gebhart/patrepeval huggingface dataset:
Localized Synchrotron Irradiation of Mouse Skin Induces Persistent Systemic Genotoxic and Immune Responses (2017)

The importance of nontargeted (systemic) effects of ionizing radiation is attracting increasing attention. Exploiting synchrotron radiation generated by the Imaging and Medical Beamline at the Australian Synchrotron, we studied radiation-induced nontargeted effects in C57BL/6 mice. Mice were locally irradiated with a synchrotron X-ray broad beam and a multiplanar microbeam radiotherapy beam. To assess the influence of the beam configurations and variations in peak dose and irradiated area in the response of normal tissues outside the irradiated field at 1 and 4 days after irradiation, we monitored oxidatively induced clustered DNA lesions (OCDL), DNA double-strand breaks (DSB), apoptosis, and the local and systemic immune responses. All radiation settings induced pronounced persistent systemic effects in mice, which resulted from even short exposures of a small irradiated area. OCDLs were elevated in a wide variety of unirradiated normal tissues. In out-of-field duodenum, there was a trend for elevated apoptotic cell death under most irradiation conditions; however, DSBs were elevated only after exposure to lower doses. These genotoxic events were accompanied by changes in plasma concentrations of macrophage-derived cytokine, eotaxin, IL10, TIMP1, VEGF, TGFβ1, and TGFβ2, along with changes in tissues in frequencies of macrophages, neutrophils, and T lymphocytes. Overall, our findings have implications for the planning of therapeutic and diagnostic radiation treatments to reduce the risk of radiation-related adverse systemic effects. <i>Cancer Res; 77(22); 6389-99. ©2017 AACR</i>.
Free-Breathing Radial 3D Fat-Suppressed T1-Weighted Gradient Echo Sequence (2011)

: Radial VIBE can be performed during free breathing for contrast-enhanced imaging of the liver with comparable image quality to BH VIBE. However, further work is necessary to shorten the acquisition time to perform dynamic imaging.
A rapid and efficient method for site-directed mutagenesis using one- step overlap extension PCR (1997)

A rapid method is described to efficiently perform site-directed mutagenesis based on overlap extension polymerase chain reaction (OE-PCR). Two template DNA molecules in different orientations relative to only one universal primer were amplified in parallel. By choosing a high dilution of mutagenic primers it was possible to run an overlap extension PCR in only one reaction without purification of intermediate products. This method which we have named one-step overlap extension PCR (OOE-PCR) can in principle be applied to every DNA fragment which can be cloned into a multiple cloning site of any common cloning vector.
Vaccines for the Prevention of Human Cytomegalovirus Infection (1990)

The status of vaccination against cytomegalovirus (CMV) at the end of 1988 was as follows: (1) The Towne live attenuated vaccine produces humoral and cellular immune responses without viral excretion or demonstrated latency. (2) The Towne vaccine partially protects seronegative renal transplant recipients from severe CMV disease but does not prevent them from getting infected. (3) In healthy subjects the live vaccine is also protective, but protection is related to challenge dose. Vaccine-derived immunity is equivalent to natural immunity for prevention of disease but at higher challenge doses is less protective for prevention of infection. (4) The viral envelope contains proteins that can stimulate humoral and cellular immune responses, although it is not yet clear whether the responses are as protective as those following infection. (5) One glycoprotein of the envelope, the 55-58K protein, can stimulate the same responses. If large amounts of this protein can be produced by molecular biologic techniques, this protein might be used as a subunit vaccine. (6) Target groups for vaccination would include seronegative healthy women and seronegative or seropositive recipients of solid organ transplants.
Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity (2014)

