gebhart/patrepeval huggingface dataset:
Current Treatment Strategies for Castration-Resistant Prostate Cancer (2011)

Prostate cancer is the most common cancer in men in United States and the fifth most common cancer in men in Korea. Although the majority of patients with metastatic prostate cancer initially respond to androgen deprivation therapy, almost all patients will eventually progress to develop castration-resistant prostate cancer (CRPC). Treatment options for CRPC remain limited. Prostate cancer was considered unresponsive to chemotherapy until the mid-1990s, when mitoxantrone combined with prednisone was shown to play a role in the palliative treatment of patients with CRPC. In 2004, two large randomized clinical trials demonstrated for the first time a small but significant survival advantage of docetaxel-based chemotherapy compared with mitoxantrone in patients with metastatic CRPC. Recently, cabazitaxel was shown to improve survival in patients with metastatic CRPC who progressed after docetaxel-based chemotherapy. Sipuleucel-T was also demonstrated to improve overall survival in patients with asymptomatic or minimally symptomatic metastatic CRPC. Along with mitoxantrone and docetaxel, cabazitaxel and sipuleucel-T are now approved for use in metastatic CRPC by the US Food and Drug Administration. There have been multiple early-phase clinical trials of various agents for the treatment of CRPC, and some are in phase III development. This review focuses on the key clinical trials of various treatment options of CRPC currently in use and under investigation.
Insulin-Induced Phosphorylation and Activation of Cyclic Nucleotide Phosphodiesterase 3B by the Serine-Threonine Kinase Akt (1999)

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in adipocytes in a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation and activation of endogenous or recombinant PDE3B in 3T3-L1 adipocytes have now been shown to be inhibited by a dominant-negative mutant of the serine-threonine kinase Akt, suggesting that Akt is necessary for insulin-induced phosphorylation and activation of PDE3B. Serine-273 of mouse PDE3B is located within a motif (RXRXXS) that is preferentially phosphorylated by Akt. A mutant PDE3B in which serine-273 was replaced by alanine was not phosphorylated either in response to insulin in intact cells or by purified Akt in vitro. In contrast, PDE3B mutants in which alanine was substituted for either serine-296 or serine-421, each of which lies within a sequence (RRXS) preferentially phosphorylated by cAMP-dependent protein kinase, were phosphorylated by Akt in vitro or in response to insulin in intact cells. Moreover, the serine-273 mutant of PDE3B was not activated by insulin when expressed in adipocytes. These results suggest that PDE3B is a physiological substrate of Akt and that Akt-mediated phosphorylation of PDE3B on serine-273 is important for insulin-induced activation of PDE3B.
Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled .sigma. binding site (1993)

A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [3H]-N,N'-di-o-tolylguanidine ([3H]DTG) and [3H]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([3H]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [3H]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [3H]DTG than [3H]-(+)-PPP-labeled sigma sites, suggesting that [3H]DTG and [3H]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [3H]DTG-labeled sigma site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept [b] indole (40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [3H]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [3H]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [3H]DTG- and [3H]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.
Identification of Genes Overexpressed in Head and Neck Squamous Cell Carcinoma Using a Combination of Complementary DNA Subtraction and Microarray Analysis (2000)

We report the identification of nine known genes that are significantly overexpressed in HNSCC as compared to normal tissue using subtractive and microarray technology. In addition, we present four previously unidentified genes that are overexpressed in a subset of tumors. These genes will be developed as tumor markers and vaccine candidates.
Dielectrophoretic separation of cells: Continuous separation (1995)

