gebhart/patrepeval huggingface dataset:
Prostate Cancer Cell-Adipocyte Interaction (2003)

Prostate cancer is one of the leading causes of death among men in the United States, and acquisition of hormone resistance (androgen independence) by cancer cells is a fatal event during the natural history of prostate cancer. Obesity is another serious health problem and has been shown to be associated with prostate cancer. However, little is known about the molecular basis of this association. Here we show that factor(s) secreted from adipocytes stimulate prostate cancer cell proliferation. Leptin is one of the major adipose cytokines, and it controls body weight homeostasis through food intake and energy expenditure. We identify leptin as a novel growth factor in androgen-independent prostate cancer cell growth. Strikingly, leptin stimulates cell proliferation specifically in androgen-independent DU145 and PC-3 prostate cancer cells but not in androgen-dependent LNCaP-FGC cells, although both cell types express functional leptin receptor isoforms. c-Jun NH2-terminal kinase (JNK) has been shown recently to play a crucial role in obesity and insulin resistance. Intriguingly, leptin induces JNK activation in androgen-independent prostate cancer cells, and the pharmacological inhibition of JNK blocked the leptin stimulation of androgen-independent prostate cancer cell proliferation. This suggests that JNK activation is required for leptin-mediated, androgen-independent prostate cancer cell proliferation. Furthermore, other cytokines produced by adipocytes and critical for body weight homeostasis cooperate with leptin in androgen-independent prostate cancer cell proliferation: interleukin-6 and insulin-like growth factor I demonstrate additive and synergistic effects on the leptin stimulation of androgen-independent prostate cancer cell proliferation, respectively. Therefore, adipose cytokines, as well as JNK, are key mediators between obesity and hormone-resistant prostate cancer and could be therapeutic targets.
High dose radiolabeled antibody therapy of lymphoma. (1990)

A trial has been initiated testing the effects of high dose radiolabeled monoclonal antibody administered in conjunction with marrow transplantation for treatment of lymphoma. This study is based on observations in mice demonstrating that radiolabeled antibody against a normal lymphocyte-associate antigen can induce regression of lymphoma masses. These preclinical studies also showed that large amounts of antibody are needed to achieve adequate biodistribution in vivo and that potentially curative doses of radionuclide induce substantial hematopoietic toxicity. Consequently, in patients with recurrent lymphoma, we are first evaluating the influence of dose on the biodistribution of a pan B-cell antibody, MB-1 (anti-CD37). In four patients, the biodistribution studies indicated that at the highest amount of antibody tested 131I-labeled antibody MB-1 (10 mg/kg) could deliver more radiation to tumor than to normal organs. These patients were treated with antibody MB-1 labeled with 250 to 482 mCi 131I estimated to deliver 380 to 1570 cGy to normal organs and 850 to 4260 cGy to tumor. Myelosuppression occurred in all patients and required infusion of cryopreserved marrow in one patient. Complete tumor regressions were observed in each patient. In three other patients with splenomegaly and/or large tumor burden, biodistribution studies indicated that 131I-labeled antibody could not deliver more radiation to tumor than to normal organs and these patients were not treated. Thus, tumor burden and spleen size may determine the feasibility of treatment with radiolabeled antibody. Treatment with this antibody labeled with high doses of 131I was well tolerated and may prove therapeutically useful. These studies are being continued to determine the maximal doses of radiation that can be tolerated by nonhematopoietic tissues after infusion of 131I-labeled antibody.
Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts (2006)

