gebhart/patrepeval huggingface dataset:
Exclusively targeting β-secretase to lipid rafts by GPI-anchor addition up-regulates β-site processing of the amyloid precursor protein (2003)

beta-Secretase (BACE, Asp-2) is a transmembrane aspartic proteinase responsible for cleaving the amyloid precursor protein (APP) to generate the soluble ectodomain sAPPbeta and its C-terminal fragment CTFbeta. CTFbeta is subsequently cleaved by gamma-secretase to produce the neurotoxic/synaptotoxic amyloid-beta peptide (Abeta) that accumulates in Alzheimer's disease. Indirect evidence has suggested that amyloidogenic APP processing may preferentially occur in lipid rafts. Here, we show that relatively little wild-type BACE is found in rafts prepared from a human neuroblastoma cell line (SH-SY5Y) by using Triton X-100 as detergent. To investigate further the significance of lipid rafts in APP processing, a glycosylphosphatidylinositol (GPI) anchor has been added to BACE, replacing the transmembrane and C-terminal domains. The GPI anchor targets the enzyme exclusively to lipid raft domains. Expression of GPIBACE substantially up-regulates the secretion of both sAPPbeta and amyloid-beta peptide over levels observed from cells overexpressing wild-type BACE. This effect was reversed when the lipid rafts were disrupted by depleting cellular cholesterol levels. These results suggest that processing of APP to the amyloid-beta peptide occurs predominantly in lipid rafts and that BACE is the rate-limiting enzyme in this process. The processing of the APP695 isoform by GPI-BACE was up-regulated 20-fold compared with wild-type BACE, whereas only a 2-fold increase in the processing of APP751/770 was seen, implying a differential compartmentation of the APP isoforms. Changes in the local membrane environment during aging may facilitate the cosegregation of APP and BACE leading to increased beta-amyloid production.
A New Pyridazine Series of GABAA α5 Ligands (2005)

Screening of the Merck compound collection identified 6 as an unusually simple, low molecular weight hit with moderate affinity for GABAA receptors. The structural novelty of 6, compared to our advanced series of GABAA alpha5 inverse agonists, made it an attractive molecule for further exploration. This paper will describe the evolution of 6 into a new series of ligands with nanomolar affinity and functional selectivity for GABAA alpha5 receptor subtypes.
Bendamustine: Rebirth of an Old Drug (2009)

Bendamustine is a unique cytotoxic agent with structural similarities to alkylating agents and antimetabolites, but which is non-cross-resistant with alkylating agents and other drugs in vitro and in the clinic. Early clinical studies conducted in the German Democratic Republic more than 30 years ago suggested promising activity in indolent non-Hodgkin's lymphoma (NHL). Two North American trials reported responses in more than 70% of patients with chemotherapy- and rituximab-refractory disease, suggesting that bendamustine may be the most effective drug available for this patient population. Response rates of 90% to 92%, with complete remission in 55% to 60%, have been reported in patients with follicular and mantle-cell lymphoma with the combination of bendamustine and rituximab. Superiority over chlorambucil in previously untreated patients with chronic lymphocytic leukemia (CLL) led to its recent approval for this disease in the United States. Bendamustine is approved in Germany for the treatment of patients with indolent NHL, CLL, and multiple myeloma. Activity has also been noted in patients with breast cancer and small-cell lung cancer [corrected]. Questions related to the optimization of bendamustine therapy, including dose and schedule, role relative to other available agents, and management of toxicities, are being investigated. However, the availability of bendamustine provides another effective treatment option for patients with lymphoid malignancies.
Response of four human ovarian carcinoma cell lines to ALL‐TRANS retinoic acid: Relationship with induction of differentiation and retinoic acid receptor expression (1994)

The response of 4 human ovarian carcinoma cell lines to retinoic acid was found to be related to the histological type and degree of differentiation of these tumor cells. The 2 serous cell lines NIHOVCAR3 and OVCCR1 were the most sensitive to the antiproliferative effect of RA. This inhibition was associated with morphological and biological changes that were indicative of differentiation. The undifferentiated IGROV1 cell line was not affected by RA. Since the effects of RA are thought to be mediated by nuclear retinoic acid receptors (RARs), the expression of RARs in human ovarian cancer cells was studied. RAR alpha was detected as mRNA species of 3.1 and 2.6 kb in all 4 cell lines. RAR beta was not detected in any of the cell lines, while RAR gamma (3 kb) was expressed in all of the ovarian cancer cells but at a very low level in the RA-resistant IGROV1 cells.
The syntheses and catalytic applications of unsymmetrical ferrocene ligands (2004)

