gebhart/patrepeval huggingface dataset:
Synergistic cytotoxicity of different alkylating agents for epithelial ovarian cancer (1991)

Alkylating agents have been used individually and in combination to treat epithelial ovarian carcinoma. In this study, the cytotoxicity of 7 alkylating agents has been measured using a serial dilution clonogenic assay. When individual agents were evaluated, markedly different activity was observed against several ovarian cancer cell lines. Among 4 cell lines tested, OVCA 432 was the most sensitive to cisplatin, thiotepa and melphalan. When alkylating agents were used in combination against OVCA 432, synergistic activity was observed with cisplatin and each of several other alkylating agents including thiotepa, melphalan, 4-hydroperoxycyclophosphamide (4HC) and carboplatin. The combination of cisplatin and thiotepa also exerted synergistic activity against the OVCA 420, 429 and 433 cell lines, but had only additive or subadditive activity against the NIH:OVCAR-3 cell line. Sequential treatment of tumor cell lines with the different alkylating agents was as effective as simultaneous treatment. Synergistic anti-tumor activity in cell culture is consistent with clinical observations that alkylating agents in combination appear more effective than single agents for treatment of advanced epithelial ovarian cancer. In addition, our study suggests that cisplatin in combination with thiotepa, 4HC or melphalan might prove useful for high-dose therapy with autologous bone-marrow support.
Monoclonal antibody and synthetic peptide inhibitors of human tumor cell migration. (1990)

The processes of migration and invasion by human tumor cells are likely to involve specific cell surface receptors, such as receptors for the extracellular matrix molecules fibronectin, laminin, and collagen. We have examined the roles of several of these receptors using a set of monoclonal antibodies directed against the beta 1 integrin family, as well as a series of synthetic peptides reported to inhibit various interactions of each of these proteins with the cell surface. The most general inhibitor of tumor cell migration was found to be the anti-beta 1 monoclonal antibody 13, which inhibited the migration of human HT-1080 fibrosarcoma cells, 5637 bladder carcinoma cells, VA13 viral transformants, and HCT 116 colon carcinoma cells when fibronectin was the migration substrate. Moreover, this antibody was particularly effective in blocking cell migration on laminin, as well as migration within 3-dimensional collagen gels. It also inhibited in vitro invasiveness in a reconstituted basement membrane invasion assay (Matrigel assay) at concentrations as low as 1 microgram/ml. Integrins of the beta 1 class thus appear to play a central role in several types of migration by a variety of human tumor cell lines. Anti-alpha 5 fibronectin receptor monoclonal antibody 16 also significantly inhibited migration on fibronectin, but not on other substrates, in 3 of the 4 cell lines. Conversely, anti-alpha 2 monoclonal antibody F17 strikingly inhibited migration in 3-dimensional collagen gels, but not on other substrates, implicating the alpha 2 beta 1 integrin system in migration of tumor cells within collagenous matrices. A series of synthetic peptides previously reported to inhibit interactions of normal cells with fibronectin, laminin, and collagen were also tested as inhibitors of tumor cell migration. Peptides containing the Arg-Gly-Asp adhesive recognition signal were partially inhibitory, but with occasional exceptions, most other peptides had no effects on migration. Our results indicate the central importance of several specific beta 1 integrins in human tumor cell migration and show the effectiveness of monoclonal antibody treatment in blocking this process in vitro.
Unequal allelic expression of wild-type and mutated β-myosin in familial hypertrophic cardiomyopathy (2011)

