gebhart/patrepeval huggingface dataset:
A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression. (1995)

In order to construct a multivariate model for predicting early recurrence and cancer death for patients with stage I non-small cell lung cancer, 271 consecutive patients (mean age, 63 +/- 8 years) who were diagnosed, treated, and followed at one institution were studied. All patients were clinical stage I with head and chest/abdominal computed tomograms and radionuclide bone scans without evidence of metastatic disease. Pathological material after resection was reviewed to verify histological staging. Follow-up documented the time and location of any recurrence, was a median 56 months in duration, and was complete in all cases. Data recorded included age, sex, smoking history, presenting symptoms, pathological description, and oncoprotein staining for erbB-2 (HER-2/neu), p53, and KI-67 proliferation protein. Immunohistochemistry of oncogene expression was performed on two separate archived paraffin tumor blocks for each patient, with normal lung as control. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Data, including immunohistochemistry, were complete for all 271 patients. Actual 5-year survival was 63% and actuarial 10-year survival was 58%. Significant univariate predictors (P < 0.05) of early recurrence and cancer-death were: male sex; the presence of symptoms; chest pain; type of cough; hemoptysis; tumor size > 3 cm diameter (T2); poor differentiation; vascular invasion; erbB-2 expression; p53 expression; and a higher KI-67 proliferation index (> 5%). An additive oncogene expression curve demonstrated a 5-year survival of 72% for 136 patients without p53 or erbB-2, 58% for 108 patients who expressed either oncogene, and 38% for 27 who expressed both (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer Immunotherapy Targeting the High Molecular Weight Melanoma-Associated Antigen Protein Results in a Broad Antitumor Response and Reduction of Pericytes in the Tumor Vasculature (2008)

The high molecular weight melanoma-associated antigen (HMW-MAA), also known as melanoma chondroitin sulfate proteoglycan, has been used as a target for the immunotherapy of melanoma. This antigen is expressed on the cell surface and has a restricted distribution in normal tissues. Besides its expression in a broad range of transformed cells, this antigen is also found in pericytes, which are important for tumor angiogenesis. We generated a recombinant Listeria monocytogenes (Lm-LLO-HMW-MAA-C) that expresses and secretes a fragment of HMW-MAA (residues 2,160-2,258) fused to the first 441 residues of the listeriolysin O (LLO) protein. Immunization with Lm-LLO-HMW-MAA-C was able to impede the tumor growth of early established B16F10-HMW-MAA tumors in mice and both CD4(+) and CD8(+) T cells were required for therapeutic efficacy. Immune responses to a known HLA-A2 epitope present in the HMW-MAA(2160-2258) fragment was detected in the HLA-A2/K(b) transgenic mice immunized with Lm-LLO-HMW-MAA-C. Surprisingly, this vaccine also significantly impaired the in vivo growth of other tumorigenic cell lines, such as melanoma, renal carcinoma, and breast tumors, which were not engineered to express HMW-MAA. One hypothesis is that the vaccine could be targeting pericytes, which are important for tumor angiogenesis. In a breast tumor model, immunization with Lm-LLO-HMW-MAA-C caused CD8(+) T-cell infiltration in the tumor stroma and a significant decrease in the number of pericytes in the tumor blood vessels. In conclusion, a Lm-based vaccine against HMW-MAA can trigger cell-mediated immune responses to this antigen that can target not only tumor cells but also pericytes in the tumor vasculature.
Induction of an antibody response in cultures of human peripheral blood lymphocytes. (1976)