T cell activation is regulated by the interactions of surface receptors with stimulatory and inhibitory ligands. Programmed death-1 homolog (PD-1H, also called VISTA) is a member of the CD28 family of proteins and has been shown to act as a coinhibitory ligand on APCs that suppress T cell responses. Here, we determined that PD-1H functions as a coinhibitory receptor for CD4⁺ T cells. CD4⁺ T cells in mice lacking PD-1H exhibited a dramatically increased response to antigen stimulation. Furthermore, delivery of a PD-1H-specific agonist mAb directly inhibited CD4⁺ T cell activation both in vitro and in vivo, validating a coinhibitory function of PD-1H. In a murine model of acute hepatitis, administration of a PD-1H agonist mAb suppressed CD4⁺ T cell-mediated acute inflammation. PD-1H-deficient animals were highly resistant to tumor induction in a murine brain glioma model, and depletion of CD4⁺ T cells, but not CD8⁺ T cells, promoted tumor formation. Together, our findings suggest that PD-1H has potential as a target of immune modulation in the treatment of human inflammation and malignancies.
Increased Lipid Accumulation in the Chlamydomonas reinhardtii sta7-10 Starchless Isoamylase Mutant and Increased Carbohydrate Synthesis in Complemented Strains (2010)

The accumulation of bioenergy carriers was assessed in two starchless mutants of Chlamydomonas reinhardtii (the sta6 [ADP-glucose pyrophosphorylase] and sta7-10 [isoamylase] mutants), a control strain (CC124), and two complemented strains of the sta7-10 mutant. The results indicate that the genetic blockage of starch synthesis in the sta6 and sta7-10 mutants increases the accumulation of lipids on a cellular basis during nitrogen deprivation relative to that in the CC124 control as determined by conversion to fatty acid methyl esters. However, this increased level of lipid accumulation is energetically insufficient to completely offset the loss of cellular starch that is synthesized by CC124 during nitrogen deprivation. We therefore investigated acetate utilization and O(2) evolution to obtain further insights into the physiological adjustments utilized by the two starchless mutants in the absence of starch synthesis. The results demonstrate that both starchless mutants metabolize less acetate and have more severely attenuated levels of photosynthetic O(2) evolution than CC124, indicating that a decrease in overall anabolic processes is a significant physiological response in the starchless mutants during nitrogen deprivation. Interestingly, two independent sta7-10:STA7 complemented strains exhibited significantly greater quantities of cellular starch and lipid than CC124 during acclimation to nitrogen deprivation. Moreover, the complemented strains synthesized significant quantities of starch even when cultured in nutrient-replete medium.
Quasiparticle band structures of short-period superlattices and ordered alloys of AlN and GaN (1994)

Quasiparticle band structures of short-period superlattices and ordered alloys of AlN and GaN are calculated using the GW approximation. The calculated gaps range from 3.1 eV to 5.8 eV. Two types of structural materials are studied: zinc-blende superlattices in the (111) direction and hexagonal wurtzite superlattices and ordered alloys in the (001) direction. Comparisons between band structures of these materials using folding of Brillouin zone points and the transition from an indirect to direct gap semiconductor in the zinc-blende compounds are discussed. All of the wurtzite structures studied are found to have direct band gaps with values between 3.5 and 5.8 eV. The 1\ifmmode\times\else\texttimes\fi{}1 and 1\ifmmode\times\else\texttimes\fi{}2 AlN/GaN zinc-blende superlattices have direct gaps of 4.4 eV and 4.3 eV, respectively, whereas the 2\ifmmode\times\else\texttimes\fi{}1 AlN/GaN superlattice gap is 4.6 eV and is indirect. Several fundamental gaps are predicted and remain to be tested by experiment.
[Stromal bone marrow cells and the hematopoietic microenvironment]. (1982)

Stromal clonogenic fibroblasts of the bone marrow possessing osteogenic potential are responsible for hemopoietic bone marrow microenvironment. These cells may be recovered from the bone marrow by cloning in cell cultures; their progeny cells upon retransplantation into the body form new bone marrow organs. Microenvironmental cells are histogenetically independent of hemopoietic cells. In bone marrow cell suspensions prepared by bone marrow tissues trypsinization stromal clonogenic cells are present in greater concentrations than in those prepared by mechanical mincing of the bone marrow tissue. New ectopic bone marrow organs may be created by transplantation of trypsinized suspensions in porous sponges.
Generation of osteoclast-inductive and osteoclastogenic cell lines from the H-2KbtsA58 transgenic mouse. (1993)