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level. Relative abundance of mutated versus wild-type MYH7-mRNA was determined by a specific restriction digest approach and by real-time PCR (RT-qPCR). Fourteen samples from M. soleus and myocardium of 12 genotyped and clinically well-characterized FHC patients were analyzed. The fraction of mutated MYH7-mRNA in five patients with mutation R723G averaged to 66 and 68% of total MYH7-mRNA in soleus and myocardium, respectively. For mutations I736T, R719W and V606M, fractions of mutated MYH7-mRNA in M. soleus were 39, 57 and 29%, respectively. For all mutations, unequal abundance was similar at the protein level. Importantly, fractions of mutated transcripts were comparable among siblings, in younger relatives and unrelated carriers of the same mutation. Hence, the extent of unequal expression of mutated versus wild-type transcript and protein is characteristic for each mutation, implying cis-acting regulatory mechanisms. Bioinformatics suggest mRNA stability or splicing effectors to be affected by certain mutations. Intriguingly, we observed a correlation between disease expression and fraction of mutated mRNA and protein. This strongly suggests that mutation-specific allelic imbalance represents a new pathogenic factor for FHC.
Prophylactic, therapeutic and immune enhancement effect of liposome‐encapsulated PolyICLC on highly pathogenic H5N1 influenza infection (2010)

Taken together, the data obtained in the present study suggest that strong consideration should be given for the use of LE-PolyICLC as prophylactic and therapeutic agents and also as a vaccination adjuvant to combat highly pathogenic influenza infection and its associated complications such as pulmonary fibrosis.
Wetting Properties of Flat and Porous Silicon Surfaces Coated with a Spiropyran (2007)

We report the immobilization and characterization of a spiropyran (SP) derivative (1) on smooth Si(100) and porous H-terminated silicon surfaces through a thermal hydrosilylation protocol. Under visible light exposure the SP is in a closed, hydrophobic form, whereas under UV irradiation it converts to a polar, hydrophilic open form named merocyanine (MC). The SP-MC photoinduced isomerization gives a small contact angle (CA) change of 9 degrees for smooth Si(100) samples under sequential irradiation cycles with white and UV light. Irradiation of porous silicon (PS) surfaces, under the same conditions, gave a CA change of 11 degrees. Treatment of PS surfaces, bearing the MC form of chromophore 1, with cobalt(II) ions enhances the wettability switching of the PS surface to a much larger extent, giving rise to a CA variation as high as 32 degrees.
Handbook of Food Analysis (2004)

This three-volume handbook supplies food chemists with essential information on the physical and chemical properties of nutrients, descriptions of analytical techniques, and an assessment of their procedural reliability. Volume 3 explores the usage and results of chemometrics, differential scanning calorimetry, chromatographic and electrophoretic t
Characterization of Placental Bikunin, a Novel Human Serine Protease Inhibitor (1997)

We reported previously the cloning of a novel human serine protease inhibitor containing two Kunitz-like domains, designated as placental bikunin, and the subsequent purification of a natural counterpart from human placental tissue (Marlor, C. W., Delaria, K. A., Davis, G., Muller, D. K., Greve, J. M., and Tamburini, P. P. (1997) J. Biol. Chem. 272, 12202-12208). In this report, the 170 residue extracellular domain of placental bikunin (placental bikunin(1-170)) was expressed in baculovirus-infected Sf9 cells using its putative signal peptide. The resulting 21.3-kDa protein accumulated in the medium with the signal peptide removed and could be highly purified by sequential kallikrein-Sepharose and C18 reverse-phase chromatography. To provide insights as to the potential in vivo functions of this protein, we performed an extensive investigation of the inhibitory properties of recombinant placental bikunin(1-170) and both of its synthetically prepared Kunitz domains. All three proteins inhibited a number of serine proteases involved in the intrinsic pathway of blood coagulation and fibrinolysis. Placental bikunin(1-170) formed inhibitor-protease complexes with a 1:2 stoichiometry and strongly inhibited human plasmin (Ki = 0.1 nM), human tissue kallikrein (Ki = 0.1 nM), human plasma kallikrein (Ki = 0.3 nM) and human factor XIa (Ki = 6 nM). Conversely, this protein was a weaker inhibitor of factor VIIa-tissue factor (Ki = 1.6 microM), factor IXa (Ki = 206 nM), factor Xa (Ki = 364 nM), and factor XIIa (Ki = 430 nM). This specificity profile was to a large extent mimicked, albeit with reduced potency, by the individual Kunitz domains. As predicted from this in vitro specificity profile, recombinant placental bikunin(1-170) prolonged the clotting time in an activated partial thromboplastin time assay.
AppMap: exploring user interface visualizations (2011)