A culture system is descirbed which provides adequate conditions for in vitro immunization of humand peripheral blood lymphocytes to heterologous erythrocytes. Making use of this method we could obtain, with a number of different donors, an antibody response which peaked at about day 8 of culture with 30-300 plaque-forming cells (PFC) per 10(6) input lymphocytes. However, in a number of experiments poor or negative results were obtained, even with donors that had previously given good response. This variability in the results was shown not to be due to a too low number of precursor cells present in the blood and could be overcome by treating the cells, before initiation of the culture, with a factor produced by mouse T cells educated to sheep erythrocytes (SRBC). Under these conditions a PFC responce was obtained which peaked at about day 8 and which in some experiments could be as high as 20,000 PFC per 10(6) input lymphocytes. Paralleling the increase in PFC was an increase in cell number. The cells recovered from the treated cultures were at all times more numerous than in the nontreated cultures. The height of both the proliferative and antibody-producing responses varied from experiment to experiment, a higher proliferative response, accompanying a higher PFC response. Although the mechanisms that are at the basis of the antibody response in vitro described in this paper still need to be clarified, this system may become a useful tool in studying the immune response in man.
Erratum to: Fibrinogen production is enhanced in an in-vitro model of non-alcoholic fatty liver disease: an isolated risk factor for cardiovascular events? (2016)

Cardiovascular disease (CVD) remains the major cause of excess mortality in patients with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the individual contribution of NAFLD to CVD risk factors in the absence of pathogenic influences from other comorbidities often found in NAFLD patients, by using an established in-vitro model of hepatic steatosis.Histopathological events in non-alcoholic fatty liver disease were recapitulated by focused metabolic nutrient overload of hepatoblastoma C3A cells, using oleate-treated-cells and untreated controls for comparison. Microarray and proteomic data from cell culture experiments were integrated into a custom-built systems biology database and proteogenomics analysis performed. Candidate genes with significant dysregulation and concomitant changes in protein abundance were identified and STRING association and enrichment analysis performed to identify putative pathogenic pathways.The search strategy yielded 3 candidate genes that were specifically and significantly up-regulated in nutrient-overloaded cells compared to untreated controls: fibrinogen alpha chain (2.2 fold), fibrinogen beta chain (2.3 fold) and fibrinogen gamma chain (2.1 fold) (all rank products pfp <0.05). Fibrinogen alpha and gamma chain also demonstrated significant concomitant increases in protein abundance (3.8-fold and 2.0-fold, respectively, p <0.05).In-vitro modelling of NAFLD and reactive oxygen species formation in nutrient overloaded C3A cells, in the absence of pathogenic influences from other comorbidities, suggests that NAFLD is an isolated determinant of CVD. Nutrient overload-induced up-regulation of all three fibrinogen component subunits of the coagulation cascade provides a possible mechanism to explain the excess CVD mortality observed in NAFLD patients.
Acute Migraine Treatment: Patterns of Use and Satisfaction in a Clinical Population (2006)

Migraine patients have treatment preferences. They generally want a drug that provides complete headache relief, and they are often satisfied with the current treatment options.
Salmonella Synthesizing 1-Monophosphorylated Lipopolysaccharide Exhibits Low Endotoxic Activity while Retaining Its Immunogenicity (2011)

The development of safe live, attenuated Salmonella vaccines may be facilitated by detoxification of its LPS. Recent characterization of the lipid A 1-phosphatase, LpxE, from Francisella tularensis allowed us to construct recombinant, plasmid-free strains of Salmonella that produce predominantly 1-dephosphorylated lipid A, similar to the adjuvant approved for human use. Complete lipid A 1-dephosphorylation was also confirmed under low pH, low Mg(2+) culture conditions, which induce lipid A modifications. LpxE expression in Salmonella reduced its virulence in mice by five orders of magnitude. Moreover, mice inoculated with these detoxified strains were protected against wild-type challenge. Candidate Salmonella vaccine strains synthesizing pneumococcal surface protein A (PspA) were also confirmed to possess nearly complete lipid A 1-dephosphorylation. After inoculation by the LpxE/PspA strains, mice produced robust levels of anti-PspA Abs and showed significantly improved survival against challenge with wild-type Streptococcus pneumoniae WU2 compared with vector-only-immunized mice, validating Salmonella synthesizing 1-dephosphorylated lipid A as an Ag-delivery system.
Basic and clinical aspects of fibrinolysis and thrombolysis (1991)

LOOD CONTAINS an enzymatic system called the
An efficient dose calculation strategy for intensity modulated proton therapy (2011)

