gebhart/patrepeval huggingface dataset:
Exological relationships of bacteria involved in a simple, mixed anaerobic infection (1980)

Infectivity of Bacteroides asaccharolyticus (formerly B. melaninogenicus subsp. asaccharolyticus; see S. M. Finegold and E. M. Barnes, Int. J. Syst. Bacteriol. 27:388--391, 1977) was dependent on the presence of a second organism. An infective consortium consisting of B. asaccharolyticus and Klebsiella pneumoniae was defined. Neither organism was infective alone, but the Klebsiella could be replaced by organisms of a number of different genera. The nature of the infection appeared to be determined by the length of the lag period preceding the initiation of growth of B. asaccharolyticus. A rapid onset of growth led to the severe spreading form of the disease, whereas a slow initiation of growth resulted in the formation of a localized, self-limiting abscess. B. asaccharolyticus depends on the second or "helper" organism to produce a required growth factor which is not present at the inoculation site. The growth factor was shown to be succinate which was able to replace the hemin requirement. The dependency on succinate produced by K. pneumoniae was demonstrated in agar medium, in liquid culture, and in the infectivity assay. Any organism which produced succinate was able to stimulate growth of B. asaccharolyticus on agar medium and could replace K. pneumoniae as a member of the infectious consortium. The need for the second organism could be eliminated by inoculating B. asaccharolyticus together with agar-immobilized succinate or hemin.
Molecular genetic basis of familial ALS (1996)

Familial amytrophic lateral sclerosis (FALS) is transmitted in a mendelian fashion as an autosomal dominant (DFALS) or an autosomal recessive (RFALS) trait. Both DFALS and RFALS are genetically heterogeneous. Fifteen percent of DFALS families have mutations in the gene for Cu, Zn superoxide dismutase (SOD1) which is coded on chromosome 21. The locus for one form of RFALS maps to chromosome 2q33. Forty-six mutations in the SOD1 gene have been reported in DFALS families. These mutations result in decreased SOD1 activity and shortened half-life of the protein in most instances. Transgenic mice overexpressing mutated SOD1 protein develop an ALS-like disease which suggests that the degeneration of motor neurons in DFALS is caused by the gain of a novel toxic function by mutated SOD1 rather than by the decrease of SOD1 activity. Several possible mechanisms of the novel neurotoxic function of mutated SOD1 are discussed.
Genetic Programming III: Darwinian Invention and Problem Solving (1999)

From the Publisher:
Genetic programming (GP) is a method for getting a computer to solve a problem by telling it what needs to be done instead of how to do it. Koza, Bennett, Andre, and Keane present genetically evolved solutions to dozens of problems of design, control, classification, system identification, and computational molecular biology. Among the solutions are 14 results competitive with human-produced results, including 10 rediscoveries of previously patented inventions.
Induction of the heat shock regulon does not produce thermotolerance in Escherichia coli. (1987)

The addition of isopropyl thio-beta-D-galactoside (IPTG) to Escherichia coli cells containing multiple copies of the heat shock regulatory gene htpR (rpoH) under the control of an IPTG-inducible promoter (P-tac) induced 15 of the 17 polypeptides of the heat shock (HTP) regulon. The time course and magnitude of the induction closely resembled that caused by a shift to 42 degrees C. Nevertheless the two means of inducing the heat shock regulon differed in outcome. Cultures grown at 28 degrees C and induced by incubation at 42 degrees C for 15 min gave significant protection against a challenge temperature of 50 degrees C, but no protection was afforded by a 15-min IPTG treatment at 28 degrees C. It could be shown that there was no interference by IPTG with the development of thermotolerance at 42 degrees C. Also, treatment of a wild strain of E. coli with various toxic agents revealed no correlation between the development of thermotolerance and the induction of any subset of the heat shock proteins. Thermotolerance appears to develop by processes other than the htpR-dependent induction of heat shock proteins.
Distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP (2003)