Dielectrophoresis is the movement of particles in non-uniform alternating and direct current (AC, DC) electric fields. When nonuniform electric fields are created between microelectrodes, cells will redistribute themselves around the electrodes, the force holding the cells in place dependig on the local electric field and on the electrical properties of the cells themselves and the suspending medium. Steric drag forces produced by a gentle fluid flow in the chamber can be used to separate cells by selectively lifting cells from potential energy wells produced by the electric field. The technique is demonstrated in the batch separation of bacteria, yeast cells, and plant cells. Continuous separation and extraction of two cell types can be achieved by repeated reversing of the fluid flow direction in phase with the switching on and off of the applied voltage, and the efficacy of the technique is demonstrated for viable and nonviable (heat-treated) yeast cells. (c) 1995 John Wiley & Sons, Inc.
HUMAN T CELL RESPONSES AGAINST MELANOMA (2005)

Many antigens recognized by autologous T lymphocytes have been identified on human melanoma. Melanoma patients usually mount a spontaneous T cell response against their tumor. But at some point, the responder T cells become ineffective, probably because of a local immunosuppressive process occurring at the tumor sites. Therapeutic vaccination of metastatic melanoma patients with these antigens is followed by tumor regressions only in a small minority of the patients. The T cell responses to the vaccines show correlation with the tumor regressions. The local immunosuppression may be the cause of the lack of vaccination effectiveness that is observed in most patients. In patients who do respond to the vaccine, the antivaccine T cells probably succeed in reversing focally this immunosuppression and trigger a broad activation of other antitumor T cells, which proceed to destroy the tumor.
A computational analysis of protein-DNA complex structures (2000)

Proteins that bind DNA are fundamental to all areas of genetic activity within the cell. To understand how such proteins function, it is necessary to explore the process of recognition and binding to their target DNA sequences. This work presents a comprehensive study of 129 protein-DNA complex structures from the Brookhaven Protein Data Bank and the interactions that are found between the two molecules on binding. NUCPLOT, a software tool that generates schematic plots of intermolecular hydrogen bonds and van der Waals contacts, is described. The resulting diagram is clear, simple and intuitive; it allows immediate identification of the important interactions in the complex and facilitates the study of these structures. NUCPLOT is a completely automated program that can be used for any protein-DNA complex and will also work for certain protein-RNA structures. Also described is a statistical analysis of protein-DNA interactions at an atomic level. Inspection of hydrogen bonds, water-mediated contacts and van der Waals contacts reveals much interdependence between the amino acid and nucleotide base type. These observations are rationalised by inspecting the stereochemistry of the amino acid side chains and base edges exposed in the DNA structure. An interactive Web-based atlas of protein side chain-base contacts is presented as part of the work. Later, the role of the α-helix in DNA-binding by proteins is surveyed - one of the most prevalent methods of direct sequence recognition in the DNA major groove. Comparison of these α-helices from different structural families reveals that there are common binding-orientations between proteins with similar functional requirements. However, examination of the contacts uncovers a very diverse range of interactions between the α-helix and DNA. Finally, sequence conservation in DNA-binding proteins is studied. Amino acids that interact with DNA are generally more conserved than the rest of the protein surface. However, there are significant mutations at key interacting positions, which are expected to discriminate between different DNA sequences. Proteins with comparable structures but alternative functions are explored to see how they have evolved to recognise distinct target sequences and therefore regulate different cellular pathways.
Expression of CD133 on leukemia-initiating cells in childhood ALL (2009)

