gebhart/patrepeval huggingface dataset:
Ovarian cancer family and prophylactic choices. (1992)

A subject from a family with ovarian cancer who has developed bilateral medullary carcinoma of the breast at the age of 40 is presented. The family is consistent with dominant inheritance of ovarian cancer and 12 female family members at 12.5%, 25%, and 50% risk, including our case, have undergone bilateral prophylactic oophorectomy and been given hormone replacement therapy. Despite the risk of further primary tumours of the breast our patient chose to have treatment with wide excision and radiotherapy. The implications for screening, prophylaxis, and hormone replacement therapy for this family are discussed.
Immunological, biochemical, ultrastructural, and electrophysiological characteristics of a human glioblastoma-derived cell culture line (1982)

This report presents the results of a study using multiple techniques of the established human cell line, LM, which has been developed in culture medium from a patient with a right temporoparietal glioblastoma. This cell line has human subtetraploid karyotype and has several features of a transformed line in culture. These include continuous propagation for 10 years, ability to form tumor nodules when transplanted into immunologically suppressed hamsters, and pleomorphic appearance. Ultrastructurally, it is characterized by multiple nuclei, few actin cables, and numerous surface-membrane microvilli, as well as abundant 9- to 10-nm cytoplasmic filaments. By its immunological reactivity, the line can be shown to contain glial fibrillary acidic protein at low levels, consistent with its glial origin and continued nature. Dibutyryl cyclic adenosine monophosphate (db-cAMP) induces formation of long astrocytic-like processes as well. Its membrane electrical characteristics include a low resting membrane potential and short time constant. Used in a microtiter antiglioma antibody cytotoxicity assay, LM yields a positive reaction to antibodies in the sera of 80% of patients with astrocytomas and only 9% of normal blood-bank donors, suggesting that it shares common antigens with other astrocytic tumor lines. The varied characteristics of this glioblastoma-derived line emphasize the "multiforme" nature on the neoplasm and suggest that for characterization of any such line, multiple parameters are necessary to allow comparison with other long-term glioblastoma lines in the literature. The usefulness of the LM line in in vitro cell biological, immunological, chemotherapeutic, and radiobiological studies of gliomas makes such efforts very worthwhile.
The Symmetrical Structure of Structural Maintenance of Chromosomes (SMC) and MukB Proteins: Long, Antiparallel Coiled Coils, Folded at a Flexible Hinge (1998)

Structural maintenance of chromosomes (SMC) proteins function in chromosome condensation and several other aspects of DNA processing. They are large proteins characterized by an NH2-terminal nucleotide triphosphate (NTP)-binding domain, two long segments of coiled coil separated by a hinge, and a COOH-terminal domain. Here, we have visualized by EM the SMC protein from Bacillus subtilis (BsSMC) and MukB from Escherichia coli, which we argue is a divergent SMC protein. Both BsSMC and MukB show two thin rods with globular domains at the ends emerging from the hinge. The hinge appears to be quite flexible: the arms can open up to 180 degrees, separating the terminal domains by 100 nm, or close to near 0 degrees, bringing the terminal globular domains together. A surprising observation is that the approximately 300-amino acid-long coiled coils are in an antiparallel arrangement. Known coiled coils are almost all parallel, and the longest antiparallel coiled coils known previously are 35-45 amino acids long. This antiparallel arrangement produces a symmetrical molecule with both an NH2- and a COOH-terminal domain at each end. The SMC molecule therefore has two complete and identical functional domains at the ends of the long arms. The bifunctional symmetry and a possible scissoring action at the hinge should provide unique biomechanical properties to the SMC proteins.
Collective cell movement in primary melanoma explants: plasticity of cell-cell interaction, beta1-integrin function, and migration strategies. (2002)

Collective cell movement represents an efficient dissemination strategy in neoplastic epithelial and mesenchymal cancer. In primary melanoma explants cultured in three-dimensional collagen lattices, invasive migration of multicellular clusters was dependent on the function of beta1 integrins, as shown by preferential beta1-integrin expression and clustering in a subset of promigratory cells at the leading edge ("guiding cells") and the abrogation of multicellular migration by adhesion-perturbing anti-beta1-integrin antibody. Interference with beta1-integrin function induced complex changes in cluster polarity and cohesion, including development of two or several opposing leading edges, cluster disruption, and the detachment of individual cells followed by beta1-integrin-independent "amoeboid" crawling and dissemination. The conversion from beta1-integrin-dependent collective movement to beta1-integrin-independent single-cell motility suggests efficient cellular and molecular plasticity in tumor cell migration strategies.
Identification of elements involved in transcriptional regulation of the Escherichia coli cad operon by external pH (1992)

