gebhart/patrepeval huggingface dataset:
Xenogeneic Graft-versus-Host-Disease in NOD-scid IL-2Rγnull Mice Display a T-Effector Memory Phenotype (2012)

The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD.
A phase I study of E7080 in patients (pts) with advanced malignancies (2008)

3526 Background: E7080 is a potent inhibitor of the split-kinase family of transmembrane growth factor receptors including VEGFRs 1 and 2, and also potently inhibits FGFR-1 and PDGFR-β tyrosine kinase activities. E7080 inhibited VEGF-driven umbilical vein endothelial cell proliferation and tube formation in vitro, and inhibited tumor growth in H460 and Colo205 mouse xenografts models in vivo at doses of 1–100mg/kg. Methods: The primary objective of this study was to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of E7080 in pts with advanced solid tumors refractory to standard therapies. Eligible pts were those with ECOG PS < 2 and adequate haematologic, renal and hepatic function. E7080 was administered orally on a once daily continuous schedule in 4-week cycles. Dose escalation was by an accelerated design (100% dose increases until the 1st pt experienced toxicity ≥ grade 2). Samples for pharmacokinetic (PK) analyses were collected on days 1, 8, 15, 22 and 29. A food effect PK sub-study is ongoing at the MTD. Results: 59 pts (35 m, 24 f), median age = 55 yrs (range 25–84) were treated at dose levels (mg/day) of 0.2, 0.4, 0.8, 1.6, 3.2, 6.4, 12.5, 16, 20, 25 and 32 mg. Median number cycles = 5 (0–22). 53 pts are evaluable for toxicity so far. DLTs included 2 pts at 32mg (both proteinuria), 1 pt each at 16mg (hypertension), 12.5mg (proteinuria) and 6.4mg (febrile neutropenia). The MTD is 25mg daily. Dose reductions (n=12pts) were most commonly for ≥ grade 2 proteinuria (5 pts) and hypertension (5 pts). Other grade 3/4 toxicities include haemorrhage and thrombosis (n=1) and tachycardia (n=1). 37 pts are now evaluable for response: 5 pts have confirmed PR (1 sarcoma, 2 melanoma, 2 renal carcinoma), 25 pts have had stable disease for a median of 16 weeks (range 8–88). The PK was described by a 2- compartment model. Clearance was linear with dose and unchanged with multiple dosing. A saturable decrease in the distribution volume was observed with dose from 0.2 up to 1.6 mg. The covariate and food effect analyses will be reported in the full presentation. Conclusions: E7080 displays linear PK and is safe and well tolerated at doses up to 25mg daily with signs of anti-cancer activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eisai Medical Research Eisai Medical Research Eisai Medical Research
Binding of Human Phospholipase A2 Type II to Proteoglycans (1996)

Phospholipase A2 acting on low density lipoproteins in the extracellular arterial intima may form proinflammatory lipid mediators. Human nonpancreatic secretory phospholipase A2 has three regions that may associate with sulfated glycosaminoglycans. The apoB-100 molecule in low density lipoproteins also has glycosaminoglycan binding regions that could mediate its retention in the arterial intima. Here we report that human nonpancreatic phospholipase A2 isolated from a transfected cell line binds to glycosaminoglycans secreted by cultured human arterial smooth muscle cells. A gel mobility shift assay showed that the affinity of phospholipase A2 for glycosaminoglycans from a heparan sulfate/chondroitin sulfate proteoglycan was higher than for chondroitin sulfate glycosaminoglycans from a larger versican-like proteoglycan. Affinity chromatography confirmed these results. All glycosaminoglycans tested, at concentrations up to 100 microM, increased the activity of phospholipase A2 toward phosphatidylcholine liposomes. Above this concentration, heparan sulfate and heparin inhibited the enzyme. Heparin and chondroitin 6-sulfate increased phospholipase A2 activity on low density lipoproteins up to 4-fold at 100 microM, whereas heparan sulfate had no effect. The results indicate that human nonpancreatic secretory phospholipase A2 interacts with proteoglycans via their glycosaminoglycan moiety and that the enzyme activity may be modulated by the association of the enzyme and its substrate to the sulfated polysaccharides.
High-Q microsphere cavity for laser stabilization and optoelectronic microwave oscillator (1999)