Optimization of therapy for childhood acute lymphoblastic leukemia (ALL) requires a greater understanding of the cells that proliferate to maintain this malignancy because a significant number of cases relapse, resulting from failure to eradicate the disease. Putative ALL stem cells may be resistant to therapy and subsequent relapses may arise from these cells. We investigated expression of CD133, CD19, and CD38 in pediatric B-ALL. Cytogenetic and molecular analyses demonstrated that karyotypically aberrant cells were present in both CD133(+)/CD19(+) and CD133(+)/CD19(-) subfractions, as were most of the antigen receptor gene rearrangements. However, ALL cells capable of long-term proliferation in vitro and in vivo were derived from the CD133(+)/CD19(-) subfraction. Moreover, these CD133(+)/CD19(-) cells could self-renew to engraft serial nonobese diabetic-severe combined immunodeficient recipients and differentiate in vivo to produce leukemias with similar immunophenotypes and karyotypes to the diagnostic samples. Furthermore, these CD133(+)/CD19(-) ALL cells were more resistant to treatment with dexamethasone and vincristine, key components in childhood ALL therapy, than the bulk leukemia population. Similar results were obtained using cells sorted for CD133 and CD38, with only the CD133(+)/CD38(-) subfraction demonstrating xenograft repopulating capacity. These data suggest that leukemia-initiating cells in childhood B-ALL have a primitive CD133(+)/CD19(-) and CD38(-) phenotype.
An Intramolecular [2 + 3] Cycloaddition Route to Fused 5-Heterosubstituted Tetrazoles (2001)

[reaction: see text] Fused 5-heterotetrazole ring systems are synthesized in high yield via intramolecular [2 + 3] cycloadditions of organic azides and heteroatom-substituted nitriles. Cyanates, thiocyanates, and cyanamides are all competent dipolarophiles for this reaction. A variety of scaffolds are tolerated when the new enclosed ring is five- or six-membered.
Cloning and characterization of human SHIP, the 145-kD inositol 5- phosphatase that associates with SHC after cytokine stimulation (1996)

We recently cloned and sequenced a cDNA encoding a 145-kD protein from the murine hematopoietic cell line B6SUtA, that becomes tyrosine phosphorylated and associated with Shc after cytokine stimulation. Based on its domains and enzymatic activity, we named this protein SHIP for SH2-containing inositol phosphatase (Damen et al, Proc Natl Acad Sci USA 93:1689, 1996). We describe here the cloning of the human homologue of murine SHIP (mSHIP) from a human megakaryocytic cell line (MO7e) lambda gt11 cDNA library using two nonoverlapping mSHIP cDNA fragments as probes. Northern blot analysis suggests that human SHIP (hSHIP) is expressed as a 5.3-kb mRNA in human bone marrow and a wide variety of other tissues. Sequence analysis of this cDNA predicts a protein of 1188 amino acids exhibiting 87.2% overall sequence identity with mSHIP. Contained within the defined open reading frame is an N-terminal, group l src homology 2 (SH2) domain; three NXXY motifs that, if phosphorylated, could be bound by phosphotyrosine binding (PTB) domains; a C-terminal proline-rich region; and two centrally located inositol polyphosphate 5-phosphatase motifs. Fluorescence in situ hybridization, using the full-length hSHIP cDNA as a probe, mapped hSHIP to the long arm of chromosome 2 at the border between 2q36 and 2q37.
Aerosolized Prostacyclin and Iloprost in Severe Pulmonary Hypertension (1996)

Aerosolization of prostacyclin or its stable analog iloprost causes selective pulmonary vasodilatation, increases cardiac output, and improves venous and arterial oxygenation in patients with severe pulmonary hypertension. Thus, it may offer a new strategy for treatment of this disease.
Toxoplasma gondiiAntigen-Pulsed-Dendritic Cell-Derived Exosomes Induce a Protective Immune Response againstT. gondiiInfection (2004)

It was previously demonstrated that immunizing mice with spleen dendritic cells (DCs) that had been pulsed ex vivo with Toxoplasma gondii antigens triggers a systemic Th1-biased specific immune response and induces protection against infection. T. gondii can cause severe sequelae in the fetuses of mothers who acquire the infection during pregnancy, as well as life-threatening neuropathy in immunocompromised patients, in particular those with AIDS. Here, we investigate the efficacy of a novel cell-free vaccine composed of DC exosomes, which are secreted antigen-presenting vesicles that express functional major histocompatibility complex class I and II and T-cell-costimulatory molecules. They have already been shown to induce potent antitumor immune responses. We investigated the potential of DC2.4 cell line-derived exosomes to induce protective immunity against toxoplasmosis. Our data show that most adoptively transferred T. gondii-pulsed DC-derived exosomes were transferred to the spleen, elicited a strong systemic Th1-modulated Toxoplasma-specific immune response in vivo, and conferred good protection against infection. These findings support the possibility that DC-derived exosomes can be used for T. gondii immunoprophylaxis and for immunoprophylaxis against many other pathogens.
Correlation of vascular endothelial growth factor expression with fibroblast growth factor-8 expression and clinico-pathologic parameters in human prostate cancer (2001)