Vaccination with dendritic cells (DCs) as professional antigen presenting cells generated from autologous leukemic blasts might elicit anti-leukemic T cell responses in patients with acute myeloid leukemia (AML). To test this hypothesis, autologous AML-DC were generated under good manufacturing practice (GMP) conditions and injected s.c. into five AML patients up to four times at a biweekly interval. No severe adverse side effects were observed. Three patients remained in a stable condition for 5.5-13 months and two patients died from rapidly progressive AML. Compared to the initial T cell frequency, enzyme linked immunosorbent spot (ELISPOT) assays revealed a significant increase of granzyme B releasing CD8+ T cells specifically recognizing the PRAME derived peptide (ALYVDSLFFL), a leukemia associated antigen expressed by AML blasts. The cytokine levels in the serum of vaccination AML patients as assessed by cytokine bead assay changed over the period of vaccination to an elevated type 1 T helper cell pattern. Interferon gamma production by CD4+ T helper cells increased during vaccination. In summary, we demonstrated that autologous AML-DC vaccination is well tolerated and can result in an enhanced and specific response of cytotoxic T cells in AML patients.
Matching on the Estimated Propensity Score (2009)

Propensity score matching estimators In this article, we derive the large sample distribution of propensity score matching estimators. Our derivations take into account that the propensity score is itself estimated in a first step, prior to matching. We prove that first step estimation of the propensity score affects the large sample distribution of propensity score matching estimators. Moreover, we derive an adjustment to the large sample variance of propensity score matching estimators that corrects for first step estimation of the propensity score. In spite of the great popularity of propensity score matching estimators, these results were previously unavailable in the literature.
Myeloperoxidase-targeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis (2008)

Inflammatory demyelinating plaques are the pathologic hallmark of active multiple sclerosis and often precede clinical manifestations. Non-invasive early detection of active plaques would thus be crucial in establishing pre-symptomatic diagnosis and could lead to early preventive treatment strategies. Using murine experimental autoimmune encephalomyelitis as a model of multiple sclerosis, we demonstrate that a prototype paramagnetic myeloperoxidase (MPO) sensor can detect and confirm more, smaller, and earlier active inflammatory lesions in living mice by in vivo MRI. We show that MPO expression corresponded with areas of inflammatory cell infiltration and demyelination, and higher MPO activity as detected by MPO imaging, biochemical assays, and histopathological analyses correlated with increased clinical disease severity. Our findings present a potential new translational approach for specific non-invasive inflammatory plaque imaging. This approach could be used in longitudinal studies to identify active demyelinating plaques as well as to more accurately track disease course following treatment in clinical trials.
The first synchrotron infrared beamlines at the advanced light source: Spectromicroscopy and fast timing (2001)

Two recently commissioned infrared beamlines on the 1.4 bending magnet port at the Advanced Light Source, LBNL, are described. Using a synchrotron as an IR source provides three primary advantages: increased brightness, very fast light pulses, and enhanced far-IR flux. The considerable brightness advantage manifests itself most beneficially when performing spectroscopy on a microscopic length scale. Beamline (BL) 1.4.3 is a dedicated FTIR spectromicroscopy beamline, where a diffraction-limited spot size using the synchrotron source is utilized. BL 1.4.2 consists of a vacuum FTIR bench with a wide spectral range and step-scan capability. This BL makes use of the pulsed nature of the synchrotron light as well as the far-IR flux. Fast timing is demonstrated by observing the pulses from the electron bunch storage pattern at the ALS. Results from several experiments from both IR beamlines will be presented as an overview of the IR research currently being done at the ALS.
Epstein-Barr Virus gH Is Essential for Penetration of B Cells but Also Plays a Role in Attachment of Virus to Epithelial Cells (2000)

