gebhart/patrepeval huggingface dataset:
GENETIC DIVERSITY AND TEMPORAL VARIATION IN THE E. COLI POPULATION OF A HUMAN HOST (1981)

Electrophoretic techniques were employed to study variation in chromosomal genes encoding enzymes and in the distribution of cryptic plasmids in the E. coli population of a human host over an 11-month period. Thirteen of the 15 enzymes studied were polymorphic, and mean genetic diversity per locus was 0.39. Among 550 clones isolated from fecal samples, protein electrophoresis revealed 53 distinct electrophoretic types (ETs). Most ETs appeared on only one or a few days and were considered transients, but two (ET-12 and ET-13) were observed many times over extended periods and represented residents. Complete turnover in the transient ETs in the population occurred in periods of from two weeks to a month. ETs appearing in one month showed no particular genetic similarity to those of the previous month. - All but 4 of the 53 ETs carried one or more "cryptic" plasmids with molecular weights ranging from 1 to 80 megadaltons. With few exceptions, the plasmid composition of each ET was unique. In the course of the 11-month sampling period, there were changes in the plasmid profiles of the resident strains ET-12 and ET-13, and also in the profile of a recurrent strain, ET-2, which was isolated on four days. Modification of the plasmid profile of ET-12 involved the sequential addition of relatively high molecular weight bands. For ET-2 and ET-13, the changes in the plasmid profiles were radical, suggesting invasions of new cell types rather than merely the addition and deletion of plasmids. - The results of this study provide three lines of evidence that recombination plays a minor role in the generation of genetic diversity in the E. coli population of a single host. (1) Several pairs of loci were in strong linkage disequilibrium; compared to a randomly generated array of genotypes, the sample of ETs contained an excess of pairs differing at one or two loci and too many pairs with highly distinctive combinations of electromorphs. (2) In most cases where pairs of ETs differed at a single locus and, therefore, could reasonably have been generated by phage- or plasmid-mobilized gene transfer, the plasmid profiles of the pair members were radically different and/or the potentially transmitted alleles were not present in other ETs in the population. (3) Although ET-12 was abundant, being represented by 252 of the 550 clones sampled, the electrophoretic type most similar to ET-12 different from it at six loci, and ET-12 carried two unique alleles. We conclude that most of the genetic diversity observed in this human host is a consequence of successive invasions of E. coli genotypes.
Texture and anisotropy (2004)

A large number of polycrystalline materials, both manmade and natural, display preferred orientation of crystallites. Such alignment has a profound effect on anisotropy of physical properties. Preferred orientation or texture forms during growth or deformation and is modified during recrystallization or phase transformations and theories exist to predict its origin. Different methods are applied to characterize orientation patterns and determine the orientation distribution, most of them relying on diffraction. Conventionally x-ray pole-figure goniometers are used. More recently single orientation measurements are performed with electron microscopes, both SEM and TEM. For special applications, particularly texture analysis at non-ambient conditions, neutron diffraction and synchrotron x-rays have distinct advantages. The review emphasizes such new possibilities.
MUTATIONAL SPECIFICITY IN BACTERIA (1983)

INTRODUCTIO N . . . . ..... . . . . . . . . . . . . . . . . . . ... .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1 5 Definitions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1 6 MUTAGENI C PATHWAyS . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216 SPECIFI CITY OF SOS-DEPENDE NT MUTAGENS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218 Compounds Forming Bulky Adducts . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .... . . . . . . . . . . . .. . . . . . . . . . 2 19 Antitumor Drugs .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2 1 Mutations Resulting from the Induction of the SOS System-Untargeted Mutagenesis? 222 Ultraviolet Light . . . . . . . . . . . . . . . . . . ... :... . . . . . . . . . . ....... . . . . . . . . . . . ..... . . . . . . . . . . ... . . . . . . . . . . . 226 HOTSPOTS-S ITE SPE CIFICITy . ...... . . . . . . . . . . . ...... . . . . . . . . . . ..... . . . . . . . . . ,... . . . . . . . . . . . . 230 FRAMESHIFTS . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... . . . 231 Mechanisms of Frameshift Mutagenesis . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . 234
Tolerance Induction and Endogenous Regeneration of Pancreatic β-Cells in Established Autoimmune Diabetes (2004)