With submillimeter size and optical Q up to approximately 10<SUP>10</SUP>, microspheres with whispering-gallery (WG) modes are attractive new component for fiber-optics/photonics applications and a potential core in ultra-compact high- spectral-purity optical and microwave oscillators. In addition to earlier demonstrated optical locking of diode laser to WG mode in a microsphere, we report on microsphere application in the microwave optoelectronic oscillator, OEO. In OEO, a steady-state microwave modulation of optical carrier is obtained in a closed loop including electro- optical modulator, fiber-optic delay, detector and microwave amplifier. OEO demonstrates exceptionally low phase noise (-140 dBc/Hz at 10 kHz from approximately 10 GHz carrier) with a fiber length approximately 2 km. Current technology allows to put all parts of the OEO, except the fiber, on the same chip. Microspheres, with their demonstrated Q equivalent to a kilometer fiber storage, can replace fiber delays in a truly integrated device. We have obtained microwave oscillation in microsphere-based OEO at 5 to 18 GHz, with 1310 nm and 1550 nm optical carrier, in two configurations: (1) with external DFB pump laser, and (2) with a ring laser including microsphere and a fiber optic amplifier. Also reported is a simple and efficient fiber coupler for microspheres facilitating their integration with existing fiber optics devices.
Transcutaneous electrical nerve stimulation for acute pain (2009)

Due to insufficient extractable data in the studies included in this review, we are unable to make any definitive conclusions about the effectiveness of TENS as an isolated treatment for acute pain in adults.
Production and use of nuclear tracks: imprinting structure on solids (1983)

Latent nuclear tracks are damaged zones, created along the paths of rapidly moving ions in solids. They are stored indefinitely in many insulators and can be used to initiate a phase separation process by one of several procedures that remove, collect, or transform material along the latent track. The resulting two-step technique is based on separate inscription and development stages, similar to the lithographic techniques using visible light, uv, x rays, or electrons. In contrast to these other techniques, however, it is applicable even to mechanically very stable, chemically inert, radiation-resistant dielectric materials. The most common development procedure is track etching, which acts as a chemical "amplifier" that dissolves the damaged zone of the latent track preferentially, creating etch pits or channels that can be extremely fine. Etched track diameters start around 10 nm and increase linearly with the etching time. The most outstanding feature of the technique is that one single particle is sufficient to create a developable damage. This unique combination of recording and revealing properties makes possible a single-particle structuring tool with a very wide array of applications. With the advent of high-energy, heavy-ion accelerators, with ion ranges between micrometers and centimeters, large-scale application of the technique to the imprinting of structure onto solids has become possible. At present, most frequently random track arrays are employed to induce global property changes of the solid volume or surface. In the future, scanning ion microbeam technology will make possible local generation of oriented track structures with high precision. This "ultimate" microtool should provide the versatility of a computer-controlled mechanical lathe. This review describes the processes involved in track generation. It outlines applications that are on the verge of being commercialized at present and considers future possibilities.
Piezomagnetic and elastic properties of metallic glass alloys Fe67CO18B14Si1 and Fe81B13.5Si3.5C2 (1983)

The piezomagnetic and elastic properties of two metallic glass alloys Fe67Co18B14Si1 (Metglas 2605CO) and Fe81B13.5Si3.5C2 (Metglas 2605SC) are presented. The Metglas 2605CO and 2605SC alloys show optimum magnetomechanical coupling coefficient k33, change of Young’s modulus as a function of applied field ΔE/E, and piezomagnetic strain constant d33 values of 0.76, 0.79, 88×10−9 m/A and 0.90, 4.72, 400×10−9 m/A, respectively. The ΔE/E and d33 values of the 2605SC alloy are the largest ever reported. This alloy has a hydrophone figure-of-merit that far exceeds the corresponding value of a commonly used piezoelectric ceramic, PZT4. Both of these commercially available alloys should find considerable use in transduction devices such as sensors or variable acoustic delay lines.
Sinusitis of the Maxillary Antrum (1975)

