gebhart/patrepeval huggingface dataset:
Expression of p53, MDM2, and p21 Proteins in High-Grade Cervical Intraepithelial Neoplasia and Relationship to Human Papillomavirus Infection (1999)

The relationship between human papillomavirus (HPV) infection and cell cycle regulators p53, MDM2, and p21 in cervical intraepithelial neoplasia (CIN) has not been investigated. p53, MDM2, and p21 immunoreactivity were analyzed with respect to HPV DNA status in high-grade CIN (CIN II-III). Formalin-fixed, paraffin-embedded tissue sections from 169 biopsy specimens with high-grade CIN were examined for HPV DNA by polymerase chain reaction with the L1 and E1 consensus primers Gp5+/6+ and CpI/CpIIG. HPV-positive specimens were typed with the E6 type-specific primers for HPV 16 and 18. The biopsy specimens were stained with the monoclonal antibodies p53, MDM2, and p21. The interpretation of nuclear staining was regarded as focal (< 5%), regional (5% to 50%), or diffuse (> 50%). HPV DNA was found in 156 cases (92%); 122 (78%) were positive for HPV 16, 18, or both. Immunohistochemically, p53 was detected in 50 specimens (30%); nuclear staining was mainly focal. Focal nuclear staining for MDM2 was found in 6 specimens (4%), and regional and diffuse nuclear staining for p21 was present in 137 (81%). Significant correlation was found only between p53 and MDM2 immunoreactivity. These results indicate that there is no correlation between HPV status and expression of the cell cycle regulators p53, MDM2, and p21. Inactivation of p21 and p53 protein may be important, and MDM2 abnormalities seem to play a minor role in the development of high-grade CIN.
Cyclin-Dependent Kinase Inhibitors Sensitize Tumor Cells to Nutlin-Induced Apoptosis: a Potent Drug Combination (2007)

Current chemotherapy focuses on the use of genotoxic drugs that may induce general DNA damage in cancer cells but also high levels of toxicity in normal tissues. Nongenotoxic activation of p53 by targeting specific molecular pathways therefore provides an attractive therapeutic strategy in cancers with wild-type p53. Here, we explored the antitumor potential of cyclin-dependent kinase (CDK) inhibitors in combination with a small molecule inhibitor of p53-murine double minute 2 (MDM2) interaction. We show that low doses of CDK inhibitors roscovitine and DRB synergize with the MDM2 antagonist nutlin-3a in the induction of p53 activity and promote p53-dependent apoptosis in a dose- and time-dependent manner. Statistical measurement of the combination effects shows that the drug combination is additive on the reduction of cell viability and synergistic on inducing apoptosis, a critical end point of cytotoxic drugs. The degree of apoptosis observed 24 to 48 h after drug treatment correlated with the accumulation of p53 protein and concomitant induction of proapoptotic proteins Puma and PIG3. The antiproliferative and cytotoxic effects of this drug combination are validated in a range of tumor-derived cells including melanoma, colon carcinoma, breast adenocarcinoma, and hepatocarcinoma cells. Furthermore, this drug combination does not induce phosphorylation of Ser(15) on p53 and does not induce genotoxic stress in the cell. Given that many cytotoxic drugs rely on their ability to induce apoptosis via DNA damage-mediated activation of p53, the data presented here may provide a new therapeutic approach for the use of CDK inhibitors and MDM2 antagonists in combinatorial drug therapy.
Vaccines (2007)

Recent scientific advances have expanded our understanding of the immune system and its response to malignant cells. Clinical trials are under way that attempt to translate this knowledge into effective cancer therapies. Vaccine therapy, an innovative approach to cancer treatment, attempts to activate the immune system to recognize cancer cells and eliminate them from the body. Preventive vaccines that already have been approved will have an impact on the incidence of certain cancers, and research is ongoing into treatment vaccines for various cancers.
An Improved Suction Device for Draining Wounds (1972)

A bellows suction device is described for draining wounds that is similar to the Hemovac, but has certain advantages. These include valves to avoid contamination via back flow through the inlet and loss of suction via the outlet, and a calibrated reservoir to measure drainage.
RETRACTED ARTICLE: Belinostat and panobinostat (HDACI): in vitro and in vivo studies in thyroid cancer (2013)

