gebhart/patrepeval huggingface dataset:
Autocrine Prolactin Promotes Prostate Cancer Cell Growth via Janus Kinase-2-Signal Transducer and Activator of Transcription-5a/b Signaling Pathway (2007)

The molecular mechanisms that promote progression of localized prostate cancer to hormone-refractory and disseminated disease are poorly understood. Prolactin (Prl) is a local growth factor produced in high-grade prostate cancer, and exogenously added Prl in tissue or explant cultures of normal and malignant prostate is a strong mitogen and survival factor for prostate epithelium. The key signaling proteins that mediate the biological effects of Prl in prostate cancer are Signal Transducer and Activator of Transcription (Stat)-5a/5b via activation of Janus kinase-2. Importantly, inhibition of Stat5a/b in prostate cancer cells induces apoptotic death. Using a specific Prl receptor antagonist (Delta1-9G129R-hPRL), we demonstrate here for the first time that autocrine Prl in androgen-independent human prostate cancer cells promotes cell viability via Stat5 signaling pathway. Furthermore, we examined a unique clinical material of human hormone refractory prostate cancers and metastases and show that autocrine Prl is expressed in 54% of hormone-refractory clinical human prostate cancers and 62% prostate cancer metastases. Finally, we demonstrate that autocrine Prl is expressed from both the proximal and distal promoters of the Prl gene in clinical human prostate cancers and in vivo and in vitro human prostate cancer models, independently of pituitary transcription factor-1 (Pit-1). Collectively, the data provide novel evidence for the concept that autocrine Prl signaling pathway is involved in growth of hormone-refractory and metastatic prostate cancer. The study also provides support for the use of Prl receptor antagonists or other therapeutic strategies to block the Prl-Janus kinase-2-Stat5 signaling pathway in advanced prostate cancer.
Application of a modified indirect fluorescent antibody test to the detection of antibodies to bovine respiratory syncytial virus in Ontario cattle. (1986)

A modified indirect fluorescent antibody test for the detection of serum antibodies to bovine respiratory syncytial virus was developed. The test made use of Terasaki plastic microtiter plates in which bovine respiratory syncytial virus (Saskatchewan strain) infected Georgia bovine kidney cells were grown and fixed in situ by a modified acetone fixation procedure. Evans blue dye was used as a counterstain to reduce nonspecific fluorescence. In a study of 986 field sera from a geographically broad cross-section of mature Ontario cattle, 95% of the samples were found to be positive at or above a 1:2 dilution. No seronegative regions, counties or herds were identified. When representative samples covering a range of indirect fluorescent antibody titers were further examined by a microtiter virus neutralization assay, a significant agreement was found between the two tests. Up to a fourfold decrease in titer was observed when antigen coated plates were stored at -70 degrees C for four months. The modified indirect fluorescent antibody test for bovine respiratory syncytial virus antibody detection proved to be a rapid, practical procedure for use in the diagnostic laboratory. This study confirms that bovine respiratory syncytial virus is widespread in the Ontario cattle population and that most mature cattle can be assumed to have been exposed to this virus.
Cdc13p: A Single-Strand Telomeric DNA-Binding Protein with a Dual Role in Yeast Telomere Maintenance (1996)

The CDC13 gene has previously been implicated in the maintenance of telomere integrity in Saccharomyces cerevisiae. With the use of two classes of mutations, here it is shown that CDC13 has two discrete roles at the telomere. The cdc13-2est mutation perturbs a function required in vivo for telomerase regulation but not in vitro for enzyme activity, whereas cdc13-1ts defines a separate essential role at the telomere. In vitro, purified Cdc13p binds to single-strand yeast telomeric DNA. Therefore, Cdc13p is a telomere-binding protein required to protect the telomere and mediate access of telomerase to the chromosomal terminus.
[Addition of ketamine infusion to patient controlled analgesia with intravenous morphine after abdominal hysterectomy]. (2006)