Studies aimed at the understanding of the multifactorial development of autoimmune diabetes have made substantial contributions toward elucidating the molecular mechanisms that open the road to an effective prevention of defective immune responses. Immunomodulatory regimens capable of inducing tolerance are shown to be effective even in the reversal of established autoimmune diabetes in animal models. Experimental trials including the reeducation of autoreactive T cells, depletion of macrophages, dendritic cells, and T cells, as well as the use of monoclonal antibodies, have yielded encouraging results, but have not yet been translated into beneficial clinical outcomes. In addition, we are now seeing an emergence of promising new directions aimed at the induction of islet regeneration by endogenous factors, suggesting that the repair of pancreatic tissue is possible without the need for an engraftment of donor tissue. These recent waves of technological progress have injected new hope for a combined therapy to offer diabetic patients long-term benefits of insulin independence. This article reviews the latest findings on diabetic pathogenesis and discusses promising avenues to tolerance induction and islet regeneration.
Evaluation of the degree of turbidity of cataract lens and its correlation with retinal visual acuity (1999)

Experimental in vitro studies of speckle-modulated laser field arising after transmission through different type of human cataractous lenses are presented. Computer analysis of digital imaging has allowed to determinate the degree of destruction of spatial coherence scattered laser beam and the angle of resolution of the retina using Retinal Analyzer of Vision (AROL-1) in diagnosis of cataract. Measurement of retinal visual acuity (RVA) in 135 patient with different types of cataract (senile, complicated, posterior capsular) before and after cataract extraction and also in vitro measurement of RVA with extracted cataractal lenses has shown that laser retinometer can be used for evaluating visual acuity within 0.3 - 1, practically for all types of cataracts.
The CLCA Gene Family: Putative Therapeutic Target for Respiratory Diseases (2009)

The CLCA proteins were first shown to exist in bovine trachea and named as chloride channels calcium activated (CLCA) due to the calcium-dependent chloride conductance that appeared to be activated on expression of these proteins in trachea and other secretory epithelial cells. Since their initial discovery the CLCA gene family has grown extensively and family members have been identified in bovine, human, murine, equine and porcine tissues. The CLCA proteins appear to have a role to play in chloride conductance across epithelial cells and hence epithelial fluid secretion; cell-cell adhesion, apoptosis, cell cycle control and tumorgenesis and metastasis; mucous production and cell signalling in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). There are four human homologues; hCLCA1, hCLCA2, hCLCA3 and hCLCA4. Interest in these proteins has gathered pace with the description of hCLCA1's involvement in several human respiratory diseases. This review will describe the CLCA gene family and then move on to look at the growing body of evidence that suggests that at least hCLCA1 has an important role in the pathogenesis of respiratory disease such as asthma, COPD and cystic fibrosis (CF).
Genomic markers of panitumumab resistance including ERBB2/HER2 in a phase II study of KRAS wild-type (wt) metastatic colorectal cancer (mCRC) (2016)

A prospective study was conducted to identify biomarkers associated with resistance to panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). Patients with previously treated, codon 12/13 KRAS wt, mCRC were prospectively administered panitumumab 6 mg/kg IV q2weeks. Of 34 panitumumab-treated patients, 11 (32%) had progressive disease at 8 weeks and were classified as non-responders. A Nanostring nCounter-based assay identified a 5-gene expression signature (ERBB2, MLPH, IRX3, MYRF, and KLK6) associated with panitumumab resistance (P = 0.001). Immunohistochemistry and in situ hybridization determined that the HER2 (ERBB2) protein was overexpressed in 4/11 non-responding and 0/21 responding cases (P = 0.035). Two non-responding tumors had ERBB2 gene amplification only, and one demonstrated both ERBB2 amplification and mutation. A non-codon 12/13 KRAS mutation occurred in one panitumumab-resistant patient and was mutually exclusive with ERBB2/HER2 abnormalities. This study identifies a 5-gene signature associated with non-response to single agent panitumumab, including a subgroup of non-responders with evidence of aberrant ERBB2/HER2 signaling. KRAS wt tumors resistant to EGFRi may be identified by gene signature analysis, and the HER2 pathway plays an important role in resistance to therapy.
Non-heme iron enzymes: Contrasts to heme catalysis (2003)