How lipopolysaccharide (LPS) signals through toll-like receptors (TLRs) to induce nuclear factor (NF)-kappa B inflammatory cytokines in sepsis remains unclear. Major candidates for that process are myeloid differentiation protein 88 (MyD88) and MyD88 adaptor-like/TIR domain-containing adaptor protein (Mal/TIRAP) but their role needs to be further defined. Here, we have examined the role of MyD88 and Mal/TIRAP in primary human cells of nonmyeloid and myeloid origin as physiologically relevant systems. We found that MyD88 and Mal/TIRAP are essential for LPS-induced I kappa B alpha phosphorylation, NF-kappa B activation, and interleukin 6 (IL-6) or IL-8 production in fibroblasts and endothelial cells in a pathway that also requires IKK2. In contrast, in macrophages neither MyD88, Mal/TIRAP, nor I kappa B kinase 2 (IKK2) are required for NF-kappa B activation or tumor necrosis factor alpha (TNF alpha), IL-6, or IL-8 production, although Mal/TIRAP is still involved in the production of interferon beta (IFN beta). Differential usage of TLRs may account for that, as in macrophages but not fibroblasts or endothelial cells, TLR4 is expressed in high levels at the cell surface, and neutralization of TLR4 but not TLR2 blocks LPS signaling. These observations demonstrate for the first time the existence of 2 distinct pathways of LPS-induced NF-kappa B activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of TLR4, MyD88, Mal/TIRAP, and IKK2, and reveal a layer of complexity not previously expected.
Mapping of DNA markers close to the fraglle site on the human X chromosome at Xq25–3 (1987)

We report the identification of a new RFLP detected by the DNA probe MN12, which is linked to both the fragile site on the X chromosome at Xq27.3 and the highly polymorphic locus detected by St14 (DXS52). In situ mapping confirms the localisation of MN12 distal to the fragile site. A detailed physical analysis of this region of the X chromosome using pulsed-field gel electrophoresis has shown that MN12, St14 and DX13 (DXS15) are physically linked within a region of 470kb. A long range restriction map around the MN12 locus reveals at least two candidate HTF islands, suggesting the existence of expressed sequences in this region.
Analysis of glycosaminoglycan‐derived disaccharides in biologic samples by capillary electrophoresis and protocol for sequencing glycosaminoglycans (2002)

Glycosaminoglycans are biologically significant carbohydrates which either as free chains (hyaluronan) or constituents of proteoglycans (chondroitin/dermatan sulfates, heparin, heparan sulfate and keratan sulfate) participate and regulate several cellular events and (patho)physiological processes. Capillary electrophoresis, due to its high resolving power and sensitivity, has been successfully used for the analysis of glycosaminoglycans. Determination of compositional characteristics, such as disaccharide sulfation pattern, is a useful prerequisite for elucidating the interactions of glycosaminoglycans with matrix effective molecules and, therefore, essential in understanding the biological functions of proteoglycans. The interest in the field of characterization of such biologically important carbohydrates is soaring and advances in this field will signal a new revolution in the area of glycomics equivalent to that of genomics and proteomics. This review focuses on the capillary electrophoresis methods used to determine the disaccharide pattern of glycosaminoglycans in various biologic samples as well as advances in the sequence analysis of glycosaminoglycans using both chromatographic and electrophoretic techniques.
The Risk Associated with Aprotinin in Cardiac Surgery (2006)

The association between aprotinin and serious end-organ damage indicates that continued use is not prudent. In contrast, the less expensive generic medications aminocaproic acid and tranexamic acid are safe alternatives.
Expression of the antiproliferative gene TIS21 at the onset of neurogenesis identifies single neuroepithelial cells that switch from proliferative to neuron-generating division (1999)