Expression of the lysine decarboxylase gene (cadA) of Escherichia coli is induced upon external acidification. To dissect the molecular mechanisms responsible for this regulation, we analyzed a 4.2-kbp region upstream from cadA. DNA sequencing revealed two long open reading frames upstream of and on the same strand as cadA. One of these, cadB, is 444 codons long and is situated immediately upstream of cadA. Transcriptional fusions between fragments upstream of cadA and lacZ, Northern (RNA) hybridization, primer extension, and site-directed mutagenesis experiments defined a promoter, Pcad, upstream of cadB that was responsible for pH-regulated expression of cadA. Upstream of Pcad is an open reading frame, cadC, consisting of 512 codons. The predicted amino terminal region of the cadC gene product (CadC) resembles the carboxy-terminal domain of prokaryotic transcriptional activators involved in environmental sensing. Tn10 insertions within or immediately upstream of cadC abolished Pcad activity, suggesting that cadC encodes a positive transcription factor. Expression of plasmid-borne cadC in the Tn10 mutants restored Pcad activity, while introduction of a plasmid expressing truncated CadC resulted in the inability to complement. The presence of Pcad on a multicopy plasmid was found to lower expression arising from chromosomal Pcad, suggesting that a positive-acting factor is limiting. Our data suggests that cadA, cadB, and the acid-inducible Pcad comprise, at least in part, the cad operon which is under control of the cadC product.
An Optimized Synthesis of 2-Methoxyestradiol, A Naturally Occurring Human Metabolite with Anticancer Activity (1998)

Abstract 2-Methoxyestradiol, a naturally occurring human metabolite with demonstrated anticancer activity, has been synthesized in three steps and 76% yield from the bis(MOM) ether of 2-formylestradiol.
Combined spinal–epidural techniques (2000)

The combined spinal-epidural technique has been used increasingly over the last decade. Combined spinal-epidural may achieve rapid onset, profound regional blockade with the facility to modify or prolong the block. A variety of techniques and devices have been proposed. The technique cannot be considered simply as an isolated spinal block followed by an isolated epidural block as combining the techniques may alter each block. This review concentrates on technical and procedural aspects of combined spinal-epidural. Needle-through-needle, separate-needle and combined-needle techniques are described and modifications discussed. Failure rates and causes are reviewed. The problems of performing a spinal block before epidural blockade (potential for unrecognised placement of an epidural catheter, inability to detect paraesthesia during epidural placement, difficulty in testing the epidural, delay in positioning the patient) are described and evaluated. Problems of performing spinal block after epidural blockade (risk of catheter or spinal needle damage) are considered. Mechanisms of modification of spinal blockade by subsequent epidural drug administration are discussed. The review considers choice of technique, needle type, patient positioning and paramedian vs. midline approach. Finally, complications associated with combined spinal-epidural are reviewed.
Advanced glycation end products and diabetic foot disease (2008)

Diabetic foot disease is an important complication of diabetes. The development and outcome of foot ulcers are related to the interplay between numerous diabetes-related factors such as nerve dysfunction, impaired wound healing and microvascular and/or macrovascular disease.The formation of advanced glycation end products (AGEs) has been recognized as an important pathophysiological mechanism in the development of diabetic complications. Several mechanisms have been proposed by which AGEs lead to diabetic complications such as the accumulation of AGEs in the extracellular matrix causing aberrant cross-linking, the binding of circulating AGEs to the receptor of AGEs (RAGE) on different cell types and activation of key cell signalling pathways with subsequent modulation of gene expression, and intracellular AGE formation leading to quenching of nitric oxide and impaired function of growth factors. In the last decade, many experimental studies have shown that these effects of AGE formation may play a role in the pathogenesis of micro- and macrovascular complications of diabetes, diabetic neuropathy and impaired wound healing. In recent years also, several clinical studies have shown that glycation is an important pathway in the pathophysiology of those complications that predispose to the development of foot ulcers. Currently, there are a number of ways to prevent or decrease glycation and glycation-induced tissue damage. Although not in the area of neuropathy or wound healing, recent clinical studies have shown that the AGE-breakers may be able to decrease adverse vascular effects of glycation with few side effects.
The Human WASP-interacting Protein, WIP, Activates the Cell Polarity Pathway in Yeast (1999)

