gebhart/patrepeval huggingface dataset:
Validation of a new classifier for the automated analysis of the human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer specimens (2013)

Amplification of the human epidermal growth factor receptor 2 (HER2) is a prognostic marker for poor clinical outcome and a predictive marker for therapeutic response to targeted therapies in breast cancer patients. With the introduction of anti-HER2 therapies, accurate assessment of HER2 status has become essential. Fluorescence in situ hybridization (FISH) is a widely used technique for the determination of HER2 status in breast cancer. However, the manual signal enumeration is time-consuming. Therefore, several companies like MetaSystem have developed automated image analysis software. Some of these signal enumeration software employ the so called "tile-sampling classifier", a programming algorithm through which the software quantifies fluorescent signals in images on the basis of square tiles of fixed dimensions. Considering that the size of tile does not always correspond to the size of a single tumor cell nucleus, some users argue that this analysis method might not completely reflect the biology of cells. For that reason, MetaSystems has developed a new classifier which is able to recognize nuclei within tissue sections in order to determine the HER2 amplification status on nuclei basis. We call this new programming algorithm "nuclei-sampling classifier". In this study, we evaluated the accuracy of the "nuclei-sampling classifier" in determining HER2 gene amplification by FISH in nuclei of breast cancer cells. To this aim, we randomly selected from our cohort 64 breast cancer specimens (32 nonamplified and 32 amplified) and we compared results obtained through manual scoring and through this new classifier. The new classifier automatically recognized individual nuclei. The automated analysis was followed by an optional human correction, during which the user interacted with the software in order to improve the selection of cell nuclei automatically selected. Overall concordance between manual scoring and automated nuclei-sampling analysis was 98.4% (100% for nonamplified cases and 96.9% for amplified cases). However, after human correction, concordance between the two methods was 100%. We conclude that the nuclei-based classifier is a new available tool for automated quantitative HER2 FISH signals analysis in nuclei in breast cancer specimen and it can be used for clinical purposes.
Selective antagonism of 5-fluorouracil cytotoxicity by 4-hydroxypyrazolopyrimidine (allopurinol) in vitro. (1979)

Abstract Allopurinol (HPP) antagonized the growth-inhibitory activity of 5-fluorouracil (FUra) in L5178Y cells in culture as well as in a number of other murine leukemic cell lines. HPP depressed the incorporation of FUra into fluoropyrimidine nucleotides in L5178Y cells by interfering with the conversion of FUra to 5-fluorouridine 5′-phosphate; decreased concentrations of FUra nucleoside triphosphate also reduced the incorporation of FUra into RNA. HPP prevented the inhibition of deoxyuridine incorporation into DNA via thymidylate synthetase caused by FUra alone, presumably by reduction in the formation of 5-fluorodeoxyuridine 5′-phosphate. The site of HPP action consistent with these observations is inhibition of orotidylate decarboxylase resulting in the accumulation of intracellular orotate. The increased intracellular orotate is believed to compete with FUra for conversion to nucleotide form in those cells that activate FUra via an orotate phosphoribosyltransferase pathway. Further evidence for this mechanism was the finding that uridine nullified the HPP antagonism of FUra growth inhibition in L5178Y cells and prevented the accumulation of intracellular orotate caused by HPP alone. In contrast, HPP did not reduce FUra cytotoxicity in two other cell lines, Walker 256 and HeLa, which appear to anabolize FUra via the uridine phosphorylase and uridine kinase pathway. Furthermore, other inhibitors of orotidylate decarboxylase such as oxypurinol and pyrazofurin did not antagonize FUra cytotoxicity in Walker 256 cells as had been observed with L5178Y.
Estimating the Quality of Data in Relational Databases. (1996)