Interest in the chemistry of ferrocene remains intense, largely due to applications within catalysis. New synthetic routes to unsymmetrical ferrocene ligands have provided another facet to this area, as substituents can be designed to be electronically- and/or sterically-distinct in order to affect the environment around the catalytically-active metal centre. This critical review provides a concise summary of the synthetic routes that have been applied to the synthesis of unsymmetrical ferrocene ligands, along with a systematic survey of the applications of these ligands in homogeneous catalysis. The aim is to help the reader select a suitable ferrocenediyl ligand for a particular synthetic application, and in the synthesis of ligands that require particular structural and/or electronic features.
ATM, CTLA4, MNDA, andHEM1in High versus Low CD38–Expressing B-Cell Chronic Lymphocytic Leukemia (2007)

These results identify the possible genes that may be involved in cell proliferation and survival and, thus, determining the clinical behavior of CLL patients expressing high or low CD38.
Cationization of protein antigens. II. Alteration of regulatory properties. (1987)

Immunoregulatory effects of cationized bovine serum albumin (cBSA) and native bovine serum albumin (nBSA) have been investigated. Intravenous administration of nBSA to BDF1 mice substantially suppressed the antibody response to subsequent immunization with either nBSA or cBSA, whereas pretreatment with cBSA by the same route significantly enhanced the responses to both antigens. The functional properties of BSA-specific T and B cells from mice immunized with cBSA or nBSA were examined in reconstitution experiments in which splenic T populations together with B cells were transferred into irradiated syngeneic recipients. Transfer of splenic T cells from mice primed with nBSA caused profound suppression of the response to subsequent immunization with nBSA or cBSA, whereas transfer of either B or T cells from cBSA treated mice produced an enhanced response to both antigens. C57BL/6 mice, which are considered to be low responders to BSA, produced a significant antibody response to BSA when immunized with cBSA. In contrast, immunization with nBSA did not produce measureable amounts of antibody in mice of this strain. Our data clearly demonstrate that cationized BSA exhibits unique immunogenic properties due to alterations in the self-regulation of the immune response.
The impact of preventive HPV vaccination. (2006)

The clearly defined causation by papillomavirus (HPV) and precursor lesions of cervical cancer have made this cancer largely preventable through Pap screening programs, and now by vaccination with Gardasil. This represents an important public health success story and here the authors summarize the potential impact of preventive HPV vaccination and some of the outstanding questions.
Patterned electrode vertical field effect transistor fabricated using block copolymer nanotemplates (2009)

We report the design and implementation of a vertical organic field effect transistor which is compatible with standard device fabrication technology and is well described by a self consistent device model. The active semiconductor is a film of C60 molecules, and the device operation is based on the architecture of the nanopatterned source electrode. The relatively high resolution fabrication process and maintaining the low-cost and simplicity associated with organic electronics, necessitates unconventional fabrication techniques such as soft lithography. Block copolymer self-assembled nanotemplates enable the production of conductive, gridlike metal electrode. The devices reported here exhibit On/Off ratio of 104.
Early ocular chemokine gene expression and leukocyte infiltration after high-risk corneal transplantation. (2005)

These results suggest that increased expression of gene products for select chemokines, in particular those that mediate recruitment of innate immune cells, in the early period after HR corneal transplantation is related to the enhanced leukocytic infiltration of grafts observed in HR keratoplasty.
Activation of SoxR-dependent Transcription in Vitro by Noncatalytic or NifS-mediated Assembly of [2Fe-2S[ Clusters into Apo-SoxR (1996)