The development of osteoclastic cell lines would greatly facilitate analysis of the cellular and molecular biology of bone resorption. Several cell lines have previously been reported to be capable of osteoclastic differentiation. However, such cell lines form at best only occasional excavations, suggesting that osteoclastic differentiation is either incomplete or that osteoclasts represent a very small proportion of the cells present. We have used the recently developed H-2KbtsA58 transgenic mouse, in which the interferon-inducible major mouse histocompatibility complex H-2Kb promoter drives the temperature-sensitive (ts) immortalizing gene of simian virus 40 (tsA58), to develop cell lines from bone marrow with high efficiency. Bone marrow cells were incubated with gamma interferon at 33 degrees C, then cloned, and expanded. The cell lines were characterized at 39.5 degrees C in the absence of gamma interferon. First, stromal cell lines were established that induced osteclast formation (resorption of bone slices) when cocultured with hemopoietic spleen cells. Some of the stromal cell lines so generated were able to resorb approximately 30 mm2/cm2 of bone surface. We then established cell lines of hemopoietic origin, several of which possess osteoclastic potential. When these osteoclast-precursor cell lines were cocultured with stromal cell lines, extensive bone resorption was observed. Osteoclast formation did not occur if the precursor cell lines were incubated on bone slices without stromal cells; osteoclast formation was also dependent upon the presence of 1 alpha,25-dihydroxyvitamin D3. These cell lines represent a model for osteoclast formation and a valuable resource for identification of the mechanisms and factors that regulate osteoclast differentiation and function.
Streptococcal Toxic-Shock Syndrome: Spectrum of Disease, Pathogenesis, and New Concepts in Treatment (1995)

Since the 1980s there has been a marked increase in the recognition and reporting of highly invasive group A streptococcal infections with or without necrotizing fasciitis associated with shock and organ failure. Such dramatic cases have been defined as streptococcal toxic-shock syndrome. Strains of group A streptococci isolated from patients with invasive disease have been predominantly M types 1 and 3 that produce pyrogenic exotoxin A or B or both. In this paper, the clinical and demographic features of streptococcal bacteremia, myositis, and necrotizing fasciitis are presented and compared to those of streptococcal toxic-shock syndrome. Current concepts in the pathogenesis of invasive streptococcal infection are also presented, with emphasis on the interaction between group A Streptococcus virulence factors and host defense mechanisms. Finally, new concepts in the treatment of streptococcal toxic-shock syndrome are discussed.
Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy (2008)

The identification of intracellular signaling cascades important for the growth and survival of cancer cells has led to the development of targeted cancer therapeutics aimed at blocking these signals. The mitogen-activated protein kinase (MAPK) pathway has a well-defined role in cancer biology and has been an important target in the development of targeted therapies. Recently, several small-molecule inhibitors of MAPK/extracellular signal-regulated kinase kinase (MEK), a key intermediary of MAPK signaling, have been developed and are currently being tested in clinical trials. Herein, we review the MAPK pathway, the development of small-molecule MEK inhibitors, and the results obtained to date with MEK inhibitors in human cancer trials.
The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver (1963)

Rats were fed various levels of either ethyl linoleate, ethyl arachidonate, or ethyl linolenate. Weight gain, fat-deficiency status, and fatty acid composition of the liver lipids were determined.Dietary linoleate, fed in excess of 1% of calories, maintained good growth and cured fat deficiency. Increasing amounts of dietary linoleate were stored in the liver lipids and converted into fatty acids of the linoleate family—20:4 and 22:4. The concentration of 20:3 was decreased. Dietary arachidonate cured fat deficiency three times more effectively than linoleate. Increasing amounts of dietary arachidonate were stored in liver lipids and converted to 22:5ω6. The level of 20:3 was lowered three times more effectively than when linoleate was fed. No fatty acids of the linolenate family were synthesized from linoleate or arachidonate.Dietary linolenate did not support weight gain as efficiently as did linoleate or arachidonate. Fat-deficiency symptoms could not be cured completely. Increasing amounts of dietary linolenate increased the levels of fatty acids of the linolenate family; linolenic acid was stored, and 20:5, 22:5ω3, and 22:6 were synthesized from linolenate. The level of 20:3 was lowered in the same fashion as when linoleate or arachidonate was fed. Thr level of 20:4 was decreased with increasing amounts of dietary linolenate.
Signal joint of immunoglobulin Vλ1‐Jλ and novel joints of chimeric V pseudogenes on extrachromosomal circular DNA from chicken bursa (1993)

