gebhart/patrepeval huggingface dataset:
Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early embryos. Homology to pancreatic ribonucleases. (1991)

Rana pipiens oocytes and early embryos contain large amounts of a basic protein with antiproliferative/cytotoxic activity against several tumor cell lines in vitro (Darzynkiewicz, Z., Carter, S. P., Mikulski, S. M., Ardelt, W., and Shogen, K. (1988) Cell Tissue Kinet. 21, 169-182; Mikulski, S.M., Viera, A., Ardelt, W., Menduke, H., and Shogen, K. (1990) Cell Tissue Kinet. 23, 237-246), as well as antitumor activity in vivo (Mikulski, S. M., Ardelt, W., Shogen, K., Bernstein, E. H., and Menduke, H. (1990) J. Natl. Cancer Inst. 82, 151-153). The protein, provisionally named P-30 Protein, was purified to homogeneity from early embryos and characterized. It is a single-chain protein consisting of 104 amino acid residues in the following sequence: less than Glu1-Asp-Trp-Leu-Thr-Phe-Gln-Lys-Lys-His-Ile-Thr-Asn-Thr- Arg15-Asp-Val-Asp-Cys-Asp-Ans-Ile-Met-Ser-Thr-Asn-Leu-Phe-His-C ys30-Lys-Asp-Lys - Asn-Thr-Phe-Ile-Tyr-Ser-Arg-Pro-Glu-Pro-Val-Lys45-Ala-Ile-Cys-Lys- Gly-Ile-Ile- Ala-Ser-Lys-Asn-Val-Leu-Thr-Thr60-Ser-Glu-Phe-Tyr-Leu-Ser-Asp -Cys-Asn-Val-Thr-Ser-Arg-Por-Cys75-Lys-Tyr-Lys-Leu-Lys-Lys-Ser-Thr -Asn-Lys-Phe- Cys-Val-Thr-Cys90-Glu-Asn-Gln-Ala-Pro-Val-His-Phe-Val-Gly-Val-Gly- Ser-Cys104-OH . Its molecular weight calculated from the sequence is 11,819. The sequence homology clearly indicates that the protein belongs to the superfamily of pancreatic ribonuclease. It is also demonstrated that it indeed exhibits a ribonucleolytic activity against highly polymerized RNA and that this activity seems to be essential for its antiproliferative/cytotoxic effects.
Provisioning for large scale cloud computing services (2012)

Resource provisioning, the task of planning sufficient amounts of resources to meet service level agreements, has become an important management task in emerging cloud computing services. In this paper, we present a stochastic modeling approach to guide the resource provisioning task for future service clouds as the demand grows large. We focus on on-demand services and consider service availability as the key quality of service constraint. A specific scenario under consideration is when resources can be measured in base instances. We develop an asymptotic provisioning methodology that utilizes tight performance bounds for the Erlang loss system to determine the minimum capacity levels that meet the service availability requirements. We show that our provisioning solutions are not only asymptotically exact but also provide better QoS guarantees at all load conditions.
Particle digestibility is required for induction of the phosphatidylserine recognition mechanism used by murine macrophages to phagocytose apoptotic cells. (1993)

One of the characteristic features of programmed cell death in vivo is the rapid recognition and removal of apoptotic cells by macrophages. Although there are several potential mechanisms by which the macrophage can identify a cell as apoptotic, it has been shown recently that murine-elicited macrophages stereospecifically recognize phosphatidylserine (PS) exposed on the surface of apoptotic cells. The particulate stimulus, beta-1, 3-glucan, stimulates bone marrow-derived macrophages to express several characteristics of inflammatory macrophages, and induced these cells to recognize PS on apoptotic cells; this activity was correlated with the ability to form rosettes with PS-expressing RBC. Induction of PS recognition in bone marrow-derived macrophages was associated with digestibility of the stimulus, because L, but not D amino acid particles or latex, were able to stimulate macrophage recognition of PS. The requirement for digestibility could be bypassed by the addition of exogenous TGF-beta, which induced macrophage recognition of PS after stimulation with either latex or D amino acid particles. That endogenously produced TGF-beta played a role in the glucan-stimulated response was indicated by the ability of anti-TGF-beta antibodies to inhibit digestible particle-induced recognition of PS. The induction of the PS recognition mechanism correlated well with the expression of other markers for the inflammatory phenotype. These studies indicate that the PS receptor may be a marker for the inflammatory phenotype, which appears to be induced by the phagocytosis of particulate digestible stimuli. Endogenously produced TGF-beta is suggested to play an autocrine or paracrine priming role in the induction of the PS receptor.
Administered dose and tumor dose of bleomycin labeled with cobalt-57 in mice and men. (1990)