SoxR is a transcriptional activator that senses superoxide and nitric oxide stress in Escherichia coli. The active protein isolated from E. coli contains a pair of [2Fe-2S] clusters per SoxR dimer. We previously demonstrated that the iron-free protein (apo-SoxR), isolated during purification in thiol-containing buffers, binds soxS promoter DNA with an affinity equal to that of the metalloprotein (Fe-SoxR), but lacks significant ability to activate transcription in vitro. Here we demonstrate the reversibility of this process: the full transcriptional activity of SoxR can be restored by in vitro assembly of iron-sulfur clusters into the apoprotein. Two methods were used to synthesize the metallocenters of SoxR: (i) nonenzymatic, in which apo-SoxR, incubated in the presence of iron, inorganic sulfide, and a reducing agent, regained full transcriptional activity in 5-6 h; (ii) enzymatic, in which NifS protein of Azotobacter vinelandii regenerated active Fe-SoxR in as little as 2 min. Analysis by electron paramagnetic resonance spectroscopy indicated that binuclear [2Fe-2S] clusters were restored by both the enzymatic and nonenzymatic reconstitutions. A mutant SoxR protein missing one of its four cysteine residues failed to undergo either transcriptional activation or the formation of [2Fe-2S] centers, even in the presence of NifS. Thus, only the presence of an iron-sulfur center is required to restore transcriptional activity to apo-SoxR. Moreover, the catalytic generation of [2Fe-2S] centers extends the known specificity of this enzyme beyond that already shown for [4Fe-4S] centers. Catalytic generation of [2Fe-2S]-containing SoxR could allow for rapid activation of this transcription factor in vivo.
Cell-surface antigens of melanoma recognized by human monoclonal antibodies. (1987)

Human monoclonal antibodies (mAbs) were derived from lymph node lymphocytes and peripheral blood lymphocytes (PBL) from patients with melanoma. Four methods for generating human mAbs were compared: fusion with human [LICR-LON-HMy-2 (LICR-2)] or mouse (NS-1) cells; transformation by Epstein-Barr virus (EBV); and EBV transformation followed by NS-1 fusion. NS-1 fusion with lymph node lymphocytes resulted in a higher number of growing hybrids than LICR-2 fusion. Virtually no hybrids were obtained from NS-1 or LICR-2 fusions with PBL. EBV transformed lymphocytes from lymph node and peripheral blood with equal efficiency, and the yield of proliferating cultures for antibody screening was more than 10- to 30-fold greater than that obtained by fusion techniques. However, once antibody-producing cultures had been identified, stability and clonability of EBV-transformed cells were poorer than that of NS-1 hybrid cells. To combine the strengths of both methods, cultures of EBV-transformed cells were fused with NS-1; and hybrid clones were isolated that showed vigorous growth, clonability, and stable antibody secretion. Detailed specificity analysis of the mAbs produced by six of these clones indicated detection of a class 1 (unique) melanoma antigen, a class 3 melanoma antigen, and four ganglioside antigens (GD3, GM3, and two other, as yet uncharacterized, heterophile antigens).
An autoanti‐Kpb immunoglobulin M that simulates antigen suppression (2009)

In antigen loss, antibody masking is excluded by a negative DAT. However, because typical DAT reagent does not detect IgM, such reasoning was inaccurate in the current case. In addition, an anti-Kp(b) resulted in RBCs typing k-, even though no anti-k was detected. Overall, this case suggests that an IgM may mask adjacent epitopes and illustrates the potential to mistake a non-IgG autoantibody as antigen loss.
Mice Lacking the Plasminogen Activator Inhibitor 1 Are Protected from Trabecular Bone Loss Induced by Estrogen Deficiency (2000)

