gebhart/patrepeval huggingface dataset:
Demonstration of clonable alloreactive host T cells in a primate model for bone marrow transplantation. (1986)

The phenomenon of marrow rejection following supralethal radiochemotherapy was explained in the past mainly by non-T-cell mechanisms known to be resistant to high-dose irradiation. In the present study a low but significant number of radiochemoresistant-clonable T cells was found in the peripheral blood and spleen of Rhesus monkeys following the cytoreductive protocol used for treatment of leukemia patients prior to bone marrow transplantation. More than 95% of the clonable cells are concentrated in the spleen 5 days after transplant. The cells possess immune memory as demonstrated by the generation of alloreactive-specific cytotoxicity. The present findings suggest that host-versus-graft activity may be mediated by alloreactive T cells. It is hoped that elimination of such cells prior to bone marrow transplantation will increase the engraftment rate of HLA-nonidentical marrow in leukemia patients.
Fabrication of metallic nanowires with a scanning tunneling microscope (1995)

A procedure to pattern thin metal films on a nanometer scale with a scanning tunneling microscope (STM) operating in air is reported. A 30 nm film of hydrogenated amorphous silicon (a-Si:H) is deposited on a 10 nm film of TaIr. Applying a negative voltage between the STM tip and the a-Si:H film causes the local oxidation of a-Si:H. The oxide which is formed is used as a mask to wet etch the not-oxidized a-Si:H and subsequently, the remaining pattern is transferred into the metal film by Ar ion milling. Metal wires as narrow as 40 nm have been fabricated. Since a-Si:H can be deposited in very thin layers on almost any substrate, the presented procedure can be applied to structure all kind of thin films on a nanometer scale.
The origin and efficient derivation of embryonic stem cells in the mouse (1997)

By explanting tissues isolated microsurgically from implanting strain 129 mouse blastocysts individually on STO feeder cells we have established that embryonic stem (ES) cells originate from the epiblast (primitive ectoderm). Isolated early epiblasts yielded ES cell lines at a substantially higher frequency than intact blastocysts regardless of whether they were explanted whole or as strictly single-cell suspensions. When explanted from delayed-implanting 129 blastocysts, epiblasts gave lines consistently in 100% of cases. If primary embryonic fibroblasts rather than STO cells were used as feeders, germline-competent ES cell lines were obtained readily from epiblasts of delayed-implanting blastocysts of several hitherto refractory strains, particularly when recombinant leukemia inhibitory factor was included in the medium during the initial period of culture. Because lines were obtained from the nonpermissive CBA/Ca strain at a rate of up to 56%, this approach to the derivation of germline-competent ES cell lines may not only prove generic for the mouse but also worth pursuing in other species of mammal.
Flow synchronization protocol (1994)

Presents an adaptive flow synchronization protocol that permits synchronized delivery of data to and from geographically distributed sites. Applications include inter-stream synchronization, synchronized delivery of information in a multisite conference, and synchronization for concurrency control in distributed computations. The contributions of this protocol in the area of flow synchronization are the ability to synchronize over arbitrary topologies, the introduction of an adaptive synchronization delay, the flexibility to maintain multiple synchronization groups, and the use of a modular architecture that permits the application to tailor synchronization calculations to its service requirements. The authors take advantage of network protocols capable of maintaining network clock synchronization in the millisecond range.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Genetic Modification of Tumor-Infiltrating Lymphocytes via Retroviral Transduction (2021)

Adoptive T cell therapy (ACT) holds great promise for cancer treatment. One approach, which has regained wide interest in recent years, employs antitumor T cells isolated from tumor lesions ("tumor-infiltrating lymphocytes" or TIL). It is now appreciated that a considerable proportion of anti-melanoma TIL recognize new HLA-binding peptides resulting from somatic mutations, which occurred during tumor progression. The clinical efficacy of TIL can potentially be improved <i>via</i> their genetic modification, designed to enhance their survival, homing capacity, resistance to suppression, tumor killing ability and additional properties of clinical relevance. Successful implementation of such gene-based strategies critically depends on efficient and reproducible protocols for gene delivery into clinical TIL preparations. Here we describe an optimized protocol for the retroviral transduction of TIL. As the experimental system we employed anti-melanoma TIL cultures prepared from four patients, recombinant retrovirus encoding an anti-CD19 chimeric antigen receptor (CAR) as a model gene of interest and CD19+ and CD19- human cell lines serving as target cells. Transduction on day 7 of the rapid expansion protocol (REP) resulted in 69 ± 8% CAR positive TIL. Transduced, but not untransduced TIL, from the four patients responded robustly to CD19+, but not CD19- cell lines, as judged by substantial secretion of IFN-γ following co-culture. In light of the rekindled interest in antitumor TIL, this protocol can be incorporated into a broad range of gene-based approaches for improving the in-vivo survival and functionality of TIL in the clinical setting.
Structure and expression of an ethylene-related mRNA from tomato (1987)