In our study we aimed to reduce postoperative morphine consumption, prevent adverse effects of morphine, and improve analgesic quality via adding analgesic doses of ketamine infusion to intravenous morphine-patient controlled analgesia (PCA). After local ethics committee approval, 45 patients scheduled for total abdominal hysterectomy were included in the study. In the postoperative period the patients were separated into two groups randomly. After starting morphine-PCA in both groups, one group received ketamine infusion (Group K: n= 22), while the other group received saline infusion (Group S: n= 23) for 24 hours. There was no significant difference between the postoperative systolic and diastolic arterial pressures, heart rate and respiratory rate values. Visual Analogue Scale and Verbal Rating Scale measures was significantly lower in Group K (p<0.01). Total morphine consumption was higher in Group S (p<0.05). Sedation scores were significantly lower in Group K (p<0.05). When adverse effects were evaluated we found that nausea was higher in Group S (p<0.05), while there was no difference in the other side effects (p>0.05). Patient satisfaction was better in the 24th and 48th hours in Group K and was found to be statistically significant (p<0.05). Our results suggest that ketamine infusion added to opioids for postoperative analgesia, reduces total opioid requirement and prevents side effects.
Imiquimod a new adjuvant for telomerase peptide vaccine: A phase I trial in patients with inoperable pancreatic cancer (2005)

9623 Background Telomerase is a key enzyme in the process of immortalization of cancer cells and as such it holds a pivotal role in carcinogenesis. The catalytic subunit of telomerase, hTERT is expressed in 85–90% of pancreatic cancers. We have previously demonstrated that vaccination of inoperable pancreatic cancer patients with the telomerase peptide GV1001 in combination with GM-CSF, results in a high frequency of immune responders (75%). Recently it has been focus on imiquimod, an immune modulator, as a potential new adjuvant for peptide vaccination. Imiquimod acts via stimulation of Toll-like receptor 7 on antigen presenting cells, resulting in production of the cytokines IL-12, INF- α and INF-β, and thus creates a broader inflammatory response than GM-CSF. Methods The present study was performed to determine safety and immunogenecity of GV1001 using imiquimod as an adjuvant. Fourteen patients with non-resectable pancreatic cancer, were recruited into a phase I trial. The patients were vaccinated eight times over a 10 week regimen. Imiquimod (Aldara, 3M) was applied on the skin at the injection site 24 and 3 hours before intradermal injection of GV1001. The patients were evaluated on a regular basis: biochemically, radiologically and clinically. Immune responses were measured as skin reaction (DTH) and T-cell responses in vitro. Patients were offered monthly booster vaccinations as follow up treatment. Results Immune response was detected in 5 (35.7%) of the 13 evaluable patients (at least finishing week 4). One additional patient became immune responder after the second booster vaccination, resulting in an overall response rate of 46%. Conclusion The study documented that the use of Imiquimod in combination with GV1001 was well tolerated; there were no signs of toxicity, nor serious adverse events. Moore data is necessary to determine wether imiquimod may be used alone or in combination with GM-CSF, as adjuvant for peptide vaccination. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GemVax GemVax GemVax GemVax GemVax
Characteristics of a cell line established from a patient with multiple osteosarcoma, appearing 13 years after treatment for bilateral retinoblastoma (1986)

An osteosarcoma cell line, OHS, was established from a patient with multiple skeletal manifestations of osteosarcoma, developing after bilateral retinoblastoma. The tumor cells expressed sarcoma-associated antigens and showed rapid growth in monolayers and as multicellular spheroids. They formed distinct colonies in soft agar, and subcutaneous tumors in nude mice. Morphological studies indicated that OHS cells had retained important characteristics of the cells of origin. No deletion of the retinoblastoma genes on chromosome 13q14 could be demonstrated with the banding techniques used. However, cytogenetic studies revealed double minute chromosomes, as evidence of gene amplification, as well as translocations involving chromosomes 1,6,11 and 13. The OHS line can be used to study the genetic basis of tumor initiation and growth, and to elucidate factors predisposing for second primary cancers in retinoblastoma patients.
Effect of CPP-ACP paste on tooth mineralization: an FE-SEM study (2007)