Abstract Bone turnover requires the interaction of several proteases during the resorption phase. Indirect evidence suggests that the plasminogen activator/plasmin pathway is involved in bone resorption and turnover, and recently we have shown that this cascade plays a role in the degradation of nonmineralized bone matrix in vitro. To elucidate the role of the plasminogen activator inhibitor 1 (PAI-1) in bone turnover in vivo, bone metabolism was analyzed in mice deficient in the expression of PAI-1 gene (PAI-1−/−) at baseline (8-week-old mice) and 4 weeks after ovariectomy (OVX) or sham operation (Sham) and compared with wild-type (WT) mice. PAI-1 inactivation was without any effect on bone metabolism at baseline or in Sham mice. However, significant differences were observed in the response of WT and PAI-1−/− mice to ovariectomy. The OVX WT mice showed, as expected, decreased trabecular bone volume (BV/TV) and increased osteoid surface (OS/BS) and bone formation rate (BFR), as assessed by histomorphometric analysis of the proximal tibial metaphysis. In contrast, no significant change in any of the histomorphometric variables studied was detected in PAI-1−/− mice after ovariectomy. As a result, the OVX PAI-1−/− had a significantly higher BV/TV, lower OS/BS, lower mineral apposition rate (MAR) and BFR when compared with the OVX WT mice. However, a comparable decrease in the cortical thickness was observed in OVX PAI-1−/− and WT mice. In addition, the cortical mineral content and density assessed in the distal femoral metaphysis by peripheral quantitative computed tomography (pQCT), decreased significantly after ovariectomy, without difference between PAI-1−/− mice and WT mice. In conclusion, basal bone turnover and bone mass are only minimally affected by PAI-1 inactivation. In conditions of estrogen deficiency, PAI-1 inactivation protects against trabecular bone loss but does not affect cortical bone loss, suggesting a site-specific role for PAI-1 in bone turnover.
Investigations on the catalytic systems diethylzinc/Di‐ and trihydroxybenzenes in the copolymerization of carbon dioxide with propylene oxide (1976)

Abstract Investigations on the reactions of diethylzinc ( 1 ) with resorcinol ( 2 ) and phloroglucinol ( 8 ) were carried out for different mole ratios of the reactants. It was found that the reaction of 1 with 2 at a mole ratio of 1:1 is a two step process. In the first step 1 reacts very rapidly with half of applied 2 yielding di(ethylzinc) resorcinolate ( 6 ), which then reacts slowly with the remaining amount of 2 . It was found that zinc 3‐ethylzincoxyphenolate resorcinolate ( 5 ) formed in the second step is an active catalyst of the copolymerization reaction of carbon dioxide with propylene oxide. The reaction of 1 with 8 shows a similar course.
Damage Detection Using Optical Measurements and Wavelets (2002)

The paper presents an application of the wavelet transform for damage detection based on optical measurements. A number of important issues that need to be considered when image sequences are used for vibration analysis are discussed. These include: correspondence of image features from image to image, image calibration and spatial resolution. The principles of image edge detection are discussed and a comparison between the wavelet approach and the classical method is presented. A novel damage detection method based on optically measured mode-shape data is proposed. The method is illustrated using a simple cantilever beam experiment. The major advantage of the method is the significantly increased number of discrete points used to describe mode shapes. This is in contrast to classical techniques where in practice a small number of measurement points are obtained from a limited number of sensors.
Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats (1992)

The effects of insulin-like growth factor-I (IGF-I) on the gut of 150 g dexamethasone-treated rats were compared with those of two analogues with reduced affinity for IGF-binding proteins, des(1-3)IGF-I and LR3IGF-I, an N-terminal-extended variant. Administration of IGF-I for 7 days to rats made catabolic by co-treatment with dexamethasone induced a dose-dependent increase in total gut weight, with the highest dose of IGF-I (695 micrograms/day) increasing gut weight by up to 60%, and gut weight as a fraction of body weight by up to 32%. Effects were apparent in all regions of the gut examined, including the stomach, small intestine and colon. Histological and biochemical analyses of the intestine showed that cross-sectional mass, rather than gut length, was increased, and proportional increases in wet weight, protein and DNA content per unit length were measured in both the mucosa and muscularis layers. The rate of duodenal protein synthesis measured on day 7 of treatment was not increased by IGF-I treatment. The IGF-I analogues had qualitatively similar effects to IGF-I, but were consistently severalfold more potent, providing evidence that IGF-binding proteins reduce the biological activity of exogenous IGF-I in the gut. The results indicate that the gut is one of the most sensitive IGF-I target tissues, and that potency in vivo correlates with a reduced interaction with IGF-binding proteins.
Existence of the Canonical Wnt Signaling Pathway in the Human Trabecular Meshwork (2012)

There is a canonical Wnt signaling pathway in the TM, and this canonical Wnt pathway, but not the noncanonical Wnt signaling pathway, regulates IOP.
9‐Phenanthrol inhibits human TRPM4 but not TRPM5 cationic channels (2008)

We identify 9-phenanthrol as a TRPM4 inhibitor, without effects on TRPM5. It could be valuable in investigating the physiological functions of TRPM4, as distinct from those of TRPM5.
Intraoperative conformal optimization for transperineal prostate implantation using magnetic resonance spectroscopic imaging. (2001)

