gebhart/patrepeval huggingface dataset:
Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors (2009)

The epidermal growth factor receptor- (EGFR-) directed antibody, cetuximab, was FDA-approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 2006. Additional EGFR-targeting agents in clinical development for SCCHN include other EGFR-directed antibodies, tyrosine kinase inhibitors and antisense DNA. Although the majority of SCCHN overexpress EGFR, SCCHN clinical responses to EGFR-targeting agents have been modest. Molecular predictors for SCCHN response to EGFR-targeted therapies have not been identified. However, molecular correlate studies in lung cancer and colon cancer, which have EGFR-targeted therapeutics FDA-approved for treatment, may provide insights. We describe candidate predictive markers for SCCHN response to EGFR-targeted therapies and their prevalence in SCCHN. Clinical response will likely be improved by targeted therapy combination treatments. Src family kinases mediate EGFR-dependent and -independent tumor progression pathways in many cancers including SCCHN. Several Src-targeting agents are in clinical development for solid malignancies. Molecular correlate studies for Src-targeting therapies are few and biomarkers correlated with patient response are limited. Identifying SCCHN patients who will respond to combined EGFR- and Src-targeting will require further characterization of molecular correlates. We discuss rationale for EGFR and Src co-targeting for SCCHN treatment and describe recent clinical trials implementing combined Src- and EGFR-targeted therapeutics.
A Gene Regulatory Network Cooperatively Controlled by Pdx1 and Sox9 Governs Lineage Allocation of Foregut Progenitor Cells (2015)

The generation of pancreas, liver, and intestine from a common pool of progenitors in the foregut endoderm requires the establishment of organ boundaries. How dorsal foregut progenitors activate pancreatic genes and evade the intestinal lineage choice remains unclear. Here, we identify Pdx1 and Sox9 as cooperative inducers of a gene regulatory network that distinguishes the pancreatic from the intestinal lineage. Genetic studies demonstrate dual and cooperative functions for Pdx1 and Sox9 in pancreatic lineage induction and repression of the intestinal lineage choice. Pdx1 and Sox9 bind to regulatory sequences near pancreatic and intestinal differentiation genes and jointly regulate their expression, revealing direct cooperative roles for Pdx1 and Sox9 in gene activation and repression. Our study identifies Pdx1 and Sox9 as important regulators of a transcription factor network that initiates pancreatic fate and sheds light on the gene regulatory circuitry that governs the development of distinct organs from multi-lineage-competent foregut progenitors.
Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors (2014)

The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease.
CASE Weight Test: A hands on approach to comparing and selecting CASE tools at Twentieth Century Services (2016)

Citation: Eaton, R. &amp; Hayes, K. (1991). CASE Weight Test: A hands on approach to comparing and selecting CASE tools at Twentieth Century Services. CASE Trends: The Magazine for Computer-Aided Software Engineering, 3(8), 18-19
Numerical Modeling of Radial, Astigmatic, and Hexagonal Keratotomy (1992)

The proposed computational model of the cornea and the effects of surgical procedures on it is based on a number of important simplifying assumptions regarding the mechanical properties and structure of the corneal tissue at the ultrastructure level. The encouraging results found with present model suggest that further development and refinement will be useful.
Murine epidermal growth factor (EGF) fragment (33-42) inhibits both EGF- and laminin-dependent endothelial cell motility and angiogenesis. (1995)

Laminin, murine epidermal growth factor (mEGF), and the synthetic laminin peptide Lam.B1(925-933) (a linear peptide from the B1 chain of murine laminin, CDPGY1GSR-amide) all stimulate endothelial cell motility above basal rates, whereas a synthetic mEGF fragment, mEGF33-42 (a linear peptide from the C-loop of mEGF, acetyl-C-[S-Acm]-VIGYSGDR-C-[S-Acm]-amide), inhibits motility. In both human SK HEP-1 and embryonic chick endothelial cells, mEGF33-42 blocks both EGF- and laminin-stimulated locomotion of endothelial cells. In vivo, mEGF33-42 also blocks both laminin- and mEGF-induced angiogenesis in the chick. In the human cell line. Lam.B1(925-933) has an additive effect in coincubation with either laminin or mEGF, but it blocks their effects in the chick cells. Lam.B1(925-933) alone stimulates angiogenesis in the chick but blocks laminin-induced angiogenesis. Thus, mEGF33-42 acts as a general laminin antagonist, whereas Lam.B1(925-933) acts as a laminin agonist in human cells, but in chick cells it acts as a partial antagonist. We propose that the presence of an anionic group at the eighth residue of mEGF33-42 may be the source of the antagonistic effects seen with this peptide as compared with the laminin fragment. These findings have important implications in the design of human antiangiogenic agents, and also in the use of chick models in the study of human disease.
A Critical Intramolecular Interaction for Protein Kinase Cϵ Translocation (2004)

