gebhart/patrepeval huggingface dataset:
Predicting response and survival in chemotherapy-treated triple-negative breast cancer (2014)

The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.
Quantification of Y chromosome bearing spermatozoa of cattle using in situ hybridization (1991)

An easy assay for quantification of Y chromosome-bearing sperm (Y-sperm) is needed, especially to monitor sperm separation techniques. In the present study a tritiated bovine male-specific DNA fragment was tested for identification of Y-sperm by in situ hybridization. A protocol for in situ hybridization to bovine sperm was developed and used to study the proportion of Y-sperm of 12 bulls. The usefulness of the method in optimization of sperm separation procedures is illustrated through analysis of fractions of sperm separated by Percoll density gradient centrifugation.
A two‐dimensional gel protein database of noncultured total normal human epidermal keratinocytes: Identification of proteins strongly up‐regulated in psoriatic epidermis (1990)

A two-dimensional (2-D) gel database of proteins from noncultured total normal human epidermal keratinocytes has been established. A total of 1449 [35S]methionine labelled proteins (1112 isoelectric focusing, 337 nonequilibrium pH gradient electrophoresis) were resolved and recorded using computer assisted (PDQ-SCAN and PDQUEST software) 2-D gel electrophoresis. By matching the protein patterns of total keratinocytes and transformed human amnion cells (master database; Celis et al., Leukemia 1988, 2, 561-602) as well as by 2-D immunoblotting and microsequencing of keratinocyte proteins, it was possible to identify 72 polypeptides in the keratinocyte database. The database also includes data on polypeptides that are synthesized at a higher level by keratinocytes enriched in basal cells, and on six secreted proteins which are produced, albeit at a reduced rate, by normal keratinocytes and that are strongly up-regulated in psoriatic epidermis (Celis et al., FEBS Letters, in press).
The Measurement of Liquidity (1982)

Liquidity measurement is an integral part of financial statement analysis, particularly in credit evaluations, and liquidity ratios are frequently employed in empirical research in accounting. Interest in this topic has increased recently because of the changes and potential changes in financial reporting requirements. The Securities and Exchange Commission now requires that each firm's annual report and 10-K include a discussion of its liquidity position, while the Financial Accounting Standards Board (FASB) has published a discussion memorandum entitled Reporting Funds Flows, Liquidity, and Financial Flexibility. One issue raised by this discussion memorandum is Should summary indicators of liquidity be provided (in financial reports)? Please specify the most useful summary indicators, giving reasons for your choice. (See FASB [1980].) There is disagreement about what constitutes a good summary indicator or measure of liquidity. Several researchers have proposed liquidity measures that incorporate cash flows in response to criticisms of the static nature of balance sheet ratios. While their proposed measures are intuitively appealing, there is rarely either a theoretical or empirical basis for preferring one over any others. In those instances wherein measures with a theoretical basis are proposed, their implementation is severely hampered by restrictive assumptions regarding when they may be applied. The purpose of this paper is to propose liquidity measures that are not subject to these limitations. We employ an axiomatic description of a firm's liquidity policy and liquidity position to obtain an expression for the likelihood that the firm will exhaust its liquid reserves (become technically insolvent). This expression may be used directly to assess
A Molecularly Annotated Model of Patient-Derived Colon Cancer Stem–Like Cells to Assess Genetic and Nongenetic Mechanisms of Resistance to Anti-EGFR Therapy (2017)

