gebhart/patrepeval huggingface dataset:
Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neutrophil (1992)

The tyrosine kinase inhibitors ST271, ST638 and erbstatin inhibited phospholipase D (PLD) activity in human neutrophils stimulated by fMet-Leu-Phe, platelet-activating factor and leukotriene B4. These compounds did not inhibit phorbol ester-stimulated PLD, indicating that they do not inhibit PLD per se, but probably act at a site between the receptor and the phospholipase. In contrast, the protein kinase C inhibitor Ro-31-8220 inhibited phorbol 12,13-dibutyrate- but not fMet-Leu-Phe-stimulated PLD activity, arguing against the involvement of protein kinase C in the receptor-mediated activation of PLD. ST271 did not inhibit Ins(1,4,5)P3 generation, but did inhibit protein tyrosine phosphorylation stimulated by fMet-Leu-Phe. The phosphotyrosine phosphatase inhibitor pervanadate increased tyrosine phosphorylation and stimulated PLD. These results suggest that tyrosine kinase activity is involved in receptor coupling to PLD but not to PtdIns(4,5)P2-specific phospholipase C in the human neutrophil.
Itraconazole Inhibits Enterovirus Replication by Targeting the Oxysterol-Binding Protein (2015)

Itraconazole (ITZ) is a well-known antifungal agent that also has anticancer activity. In this study, we identify ITZ as a broad-spectrum inhibitor of enteroviruses (e.g., poliovirus, coxsackievirus, enterovirus-71, rhinovirus). We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication, whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e., shuttling of cholesterol and phosphatidylinositol-4-phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.
The Development of Atypical Hemolytic Uremic Syndrome Depends on Complement C5 (2010)

Gene variants in the alternative pathway of the complement system strongly associate with atypical hemolytic uremic syndrome (aHUS), presumably by predisposing to increased complement activation within the kidney. Complement factor H (CFH) is the major regulator of complement activation through the alternative pathway. Factor H-deficient mice transgenically expressing a mutant CFH protein (Cfh(-/-).FHΔ16-20) that functionally mimics the CFH mutations reported in aHUS patients spontaneously develop thrombotic microangiopathy. To investigate the role of complement C5 activation in this aHUS model, we generated C5-deficient Cfh(-/-).FHΔ16-20 mice. Both C5-sufficient and C5-deficient Cfh(-/-).FHΔ16-20 mice had abnormal C3 deposition within the kidney, but spontaneous aHUS did not develop in any of the C5-deficient mice. Furthermore, although Cfh(-/-).FHΔ16-20 animals demonstrated marked hypersensitivity to experimentally triggered renal injury, animals with concomitant C5 deficiency did not. These data demonstrate a critical role for C5 activation in both spontaneous aHUS and experimentally triggered renal injury in animals with defective complement factor H function. This study provides a rationale to investigate therapeutic inhibition of C5 in human aHUS.
The effect of chlorpromazine on endotoxin-induced uveitis in the Lewis rat (1992)

Chlorpromazine (CPZ) has been used extensively in the treatment of psychiatric disorders, and has recently been shown to possess systemic anti-inflammatory properties as well. To investigate the potential effects of CPZ on ocular inflammation, we evaluated its action on endotoxin-induced uveitis (EIU) in Lewis rats. At three different dosage levels, CPZ produced highly significant reductions in the mean aqueous aspirate inflammatory cell counts and histological inflammatory scores as compared to controls treated with vehicle only. Analysis of aqueous fluid demonstrated a similar decrease in protein concentration and phospholipase A2 (PLA-2) activity in the treated animals. The ability of CPZ to inhibit the development of EIU may be related to its properties as a calcium channel blocker and inhibitor of the enzyme phospholipase A2.
Cooperative Caching for Chip Multiprocessors (2006)

