gebhart/patrepeval huggingface dataset:
Nucleic Acid Detection Methods (2023)

The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3'-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated.
High Precision Imaging of Microscopic Spread of Glioblastoma with a Targeted Ultrasensitive SERRS Molecular Imaging Probe (2016)

The dismal prognosis of patients with malignant brain tumors such as glioblastoma multiforme (GBM) is attributed mostly to their diffuse growth pattern and early microscopic tumor spread to distant regions of the brain. Because the microscopic tumor foci cannot be visualized with current imaging modalities, it remains impossible to direct treatments optimally. Here we explored the ability of integrin-targeted surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles to depict the true tumor extent in a GBM mouse model that closely mimics the pathology in humans. The recently developed SERRS-nanoparticles have a sensitivity of detection in the femtomolar range. An RGD-peptide-conjugated version for integrin-targeting (RGD-SERRS) was compared directly to its non-targeted RAD-SERRS control in the same mice via Raman multiplexing. Pre-blocking with RGD peptide before injection of RGD-SERRS nanoparticles was used to verify the specificity of integrin-targeting. In contrast to the current belief that the enhanced permeability and retention (EPR) effect results in a baseline uptake of nanoparticles regardless of their surface chemistry, integrin-targeting was shown to be highly specific, with markedly lower accumulation after pre-blocking. While the non-targeted SERRS particles enabled delineation of the main tumor, the RGD-SERRS nanoparticles afforded a major improvement in visualization of the true extent and the diffuse margins of the main tumor. This included the detection of unexpected tumor areas distant to the main tumor, tracks of migrating cells of 2-3 cells in diameter, and even isolated distant tumor cell clusters of less than 5 cells. This Raman spectroscopy-based nanoparticle-imaging technology holds promise to allow high precision visualization of the true extent of malignant brain tumors.
Activation of progelatinase B in synovial fluids of patients with rheumatoid arthritis, with reference to stromelysin-1 and tissue inhibitor of matrix metalloproteinase-1. (1999)

The balance between the concentrations of stromelysin-1 and of TIMP-1 in the synovial fluid appears to determine whether the progelatinase B molecule causes conversion into the active form.
MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation (2009)

Increasing evidence shows aberrant hypermethylation of genes occurring in and potentially contributing to pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDSs), are responsive to DNA methyltransferase inhibitors. To determine the extent of promoter hypermethylation in such tumors, we compared the distribution of DNA methylation of 14 000 promoters in MDS and secondary acute myeloid leukemia (AML) patients enrolled in a phase 1 trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34(+) bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34(+) bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu-poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. This trial was registered at www.clinicaltrials.gov as J0443.
On the Theory of Apportionment (1935)

1. If in an accepted sense, P is the probability that one method of treatment, T,, is better than a rival, T2, we may develop a system of apportionment such that the proportionate use of T1 is f(p), a monotolle increasing functioni, rather than make no discriminationi at all up to a certaini poinit and then finally entirely reject one or the other. The only paper * which has so far appeared in his field, as far as I am aware, is one by myself in a recent issue of Biometrilca. In this paper I have considered the case of choice between two such rival treatments,t and for symmetry suggested that f (QI f(p) where Q = 1 P. Then the riski of assignmenit to T1 when it is not the better is Q f(p), while the correspondinig risk for T2 is P f.(Q Accordingly, I suggested further that we set f(p) P, which is a necessary and sufficient conditioni that these two risks be equal. Their sum, the total qrisk, is then 2PQ. A special case was considered wherein the result of use of Ti at any given trial is either success or failure, the probability of failure being an unkniownl, pi, a priori (independenitly for i 1, , kc) equally likely to lie in either of any two equal intervals in the possible range, (0, 1). It is further assumed that for a given Ti we have an experience of exactly ni indepenidenit trials, the number of su?ccesses being si and of failu-res being ri = si-; and the probability of obtaininig such a sample is
Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy (2006)