In traditional graphical user interfaces, the majority of UI elements are hidden to the user in the default view, as application designers and users desire more space for their application data. We explore the benefits of dedicating additional screen space for presenting an alternative visualization of an application’s user interface. Some potential benefits are to assist users in examining complex software, understanding the extent of an application’s capabilities, and exploring the available features. We propose user interface visualizations, alternative representations of an application’s interface augmented with usage information. We introduce a design space for UI visualizations and describe some initial prototypes and insights based on this design space. We then present AppMap, our new design, which displays the entire function set of AutoCAD and allows the user to interactively explore the visualization which is augmented with visual overlays displaying analytical data about the functions and their relations. In our initial studies, users welcomed this new presentation of functionality, and the unique information that it presents. While it may not be their primary purpose, a GUI also inherently serves as a visual representation of what features the system has to offer, and as a tool for exploring and becoming aware of those features [30]. But, because this is not their primary purpose, we argue that traditional user interfaces are not optimally designed to provide awareness and exploration of features. For instance, users rarely have the ability to graphically view the entire scope of the software’s functionality, and how those functions relate to one another. As such, becoming aware of relevant functionality, and establishing an overall familiarity with an application can be challenging, especially for complex software applications. For example, Grossman et al. found that functionality awareness was a specific learnability problem impeding both novice and expert users from completing tasks efficiently or at all [15].
Deterministic beamforming for enhanced vertical sectorization and array pattern compensation (2012)

The paper studies deterministic beamforming for advanced base station antenna technologies including vertical sectorization and array pattern compensation. First, an optimized vertical sectorization beamforming design in terms of low inter-vertical sector interference is proposed. The performance gains in terms of the users' sum rate of the proposed technique against unoptimized vertical sectorization in a simple multi-user system scenario are shown. The work also investigates certain novel beampattern recovery approaches studying the capabilities of advanced base station antenna systems to partially compensate for the distortion caused to the array diagram upon transmit branch failure. The schemes are applied to a specific active antenna product architecture suitable for base stations with advanced beamforming capabilities yet with low hardware complexity and cost footprint.
RNA Silencing and the Mobile Silencing Signal (2002)

RNA silencing is a sequence-specific RNA degradation mechanism that occurs in a broad range of eukaryotic organisms including fungi (quelling), animals (RNA interference [RNAi]), and plants (post-transcriptional gene silencing). In all these organisms, the process is triggered by double-stranded RNA
Seborrheic Skin and Acne vulgaris as Protective Factors against the Development of Basal Cell Epithelioma (1991)

This study was conducted in order to evaluate a possible protective role of seborrheic complexion and a history of acne on the development of basal cell epithelioma (BCE). For this purpose, 77 patients with this tumor were examined and asked to fill out a questionnaire. The questionnaire included demographic data and questions about skin type, eye and hair colors, sun exposure habits and a past history of acne. The nature, number and location of tumors, the texture of skin and acne scars were noted by a physician. A group of 93 age-, sex- and skin-color-matched patients served as controls. The results show a clear relationship between seborrheic features and a lower risk of developing BCE, after controlling for solar exposure using the Mantel-Haenszel summary measure. The same trend was found in patients with a history of acne. Whether ultraviolet light absorption by sebum, an anticancer activity of Propionibacterium acnes or other factors play a protective role against the development of BCE is as yet unclear.
Hardware Trojan prevention using layout-level design approach (2015)

Hardware Trojans (HTs) are ultimately a dangerous threat in semiconductor industry. The serious impact of HTs in security applications and global economy brings extreme importance to their detection and prevention techniques. This paper focuses on developing a HT prevention techniques through a layout level design approach. The principle is to let no available space on silicon for an attacker to insert a HT. Experiments determine the maximum occupational rate and critical empty spaces while filling with standard cells. The proposed technique makes HT insertion nearly impossible.
Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro. (2008)

Fractionated ionizing radiation can lead to the development of radiation resistance. Altered gene profiles of radioresistant cell line may provide new insights into mechanisms underlying clinical radioresistance for NSCLC.
Inside-out signaling through integrins. (1996)