While intensity-modulated proton therapy (IMPT) has great potential to improve the therapeutic efficacy of radiotherapy, IMPT optimization can be computationally demanding, particularly for large and complex tumors. Here we propose a dose calculation strategy to accelerate IMPT optimization while reducing memory requirements. By using two adjustable threshold parameters, our method separates dose contributions from proton beamlets into major and minor components for each dose voxel. The optimization proceeds with two levels of iterations: in inner iterations, doses are updated in correspondence with changes in beamlet intensities from only the major contributions while keeping the portions from the minor contributions constant; in outer iterations, doses are recalculated exactly by considering both major and minor contributions. Since the number of elements in the influence matrix for major contributions is relatively small, each inner iteration proceeds quickly. Each outer iteration requires a longer computation time, but only a few such iterations are needed. Our study shows that the proposed strategy leads to nearly identical dose distributions as those optimized with the full influence matrix, but reducing computing time by at least a factor of 3 and internal memory requirements by a factor of 10 or more. In addition, we show that the proposed approach could enhance other optimization-related applications such as optimizing beam angles. By using an advanced lung cancer case that would demand large computing resources by conventional optimization approach, we show how our method may potentially help improve IMPT treatment planning in real clinical situations.
Animal Cell Electroporation and Electrofusion Protocols (1995)

The ability to introduce macromolecules into animal cells, includ­ ing DNA, RNA, proteins, and other bioactive compounds has facili­ tated a broad range of biological studies, from biochemistry and biophysics to molecular biology, cell biology, and whole animal stud­ ies. Gene transfer technology in particular will continue to play an essential role in studies aimed at improving our understanding of the relationships between the gene structure and function, and it has impor­ tant practical applications in both biotechnology and biomedicine, as evidenced by the current intense interest in gene therapy. Although DNA and other macromolecules may be introduced into cells by a variety of methods, including chemical treatments and microinjection, el- troporation has proven to be simpler to perform, more efficient, and effective with a wider variety of cell types than other techniques. The early and broad success of electric field-mediated DNA transfer soon prompted researchers to investigate electroporation for transferring other types of molecules into cells, including RNA, enzymes, antibodies, and analytic dyes. Animal Cell Electroporation and Electrofusion Protocols begins with three chapters that describe the theoretical and practical aspects of electroporation, including a review of the commercially available instrumentation. These introductory chapters will be of particular inter­ est to those new to electric field technologies and to those developing protocols for as yet untested species or cell types. Nineteen chapters follow that present well-tested protocols for electroporation of proteins and DNA into insect, fish, and mammalian cells
Hybridization of DNA and PNA Molecular Beacons to Single-Stranded and Double-Stranded DNA Targets (2002)

Molecular beacons are sensitive fluorescent probes hybridizing selectively to designated DNA and RNA targets. They have recently become practical tools for quantitative real-time monitoring of single-stranded nucleic acids. Here, we comparatively study the performance of a variety of such probes, stemless and stem-containing DNA and PNA (peptide nucleic acid) beacons, in Tris-buffer solutions containing various concentrations of NaCl and MgCl(2). We demonstrate that different molecular beacons respond differently to the change of salt concentration, which could be attributed to the differences in their backbones and constructions. We have found that the stemless PNA beacon hybridizes rapidly to the complementary oligodeoxynucleotide and is less sensitive than the DNA beacons to the change of salt thus allowing effective detection of nucleic acid targets under various conditions. Though we found stemless DNA beacons improper for diagnostic purposes due to high background fluorescence, we believe that use of these DNA and similar RNA constructs in molecular-biophysical studies may be helpful for analysis of conformational flexibility of single-stranded nucleic acids. With the aid of PNA "openers", molecular beacons were employed for the detection of a chosen target sequence directly in double-stranded DNA (dsDNA). Conditions are found where the stemless PNA beacon strongly discriminates the complementary versus mismatched dsDNA targets. Together with the insensitivity of PNA beacons to the presence of salt and DNA-binding/processing proteins, the latter results demonstrate the potential of these probes as robust tools for recognition of specific sequences within dsDNA without denaturation and deproteinization of duplex DNA.
Intravesical Evans Strain BCG Therapy: Quantitative Immunohistochemical Analysis of the Immune Response within the Bladder Wall (1992)