In summary, these HDACIs either alone or combined with selected TKIs may have a role in treatment of aggressive thyroid cancer.
Adaptive pulse shaping of phase and amplitude of an amplified femtosecond pulse laser by direct reference to frequency-resolved optical gating traces (2002)

By adaptive control of both spectral phase and amplitude of seed pulses with an acousto-optic programmable dispersion filter located before a pulse stretcher, accurate pulse shaping was achieved for ultrashort laser pulses delivered through a regenerative amplifier. Two-dimensional patterns obtained from frequency-resolved optical gating were used for calculating cost functions in an adaptive control algorithm without pulse shape reconstruction during the control of pulse shape.
The potential of III‐V semiconductors as terrestrial photovoltaic devices (2006)

Abstract III‐V semiconductors, GaAs and in particular InGaP, are used in many different electronic applications, such as high power and high frequency devices, laser diodes and high brightness LED. Their direct bandgap and high reliability make them ideal candidates for the realisation of high efficiency solar cells: in the past years they have been successfully used as power sources for satellites in space, where they are able to produce electricity from sunlight with an overall efficiency of around 30%. Nowadays, the use of arsenides and phosphides as photovoltaic (PV) devices is confined only to space applications since their price is much higher than conventional Si flat panel modules, the leading PV market technology. But with the introduction of multijunction solar cells capable of operating in high concentration solar light, the area and, therefore, the cost of these cells can be reduced and will eventually find an application and market also on Earth. This article will review the situation of semiconductor solar cell materials, focusing on Si, GaAs, InGaP and multijunction solar cells and will discuss future trends and possibilities of bringing III‐V technology from space to Earth. Copyright © 2006 John Wiley &amp; Sons, Ltd.
Molecular cloning of complementary DNA to mouse tissue plasminogen activator mRNA and its expression during F9 teratocarcinoma cell differentiation. (1988)

Two tissue plasminogen activator (tPA) cDNA clones were isolated from mouse cDNA libraries and characterized. The sequence coding for mature mouse tPA protein including its 29-residue signal peptide, as well as that for the 3' and part of the 5'-nontranslated regions of the mRNA was determined. The mature protein consists of 530 amino acids and is encoded by a transcript of approximately 2800 nucleotides. The mouse tPA protein has 81% homology with its human counterpart, and amino acid sequence conservations suggest that the multidomain-like structure found for human tPA is maintained in the mouse enzyme. The tPA cDNA has been used as a probe to analyze tPA gene expression during F9 cell differentiation. tPA mRNA is not detected in F9 stem cells. When F9 cells are induced to differentiate with retinoic acid and dibutyryl cyclic AMP, tPA mRNA accumulates. We demonstrate that this induction occurs at least in part because of an increase in tPA gene transcription.
Laser-induced autofluorescence microscopy of normal and tumor human colonic tissue (2004)

Laser-induced autofluorescence (LIAF) spectroscopy has been found to be a promising tool for early cancer diagnosis in various organs, but the reasons responsible for the spectral differences between normal and diseased tissue are still not well understood. In this study, a microspectrophotometer (MSP) system was used to identify the microscopic origins of tissue autofluorescence in the colon under the excitation of a helium-cadmium laser at 442 nm. Colonic tissue samples (normal: n=8, adenocarcinoma: n=10) were obtained from 12 patients with known or suspected malignancies of the colon. The intrinsic fluorescence spectra and images of fresh tissue sections prepared from normal and tumor colonic tissue were measured by the MSP system. Three distinct tissue layers of the colon were found for fluorescence, the mucosa, the submucosa and the muscularis propria, with submucosa being the most fluorescent. Differences in the spectral shape and intensity of the intrinsic fluorescence originating from different colonic layers indicate that fundamentally different fluorophores may be present in the respective tissue layers. There was no significant difference in the intrinsic fluorescence features of the submucosa between normal and tumor colonic tissue, but the fluorescence intensity of the submucosa in tumor tissue was significantly reduced due to the infiltration of tumor cells into the submucosa. The intrinsic fluorescence spectrum peaking at about 520 nm for tumor stroma appeared more evident than that of normal lamina propria. Limited areas of the lamina propria layer in some adenocarcinoma colon exhibited an emission band at about 635 nm, which was attributed to endogenous porphyrins in tumor. Autofluorescence microscopy revealed that differences in the clinically measured autofluorescence spectra between normal and tumor tissue were mainly due to thickening of the tumor mucosa resulting in a reduced submucosa fluorescence contribution, as well as the increased hemoglobin absorption in tumor tissue. Therefore, investigation of the microscopic origins of tissue autofluorescence and images can provide new insights into morphological structures and biochemical components of tissues, which are vital to improve the implementation of the LIAF technique for non-invasive in vivo tissue diagnostics.
Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease (2006)