Non-heme iron enzymes catalyze a wide range of O(2) reactions, paralleling those of heme systems. Non-heme iron active sites are, however, much more difficult to study because they do not exhibit the intense spectral features characteristic of the porphyrin ligand. A spectroscopic methodology was developed that provides significant mechanistic insight into the reactivity of non-heme ferrous active sites. These studies reveal a general mechanistic strategy used by these enzymes and differences in substrate and cofactor interactions dependent on their requirement for activation by iron. Contributions to O(2) activation have been elucidated for non-heme relative to heme ligand sets, and major differences in reactivity are defined with respect to the heterolytic and homolytic cleavage of O-O bonds.
THE PHARMACOKINETICS, SAFETY AND ENDOCRINE EFFECTS OF AUTHENTIC BIOSYNTHETIC HUMAN GROWTH HORMONE IN NORMAL SUBJECTS (1989)

SUMMARY The pharmacokinetics, safety and endocrine effects of an authentic human growth hormone (bio‐hGH), produced by the expression of genomic hGH in a mammalian cell line, were studied in six healthy young men who were administered 0.2 U/kg/day subcutaneously for five consecutive days. Changes in sodium balance and in thyroid function were studied during the week of bio‐hGH administration and safety parameters were monitored over a 3‐week period. Growth hormone levels reached a mean (±SD) peak of 106 ± 10 mIU/1 at 3.3 ± 0.5 h following the first dose and resulted in a significant rise of somatomedin C, free fatty acids, fasting blood glucose and insulin concentrations. Bio‐hGH administration resulted in a significant increase in body weight (80.0± 4.5 to 81.1 ± 4.3 kg; P &lt;0.01) which was associated with a marked reduction in urinary sodium excretion (196 ± 38 to 45 ± 20 mmol/day; P &lt;0.025). Serum T3 increased during bio‐hGH administration and was asssociated with reciprocal changes in free thyroxine and TSH concentrations. Cardiac, hepatic, renal, biochemical, haematological, endocrinological and immunological functions remained normal throughout the study. No antibodies to hGH or to host cell protein developed during the study. The results show that bio‐hGH is safe in the short term, well tolerated, possesses pharmacokinetic and biological properties similar to pituitary hGH, and has distinct effects on sodium balance and on thyroid function. This study stresses the need to monitor patients for effects on sodium retention, carbohydrate metabolism and thyroid function when using hGH doses of 1.0 U/kg/week (40U/m 2 /week) or more in patients with GH responsive short stature.
Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line (1993)

Previous studies have shown that the bcl-2 gene encodes a mitochondrial protein that contributes to neoplastic cell expansion primarily by promoting cell survival through interference with "programmed cell death" (PCD), also termed "apoptosis." Because many chemotherapeutic drugs are capable of initiating pathways leading to apoptosis, we determined whether deregulated bcl-2 expression could render cells resistant to several drugs commonly used in the treatment of non-Hodgkin's lymphomas, including dexamethasone (DEX), methotrexate (MTX), 1-beta-D-arabinofuranosyl-cytosine (Ara-C), etoposide (VP-16), vincristine (VC), cisplatin (CP), and hydroperoxycyclophosphamide (4-HC). For these experiments, we achieved high levels of p26-Bcl-2 protein production in a human pre-B-cell leukemia line 697 by stable infection with a recombinant bcl-2-containing retrovirus and then compared these cells with control virus-infected 697 cells. Control 697 cells were induced to undergo apoptosis by all drugs tested as defined by DNA degradation into oligonucleosomal-length fragments, cell shrinkage, and subsequent cell death. In contrast, 697 cells with elevated Bcl-2 protein levels exhibited strikingly prolonged cell survival and markedly reduced DNA fragmentation when cultured in the presence of these antineoplastic agents. Although high levels of Bcl-2 protein protected 697 cells from the acute cytotoxic effects of DEX and the other drugs tested, Bcl-2 did not prevent these drugs from suppressing the proliferation of 697 cells. However, when 697 cells were treated with DEX or MTX for 3 days, then washed and cultured in semisolid media without drugs, bcl-2-virus-infected cells gave rise to colonies at much higher frequencies than 697 cells stably infected with control virus. These results indicate that by protecting 697 leukemic cells from the acute cytotoxicity of DEX and some other chemotherapeutic drugs, high levels of p26-Bcl-2 can create the opportunity for re-initiation of cell growth when drugs are withdrawn. The findings may be relevant to clinical correlative studies of non-Hodgkin's lymphoma patients that have found an association between worse prognosis and bcl-2 gene rearrangements or t[14;18] translocations.
SELECTIN-CARBOHYDRATE INTERACTIONS AND THE INITIATION OF THE INFLAMMATORY RESPONSE (1995)

