblasts is determined by the concentration of calcium. Proliferation, rapid when the calcium concentration is physiological, decreases when the calcium concentration is reduced. At a very low calcium concentration, in this culture medium, normal fibroblasts are maintained without proliferation, whereas those infected with Rous sarcoma virus proliferate rapidly. This proliferative inactivity of normal fibroblasts does not involve contact-inhibition, since the effect is observed at low, as well as higher, culture densities. When a physiological amount of calcium is added to cultures of normal fibroblasts that have been maintained in very low calcium-plasma medium for 3 days, labeled thymidine uptake and protein synthesis are strongly stimulated, and cell division follows. The use of heat-inactivated chicken serum, instead of plasma, in this medium appears to strongly sensitize normal fibroblasts to the mitogenic action of calcium. In a plasma-containing culture medium of physiological calcium concentration and a folate concentration of 5 mug/liter, neither normal nor Rous sarcoma virus-infected fibroblasts proliferate to an appreciable extent. The use of serum, however, instead of plasma results in rapid proliferation of both normal and infected cells, as does increase in the folate concentration of the plasma-containing medium to 100 mug/liter.The fact that while normal fibroblasts are maintained without proliferation in low calcium-plasma medium, Rous sarcoma virus-infected fibroblasts proliferate rapidly, indicates that the effect of calcium is regulatory rather than permissive. These results suggest that the proliferation of normal fibroblasts is initiated by a cellular function involving calcium, and that the autonomous proliferation of the neoplastic fibroblasts results either from increased calcium uptake or from an alteration or a hypass of that function. The results also suggest that serum contains a mitogenic factor(s) not present in plasma, possibly a "wound hormone" for fibroblasts.