With more and more electronic information sources becoming widely available, the issue of the quality of these, often-competing, sources has become germane. We propose a standard for rating information sources with respect to their quality. An important consideration is that the quality of information sources often varies considerably when specific areas within these sources are considered. This implies that the assignment of a single rating of quality to an information source is usually unsatisfactory. Of course, to the user of an information source the overall quality of the source may not be as important as the quality of the specific information that this user is extracting from the source. Therefore, methods must be developed that will derive reliable estimates of the quality of the information provided to users, from the quality specifications that have been assigned to the sources. Our work here bears on all these concerns. We describe an approach that uses dual quality measures that gauge the distance of the information in a database from the truth. We then propose to combine manual verification with statistical methods to arrive at useful estimates of the quality of databases. We consider the variance in quality by isolating areas of databases that are homogeneous with respect to quality, and then estimating the quality of each separate area. These composite estimates may be regarded as quality specifications that will be affixed to each database. Finally, we show how to derive quality estimates for individual queries from such quality specifications. This work was supported in part by DARPA grants N0014-92-J-4038 and N0060-96-D-3202. 94
Gene Therapy For Spinal Cord Injury And Disease (2002)

An incomplete understanding of the pathological processes involved in neurodegeneration and dysfunction of spinal cord injuries and diseases makes these disorders difficult to treat. Repair of damaged or genetically impaired spinal cord also has been limited by the complexity, cellular heterogeneity, and relative inaccessibility of the tissue. Thus, therapeutic options for the treatment of either chronic spinal cord diseases such as amyotrophic lateral sclerosis or acute spinal cord injuries have been rather limited. Potential new therapeutic targets are being identified as our understanding of the molecular pathology involved in neural injury and regeneration increases. Recent advances in gene transfer techniques have made gene therapy a more realistic and viable strategy for the treatment of a broad range of spinal cord disorders. This review summarizes the current state of knowledge regarding the limitations and recent advances in gene therapy and potential application of this technology toward spinal cord injury and disease.
Few FH mutations in sporadic counterparts of tumor types observed in hereditary leiomyomatosis and renal cell cancer families. (2002)

Loss of function mutations in the fumarate hydratase (fumarase, FH) gene were recently identified as the cause for dominantly inherited uterine and cutaneous leiomyomas and renal cell cancer. To further evaluate the role of FH in tumorigenesis, we screened FH mutations from tumor types seen in hereditary leiomyomatosis and renal cell cancer mutation carriers-41 uterine and 10 cutaneous leiomyomas, 52 renal cell carcinomas, 53 sarcomas, 29 prostate carcinomas, and 15 lobular breast carcinomas. Few mutations were detected. Biallelic inactivation of FH was found in one uterine leiomyosarcoma, one cutaneous leiomyoma, and one soft tissue sarcoma. Whereas the two former lesions were shown to originate from a germ-line mutation, the soft tissue sarcoma is to our knowledge the first example of purely somatic inactivation of FH in tumors.
Segmental flexibility of immunoglobulin G antibody molecules in solution: a new interpretation (1981)

We propose a new model for the segmental flexibility of immunoglobulin G (IgG). The flexibility of native and mildly reduced anti-5-(dimethylamino)naphthalene-1-sulfonyl (anti-dansyl) antibody was reexamined by nanosecond fluorescence spectroscopy using deconvolution and lamp-shift corrections. The rabbit antibodies used for this study were purified of dimers and other aggregates. The original results indicated that the decay of fluorescence anisotropy involved two rotational correlation times. It was suggested that the short rotational correlation time, phi s, represented a flexible Fab arm motion over a restricted angle and that the long correlation time, phi L, represented global tumbling of the molecule [Yguerabide, J., Epstein, H. F., & Stryer, L. (1970) J. Mol. Biol. 51, 573--590]. Our new data indicate that the long correlation time primarily represents motions of the Fab segments and not global tumbling of the entire molecule. This interpretation implies a more flexible model for IgG. Thus, in solution the antibody arms appear to move over a wide angle and are not restricted to 33 degrees as was suggested in the earlier model. Simple diffusion calculations and other evidence suggest that phi s may represent V-module flexibility about the switch peptides or Fab twisting around its long axis, whereas phi L may represent wagging or wobbling motions of the Fab arms about the hinge region. The faster motions appear to occur over small angles whereas the slower wagging or wobbling motions responsible for most of the decay of anisotropy appear to be much less restricted. The biological function of IgG and anisotropy changes resulting from hinge disulfide cleavage are interpreted in terms of the proposed model. We also demonstrate a useful method for comparison of time-dependent and steady-state fluorescence polarization data.
Retrieval properties of neural networks with hierarchical clustering (1991)