<b>Purpose:</b> Patient-derived xenografts ("<i>xenopatients</i>") of colorectal cancer metastases have been essential to identify genetic determinants of resistance to the anti-EGFR antibody cetuximab and to explore new therapeutic strategies. From xenopatients, a genetically annotated collection of stem-like cultures ("<i>xenospheres</i>") was generated and characterized for response to targeted therapies.<b>Experimental Design:</b> Xenospheres underwent exome-sequencing analysis, gene expression profile, and <i>in vitro</i> targeted treatments to assess genetic, biological, and pharmacologic correspondence with xenopatients, and to investigate nongenetic biomarkers of therapeutic resistance. The outcome of EGFR family inhibition was tested in an <i>NRG1</i>-expressing <i>in vivo</i> model.<b>Results:</b> Xenospheres faithfully retained the genetic make-up of their matched xenopatients over <i>in vitro</i> and <i>in vivo</i> passages. Frequent and rare genetic lesions triggering primary resistance to cetuximab through constitutive activation of the RAS signaling pathway were conserved, as well as the vulnerability to their respective targeted treatments. Xenospheres lacking such alterations (RAS<sup>wt</sup>) were highly sensitive to cetuximab, but were protected by ligands activating the EGFR family, mostly NRG1. Upon reconstitution of <i>NRG1</i> expression, xenospheres displayed increased tumorigenic potential <i>in vivo</i> and generated tumors completely resistant to cetuximab, and sensitive only to comprehensive EGFR family inhibition.<b>Conclusions:</b> Xenospheres are a reliable model to identify both genetic and nongenetic mechanisms of response and resistance to targeted therapies in colorectal cancer. In the absence of RAS pathway mutations, NRG1 and other EGFR ligands can play a major role in conferring primary cetuximab resistance, indicating that comprehensive inhibition of the EGFR family is required to achieve a significant therapeutic response. <i>Clin Cancer Res; 24(4); 807-20. ©2017 AACR</i><i>See related commentary by Napolitano and Ciardiello, p. 727</i>.
Pulmonary Clearance of Moraxella catarrhalis in an Animal Model (1992)

The virulence mechanisms of Moraxella catarrhalis that are involved in producing pulmonary infection are unknown. A well-characterized murine model was used to study the pulmonary clearance of M. catarrhalis and analyze the histopathologic changes and the role of phagocytic cells in the infected lungs. Ten strains of M. catarrhalis from various isolation sites were evaluated for their ability to resist pulmonary clearance. The rates of clearance of these strains, based on the percentage of the original inoculum remaining at 6 h after challenge, varied considerably. Histopathologic examination of lungs infected with 2 strains that exhibited very different clearance rates revealed similar pathologic responses. Analysis of the phagocytic cell response to these 2 strains revealed significant alveolar recruitment of granulocytes at 3, 6, and 24 h after bacterial challenge. However, granulocyte recruitment in response to strain B22, which was cleared readily, was significantly greater than to strain 035E, which resisted pulmonary clearance. This model system should facilitate investigation of the molecular basis of the interaction between M. catarrhalis and the lower respiratory tract.
A new approach to amplifier linearization by the generalized baseband signal injection method (2002)

The authors present a new technique for the reduction of third-order intermodulation distortion (IMD) in microwave amplifiers. A baseband predistortion signal is injected into a diode circuitry and the main amplifier to mix with the fundamental to generate a canceling signal for the suppression of the inherent IMD component. The proposed method can achieve higher linearity performance, in comparison to the conventional difference-frequency approach, and unlike many other techniques, no RF circuitry, such as variable gain amplifiers and phase-shifters, is needed other than baseband amplifiers. Both two-tone and vector signal measurement results are included.
Hydraulic and acoustic properties as a function of porosity in Fontainebleau Sandstone (1985)

Laboratory measurements have been made of the permeability ( k ), free porosity (ϕ L ), compressional velocities ( V P or V E ), and compressional attenuations ( Q P or Q E ) in Fontainebleau sandstone over a continuous range of porosities ϕ from 3 to 28%. This large variation was achieved without any composition change: Fontainebleau sandstone is made of fine quartz grains with regular grain size (≈250 μm). Permeability was measured with a falling head permeameter. Velocities and attenuations were obtained either through an ultrasonic experiment for frequencies around 500 kHz or through a resonant bar technique experiment for frequencies around 5 kHz and in both cases with varying water saturation. The results show an excellent correlation between permeability k and total porosity ϕ for all our samples. For low porosities (ϕ = 3% to 9%), permeability (in millidarcies) is 2.75×10 −5 (ϕ) 7.33 , while for high porosities (ϕ = 9% to 28%), permeability k (in millidarcies) is given by 0.303(ϕ) 3.05 . The correlation is also excellent between free porosity and total porosity. On the other hand the correlation between acoustic properties and total porosity is not as clear as for hydraulic properties whatever the frequency (500 kHz or 5 kHz) or the water saturation. On the average, velocity decreases, and attenuation roughly increases with increasing total porosity. Velocity and attenuation values are related to the variation of grain contact structure, and two samples with the same porosity and permeability may exhibit different velocities and attenuations. The clear correlation between hydraulic properties and porosity is related to constant grain size, while the lack of correlation for acoustic properties emphasizes the importance of the microstructure.
Hetero-Domain Interactions as a Mechanism for the Regulation of Connexin Channels (1999)