The orderly migration of various white blood cell types to inflammatory sites is a highly regulated process that involves a diversity of adhesion and signaling molecules. This cellular influx is initiated by relatively low affinity interactions that allow for leukocytes to roll along the vascular surface. This rolling phenomenon is mediated by adhesive interactions between lectin containing adhesion molecules, termed selectins, on both the vascular endothelium and leukocytes, and carbohydrate ligands immobilized on mucin-like scaffolds. This adhesion allows for a rapid recognition of various cell types under the conditions of vascular flow, with the result that inflammatory cells are specifically decelerated adjacent to sites of inflammation. This review focuses on the various biochemical aspects of the interactions between the selectins and their cognate carbohydrate ligands, with an emphasis on the importance of these adhesive events to the inflammatory response.
Effect of recombinant human interferon-alpha A/D on in vivo murine tumor cell growth. (1988)

We investigated the effect of human recombinant interferon-alpha A/D A/D-IFN), which is known to delay the growth of murine tumor cells, on the growth of S1 and R1 subline cells of murine Meth A fibrosarcoma in the peritoneal cavity of mice. In vitro growth of S1 cells was sensitive to, and that of R1 cells was resistant to, the direct effect of A/D-IFN, as with murine natural IFN-alpha/beta, which was used originally to isolate these sublines. In vivo, however, the growth of not only S1 cells but also R1 cells was suppressed by the administration of A/D-IFN, and the survival time of tumor-bearing mice was prolonged. Although A/D-IFN had a direct effect on S1 cells in vivo, R1 cells were susceptible only to the indirect effect via the host cells. Macrophages (M phi) harvested from the peritoneal cavity of A/D-IFN-treated mice bearing ascitic R1 cells were very effective in suppressing the in vitro growth of R1 cells; those from non-R1-bearing A/D-IFN-treated mice were less effective. The results of in vitro experiments indicate that M phi are very probably activated by the synergism of A/D-IFN and M phi diameter-activating factor(s) produced by lymphoid cells in tumor-bearing mice.
Inactivation of the mouse sperm receptor, mZP3, by site-directed mutagenesis of individual serine residues located at the combining site for sperm (1998)

To initiate fertilization, mouse sperm bind to Ser- (O-) linked oligosaccharides located at the sperm combining site of zona pellucida glycoprotein mZP3. Apparently, the oligosaccharides are present on one or more of five Ser residues clustered in the carboxyl-terminal region of the mZP3 polypeptide. Here, each of the Ser residues, as well as an intervening Asn residue, was converted to a small, nonhydroxy amino acid by site-directed mutagenesis. Mouse embryonal carcinoma (EC) cells were then stably transfected with the wild-type and mutated mZP3 genes. In each case, transfected cells synthesized and secreted recombinant EC-mZP3 into the culture medium. The glycoproteins were partially purified and assayed for their ability to inhibit binding of sperm to ovulated eggs in vitro. As compared with wild-type EC-mZP3, mutations of Ser-329, Ser-331, or Ser-333 had no effect on sperm receptor activity. Mutation of Asn-330, a potential N-linked glycosylation site, also had no effect on sperm receptor activity. On the other hand, mutation of either Ser-332 or Ser-334, or mutation of Ser-332, Ser-333, and Ser-334, resulted in complete inactivation of EC-mZP3 as a sperm receptor. These results suggest that Ser-332 and Ser-334, residues conserved in mouse, hamster, and human ZP3, are essential for sperm receptor activity.
Megabase-Scale Mapping of the HLA Gene Complex by Pulsed Field Gel Electrophoresis (1987)