The premise of this review is that apolipoprotein (apo) E4 is much more than a contributing factor to neurodegeneration. ApoE has critical functions in redistributing lipids among CNS cells for normal lipid homeostasis, repairing injured neurons, maintaining synapto-dendritic connections, and scavenging toxins. In multiple pathways affecting neuropathology, including Alzheimer's disease, apoE acts directly or in concert with age, head injury, oxidative stress, ischemia, inflammation, and excess amyloid beta peptide production to cause neurological disorders, accelerating progression, altering prognosis, or lowering age of onset. We envision that unique structural features of apoE4 are responsible for apoE4-associated neuropathology. Although the structures of apoE2, apoE3, and apoE4 are in dynamic equilibrium, apoE4, which is detrimental in a variety of neurological disorders, is more likely to assume a pathological conformation. Importantly, apoE4 displays domain interaction (an interaction between the N- and C-terminal domains of the protein that results in a compact structure) and molten globule formation (the formation of stable, reactive intermediates with potentially pathological activities). In response to CNS stress or injury, neurons can synthesize apoE. ApoE4 uniquely undergoes neuron-specific proteolysis, resulting in bioactive toxic fragments that enter the cytosol, alter the cytoskeleton, disrupt mitochondrial energy balance, and cause cell death. Our findings suggest potential therapeutic strategies, including the use of "structure correctors" to convert apoE4 to an "apoE3-like" molecule, protease inhibitors to prevent the generation of toxic apoE4 fragments, and "mitochondrial protectors" to prevent cellular energy disruption.
Directed evolution for the development of conformation-specific affinity reagents using yeast display (2005)

Yeast display is a powerful tool for increasing the affinity and thermal stability of scFv antibodies through directed evolution. Mammalian calmodulin (CaM) is a highly conserved signaling protein that undergoes structural changes upon Ca(2+) binding. In an attempt to generate conformation-specific antibodies for proteomic applications, a selection against CaM was undertaken. Flow cytometry-based screening strategies to isolate easily scFv recognizing CaM in either the Ca(2+)-bound (Ca(2+)-CaM) or Ca(2+)-free (apo-CaM) states are presented. Both full-length scFv and single-domain VH only clones were isolated. One scFv clone having very high affinity (K(d) = 0.8 nM) and specificity (>1000-fold) for Ca(2+)-CaM was obtained from de novo selections. Subsequent directed evolution allowed the development of antibodies with higher affinity (K(d) = 1 nM) and specificity (>300-fold) for apo-CaM from a parental single-domain clone with both a modest affinity and specificity for that particular isoform. CaM-binding activity was unexpectedly lost upon conversion of both conformation-specific clones into soluble fragments. However, these results demonstrate that conformation-specific antibodies can be quickly and easily isolated by directed evolution using the yeast display platform.
Mobile Robots: Motor Challenges and Materials Solutions (2007)

Bolted-down robots labor in our factories, performing the same task over and over again. Where are the robots that run and jump? Equaling human performance is very difficult for many reasons, including the basic challenge of demonstrating motors and transmissions that efficiently match the power per unit mass of muscle. In order to exceed animal agility, new actuators are needed. Materials that change dimension in response to applied voltage, so-called artificial muscle technologies, outperform muscle in most respects and so provide a promising means of improving robots. In the longer term, robots powered by atomically perfect fibers will outrun us all.
Potency and Selectivity of the Cathepsin L Propeptide as an Inhibitor of Cysteine Proteases (1996)