This paper presents CMP Cooperative Caching, a unified framework to manage a CMP's aggregate on-chip cache resources. Cooperative caching combines the strengths of private and shared cache organizations by forming an aggregate "shared" cache through cooperation among private caches. Locally active data are attracted to the private caches by their accessing processors to reduce remote on-chip references, while globally active data are cooperatively identified and kept in the aggregate cache to reduce off-chip accesses. Examples of cooperation include cache-to-cache transfers of clean data, replication-aware data replacement, and global replacement of inactive data. These policies can be implemented by modifying an existing cache replacement policy and cache coherence protocol, or by the new implementation of a directory-based protocol presented in this paper. Our evaluation using full-system simulation shows that cooperative caching achieves an off-chip miss rate similar to that of a shared cache, and a local cache hit rate similar to that of using private caches. Cooperative caching performs robustly over a range of system/cache sizes and memory latencies. For an 8-core CMP with 1MB L2 cache per core, the best cooperative caching scheme improves the performance of multithreaded commercial workloads by 5-11% compared with a shared cache and 4-38% compared with private caches. For a 4-core CMP running multiprogrammed SPEC2000 workloads, cooperative caching is on average 11% and 6% faster than shared and private cache organizations, respectively.
A biomechanical analysis of solvent-dehydrated and freeze-dried human fascia lata allografts (1992)

Fascia lata is used as a graft material in a variety of orthopaedic procedures. Allograft fascia lata offers an increased cross-sectional area of material and eliminates the morbidity associated with the harvesting of autologous tissues. However, the structural uniformity of such large grafts has been questioned. Processing techniques used in the sterilization and storage of such grafts is varied and represents a potential source of variation in the mechanical properties of allograft specimens. The results of this study suggest that a commercially available solvent-dehydrated form of fascia lata provides a more suitable grafting material than freeze-dried specimens obtained from tissue banks.
Human circulating influenza-CD4 + ICOS1 + IL-21 + T cells expand after vaccination, exert helper function, and predict antibody responses (2013)

Protection against influenza is mediated by neutralizing antibodies, and their induction at high and sustained titers is key for successful vaccination. Optimal B cells activation requires delivery of help from CD4(+) T lymphocytes. In lymph nodes and tonsils, T-follicular helper cells have been identified as the T cells subset specialized in helping B lymphocytes, with interleukin-21 (IL-21) and inducible costimulatory molecule (ICOS1) playing a central role for this function. We followed the expansion of antigen-specific IL-21(+) CD4(+) T cells upon influenza vaccination in adults. We show that, after an overnight in vitro stimulation, influenza-specific IL-21(+) CD4(+) T cells can be measured in human blood, accumulate in the CXCR5(-)ICOS1(+) population, and increase in frequency after vaccination. The expansion of influenza-specific ICOS1(+)IL-21(+) CD4(+) T cells associates with and predicts the rise of functionally active antibodies to avian H5N1. We also show that blood-derived CXCR5(-)ICOS1(+) CD4(+) T cells exert helper function in vitro and support the differentiation of influenza specific B cells in an ICOS1- and IL-21-dependent manner. We propose that the expansion of antigen-specific ICOS1(+)IL-21(+) CD4(+) T cells in blood is an early marker of vaccine immunogenicity and an important immune parameter for the evaluation of novel vaccination strategies.
Late-Stage Deoxyfluorination of Alcohols with PhenoFluor (2013)

An operationally simple protocol for the selective deoxyfluorination of structurally complex alcohols is presented. Several fluorinated derivatives of natural products and pharmaceuticals have been prepared to showcase the potential of the method for late-stage diversification and its functional group compatibility. A series of simple guidelines for predicting the selectivity in substrates with multiple alcohols is given.
Interhelical contacts are required for the helix bundle fold of apolipophorin III and its ability to interact with lipoproteins (1998)