Tumor concentrations of the chemotherapeutic drug, bleomycin, labeled with cobalt-57 (Co-bleo) were compared in mouse tumor models and in human lung tumors using quantitative single-photon emission computed tomography. Drug concentrations in histologically similar human tumors showed marked variability for the same injected dose (ID). Small cell carcinomas showed concentrations between 1.09 and 8.85 %ID/cc x 10(-3) while non-small cell lung tumors showed a concentration variation between 0.36 and 6.75 %ID/cc x 10(-3). In contrast to the situation in human tumors, uptake in mouse tumors showed only slight variability in animals with the same tumor model. EMT-6 tumors in mice showed at 6 hr significantly higher uptake of Co-bleo (p less than 0.001) and significantly higher tumor-to-lung ratio (p less than 0.001) when compared to murine fibrosarcomas. The EMT-6 tumors in contrast to the fibrosarcomas responded to bleomycin treatment in a dose dependent manner. The results indicate that while in mice the tumor dose closely follows the administered dose, in humans, the tumor dose and the tumor-to-lung ratio in the individual patient cannot be predicted from the administered dose.
B-cell differentiation following autologous, conventional, or T-cell depleted bone marrow transplantation: a recapitulation of normal B-cell ontogeny (1990)

The circulating lymphocytes of 88 consecutive patients following autologous, conventional, or T-cell depleted bone marrow transplantation were serially analyzed for B-cell surface antigen expression and function. In the majority of patients, except for those who developed chronic graft-versus-host disease, the number of circulating CD20+ B cell normalized by the fourth posttransplant month. The earliest detectable B cells normally expressed HLA-DR, CD19, surface immunoglobulin (slg), CD21, Leu-8, and lacked expression of CD10 (CALLA). In addition, the circulating B cells expressed CD1c, CD38, CD5, and CD23 for the first year following transplant, antigens that are normally expressed on a small percentage of circulating B cells in normal adults, but highly expressed on cord blood B cells. Similar to cord blood B cells, patient B cells isolated during the first year following transplant, proliferated normally to Staphylococcus aureus Cowan strain I (SAC), and produced IgM, but minimal or no IgG when stimulated with pokeweed mitogen and SAC, unlike normal adult B cells that produce both. The similar phenotype and function of posttransplant and cord blood B cells, and their similar rate of decline in patients and normal children adds further evidence to support the hypothesis that B-cell differentiation posttransplant is recapitulating normal B-cell ontogeny.
Clinical Experience with the 3M Microvascular Coupling Anastomotic Device in 100 Free-Tissue Transfers (1994)

The microvascular surgical anastomosis remains one of the most technically sensitive aspects of free-tissue transfers. To facilitate these often time-consuming, difficult anastomoses, various anastomotic coupling systems have been introduced. The 3M microvascular anastomotic coupling device, a polyethylene ring-pin device, was found to be highly successful in numerous animal studies. It has been available for use in human subjects for the last 4 years, but clinical experience remains sparse. Our clinical experience with the 3M coupler is reported in 100 free-tissue transfers. The average anastomotic time was 4 minutes. Mean follow-up was 8.6 months, and flap survival was 100 percent. The overall success rate for 3M (MACD) coupler use in microvascular anastomoses is 98.4 percent (121 of 123). Nine abandoned anastomoses were converted to sutured anastomoses intraoperatively. The over-all failure rate for 3M coupler anastomoses is 1.6 percent (2 of 123). We conclude that the 3M device is best suited for minimally discrepant, soft, pliable venous microvascular anastomoses and is unsuitable for end-to-side anastomoses in clinical situations. When carefully and selectively employed by a trained microvascular surgeon, the 3M coupler can be a safe, fast, and reliable adjunct for free-tissue transfers.
Determination of cortical bone porosity and pore size distribution using a low field pulsed NMR approach (2003)