Twenty-four adults with clinical evidence of sinusitis were studied by 65 needle punctures of the maxillary antrum. Fourteen of 15 sinuses with normal transillumination and 19 of 26 that were dull had normal aspirates, whereas 24 of 24 that were opaque had abnormal aspirates (P less than 0.001). Marked mucosal thickening as determined radiologically (Water's view) was associated with abnormal aspirates whereas lesser mucosal thickening was not (P less than 0.001). In acute sinusitis, there was a strong correlation between high aspirate leukocyte counts (greater than 1000 per cubic millimeter) and infection as manifested by bacterial titers of greater than 10(5) per milliliter or the isolation of virus fungus (P greater than 0.001). Anterior-nasal-swab cultures correlated poorly with direct aspirate culters. Organisms frequently recovered from the sinus included Haemophilus influenzae, Strepto coccus pneumoniae, and anaerobic bacteria. Rhinovirus was recovered twice. Antibiotics were usedful in patients with acute sinusitis if the organism was sensitive in vitro (P less than 0.001).
Identification of a 170 kDa membrane kinase with increased activity in KB‐V1 multidrug resistant cells (1993)

Using an in situ kinase assay we have identified kinases that are elevated in some multidrug resistant cells. Kinases were detected by measurement of 32P incorporation in proteins that were renatured after being subjected to SDS-polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride membranes [Ferrell and Martin: J Biol Chem 264:20723-20729, 1989; Mol Cell Biol 10:3020-3026, 1990]. Kinases at 79, 84, and 92 kDa showed increased activity in the multidrug resistant human KB-V1 cells as compared to the sensitive parental KB-3-1 cells. The KB-V1 multidrug resistant cell line exhibited a 170 kDa membrane associated kinase activity that was not present in the parental drug sensitive line. The 170 kDa kinase activity was not affected by Ca++, phosphatidylserine, or cAMP, but was diminished after incubation in the presence of the kinase inhibitors staurosporine, K252a and KT5720. The 170 kDa kinase activity phosphorylated mainly threonine, with no evidence of tyrosine phosphorylation, and was not identical to either the multidrug resistance associated P-glycoprotein or the EGF receptor. Other multidrug resistant cell lines also showed elevated 170 kDa kinase activity, such as the human breast cancer MCF-7/Adr(R) and murine melanoma B16/Adr(R) cells, but the activity was not present in murine leukemia P-388 sensitive or multidrug resistant cells.
Production of TNF-alpha ex vivo is predictive of an immune response to flu vaccination in a frail elderly population (2016)

Production of TNFα appears to be primordial for an efficient vaccine response, and may provide a predictive marker for the humoral response to vaccination. It may also provide the basis for evaluating agents designed to rescue TNFα-producing cells. This study emphasises a need to rescue TNF-producing cell function.
A phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advanced stage ovarian, primary peritoneal, and fallopian tube cancer (2005)

5047 Background: Elevated expression of EGFR in ovarian cancer is associated with poor prognosis. This study is being conducted to assess the feasibility of adding the anti-EGFR antibody cetuximab (C225) to standard upfront chemotherapy for ovarian cancer. Methods: Previously untreated patients (pts) with stage III or IV epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma are eligible for this study. KPS must be ≥70% and tumors must be EGFR positive. Pts receive an initial dose of C225 of 400 mg/m2 on Day 1 of Cycle 1, followed by 250 mg/m2 weekly. Paclitaxel (P, 175 mg/m2) and carboplatin (C, AUC=6mg/ml.min) are given on D1 of each 3-wk cycle. Pts may receive a max. of 6 cycles during initial treatment. Pts with complete clinical response (cCR) receive 6 months consolidation with weekly C225. The primary objective is progression-free survival (PFS); response rate and toxicity are also assessed. A total of 39 eligible pts are planned for accrual; 31 pts have been accrued to date. Results: The first 17 pts completing 6 cycles of initial treatment are reported. Median age 54 yrs. (range 37–75). 10 pts (IIIA-1, IIIB-1, IIIC-8) were opt debulked, 4 pts (IIIC-4) subopt debulked and 3 pts were Stage IV. 71% ovarian, 23% primary peritoneal, 6% fallopian tube carcinoma. Histology: 100% serous adenocarcinoma. 15 of 17 pts were evaluable for response; 2 pts with wrong diagnosis were unevaluable. 13 pts (87%) had unconfirmed cCR. 10 (100%) of opt debulked pts and 3 (75%) of subopt debulked pts had cCR. 15 pts (88%) received the planned dose of C225; 16 pts (94%) and 17 pts (100%) received planned doses of P and C, respectively. Median no. (range): C225 doses, 18 (1–18); C225 doses/cycle, 3 (1–3); and cycles of C225/P/C completed, 6 (1–6). Gr 3 toxicities: febrile neutropenia (12%), diarrhea (6%), and hypersensitivity (6%). No Gr 4 toxicities were noted. Fifteen pts (88%) had acneform rash (Gr 1/2 53%/35%). Conclusions: Preliminary data for this ongoing study indicate the combination of C225 with P and C is well tolerated in this patient population. Data on tolerability of prolonged maintenance cetuximab will be available for presentation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Maternal Exposure to Benzo[A]Pyrene Alters Development of T Lymphocytes in Offspring (1999)

Childhood cancer has been increasing significantly over the past two decades in the United States, suggesting that environmental exposures may be playing a causative role. One such cause may be maternal smoking during pregnancy. Suspected carcinogens in cigarette smoke and environmental pollution include N-nitrosamines and polycyclic aromatic hydrocarbons, which may be several micrograms per exposure. Previously, we have shown that mouse progeny of mothers exposed to benzo[a]pyrene (B[a]P) during midpregnancy had abnormalities in their humoral and cell-mediated immune response. Immunodeficiency was detectable during gestation, at one week after birth and persisted for 18 months. Tumor incidences in progeny were eight to 10-fold higher than in controls. The present study compared frequencies of CD4+, CD8+, V gamma 2+, and V beta 8+ T cells in progeny following in utero exposure to B[a]P. The significant reduction in newborn CD4+CD8+, CD4+CD8+V beta 8+ thymocytes and CD4+ splenocytes from 1-week-old progeny, suggests that B[a]P induces abnormal changes in developing T cells. These early alterations may lead to postnatal T cell suppression, thus providing a more suitable environment for the growth of tumors later in life. These results suggest that developmental immunosuppression mediated by B[a]P may play a critical role in the relationship between maternal exposures and childhood carcinogenesis.
Inhibition of T cell apoptosis by IFN-β rapidly reverses nuclear translocation of protein kinase C-δ (1999)

Type I interferons rescue activated human T cells from cytokine deprivation-induced apoptosis. Our data now show that IFN-beta also rapidly inhibits apoptotic signals induced through the Fas receptor (CD95) in human T cells. To identify upstream signaling elements that could be targets of IFN-beta, we have studied protein kinase C (PKC). PKC-delta is actively involved in the regulation of apoptosis and immunofluorescence staining revealed that early in apoptosis PKC-delta accumulated in the nucleus. Addition of IFN-beta to T cells already deprived of survival factors or treated with anti-Fas antibody caused a rapid retranslocation of PKC-delta away from the nucleus. Furthermore, the generation of a constitutively active catalytic fragment by cleavage of PKC-delta by caspase 3 occurred only after translocation of full-length PKC-delta to the nucleus. IFN-beta also inhibited caspase 3 and the proteolytic activation of PKC-delta. We conclude from these studies that nuclear translocation of PKC-delta is an early event in T cell apoptosis and that IFN-beta rapidly reverses this process.
Packet reservation multiple access for local wireless communications (2003)

Packet reservation multiple-access (PRMA) allows a variety of information sources to share the same wireless access channel. Some of the sources, such as speech terminals, are classified as periodic and others, such as signaling are classified as random. Packets from all sources contend for access to channel time slots. When a periodic information terminal succeeds in gaining access, it reserves subsequent time slots for uncontested transmission. Computer simulations reveal that PRMA combines high bandwidth efficiency with low control complexity and the flexibility to accept information from a diversity of sources. It is considered a promising technique for wireless access to future telecommunications networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Glutamine-dependent nitrogen transfer in Escherichia coli asparagine synthetase B. Searching for the catalytic triad. (1994)

The mechanism of nitrogen transfer in glutamine-dependent amidotransferases remains to be unambiguously established. We now report the overexpression, purification, and kinetic characterization of both the glutamine- and ammonia-dependent activities of Escherichia coli asparagine synthetase B (AS-B) and a series of mutants. In common with other members of the purF family of amidotransferases, the recombinant enzyme possesses an NH2-terminal cysteine residue. Replacement of Cys-1 by either alanine or serine results in a loss of glutaminase and glutamine-dependent activity, without out any significant effect upon ammonia-dependent asparagine synthesis. As previously observed for human AS (Sheng, S., Moraga-Amador, D., Van Heeke, G., Allison, R. D., Richards, N. G. J., and Schuster, S. M. (1993) J. Biol. Chem. 268, 16771-16780), glutamine is an inhibitor of the ammonia-dependent reaction catalyzed by both the Cys-1-->Ala (C1A) and Cys-1-->Ser (C1S) mutants of AS-B. In the case of C1A, the inhibition pattern suggests that an abortive complex is formed. This is consistent with a recent proposal implicating the formation of an imide intermediate in the nitrogen transfer reaction (Richards, N. G. J., and Schuster, S. M. (1992) FEBS Lett. 313, 98-102). In contrast, glutamine appears to be only a competitive inhibitor of the ammonia-dependent activity of C1S. Cys-1 does not appear to be required for glutamine binding. Replacement of Asp-33 by either asparagine or glutamic acid has little effect on the kinetic properties of the mutant enzymes when compared to wild-type AS-B. Cys-1 and Asp-33 are cognate to residues Cys-1 and Asp-29 in glutamine phosphoribosylpyrophosphate amidotransferase which have been proposed to be members of a catalytic triad responsible for mediating nitrogen transfer in this enzyme (Mei, B., and Zalkin, H. (1989) J. Biol. Chem. 264, 16613-16619). In the case of AS-B, although Cys-1 is essential for glutamine-dependent activity, Asp-33 does not appear to participate in mediating nitrogen transfer. In an effort to locate other residues which might form part of a "catalytic triad" in the glutamine amidotransferase domain of AS-B, we have expressed and characterized mutant proteins in which His-29 and His-80, which are conserved within the glutamine amidotransferase domain of purF amidotransferases, are replaced by alanine (H29A and H80A).(ABSTRACT TRUNCATED AT 400 WORDS)
Primary Umbilical Endometriosis: Case Report and Literature Review. (2009)

Primary umbilical endometriosis is defined as presence of ectopic endometrial glands within umbilicus without prior history of pelvic endometriosis. It is rare presentation in all cases of endometriosis, especially in Asians. We reported a 37 year-old female patient presented as an umbilical mass with cyclic bleeding who received complete surgical resection of umbilical lesion. Primary umbilical reconstruction was done. Good aesthetic result was obtained after 6 months follow-up. During the follow up of 10 years period, no recurrence was found. The epidemiology, clinical symptoms, pathophysiology, treatment and differential diagnosis of umbilical lesion were reviewed.