Apolipophorin-III (apoLp-III) from the insect, Manduca sexta, is a 166-residue exchangeable apolipoprotein that plays a critical role in the dynamics of plasma lipoprotein interconversions. Our previous work indicated that a 36-residue C-terminal peptide fragment, generated by cyanogen bromide digestion of apoLp-III, was unable to bind to lipid surfaces (Narayanaswami V, Kay CM, Oikawa K, Ryan RO, 1994, Biochemistry 33:13312-13320), and showed no secondary structure in aqueous solution. In this paper, we have performed structural studies of this peptide (E131-Q166) complexed with SDS detergent micelles, or in the presence of the helix-inducing solvent trifluoroethanol (TFE), by two-dimensional 1H NMR spectroscopy. The peptide adopts an alpha-helical structure in the presence of both SDS and 50% TFE. The lipid-bound structure of the peptide, generated from the NMR NOE data, showed an elongated, slightly curved alpha-helix. Despite its high alpha-helix forming propensity, the peptide requires alpha helix-promoting environment to adopt an alpha-helical structure. This indicates the importance of the surrounding chemical environment and implies that, in the absence of lipid, tertiary contacts in the folded protein play a role in maintaining its structural integrity. Furthermore, the data suggest that the amphipathic helix bundle organization serves as a prerequisite structural motif for the reversible lipoprotein-binding activity of M. sexta apoLp-III.
Wavelet Threshold Estimators for Data with Correlated Noise (1997)

Summary Wavelet threshold estimators for data with stationary correlated noise are constructed by applying a level-dependent soft threshold to the coefficients in the wavelet transform. A variety of threshold choices is proposed, including one based on an unbiased estimate of mean-squared error. The practical performance of the method is demonstrated on examples, including data from a neurophysiological context. The theoretical properties of the estimators are investigated by comparing them with an ideal but unattainable ‘bench-mark', that can be considered in the wavelet context as the risk obtained by ideal spatial adaptivity, and more generally is obtained by the use of an ‘oracle' that provides information that is not actually available in the data. It is shown that the level-dependent threshold estimator performs well relative to the bench-mark risk, and that its minimax behaviour cannot be improved on in order of magnitude by any other estimator. The wavelet domain structure of both short- and long-range dependent noise is considered, and in both cases it is shown that the estimators have near optimal behaviour simultaneously in a wide range of function classes, adapting automatically to the regularity properties of the underlying model. The proofs of the main results are obtained by considering a more general multivariate normal decision theoretic problem.
Androgen receptor decoy molecules block the growth of prostate cancer (2007)

The androgen receptor (AR) is activated by both ligand-dependent and -independent mechanisms. Current therapies for prostate cancer target the ligand-binding domain in the C terminus of the AR. However, ligand-independent activation of the AR occurs by the N-terminal domain (NTD), making the NTD a potential novel target for the treatment of hormone refractory prostate cancer. A possible therapeutic approach is to overexpress an AR NTD peptide to create decoy molecules that competitively bind the interacting proteins required for activation of the endogenous full-length AR. We provide evidence that in vivo expression of AR NTD decoys decreased tumor incidence and inhibited the growth of prostate cancer tumors. This growth inhibition was characterized by a 10-fold decrease in serum levels of prostate-specific antigen (PSA) (46.7 ng/ml+/-19.9 vs. 432.4 ng/ml+/-201.3; P=0.0299) and a 4-fold decrease in tumor volume (92.2 mm3+/-43.4 vs. 331.4 mm3+/-85.5; P=0.011). AR NTD decoy molecules also delayed hormonal progression, as determined by time to rising PSA levels after castration of the host. The tumors treated with AR NTD decoys contained more apoptotic cells and fewer proliferating cells, whereas no effect was seen on the viability of cells that did not depend on the AR. This work provides further evidence of the importance of the NTD of the AR in the progression of prostate cancer and presents a target for the development of antagonists of the AR in the clinical management of this disease.
ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential? (1996)

