gebhart/patrepeval huggingface dataset:
Glutamate, the Dominant Excitatory Transmitter in Neuroendocrine Regulation (1990)

Glutamate has been found to play an unexpectedly important role in neuroendocrine regulation in the hypothalamus, as revealed in converging experiments with ultrastructural immunocytochemistry, optical physiology with a calcium-sensitive dye, and intracellular electrical recording. There were large amounts of glutamate in boutons making synaptic contact with neuroendocrine neurons in the arcuate, paraventricular, and supraoptic nuclei. Almost all medial hypothalamic neurons responded to glutamate and to the glutamate agonists quisqualate and kainate with a consistent increase in intracellular calcium. In all magnocellular and parvocellular neurons of the paraventricular and arcuate nuclei tested, the non-NMDA (non-N-methyl-D-aspartate) glutamate antagonist CNQX (cyano-2,3-dihydroxy-7-nitroquinoxaline) reduced electrically stimulated and spontaneous excitatory postsynaptic potentials, suggesting that the endogenous neurotransmitter is an excitatory amino acid acting primarily on non-NMDA receptors. These results indicate that glutamate plays a major, widespread role in the control of neuroendocrine neurons.
Requirements for a location-based access control model (2008)

Location-based access control (LBAC) takes a mobile user's current position into account when making the decision if he should be allowed to access a particular resource like a file or service. For example using LBAC we can enforce that a nurse is only allowed to view a patient's data using a PDA when she stays at the premises of the hospital. There are a couple of research papers that propose data models for LBAC; almost all of them are extensions of Role-based Access Control (RBAC). In the paper at hand we first motivate the employment of LBAC by some application scenarios before we review the most important LBAC-models. Despite the body of research in the field of LBAC we could identify requirements that cannot be covered with the available models; these requirements are discussed in detail.
Normal Cells Control the Growth of Neighboring Transformed Cells Independent of Gap Junctional Communication and Src Activity (2004)

The growth of many types of cancer cells can be controlled by surrounding normal cells. However, mechanisms underlying this phenomenon have not been defined. We used a layered culture system to investigate how nontransformed cells suppress the growth of neighboring transformed cells. Direct physical contact between transformed and nontransformed cells was required for growth suppression of transformed cells in this system; communication by diffusible factors was not sufficient. However, significant gap junctional communication was not required, indicating that other intercellular junctions mediated this growth regulatory response. We also report that the Src kinase activity in transformed cells was not directly inhibited by contact with nontransformed cells. Instead, nontransformed cells increased the expression of serum deprivation-response protein and the transcription factor four and a half LIM domain 1 in tumor cells. In addition, these results suggest mechanisms by which normal cells may block Wnt signaling, inhibit insulin-like growth factor activity, and promote host recognition of neighboring tumor cells.
Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans (2009)

Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).
Roles for Mismatch Repair Factors in Regulating Genetic Recombination (2000)

Click to increase image sizeClick to decrease image size ACKNOWLEDGMENTSWe thank James Haber, Neal Sugawara, and Barbara Studamire for engaging us in many stimulating discussions and members of the Alani Laboratory for critical reading and discussion of the manuscript. We are also grateful for the contributions of N. Sugawara and J. Haber that led to the development of Fig. 2.This work was supported by NIH grant GM53085 and Hatch grant NYC-165-6424.
Isolation of a retroviruslike sequence from the TL locus of the C57BL/10 murine major histocompatibility complex (1986)

Two retroviruslike sequences have been isolated from the TL locus of the major histocompatibility complex of C57BL/10 mice. One sequence (TLev2) hybridizes only with probes derived from the pol region of the murine leukemia provirus AKR; the other sequence (TLev1) hybridizes with gag, pol, and env AKR region probes. This 9-kilobase endogenous, TL region-associated virus (TLev1) has been further characterized. The TLev1 genome has been shown to contain murine leukemia virus-related sequences bounded by retroviruslike, VL30 long terminal repeats. Hybridization of TLev1-derived probes to mouse genomic digests reveals multiple copies which show distinct patterns compared with those observed with murine leukemia virus probes. The study of TLev1 may prove significant with respect to the interaction of retroviral sequences within the genome, expression of genes within the TL locus, and polymorphisms within the major histocompatibility complex.
Dual role of phagocytic NADPH oxidase in bacterial killing (2004)