Previous studies have demonstrated that is is the local immune response which is of importance for the anti-tumour activity of BCG therapy. We have investigated this by quantitative immunohistochemical analysis of serial bladder mucosal biopsies taken before, during and after an eight week course of intravesical Evans strain BCG therapy and three monthly thereafter in 16 patients (15 extensive CIS and one extensive G2pTa papillary tumour). This particular group of patients had a 67% complete response rate at six months post-treatment. The main findings on immunohistochemical analysis were the universal induction of MHC Class II antigens by urothelial cells which was statistically significant up to 6 months after completion of therapy, coupled with a T cell dominated cystitis. Increases in CD3+ T cell infiltration of the lamina propria and that of the CD4+ "Helper" subset which predominated were significant up to 3 months post-therapy and these cells showed evidence of increased immunological activation as shown by increased interleukin-2 receptor and MHC Class II antigen expression. There were also significant increases in CD68+ macrophage and the incidence of CD22+ B cell aggregates but CD57+ NK cells were sparse both before and after therapy. The degree of mononuclear cell infiltration for all markers examined (except CD57) was significantly greater in those biopsies in which the urothelial cells expressed MHC Class II antigens than in those that did not. Also the degree of T cell infiltration (CD3, CD4 and CD8) was significantly greater in the eight patients deemed to have had a complete response compared to those seven with a partial response or treatment failure. These results are discussed in terms of possible mechanisms of action for BCG therapy and in particular the role of enhanced antigen presentation by tumour cells.
Sequencing of eleven introns in genomic DNA encoding rat glucagon receptor and multiple alternative splicing of its mRNA (1994)

We used the PCR (polymerase chain reaction) to amplify fragments of glucagon receptor DNA from genomic DNA. Sequencing of the subcloned fragments demonstrated that genomic DNA encoding the glucagon receptor spans over 12 exons interrupted by 11 introns. The introns were located mainly at the 5' end and in the core domain of the glucagon receptor CDS totalling 23 kb. Intron positions were similar to the positions of introns in growth hormone-releasing hormone receptor and parathyroid hormone receptor, two receptors belonging to the same receptor family as the glucagon receptor. This high number of introns might be the cause of the mRNA polymorphism observed at the 5' end: when PCR was performed on cDNA using primers amplifying the central or 3' end cDNA fragments, a single band corresponding to the cloned cDNA was observed. In contrast, if primers amplifying cDNA fragments corresponding to nucleotides -8 to 680 of CDS were used, cDNA fragments of approximately 500 bp, 600 bp, 700 bp, 800 bp and 900 bp were specifically and reproducibly amplified. Sequencing of these fragments showed either incomplete intron removal or splicing at alternative positions. Two of these sequenced variants were translatable in putative glucagon receptor variants: (1) unsplicing of intron III (81 bp) gave an additional 27 amino acid sequence after Lys91 in the N-terminal domain of the receptor. In the liver, where the normal CDS represented about one third of the mRNA molecules, this mRNA variant represented 18% of total mRNA forms; (2) a 21 bp deletion in exon V giving rise to a putative deletion of 7 amino acids in glucagon receptor (delta 64-84 CDS) was also relatively abundant in the liver (10%). The observed polymorphism of the glucagon receptor mRNA may contribute to the regulation of glucagon receptor expression and perhaps to the heterogeneity of these receptors.
A DNA Nanomachine Based on a Duplex–Triplex Transition (2004)

Making DNA work: A DNA nanomachine with a mechanism based on a DNA duplex–triplex transition (see figure) was constructed. The key component is a DNA triplex that contains C+GC triplets and is only stable under acidic conditions. The DNA machine uses H+ and OH− ions as fuel and its only waste products are H2O and NaCl.
Adverse drug reactions. A critical review. (1975)