Rapid and yet precisely controlled changes in cell adhesion are a hallmark of a number of basic physiological processes. Many of these processes directly impact upon nephrology, including: (1) cell migration, which occurs during leukocyte infiltration into inflammatory sites (e.g., in glomerulonephritis, interstitial nephritis, and renal transplant rejection) and during embryogenesis (e.g., in development of the genitourinary system): and (2) platelet aggregation at sites of clot formation (e.g., in glomerulonephritis). The integrins are a family of adhesion molecules whose function is controlled by the cells that express them, and this properly makes them eminently suitable receptors for those situations that demand flexibility of the cellular adhesive phenotype. The control of integrin function occurs via regulatory signals that originate within the cell cytoplasm and are then transmitted to the external ligand-binding domain of the receptor. The generation and transmission of these "inside-out" signals are the subjects of intensive research that will be summarized in this review article.
Stable pyrano[2,3-b]quinoxalines and pyrano[2,3-g]pteridines related to molybdopterin (2001)

The syntheses of the quinoxaline and pteridine proligands (3 and 4) related to molybdopterin are described and 3 has been characterised complexed via its dithiolene group to a CpCo(III) centre (5). Each of 3–5 has the sensitive hemiaminal unit of molybdopterin, unprotected, verifying its stability in vitro.
In-cell PCR from mRNA: amplifying and linking the rearranged immunoglobulin heavy and light chain V-genes within single cells (1992)

We describe a process for the identification of mRNAs within single cells, as demonstrated with the immunoglobulin (Ig) variable region (V) genes of two mouse hybridoma cell lines and the bcr-abl fusion gene of the human K562 myeloid leukaemia line. The cells were fixed and permeabilised, the mRNA reverse transcribed to cDNA and the cDNA amplified by the polymerase chain reaction (PCR). After using fluorescent PCR primers, the amplified DNA could be detected within the cells as demonstrated by confocal fluorescence microscopy and flow cytometry. Furthermore the amplified Ig VH and VL DNA could be assembled within the same cell using suitable PCR primers. We detected no cross-contamination of amplified DNA between cells: the DNA isolated from mixtures of two hybridoma cell lines (B1-8 and NQ10/12.5) treated to in-cell PCR and assembly, was shown by cloning to correspond to the combinations of VH and VL genes of the parent hybridomas. We forsee diverse applications of in-cell assembly by PCR, especially for the analysis of the combinations of chains of rearranged Ig or T cell receptor (TCR) V-genes in a population of cells, and the construction of human antibodies from the V-genes of immune B-lymphocytes.
Modification of the Terminal Residue of Apelin-13 Antagonizes Its Hypotensive Action (2004)

The apelin peptide is the endogenous ligand for the apelin G protein-coupled receptor. The distribution of the apelin peptides and receptor are widespread in the central nervous system and periphery, with reported roles in the hypothalamic-pituitary-adrenal axis, blood pressure regulation and as one of the most potent positive inotropic substances yet identified. In this report, we show that in native tissues preproapelin exists as a dimer. Dimeric preproapelin was reduced to monomers by dithiothreitol treatment, indicating disulfide linkages. To evaluate the role of the carboxyl-terminal phenylalanine in the hypotensive action of apelin-13, analogs were generated and tested for their role on blood pressure regulation. Injections of apelin-13 and apelin-12 (15 microg/kg) into spontaneously hypertensive rats lowered systolic and diastolic blood pressure to result in decreases of approximately 60% and 15% in mean arterial blood pressure, respectively. Apelin-13(13[D-Phe]) treatment did not differ from apelin-13 in either efficacy or duration of effect, whereas apelin-13(F13A) revealed a loss of function. However, concomitant administration of apelin-13(F13A) (30 microg/kg) blocked hypotensive effects of apelin-13 (15 microg/kg), which revealed that apelin-13(F13A) behaved as an apelin-specific antagonist.
Method development for the quantitation of ABT‐578 in rabbit artery tissue by 96‐well liquid‐liquid extraction and liquid chromatography/tandem mass spectrometric detection (2004)