By using the statistical mechanics formulation of Amit, Gutfreund and Sompolinsky (1985) the authors investigate the retrieval properties of a model for neural networks that exhibits the same organization into clusters as Dyson's hierarchical model for ferromagnetism, combined with Hebb's learning algorithm for a non-extensive number of stored patterns. They show that if the number of clusters l<or=4 the model is able to retrieve perfectly a family of 'descendants' together with a 'pure' embedded pattern, which appear as local minima of the free energy through a series of discontinuous transitions when the temperature (noise) is reduced. The highest critical temperature is for retrieval of the embedded patterns, that occur through a second order, continuous transition and remain as the global minima of the free energy. The 'descendants' differ from the 'ancestor' in the signs of the cluster overlaps. However, when the number of partitions in clusters increases there appear 'blurred' solutions, that consist in an arbitrary mixture of 'descendants' of a given pattern and may hinder the perfect retrieval. The number n(l) of mixed solutions increases exponentially with the cluster number, n(l) approximately=e0.45l, for large values of l.
A PRELIMINARY STUDY ON THE INTERFERON-α TREATMENT FOR XEROSTOMIA OF SJÖGREN'S SYNDROME (1993)

We studied the therapeutic effect of interferon-alpha on the xerostomia of Sjögren's syndrome by injecting 1 x 10(6) units of interferon-alpha intramuscularly once weekly. Saliva production was quantitated by the Saxon test. Variation of saliva production measured at monthly intervals during the 3-month period prior to administration of interferon-alpha was within +/- 0.30 g/2 min. After administration of interferon-alpha, saliva production increased to greater than 0.30 g/2 min in six patients, and the increase was statistically significant by the paired t-test (P = 0.002). The result suggests a beneficial effect of this agent in increasing the saliva production of patients with primary Sjögren's syndrome.
Leiomyosarcoma of veins.Report of 2 cases and review of the literature (1960)

hioom MUSCLE tumors are common in the S uterus and by no means rare in the gastrointestinal tract, retroperitoneum, and superficial soft tissues. However, they have seldom been recorded as arising from large blood vessels. ,4be11,2 reporting 2 cases of leiomyosarcoma of the inferior vena cava, could cull only 6 tumors of smooth muscle, benign and malignant, that arose from the wall of the inferior rena cava. Stout and Hi11,28 in a review of 36 leiomyosarcomas of the superficial soft tissues, found only 1 arising in a large vein. This paper presents 2 cases of leiomyosarcoma, one primary in the inferior vena cava and the other in the right internal jugular vein, and reviews 27 previously reported tumors arising in major veins (Table
Pressure generation due to a temperature discontinuity at a liquid-liquid plane interface (1978)

Using a simplified equation of state, an analytic solution for the temperature, pressure, velocity, and acceleration of two semi-infinite liquids initially at two distinct temperatures is obtained by ignoring the effects of the generated pressure on the temperature distribution. It is found that the pressure wave generated in the cooler medium by the temperature discontinuity develops into a shock after passing through the thermal boundary layer. The cooler material is initially accelerated into the hotter material and thus if the cooler material is lighter, the interface is Raleigh–Taylor unstable. The pressures and velocities at the interface relax with a characteristic time τ=α/c2, where α is the thermal diffusivity and c is the speed of sound. For the particular case of liquid Na in contact with liquid UO2 specific results are given. The linearized approximation is compared with exact numerical integration of the full hydrodynamic equations and reasonable agreement is found.
Dual Organocatalysis: Asymmetric Allylic–Allylic Alkylation of α,α‐Dicyanoalkenes and Morita–Baylis–Hillman Carbonates (2009)