Messenger RNAs homologous to a cDNA clone (pTOM 13) derived from a ripe-tomato-specific cDNA library are expressed during tomato fruit ripening and after the wounding of leaf and green fruit material. Both responses involve the synthesis of the hormone ethylene. Accumulation of the pTOM 13--homologous RNA during ripening is rapid and sustained, and reaches its maximum level in orange fruit. Following mechanical wounding of tomato leaves a pTOM 13--homologous RNA shows rapid induction within 30 minutes, which occurs before maximal ethylene evolution (2-3 h). This RNA also accumulates following the wounding of green tomato fruit. Northern blot analysis of poly(A)+ RNA indicates that the length of the mRNA is about 1400 nucleotides. Nucleotide sequence analysis showed the cDNA insert to contain the complete coding region of the pTOM 13 protein (33.5 kD) and an unusual 5' structure of ten dT-nucleotides. Hybridisation of the pTOM 13 cDNA insert to Southern blots of tomato DNA indicates the presence of only a small number of homologous sequences in the tomato genome.
Optimizing Bone Health and Calcium Intakes of Infants, Children, and Adolescents (2006)

Most older children and adolescents in the United States currently do not achieve the recommended intake of calcium. Maintaining adequate calcium intake during childhood and adolescence is necessary for the development of peak bone mass, which may be important in reducing the risk of fractures and osteoporosis later in life. Optimal calcium intake is especially relevant during adolescence, when most bone mineral accretion occurs. Because of the influence of the family's diet on the diet of children and adolescents, adequate calcium intake by all members of the family is important. Assessment of calcium intake can be performed in the physician's office. A well-rounded diet including low-fat dairy products, fruits, and vegetables and appropriate physical activity are important for achieving good bone health. Establishing these practices in childhood is important so that they will be followed throughout the life span.
Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans (2009)

In cell line and animal models, sweet and bitter tastants induce secretion of signaling peptides (e.g., glucagon-like peptide-1 and cholecystokinin) and slow gastric emptying (GE). Whether human GE and appetite responses are regulated by the sweetness or bitterness per se of ingested food is, however, unknown. We aimed to determine whether intragastric infusion of "equisweet" (Study A) or "equibitter" (Study B) solutions slow GE to the same extent, and whether a glucose solution made sweeter by the addition of saccharin will slow GE more potently than glucose alone. Healthy nonobese subjects were studied in a single-blind, randomized fashion. Subjects received 500-ml intragastric infusions of predetermined equisweet solutions of glucose (560 mosmol/kgH(2)O), fructose (290 mosmol/kgH(2)O), aspartame (200 mg), and saccharin (50 mg); twice as sweet glucose + saccharin, water (volumetric control) (Study A); or equibitter solutions of quinine (0.198 mM), naringin (1 mM), or water (Study B). GE was evaluated using a [(13)C]acetate breath test, and hunger and fullness were scored using visual analog scales. In Study A, equisweet solutions did not empty similarly. Fructose, aspartame, and saccharin did not slow GE compared with water, but glucose did (P < 0.05). There was no additional effect of the sweeter glucose + saccharin solution (P > 0.05, compared with glucose alone). In Study B, neither bitter tastant slowed GE compared with water. None of the solutions modulated perceptions of hunger or fullness. We conclude that, in humans, the presence of sweetness and bitterness taste per se in ingested solutions does not appear to signal to influence GE or appetite perceptions.
Convergent evolution with combinatorial peptides (2000)

Once the sequence of a genome is in hand, understanding the function of its encoded proteins becomes a task of paramount importance. Much like the biochemists who first outlined different biochemical pathways, many genomic scientists are engaged in determining which proteins interact with which proteins, thereby establishing a protein interaction network. While these interactions have evolved in regard to their specificity, affinity and cellular function over billions of years, it is possible in the laboratory to isolate peptides from combinatorial libraries that bind to the same proteins with similar specificity, affinity and primary structures, which resemble those of the natural interacting proteins. We have termed this phenomenon ‘convergent evolution’. In this review, we highlight various examples of convergent evolution that have been uncovered in experiments dissecting protein–protein interactions with combinatorial peptides. Thus, a fruitful approach for mapping protein–protein interactions is to isolate peptide ligands to a target protein and identify candidate interacting proteins in a sequenced genome by computer analysis.
BAFF-R, a Newly Identified TNF Receptor That Specifically Interacts with BAFF (2001)

B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.
Photoluminescence of C60 nanocrystals embedded in a SiO matrix (1998)