We isolated extrachromosomal circular DNA from the bursa of 18-day chick embryos and cloned their BamHI fragments into a phage vector. We found examples of the signal joint fused by V lambda 1-J lambda rearrangement and the sequences homologous to V lambda 1 segments that showed: (1) clustered V pseudogene (psi V) germ-line segments containing new psi V26, (2) a head-to-tail duplication of psi V13-psi V12 region and (3) chimeric structures composed of 5'-V lambda 1 and 3'-psi V segments. Both intrachromosomal tandem duplications and extrachromosomal circles may be generated by unscheduled DNA synthesis and recombination. The chimeric structure of V lambda 1 joined with upstream psi V segments suggests the involvement of V gene replacement for somatic diversification of the immunoglobulin genes in addition to a mechanism of segmental gene conversion.
Cocoa Reduces Blood Pressure and Insulin Resistance and Improves Endothelium-Dependent Vasodilation in Hypertensives (2005)

Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, P<0.0001; 24-hour diastolic BP -8.5+/-5.0 mm Hg, P<0.0001) but not WC. DC but not WC decreased HOMA-IR (P<0.0001), but it improved QUICKI, ISI, and FMD. DC also decreased serum LDL cholesterol (from 3.4+/-0.5 to 3.0+/-0.6 mmol/L; P<0.05). In summary, DC decreased BP and serum LDL cholesterol, improved FMD, and ameliorated insulin sensitivity in hypertensives. These results suggest that, while balancing total calorie intake, flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH.
Central and Peripheral Corneal Thickness in Keratoconus and Normal Patient Groups (1994)

Central and peripheral (superior, inferior, nasal, and temporal) corneal thickness was measured in patients with and without keratoconus using ultrasonic pachometry. In 28 normal eyes (14 patients) mean central corneal thickness (CCT) was 0.56 +/- 0.02 mm and the mean difference in thickness between the mean peripheral corneal thickness (PCT) and CCT was 0.24 mm. In 28 keratoconic eyes (14 patients) CCT was 0.52 +/- 0.04 mm, and PCT-CCT was 0.29 mm. For keratoconic right eyes, CCT and PCT-CCT were significantly different from normals (p = 0.01). Additional studies within the normal patient group showed no diurnal or day-to-day variations in CCT; they also confirmed the repeatability of the measurements.
The role of wild-type and mutated N-ras in the malignant transformation of liver cells (2000)

In order to determine the role of N-ras overexpression and mutation in malignant liver cell transformation, wild-type and mutated N-ras were transfected into the rat liver epithelial cell line OC/CDE 22, and N-ras expression, growth kinetics, growth in soft agar, and tumorigenicity in vivo as well as the involvement of the mitogen-activated protein kinase (MAPK) signal transduction pathway in the expression of the malignant phenotype were analyzed. Although OC/CDE 22 cells transfected with wild-type N-ras showed a high expression of N-ras at the mRNA and protein levels, the cells did not grow in soft agar and were not tumorigenic in vivo. In contrast, OC/CDE 22 cells transfected with mutated N-ras showed anchorage-independent growth and were tumorigenic. When cultured in fetal bovine serum-supplemented medium, OC/CDE 22 cells expressing mutant N-ras showed a higher proliferation rate than nontransfected OC/CDE 22 cells or OC/CDE 22 cells transfected with wild-type N-ras. When held in serum-free medium, untreated OC/CDE 22 cells did not grow at all, while OC/CDE 22 cells transfected with wild-type or mutant N-ras proliferated at a similar rate, which can be explained by the high MAPK activity in these cells. Selective inhibition of the MAPK cascade abolished the growth of OC/CDE 22 cells carrying mutant N-ras in soft agar; furthermore, these cells ceased pile up and formed monolayers on Petri dishes. Thus, activation of the MAPK signaling pathway, though alone not sufficient to malignantly transform liver cells (as shown in liver cells overexpressing wild-type N-ras), is not only essential for growth control but also for the expression of the malignant phenotype (as demonstrated in liver cells transformed by mutated N-ras).
Flexibility of the B-DNA backbone: effects of local and neighbouring sequences on pyrimidine-purine steps (1998)