At the onset of mammalian neurogenesis, neuroepithelial (NE) cells switch from proliferative to neuron-generating divisions. Understanding the molecular basis of this switch requires the ability to distinguish between these two types of division. Here we show that in the mouse ventricular zone, expression of the mRNA of the antiproliferative gene TIS21 (PC3, BTG2) (i) starts at the onset of neurogenesis, (ii) is confined to a subpopulation of NE cells that increases in correlation with the progression of neurogenesis, and (iii) is not detected in newborn neurons. Expression of the TIS21 mRNA in the NE cells occurs transiently during the cell cycle, i.e., in the G1 phase. In contrast to the TIS21 mRNA, the TIS21 protein persists through the division of NE cells and is inherited by the neurons, where it remains detectable during neuronal migration and the initial phase of differentiation. Our observations indicate that the TIS21 gene is specifically expressed in those NE cells that, at their next division, will generate postmitotic neurons, but not in proliferating NE cells. Using TIS21 as a marker, we find that the switch from proliferative to neuron-generating divisions is initiated in single NE cells rather than in synchronized neighboring cells.
Defining the cell lineages of the islets of Langerhans using transgenic mice (2002)

In this Special Issue of the Int. J. Dev. Biol., we summarize our own studies on the development of the mouse endocrine pancreas, with special emphasis on the cell lineage relationships between the four islet cell types. Considerable knowledge concerning the ontogeny of the endocrine pancreas has been gained in recent years, mainly through the use of two complementary genetic approaches in mice: gene inactivation and genetic labelling of precursor cells. However, neither gene inactivation in KO mice nor co-localisation of hormones in single cells during development can be taken as evidence for cell lineage relationships among different cell types. The beta-cell lineage analysis was started by selectively ablating specific islet cell types in transgenic mice. We used the diphtheria toxin A subunit coding region under the control of insulin, glucagon or pancreatic polypeptide (PP) promoters, in order to eliminate insulin-, glucagon- or PP-expressing cells, respectively. Contrary to the common view, we demonstrated that glucagon cells are not precursors of insulin-producing cells. These results were in addition the first evidence of a close ontogenetic relationship between insulin and somatostatin cells. We pursued these analyses using a novel, more subtle approach: progenitor cell labelling through the expression of Cre recombinase in doubly transgenic mice. We were able to unequivocally establish that 1) adult glucagon- and insulin-producing cells derive from precursors which have never transcribed insulin or glucagon, respectively; 2) insulin cell progenitors, but not glucagon cell progenitors transcribe the PP gene and 3) adult glucagon cells derive from progenitors which do express pdx1.
Small molecule inhibitors of divalent metal transporter-1 (2009)

Divalent metal transporter-1 (DMT1) is a divalent cation transporter that plays a key role in iron metabolism by mediating ferrous iron uptake across the small intestine. We have previously identified several small molecule inhibitors of iron uptake (4). Using a cell line that stably overexpresses DMT1, we screened the ability of these inhibitors to specifically block this transporter's activity. One compound, NSC306711, inhibited DMT1-mediated iron uptake in a reversible and competitive manner. This inhibitor is a polysulfonated dye containing two copper centers. Although one of these two sites could be chelated by Triethylenetetramine copper chelation did not perturb NSC306711 inhibition of DMT1 activity. Several other polysulfonated dyes with structural features similar to NSC306711 were identified as potential DMT1 transport inhibitors. This study characterizes important pharmacological tools that can be used to probe DMT1's mechanism of iron transport and its role in iron metabolism.
Continuous-Flow, Rapid Lysis Devices for Biodefense Nucleic Acid Diagnostic Systems (2009)

Two mechanical lysis devices have been developed as compact, robust components to provide rapid sample preparation for nucleic acid diagnostic systems. One such component, known as the Micro Bead-Beater™ (μBB™, BBTM, Claremont BioSolutions, Upland, CA), is a compact device that is capable of ultrarapid lysis (&gt;90% lysis in 30 s) of micro volumes (&lt;80 μL) of Bacillus spores in a continuous-flow format or in a disposable single-tube format. The μBB is also capable of processing much larger volumes of solutions containing spores or vegetative cells using a continuous-flow mode. A second mechanical lysis device designed as a disposable component is the microfluidic bead blender, which uses a small electric motor to spin vanes within the bead-laden solution. DNA quantification results using dsDNA-binding fluorescence dyes and real-time PCR are presented, comparing the lysis of Bacillus subtilis spores using the μBB™ with other well-known lysis techniques. Nanoscale imaging results obtained using scanning electron microscopy and transmission electron microscopy on B. subtilis spores lyzed using the μBB™ are also presented
THe genetics of familial breast cancer. (1996)