Nanometer-sized C60 crystals in a SiO matrix were grown by an inert gas evaporation method. The size of the nanocrystal was varied by changing the evaporation time of the SiO material. We have successfully prepared well-dispersed (C60)n nanocrystals (n∼103) with a narrow size distribution in SiO. The photoluminescence of the C60 nanocrystals in SiO has been investigated and we have found that the photoluminescence spectra were significantly different from that of the C60 solid form (C60 film). Results indicate that the vibronic coupling of the C60 nanocrystals in SiO is strong compared with that of the solid form of C60.
Clinical experiences with G17DT in gastrointestinal malignancies (2006)

The development of new agents for the treatment of gastrointestinal malignancies is increasing in pace and importance. The discovery of novel targets, namely the epidermal growth factor receptor and vascular endothelial growth factor, have sparked an explosion of new agents being tested in gastrointestinal malignancies. Clearly, novel agents and approaches are required. G17DT is a novel immunoconjugate designed to elicit a humoral response against the N-terminal end of G17 gastrin. In this overview, the authors summarize the clinical research focused on gastrointestinal tract cancers to date. In total, there is a clear signal of efficacy with this compound, although further testing is required in order for this efficacy to be demonstrated in a manner that will support regulatory approval.
A SENSITIVE METHOD FOR THE ASSAY OF 5‐HYDROXYTRYPTAMINE (1957)

The movements of a strip of fundus from a rat stomach, suspended in a 5 ml. bath at 37 degrees , are recorded by a spring-loaded lever. The muscle is stretched for 15 to 30 sec. between contractions. 1 ng. 5-Hydroxytryptamine (5-HT), 10 ng. acetylcholine or 2 to 10 mug. of histamine all produce contractions, giving tracings about 4 cm. high. In the presence of hyoscine (10(-7)) low concentrations of 5-HT can be assayed directly from mixtures of the three substances. Sympathomimetic amines interfere with the assay, but this can be overcome. The preparation is robust, potentially suitable for use with an automatic assay apparatus and 10 to 100 times more sensitive than the rat uterus.
The anatomy of melancholia – focal abnormalities of cerebral blood flow in major depression (1992)

Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P less than 0.05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P less than 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.
Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme. (1993)

These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia.
[Time course of inhibition of caffeine elimination in response to the oral depot contraceptive agent Deposiston. Hormonal contraceptives and caffeine elimination]. (1991)

In the course of six months, the influence of the oral depot contraceptive, Deposiston (3 mg ethinylestradiol sulphonate and 10 mg norethisterone acetate per menstrual cycle) on the pharmacokinetics of caffeine as a model substance was studied in seven women in intraindividual comparison. The first examination began prior to administration of Deposition. The women were subjected to little challenge as saliva was used as the measuring compartment. Deposiston was found markedly delay the elimination half-life life of caffeine (p less than 0.05): t1/2 prior to therapy 4.9 +/- 2.6 h and, after as little as 2 mg ethinylestradiol sulphonate 8.0 +/- 3.5 h. In contrast to the effect observed for preparations containing less estrogen, these longer half-lives persisted throughout the trial. As expected, the AUC values were slightly elevated during this period, whereas clearance values were reduced.
Evaluation of EMD 128 130 occupancy of the 5-HT1A and the D2 receptor: a human PET study with [11]WAY-100635 and [11C]raclopride (2002)

The use of so-called, atypical antipsychotic medication is becoming more widespread in the treatment of psychotic disorders. EMD 128 130 is a novel compound acting as an agonist at the 5-HT1A receptor, and as an antagonist at the dopamine-2 (D2) receptor. This dual action may confer additional benefits over selective D2 antagonists in the treatment of psychotic disorders. In this study, we investigated the occupancy of EMD 128 130 in vivo at the human D2 and 5-HT1A receptors with positron emission tomography using the radiotracers [11C]raclopride and [11C]WAY-100635. Seven healthy volunteers were examined before and after 5 days of treatment with EMD 128 130, administered in an incremental dose building up to 50 mg, b.d. A significant occupancy was demonstrated at the human D2 receptor (40% following a dose of 50 mg, b.d.) while there was no consistent effect observed at the 5-HT1A receptor, despite a similar affinity of EMD 128 130 for cloned human D2 and 5-HT1A receptors, and the presence of typical, central 5-HT1A agonist side-effects. The differential effects of EMD 128 130 at the D2 and the 5-HT1A receptor (antagonist at D2 receptor, agonist at the 5-HTIA receptor) may explain the differences in occupancy observed.
An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder (2004)