Disruption of intramolecular interactions, translocation from one intracellular compartment to another, and binding to isozyme-specific anchoring proteins termed RACKs, accompany protein kinase C (PKC) activation. We hypothesized that in inactive epsilonPKC, the RACK-binding site is engaged in an intramolecular interaction with a sequence resembling its RACK, termed psiepsilonRACK. An amino acid difference between the psiepsilonRACK sequence in epsilonPKC and its homologous sequence in epsilonRACK constitutes a change from a polar non-charged amino acid (asparagine) in epsilonRACK to a polar charged amino acid (aspartate) in epsilonPKC. Here we show that mutating the aspartate to asparagine in epsilonPKC increased intramolecular interaction as indicated by increased resistance to proteolysis, and slower hormone- or PMA-induced translocation in cells. Substituting aspartate for a non-polar amino acid (alanine) resulted in binding to epsilonRACK without activators, in vitro, and increased translocation rate upon activation in cells. Mathematical modeling suggests that translocation is at least a two-step process. Together our data suggest that intramolecular interaction between the psiepsilonRACK site and RACK-binding site within epsilonPKC is critical and rate limiting in the process of PKC translocation.
Direct Detection of Bacterial Biofilms on the Middle-Ear Mucosa of Children With Chronic Otitis Media (2006)

Direct detection of biofilms on MEM biopsy specimens from children with OME and recurrent OM supports the hypothesis that these chronic middle-ear disorders are biofilm-related.
Cytokines in Multiple Myeloma (2007)

Multiple myeloma (MM) is a clonal plasma cell neoplasm which remains incurable despite conventional therapy; and new treatment strategies are therefore urgently required (1,2). MM cells predominantly localize in bone marrow (BM), and their interaction with BM stromal cells (BMSCs) stimulates transcription and secretion of cytokines from BMSCs. Cytokines in turn not only promote the growth and survival of MM cells, but also reduce efficacy of conventional drugs (2). For example, adherence of MM cells to BMSCs triggers interleukin-6 (IL-6) and insulin-like growth factor-I (IGF-I), and vascular endothelial growth factor (VEGF) production from BMSCs, which induces MM cell growth and protect against dexamethasone (Dex)-induced MM apoptosis (3–8). High serum levels of IL-6 and IGF-I in MM patients (9,10) also correlate with clinical drug-resistance in MM. Cytokines trigger three signaling cascades in MM cells: mitogen-activated extracellular kinase 2(MEK)/extracellular signal-regulated kinase (ERK); phosphatidylinositol-3 kinase (PI3-kinase)/AKT; and Janus kinases (JAK)-signal transducer and activator of transcription (STAT) pathways. Novel treatment strategies based on targeting these signaling pathways are now being designed to block cytokine-mediated growth/survival and drug-resistance. In this chapter, we review the role of various cytokines in the biology of MM, as well as novel therapies that overcome cytokine-mediated growth, survival, migration and chemoresistance.
High Linearity and Efficiency Microwave PAs (2004)

An overview on linearity and efficiency performance optimisation in power amplifier (PA) is presented, stressing the required trade-off demanded to PA designers. For efficiency improvement, the harmonic tuning strategies are discussed, with their advantages and major drawbacks. For linearity improvement, the IMD sweet spot optimisation strategies is presented as a solution to obtain low intermodulation near PA saturated condition, resulting in efficiency enhancement with respect to back-off approaches.
Efficient reprogramming of human and mouse primary extra‐embryonic cells to pluripotent stem cells (2009)

Practical clinical applications for current induced pluripotent stem cell (iPSC) technologies are hindered by very low generation efficiencies. Here, we demonstrate that newborn human (h) and mouse (m) extra-embryonic amnion (AM) and yolk-sac (YS) cells, in which endogenous KLF4/Klf4, c-MYC/c-Myc and RONIN/Ronin are expressed, can be reprogrammed to hiPSCs and miPSCs with efficiencies for AM cells of 0.02% and 0.1%, respectively. Both hiPSC and miPSCs are indistinguishable from embryonic stem cells in colony morphology, expression of pluripotency markers, global gene expression profile, DNA methylation status of OCT4 and NANOG, teratoma formation and, in the case of miPSCs, generation of germline transmissible chimeric mice. As copious amounts of human AM cells can be collected without invasion, and stored long term by conventional means without requirement for in vitro culture, they represent an ideal source for cell banking and subsequent 'on demand' generation of hiPSCs for personal regenerative and pharmaceutical applications.
Human dendritic cells and macrophages. In situ immunophenotypic definition of subsets that exhibit specific morphologic and microenvironmental characteristics. (1985)