Because studies of breast cancer patients and their relatives provide statistical evidence for involvement of autosomal dominant genes, the identification of specific genetic effects has long been the focus of efforts to identify women at exceedingly high risk. BRCA1, a gene that confers greatly increased susceptibility to breast and ovarian cancer, was isolated in 1994, capping an intense analysis by a large number of groups of a complex phenotype. BRCA1 is a large gene and shows only limited homology to other known genes. Near the amino terminus of the predicted protein is a RING finger motif. In addition, a leucine heptad repeat appears in the interior of the sequence. Several groups have looked extensively for somatic BRCAI mutations in breast and ovarian tumors. The frequency of somatic mutations in ovarian tumors is low, and to date no somatic mutations have been found in breast tumors. More research is needed to define the role of BRCA1 in sporadic tumors. A second locus associated with predisposition to early onset breast cancer, BRCA2, has been localized to chromosome 13q. Positional cloning of this gene is well advanced and analysis of its biology and mutation spectrum is eagerly awaited. As the BRCA1 and BRCA2 genes are characterized further, a diagnostic test for breast cancer susceptibility becomes feasible.
On location-restricted services (1999)

Monitoring the location of user equipment is an important problem in many industries, including direct broadcasting satellites and others, where the physical location of the user determines the availability of the service or is crucial for the security or operation of the service. In this article we study four schemes for detecting the movement of user equipment, such as a set-top terminal, wireless local loop (fixed wireless) phones, and other "nonmovable" equipment, using existing (or emerging) communication infrastructures. The first two schemes are network-centric, which means that the network infrastructure determines the location. The two other schemes are terminal-centric, which means that they rely on the user's device. We start with the currently used scheme, which is based on the telephone network's caller ID features, and show how it can be undermined. Then we describe three more robust schemes: one that uses the cellular phone's enhanced 911 service, one that uses the Global Positioning System, and one that measures the time-difference-of-arrival of the satellite's broadcast. We discuss the accuracy, features, and vulnerabilities of each scheme. We also present possible attacks on these schemes that allow the attackers to conceal their movement, and evaluate the complexity and cost of the attacks.
IOIBD technical review on endoscopic indices for Crohn's disease clinical trials (2015)

At the end of the voting process, the investigators ranked first a >50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) or Crohn's Disease Endoscopic Index of Severity for the definition of endoscopic response, and an SES-CD 0-2 for the definition of endoscopic remission in CD. All experts agreed on a Rutgeerts' score i0-i1 for the definition of endoscopic remission after surgery.
Khafrefungin, a Novel Inhibitor of Sphingolipid Synthesis (1997)

In the course of screening for antifungal agents we have discovered a novel compound isolated from an endophytic fungus that inhibits fungal sphingolipid synthesis. Khafrefungin, which is composed of aldonic acid linked via an ester to a C22 modified alkyl chain, has fungicidal activity against Candida albicans, Cryptococcus neoformans, and Saccharomyces cerevisiae. Sphingolipid synthesis is inhibited in these organisms at the step in which phosphoinositol is transferred to ceramide, resulting in accumulation of ceramide and loss of all of the complex sphingolipids. In vitro, khafrefungin inhibits the inositol phosphoceramide synthase of C. albicans with an IC50 of 0.6 nM. Khafrefungin does not inhibit the synthesis of mammalian sphingolipids thus making this the first reported compound that is specific for the fungal pathway.
Modulation of the trans-suppression activity of hepatitis C virus core protein by phosphorylation (1995)