The ret/PTC oncogene is unique to papillary thyroid cancer.Three forms of this oncogene, formed by translocation of three different genes to the tyrosine kinase domain of the ret protooncogene,
TIMP-1 Production by Human Scleral Fibroblast Decreases in Response to Cyclic Mechanical Stretching (2001)

The production of TIMP-1 by human scleral fibroblasts was suppressed by cyclic mechanical stretching. Mechanical strain would be one factor to regulate the homeostasis of extracellular matrix in the sclera.
Screening for lung cancer (2013)

Lung cancer is a major global health issue and will remain so for decades to come. Lung cancer screening has the potential to reduce mortality from this disease and represents one of the most exciting developments in recent years. Screening appears to have taken hold in the US, yet has received a more cautious reception in other countries, probably due to a lack of accurate cost-effectiveness data and implementation capacity uncertainties. Refinement of screening using risk prediction to select the highest risk candidates is the next challenge and, coupled with an integrated smoking cessation program, could substantially improve cost-effectiveness. Future research will determine if biomarkers in biological samples will offer a low cost and minimally invasive method of screening and early detection. In this paper we review the development of lung cancer screening to date, the current state of the art and future directions for research.
GD2-mediated melanoma cell targeting and cytotoxicity of liposome-entrapped fenretinide (1999)

Melanoma is a highly malignant and increasingly common neoplasm. Because metastatic melanoma remains incurable, new treatment approaches are needed. Immunoliposomes have been previously shown to enhance the selective localization of immunoliposome-entrapped drugs to solid tumors with improvements in the therapeutic index of the drugs. Previously, we reported that the synthetic retinoid fenretinide (HPR) is an inducer of apoptosis in neuroblastoma (NB) cells, sharing the neuroectodermal origin with melanoma cells. HPR is a strong inducer of apoptosis also in melanoma cells, although at doses 10-fold higher than those achievable clinically. Thus, our purpose was to investigate the in vitro potentiation of its cytotoxic effect on melanoma cells in combination with long-circulating GD2-targeted immunoliposomes. GD2 is a disialoganglioside extensively expressed on tumors of neuroectodermal origin, including melanoma. Murine anti-GD2 antibody (Ab) 14.G2a and its human/mouse chimeric variant ch14.18 have been ligated to sterically stabilized liposomes by covalent coupling of Ab to the polyethylene glycol (PEG) terminus. Ab-bearing liposomes showed specific, competitive binding to and uptake by various melanoma cell lines compared with liposomes bearing non-specific isotype-matched Abs or Ab-free liposomes. Cytotoxicity was evaluated after 2 hr treatment, followed by extensive washing and 72 hr incubation. This treatment protocol was designed to minimize non-specific adsorption of liposomes to the cells, while allowing for maximum Ab-mediated binding. When melanoma cells were incubated with 30 microM HPR entrapped in anti-GD2 liposomes, a significant reduction in cellular growth was observed compared to free HPR, entrapped HPR in Ab-free liposomes or empty liposomes. Cytotoxicity was not evident in tumor cell lines of other origins that did not express GD2. Growth of NB cells was also inhibited by immunoliposomes with entrapped HPR.
Effect of Ultrasonic Treatment on the Solidification Microstructure of Die-Cast 35CrMo Steel (2016)

The effects of ultrasonic treatment (UST) on the solidification microstructure of a 35CrMo steel cast ingot were investigated. To avoid the erosion of a high-temperature melt, a T-shaped ultrasonic waveguide unit was used to introduce ultrasonic vibrations into a 35CrMo steel die casting melt. The experimental results show that the microstructure of the ingot was refined by ultrasonic treatment. While the microstructure of untreated 35CrMo steel is coarse dendritic grains, after the introduction of ultrasonic treatment, the solidification microstructure transforms from coarse dendritic to equiaxed grains, and the dendrites are also refined. Samples from different positions of the ingots were subjected to different ultrasonic effects, and the effects on grain refinement also varied due to the severe attenuation of the ultrasound in the melt. The mechanisms of grain refinement using ultrasonic treatment for 35CrMo steel melt are presented.
Efficient priming of PCR with short oligonucleotides conjugated to a minor groove binder (1997)