Quantitative determination of drug concentrations in tissue samples can provide critical information for drug metabolism, kinetics, and toxicity evaluations. For analysis of tissue samples using liquid chromatography/tandem mass spectrometric (LC/MS/MS) detection, homogenization is a critical step in achieving good assay performance. Assay performance can be closely evaluated by spiking the drug directly into tissue samples prior to homogenization. It is especially important to include this assay evaluation for the analysis of artery tissue samples because artery tissue is very elastic, making it quite a challenge to develop an effective procedure for homogenization. An LC/MS/MS assay in 96-well format using liquid-liquid extraction was developed for analyzing ABT-578 in rabbit artery samples. Tissue quality control samples were prepared by spiking ABT-578 stock solutions directly into the tissue before homogenization. The usage of the tissue control samples gives a thorough evaluation of the sample preparation process that includes both homogenization and sample extraction. A 20% blood in saline solution was used as a homogenization solution. Calibration standards were made by spiking ABT-578 into rabbit whole blood. Blood quality control samples were also prepared by spiking ABT-578 into rabbit whole blood. These blood QC samples were used to confirm the validity of the calibration curve. A lower limit of quantitation of 0.050 ng/mL was achieved. The linear dynamic range of blood standards was from 0.050-30.3 ng/mL with the correlation coefficient (r) ranging from 0.9969-0.9996. Overall %CV was between 1.3 and 7.0%, and analytical recovery was between 98.2 and 105.8% for blood QC samples. The %CVs for tissue QC samples were between 6.7 and 13.0%, and analytical recovery after correction was between 93.5 and 114.3%.
The Early Progenitors of Mouse Dendritic Cells and Plasmacytoid Predendritic Cells Are within the Bone Marrow Hemopoietic Precursors Expressing Flt3 (2003)

Flt3 ligand (Flt3L) is a growth factor for hemopoietic progenitors and can promote the expansion of both conventional dendritic cells (DCs) and plasmacytoid predendritic cells (p-preDCs). The cells responding to Flt3L treatment and the precursors for the DCs and p-preDCs had not been fully characterized. We examined different mouse bone marrow (BM) hemopoietic precursor populations for the surface expression of Flt3 and tested them for early DC and p-preDC precursor activity. Most DC precursor activity, other than that given by multipotent hemopoietic stem cells, was within the downstream precursors expressing Flt3. The majority of mouse BM common lymphoid precursors expressed high levels of Flt3 and these were the most efficient precursors of both DCs and p-preDCs. In contrast, only a small proportion of the common myeloid precursors (CMPs) expressed Flt3, but the precursor activity for both DCs and p-preDCs was within this minor Flt3+ CMP fraction. The granulocyte and macrophage precursors and pro-B cells did not express Flt3 and had no DC or p-preDC precursor activity. These findings demonstrate that the early precursors for all DC subtypes are within the BM Flt3+ precursor populations, regardless of their lymphoid or myeloid lineage orientation.
Tomorrow's skeleton staff: mesenchymal stem cells and the repair of bone and cartilage (2004)

Stem cells are regenerating medicine. Advances in stem cell biology, and bone marrow-derived mesenchymal stem cells in particular, are demonstrating that many clinical options once thought to be science fiction may be attainable as fact. The extra- and intra-cellular signalling used by stem cells as they differentiate into lineages appropriate to their destination are becoming understood. Thus, the growth stimuli afforded by LIF, FGF-2 and HGF, as well as the complementary roles of Wnt and Dickkopf-1 in stem cell proliferation are evident. The ability to direct multi-lineage mesenchymal stem sell (MSC) potential towards an osteogenic phenotype by stimulation with Menin and Shh are important, as are the modulatory roles of Notch-1 and PPARgamma. Control of chondrocytic differentiation is effected by interplay of Brachyury, BMP-4 and TGFbeta3. Smads 1, 4 and 5 also play a role in these phenotypic expressions. The ability to culture MSC has led to their use in tissue repair, both as precursor and differentiated cell substitutes, and with successful animal models of bone and cartilage repair using MSC, their clinical use is accelerating. However, MSC also suppress some T-cell functions in transplanted hosts, and could facilitate tumour growth, so a cautious approach is needed.