Mouse glioma 261 (Gl261) cells are used frequently in experimental glioblastoma therapy; however, no detailed description of the Gl261 tumor model is available. Here we present that Gl261 cells carry point mutations in the K-ras and p53 genes. Basal major histocompatibility complex (MHC)I, but not MHCII, expression was detected in Gl261 cells. The introduction of interferon-gamma-encoding genes increased expression of both MHCI and MHCII. A low amount of B7-1 and B7-2 RNA was detected in wild-type cells, but cytokine production did not change expression levels. Gl261 cells were transduced efficiently by adenoviral vectors; the infectivity of retroviral vectors was limited. Low numbers of transplanted Gl261 cells formed both subcutaneous and intracranial tumors in C57BL/6 mice. The cells were moderately immunogenic: prevaccination of mice with irradiated tumor cells 7 days before intracranial tumor challenge prevented tumor formation in approximately 90% of mice. When vaccination was carried out on the day or 3 days after tumor challenge, no surviving animals could be found. In vitro-growing cells were radiosensitive: less than 2 Gy was required to achieve 50% cell mortality. Local tumor irradiation with 4 Gy X-rays in brain tumor-bearing mice slowed down tumor progression, but none of the mice were cured off the tumor. In conclusion, the Gl261 brain tumor model might be efficiently used to study the antitumor effects of various therapeutic modalities, but the moderate immunogenicity of the cells should be considered.
Employing EM and Pool-Based Active Learning for Text Classification (1998)

This paper shows how a text classifier&amp;apos;s need for labeled training documents can be reduced by taking advantage of a large pool of unlabeled documents. We modify the Query-by-Committee (QBC) method of active learning to use the unlabeled pool for explicitly estimating document density when selecting examples for labeling. Then active learning is combined with Expectation-Maximization in order to &amp;quot;fill in&amp;quot; the class labels of those documents that remain unlabeled. Experimental results show that the improvements to active learning require less than two-thirds as many labeled training examples as previous QBC approaches, and that the combination of EM and active learning requires only slightly more than half as many labeled training examples to achieve the same accuracy as either the improved active learning or EM alone.
Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a). (1993)

The B apolipoproteins, apo-B48 and apo-B100, are key structural proteins in those classes of lipoproteins considered to be atherogenic [e.g., chylomicron remnants, beta-VLDL, LDL, oxidized LDL, and Lp(a)]. Here we describe the development of transgenic mice expressing high levels of human apo-B48 and apo-B100. A 79.5-kb human genomic DNA fragment containing the entire human apo-B gene was isolated from a P1 bacteriophage library and microinjected into fertilized mouse eggs. 16 transgenic founders expressing human apo-B were generated, and the animals with the highest expression had plasma apo-B100 levels nearly as high as those of normolipidemic humans (approximately 50 mg/dl). The human apo-B100 in transgenic mouse plasma was present largely in lipoproteins of the LDL class as shown by agarose gel electrophoresis, chromatography on a Superose 6 column, and density gradient ultracentrifugation. When the human apo-B transgenic founders were crossed with transgenic mice expressing human apo(a), the offspring that expressed both transgenes had high plasma levels of human Lp(a). Both the human apo-B and Lp(a) transgenic mice will be valuable resources for studying apo-B metabolism and the role of apo-B and Lp(a) in atherosclerosis.
Low molecular weight, non-peptide fibrinogen receptor antagonists (1992)

The tetrapeptide H-Arg-Gly-Asp-Ser-OH (1) (RGDS), representing a recognition sequence of fibrinogen for its platelet receptor GP IIb-IIIa (integrin alpha IIb beta 3), served as lead compound for the development of highly potent and selective fibrinogen receptor antagonists. Replacement of the N-terminal arginine by p-amidinophenylalanine or the Gly moiety by m-aminobenzoic acid led to compounds which are superior to the lead peptide with regard to activity and selectivity for GP IIb-IIIa vs the closely related vitronectin receptor alpha v beta 3. By random screening [(p-amidinobenzenesulfonamido)ethyl]-p-phenoxyacetic acid derivatives have been identified as fibrinogen receptor antagonists. Further structure-activity relationship studies culminated in the preparation of N-[N-[N-(p-amidinobenzoyl)-beta-alanyl]-L-alpha-aspartyl]-3-phenyl-L- alanine (29h, Ro 43-5054) and [[1-[N-(p-amidinobenzoyl)-L-tyrosyl]-4-piperidinyl]oxy]acetic acid (37f, Ro 44-9883), which exhibit very high activity as platelet aggregation inhibitors (IC50s 0.06 and 0.03 microM, respectively, human PRP/ADP) as well as marked selectivity for GP IIb-IIIa vs alpha v beta 3. Since the activity of 37f in dogs declines according to a two-compartment model with an initial phase having a t1/2 of 8 min and a second phase with a t1/2 of 110 min, this compound is a suitable candidate for the development as iv platelet inhibitor.
An In Vitro Model of Traumatic Neuronal Injury: Loading Rate-Dependent Changes in Acute Cytosolic Calcium and Lactate Dehydrogenase Release (1997)