Entry of Epstein-Barr virus (EBV) into B cells is initiated by attachment of glycoprotein gp350 to the complement receptor type 2 (CR2). A complex of three glycoproteins, gH, gL, and gp42, is subsequently required for penetration. Gp42 binds to HLA class II, which functions as an entry mediator or coreceptor and, by analogy with other herpesviruses, gH is then thought to be involved virus-cell fusion. However, entry of virus into epithelial cells is thought to be different. It can be initiated by attachment by an unknown glycoprotein in the absence of CR2. There is no interaction between gp42 and HLA class II and instead a distinct complex of only the two glycoproteins gH and gL interacts with a novel entry mediator. Again, by analogy with other viruses gH is thought to be critical to fusion. To investigate further the different roles of gH in infection of the two cell types and to examine its influence on the assembly of the gH-gL-gp42 complex, we constructed two viruses, one in which the gH open reading frame was interrupted by a cassette expressing a neomycin resistance gene and the gene for green fluorescent protein and one as a control in which the neighboring nonessential thymidine kinase gene was interrupted with the same cassette. Virus lacking gH exited from cells normally, although loss of gH resulted in rapid turnover of gL and gp42 as well. The virus bound normally to B lymphocytes but could not infect them unless cells and bound virus were treated with polyethylene glycol to induce fusion. In contrast, virus that lacked the gH complex was impaired in attachment to epithelial cells and the effects of monoclonal antibodies to gH implied that this resulted from loss of gH rather than other members of the complex. These results suggest a role for gH in both attachment and penetration into epithelial cells.
Chemical components and properties of core–shell acrylate latex containing fluorine in the shell and their films (2005)

Abstract Core–shell acrylate latices containing fluorine in the shell were prepared by semicontinuous emulsion polymerization. The chemical components of the latices were determined by Fourier transform infrared, ion‐selective electrode analysis, and differential scanning calorimetry. The average size and morphology of the latex particles were characterized by photocorrelation spectroscopy and transmission electron microscopy, respectively. The latex particles were mainly composed of a non‐fluorine core and a fluorinated shell. The dynamic water contact angles of the latex films from the Wilhelmy method indicated that the latex films containing fluorine in the shell could be wetted by water only with difficulty. The amount of the fluoromonomer played an important role in the modification on the water contact angles, water absorption, and thermal stability of the latex films. In comparison with a random structure, the core–shell structure was more effective for improving the thermal properties of the latex films. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 107–114, 2006
Fuzzy neural systems for decision making (1991)

A stock selection strategy based on an artificial fuzzy neural system is described from a general system-design perspective. The authors suggest the concept of a neural gate which is similar to the processing element in an artificial neural system but generalized into handling various types of information such as fuzzy logic, probabilistic, and Boolean information combined. Forecasting of stock market returns, assessment of country risk, and rating of stocks based on fuzzy rules, probabilistic, and Boolean data are areas where systems using these neural gates may be applied. A database containing about 800 sets of company data for the preceding three years where each set represents one stock was used to test the intelligent stock selection system considered.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effect of Preexisting Immunity to Salmonella on the Immune Response to Recombinant Salmonella enterica Serovar Typhimurium Expressing a Porphyromonas gingivalis Hemagglutinin (2000)

Recombinant Salmonella strains expressing foreign heterologous genes have been extensively studied as live oral vaccine delivery vectors. We have investigated the mucosal and systemic immune responses following oral immunization with a recombinant Salmonella enterica serovar Typhimurium expressing the hemagglutinin HagB from Porphyromonas gingivalis, a suspected etiological agent of adult periodontal disease. We have previously shown a primary mucosal and systemic response following oral immunization with chi4072/pDMD1 and recall responses following boosting at 14 weeks after primary immunization. In this study, we examined the effects of earlier boosting as well as the effects of deliberately induced immunity to the Salmonella carrier strain on subsequent immune responses. Mice boosted at week 7 following immunization, a point which corresponded to the peak of the primary response, generally showed lower responses than those boosted at week 14. When mice were preimmunized with the Salmonella carrier alone and then immunized with the recombinant strain 7 or 14 weeks later, significant reductions were seen for serum immunoglobulin G (IgG) antibodies at week 14 and for salivary IgA at week 7. No reductions were seen in serum IgA or vaginal wash IgA antibodies. Mice appear to be refractory to boosting with orally administered salmonellae at 7 weeks. Deliberate immunization with the carrier strain did not appreciably affect recall responses at 14 weeks, with the exception of the serum IgG responses, nor did it affect colonization of the Peyer's patches.
Ploidy differences between hormone‐ and chemical carcinogen–induced rat mammary neoplasms: Comparison to invasive human ductal breast cancer* (2002)