WIP, the Wiskott-Aldrich syndrome protein-interacting protein, is a human protein involved in actin polymerization and redistribution in lymphoid cells. The mechanism by which WIP reorganizes actin cytoskeleton is unknown. WIP is similar to yeast verprolin, an actin- and myosin-interacting protein required for polarized morphogenesis. To determine whether WIP and verprolin are functional homologues, we analyzed the function of WIP in yeast. WIP suppresses the growth defects of VRP1 missense and null mutations as well as the defects in cytoskeletal organization and endocytosis observed in vrp1-1 cells. The ability of WIP to replace verprolin is dependent on its WH2 actin binding domain and a putative profilin binding domain. Immunofluorescence localization of WIP in yeast cells reveals a pattern consistent with its function at the cortical sites of growth. Thus, like verprolin, WIP functions in yeast to link the polarity development pathway and the actin cytoskeleton to generate cytoskeletal asymmetry. A role for WIP in cell polarity provides a framework for unifying, under a common paradigm, distinct molecular defects associated with immunodeficiencies like Wiskott-Aldrich syndrome.
Inhibition of Chaperone Activity Is a Shared Property of Several Cu,Zn-Superoxide Dismutase Mutants That Cause Amyotrophic Lateral Sclerosis (2005)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron degeneration, paralysis, and death. Mutant Cu,Zn-superoxide dismutase (SOD1) causes a subset of ALS by an unidentified toxic property. Increasing evidence suggests that chaperone dysfunction plays a role in motor neuron degeneration in ALS. To investigate the relationship between mutant SOD1 expression and chaperone dysfunction, we measured chaperone function in central nervous system tissue lysates from normal mice and transgenic mice expressing human SOD1 variants. We observed a significant decrease in chaperone activity in tissues from mice expressing ALS-linked mutant SOD1 but not control mice expressing human wild type SOD1. This decrease was detected only in the spinal cord, became apparent by 60 days of age (before the onset of muscle weakness and significant motor neuron loss), and persisted throughout the late stages. In addition, this impairment of chaperone activity occurred only in cytosolic but not in mitochondrial and nuclear fractions. Furthermore, multiple recombinant human SOD1 mutants with differing biochemical and biophysical properties inhibited chaperone function in a cell-free extract of normal mouse spinal cords. Thus, mutant SOD1 proteins may impair chaperone function independent of gene expression in vivo, and this inhibition may be a shared property of ALS-linked mutant SOD1 proteins.
Expression of the arylsulfatase gene from theβ2-tubulin promoter inChlamydomonas reinhardtii (1992)

Arylsulfatase, produced by Chlamydomonas reinhardtii during sulfur-limited growth, is secreted into the periplasmic space and is readily assayed using a chromogenic substrate. To assess the usefulness of the gene encoding arylsulfatase (ars) as a reporter gene in C. reinhardtii, we have fused the promoter region of the beta 2-tubulin gene (tubB2) to the coding region of an ars genomic clone to form a tubB2/ars chimeric sequence. This construct was introduced into C. reinhardtii, strain CC425 (cw-15, arg-2), via cotransformation with the argininosuccinate lyase gene (which complements the arg-2 lesion) (1). Transformants expressing arylsulfatase (Ars) in sulfur-sufficient medium were isolated and subsequently shown to contain the tubB2/ars gene. RNA analysis determined that tubB2/ars transcripts accumulated in these cells. Abundance of the chimeric transcript increased immediately following deflagellation in a manner similar to that of the endogenous tubB2 transcript. Thus, chimeric genes incorporating ars coding sequences and heterologous promoters can be used to examine regulated gene expression in C. reinhardtii.
Properties of Purine Nucleoside Phosphorylase (PNP) of Mammalian and Bacterial Origin (1990)

Purine nucleoside phosphorylase (PNP), from calf spleen, human erythrocytes and E. coli have been examined with regard to structural requirements of substrates and inhibitors. Kinetic parameters (Km, Vmax/Km) for a variety of N(1) and/or N(7)-methylated analogues of guanosine, inosine and adenosine have been evaluated for all three enzymes. The substrate and/or inhibitor properties of purine riboside, 1,6-dihydropurine riboside, some deazapurine nucleosides: 3-deaza- and 7-deazainosine, 1,3-dideazapurine riboside (ribobenzimidazole), and a variety of acyclonucleosides, have been determined with mammalian and bacterial enzymes. Overall results indicate distinct similarities of kinetic properties and structural requirements of the two mammalian enzymes, although there are some differences as well. The N(1) and O6 of the purine ring are necessary for substrate-inhibitor activity and constitute a binding site for the mammalian (but not the bacterial) enzymes. Moreover, nucleosides lacking the N(3) undergo phosphorolysis and those lacking N(7) are inhibitors (but not substrates). Methylation of the ring N(7) leads to two overlapping effects: labilization of the glycosidic bond, and impediment to protonation at this site by the enzyme, a postulated prerequisite for enzymatic phosphorolysis. It is proposed that a histidine interacts with N(1) as a donor and O6 as an acceptor. Alternatively N(1)-H and C(2)-NH2 may serve as donors for hydrogen bonds with a glutamate residue. The less specific E. coli enzyme phosphorolyses all purine ring modified nucleosides but 7-deazainosine which is only an inhibitor. On the other hand, the bacterial enzyme exhibits decreased activity towards N(7)-methylated nucleosides and lack of affinity for a majority of the tested acyclonucleoside inhibitors of the mammalian enzymes. The foregoing results underline the fundamental differences between mammalian and bacterial enzymes, including variations in the binding sites for the purine ring.
Bioenergetic Response of the Extreme Thermoacidophile Metallosphaera sedula to Thermal and Nutritional Stresses (1995)