The classical model of bacterial killing by phagocytic cells has been recently challenged by questioning the toxic effect of oxygen products and attributing the fundamental role to K(+) ions in releasing antimicrobial proteins within the phagosome. In the present study we followed O(2)(*-) production, changes of membrane potential, K(+) efflux, and bacterial killing in the presence of increasing concentrations of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium. Efficiency of bacterial killing was assessed on the basis of bacterial survival measured by a new semiautomated method. Very low rates of O(2)(*-) production were accompanied by significant membrane depolarization and K(+) release and parallel improvement of bacterial killing. When O(2)(*-) production exceeded 20% of its maximal capacity, no further change was detected in the membrane potential and only minimal further K(+) efflux occurred, yet bacterial survival decreased parallel to the increase of O(2)(*-) production. The presented results indicate that both electrophysiological changes (depolarization and consequent ion movements) and the chemical effect of reactive oxygen species play a significant role in the killing of certain pathogens. The observation that an increase of membrane depolarization can compensate for decreased O(2)(*-) production may be important for potential therapeutic applications.
Tissue‐Engineered Skin Containing Mesenchymal Stem Cells Improves Burn Wounds (2008)

There is increasing evidence showing that adult stem cells are useful for tissue regeneration. Bone marrow mesenchymal stem cells (MSCs) are self-renewing and are potent in differentiating into multiple cells and tissues. To investigate the practicability of repairing burn wounds with tissue-engineered (TE) skin combined with bone MSCs, we established a burn wound model in the porcine skin. With a controlling temperature and time of the burning device to obtain different degrees of burn wounds, a deep dermal partial thickness burn was introduced to the porcine skin using a heated-brass contact injury at 100 degrees C for 20 s. Collagen-GAG scaffolds were utilized as the matrix; MSCs separated from pigs were seeded on them to form the skin equivalent. When grafted to the burn wounds, the TE skin containing MSCs showed better healing and keratinization, less wound contraction, and more vascularization. Grafts proliferated well and contributed to the neo-tissues. These data suggest that TE skin containing MSCs in a burn defect can accelerate wound healing and receive satisfactory effects.
Complete regression of human B-cell lymphoma xenografts in mice treated with recombinant anti-CD22 immunotoxin RFB4(dsFv)-PE38 at doses tolerated by cynomolgus monkeys (1999)

RFB4(dsFv)-PE38 is a recombinant immunotoxin in which the variable light domain (V(L)) is disulfide bonded via cysteine residues to the variable heavy domain (V(H)), which in turn is fused to PE38, a mutant form of Pseudomonas exotoxin A. RFB4 binds to CD22, which is a differentiation antigen expressed on the majority of B-cell leukemias and lymphomas. To examine the potential efficacy of RFB4(dsFv)-PE38 when administered at a dose schedule appropriate for phase I testing, mice bearing CA46 human CD22+ Burkitt's lymphoma xenografts were treated on alternate days i.v. for 3 doses (QOD x 3). Complete regressions were observed in 80% and 100% of mice treated with 200 and 275 microg/kg QOD x 3, respectively. The higher dose was 27% of the LD50 and 34% of the LD10 in mice. Because RFB4(dsFv)-PE38 is stable at 37 degrees C, it could also be given by continuous infusion using pumps placed in the peritoneal cavity; complete regressions also resulted from this mode of administration. To study toxicology, a pilot toxicology study of RFB4(dsFv)-PE38 was undertaken in cynomolgus monkeys, which like humans but unlike mice have CD22, which binds RFB4. Doses of 100 and 500 microg/kg i.v. QOD x 3 were well tolerated, indicating that a dose that cured tumors in mice was tolerated by primates. Based on these preclinical results, RFB4(dsFv)-PE38 is being developed for the treatment of patients with CD22-positive leukemias and lymphomas.
A Neuropharmacological Evaluation of Felbamate as a Novel Anticonvulsant (1992)

Felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM) was subjected to a series of carefully selected in vivo and in vitro tests to provide additional insight into mechanism of action, margin of safety, and clinical potential. FBM was effective against intracerebroventricular (i.c.v.) N-methyl-D-aspartate (NMDA)-induced clonus and i.c.v. NMDA- and quisqualic acid (quis)-induced forelimb tonic extension in mice and ineffective against i.c.v. quis-induced clonus in mice. FBM was also effective in preventing the expression of Stage 5 kindled seizures in corneal-kindled rats. The calculated protective indices (rotorod median toxic dose divided by anticonvulsant median effective dose) ranged from 28 to 146 for those tests in which FBM displayed activity. With the in vitro tests, FBM did not significantly displace [3H]MK-801 from its binding site. In contrast, FBM was effective in blocking sustained repetitive firing in mouse spinal cord neurons grown in tissue culture (median inhibitory concentration 67 micrograms/ml). This effect on repetitive firing suggests indirectly that FBM modulates sodium channel conductance. The results, when compared to similar data for phenytoin, carbamazepine, valproate, and ethosuximide, support the concept that FBM is a relatively nontoxic agent with a unique profile of anticonvulsant action, a broad margin of safety, and a clinical potential that includes at least generalized tonic-clonic and complex partial seizures.
Preliminary experience with percutaneous laser disc decompression in the treatment of sciatica. (1995)

Percutaneous laser disc decompression can relieve sciatica caused by a herniated intervertebral disc. The technique requires limited use of health resources. Preliminary results suggest that an early return to work can be expected in patients successfully relieved of their leg pain.
Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor complex (1998)

The leukocyte receptor complex (LRC) on human chromosome 19q13.4 encompasses at least four families of related genes: immunoglobulin-like transcripts (ILT), killer cell inhibitory receptors (KIR), the leukocyte-associated inhibitory receptors (LAIR) and the Fcalpha receptor (Fc(alpha)R). We determined the genomic organization of a region of DNA spanning the junction of the ILT and KIR gene complexes. Extensive sequence data were collected for ILT3, two novel genes, ILT9 and ILT10, and one novel KIR locus (KIRCI). These loci, along with other reported sequences from the region, encoded a leader sequence split into two exons, upstream of two to four immunoglobulin (Ig) domains, each on a separate exon. Downstream of the Ig domains, however, the organization differs markedly between inhibitory and activating ILT. These data are consistent with a highly conserved gene arrangement for all superfamily members suggesting duplication of primordial sequences. ILT3 and KIRCI were in the same head-to-tail orientation as has been described for other KIR loci which may facilitate addition or loss of genes between different haplotypes.
Identification of a Mycobacterium bovis BCG 45/47-kilodalton antigen complex, an immunodominant target for antibody response after immunization with living bacteria (1993)