To ascertain differences between solely hormone- and chemical carcinogen-induced murine mammary gland tumors (MGTs), a direct comparison of their ploidy status was assessed. Nuclear image cytometry (NIC) was used to evaluate ploidy in ductal carcinoma in situ (DCIS) and MGTs induced solely by 17beta-estradiol (E(2)) in female A-strain Copenhagen Irish hooded gene rats (ACI) and E(2) plus testosterone propionate in male Noble rats. These results were compared to ploidy data from primary MGTs induced by two synthetic carcinogens, 7,12-dimethylbenz[a]antracene and nitrosomethylurea in female Brown Lewis Norway rats and an environmental carcinogen, 6-nitrochrysene, in female Sprague-Dawley rats. Both DCIS and primary MGTs induced solely by hormones were highly aneuploid (> 84%), whereas MGTs induced by either synthetic or environmental carcinogens were primarily diploid (> 85%). Examination of 76 metaphase plates obtained from eight individual E(2)-induced ACI female rat MGTs revealed the following consistent chromosome alterations: gains in chromosomes 7, 11, 12, 13, 19, and 20 and loss of chromosome 12. On Southern blot analysis, six of nine ACI female rat primary E(2)-induced MGTs (66%) exhibited amplified copy numbers (range: 3.4-6.9 copies) of the c-myc gene. Fluorescence in situ hybridization (FISH) analysis of these MGTs revealed specific fluorescent hybridization signals for c-myc (7q33) on all three homologs of a trisomy in chromosome 7. NIC analysis of 140 successive nonfamilial sporadic invasive human ductal breast cancers (BCs) showed an aneuploid frequency of 61%, while 31 DCISs revealed a 71% aneuploid frequency. These results clearly demonstrate that the female ACI rat E(2)-induced MGTs more closely resemble invasive human DCIS and ductal BC in two pertinent aspects: they are highly aneuploid compared with chemical carcinogen-induced MGTs and exhibit a high frequency of c-myc amplification.
Long-term correction of glycogen storage disease type II with a hybrid Ad-AAV vector (2003)

We administered an adenovirus-adeno-associated virus (Ad-AAV) vector encoding human acid alpha-glucosidase (hGAA) to acid alpha-glucosidase-knockout (GAA-KO) mice on day 3 of life by gastrocnemius injection. In contrast to previous results for muscle-targeted Ad vector in adult GAA-KO mice, the muscles of the hindlimb showed reduced glycogen content and persistent hGAA for as long as 6 months after neonatal Ad-AAV vector administration. Not only the injected gastrocnemius muscles, but also the hamstrings and quadriceps muscles produced therapeutic levels of hGAA as a result of widespread transduction with the Ad-AAV vector; moreover, hGAA activity was 50-fold elevated as compared to normal mice. Vector RNA was detected in the hindlimb muscles, the hearts, and the livers by northern blot analysis and/or by RT-PCR for as long as 6 months. The low levels of hGAA detected in the heart were attributable to transduction with the Ad-AAV vector, not to secretion of hGAA by the injected muscle and uptake by the heart. Finally, although an antibody response to hGAA was present, it did not prevent the correction of glycogen storage in the skeletal muscle of GAA-KO mice.
Design, Synthesis, and Characterization of High-Affinity, Systemically-Active Galanin Analogues with Potent Anticonvulsant Activities (2008)