In the study of the genetic structure of mammalian chromosomes, there exists a "resolution gap" between molecular cloning experiments and meiotic linkage analyses. This gap has discouraged attempts to construct full-scale genetic maps of mammalian chromosomes. The organization of the human major histocompatibility complex was examined within this range by pulsed field gel electrophoresis. The data obtained indicate that the complex spans over 3000 kilobases and enable the construction of a megabase-scale molecular map. These results indicate that the techniques employed in DNA extraction, enzymatic digestion, electrophoresis, and hybridization are suitable for the efficient analysis of megabase regions of mammalian chromosomes and effectively bridge the resolution gap between molecular cloning and classical genetics.
In vitro synergistic activity between bismuth subcitrate and various antimicrobial agents against Campylobacter pyloridis (C. pylori) (1987)

The in vitro interactions between bismuth subcitrate and a variety of antimicrobial agents against 12 Campylobacter pyloridis (C. pylori) isolates were studied by the agar dilution checkerboard technique. The combination of bismuth subcitrate with the older quinolone, oxolinic acid, produced synergistic activity against all strains. This observation, however, could not be extended to the (aryl) fluoroquinolones, norfloxacin, ofloxacin, and difloxacin, since synergy was rare or absent when bismuth subcitrate was combined with these antibiotics. Among the other antimicrobial agents tested, rifampin and the beta-lactams frequently showed showed MICs for C. pyloridis similar to those of bismuth subcitrate.
MECHANOSENSITIVE CHANNELS OFESCHERICHIA COLI:The MscL Gene, Protein, and Activities (1997)

Although mechanosensory responses are ubiquitous and diverse, the molecular bases of mechanosensation in most cases remain mysterious MscL, a mechanosensitive channel of large conductance of Escherichia coli and its bacterial homologues are the first and currently only channel molecules shown to directly sense mechanical stretch of the membrane. In response to the tension conveyed via the lipid bilayer, MscL increases its open probability by several orders of magnitude. In the present review we describe the identification, cloning, and first sets of biophysical and structural data on this simplest mechanosensory molecule. We discovered a 2.5-ns mechanosensitive conductance in giant E. coli spheroplasts. Using chromatographies to enrich the target and patch clamp to assay the channel activity in liposome-reconstituted fractions, we identified the MscL protein and cloned the mscL gene. MscL comprises 136 amino acid residues (15 kDa), with two highly hydrophobic regions, and resides in the inner membrane of the bacterium. PhoA-fusion experiments indicate that the protein spans the membrane twice with both termini in the cytoplasm. Spectroscopic techniques show that it is highly helical. Expression of MscL tandems and covalent cross-linking suggest that the active channel complex is a homo-hexamer. We have identified several residues, which when deleted or substituted, affect channel kinetics or mechanosensitivity. Although unique when discovered, highly conserved MscL homologues in both gram-negative and gram-positive bacteria have been found, suggesting their ubiquitous importance among bacteria.
Oxidative stress: the role of cytochromes P450 in oxygen activation (2002)

Abstract Oxidative stress is associated with a number of degenerative disease states, such as cancer and AIDS. Fundamental to oxidative stress is the generation of superoxide, peroxide and other reactive oxygen species (ROS). This review focuses on the importance of cytochrome P450 (CYP) enzymes in the activation of oxygen and ROS generation, together with a discussion of defence mechanisms which can offer protection against oxidative stress. © 2002 Society of Chemical Industry.
Analysis of Interpenetrating Polymer Networks via Quartz Crystal Microbalance with Dissipation Monitoring (2005)

A quartz crystal microbalance with dissipation monitoring (QCM-D) was used to assess the physical properties of interpenetrating polymer networks (IPNs) through swelling experiments in ambient humidity and in phosphate-buffered saline (PBS), pH 7.4. The IPNs, based on acrylamide (AAm) and poly(ethylene glycol) (pEG), swell from thin, rigid films when dry (16.7 +/- 5.2 nm on Si/SiO(2)) to expanded, viscoelastic films when hydrated (107 +/- 24.2 nm on Si/SiO2). The dry IPNs could be analyzed using the Sauerbrey relationship, but for the hydrated films it was necessary to interpret QCM-D data with a Kelvin-Voigt viscoelastic model. A complex modulus |G| of 116 +/- 38.1 kPa for the swollen IPN surface on Si/SiO2 was defined by the model. The QCM-D was also employed to quantify the adsorption of human fibrinogen, a protein important in thrombus formation, onto the IPNs. Fibrinogen adsorption studies demonstrated the sensitivity of the QCM-D, as well as confirmed the nonfouling nature of the IPN surface, where less than 5 ng/cm2 of fibrinogen was adsorbed.