The first highly enantioselective allylic-allylic alkylation of alpha,alpha-dicyanoalkenes and Morita-Baylis-Hillman carbonates by dual catalysis of (DHQD)(2)AQN and (S)-BINOL has been investigated. Excellent stereoselectivities have been achieved for a broad spectrum of substrates (d.r. > 99:1, up to 99 % ee). The multifunctional allylic products could be efficiently converted to a range of complex chiral cyclic frameworks. EWG = electron-withdrawing group, (DHQD)(2)AQN = hydroquinidine (anthraquinone-1,4-diyl) diether, (S)-BINOL = (S)-(-)-1,1'-bi-2-naphthol.
Enhanced spin accumulation obtained by inserting low-resistance MgO interface in metallic lateral spin valves (2010)

We have systematically investigated the interface contributions to the spin injection characteristics in permalloy/MgO/Ag lateral spin valves. The spin valve signal remarkably increases with MgO thickness and reaches a maximum when the interface resistance is about 100 fΩ m2 for 1 nm thick MgO, which is two orders of magnitude lower than that of the typical tunnel junction. Our quantitative analysis based on the spin-dependent diffusion equation considering variable spin polarization in the MgO layer well describes the observed trend in the spin valve signals.
Targeting Metabolic Syndrome (2004)

Metabolic syndrome has been recognised as a cluster of risk factors contributing to the development of cardiovascular diseases. Different diagnostic criteria have been proposed and the consensus focuses on four major risk factors: obesity, diabetes, dyslipidaemia and hypertension. Although treatment options are available to treat each component separately, a highly effective agent for metabolic syndrome has yet to be developed. To explore the clinical definition of metabolic syndrome and potential molecular targets that can be modulated for treatment purpose, a meeting entitled 'Targeting Metabolic Syndrome' was organised in 2004 by IBC USA Conferences, Inc. This article highlights discussions related to the clinical correlates and pathophysiology of metabolic syndrome, and reviews some of the promising drug discovery efforts. Metabolic syndrome should be treatable and preventable if obesity and insulin resistance are well controlled. New regulatory guidelines need to be developed as new treatment options are being investigated. From a broad spectrum of potential mechanisms encompassing central nervous system targets and peripheral targets for pharmacological intervention, a few promising molecular targets have emerged. Modulating these is expected to treat at least some components of metabolic syndrome.
A guide to COBOL programming (1970)

A guide to COBOL programming , A guide to COBOL programming , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Copy-based versus edit-based version management schemes for structured documents (2002)

Managing multiple versions of XML documents and semistructured data represents a problem of growing interest. Traditional version control methods, such as RCS, use edit scripts representing changes in the document to support the incremental reconstruction of different versions. The edit-based approaches have been enhanced with a replication scheme called UBCC (Chien et al., 2000). UBCC is based on the notion of page usefulness and ensures effective management for multi-version documents in terms of both retrieval and storage cost. These improvements notwithstanding, the edit-based representation suffers from limited generality and flexibility-e.g., it cannot represent changes such as rearranging the document or duplicating parts of its content. To solve these problems, the paper proposes a copy-based UBCC versioning scheme, which also provides a simpler format for the electronic exchange of multi-version documents. With the objective of matching the performance of the edit-based UBCC technique, we develop algorithms that enhance the copy-based UBCC scheme with page usefulness management. We also present results of various experiments that test the storage and retrieval performance of the new copy-based approach, and compare it with that of the edit-based UBCC approach.
Evaluation of a direct injection high-efficiency nebulizer (DIHEN) by comparison with a high-efficiency nebulizer (HEN) coupled to a cyclonic spray chamber as a liquid sample introduction system for ICP-AES (2001)