Galanin is an endogenous neuropeptide that modulates seizures in the brain. Because this neuropeptide does not penetrate the blood-brain barrier, we designed truncated galanin analogues in which nonessential amino acid residues were replaced by cationic and/or lipoamino acid residues. The analogues prevented seizures in the 6 Hz mouse model of epilepsy following intraperitoneal administration. The most active analogue, Gal-B2 (NAX 5055), contained the -Lys-Lys-Lys(palmitoyl)-Lys-NH(2) motif and exhibited high affinity for galanin receptors (K(i) = 3.5 nM and 51.5 nM for GalR1 and GalR2, respectively), logD = 1.24, minimal helical conformation and improved metabolic stability. Structure-activity-relationship analysis suggested that cationization combined with position-specific lipidization was critical for improving the systemic activity of the analogues. Because the anticonvulsant activity of galanin is mediated by the receptors located in hippocampus and other limbic brain structures, our data suggest that these analogues penetrate into the brain. Gal-B2 may lead to development of first-in-class antiepileptic drugs.
Overexpression of integral membrane proteins for structural studies (1995)

Determination of the structure of integral membrane proteins is a challenging task that is essential to understand how fundamental biological processes (such as photosynthesis, respiration and solute translocation) function at the atomic level. Crystallisation of membrane proteins in 3D has led to the determination of four atomic resolution structures [photosynthetic reaction centres (Allen et al . 1987; Chang et al . 1991; Deisenhofer &amp; Michel, 1989; Ermler et al . 1994); porins (Cowan et al . 1992; Schirmer et al . 1995; Weiss et al . 1991); prostaglandin H 2 synthase (Picot et al . 1994); light harvesting complex (McDermott et al . 1995)], and crystals of membrane proteins formed in the plane of the lipid bilayer (2D crystals) have produced two more structures [bacteriorhodopsin (Henderson et al . 1990); light harvesting complex (Kühlbrandt et al . 1994)].
Retroviruses and primate evolution (2000)

Human endogenous retroviruses (HERVs), probably representing footprints of ancient germ-cell retroviral infections, occupy about 1% of the human genome. HERVs can influence genome regulation through expression of retroviral genes, either via genomic rearrangements following HERV integrations or through the involvement of HERV LTRs in the regulation of gene expression. Some HERVs emerged in the genome over 30 MYr ago, while others have appeared rather recently, at about the time of hominid and ape lineages divergence. HERVs might have conferred antiviral resistance on early human ancestors, thus helping them to survive. Furthermore, newly integrated HERVs could have changed the pattern of gene expression and therefore played a significant role in the evolution and divergence of Hominoidea superfamily. Comparative analysis of HERVs, HERV LTRs, neighboring genes, and their regulatory interplay in the human and ape genomes will help us to understand the possible impact of HERVs on evolution and genome regulation in the primates. BioEssays 22:161–171, 2000. ©2000 John Wiley & Sons, Inc.
Affinity Purification Probes of Potential Use To Investigate the Endogenous Hsp70 Interactome in Cancer (2014)

Heat shock protein 70 (Hsp70) is a family of proteins with key roles in regulating malignancy. Cancer cells rely on Hsp70 to inhibit apoptosis, regulate senescence and autophagy, and maintain the stability of numerous onco-proteins. Despite these important biological functions in cancer, robust chemical tools that enable the analysis of the Hsp70-regulated proteome in a tumor-by-tumor manner are yet unavailable. Here we take advantage of a recently reported Hsp70 ligand to design and develop an affinity purification chemical toolset for potential use in the investigation of the endogenous Hsp70-interacting proteome in cancer. We demonstrate that these tools lock Hsp70 in complex with onco-client proteins and effectively isolate Hsp70 complexes for identification through biochemical techniques. Using these tools we provide proof-of-concept analyses that glimpse into the complex roles played by Hsp70 in maintaining a multitude of cell-specific malignancy-driving proteins.
Phylogenetic structure of the prokaryotic domain: The primary kingdoms (1977)

A phylogenetic analysis based upon ribosomal RNA sequence characterization reveals that living systems represent one of three aboriginal lines of descent: (i) the eubacteria, comprising all typical bacteria; (ii) the archaebacteria, containing methanogenic bacteria; and (iii) the urkaryotes, now represented in the cytoplasmic component of eukaryotic cells.