The cathepsin L propeptide (phcl-2) was expressed in Saccharomyces cerevisiae using a human procathepsin L/alpha-factor fusion construct containing a stop codon at position -1 (the C-terminal amino acid of the proregion). Since the yield after purification was very low, the cathepsin L propeptide was also obtained by an alternate procedure through controlled processing of an inactive mutant of procathepsin L (Cys25Ser/Thrl10Ala) expressed in Pichia pastoris, by small amounts of cathepsin L. The peptide resulting from the cleavage of the proenzyme (phcl-1) was then purified by HPLC. The purified propeptides were characterized by N-terminal sequencing and mass spectrometry and correspond to incomplete forms of the proregion (87 and 81 aa for phcl-1 and phcl-2 respectively, compared to 96 aa for the complete cathepsin L propeptide). The two peptides were found to be potent and selective inhibitors of cathepsin L at pH 5.5, with Ki values of 0.088 nM for phcl-1 and 0.66 nM for phcl-2. The Ki for inhibition of cathepsin S was much higher (44.6 nM with phcl-1), and no inhibition of cathepsin B or papain could be detected at up to 1 microM of the propeptide. The inhibitory activity was also found to be strongly pH-dependent. Two synthetic peptides of 75 and 44 aa corresponding to N-terminal truncated versions of the propeptide were also prepared by solid phase synthesis and displayed Ki values of 11 nM and 2900 nM, respectively, against cathepsin L. The data obtained for the 4 propeptide derivatives of various lengths indicate that the first 20 residues in the N-terminal region of the propeptide are more important for inhibition than the C-terminal region which contributes little to the overall inhibitory activity.
Polymercaptosiloxane Anchor Films for Robust Immobilization of Biomolecules to Gold Supports (2003)

A central requirement in modification of solid surfaces with biological polymers is to tether the molecule of interest permanently and in a well-defined attachment geometry. Gold is perhaps the most popular metal support for research applications, yet it suffers from a lack of methods for producing robust biomolecular films that can withstand prolonged use, especially at elevated temperatures. In this report, the stability issue is addressed by first self-assembling a nanometer thick layer of a thiol-derivatized polysiloxane, poly(mercaptopropyl)methylsiloxane (PMPMS), on the gold support. Multivalent binding of the polymer thiols to the gold, combined with the polymer's hydrophobic nature, causes it to irreversibly adhere to the metal support. Thiol-terminated, 20mer DNA oligonucleotides are subsequently covalently linked to the PMPMS film using bismaleimide cross-linkers. Immobilization coverages of up to ∼1 × 1013 strands/cm2 have been demonstrated. Significantly, the DNA monolayers can withstand prolonged exposure to near 100 °C conditions with minimal loss of strands from the solid support. The immobilized oligonucleotides retain ability to undergo sequence-specific hybridization, opening up applications in diagnostic and related areas.
NADALINE connectionist learning vs. linear regression at a lamp manufacturing plant (2003)

The results of applying connectionist learning methods to find cause and effect relationships on a manufacturing line are described. The NADALINE learning algorithm is used to extract linear relationships between production variables and a quality measure. The result of NADALINE learning is compared with that of a conventional linear regression technique. These results show that a simple connectionist algorithm can operate using limited computing power, online, and give a meaningful interpretation of a manufacturing process. Possibilities of using these interpretations for control are explored. Filtering methods that were used to make the historical data more manageable are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
31 GHz Ge n-i-p waveguide photodetectors on Silicon-on-Insulator substrate (2007)

We report on evanescently coupled Ge waveguide photodetectors that are grown on top of Si rib waveguides. A Ge waveguide detector with a width of 7.4mum and length of 50 mum demonstrated an optical bandwidth of 31.3 GHz at -2V for 1550nm. In addition, a responsivity of 0.89 A/W at 1550 nm and dark current of 169 nA were measured from this detector at -2V. A higher responsivity of 1.16 A/W was also measured from a longer Ge waveguide detector (4.4 x 100 mum2), with a corresponding bandwidth of 29.4 GHz at -2V. An open eye diagram at 40 Gb/s is also shown.
Stereospecific Nicotine Receptors on Rat Brain Membranes (1980)