In the present work the advantages and limitations of introducing the sample directly into the plasma through the use of a direct injection high-efficiency nebulizer (DIHEN) have been evaluated in ICP-AES. The reference system was a high-efficiency nebulizer (HEN), precursor of the DIHEN, coupled to a cyclonic spray chamber. It was found that the plasma can only be operated under non-robust conditions because of the high solvent loading. The issues considered in the present work were: (i) the aerosol characteristics; (ii) the ICP-AES analytical figures of merit; and (iii) the interferences induced by the presence of inorganic as well as organic matrices. The results indicated that the aerosols obtained by the DIHEN are coarser than those leaving the cyclonic spray chamber. Nonetheless, and due to the higher analyte transport efficiency, the DIHEN affords ICP-AES sensitivities and LODs up to 10–18 times better than the cyclonic spray chamber. Also, it was found that, under the plasma conditions tested, the optimum nebulizer gas and liquid flow rates in terms of sensitivity for the DIHEN were very different from those for the HEN with the cyclonic spray chamber. In the first case, the signal peaked at rather low liquid (Ql) and gas (Qg) flow rates, whereas for the cyclonic spray chamber moderate and/or high liquid and gas flow rates were advisable. Under a given set of plasma conditions, the DIHEN has been proven to produce problems due to deterioration in the plasma, derived from the higher solvent load with respect to the HEN coupled to the cyclonic spray chamber. Despite these findings and the fact that a non-robust plasma was used, the matrix effects for inorganic and organic species were significantly minimized, for a low Ql and for some lines, in the case of the DIHEN.
Reversible Structural Switching of a DNA−DDAB Film (2009)

We describe the novel structure and behavior of a DNA-DDAB complex film cast from an organic solvent and exhibiting a structural switching transition as it is dried or wetted with water. The film was easily prepared by formation of a complex between the negatively charged phosphate groups of DNA and the positively charged headgroup of the surfactant DDAB. This complex was then purified, dried, dissolved in 2-propanol, and cast onto a glass slide to form a self-standing film by means of slow evaporation. While the structure of the dried film was found to be composed of single-stranded DNA and a monolayer of DDAB, upon hydration of the film, the structure switched to double-stranded DNA complexed to a bilayer of DDAB. We expect this phenomenon to serve as a useful model for the design of new responsive materials and programmable self-assembly.
Polarity-induced oxygen vacancies at<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mtext>LaAlO</mml:mtext></mml:mrow><mml:mn>3</mml:mn></mml:msub><mml:mo>∕</mml:mo><mml:msub><mml:mrow><mml:mtext>SrTiO</mml:mtext></mml:mrow><mml:mn>3</mml:mn></mml:msub></mml:mrow></mml:math>interfaces (2010)

Using first-principles density-functional-theory calculations, we find a strong position and thickness dependence of the formation energy of oxygen vacancies in ${\text{LaAlO}}_{3}\ensuremath{\mid}{\text{SrTiO}}_{3}$ $(\text{LAO}\ensuremath{\mid}\text{STO})$ multilayers and interpret this with an analytical capacitor model. Oxygen vacancies are preferentially formed at $p$-type $\text{SrO}\ensuremath{\mid}{\text{AlO}}_{2}$ rather than at $n$-type $\text{LaO}\ensuremath{\mid}{\text{TiO}}_{2}$ interfaces; the excess electrons introduced by the oxygen vacancies reduce their energy by moving to the $n$-type interface. This asymmetric behavior makes an important contribution to the conducting (insulating) nature of $n$-type ($p$-type) interfaces while providing a natural explanation for the failure to detect evidence for the polar catastrophe in the form of core level shifts.
In Situ Hybridization—A Guided Tour (1991)

Summary: This article describes the use of in situ hybridization to study gene expression. We consider the advantages of this technique in comparison to other methods for analyzing gene expression at the level of messenger RNAs, and compare the information that can be obtained by localization of mRNAs by in situ hybridization versus localization of proteins by immunohistochemistry. We describe applications of in situ hybridization to the study of normal and abnormal development and tissue function. We then present the protocol developed in our laboratory as a framework for detailed discussion of each of the steps in the procedure, and comment on the relative merits of different options at each step. Individual steps discussed include tissue fixation and prehybridization treatments, choice of probes, hybridization parameters (probe concentration, time, and temperature), posthybridization washes, choice of isotopes and nonisotopic methods for detecting hybridized probe, and autoradiography. Finally, we discuss controls that can be used to increase the reliability, specificity and quantitative accuracy of the data obtained.