The data on adverse drug reactions (ADRs) are incomplete, unrepresentative, uncontrolled, and lacking in operational criteria for identifying ADRs. No quantitative conclusions can be drawn from the reported data in regard to morbidity, mortality, or the underlying causes of ADRs, and attempts to extrapolate the available data to the general population would be invalid and perhaps misleading. To evaluate the impact as well as the causes of ADRs, representative populations, including general hospital and ambulatory patients of all medical specialties, must be studied, and operationally defined criteria must be used to establish the presence of an ADR in a prospective study that incorporates appropriate control populations. Similar studies on the benefits of drug use are needed to provide perspective on the risk-benefit aspects of drug therapy. Until such studies are performed, estimates of the nature and scope of the ADR problem can be only guesses.
Light-harvesting Complexes (LHCs) Cluster Spontaneously in Membrane Environment Leading to Shortening of Their Excited State Lifetimes (2016)

The light reactions of photosynthesis, which include light-harvesting and charge separation, take place in the amphiphilic environment of the thylakoid membrane. The light-harvesting complex II (LHCII) is the main responsible for light absorption in plants and green algae and is involved in photoprotective mechanisms that regulate the amount of excited states in the membrane. The dual function of LHCII has been extensively studied in detergent micelles, but recent results have indicated that the properties of this complex differ in a lipid environment. In this work we checked these suggestions by studying LHCII in liposomes. By combining bulk and single molecule measurements, we monitored the fluorescence characteristics of liposomes containing single complexes up to densely packed proteoliposomes. We show that the natural lipid environment per se does not alter the properties of LHCII, which for single complexes remain very similar to that in detergent. However, we show that LHCII has the strong tendency to cluster in the membrane and that protein interactions and the extent of crowding modulate the lifetimes of the excited state in the membrane. Finally, the presence of LHCII monomers at low concentrations of complexes per liposome is discussed.
Mastering Sybase SQL Server 11 (1997)

Physical storage buffer cache management databases transaction log, users, logins, groups, database users and aliases transact SQL SQL server transactions views the tempo database locking stored procedures triggers database design permissions system procedures catalogue procedures DBA facilities auditing disk mirroring back-up and recovery utility programs when things go wrong system tables appendices: case study - data warehousing multiprocessor SQL servers distributed SQL server systems installing and configuring a SQL server.
Correction of the enzyme deficiency in hematopoietic cells of Gaucher patients using a clinically acceptable retroviral supernatant transduction protocol. (1994)

Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme glucocerebrosidase (GC), and is an excellent candidate for gene replacement therapy. To develop a clinically acceptable protocol for this purpose, we created two amplified (A) high-titer retroviral vector-producer cell lines to efficiently transduce hematopoietic stem and progenitor cells. GP+envAm12/A-LGSN (A-LGSN), contained the GC cDNA driven by the retroviral long terminal repeat (LTR) and the neomycin phosphotransferase gene expressed from the simian virus 40 early promoter. GP+envAm12/A-LG4 (A-LG4) contained only the GC gene driven by the LTR. Both A-LGSN and A-LG4 contained multiple proviral copies and gave approximately 10-fold higher titers on 3T3 cells compared to their unamplified counterparts. These vectors were packaged in GP+envAm12 cells because vectors produced in this cell line transduced hematopoietic cells more efficiently than other packaging cells tested. Bone marrow mononuclear cells and purified CD34+ cells were infected with virus supernatants four times in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor (SCF) over 96 hours in culture. Cells were then plated in semisolid cultures and colony-forming unit-granulocyte/macrophage (CFU-GM) colonies were scored for vector presence by polymerase chain reaction (PCR). Transduction efficiency of CFU-GM colonies derived from CD34+ cells was improved considerably using the amplified vectors in the GP+envAm12 packaging line. For A-LGSN, A-LG4, and unamplified LGSN, transduction efficiencies were 41, 42, and 25%, respectively. Therefore, multiple proviral copies resulting in higher titer improves retroviral transduction of human hematopoietic progenitor cells. Hematopoietic cells from Gaucher patients were transduced and placed into long-term bone marrow culture (LTBMC). Viral supernatant from the amplified producer lines transduced long-term culture initiating cells (LTCIC) efficiently (30 to 50%) using this clinically acceptable protocol. Both sustained mRNA expression and GC enzyme production are achieved in the long-term culture of LTCIC and lead to correction of the GC deficiency in their progeny cells.