Milk and milk products, such as cheese, have been shown to exhibit anticariogenic properties in human and animal models. CPP-ACP shows an anti-caries effect by suppressing demineralization, enhancing remineralization, or possibly a combination of both. The purpose of this study was to evaluate the effect of CPP-ACP paste on demineralization by observing the treated tooth surface using an FE-SEM. The specimens were prepared by cutting enamel and dentin of bovine teeth into blocks. A few specimens were stored in 0.1 M lactic acid buffer solution for 10 min and then in artificial saliva (negative control). The remaining specimens were stored in a 10 times-diluted solution of CPP-ACP paste or a placebo paste containing no CPP-ACP for 10 min, followed by 10 min immersion in a demineralizing solution (pH = 4.75, Ca) twice a day before storage in artificial saliva. After treatment of the specimens for 3, 7, 21 and 28 days, they were fixed in 2.5% glutaraldehyde in cacodylate buffer solution, dehydrated in ascending grades of tert-butyl alcohol, and then transferred to a critical-point dryer. The surfaces were coated with a thin film of Au in a vacuum evaporator, and were observed under field emission-scanning electron microscopy (FE-SEM). The SEM observations revealed different morphological features brought about by the various storage conditions. Demineralization of the enamel and dentin surfaces was more pronounced with the longer test period in the control and negative control specimens. On the other hand, enamel and dentin specimens treated with CPP-ACP paste revealed slight changes in their morphological features. From the morphological observations of the enamel and dentin surfaces, it could be considered that the CPP-ACP paste might prevent demineralization of the tooth structure.
More than dotting the i's --- foundations for crossing-based interfaces (2002)

Today's graphical interactive systems largely depend upon pointing actions, i.e. entering an object and selecting it. In this paper we explore whether an alternate paradigm --- crossing boundaries --- may substitute or complement pointing as another fundamental interaction method. We describe an experiment in which we systematically evaluate two target-pointing tasks and four goal-crossing tasks, which differ by the direction of the movement variability constraint (collinear vs. orthogonal) and by the nature of the action (pointing vs. crossing, discrete vs. continuous). We found that participants' temporal performance in each of the six tasks was dependent on the index of difficulty formulated in the same way as in Fitts' law, but that the parameters differ by task. We also found that goal crossing completion time was shorter or no longer than pointing performance under the same index of difficulty. These regularities, as well as qualitative characterizations of crossing actions and their application in HCI, lay the foundation for designing crossing-based user interfaces
Photoresist with Low Fluorescence for Bioanalytical Applications (2007)

The negative photoresist SU-8 has found widespread use as a material in the fabrication of microelectrical-mechanical systems (MEMS). Although SU-8 has been utilized as a structural material for biological MEMS, a number of SU-8 properties limit its application in these bioanalytical devices. These attributes include its brittleness, nonspecific adsorption of biomolecules, and high fluorescence in the visible wavelengths. In addition, native SU-8 is a poor substrate for cellular adhesion. Photoresists composed of resins with epoxide side groups and photoacids were screened for their ability to serve as a low-fluorescence photoresist with sufficient resolution to generate microstructures with dimensions of 5-10 microm. The fluorescence of structures formed from 1002F photoresist (1002F resin combined with triarylsulfonium hexafluoroantimonate salts) was as much as 10 times less fluorescent than similar SU-8 microstructures. The absorbance of 1002F in the visible wavelengths was also substantially lower than that of SU-8. Microstructures or pallets with an aspect ratio as high as 4:1 could be formed permitting 1002F to be used as a structural material in the fabrication of arrays of pallets for sorting adherent cells. Several different cell types were able to adhere to native 1002F surfaces, and the viability of these cells was excellent. As with SU-8, 1002F has a weak adhesion to glass, a favorable attribute when the pallet arrays are used to sort adherent cells. A threshold, laser pulse energy of 3.5 microJ was required to release individual 50 microm, 1002F pallets from an array. Relative to SU-8, 1002F photoresist offers substantial improvements as a substrate in bioanalytical devices and is likely to find widespread use in BioMEMS.
IL-12 receptor β1 deficiency alters in vivo T follicular helper cell response in humans (2013)