Increased protection against a virulent challenge with Mycobacterium tuberculosis is induced mainly by a previous immunization with living avirulent mycobacteria, usually Mycobacterium bovis BCG. Only a transient and marginal protection is obtained after immunization with bacterial extracts or dead bacteria. Both living and heat-killed bacteria share a number of common antigens. In order to identify mycobacterial molecules which are dominant antigens during immunization with living bacteria, a two-step selection method was used. Two groups of guinea pigs were immunized either with living or with heat-killed BCG. Sera were then collected and used to select and counterselect antigens present in BCG culture filtrates. Each major fraction eluted from a series of high-pressure liquid chromatography columns (gel filtration, DEAE, and reverse-phase chromatography) was run on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred on polyvinylidene difluoride sheets. The molecules present on twin immunoblots were stained with antibodies raised in guinea pigs immunized either with living or with heat-killed BCG. Cross-reactive antigens stained in twin immunoblots were eliminated. Major antigens interacting with antibodies raised after immunization only with living bacteria were further purified. A complex of 45- and 47-kDa major molecules (45/47-kDa complex) was thus identified and further purified. The complex was found to interact only with antibodies present in sera of guinea pigs immunized with living bacteria and not at all with antibodies raised after immunization with dead bacteria. The 45/47-kDa antigen complex molecules were resolved on two-dimensional electrophoresis in three major and seven minor proteins detected with silver staining. All the molecules interacted with the antibodies present in sera of guinea pigs immunized with living BCG. The three major proteins (two at 47 kDa and one at 45 kDa) were amino-terminal sequenced. The sequence A-P-E-P-A-P-P-V-P-P-A-A-A-A-P-P-A, which was not previously reported, was the same for these three molecules. By using a competitive enzyme-linked immunosorbent assay, the concentrations of the 45/47-kDa antigen complex were measured in BCG culture filtrates, freeze-dried BCG, and dried heat-killed BCG; they were, respectively, 2, 0.01, and 0.001% of the total mass. The low or very low values compared with the high antibody concentration emphasized the ability of the 45/47-kDa complex delivered through live BCG to trigger an antibody response.
Pancreatic Cancer (2010)

Deaths from pancreatic ductal adenocarcinoma, also known as pancreatic cancer, rank fourth among cancer-related deaths in the United States, yet the causes of pancreatic cancer remain unknown. This review article summarizes recent progress in the understanding and management of pancreatic cancer.
A Brief History of the National Collegiate Athletic Association's Role in Regulating Intercollegiate Athletics (2000)

The author acknowledges the research assistance of Robert Walker.1.I often wonder whether the response is based on a feeling that I have said something cute, or whether it is founded in a deeper disquietude over the fact that I may just be right.2. Sports sections are filled with description and occasional polemics over aspects of the role of sport in society, but that discourse rarely goes beyond the superficial as to specific issues raised.For example, commentators repeatedly argue that intercollegiate athletes should be "paid" without discussing in any depth the ramifications of their suggestions on the athletes and educational institutions.Marty Lang, Pay-For-Play Versus NCAA, at http:Iwww.linkmag.com/link/FebMar_99/990121ccl-sports.html(Feb.-Mar.1999).Academics, who understand the need to study major phenomena that affect our culture in great depth, often shun the exploration of deeper ethical and moral issues related to sport.For example, once during lunch with a group of my faculty colleagues, a fellow faculty member asked me what I thought about "the game" that weekend.I responded that I did not watch the game.Almost aghast, he wondered out loud, "how can you teach sports law and not watch the game."As academics, like our journalistic counterparts, we are too often caught up in the anecdotal moment of
Extracellular superoxide dismutase, nitric oxide, and central nervous system O2 toxicity. (1992)

