gebhart/patrepeval huggingface dataset:
Enumeration of lymphokine mRNA-containing cells in vivo in a murine graft-versus-host reaction using the PCR. (1992)

A method of enumerating lymphokine mRNA-containing cells in vivo was developed by combining limiting dilution analysis with PCR amplification of cDNA. Single-hit kinetics revealed that the PCR-limiting dilution analysis could detect a single positive cell among greater than 40,000 negative cells. With this method, spleens and lymph nodes of mice undergoing an acute allogeneic graft-versus-host reaction were found to contain lymphokine mRNA-expressing cells at frequencies of 3% for interferon gamma, 0.05% for granulocyte/macrophage colony-stimulating factor, 0.002% for interleukin 3, and 0.03% for interleukin 4; these frequencies were 20- to 175-fold higher than in lymphoid tissues of normal mice. In contrast to their low frequencies of lymphokine mRNA-containing cells in vivo, graft-versus-host reaction populations restimulated in vitro for 24 hr with anti-CD3 antibody yielded frequencies ranging from 3% for interleukin 4 to nearly 70% for interferon gamma. Furthermore, lymphokine transcripts were also detected in single micromanipulated cells from these populations. Because frequencies of anti-CD3-inducible lymphokine mRNA-containing cells in normal mice were only 0.03-1%, it was concluded that lymphoid tissues of graft-versus-host reaction mice contained high frequencies of cells that had been primed for lymphokine synthesis. Only a small fraction of these cells, however, expressed lymphokine mRNAs at a given time point in vivo.
Layer-by-Layer Assembled Gold Nanoparticles for siRNA Delivery (2009)

Although uptake into cells is highly complex and regulated, heterogeneous particle collectives are usually employed to deliver small interfering RNA (siRNA) to cells. Within these collectives, it is difficult to accurately identify the active species, and a decrease in efficacy is inherent to such preparations. Here, we demonstrate the manufacture of uniform nanoparticles with the deposition of siRNA on gold in a layer-by-layer approach, and we further report on the cellular delivery and siRNA activity as functions of surface properties.
Expression of prostate-specific antigen and prostate-specific membrane antigen transcripts in blood cells: implications for the detection of hematogenous prostate cells and standardization (1998)

Circulating prostate cells can be detected in cancer patients by using reverse transcriptase-PCR (RT-PCR) assay for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) mRNA. A quality-control study involving a conventional RT-PCR assay was performed and, surprisingly, detected both transcripts in many negative control cell lines and in normal blood samples. The existence of an illegitimate transcription of the PSA and PSM genes was evidenced by sequence analysis of several PSM and PSA-PCR products. Sequencing indeed demonstrated the presence of a PSA or PSM polymorphism in some but not all the cell lines and patient samples, as well as a heterozygous mutation (G to A; Asp to Asn) in the Jurkat cell line. Moreover, the amount of PSA transcript in MCF-7, a PSA-negative breast line, increased after incubation with cycloheximide. Interestingly, the frequency of positivity was as high as 12% in male samples if only tested once, but dropped to 3% upon multiple testing of the same cDNA. This highlights the stochastic effects in RT-PCR results at high sensitivity, hence the importance of repetitive testing in clinical samples. Decreasing the number of cycles avoided the amplification of illegitimate transcripts but also affected the limit of detection, as evidenced with PSA and PSM cDNA containing plasmids, mixing of LNCap with normal blood samples, and the PSA-PSM-negative K562 cell line. The current data raise the need for a multicentric standardization of the RT-PCR methodology used to amplify PSA and PSM transcripts.
Adenine nucleotides stimulate migration in wounded cultures of kidney epithelial cells. (1992)

Adenine nucleotides speed structural and functional recovery when administered after experimental renal injury in the rat and stimulate proliferation of kidney epithelial cells. As cell migration is a component of renal regeneration after acute tubular necrosis, we have used an in vitro model of wound healing to study this process. High density, quiescent monkey kidney epithelial cultures were wounded by mechanically scraping away defined regions of the monolayer to simulate the effect of cell loss after tubular necrosis and the number of cells that migrated into the denuded area was counted. Migration was independent of cell proliferation. Provision of adenosine, adenine nucleotides, or cyclic AMP increased the number of migrating cells and accelerated repair of the wound. Other purine and pyrimidine nucleotides were not effective. Arginine-glycine-aspartic acid-serine peptide, which blocks the binding of extracellular fibronectin to its cell surface receptor, completely inhibited migration in the presence or absence of ADP. Very low concentrations of epidermal growth factor (K0.5 approximately 0.3 ng/ml) stimulated migration, whereas transforming growth factor-beta 2 was inhibitory (Ki approximately 0.2 ng/ml). Thus, adenosine and/or adenine nucleotides released from injured or dying renal cells, or administered exogenously, may stimulate surviving cells in the wounded nephron to migrate along the basement membrane, thereby rapidly restoring tubular structure and function.
Has the Amyloid Cascade Hypothesis for Alzheimers Disease been Proved? (2006)

After much initial debate for and against the role of amyloid in Alzheimer's disease (AD), mutations on the amyloid precursor protein (APP) and processing pathways that increase levels of the amyloid b peptide of 42 residues (Abeta42) have established that faulty function or processing of these proteins are responsible for AD pathogenesis. Given the neurotoxicity of aggregates of Ab42, the central role of this peptide in AD pathogenesis is self evident. In this article, I summarize the major pieces of evidence adduced to support the amyloid cascade hypothesis and point out their limitations.
Behavioral signs of acute pain produced by application of endothelin-1 to rat sciatic nerve (1998)

We examined whether endothelin-1 (ET-1), a potent vasoconstrictive peptide secreted in high concentration by metastatic prostate cancer cells, produces endothelin receptor-dependent pain behavior when applied to rat sciatic nerve. ET-1 (200-800 microM) applied to the epineurial surface of rat sciatic nerve produced reliable, robust, unilateral hindpaw flinching lasting 60 min. Pre-emptive systemic morphine completely blocked this effect in a naloxone-reversible manner, suggesting that this behavior was pain-related. Equipotent doses of epineurially applied epinephrine had no effect, suggesting that ET-1 effects are on tissue sites other than sciatic nerve microvessels. Prior and co-administration of BQ-123, an endothelin-A (ET(A)) receptor antagonist, also blocked ET-1-induced hindpaw flinching establishing that pain behavior induced by ET-1 application to rat sciatic nerve is ET(A) receptor mediated.
An Introduction to Support Vector Machines and Other Kernel-based Learning Methods (2000)

This is the first comprehensive introduction to Support Vector Machines (SVMs), a generation learning system based on recent advances in statistical learning theory. SVMs deliver state-of-the-art performance in real-world applications such as text categorisation, hand-written character recognition, image classification, biosequences analysis, etc., and are now established as one of the standard tools for machine learning and data mining. Students will find the book both stimulating and accessible, while practitioners will be guided smoothly through the material required for a good grasp of the theory and its applications. The concepts are introduced gradually in accessible and self-contained stages, while the presentation is rigorous and thorough. Pointers to relevant literature and web sites containing software ensure that it forms an ideal starting point for further study. Equally, the book and its associated web site will guide practitioners to updated literature, new applications, and on-line software.
ERBB3/HER2 Signaling Promotes Resistance to EGFR Blockade in Head and Neck and Colorectal Cancer Models (2014)

EGFR blocking antibodies are approved for the treatment of colorectal cancer and head and neck squamous cell carcinoma (HNSCC). Although ERBB3 signaling has been proposed to limit the effectiveness of EGFR inhibitors, the underlying molecular mechanisms are not fully understood. To gain insight into these mechanisms, we generated potent blocking antibodies against ERBB3 (REGN1400) and EGFR (REGN955). We show that EGFR and ERBB3 are coactivated in multiple HNSCC cell lines and that combined blockade of EGFR and ERBB3 inhibits growth of these cell lines more effectively than blockade of either receptor alone. Blockade of EGFR with REGN955 strongly inhibited activation of ERK in HNSCC cell lines, whereas blockade of ERBB3 with REGN1400 strongly inhibited activation of Akt; only the combination of the 2 antibodies blocked both of these essential downstream pathways. We used a HER2 blocking antibody to show that ERBB3 phosphorylation in HNSCC and colorectal cancer cells is strictly dependent on association with HER2, but not EGFR, and that neuregulin 1 activates ERBB3/HER2 signaling to reverse the effect of EGFR blockade on colorectal cancer cell growth. Finally, although REGN1400 and REGN955 as single agents slowed the growth of HNSCC and colorectal cancer xenografts, the combination of REGN1400 plus REGN955 caused significant tumor regression. Our results indicate that activation of the Akt survival pathway by ERBB3/HER2 limits the effectiveness of EGFR inhibition, suggesting that REGN1400, which is currently in a phase I clinical trial, could provide benefit when combined with EGFR blocking antibodies.
Stahlkocher (1989)

Zhang Zongjiang ist 36 und verheiratet. Er hat einen Sohn, der noch in die Grundschule geht. Zhang ist nicht groß, aber stämmig mit Muskeln wie ein Preisboxer. Er hat ein eindrucksvolles Gesicht mit starken Backenknochen, ein kantiges Kinn und neugierige Augen. Er wirkt müde und sieht mindestens fünf Jahre älter aus, als er ist. Über seine Stirn ziehen sich drei parallele Linien, und auch um seine Augen haben sich die Falten ringförmig eingegraben. Seine Gesichtshaut ist dunkelrot. Das kommt von der sengenden Hitze und dem Rauch, denen er ununterbrochen ausgesetzt ist.
Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia (2007)

B-cell chronic lymphocytic leukaemia (B-CLL) is characterised by the progressive accumulation of monoclonal CD5(+) B cells. In a previous study, we have analysed the expression profile of apoptosis-regulating genes using a cDNA-based microarray and found overexpression of the antiapoptotic bcl-2 family member, bfl-1, in B-CLL cells with an apoptosis-resistant phenotype. In this study, bfl-1 mRNA levels have been determined by competitive PCR in an extended population of B-CLL patients to characterise its role in disease progression and development of chemoresistance. bfl-1 levels were significantly higher in patients with no response (NR) to last chemotherapy than in patients responding (partial response (PR)) to last chemotherapy (P<0.05) and in patients who had not required treatment (P<0.05). We found no correlation between bfl-1 mRNA levels and disease progression, IGHV mutational status or other clinical parameters. In addition, bfl-1 mRNA levels were inversely correlated with apoptotic response to in vitro fludarabine treatment of B-CLL cells. Specific downregulation of bfl-1 using siRNA induced apoptosis in resistant cells. Our data suggest that bfl-1 contributes to chemoresistance and might be a therapeutic target in B-CLL.
Prospective monitoring trial for carcinoma of colon and rectum after surgical resection. (1989)

In 1978, a prospective program was initiated to evaluate postoperative monitoring of patients after resection of carcinoma of the colon and rectum. The program included clinical examination, interval endoscopy, measurement of carcinoembryonic antigen (CEA), selected liver function tests (alkaline phosphatase and gamma glutamyl transferase) and roentgenologic testing: roentgenograms of the chest, barium enema, intravenous pyelogram (IVP) and computerized axial tomographic (CAT) scan. Of the initial 226 patients enrolled, 179 had at least one abnormal elevation of the CEA level, and in 70 (39 per cent), recurrence developed. Of the 70 with recurrence, 62 (89 per cent) had elevated CEA levels (greater than 3.0 nanograms per milliliter) prior to detection of recurrence by other means. Eight patients had normal levels (two were false-negative and the other six were tested at inappropriate times). Although other test results often complemented CEA, they were generally less sensitive for early detection. Selective use of these tests frequently documented site and extent of recurrence. The detection sensitivity of these other tests was highest with CAT scan (83 per cent), followed by barium enema and endoscopy (56 and 46 per cent). Forty-five patients underwent re-exploration. Recurrence was found in 42, of whom 23 had resectable disease (five of 11, liver; 17 of 24, local or pelvis, and one of one, lung). In three patients, nothing abnormal was found at exploration; two of these patients ultimately had metastases develop. The median survival time was 43 months and the estimated five year survival rate was 38 per cent. CEA is the best over-all indicator of early recurrence and frequent testing at short intervals is most important. Periodic clinical examination and selected other studies are also essential for early documentation of recurrence. Second-look surgical procedures appear beneficial for survival time in selected patients.
Myoglobin Immunoassay Utilizing Directional Surface Plasmon-Coupled Emission (2004)

We described an immunoassay for the cardiac marker myoglobin on a thin silver mirror surface using surface plasmon-coupled emission (SPCE). SPCE occurs for fluorophores in proximity (within approximately 200 nm) of a thin metal film (in our case, silver) and results in a highly directional radiation through a glass substrate at a well-defined angle from the normal axis. We used the effect of SPCE to develop a myoglobin immunoassay on the silver mirror surface deposited on a glass substrate. Binding of the labeled anti-myoglobin antibodies led to the enhanced fluorescence emission at a specific angle of 72 degrees . The directional and enhanced directional fluorescence emission enables detection of myoglobin over a wide range of concentrations from subnormal to the elevated level of this cardiac marker. Utilizing SPCE allowed us also to demonstrate significant background suppression (from serum or whole blood) in the myoglobin immunoassay. We expect SPCE to become a powerful technique for performing immunoassays for many biomarkers in surface-bound assays.
Design and characterization of a 256x64-pixel single-photon imager in CMOS for a MEMS-based laser scanning time-of-flight sensor (2012)

We introduce an optical time-of-flight image sensor taking advantage of a MEMS-based laser scanning device. Unlike previous approaches, our concept benefits from the high timing resolution and the digital signal flexibility of single-photon pixels in CMOS to allow for a nearly ideal cooperation between the image sensor and the scanning device. This technique enables a high signal-to-background light ratio to be obtained, while simultaneously relaxing the constraint on size of the MEMS mirror. These conditions are critical for devising practical and low-cost depth sensors intended to operate in uncontrolled environments, such as outdoors. A proof-of-concept prototype capable of operating in real-time was implemented. This paper focuses on the design and characterization of a 256 x 64-pixel image sensor, which also comprises an event-driven readout circuit, an array of 64 row-level high-throughput time-to-digital converters, and a 16 Gbit/s global readout circuit. Quantitative evaluation of the sensor under 2 klux of background light revealed a repeatability error of 13.5 cm throughout the distance range of 20 meters.
Controversy of critical layer thickness for InGaAs/GaAs strained-layer epitaxy (1988)

The critical layer thickness for InxGa1−xAs layers in InxGa1−xAs/GaAs single strained quantum wells (SSQW’s) and strained-layer superlattices (SLS’s) are investigated. Photoluminescence microscopy (PLM) images and x-ray rocking curves for two series of SSQW and SLS structures corresponding to many different layer thicknesses were obtained. We find that the PLM technique, which directly images dislocations and is sensitive to low dislocation densities, is much more suitable for determining the onset of dislocation creation. The x-ray technique can detect lattice relaxation by dislocations but only at relatively high densities of dislocations. Using the former technique, we determine critical thicknesses of 190 Å for SSQW’s and 250 Å for SLS’s with x≊0.2. These results are near the theoretical predictions of J. W. Matthews, S. Mader, and T. B. Light [J. Appl. Phys. 41, 3800 (1970)] (150 and 300 Å, respectively) and are much lower than results obtained by x-ray or other techniques which sense lattice relaxation.
Structure-guided reprogramming of serine recombinase DNA sequence specificity (2010)

Routine manipulation of cellular genomes is contingent upon the development of proteins and enzymes with programmable DNA sequence specificity. Here we describe the structure-guided reprogramming of the DNA sequence specificity of the invertase Gin from bacteriophage Mu and Tn3 resolvase from Escherichia coli. Structure-guided and comparative sequence analyses were used to predict a network of amino acid residues that mediate resolvase and invertase DNA sequence specificity. Using saturation mutagenesis and iterative rounds of positive antibiotic selection, we identified extensively redesigned and highly convergent resolvase and invertase populations in the context of engineered zinc-finger recombinase (ZFR) fusion proteins. Reprogrammed variants selectively catalyzed recombination of nonnative DNA sequences > 10,000-fold more effectively than their parental enzymes. Alanine-scanning mutagenesis revealed the molecular basis of resolvase and invertase DNA sequence specificity. When used as rationally designed ZFR heterodimers, the reprogrammed enzyme variants site-specifically modified unnatural and asymmetric DNA sequences. Early studies on the directed evolution of serine recombinase DNA sequence specificity produced enzymes with relaxed substrate specificity as a result of randomly incorporated mutations. In the current study, we focused our mutagenesis exclusively on DNA determinants, leading to redesigned enzymes that remained highly specific and directed transgene integration into the human genome with > 80% accuracy. These results demonstrate that unique resolvase and invertase derivatives can be developed to site-specifically modify the human genome in the context of zinc-finger recombinase fusion proteins.
Thiadiazole—a Promising Structure in Medicinal Chemistry (2012)

Many compounds containing a five-membered heterocyclic ring display exceptional chemical properties and versatile biological activities. In this Minireview, thiadiazoles are summarized according to their therapeutic potential, highlighting the versatility of this scaffold in medicinal chemistry. The unique properties of thiadiazoles are also discussed in relation to their potential effect on activity. Thiadiazole is a bioisostere of pyrimidine and oxadiazole, and given the prevalence of pyrimidine in nature it is unsurprising that thiadiazoles exhibit significant therapeutic potential. The sulfur atom of the thiadiazole imparts improved liposolubility, and the mesoionic nature of thiadiazoles makes these compounds better able to cross cellular membranes. By summarizing the thiadiazole-containing compounds reported in recent decades, we aim to give a brief introduction to their synthesis and diverse biological activities, such as anti-inflammatory, anticancer, antibacterial, antifungal, antiviral, antiparasitic, anticonvulsant, anticoagulant, antidiabetic, and to show the significant utility of the thiadiazole scaffolds in medicinal chemistry.
Electrical Pacing for Dynamic Treatment of Unilateral Vocal Cord Paralysis (1991)

In order to explore the possibility of clinical application of laryngeal pacing as a treatment for unilateral vocal cord paralysis, we examined the reactivity of atrophic muscle to electrical stimulation in dogs whose recurrent laryngeal nerves were damaged by crushing, dissection followed by resuturing, or a 3-cm neurectomy. The threshold level to induce enough vocal cord adduction reached the maximum at 2 weeks after nerve injury, decreased with time, and never surpassed 7 V in each case. On the basis of results of these preliminary probings, laryngeal pacing was conducted on a dog 15 months after resection of the laryngeal nerve. Adduction of the paralyzed vocal cord for synchrony with the intact cord was achieved by 7 V of electrical stimulation of the thyroarytenoid muscle that was triggered by signals from the cricothyroid muscle.
Increased Activated Human T Cell Lymphotropic Virus Type I (HTLV‐I) Tax11‐19–Specific Memory and Effector CD8+Cells in Patients with HTLV‐I–Associated Myelopathy/Tropical Spastic Paraparesis: Correlation with HTLV‐I Provirus Load (2001)

To discern the T cell subtype associated with T cell differentiation, the expression of CD45RA and CD27 was measured from total CD8(high) cells and from human T cell lymphotropic virus type I (HTLV-I) Tax11-19 peptide-specific CD8(+) cells in peripheral blood lymphocytes of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phenotypically defined memory and/or effector cells (CD45RA(-)CD27(+), CD45RA(+)CD27(-), and CD45RA(-)CD27(-)) were increased in HAM/TSP CD8(+) cells, compared with those of HTLV-I-seronegative healthy control subjects. The percentage of human leukocyte antigen (HLA)-DR-positive cells was also increased in CD8(+) cells of HAM/TSP, compared with those in HLA-DR(+)CD8(+) cells of healthy control subjects. HTLV-I provirus load correlated with the frequency of Tax11-19-specific CD8(+) cells. The high frequency of memory and/or effector type HTLV-I Tax11-19-specific CD8(+) cells suggests that continuous restimulation driven by HTLV-I antigens in vivo may be associated with the pathogenesis of HAM/TSP.
Effect of tumor cells and tumor microenvironment on NK‐cell function (2014)

The ability of tumors to manage an immune-mediated attack has been recently included in the "next generation" of cancer hallmarks. In solid tumors, the microenvironment that is generated during the first steps of tumor development has a pivotal role in immune regulation. An intricate net of cross-interactions occurring between tumor components, stromal cells, and resident or recruited immune cells skews the possible acute inflammatory response toward an aberrant ineffective chronic inflammatory status that favors the evasion from the host's defenses. Natural killer (NK) cells have powerful cytotoxic activity, but their activity may be eluded by the tumor microenvironment. Immunosubversion, immunoediting or immunoselection of poorly immunogenic tumor cells and interference with tumor infiltration play a major role in evading NK-cell responses to tumors. Tumor cells, tumor-associated fibroblasts and tumor-induced aberrant immune cells (i.e. tolerogenic or suppressive macrophages, dendritic cells (DCs) and T cells) can interfere with NK-cell activation pathways or the complex receptor array that regulate NK-cell activation and antitumor activity. Thus, the definition of tumor microenvironment-related immunosuppressive factors, along with the identification of new classes of tissue-residing NK-like innate lymphoid cells, represent key issues to design effective NK-cell-based therapies of solid tumors.