Using a panel of monoclonal antibodies and antisera in situ, the authors have defined subsets of human dendritic cells and macrophages that exhibit specific morphologic and microenvironmental characteristics. All subsets contained cells that reacted with antibodies directed against HLA-A,B,C, HLA-Dr, leukocyte common, Leu-M3, and Leu-3(T4) antigens. R4/23 and anti-S100 defined three major subsets. R4/23+, S100- cells constituted the B-cell-related follicular dendritic cells, which were identified only within the germinal center/mantle microenvironment of lymphoid follicles. R4/23-, S100+ cells constituted the T-cell-related dendritic cell subset. Anti-Leu-6(T6) further subdivided this group into Leu-6(T6)- interdigitating cells within the T-cell microenvironments of lymphoid organs and Leu-6(T6)+ Langerhans cells found predominantly in epithelial microenvironments, especially the skin. R4/23-, S100- cells constituted the nondendritic tissue macrophage subset which was widely distributed, primarily outside of dendritic-cell microenvironments. These data indicate that although dendritic cells and macrophages share several common antigenic features, morphologically and microenvironmentally distinct subsets express distinct immunologic phenotypes. Such data may provide insight into the ontogeny and function of these subsets and constitute a basis for the comparison of normal dendritic cells and macrophages to various histiocytic proliferative disorders.
Highly Selective Catalytic Conversion of Phenolic Bio‐Oil to Alkanes (2009)

Abstract Öl und Wasser : Eine neue energieeffiziente und atomökonomische katalytische Produktion von Alkanen und Methanol durch Veredelung der phenolischen Fraktion von Bioöl wird vorgestellt. Der in wässriger Phase durchgeführte Eintopf‐Hydrodesoxygenierungsprozess nutzt zwei Katalysatoren, was die Teilreaktionen Hydrierung, Hydrolyse und Dehydratisierung erleichtert. magnified image
The application of electromagnetic measurements for the assessment of skin passed steel samples (2016)

This paper begins by exploring the relationship between magnetic properties such as coercive field, RMS Magnetic Barkhausen Noise (MBN), initial and differential permeability and percentage elongation of skin passed samples for three different steels; interstitial free, micro alloyed and dual phase. A closed magnetic loop system is used to measure the fundamental magnetisation properties and a system based on an impedance analyser and a cylindrical coil is used to determine low field differential permeability. The results show that coercive field increases consistently with increasing percentage elongation for all three steels, as increasing material hardness causes an increase in magnetic hardness and a corresponding increase in coercive field. This effect levels off at higher values as dislocation density saturates. As would be expected, the inverse trend is observed for differential permeability. Similar results are also reported for MBN and initial and low field differential permeability measurements for the interstitial free and dual phase steel, but the behaviour for the micro alloyed samples appears to be more complex. Finally, the paper considers the response of two on-line measurement systems that exploit these magnetic relations. The first system applies pulse excitation and measures the resulting remnant magnetisation and the second analyses the harmonic response from AC excitation. Both systems can detect microstructural changes associated with varying magnetic properties during strip production.
Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome (2014)

Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by developmental abnormalities in several organs including the liver, heart, eyes, vertebrae, kidneys, and face. The majority (90-94%) of ALGS cases are caused by mutations in the JAG1 (JAGGED1) gene, and in a small percent of patients (∼1%) mutations in the NOTCH2 gene have been described. Both genes are involved in the Notch signaling pathway. To date, over 440 different JAG1 gene mutations and ten NOTCH2 mutations have been identified in ALGS patients. The present study was conducted on a group of 35 Polish ALGS patients and revealed JAG1 gene mutations in 26 of them. Twenty-three different mutations were detected including 13 novel point mutations and six large deletions affecting the JAG1 gene. Review of all mutations identified to date in individuals from Poland allowed us to propose an effective diagnostic strategy based on the mutations identified in the reported patients of Polish descent. However, the distribution of mutations seen in this cohort was not substantively different than the mutation distribution in other reported populations.
Three-dimensional laser direct writing: Applications to multichip modules (1994)

Laser direct write deposition and etching have been developed for uses on multichip modules. Instrumentation has been demonstrated for these and other applications on substrates with significant three-dimensional topography.
Oligonucleotides as Research, Diagnostic, and Therapeutic Agents (1995)

Rapid drug discovery is a pressing need in the pharmaceutical industry. As new target proteins are proposed for therapeutic intervention, the methods of random screening or rational drug design may not be adequate to the challenge. SELEX1(1) -derived oligonucleotides, possessing shapes that interact with target molecules, may provide a surprising alternative to other ligand discovery technologies. In addition, the technology leads to a novel research idea that may enrich our understanding of the mechanisms by which cells and organisms integrate their metabolic activities.
Context-Aware Saliency Detection (2011)