The bioenergetic response of the extremely thermoacidophilic archaeon Metallosphaera sedula to thermal and nutritional stresses was examined. Continuous cultures (pH 2.0, 70(deg)C, and dilution rate of 0.05 h(sup-1)) in which the levels of Casamino Acids and ferrous iron in growth media were reduced by a step change of 25 to 50% resulted in higher levels of several proteins, including a 62-kDa protein immunologically related to the molecular chaperone designated thermophilic factor 55 in Sulfolobus shibatae (J. D. Trent, J. Osipiuk, and T. Pinkau, J. Bacteriol. 172:1478-1484, 1990), on sodium dodecyl sulfate-polyacrylamide gels. The 62-kDa protein was also noted at elevated levels in cells that had been shifted from 70 to either 80 or 85(deg)C. The proton motive force ((Delta)p), transmembrane pH ((Delta)pH), and membrane potential ((Delta)(psi)) were determined for samples obtained from continuous cultures (pH 2.0, 70(deg)C, and dilution rate of 0.05 h(sup-1)) and incubated under nutritionally and/or thermally stressed and unstressed conditions. At 70(deg)C under optimal growth conditions, M. sedula was typically found to have a (Delta)p of approximately -190 to -200 mV, the result of an intracellular pH of 5.4 (extracellular pH, 2.0) and a (Delta)(psi) of +40 to +50 mV (positive inside). After cells had been shifted to either 80 or 85(deg)C, (Delta)(psi) decreased to nearly 0 mV and internal pH approached 4.0 within 4 h of the shift; respiratory activity, as evidenced by iron speciation in parallel temperature-shifted cultures on iron pyrite, had ceased by this point. If cultures shifted from 70 to 80(deg)C were shifted back to 70(deg)C after 4 h, cells were able to regain pyrite oxidation capacity and internal pH increased to nearly normal levels after 13 h. However, (Delta)(psi) remained close to 0 mV, possibly the result of enhanced ionic exchange with media upon thermal damage to cell membranes. Further, when M. sedula was subjected to an intermediate temperature shift from 73 to 79(deg)C, an increase in pyrite dissolution (ferric iron levels doubled) over that of the unshifted control at 73(deg)C was noted. The improvement in leaching was attributed to the synergistic effect of chemical and biological factors. As such, periodic exposure to higher temperatures, followed by a suitable recovery period, may provide a basis for improving bioleaching rates of acidophilic chemolithotrophs.
In Vitro Studies on the Binding, Antioxidant, and Cytotoxic Actions of Punicalagin (2007)

The protective bioactivity of punicalagin, a high molecular weight polyphenol isolated from pomegranate fruit pith and carpellary membrane, against oxidative damages to lipids, amino acids constituting the proteins, and guanosine as a model for DNA has been investigated. The ABTS*-, guanosine, and tryptophan radical generated pulse radiolytically were repaired by punicalagin, k = (0.9-15) x 10(7) dm3 mol-1 s-1. The results are rationalized on the basis of the scavenging activity of punicalagin against various one-electron oxidizing radicals, namely, .OH, N3., and NO2. . The formation of the transient species in these reactions and the rate constants of the scavenging reactions have been probed using a time-resolved kinetic spectrophotometric technique. The antioxidant action of punicalagin is expressed not only through its scavenging reactions but also by its ability to form metal chelates. Binding of punicalagin with bovine serum albumin and metal ions such as iron and copper revealed different binding affinities, whereas its binding with DNA was very weak and nonspecific. In vitro cytotoxic studies against three cell lines, namely, Vero (normal African green monkey kidney cell line), Hep-2 (human larynx epithelial cancer cell line), and A-549 (human small cell lung carcinoma cell line) showed that this polyphenol is toxic only at higher concentration.
Introduction to Digital Mobile Communication (2015)

Introduces digital mobile communications with an emphasis on digital transmission methods This book presents mathematical analyses of signals, mobile radio channels, and digital modulation methods. The new edition covers the evolution of wireless communications technologies and systems. The major new topics are OFDM (orthogonal frequency domain multiplexing), MIMO (multi-input multi-output) systems, frequency-domain equalization, the turbo codes, LDPC (low density parity check code), ACELP (algebraic code excited linear predictive) voice coding, dynamic scheduling for wireless packet data t
Cancer treatment and survivorship statistics, 2012 (2012)

Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers.