gebhart/patrepeval huggingface dataset:
A phase 2 study of lenalidomide, rituximab, cyclophosphamide, and dexamethasone (LR‐CD) for untreated low‐grade non‐Hodgkin lymphoma requiring therapy (2017)

Patients with indolent non-Hodgkin lymphoma (NHL) have multiple treatment options yet there is no consensus as to the best initial therapy. Lenalidomide, an immunomodulatory agent, has single agent activity in relapsed lymphoma. This trial was conducted to assess feasibility, efficacy, and safety of adding lenalidomide to rituximab, cyclophosphamide, and dexamethasone (LR-CD) in untreated indolent NHL patients requiring therapy. This was a single institution phase II trial. Treatment consisted of IV rituximab 375 mg/m<sup>2</sup> day 1; oral lenalidomide 20 mg days 1-21; cyclophosphamide 250 mg/m<sup>2</sup> days 1, 8, and 15; and dexamethasone 40 mg days 1, 8, 15, and 22 of a 28-day cycle. Treatment continued 2 cycles beyond best response for a maximum of 12 cycles without rituximab maintenance. Thirty-three patients were treated. Median age was 68 (43-83 years). 39% had stage IV disease. Histologic subtypes included 8 follicular lymphoma (FL), 7 marginal zone lymphoma (MZL) (1 splenic, 2 extranodal, and 4 nodal), 15 Waldenström's macroglobulinemia (WM), 1 lymphoplasmacytic lymphoma, 1 small lymphocytic lymphoma, and 1 low-grade B-cell lymphoma with plasmacytic differentiation (unable to be classified better as MZL or LPL). Hematologic toxicity was the most common adverse event. Median time of follow-up was 23.4 months (range 1.8-50.9). The overall response rate was 87.9%, with 30.3% complete response. The median duration of response was 38.7 months. The median progression free survival was 39.7 months, while median overall survival (OS) has not yet been reached. Lenalidomide can be safely added to a simple regimen of rituximab, oral cyclophosphamide, and dexamethasone and is an effective combination as initial therapy for low-grade B-cell NHL.
Cardiolipin is a normal component of human plasma lipoproteins (2000)

Anticardiolipin (anti-CL) antibodies, diagnostic for antiphospholipid antibody syndrome, are associated with increased risks of venous and arterial thrombosis. Because CL selectively enhances activated protein C/protein S-dependent anticoagulant activities in purified systems and because CL is not known to be a normal plasma component, we searched for CL in plasma. Plasma lipid extracts [chloroform/methanol (2:1, vol/vol)] were subjected to analyses by using TLC, analytical HPLC, and MS. A plasma lipid component was purified that was indistinguishable from reference CL (M:1448). When CL in 40 fasting plasma lipid extracts (20 males, 20 females) was quantitated by using HPLC, CL (mean +/- SD) was 14.9 +/- 3.7 microgram/ml (range 9.1 to 24.2) and CL was not correlated with phosphatidylserine (3.8 +/- 1.7 microgram/ml), phosphatidylethanolamine (64 +/- 20 microgram/ml), or choline-containing phospholipid (1,580 +/- 280 microgram/ml). Based on studies of fasting blood donors, CL (>/=94%) was recovered in very low density, low density, and high density lipoproteins (11 +/- 5.3%, 67 +/- 11.0%, and 17 +/- 10%, respectively), showing that the majority of plasma CL (67%) is in low density lipoprotein. Analysis of relative phospholipid contents of lipoproteins indicated that high density lipoprotein is selectively enriched in CL and phosphatidylethanolamine. These results shows that CL is a normal plasma component and suggest that the epitopes of antiphospholipid antibodies could include CL or oxidized CL in lipoproteins or in complexes with plasma proteins (e. g., beta(2)-glycoprotein I, prothrombin, protein C, or protein S) or with platelet or endothelial surface proteins.
The Role of Protective Groups in Organic Synthesis (2006)

This chapter contains sections titled: Properties of a Protective Group Historical Development Development of New Protective Groups Selection of a Protective Group from this Book Synthesis of Complex Substances. Two Examples (As Used in the Synthesis of Himastatin and Palytoxin) of the Selection, Introduction, and Removal of Protective Groups
低人口出生率和人口老化——原因、后果及政策选择 (2006)

几乎所有的欧洲国家都经历着人口出生率长期低下和由此造成的人口老化问题。目前欧洲各国的人口出生率几乎都低于人口代率（每对夫妇生育2．1个子女）。结果是，人口自然增长率进入了增长缓慢或明显下降的阶段。同时，老年人口持续增多，而劳动力人口减少。此外，多数欧洲国家的净移民仍然普遍很少。这些趋势有可能对欧洲经济造成破坏性的后果。例如：
Nucleophile-Initiated Thiol-Michael Reactions: Effect of Organocatalyst, Thiol, and Ene (2010)

A detailed evaluation of the kinetics of the thiol-Michael reaction between hexanethiol and hexyl acrylate is described. It is shown that primary amines are more effective catalysts than either secondary or tertiary amines with, for example, quantitative conversion being achieved within 500 s in the case of hexylamine with an apparent rate constant of 53.4 mol L−1 s−1 at a catalyst loading of 0.057 mol %. Certain tertiary phosphines, and especially tri-n-propylphosphine and dimethylphenylphosphine, are shown to be even more effective species even at concentrations 2 orders of magnitude lower than employed for hexylamine and performed in solution with quantitative conversions reached within ca. 100 s for both species and apparent rate constants of 1810 and 431 mol L−1 s−1, respectively. The nature of the thiol is also demonstrated to be an important consideration with mercaptoglycolate and mercaptopropionate esters being significantly more reactive than hexanethiol with reactivity mirroring the pKa of the thiols. Likewise, it is shown that the structure of the activated ene is also crucial with the degree of activation and ene-substitution pattern being important features in determining reactivity. In terms of reaction with hexanethiol in the presence of hexylamine as catalyst, it is shown that propylmaleimide > diethyl fumarate > diethyl maleate > dimethylacrylamide > acrylonitrile > ethyl crotonate > ethyl cinnamate > ethyl methacrylate.
No Change in Plasma Free Testosterone Ratio and Plasma Sex Hormone-Binding Globulin Concentration during hCG Stimulation (1984)

Plasma sex hormone-binding globulin (SHBG) levels and free testosterone ratios were determined independently after administration of hCG for 4 consecutive days to eight normal men. Correcting for nonspecific dihydrotestosterone binding, no changes in plasma SHBG were found. The free testosterone ratio, measured by equilibrium dialysis, did not change despite doubling of total plasma testosterone. The increase in plasma testosterone after hCG stimulation was due to increased production only, with equivalent changes in free testosterone concentration, and was not a result of changes in SHBG concentration.
Interaction of Slow HCI with Solid Surfaces: What Do We Know, What Should We Know? (2001)

A slow multicharged ion (MCI) which approaches a solid surface catches electrons from the latter into highly excited states and transiently becomes a neutral "hollow atom" (HA). Rapid autoionisation of this HA will be balanced by further ongoing electron capture until close surface contact where shielding sets in, and inner-shell vacancy recombination at and below the surface produces further slow electrons and characteristic fast electrons and soft X-rays. Until its complete neutralization the projectile continues to be attracted toward the surface by its decreasing image charge which causes a minimum impact velocity. Many aspect of this HA scenario have been studied by a number of groups for different ion species and - charge states at metal-, semiconductor- and insulator surfaces with a number of experimental methods. The most detailed comparison with available theory is possible if electron emission and projectile energy losses and -charge changes are studied in mutual coincidence for scattering along well defined trajectories at smooth mono-crystalline target surfaces. For insulator surfaces so called "potential sputtering" (PS) and strong secondary ion emission can be induced by the multi-electron capturing MCI. Our current understanding of the above-surface part of MCI-surface interactions is satisfactory and can also explain how "free" hollow atoms and -ions are produced by funneling MCI through thin capillaries or colliding them on clusters or fullerenes. Because of the approximately additive influence of potential- and kinetic ion energies on the resulting electron emission, for this part a straighforward definition of the term "highly charged ion" (HCI) can be given. On the other hand, processes occuring at and below the surface are so far less well understaood since they depend on the potential- and kinetic ion energies in a clearly non-additive way. This is particularly true for PS and excitation of target plasmons due to the potential MCI energy. PS and related phenomena are also of practical interest for new surface-analytical and nano-technological applications.
Radioimmunotherapy of intracerebral human glioma xenografts with 131I-labeled F(ab')2 fragments of monoclonal antibody Mel-14. (1990)

The administration of radiolabeled monoclonal antibodies to improve the treatment of malignant gliomas is dependent upon achieving effective tumor radiation dose while sparing normal tissues. We have evaluated the efficacy of 131I-labeled F(ab')2 fragment of monoclonal antibody Mel-14, an IgG2a reactive with the chondroitin sulfate proteoglycan antigen of gliomas, melanomas, and other neoplasms, in prolonging survival of athymic mice transplanted intracerebrally with D-54 MG human glioma xenografts. Studies indicated that in vitro immunoreactivity, affinity, and tumor localization in vivo of radiolabeled Mel-14 F(ab')2 were maintained at specific activities of 10-13 microCi/micrograms. Intravenous injection of 1500 microCi/115 micrograms or 2000 microCi/154 micrograms 131I-labeled Mel-14 F(ab')2 into mice 6-7 days after xenograft implantation resulted in significant survival prolongation over control animals (P = 0.009 using Wilcoxon rank sum analysis). In another experiment, 1500 microCi/126 micrograms 131I-labeled Mel-14 F(ab')2 improved survival significantly over controls (P = 0.006), while 1500 microCi/220 micrograms 131I-labeled nonspecific antibody did not (P = 0.2). Increasing the injected radiation dose to 3000 microCi 131I-labeled Mel-14 F(ab')2 did not significantly increase survival in tumor-bearing mice, because of supervening radiation toxicity. However, giving 3000 microCi 131I-labeled Mel-14 F(ab')2 in two doses of 1500 microCi, 48 h apart, did significantly prolong animal survival over controls (P = 0.001). Estimated radiation dose to tumor was 915 rad after injection of 3000 microCi 131I-labeled Mel-14 F(ab')2 in two doses, a dose higher than that delivered to normal tissues. The results of this study suggest that radiolabeled Mel-14 F(ab')2 be evaluated as an agent for radioimmunotherapy trials.
A System for Culture of Endothelial Cells in 20–50‐μm Branching Tubes (1995)

An in vitro endothelial cell culture system was constructed which mimics the geometry and hemodynamics conditions of resistance arterioles. This system can be used to examine endothelial cell responses to flow and flow gradients under defined and controllable conditions which mimic the arteriolar microcirculation.
TWIST is Expressed in Human Gliomas, Promotes Invasion (2005)

TWIST, a basic helix-loop-helix (bHLH) transcription factor that regulates mesodermal development, has been shown to promote tumor cell metastasis and to enhance survival in response to cytotoxic stress. Our analysis of rat C6 glioma cell-derived cDNA revealed TWIST expression, suggesting that the gene may play a role in the genesis and physiology of primary brain tumors. To further delineate a possible oncogenic role for TWIST in the central nervous system (CNS), we analyzed TWIST expression in human gliomas and normal brain by using reverse transcription polymerase chain reaction, Northern blot analysis, in situ hybridization, and immunohistochemistry. TWIST expression was detected in the large majority of human glioma-derived cell lines and human gliomas examined. Levels of TWIST mRNA were associated with the highest grade gliomas, and increased TWIST expression accompanied transition from low grade to high grade in vivo, suggesting a role for TWIST in promoting malignant progression. In accord, elevated TWIST mRNA abundance preceded the spontaneous malignant transformation of cultured mouse astrocytes hemizygous for p53. Overexpression of TWIST protein in a human glioma cell line significantly enhanced tumor cell invasion, a hallmark of high-grade gliomas. These findings support roles for TWIST both in early glial tumorigenesis and subsequent malignant progression. TWIST was also expressed in embryonic and fetal human brain, and in neurons, but not glia, of mature brain, indicating that, in gliomas, TWIST may promote the functions also critical for CNS development or normal neuronal physiology.
Optimizing Microneedle Arrays to Increase Skin Permeability for Transdermal Drug Delivery (2009)

Improving drug permeability in the skin is one of the most important issues for designing new methods of transdermal drug delivery. Consequently, many techniques have been proposed to effectively deliver drugs across the stratum corneum. The microneedle is a new technology to enhance transdermal delivery of high-molecular-weight drugs. This technique combines the concepts of transdermal drug delivery across the skin with patches and hypodermic injections. The microneedles have been shown experimentally to increase the skin permeability by orders of magnitude in vitro for a range of drugs that differ in molecular size and weight. Recently, other questions appeared while using these microneedles, such as how to reduce needle diameters by which the hole is produced to be as small as possible to exclude bacteria and other foreign particles. Another issue is how to correlate the skin thickness and microneedle length with the skin permeability. In this work, we have developed an optimization framework for improving skin permeability to drugs by using microneedle arrays, which considers different classifications of skin thickness arising from different races, sex groups, ages, and anatomical regions. To know the optimum design of these microneedles, the effect of the microneedle geometry (e.g., number of microneedles, microneedle radius) on skin should be determined. In this work, the optimization algorithm is presented. The outcome of this work will be used to suggest optimum microneedle designs based on the parameters of interest.
Inaccuracy of glomerular filtration rate estimation from height/plasma creatinine ratio. (1994)

Use of a height/plasma creatinine formula to estimate glomerular filtration rate (GFR) is simpler and less invasive than renal or plasma clearance methods. The aim of this study was to determine whether these formulas enabled accurate prediction of GFR measured from the plasma clearance of 51Cr labelled ethylenediaminetetra-acetic acid (51Cr-EDTA). Thirty nine patients underwent GFR measurement at least six months after potentially nephrotoxic chemotherapy. Altman-Bland analysis was performed on the measured GFR and that estimated simultaneously using the original and a modified Counahan-Barratt formula and the Schwartz formula. The limits of agreement of the estimated GFR with the measured GFR were unacceptably wide in each case, despite highly significant correlation coefficients. The bias was smallest for the modified Counahan-Barratt formula. Use of these formulas to estimate GFR in children is insufficiently accurate for research purposes and has limitations in clinical practice. Furthermore, use of correlation coefficients to evaluate different methods of measuring GFR is inappropriate.
Characterization of Human and Rat Glucagon-Like Peptide-1 Receptors in the Neurointermediate Lobe: Lack of Coupling to Either Stimulation or Inhibition of Adenylyl Cyclase* (2000)

Glucagon-like peptide-1 (GLP-1) has been shown to bind to the posterior pituitary in the rat. We examined GLP-1 binding sites in human postmortem and rat pituitaries. Dense [125I]GLP-1 binding was seen in both human and rat posterior pituitary. In rat neurointermediate lobe membranes the binding site showed a Kd of 0.2 +/- 0.01 nM and a binding capacity of 600 +/- 33 fmol/mg protein (n = 3). In human pituitary membranes the binding site showed a Kd of 0.82 +/-0.05 nM and a binding capacity of 680 +/- 93 fmol/mg protein (n = 3). Chemical cross-linking showed a relative mol wt for the receptor-ligand complex of 73,100 +/- 1,400 (n = 3) in man and 59,300 +/- 900 (n = 3) in rat. GLP-1 (1 microM) failed to increase cAMP levels measured in rat neurointermediate lobes, whereas pituitary adenylate cyclase-activating polypeptide (100 nM) increased cAMP from a basal level of 14 +/-1 to 80 +/- 4 pmol/neurointermediate lobe 15 min (n = 5; P < 0.01). GLP-1 (up to 1 microM) did not affect the pituitary adenylate cyclase-activating polypeptide-stimulated cAMP levels. GLP-1 (up to 1 microM) also did not stimulate release of vasopressin or oxytocin from isolated rat neurointermediate lobes. The posterior pituitary shows the highest density of GLP-1-binding sites yet seen, but their function and signal transduction mechanism remain unknown.
Photocleavage of Nucleic Acids (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotocleavage of Nucleic AcidsBruce ArmitageView Author Information Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213-3890 Cite this: Chem. Rev. 1998, 98, 3, 1171–1200Publication Date (Web):March 27, 1998Publication History Received21 July 1997Revised21 January 1998Published online27 March 1998Published inissue 7 May 1998https://doi.org/10.1021/cr960428+Copyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views3104Altmetric-Citations630LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (343 KB) Get e-AlertsSUBJECTS:Crystal cleavage,Genetics,Irradiation,Oxygen,Selectivity Get e-Alerts
Expression, purification, and characterization of the Drosophila kinesin motor domain produced in Escherichia coli (1993)

The Drosophila kinesin heavy-chain gene was truncated to obtain the N-terminal 401 amino acid motor domain (designated K401) containing both the microtubule and ATP binding sites. The plasmid construct with the truncated kinesin gene was used to transform Escherichia coli. After induction, K401 was expressed as soluble kinesin protein at high levels and purified to homogeneity in milligram quantities. The purified protein was active and behaved as native kinesin with respect to its steady-state kinetic properties: K401 demonstrated a very low ATPase activity (kcat = 0.01 s-1) which was stimulated approximately 1000-fold by the addition of microtubules (kcat = 10 s-1; K0.5,MT = 0.9 microM tubulin; Km,ATP = 31 microM). Like native kinesin, K401 when purified contained ADP tightly bound at its active site, and the release of ADP from the active site occurred at a rate equal to the steady-state ATPase kcat. Active-site measurements using [alpha-32P]ATP demonstrated a stoichiometry of one ATPase site per K401 molecule. Like native kinesin, K401 can also hydrolyze MgGTP, and in the presence of microtubules, the rate of hydrolysis was increased dramatically from 0.03 to 16 s-1 (K0.5,MT = 2 microM tubulin; Km,GTP = 3.5 mM). These results establish that an active kinesin motor domain can be bacterially expressed and that this domain, the N-terminal 401 amino acids of the Drosophila kinesin heavy chain without light chains or additional eukaryotic factors, has full catalytic activity with microtubules.(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of envelope-domain dynamic X-parameter model based on variable-carrier-frequency analysis (2012)

This paper studies the envelope-domain dynamic X-parameter model of RF power-amplifier nonlinear behavior. Based on the analysis of its fundamental assumptions and the main applications for inter-modulation predictions, the consideration of model sensibility to variable carrier-frequency is proposed as one criterion to evaluate the reasonableness of the mathematical modeling. The experimental results in this paper show that the dynamic X-parameters are compatible with each other only within a small neighborhood around the desired carrier frequency, which on one hand may to some extent reflect the reasonableness of the theory, and on the other hand serve to investigate the validity and limits of dynamic X-parameters from a new perspective.
ABAD enhances Aβ‐induced cell stress via mitochondrial dysfunction (2005)

Amyloid-beta peptide (Abeta) binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, is a cofactor facilitating Abeta-induced cell stress. We hypothesized that ABAD provides a direct link between Abeta and cytotoxicity via mitochondrial oxidant stress. Neurons cultured from transgenic (Tg) mice with targeted overexpression of a mutant form of amyloid precursor protein and ABAD (Tg mAPP/ABAD) displayed spontaneous generation of hydrogen peroxide and superoxide anion, and decreased ATP, as well as subsequent release of cytochrome c from mitochondria and induction of caspase-3-like activity followed by DNA fragmentation and loss of cell viability. Generation of reactive oxygen species (ROS) was associated with dysfunction at the level of mitochondrial complex IV (cytochrome c oxidase, or COX). In neurons cultured from Tg mAPP/ABAD mice, COX activity was selectively decreased, and cyanide, an inhibitor of complex IV, exacerbated leakage of ROS, induction of caspase-3-like activity, and DNA fragmentation. In vivo, Tg mAPP/ABAD mice displayed reduced levels of brain ATP and COX activity, diminished glucose utilization, as well as electrophysiological abnormalities in hippocampal slices compared with Tg mAPP mice. In contrast, neither Tg ABAD mice nor nontransgenic (non-TG) littermates showed similar changes in ATP, COX activity, glucose utilization or electrophysiological properties. Each of the genotypes (Tg ABAD, Tg mAPP and Tg mAPP/ABAD mice, and non-TG littermates) displayed normal reproductive fitness, development and lifespan (1) These findings link ABAD-induced oxidant stress to critical aspects of Alzheimer's disease (AD)-associated cellular dysfunction, suggesting a pivotal role for this enzyme in the pathogenesis of AD.