We propose a new type of saliency—context-aware saliency—which aims at detecting the image regions that represent the scene. This definition differs from previous definitions whose goal is to either identify fixation points or detect the dominant object. In accordance with our saliency definition, we present a detection algorithm which is based on four principles observed in the psychological literature. The benefits of the proposed approach are evaluated in two applications where the context of the dominant objects is just as essential as the objects themselves. In image retargeting, we demonstrate that using our saliency prevents distortions in the important regions. In summarization, we show that our saliency helps to produce compact, appealing, and informative summaries.
Cell apoptosis and proliferation in obstructive uropathy. (1998)

Distinct patterns of cell proliferation and apoptosis have been recognized for tubular, interstitial, and glomerular cells in chronic obstructive uropathy (OU). In many experimental models of OU, tubular cell apoptosis develops quickly after ureter ligation, peaks between 7 and 24 days postobtruction (about 30-fold of control), and tapers thereafter. Apoptosis initially involves the dilated collecting ducts, but subsequently spreads to other tubules. Tubular cell apoptosis probably accounts for renal tissue loss in OU because a direct correlation between its degree and the decline in dry kidney weight is well-documented. Pronounced tubular cell proliferation occurs shortly after ureter ligation, peaks at about day 6 (60-fold above control), and quickly subsides to baseline. Because the peak of tubular cell proliferation immediately precedes the onset of tubular cell apoptosis, a pathogenetic link may exist between these two processes. Interstitial cell apoptosis occurs with an increasing frequency throughout the course of OU (up to 35-fold above control). Interstitial cell proliferation appears in a bimodal pattern with the early peak coinciding with that of tubular cell proliferation and consisting mostly of fibroblasts, whereas the later peak consists mostly of inflammatory cells. Glomerular cell apoptosis and proliferation are not different from control, which explains, in part, the structural integrity of the glomeruli throughout the disease course. Although the general pathways of cell apoptosis and proliferation are well known, the molecular control of these processes in OU is poorly understood. In addition, whether apoptosis or proliferation of tubular and interstitial cells is differentially regulated remains to be studied. However, several molecules known to be activated or overexpressed in kidney with OU may modulate cell apoptosis and proliferation. The relevant functions of these molecules include induction of apoptosis (angiotensin II, reactive oxygen species, jun-N-terminal kinase, p53), inhibition of the cell cycle (transforming growth factor-beta, p21), inhibition of apoptosis (clusterin, epidermal growth factor, insulin-like growth factor, bcl-2, osteopontin), or promotion of interstitial fibroblast proliferation (platelet-derived growth factor).
Analysis of T-cell receptor alpha/beta variability in lymphocytes infiltrating a melanoma metastasis. (1992)

Multiple experimental and clinical studies have suggested that the immune system may, to some extent, control the development of melanomas. The presence of tumor-infiltrating lymphocytes could reflect an in situ immune reaction directed to the malignant cells. The characterization of T-cell receptor (TCR) expressed by tumor-infiltrating lymphocytes is one way to precisely analyze these local T-cell responses. In this study, we have assessed the TCR alpha/beta variability in tumor-infiltrating lymphocytes from a subcutaneous metastasis of a melanoma patient. Using the anchored-polymerase chain reaction 268 TCR alpha and 266 TCR beta chain transcripts have been cloned and sequenced. Their analysis shows that the T-cell infiltrate is extremely diverse, with no preferential TCR gene segment usage.
<title>LaneTrak: a vision-based automatic vehicle steering system</title> (1993)

Computer vision technology that automatically steers a passenger vehicle to keep it in its lane on a limited-access freeway is described. This system, LaneTrak, uses a forward looking monochrome CCD camera and a real-time image processing system on-board the vehicle. The image processing system identifies the lane boundaries based on lane markers and road edges. A pair of Kalman filters uses this information combined with vehicle dynamics sensor data to determine the vehicle angular heading error, lateral offset from the center of the road, and the lane curvature ahead. A preview proportional-integral control system determines the desired steering angle to keep the vehicle in the lane. The steering angle is then passed to another controller which activates an electric steering mechanism that positions the front wheels of the vehicle. We verified the full operation of LaneTrak with computer simulation before the system was designed and used a driving simulator to evaluate drivers' reaction to system failure. LaneTrak has been successfully demonstrated on a test track and on an unopened section of a limited-access freeway at highway speeds.
Comparison of scaled floating body RAM architectures (2008)

In this work, we have compared different FB-RAM architectures. Whereas highly doped PDSOI devices show high programming window and retention times for long channel devices, the SOI FinFET devices with WFIN=25nm can be scaled down to LG=50nm while still maintaining high cell margins and retention times. For the latter devices optimization of the write and especially read bias conditions is needed.