A stereospecific binding site for nicotine has been detected on rat brain membranes. Competition studies with cholinergic agonists suggest that this site is a nicotinic cholinergic receptor.
Development and characterization of three recombinant single chain antibody fragments (scFvs) directed against the CD19 antigen. (1995)

Antibodies that recognize antigens restricted to leukemia, lymphoma, and normal hematopoietic cells represent a unique opportunity to develop therapeutics, because they have the potential for relatively selective treatment of these diseases. Antibodies that recognize the CD19 antigen found on normal and malignant B cells, but not on stem cells, have been used to develop immunoconjugates. However, these conjugates are large and might be suboptimal in tumor penetration when compared to molecules using smaller single chain Fv (scFv) antibody fragments. scFv has the advantage of being a molecularly engineered homogeneous molecule. In this report, we demonstrate the cloning, expression, and binding of three anti-CD19 antibodies as scFvs. All three scFvs were successfully cloned and expressed. FVS191, derived from cell line B43, and FVS192, derived from SJ25C1, were properly refolded and bound CD19 antigen in FACS competition assays. These anti-CD19 scFv should be useful in the further development of diagnostic and therapeutic molecules.
Identification of Treponema hyodysenteriae by a rapid slide agglutination test (1981)

A rapid slide agglutination (SA) test was developed to identify the spirochaete Treponema hyodysenteriae, the causative organism of swine dysentery. The specificity of the antiserum was increased by a single absorption with two intestinal spirochaetes. Using this test, it was possible to identify 30 out of 31 spirochaetes which were beta-haemolytic and gave a positive reaction in growth inhibition (GI) tests with T hyodysenteriae antiserum. All except one of these spirochaetes were isolated from herds with a history of swine dysentery or suspected swine dysentery. The majority of the spirochaetes gave a rapid, strongly, positive reaction in the SA test but seven strains, although recognisably positive, reacted more weakly. Of 28 other spirochaetes which were weakly beta-haemolytic and did not react in GI tests with T hyodysenteriae antiserum, 27 were negative in the SA test. The remaining strain was autoagglutinable and thus could not be identified. The indole test correlated less well with the results of SA and GI tests. All 31 strains which were identified as T hyodysenteriae produced indole, but so did nine of the 28 other spirochaetes. The slide agglutination test is a potentially useful method for rapid identification of T hyodysenteriae.
Structure and function of 14-3-3 isoforms (1995)

ESMS of 14-3-3 proteins gave results which are in very close agreement to the theoretical values and verified the presence of N-acetylation. Two sets of sheep and chicken brain isoforms differ in mass by 80 Da. This suggests the presence of phosphorylation in specific isoforms which is conserved across a wide range of species. We are currently identifying this site of phosphorylation which is present specifically on isoforms that have been shown to interact with the oncogene-related protein, c- Raf. Two dimensional gel electrophoretic analysis of truncated 14-3-3 recombinant proteins has enabled us to identify the site of dimerisation at the amino terminus. Crystals of recombinant 14-3-3 and another protein kinase inhibitor (a Zn^2+-binding protein) have been obtained for X-ray structure analysis.
Oral l‐ornithine‐l‐aspartate in minimal hepatic encephalopathy: A randomized, double‐blind, placebo‐controlled trial (2013)

A 60-day oral LOLA course was not better than placebo in treating MHE, but was useful in preventing further episodes of OHE.
Feature point detection and curve approximation for early processing of free-hand sketches (2001)

Freehand sketching is both a natural and crucial part of design, yet is unsupported by current design automation software. We are working to combine the flexibility and ease of use of paper and pencil with the processing power of a computer to produce a design environment that feels as natural as paper, yet is considerably smarter. One of the most basic steps in accomplishing this is converting the original digitized pen strokes in the sketch into the intended geometric objects using feature point detection and approximation. We demonstrate how multiple sources of information can be combined for feature detection in strokes and apply this technique using two approaches to signal processing, one using simple average based thresholding and a second using scale space.