The objective of this study was first to prove the concept of a low field pulsed nuclear magnetic resonance (NMR) process for assessing the cortical porosity and pore size distribution of human bone in vitro, and then to apply the technique to detect age-related changes of bone in these parameters. The Carr-Purcell-Meiboom-Gill NMR spin echo train method is used to determine the porosity, and an inversion NMR spin-spin relaxation (T(2)) spectrum is used to assess the pore size distribution in cortical bone. Using these techniques, cortical porosity and pore size distribution of 19 specimens of human cadaveric bone, ranging from 16 to 89 years of age, were assessed. The NMR results were compared with the histomorphometric data of the same bone samples to verify the efficacy of the NMR approach. Moreover, a coefficient (surface relaxivity) relating the pore size to the T(2) relaxation time was determined empirically for the Haversian canals and the osteocytic lacunae. The results of this study demonstrate that the in vitro NMR approach using T(2) relaxation techniques can directly assess the porosity and pore size distribution (Haversian canals and osteocytic lacunae) in human cortical bone. In addition, this study indicates that the age-related changes in cortical porosity relate predominantly to Haversian canals, whereas the porosity of osteocytic lacunae appears to be independent of age.
Somatic mutation and the origin of antibody diversity. Clonal variability of the immunoglobulin produced by MOPC 21 cells in culture (1973)

Abstract A method has been developed for the screening of immunoglobulins produced by large numbers of individual clones of the mouse myeloma (MOPC 21) in tissue culture. Clones grown in agar were incubated in the presence of radioactive amino acids and applied directly onto polyacrylamide plates for isoelectric focusing. A discrete number of well‐defined immunoglobulin bands were then detected by autoradiography. The following variations between different clones were observed: 1. Variation in relative intensity of the different bands. 2. Total absence of immunoglobulin bands. 3. Variation in the position of the bands along the pH gradient. When a mutant clone exhibiting this third type of variation was purified by subcloning, only the mutant pattern was observed. Thus, the cells appear to express only a single allele, although they are known to be aneuploid. We consider the third type of variation to be relevant in the evaluation of the contribution of somatic mutation to the diversity of antibody structure.
Editorial (1990)

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Cloning of human lymphocytes using limiting dilution. (1983)

A simple technique for cloning lymphocytes at limiting dilution in microwells has been developed using phytohaemagglutinin, irradiated cells and conditioned medium containing interleukin-2. For freshly isolated peripheral blood lymphocytes, the mean frequency of clone forming cells (CFC) was 29.4% and for continuously cultured lymphocytes it was 25.5%. Quantitative considerations, mixing experiments involving HLA-A2 positive and negative cells and replating experiments indicated that growth in most of the positive microwells originated from a single cell which had a very high self-renewal capacity and underwent approximately 15 divisions during the 14 days of culture. The high plating efficiency and sustained growth observed with this technique suggests that it is the method of choice for enumerating clone forming cells or for isolating clones.
Functional interference between the ubiquitous and constitutive octamer transcription factor 1 (OTF-1) and the glucocorticoid receptor by direct protein-protein interaction involving the homeo subdomain of OTF-1. (1992)

The ubiquitous and constitutive octamer transcription factor OTF-1 (Oct 1) is the target of positive regulation by the potent herpes simplex virus trans-activator VP16, which forms a complex with the homeodomain of OTF-1. Here we present evidence that the glucocorticoid receptor can negatively regulate OTF-1 function by a mechanism that is independent of DNA binding. In vivo-expressed glucocorticoid receptor inhibited in a hormone-dependent manner activation of a minimal promoter construct carrying a functional octamer site. Moreover, expression of the receptor in vivo resulted in hormone-dependent repression of OTF-1-dependent DNA-binding activity in nuclear extract. In vitro, the DNA-binding activity of partially purified OTF-1 was repressed following incubation with purified glucocorticoid receptor. Cross-linking and immunoprecipitation experiments indicated that the functional interference may be due to a strong association between these two proteins in solution. Finally, preliminary evidence indicates that the homeo subdomain of OTF-1 that directs formation of a complex with VP16 may also be critical for interaction with the glucocorticoid receptor. Thus, OTF-1 is a target for both positive and negative regulation by protein-protein interaction. Moreover, the functional interference between OTF-1 and the glucocorticoid receptor represents a novel regulatory mechanism in the cross-coupling of signal transduction pathways of nuclear receptors and constitutive transcription factors.
C-type lectins on dendritic cells: key modulators for the induction of immune responses (2008)