We previously demonstrated that the core protein of hepatitis C virus (HCV) can suppress gene expression and replication of hepatitis B virus (HBV) in a human hepatoma cell line (HuH-7). In this study, we have characterized the phosphorylation property of HCV core protein and examined the effect of phosphorylation on its suppressive activity of HBV. Our results indicated that both the full-length HCV core protein (22 kDa) and its processed or degraded forms (14 to 18 kDa) were phosphorylated in insect cells. As demonstrated by using the glutathione S-transferase fusion protein expression system and in vitro transcription and translation system, the phosphorylation of HCV core protein was carried out by protein kinase A (PKA) and protein kinase C (PKC) in vitro. In both kinase reactions, it was determined that the phosphorylated amino acid was a serine residue. The potential phosphorylated sites in core protein were identified as residues Ser-53 and Ser-116 for PKA and Ser-53 and Ser-99 for PKC. Comparison of the phosphorylation intensities of the wild type and Ser mutants suggested that Ser-99 and Ser-116 were the major phosphorylation sites for PKC and PKA, respectively. The phosphorylation of Ser-99 and Ser-116, but not Ser-53, in HCV core protein was essential for the suppressive activity of HCV core protein on HBV gene expression and replication in HuH-7 cells. Mutation of the former two serine residues to alanine or aspartate residues led to a drastic loss of the inhibitory effects of HCV core protein on HBV gene expression (both transcription and antigen production) and pregenomic RNA encapsidation, as well as the release of HBV virus particles. In contrast, the Ser-53 mutant conferred the same level of suppressive activity as the wild type did. This property is in accordance with the observation that Ser-99 and Ser-116 are the predominant phosphorylation sites in the HCV core construct. All serine mutants (including those with mutations in PKA, PKC, and both kinase recognition sites) of HCV core protein retained the ability to translocate into the nucleus. Furthermore, wild-type HCV core protein diminished its suppressive activity when cells were treated with PKA or PKC inhibitor. In conclusion, HCV core protein is a phospho-protein and in HuH-7 cells, its trans suppression of HBV gene expression and replication is positively regulated by PKA and PKC. The role of phosphorylation in the control of trans-suppressive activity cannot be reproduced by introducing an acidic residue.(ABSTRACT TRUNCATED AT 250 WORDS)
Capillarization of the Hypertrophic Heart (1991)

The geometry of capillary networks was examined in pressure-overloaded hypertrophic rat myocardium. All hearts were exposed to a staining protocol that distinguished the arteriolar (AC) and venular (VC) regions of capillaries. In control hearts, the triangulation method (one-dimensional distance between neighboring capillaries) and the domain method (two-dimensional area surrounding capillaries) exhibited similar results, showing increased capillarization for the venular region of capillaries networks. In hypertrophic hearts, the triangulation method did not demonstrate differences between arteriolar and venular capillaries (AC = 27.2 +/- 0.4 microns, VC = 27.0 +/- 0.2 microns, p = 0.56). However, the domain method still detected smaller tissue supply regions for venular capillaries (AC = 547 +/- 6 microns 2, VC = 464 +/- 5 microns 2, p less than 0.01). To resolve this discrepancy in hypertrophic heart, we have measured capillary spacing from longitudinal sections at discrete intervals along the A-V path length. These results indicate a stepwise decrease in intercapillary distance from arteriole to venule for both groups, which would support results obtained by the domain method. A possible explanation for the discrepancy between these two methods, specific to hypertrophic heart, may be changes in the clustering patterns of arteriolar and venular capillaries.
High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients (2015)

According to our results, patients with high MACC1 expression and mutated KRAS G13 exhibited the highest risk for metachronous metastases formation. Moreover, we demonstrated that the "Traditional pathway" with an intermediate risk for metastasis formation can be further subdivided by assessing MACC1 expression into a low and high risk group with regard to MFS prognosis. This is the first report showing that identification of CRC patients at high risk for metastasis is possible by assessing MACC1 expression in combination with KRAS G13 mutation.
In vitro fertilization (IVF): a review of 3 decades of clinical innovation and technological advancement (2006)

In vitro fertilization, popularly referred to as IVF, has captured the attention of the public since its sensational introduction in 1978. Today assisted reproductive technology is available throughout most of the civilized world, and the practice is largely different from that used during the early days. Refinements in laboratory technology and clinical practice have allowed IVF to evolve into a medical procedure that is efficient, safe, readily accessible, and relatively affordable. More than 2 million IVF children have been born to date, and it is likely that continued enhancements will widen its appeal and applicability.