We developed a new in vitro model of neuronal injury using NT2-N cells to examine the effects of hydrodynamic loading rate on intraneuronal calcium dynamics and lactate dehydrogenase (LDH) release. Our apparatus consisted of a parallel disk viscometer which induced fluid shear stress with well-defined magnitudes and loading rates to cultured cells. We found that the deformation response of the cells was dependent on the severity of the insult, with increased cellular strains generated for higher shear stresses at a constant loading rate. Peak intracellular free calcium concentration correlated with strain, suggesting that mechanical deformation may regulate calcium response. Slowly applied fluid shear stress elicited no response, whereas high loading rates resulted in peak calcium increases 2.9 to 3.6 times baseline values as injury severity was increased. LDH release measured within 5 min after the insult correlated with loading rate. In addition, LDH release continued to increase out to 24 h following high loading rate conditions, demonstrating that the application of fluid shear stress led to prolonged cell damage. The acute response in NT2-N cells subjected to an insult with the CSID is dependent on the loading rate, and these results suggest that initial membrane deformation may trigger subsequent events.
Akt activation by estrogen in estrogen receptor-negative breast cancer cells. (2001)

It has been a common belief that estrogen regulates cellular responses through binding to its receptor, the estrogen receptor (ER). In the nucleus, estrogen modulates the expression of estrogen-responsive genes through the action of the ER at the transcriptional level. In the cytoplasm, the ER-dependent signaling pathway has been shown to be involved in the activation of Akt and the downstream molecules. It is not clear, however, whether estrogen can modulate cytoplasmic signaling in an ER-independent manner. Human breast cancer cell lines without detectable ERs such as MDA-MB-435 and MDA-MB-231 were treated in estrogen-depleted medium followed by a brief treatment with estrogen. The activation of Akt was evaluated by a phosphoserine antibody. Our results showed that estrogen stimulated Akt activation, as indicated by phosphorylation at Ser(473) of the oncoprotein, in ER-negative breast cancer cells. Activation of Akt by estrogen in these cells was time and dose dependent and could be blocked by inhibitors of phosphatidylinositol 3'-kinase and Src kinase but not by estrogen antagonists. Our results provide evidence as well as the mechanism of the receptor-independent function of estrogen, in which the antiapoptotic factor Akt is activated.
Radioimmunotherapy using 131I-labeled anti-CD22 monoclonal antibody (LL2) in patients with previously treated B-cell lymphomas. (1999)

Experience in using rapidly internalizing antibodies, such as the anti-CD22 antibody, for radioimmunotherapy of B-cell lymphomas is still limited. The present study was conducted to assess the efficacy and toxicity of a 131I-labeled anti-CD22 monoclonal antibody (mAb), LL2, in patients with B-cell lymphomas failing first- or second-line chemotherapy. Eligible patients were required to have measurable disease, less than 25% B cells in unseparated bone marrow, and an uptake of 99mTc-labeled LL2Fab' in at least one lymphoma lesion on immunoscintigram. Eight of nine patients examined with immunoscintigraphy were unequivocally found to have an uptake, and therapy with 131I-labeled anti-CD22 [1330 MBq/m2 (36 mCi/m2)] preceded by 20 mg of naked anti-CD22 mAb was administered. Three patients achieved partial remission (duration, 12, 3, and 2 months), and one patient with progressive lymphoma showed stable disease for 17 months. Four patients exhibited progressive disease. The toxicity was hematological. Patients with subnormal counts of neutrophils or platelets before therapy seemed to be more at risk for hematological side effects. Radioimmunotherapy in patients with B-cell lymphomas using 131I-labeled mouse anti-CD22 can induce objective remission in patients with aggressive as well as indolent lymphomas who have failed prior chemotherapy.
Light‐dependence of photosynthesis and growth in cyanobacteria: Implications for their dominance in eutrophic lakes (1987)

Abstract In eutrophic lakes cyanobacteria are favoured relative to other phytoplankton, both under stratified and mixed conditions. During stratification, gas vacuole formation allows the accumulation of dense surface scums which attain the highest possible area‐specific photosynthetic rates in aquatic environments owing to high irradiances, near‐complete harvesting of impinging light, and minimal light inhibition and photo‐oxidation. During moderate mixing, high yields of biomass can be achieved by effective light harvesting for photosynthesis (aided by phycobilin pigments) and low maintenance energy requirements at low mean irradiances. Howevrr, nitrogen fixation competes for energy and reductant with photosynthesis, and leads to a decline of light‐saturated maximum growth rates. Wind‐driven vertical mixing and lateral advection are the main causes for the instability of cyanobacterial blooms in hyper‐eutrophic lake ecosystems.
Erythropoietin mRNA levels are governed by both the rate of gene transcription and posttranscriptional events (1991)