DCs (dendritic cells) are specialized in the recognition of pathogens and play a pivotal role in the control of immune responses. DCs are also important for homoeostatic control, recognizing self-antigens and tolerizing the tissue environment. The nature of the antigen recognized tilts the balance towards immunity or tolerance. CLRs (C-type lectin receptors) expressed by DC are involved in the recognition and capture of many glycosylated self-antigens and pathogens. It is now becoming clear that these CLRs may not only serve as antigen receptors allowing internalization and antigen presentation, but also function in the recognition of glycosylated self-antigens, and as adhesion and/or signalling molecules. The expression of C-type lectins is very sensitive to maturation stimuli, leading to down-regulation as DCs mature. CLRs such as DC-SIGN (DC-specific intracellular adhesion molecule-3 grabbing non-integrin) recognizes high-mannose-containing structures and Lewis antigens (Le(x), Le(y), Le(b) and Le(a)), whereas the CLR MGL (macrophage galactose/N-acetylgalactosamine-specific C-type lectin) recognizes GalNAc. Le(x), Le(y) and GalNAc glycan structures are often expressed on tumours. We have demonstrated that glycan modification of antigen can strongly enhance MHC class I responses and the induction of antigen-specific cytotoxic T-lymphocytes, indicating that glycosylated antigen targets C-type lectin to enhance antigen-specific T-cell responses. Moreover, these CLRs induce signalling processes in DCs and specific cytokine responses in combination with TLR (Toll-like receptor) triggering. This implies that specific C-type lectin-targeted antigens can regulate T-cell polarization. Understanding the diversity of C-type lectins being expressed on DCs as well as their carbohydrate-specific recognition profiles should promote understanding of pathogen recognition in many diseases, as well as the regulation of cellular interactions of DCs that are essential in the control of immunity.
Phosphorylation of HSF1 by MAPK-Activated Protein Kinase 2 on Serine 121, Inhibits Transcriptional Activity and Promotes HSP90 Binding (2005)

Heat shock transcription factor 1 (HSF1) monitors the structural integrity of intracellular proteins and its regulation is essential for the health and longevity of eukaryotic organisms. HSF1 also plays a role in the acute inflammatory response in the negative regulation of cytokine gene transcription. Here we show, for the first time, that HSF1 is regulated by the proinflammatory protein kinase MAPKAP kinase 2 (MK2). We have shown that MK2 directly phosphorylates HSF1 and inhibits activity by decreasing its ability to bind the heat shock elements (HSE) found in the promoters of target genes encoding the HSP molecular chaperones and cytokine genes. We show that activation of HSF1 to bind HSE in hsp promoters is inhibited through the phosphorylation of a specific residue, serine 121 by MK2. A potential mechanism for MK2-induced HSF1 inactivation is suggested by the findings that phosphorylation of serine 121 enhances HSF1 binding to HSP90, a major repressor of HSF1. Dephosphorylation of serine 121 in cells exposed to non-steroidal anti-inflammatory drugs leads to HSP90 dissociation from HSF1, which then forms active DNA binding trimers. These experiments indicate a novel mechanism for the regulation of HSF1 by proinflammatory signaling and may permit HSF1 to respond rapidly to extracellular events, permitting optimal physiological regulation.
Improved engraftment of human spleen cells in NOD/LtSz-scid/scid mice as compared with C.B-17-scid/scid mice. (1995)

T and B lymphocyte-deficient mice homozygous for the severe combined immunodeficiency (SCID) mutation can be immunologically engrafted with human lymphocytes. However, low levels of human peripheral blood mononuclear cell engraftment are commonly observed, impeding full use of this model. We now demonstrate that strain background in mice homozygous for the scid mutation is a strong determinant of levels of human lymphocyte engraftment. NOD/LtSz-scid/scid mice support higher levels of engraftment of both human spleen and peripheral blood mononuclear cells than do C.B-17-scid/scid mice. We observed, using human spleen cell injected scid mice, 1), high levels of engraftment of the host peripheral lymphoid tissues with human CD45+ (leukocytes), CD3+ (T cells), CD4+ (helper/inducer), and CD8+ (suppressor/cytotoxic) lymphoid cells for up to 24 weeks in NOD/LtSz-scid/scid mice; 2), migration of high numbers of human lymphocytes to peripheral lymphoid and nonlymphoid organs in NOD/LtSz-scid/scid, but not in C.B-17-scid/scid mice; 3), higher levels of serum immunoglobulin of human origin in NOD/LtSz-scid/scid mice than in C.B-17-scid/scid mice; 4), histological lesions characteristic of human anti-mouse xenoreactivity in NOD/LtSz-scid/scid mice; and 5), human origin antibodies against filarial antigens after engraftment with native human spleen cells. The use of NOD/LtSz-scid/scid mice as recipients to achieve significantly enhanced human lymphopoietic cell engraftment will now enable human immunity to be more easily studied in animal models.
Reevaluation of the evidence that an antibody to the insulin receptor is insulinmimetic without activating the protein tyrosine kinase activity of the receptor. (1987)