Vascular endothelial growth factor (VEGF) mediates neo-angiogenesis during tumour progression and is known to cooperate with the fibroblast growth factor (FGF) system to facilitate angiogenesis in a synergistic manner. In view of this, we have investigated VEGF expression in 67 cases of prostate cancer previously characterized for fibroblast growth factor-8 (FGF-8) expression. Cytoplasmic VEGF staining was detected in malignant cells in 45 out of 67 cases. Cytoplasmic staining was found in adjacent stromal cells in 32 cases, being particularly strong around nests of invasive tumour. Positive VEGF immunoreactivity in benign glands was restricted to basal epithelium. A significant association was observed between tumour VEGF and FGF-8 expression (P = 0.004). We identified increased VEGF immunoreactivity in both malignant epithelium and adjacent stroma and both were found to be significantly associated with high tumour stage (P = 0.0047 and P = 0.0002, respectively). VEGF expression also correlated with increased serum PSA levels (P = 0.01). Among positively stained tumours, VEGF expression showed a significant association with Gleason score (P = 0.04). Cases showing positive VEGF immunoreactivity in the stroma had a significantly reduced survival rate compared to those with negative staining (P = 0.037). Cases with tumours expressing both FGF-8 in the malignant epithelium and VEGF in the adjacent stroma had a significantly worse survival rate than those with tumours negative for both, or only expressing one of the two growth factors (P = 0.029). Cox multivariate regression analysis of survival demonstrated that stromal VEGF and tumour stage were the most significant independent predictors of survival. In conclusion, we report for the first time a correlation of both tumour and stromal VEGF expression in prostate cancer with clinical parameters as well as its correlation to FGF-8 expression.
Les nouvelles formes de gestion de l'épargne : le cadre financier (1997)

New ways of managing savings : the financial framework Saving management is a process by which economic agents having funding capacities allocate resources to agents having funding requirements. After having recalled major saving management characteristics, we discuss about some determining factors and constituent elements of the saving management process, such as : risk industry development, technology (data processing, télécoms), investors information, fund management control, competition and regulation, and finally the evolution of corporate and professional limits related to saving management.
Evaluation of Potential Protective Factors Against Metabolic Syndrome in Bottlenose Dolphins: Feeding and Activity Patterns of Dolphins in Sarasota Bay, Florida (2013)

Free-ranging bottlenose dolphins (Tursiops truncatus) living in Sarasota Bay, Florida appear to have a lower risk of developing insulin resistance and metabolic syndrome compared to a group of dolphins managed under human care. Similar to humans, differences in diet and activity cycles between these groups may explain why Sarasota dolphins have lower insulin, glucose, and lipids. To identify potential protective factors against metabolic syndrome, existing and new data were incorporated to describe feeding and activity patterns of the Sarasota Bay wild dolphin community. Sarasota dolphins eat a wide variety of live fish and spend 10-20% of daylight hours foraging and feeding. Feeding occurs throughout the day, with the dolphins eating small proportions of their total daily intake in brief bouts. The natural pattern of wild dolphins is to feed as necessary and possible at any time of the day or night. Wild dolphins rarely eat dead fish or consume large amounts of prey in concentrated time periods. Wild dolphins are active throughout the day and night; they may engage in bouts of each key activity category at any time during daytime. Dive patterns of radio-tagged dolphins varied only slightly with time of day. Travel rates may be slightly lower at night, suggesting a diurnal rhythm, albeit not one involving complete, extended rest. In comparison, the managed dolphins are older; often fed a smaller variety of frozen-thawed fish types; fed fish species not in their natural diet; feedings and engaged activities are often during the day; and they are fed larger but fewer meals. In summary, potential protective factors against metabolic syndrome in dolphins may include young age, activity, and small meals fed throughout the day and night, and specific fish nutrients. These protective factors against insulin resistance and type 2 diabetes are similar to those reported in humans. Further studies may benefit humans and dolphins.
High-Resolution &lt;sup&gt;1&lt;/sup&gt;H NMR Investigations of the Oxidative Consumption of Salivary Biomolecules by a Tooth-Whitening Formulation: Relevance to Safety Issues (2012)