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder with familial and acquired forms. The familial form is associated with mutations in the perforin gene and both forms are associated with severe defects in lymphocyte cytotoxic function. We examined perforin-deficient mice as a model of HLH in order to gain insight into this poorly understood disorder. While these mice do not spontaneously develop HLH-like symptoms, we found that they manifest all of the features of HLH after infection with lymphocytic choriomeningitic virus (LCMV). Following LCMV infection, perforin-deficient mice develop fever, splenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevation of multiple serum cytokine levels, and hemophagocytosis is evident in many tissues. Investigation into how this phenotype develops has revealed that CD8+ T cells, but not natural killer (NK) cells, are necessary for the development of this disorder. Cytokine neutralization studies have revealed that interferon gamma (IFNgamma) is uniquely essential as well. Finally, the excessive amount of IFNgamma seen in affected mice appears to be driven by increased antigen presentation to CD8+ T cells. These studies provide insight into the pathophysiology of HLH, and provide new targets for specific therapeutic intervention in this fatal disorder.
Chimeric murine-human antibodies directed against folate binding receptor are efficient mediators of ovarian carcinoma cell killing. (1994)

The MOv18 (gamma 1, kappa) and MOv19 (gamma 2a, kappa) murine monoclonal antibodies (MAbs) recognize different epitopes on the human folate binding receptor which is overexpressed on 90% of nonmucinous epithelial ovarian tumors. A chimeric murine-human (human gamma 1, kappa) version of both antibodies was constructed and expressed. The genes encoding the murine heavy and light chain variable regions of the MOv18 and MOv19 MAbs were cloned from the parental hybridomas, fused with genes encoding the human heavy (gamma 1) and light (kappa) chain constant regions, respectively, and expressed in the SP2/0 murine myeloma cell line. Using human peripheral blood mononuclear cells as effector cells and conditions that provide for maximum lysis (effector target = 50:1, saturating antibody concentration), the murine MOv18 MAb (IgG1) mediated variable levels of specific cytolysis of the target ovarian cancer cell line IGROV1. In contrast, the chimeric MOv18 MAb mediated higher and more consistent lysis even at a 10-100-fold lower antibody concentration. The murine MOv19 MAb (IgG2a) mediated specific lysis of IGROV1 cells, and the chimeric version of this antibody mediated an amount of lysis at least equal to that mediated by its murine counterpart. A comparison of the ED50 values obtained for the murine MOv19 and chimeric MOv19 antibodies indicates that the chimeric MOv19 MAb was 3 to 10 times more potent than the murine MOv19 antibody. In addition, the ED50 values obtained for the chimeric MOv18 and chimeric MOv19 MAbs were similar, indicating that these MAbs are equally potent. The level of maximal lysis obtained was dependent on the number of target molecules/cell; the same high level of lysis mediated by cMOv18, MOv19, and cMOv19 was observed with both IGROV1 and OvCA432 target cells. However, only low levels of lysis were obtained when the SW626 cell line, which expresses 1 x 10(4) folate binding protein sites/cell, was used as a target. An equimolar mixture of the chimeric MOv18 and MOv19 MAbs was no more effective in the mediation of lysis than an equivalent amount of either chimeric MAb alone. These data suggest that the folate binding receptor is expressed on IGROV1 cells at a density sufficient to provide for optimal levels of antibody-mediated lysis using a single chimeric antibody directed at the folate binding receptor.
Intramolecularly Hydrogen-Bonded Peptide Conformation (1980)

Over the past few years the possible occurrence of intramolecularly hydrogen-bonded structures in linear and cyclic peptides has attracted increasing attention. In this review emphasis is given to solid-state studies, particularly by X-ray diffraction and infrared absorption techniques. Conformational energy calculations are also considered. The discussion is focused both on model peptides and biological activity polypeptide molecules. The tetrapeptide system (Formula: see text), examined allows one to discuss the extended C5 structure and the various folded conformations, namely the C7 (gamma-turn), C8, C10 (beta-turn), C11, and C13 conformations. The four latter forms may include cis peptide configurations. The oxy-analogs to the C7, C10, and C13 conformations and structures containing bifurcated hydrogen bonds are also discussed. The last sections describe intramolecularly hydrogen-bonded peptide structures involving: (1) a side-chain group, (2) the N-protecting group (in synthetic model compounds), and (3) a beta-amino acid.
Stabilization of Z DNA in Vivo by Localized Supercoiling (1989)

Biological processes such as transcription may generate domains of supercoiling on a circular DNA. The existence of these domains in Escherichia coli was investigated by the ability of different lengths of (CG) tracts, cloned upstream or downstream from the tetracycline resistance gene (tet) of pBR322, to adopt the Z structure in vivo. Segments as short as 12 base pairs adopt the Z form when cloned upstream from the tet gene (Eco RI site), whereas no Z DNA was detected when this sequence was cloned downstream (Sty I site), even with a 74-base pair (CG) tract that requires less supercoiling than shorter tracts for the B-Z transition. Hence the localized supercoil density in pBR322 can be as high as -0.038 and as low as -0.021 at different loci. These data demonstrate the existence of the Z structure for commonly found natural sequences and support the notion of domains of negative supercoiling in vivo.