The tripeptide 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI3) binds to the minor groove of DNA with high affinity. When this minor groove binder (MGB) is conjugated to the 5'-end of short oligodeoxynucleotides (ODNs), the conjugates form unusually stable hybrids with complementary DNA in which the tethered CDPI3group resides in the minor groove. We show that these conjugates can be used as PCR primers. Due to their unusually high binding affinity, conjugates as short as 8-10mers can be used to amplify DNA with good specificity and efficiency. The reduced length primers described here might be appropriate for the PCR amplification of viral sequences which possess a high degree of variability (e.g., HPV, HIV) or for recent techniques such as gene hunting and differential display which amplify multiple sequences using short primer pairs.
Diverse Members of the AvrBs3/PthA Family of Type III Effectors Are Major Virulence Determinants in Bacterial Blight Disease of Rice (2004)

AvrXa7 is a member of the avBs3/pthA gene family and the only known type III secretion system effector gene from Xanthomonas oryzae pv. oryzae with a major contribution to bacterial growth and lesion formation in bacterial blight disease of rice. We examined the general requirement for effectors of the AvrBs3/PthA family in bacterial blight of rice by identifying effectors from diverse strains of the pathogen. Inactivation of single effector genes in representative strains from Japan, Korea, and the Philippines resulted in severely limited growth in plants. Five strains harbored one gene of the avrBs3/pthA family, while one strain had two genes with the equivalent virulence activity of avrXa7. Sequence analysis revealed three genes with unique repeat arrangements in comparison to avrXa7. Comparison of the repetitive regions revealed a potential motif for the group that was also present in the repetitive region of avrBs3. However, the repetitive region of avrBs3 could not support virulence activity but, in combination with the C-terminal coding region of avrXa7, triggered a Xa7-dependent avirulence reaction. The results revealed diverse members of the avrBs3/pthA gene family with virulence activity in X. oryzae pv. oryzae and supported the hypothesis that bacterial blight disease of rice is highly dependent on a single class of type III effectors. The results also indicated that avrXa7 avirulence specificity is separable from virulence activity.
Mechanisms of mouse spleen dendritic cell function in the generation of influenza-specific, cytolytic T lymphocytes. (1992)

We have evaluated the capacity of dendritic cells to function as antigen-presenting cells (APCs) for influenza and have examined their mechanism of action. Virus-pulsed dendritic cells were 100 times more efficient than bulk spleen cells in stimulating cytotoxic T lymphocyte (CTL) formation. The induction of CTLs required neither exogenous lymphokines nor APCs in the responding T cell population. Infectious virus entered dendritic cells through intracellular acidic vacuoles and directed the synthesis of several viral proteins. If ultraviolet (UV)-inactivated or bromelain-treated viruses were used, viral protein synthesis could not be detected, and there was poor induction of CTLs. This indicated that dendritic cells were not capable of processing noninfectious virus onto major histocompatibility complex (MHC) class I molecules. However, UV-inactivated and bromelain-treated viruses were presented efficiently to class II-restricted CD4+ T cells. The CD4+ T cells crossreacted with different strains of influenza and markedly amplified CTL formation. Cell lines that lacked MHC class II, and consequently the capacity to stimulate CD4+ T cells, failed to induce CTLs unless helper lymphokines were added. Similarly, dendritic cells pulsed with the MHC class I-restricted nucleoprotein 147-155 peptide were poor stimulators in the absence of exogenous helper factors. We conclude that the function of dendritic cells as APCs for the generation of virus-specific CTLs in vitro depends measurably upon: (a) charging class I molecules with peptides derived from endogenously synthesized viral antigens, and (b) stimulating a strong CD4+ helper T cell response.