Previous studies have shown that chemical regulation of connexin43 (Cx43) depends on the presence of the carboxyl terminal (CT) domain. A particle-receptor (or "ball-and-chain") model has been proposed to explain the mechanism of gating. We tested whether the CT region behaved as a functional domain for other members of the connexin family. The pH sensitivity of wild-type and Ct-truncated connexins was quantified by use of electrophysiological and optical techniques and the Xenopus oocyte system. The CT domain of Cx45 had no role in pH regulation, although a partial role was shown for Cx37 and Cx50. A prominent effect was observed for Cx40 and Cx43. In addition, we found that the CT domain of Cx40 that was expressed as a separate fragment rescued the pH sensitivity of the truncated Cx40 (Cx40tr), which was in agreement with a particle-receptor model. Because Cx40 and Cx43 often colocalize and possibly heteromerize, we tested the pH sensitivity of Cx40tr when coexpressed with the CT domain of Cx43 (hetero-domain interactions). We found that the CT domain of Cx43 enhanced the pH sensitivity of Cx40tr; similarly, the CT domain of Cx40 restored the pH sensitivity of the truncated Cx43. In addition, the CT domain of Cx43 granted insulin sensitivity to the otherwise insulin-insensitive Cx26 or Cx32 channels. These data show that the particle-receptor model is preserved in Cx40 and the regulatory domain of one connexin can specifically interact with a channel formed by another connexin. Hetero-domain interactions could be critical for the regulation of heteromeric channels.
Synthesis of Spherical Silver Nanoparticles with Controllable Sizes in Aqueous Solutions (2007)

A new method that combines the seed technique with laser treatment of a synthesized colloid was used to prepare spherical, almost monodisperse silver nanoparticles ranging in diameter from 10 to 80 nm (±10%). Particles in the 10−40 nm size range can easily be produced in a one-step synthesis. Preparation of particles in the 40−60 nm range requires a multistep synthesis that involves laser treatment of the synthesized colloid. Particles larger than 60 nm were produced using a multistep synthesis with laser treatment of intermediate products. Appropriate “soft” conditions were developed for the laser treatment, where “soft” laser fluence was defined as the maximum possible fluence that heats and melts but does not evaporate the spherical particles and, therefore, does not change their sizes. The numerical values for this fluence were calculated for different particle diameters using the particle heating−melting−evaporation model.35,21 The criteria for application of this model are discussed.
Introduction of an activated N-ras oncogene alters the growth characteristics of the interleukin 6-dependent myeloma cell line ANBL6. (1995)

Multiple myeloma (MM) is a late-stage B-cell cancer with an unknown etiology. Activating mutations of the N-ras and K-ras oncogenes occur with a high frequency in myeloma and, therefore, may play a role in the pathogenesis of the disease. To study the role of N-ras-activating mutations in the regulation of myeloma tumor growth, we introduced a constitutively active N-ras cDNA containing a glutamine to arginine (CAA-CGA) amino acid substitution at codon 61 into the interleukin 6 (IL-6)-dependent myeloma cell line ANBL6. Expression of the mutant N-ras cDNA resulted in significant IL-6-independent growth, as well as augmentation of growth at suboptimal concentrations of IL-6. The IL-6-independent growth pattern was not the result of activation of autocrine IL-6 production in the mutant N-ras-expressing population because neutralizing antibodies to the IL-6 receptor and to IL-6 had no effect on the rate of DNA synthesis in the absence of IL-6. Furthermore, mutant N-ras expression decreased the percentage of cells undergoing apoptosis in the absence of IL-6. These data suggest that activating mutations of the ras oncogenes may result in growth factor independence accompanied by a suppression of apoptosis in MM. Therefore, the use of therapies designed to block IL-6 action in MM may have less of an impact on tumors bearing activated ras mutations.
Atomic disorder effects on half-metallicity of the full-Heusler alloysCo2(Cr1−xFex)Al:A first-principles study (2004)