The human hepatoma cell line, Hep3B, synthesizes large quantities of erythropoietin (Epo) mRNA and protein in a regulated manner in response to hypoxia and cobaltous chloride (CoCl2). To further understand the regulation of Epo gene expression, we studied the effects of hypoxia and CoCl2 on the rate of Epo gene transcription. While Northern blot analyses showed that steady-state Epo mRNA levels increase more than 50- fold in response to hypoxia or CoCl2, nuclear run-off experiments demonstrated only a 10-fold increase in Epo gene transcription in response to these stimuli. In the presence of either actinomycin D (Act D) or cycloheximide, the stability of biologically functional Epo mRNA was much greater than that observed in the absence of these agents and much greater than that which has been reported in vivo. These findings suggest that the stability of Epo mRNA is modulated by the transcription and translation of rapidly turning over gene product(s). Thus, Epo mRNA levels are determined by both the rate of gene transcription and posttranscriptional events. These experiments demonstrate a potential pitfall in estimating mRNA half-lives based on Act D chase experiments alone.
Estimating duplication by content-based sampling (2013)

We define a new technique for accurately estimating the amount of duplication in a storage volume from a small sample and we analyze its performance and accuracy. The estimate is useful for determining whether it is worthwhile to incur the overhead of deduplication. The technique works by scanning the fingerprints of every block in the volume, but only including in the sample a single copy of each fingerprint that passes a filter. The selectivity of the filter is repeatedly increased while reading the fingerprints, to produce the target sample size. We show that the required sample size for a reasonable accuracy is small and independent of the size of the volume. In addition, we define and analyze an on-line technique that, once an initial scan of all fingerprints has been performed, efficiently maintains an up-to-date estimate of the duplication as the file system is modified. Experiments with various real data sets show that the accuracy is as predicted by theory. We also prototyped the proposed technique in an enterprise storage system and measured the performance overhead using the IOzone micro-benchmark.
Construction and characterization of a deletion mutant lacking micF, a proposed regulatory gene for OmpF synthesis in Escherichia coli (1985)

A method is presented for the construction of a deletion mutant lacking the micF gene, which has been proposed to negatively regulate expression of the ompF gene. The method includes (i) construction of a temperature-sensitive plasmid containing a chromosomal fragment that carries both flanking regions of the micF gene but does not carry micF itself and (ii) replacement of the corresponding chromosomal domain with the fragment. The method is applicable to construction of a deletion mutant for any Escherichia coli chromosomal gene provided that it is dispensable. The micF deletion was confirmed by genetic and biochemical tests, including nucleotide sequence analysis. ompF expression in the micF deletion mutant thus constructed was normally regulated and was not enhanced. When micF was cloned into a high-copy-number plasmid it repressed ompF gene expression, whereas when cloned into a low-copy-number plasmid it did not. From these results, it is concluded that a single copy of the micF gene on the E. coli chromosome does not play a critical role in ompF gene expression.
Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique (2014)

Mouse models are of special interest in research since a wide variety of monoclonal antibodies and commercially defined inbred and knockout strains are available to perform mechanistic in vivo studies. While heart transplantation models using a suture technique were first successfully developed in rats, the translation into an equally widespread used murine equivalent was never achieved due the technical complexity of the microsurgical procedure. In contrast, non-suture cuff techniques, also developed initially in rats, were successfully adapted for use in mice(1-3). This technique for revascularization involves two major steps I) everting the recipient vessel over a polyethylene cuff; II) pulling the donor vessel over the formerly everted recipient vessel and holding it in place with a circumferential tie. This ensures a continuity of the endothelial layer, short operating time and very high patency rates(4). Using this technique for vascular anastomosis we performed more than 1,000 cervical heart transplants with an overall success rate of 95%. For arterial inflow the common carotid artery and the proximal aortic arch were anastomosed resulting in a retrograde perfusion of the transplanted heart. For venous drainage the pulmonary artery of the graft was anastomosed with the external jugular vein of the recipient(5). Herein, we provide additional details of this technique to supplement the video.
An alternative approach to linearly constrained adaptive beamforming (1982)

A beamforming structure is presented which can be used to implement a wide variety of linearly constrained adaptive array processors. The structure is designed for use with arrays which have been time-delay steered such that the desired signal of interest appears approximately in phase at the steered outputs. One major advantage of the new structure is the constraints can be implemented using simple hardware differencing amplifiers. The structure is shown to incorporate algorithms which have been suggested previously for use in adaptive beamforming as well as to include new approaches. It is also particularly useful for studying the effects of steering errors on array performance. Numerical examples illustrating the performance of the structure are presented.