A multicomponent evaluation of the oxidative consumption of salivary biomolecules by a hydrogen peroxide (H2O2)-containing tooth-whitening formulation has been performed using high-resolution proton (1H) nuclear magnetic resonance (NMR) spectroscopy. Unstimulated human saliva samples (n = 10) were treated with aliquots of supernatants derived from 1) the H2O2-containing whitening gel, 2) the corresponding tooth-whitening accelerant solution containing an amino-alcohol activator, and 3) a combination of these product agents pre-mixed in the recommended manner. 600 MHz 1H NMR spectra acquired on these samples demonstrated that H2O2 present in the whitening gel gave rise to the oxidative decarboxylation of salivary pyruvate (to acetate and CO2), the direct oxidation of trimethylamine and methionine (to trimethylamine-N-oxide and methionine sulphoxide respectively), and the indirect oxidative consumption of lactate and carbohydrates in general. Experiments conducted on a chemical model system confirmed the consumption of pyruvate by added H2O2, and also revealed that this method could be employed for determinations of the H2O2 content of tooth-whitening products. In conclusion, high-resolution 1H NMR analysis provides much valuable molecular information regarding the fate of tooth-whitening oxidants in human saliva, and also permits an assessment of the ability of endogenous antioxidants therein to protect against any soft tissue damage arising from the possible leakage of H2O2 from tooth-whitening application trays.
Orthopaedic Resource Day (1984)

Nursing orientees come to a new position with various backgrounds, experiences, and knowledge of orthopaedics. This article describes one solution to the problem of designing an orientation learning program. Orthopaedic Resource Day includes assessment of learners' needs, recommendations of independent study to meet the needs, and self-directed study with independent use of resources. Once the program is developed, the instructor is not committed to teach an entire day of class, but serves as resource person. The orientees, in turn, do not waste time attending lectures on familiar material, but instead pursue learning activities to strengthen identified weak areas. Orthopaedic Resource Day is congruent with present day concerns of cost and time effectiveness.
Environmental and social assessment (ESA) studies (2006)

The development objective of the Electricity Distribution and Transmission Improvement Project for Pakistan is to help increase the efficiency, reliability, and quality of electricity supply by supporting reductions in overall technical and commercial losses, increased availability of electricity, and improved voltage profile. The Project also aims to support power sector reform and investment planning and financing through technical assistance. This Environmental Assessment (EA) document evaluated impacts and suggests mitigation measures in the following areas, respectively : soil erosion and degradation, caused by grid stations and transmission lines construction activities; surface and ground water contamination; loss or damage to wildlife; damage to natural vegetation; inappropriate liquid or solid waste disposal; leakage from oils and chemicals; crop compensation; construction crews will be provided with LPG for cooking; use of firewood will not be allowed; post-construction monitoring of tower foundations will be carried out to detect early signs of soil erosion or land sliding; and finally, applicability of Pakistan's legal and environmental policy legislation and the Bank's operational safeguard policy on environmental and social matters, such as Forestry, Natural Habitats; Indigenous Peoples; Cultural Property; Projects in Disputed Areas.