We investigate the atomic disorder effects on the half-metallicity of the full-Heusler alloy ${\mathrm{Co}}_{2}({\mathrm{Cr}}_{1\ensuremath{-}x}{\mathrm{Fe}}_{x})\mathrm{Al}$ from first principles by using the Korringa-Kohn-Rostoker method with the coherent potential approximation. Our results show that disorder between Cr and Al does not significantly reduce the spin polarization of the parent alloy ${\mathrm{Co}}_{2}\mathrm{CrAl},$ while disorder between Co and Cr makes a considerable reduction of the spin polarization. It is observed that the spin polarization of ${\mathrm{Co}}_{2}({\mathrm{Cr}}_{1\ensuremath{-}x}{\mathrm{Fe}}_{x})\mathrm{Al}$ decreases with increasing Fe concentration x in both the ordered ${L2}_{1}$ and the disordered $B2$ structures, and that the effects of the disorder on the spin polarization is significant at low Fe concentrations. The results suggest that a highly spin-polarized ferromagnet with high Curie temperature will be obtained if a ${\mathrm{Co}}_{2}({\mathrm{Cr}}_{1\ensuremath{-}x}{\mathrm{Fe}}_{x})\mathrm{Al}$ with the ordered ${L2}_{1}$ structure can be fabricated at low Fe concentrations.
TLR3 and Rig-Like Receptor on Myeloid Dendritic Cells and Rig-Like Receptor on Human NK Cells Are Both Mandatory for Production of IFN-γ in Response to Double-Stranded RNA (2010)

Cross-talk between NK cells and dendritic cells (DCs) is critical for the potent therapeutic response to dsRNA, but the receptors involved remained controversial. We show in this paper that two dsRNAs, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acid [poly(I:C)], similarly engaged human TLR3, whereas only poly(I:C) triggered human RIG-I and MDA5. Both dsRNA enhanced NK cell activation within PBMCs but only poly(I:C) induced IFN-gamma. Although myeloid DCs (mDCs) were required for NK cell activation, induction of cytolytic potential and IFN-gamma production did not require contact with mDCs but was dependent on type I IFN and IL-12, respectively. Poly(I:C) but not polyadenylic-polyuridylic acid synergized with mDC-derived IL-12 for IFN-gamma production by acting directly on NK cells. Finally, the requirement of both TLR3 and Rig-like receptor (RLR) on mDCs and RLRs but not TLR3 on NK cells for IFN-gamma production was demonstrated using TLR3- and Cardif-deficient mice and human RIG-I-specific activator. Thus, we report the requirement of cotriggering TLR3 and RLR on mDCs and RLRs on NK cells for a pathogen product to induce potent innate cell activation.
Internal Fixation of the Lumbar Spine The Hartshill Rectangle (1986)

The Hartshill rectangle fixation is a modification of the Luque system of segmental spinal instrumentation. The rectangle is formed from a 3/16-in stainless steel rod and incorporates a roof that allows it to fit snugly against the lamina and provides good rotational stability. The rectangle is secured to the spine by means of doubled 0.91-mm-diameter stainless steel wires. The technique of the Hartshill system in the lumbar spine is described in detail. The system has been used in 71 patients with good relief of pain and without major complication. In the first 45 cases, a simple, flat, unwelded rectangle was used, and in the last 26 the Hartshill rectangle was employed.
The addition of adenovirus type 5 region E3 enables calydon virus 787 to eliminate distant prostate tumor xenografts. (1999)