The immunoglobulin fraction of a polyclonal anti-insulin receptor antibody (B-10) derived from a patient with severe insulin resistance and acanthosis nigricans was tested for its ability to activate the protein kinase activity of the insulin receptor and to mimic insulin action in Chinese hamster ovary cells expressing either wild type or kinase-deficient human insulin receptors. This antiserum had previously been reported to be insulinmimetic without activating the insulin receptor protein tyrosine kinase. Antibody B-10 bound to both wild type and mutant human insulin receptors, but it induced receptor down-regulation and stimulated hexose transport and thymidine incorporation into DNA only in cells expressing the wild type receptor. Furthermore, this antibody activated the kinase activity of the wild type insulin receptor in intact cells and in vitro. It is likely, therefore, that the biological activities of antibody B-10, like those of insulin, depend upon the protein tyrosine kinase activity of the insulin receptor.
Hydroxylated metabolites of tamoxifen are formed in vivo and bound to estrogen receptor in target tissues. (1981)

After in vivo administration of [3H]tamoxifen to immature female rats and chickens, polar metabolites of tamoxifen were found in plasma, liver, uterus, and oviduct. 4-Hydroxytamoxifen and M2, another hydroxylated metabolite of tamoxifen, were the major tritiated compounds of the cytosol and the KCl-nuclear extract of target tissues and appeared to occupy the estrogen receptor sites since their accumulation in these fractions was saturable, resistant to charcoal, and prevented by estradiol. In the rat uterus, 4-hydroxytamoxifen was predominant during the 24 h following the [3H]tamoxifen injection, then its concentration declined while M2 became predominant. 4-Hydroxytamoxifen was also found in chicken oviduct where tamoxifen is acting as a full estrogen antagonist. Moreover, liver, chicken oviduct, and lamb uterus were able to convert tamoxifen into 4-hydroxytamoxifen in vitro. Other estrogen target tissues, such as the rat uterus, dimethylbenz (a) anthracene-induced rat mammary tumors, and MCF7 cells, did not transform tamoxifen significantly. 4-Hydroxytamoxifen formed in vitro was able to bind selectively to estrogen receptor with a high affinity and with a low dissociation rate similar to estradiol. These results demonstrate that 4-hydroxytamoxifen is formed in vivo and retained on estrogen receptor in target tissues, due to its high affinity. Since we have separately shown that 4-hydroxytamoxifen is a full anti-estrogen, more potent than tamoxifen itself in MCF7 cells, we conclude that tamoxifen is mostly acting in vivo indirectly via hydroxylated metabolite(s).
A Compact SPICE Model for Carbon-Nanotube Field-Effect Transistors Including Nonidealities and Its Application—Part II: Full Device Model and Circuit Performance Benchmarking (2007)

This paper presents a complete circuit-compatible compact model for single-walled carbon-nanotube field-effect transistors (CNFETs) as an extension to Part 1 of this two-part paper. For the first time, a universal circuit-compatible CNFET model including the practical device nonidealities is implemented with HSPICE. In addition to the nonidealities included in the companion paper, this paper includes the elastic scattering in the channel region, the resistive source/drain (S/D), the Schottky-barrier resistance, and the parasitic gate capacitances. More than one nanotube per device can be modeled. Compared to silicon technology, the CNFETs show much better device performance based on the intrinsic gate-delay metric (six times for nFET and 14 times for pFET) than the MOSFET device at the 32-nm node, even with device nonidealities. This large speed improvement is significantly degraded (by a factor of five to eight) by interconnect capacitance in a real circuit environment. We performed circuit-performance comparison with all the standard digital library cells between CMOS random logic and CNFET random logic with HSPICE simulation. Compared to CMOS circuits, the CNFET circuits with one to ten carbon nanotubes per device is about two to ten times faster, the energy consumption per cycle is about seven to two times lower, and the energy-delay product is about 15-20 times lower, considering the realistic layout pattern and the interconnect wiring capacitance.