Using this brachytherapy optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for I 125 permanent prostate implants. This approach may have an impact on the ability to select regions within the prostate to safely employ dose escalation for patients treated with permanent interstitial implantation and to improve outcome for patients with organ-confined prostatic cancers.
Dendritic Spine "Dysgenesis" and Mental Retardation (1974)

Golgi studies reveal abnormally long, thin spines and the absence of short, thick spines on dendrites of cortical neurons in retarded children with normal karyotypes. The degree of dendritic spine loss and abnormality appears to be related to age and the severity of developmental retardation. Dendritic spine "dysgenesis" is a common feature of the microstructural pathology that occurs in profound mental retardation of unknown etiology.
Evidence for a Low-Affinity Interleukin-3 Receptor (1990)

Interleukin-3 (IL-3) regulates the proliferation of myeloid, erythroid, and lymphoid cells. Previous reports showed IL-3 binding restricted to a single high-affinity (Kd = 50-200 pin) site. Here, we demonstrate by equilibrium studies an additional binding site for IL-3 with lower apparent affinity (Kd=5-20 iym). Furthermore, kinetic analysis shows that two binding sites for IL-3 exist: IL-3 dissociates slowly from the first site (I½=4hr; k−1=2.7x10−3 min−1), whereas it dissociates rapidly (T½=4.0 min; k−1 = 0.116 min−1) from the second site. Cross-linking showed that [125I]IL-3 binding to the 115- and 140-kD proteins was not saturable at concentrations commensurate with high-affinity binding and IL-3 dissociated rapidly from these same molecules. Thus, the low affinity IL-3 receptor is a molecule(s) of 115- to 140-kD.
Vascular Consequences of Endothelial Nitric Oxide Synthase Uncoupling for the Activity and Expression of the Soluble Guanylyl Cyclase and the cGMP-Dependent Protein Kinase (2005)

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes mellitus, chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species (ROS), such as the superoxide radical, and the subsequent decrease in vascular bioavailability of nitric oxide (NO). Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include the NAD(P)H oxidase, the xanthine oxidase, and mitochondrial superoxide-producing enzymes. Superoxide produced by the NADPH oxidase may react with NO released by endothelial nitric oxide synthase (eNOS), thereby generating peroxynitrite. Peroxynitrite in turn has been shown to uncouple eNOS, thereby switching an antiatherosclerotic NO-producing enzyme to an enzyme that may initiate or even accelerate the atherosclerotic process by producing superoxide. Increased oxidative stress in the vasculature, however, is not restricted to the endothelium and has also been demonstrated to occur within the smooth muscle cell layer in the setting of hypercholesterolemia, diabetes mellitus, hypertension, congestive heart failure, and nitrate tolerance. Increased superoxide production by the endothelial and/or smooth muscle cells has important consequences with respect to signaling by the soluble guanylyl cyclase (sGC) and the cGMP-dependent protein kinase I (cGK-I), the activity and expression of which has been shown to be regulated in a redox-sensitive fashion. The present review summarizes current concepts concerning eNOS uncoupling and also focuses on the consequences for downstream signaling with respect to activity and expression of the sGC and cGK-I in various diseases.
Delta doping in silicon (1993)

Abstract Two-dimensional doping sheets (“δ-doping”) are integral parts of many novel semiconductor device concepts. Their practical realization in silicon (Si), however, was long delayed by the difficulty to introduce dopants into Si in a well-controlled way during epitaxial growth. Recent advances in the understanding of epitaxial growth and the incorporation of dopants in Si have overcome these difficulties and opened a new field in Si materials and device research. In this article, we review the growth, processing, and characterization of epitaxially grown 5-doped Si. Furthermore, we discuss the electronic subband states of such structures. Finally, we give an overview of device concepts that use 5-doping and analyze their properties.
Gilles de raiz de Vicente Huidobro: el compendio de definiciones y las hipótesis arriesgadas (1994)

Si entendemos que la obra literaria puede quedar planteada como una definición o respuesta a una pregunta, podríamos conjeturar que estas definiciones, preguntas y res­ puestas tienen que ver muy a menudo -lo que no es, por supuesto, condición necesaria, ni, por añadidura, suficiente-con el fracaso y con Ia transgresión.