CV787, a novel highly prostate-specific replication-competent adenovirus with improved efficacy, was constructed. CV787 contains the prostate-specific rat probasin promoter, driving the adenovirus type 5 (Ad5) E1A gene, and the human prostate-specific enhancer/promoter, driving the E1B gene. To improve efficacy, we constructed CV787 such that it also contains the entire Ad5 E3 region. CV787 replicates in prostate-specific antigen (PSA)+ cells as well as wild-type adenovirus, but in PSA- cells, CV787 replicates 10(4)-10(5) times less efficiently. CV787 destroys PSA+ prostate cancer cells 10,000 times more efficiently than PSA- cells. Incorporation of the Ad5 E3 region significantly improves the target cell killing ability or efficacy of CV787. In nu/nu mice carrying s.c. LNCaP xenografts, a single i.v. tail vein injection of CV787 eliminates 300-mm3 tumors within 4 weeks. CV787 could be a powerful therapeutic for human metastatic prostate cancer.
Maternal Embryonic Leucine Zipper Kinase: Key Kinase for Stem Cell Phenotype in Glioma and Other Cancers (2014)

Maternal embryonic leucine zipper kinase (MELK) is a member of the snf1/AMPK family of protein serine/threonine kinases that has recently gained significant attention in the stem cell and cancer biology field. Recent studies suggest that activation of this kinase is tightly associated with extended survival and accelerated proliferation of cancer stem cells (CSC) in various organs. Overexpression of MELK has been noted in various cancers, including colon, breast, ovaries, pancreas, prostate, and brain, making the inhibition of MELK an attractive therapeutic strategy for a variety of cancers. In the experimental cancer models, depletion of MELK by RNA interference or small molecule inhibitors induces apoptotic cell death of CSCs derived from glioblastoma multiforme and breast cancer, both in vitro and in vivo. Mechanism of action of MELK includes, yet may not be restricted to, direct binding and activation of the oncogenic transcription factors c-JUN and FOXM1 in cancer cells but not in the normal counterparts. Following these preclinical studies, the phase I clinical trial for advanced cancers with OTSSP167 started in 2013, as the first-in-class MELK inhibitor. This review summarizes the current molecular understanding of MELK and the recent preclinical studies about MELK as a cancer therapeutic target.
Luminescent detection of DNA-binding proteins (2011)

Transcription factors play a central role in cell development, differentiation and growth in biological systems due to their ability to regulate gene expression by binding to specific DNA sequences within the nucleus. The dysregulation of transcription factor signaling has been implicated in the pathogenesis of a number of cancers, developmental disorders, inflammation and autoimmunity. There is thus a high demand for convenient high-throughput methodologies able to detect sequence-specific DNA-binding proteins and monitor their DNA-binding activities. Traditional approaches for protein detection include gel mobility shift assays, DNA footprinting and enzyme-linked immunosorbent assays (ELISAs) which tend to be tedious, time-consuming, and may necessitate the use of radiographic labeling. By contrast, luminescence technologies offer the potential for rapid, sensitive and low-cost detection that are amenable to high-throughput and real-time analysis. The discoveries of molecular beacons and aptamers have spear-headed the development of new luminescent methodologies for the detection of proteins over the last decade. We survey here recent advances in the development of luminescent detection methods for DNA-binding proteins, including those based on molecular beacons, aptamer beacons, label-free techniques and exonuclease protection.
The effect of the elevated source/drain doping profile on performance and reliability of deep submicron MOSFETs (1997)

Deep submicron NMOSFETs with elevated source/drain (ESD) were fabricated using self-aligned selective epitaxial deposition and engineered ion implanted profiles in the elevated layers, Deeper source/drain (S/D) junctions give rise to improved drive current over shallower profiles when the same spacer thickness and LDD doping level are used, Shallower junctions, especially with the heavily-doped S/D residing in the elevated layer, give better immunity to drain-induced-barrier lowering (DLBL) and bulk punchthrough. Tradeoffs between short-channel behavior and drive current with regard to S/D junction depth and spacer thickness were further studied using process/device simulations to cover a broader range of structure parameters. Despite the existence of epi facets along the sidewall spacers, the elevated S/D could be used as a sacrificial layer for silicidation, without degradation of the low-leakage junctions. The effects of the elevated S/D doping profile on substrate current and hot-electron-induced degradation were measured and analyzed. The simulated results were used, for the first time, to define the range of spacer thickness and LDD doses that are required in order for the lightly-doped region in the elevated S/D to effectively suppress the lateral electric field.