The structurally correlated dihedral angles epsilon and zeta are known for their large variability within the B-DNA backbone. We have used molecular modelling to study both energetic and mechanical features of these variations which can produce BI/BII transitions. Calculations were carried out on DNA oligomers containing either YpR or RpY dinucleotides steps within various sequence environments. The results indicate that CpA and CpG steps favour the BI/BII transition more than TpA or any RpY step. The stacking energy and its intra- and inter-strand components explain these effects. Analysis of neighbouring base pairs reveals that BI/BII transitions of CpG and CpA are easiest within (Y)n(R)n sequences. These can also induce a large vibrational amplitude for TpA steps within the BI conformation.
Fusogenic segments of bovine leukemia virus and simian immunodeficiency virus are interchangeable and mediate fusion by means of oblique insertion in the lipid bilayer of their target cells. (1992)

Modified bovine leukemia virus (BLV) glycoproteins were expressed by using vaccinia virus recombinants, and their fusogenic capacities were examined by a syncytia-formation assay. This analysis indicates that (i) both BLV envelope glycoproteins gp51 and gp30 are necessary for cell fusion; (ii) insertion of the N-terminal segment of gp30 (fusion peptide) into the lipid bilayer in an oblique orientation, as predicted by computer conformational analysis, results in fusogenic capacities higher than insertion in a perpendicular or parallel orientation; and (iii) replacement of the BLV fusion peptide with its simian immunodeficiency virus counterpart does not modify the fusogenic capacity of the BLV glycoprotein.
Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental and human malignancies: a review. (1990)

The combination of interferon (IFN) and conventional chemotherapeutic agents offers a promising therapeutic approach for the treatment of cancer. However, there is as yet no consensus on optimal strategies for combining this family of compounds with other cancer therapies. While in vitro studies have demonstrated both direct cytotoxic and cytokinetic effects for IFN, a more interesting role derives from its ability to synergistically potentiate the activity of a wide variety of cytotoxic agents against multiple human and rodent tumors, both in vitro and in animal models. The interaction between IFN and cytotoxic agents in vitro is complex and depends not only on the choice of cytotoxic agent but also on the concentrations, ratios, duration, and sequence of exposure to the two drugs. Preliminary data suggest that some combinations are not merely additive but rather that IFN may biochemically modulate the cellular uptake or metabolism of the cytotoxic agent resulting in synergistic antineoplastic activity. In vivo interactions between IFN and cytotoxic agents involve an additional layer of complexity because of the potential effects of the biological agent on the host immune system and drug-metabolizing enzymes. Furthermore, IFN may have a protective effect on normal host tissues which theoretically could allow for the delivery of higher doses of cytotoxic agents. The results of early clinical trials using combinations of IFN with chemotherapeutic agents have generally been disappointing. This may be due to the inability of preclinical models to accurately predict the clinical situation or alternatively from a failure to incorporate information on dose, scheduling, and sequence of drug administration into clinical trials. Preliminary clinical studies with IFN-alpha and the fluorinated pyrimidine, 5-fluorouracil, in patients with advanced colorectal carcinoma suggest that IFN may enhance the effects of the antimetabolite. Confirmatory trials are in progress. Further trials designed to exploit the preclinical experience with combinations of IFN and cytotoxic agents are warranted.