Antibody responses represent a key immune protection mechanism. T follicular helper (Tfh) cells are the major CD4(+) T-cell subset that provides help to B cells to generate an antibody response. Tfh cells together with B cells form germinal centers (GCs), the site where high-affinity B cells are selected and differentiate into either memory B cells or long-lived plasma cells. We show here that interleukin-12 receptor β1 (IL-12Rβ1)-mediated signaling is important for in vivo Tfh response in humans. Although not prone to B cell-deficient-associated infections, subjects lacking functional IL-12Rβ1, a receptor for IL-12 and IL-23, displayed substantially less circulating memory Tfh and memory B cells than control subjects. GC formation in lymph nodes was also impaired in IL-12Rβ1-deficient subjects. Consistently, the avidity of tetanus toxoid-specific serum antibodies was substantially lower in these subjects than in age-matched controls. Tfh cells in tonsils from control individuals displayed the active form of signal transducer and activator of transcription 4 (STAT4), demonstrating that IL-12 is also acting on Tfh cells in GCs. Thus, our study shows that the IL-12-STAT4 axis is associated with the development and the functions of Tfh cells in vivo in humans.
Some practical improvements in the continual reassessment method for phase I studies (1995)

The Continual Reassessment Method (CRM) is a Bayesian phase I design whose purpose is to estimate the maximum tolerated dose of a drug that will be used in subsequent phase II and III studies. Its acceptance has been hindered by the greater duration of CRM designs compared to standard methods, as well as by concerns with excessive experimentation at high dosage levels, and with more frequent and severe toxicity. This paper presents the results of a simulation study in which one assigns more than one subject at a time to each dose level, and each dose increase is limited to one level. We show that these modifications address all of the most serious criticisms of the CRM, reducing the duration of the trial by 50-67 per cent, reducing toxicity incidence by 20-35 per cent, and lowering toxicity severity. These are achieved with minimal effects on accuracy. Most important, based on our experience at our institution, such modifications make the CRM acceptable to clinical investigators.
SSB Protein Limits RecOR Binding onto Single-stranded DNA (2007)

The RecO and RecR proteins form a complex that promotes the nucleation of RecA protein filaments onto SSB protein-coated single-stranded DNA (ssDNA). However, even when RecO and RecR proteins are provided at optimal concentrations, the loading of RecA protein is surprisingly slow, typically proceeding with a lag of 10 min or more. The rate-limiting step in RecOR-promoted RecA nucleation is the binding of RecOR protein to ssDNA, which is inhibited by SSB protein despite the documented interaction between RecO and SSB. Full activity of RecOR is seen only when RecOR is preincubated with ssDNA prior to the addition of SSB. The slow binding of RecOR to SSB-coated ssDNA involves the C terminus of SSB. When an SSB variant that lacks the C-terminal 8 amino acids is used, the capacity of RecOR to facilitate RecA loading onto the ssDNA is largely abolished. The results are used in an expanded model for RecOR action.
Electrical impedance characterization of normal and cancerous human hepatic tissue (2010)

The four-electrode method was used to measure the ex vivo complex electrical impedance of tissues from 14 hepatic tumors and the surrounding normal liver from six patients. Measurements were done in the frequency range 1-400 kHz. It was found that the conductivity of the tumor tissue was much higher than that of the normal liver tissue in this frequency range (from 0.14 +/- 0.06 S m(-1) versus 0.03 +/- 0.01 S m(-1) at 1 kHz to 0.25 +/- 0.06 S m(-1) versus 0.15 +/- 0.03 S m(-1) at 400 kHz). The Cole-Cole models were estimated from the experimental data and the four parameters (rho(0), rho(infinity), alpha, f(c)) were obtained using a least-squares fit algorithm. The Cole-Cole parameters for the cancerous and normal liver are 9 +/- 4 Omega m(-1), 2.2 +/- 0.7 Omega m(-1), 0.5 +/- 0.2, 140 +/- 103 kHz and 50 +/- 28 Omega m(-1), 3.2 +/- 0.6 Omega m(-1), 0.64 +/- 0.04, 10 +/- 7 kHz, respectively. These data can contribute to developing bioelectric applications for tissue diagnostics and in tissue treatment planning with electrical fields such as radiofrequency tissue ablation, electrochemotherapy and gene therapy with reversible electroporation, nanoscale pulsing and irreversible electroporation.
Design of a real-time trader for mobile objects in open distributed environments (2002)

Advances in wireless communication and distributed computing will create a new computing environment where mobile objects can work in real-time over heterogeneous systems anywhere and at any time. In this environment, real-time traders which can perform trading services under timing constraints are required. In this paper we identify design issues of a real-time trader for mobile objects and investigate them. Our work focuses on the design of real-time trading mechanism, trading interfaces, and the interactions of interworking traders to provide real-time trading services for mobile clients and servers.
Concomitant targeting of programmed death-1 (PD-1) and CD137 improves the efficacy of radiotherapy in a mouse model of human BRAFV600-mutant melanoma (2016)