Although reactive O2 species appear to participate in central nervous system (CNS) O2 toxicity, the exact roles of different reactive O2 species are undetermined. To study the contribution of extracellular superoxide anion (O2-) to CNS O2 toxicity we constructed transgenic mice overexpressing human extracellular superoxide dismutase (ECSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) in the brain. Remarkably, when exposed to 6 atm (1 atm = 101.3 kPA) of hyperbaric oxygen for 25 min, transgenic mice demonstrated higher mortality (83%) than nontransgenic litter-mates (33%; P < 0.017). Pretreatment with diethyldithiocarbamate, which inhibits both ECSOD and Cu/Zn superoxide dismutase (Cu/Zn SOD) activity, increased resistance to CNS O2 toxicity, in terms of both survival (100% in transgenics and 93% in nontransgenics) and resistance to seizures (4-fold increase in seizure latency in both transgenic and nontransgenic mice; P < 0.05). Thus, O2- apparently protects against CNS O2 toxicity. We hypothesized that O2- decreased toxicity by inactivating nitric oxide (NO.). To test this, we inhibited NO. synthase (EC 1.14.23) with N omega-nitro-L-arginine to determine whether NO. contributes to enhanced CNS O2 toxicity in transgenic mice. N omega-nitro-L-arginine protected both transgenic and nontransgenic mice against CNS O2 toxicity (100% survival and a 4-fold delay in time to first seizure; P < 0.05), as well as abolishing the difference in sensitivity to CNS O2 toxicity between transgenic and nontransgenic mice. These results implicate NO. as an important mediator in CNS O2 toxicity and suggest that ECSOD increases CNS O2 toxicity by inhibiting O2(-)-mediated inactivation of NO.
Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. (1992)

Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.
The beta subunit dissociates readily from the Escherichia coli DNA polymerase III holoenzyme. (1987)

Purified DNA polymerase III holoenzyme (holoenzyme) was separated by glycerol gradient sedimentation into the beta subunit and the subassembly that lacks it (pol III). In the presence of ATP, beta subunit dimer dissociated from holoenzyme with a KD of 1 nM; in the absence of ATP, the KD was greater than 5 nM. The beta subunit was known to remain tightly associated in the holoenzyme upon formation of an initiation complex with a primed template and during the course of replication. With separation from the template, holoenzyme dissociated into beta and pol III. Cycling to a new template depended on the reformation of holoenzyme. Holoenzyme was in equilibrium with pol III and the beta subunit in crude enzyme fractions as well as in pure preparations.
Nasal Carriage as a Source ofStaphylococcus aureusBacteremia (2001)

A substantial proportion of cases of S. aureus bacteremia appear to be of endogenous origin since they originate from colonies in the nasal mucosa. These results provide support for strategies to prevent systemic S. aureus infections by eliminating nasal carriage of S. aureus.
Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor. (1995)

Interleukin-6 is an essential mediator of the bone loss caused by loss of estrogens. Because loss of androgens also causes bone loss, we have examined whether the IL-6 gene is regulated by androgens, and whether IL-6 plays a role in the bone loss caused by androgen deficiency. Both testosterone and dihydrotestosterone inhibited IL-6 production by murine bone marrow-derived stromal cells. In addition, testosterone, dihydrotestosterone, and adrenal androgens inhibited the expression of a chloramphenicol acetyl transferase reporter plasmid driven by the human IL-6 promoter in HeLa cells cotransfected with an androgen receptor expression plasmid; however, these steroids were ineffective when the cells were cotransfected with an estrogen receptor expression plasmid. In accordance with the in vitro findings, orchidectomy in mice caused an increase in the replication of osteoclast progenitors in the bone marrow which could be prevented by androgen replacement or administration of an IL-6 neutralizing antibody. Moreover, bone histomorphometric analysis of trabecular bone revealed that, in contrast to IL-6 sufficient mice which exhibited increased osteoclast numbers and bone loss following orchidectomy, IL-6 deficient mice (generated by targeted gene disruption) did not. This evidence demonstrates that male sex steroids, acting through the androgen-specific receptor, inhibit the expression of the IL-6 gene; and that IL-6 mediates the upregulation of osteoclastogenesis and therefore the bone loss caused by androgen deficiency, as it does in estrogen deficiency.
Phase I and Pharmacologic Study of OSI-774, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced Solid Malignancies (2001)

The recommended dose for disease-directed studies of OSI-774 administered orally on a daily, continuous, uninterrupted schedule is 150 mg/d. OSI-774 was well tolerated, and several patients with epidermoid malignancies demonstrated either antitumor activity or relatively long periods of stable disease. The precise contribution of OSI-774 to these effects is not known.
Purification and properties of the replicative intermediate of the RNA bacteriophage R17. (1966)

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