T cell checkpoint blockade with antibodies targeting programmed cell death (ligand)-1 (PD-1/PD-L1) and/or cytotoxic T lymphocyte-antigen 4 (CTLA-4) has improved therapy outcome in melanoma patients. However, a considerable proportion of patients does not benefit even from combined α-CTLA-4 and α-PD-1 therapy. We therefore examined to which extent T cell (co)stimulation and/or stereotactic body radiation therapy (SBRT) could further enhance the therapeutic efficacy of T cell checkpoint blockade in a genetically engineered mouse melanoma model that is driven by PTEN-deficiency, and BRAFV600 mutation, as in human, but lacks the sporadic UV-induced mutations. Tumor-bearing mice were treated with different combinations of immunomodulatory antibodies (α-CTLA-4, α-PD-1, α-CD137) or interleukin-2 (IL-2) alone or in combination with SBRT. None of our immunotherapeutic approaches (alone or in combination) had any anti-tumor efficacy, while SBRT alone delayed melanoma outgrowth. However, α-CD137 combined with α-PD-1 antibodies significantly enhanced the anti-tumor effect of SBRT, while the anti-tumor effect of SBRT was not enhanced by interleukin-2, or the combination of α-CTLA-4 and α-PD-1. We conclude that α-CD137 and α-PD-1 antibodies were most effective in enhancing SBRT-induced tumor growth delay in this mouse melanoma model, outperforming the ability of IL-2, or the combination of α-CTLA-4 and α-PD-1 to synergize with SBRT. Given the high mutational load and increased immunogenicity of human melanoma with the same genotype, our findings encourage testing α-CD137 and α-PD-1 alone or in combination with SBRT clinically, particularly in patients refractory to α-CTLA-4 and/or α-PD-1 therapy.
Coalescence overgrowth of GaN nano-columns with metalorganic chemical vapor deposition (2007)

The authors demonstrate the coalescence overgrowth of GaN nano-columns on a (111) Si substrate with metalorganic chemical vapor deposition to show high-quality optical properties in the overgrown film. Plan-view scanning electron microscopy (SEM) shows coalesced surface morphology, although hexagonal structures are still visible in the images. The cross-section cathodoluminescence (CL) image shows more efficient emission in the overgrowth layer than from the nano-column layer. The plan-view CL image demonstrates that the emitted light is mainly from the hexagonal structures. The photoluminescence measurement result indicates that the emission efficiency of the overgrown layer is even higher than that of an undoped GaN thin film of high quality. The presence of hexagonal structures correlates to surface roughness values in the range of several nanometres.
Equipping staff to support people with an intellectual disability and dementia in care home settings (2005)

The knowledge, experiences and skills of direct care staff working in care home settings are essential in ensuring a good quality of life and care for a person with an intellectual disability (ID) who develops dementia. Drawing on the findings of a wider study, the issues of training, support and the wider needs of staff when trying to support a resident who develops dementia are explored, specifically as relating to the role played by staff and the need to determine their experiences and related training needs. Following an introduction to the policy and practice context for working with people with an ID and dementia, and a brief description of the research method, the authors discuss the attitudes and practices of staff; supportive changes at an organizational level; and the knowledge and training needs of staff and specific gaps in knowledge. The authors argue that, within the policy and practice context of aiming to support residents to ‘age in place’, support for staff is a crucial aspect of ensuring that such an approach is effective and provides a coordinated approach to planning, resourcing and support.
Theoretical analysis of laterally emitting terahertz-wave generation by difference-frequency generation in channel waveguides (2003)

Theoretical analysis of top- and side-emitting terahertz-wave generation by difference frequency generation in LiNbO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> channel waveguides with domain-inverted grating is presented. The analysis is based on Green's function and plane-wave expansion approaches. Mathematical expressions and numerical data for the conversion efficiency and the directionality were obtained. The results are consistent with those using two-dimensional model, but are more accurate and apply for various realistic device configurations. It was shown that higher efficiencies can be accomplished with narrow channel guides, although the radiation is highly divergent.