gebhart/patrepeval huggingface dataset:
Antitumor Activity of a Novel Bispecific Antibody That Targets the ErbB2/ErbB3 Oncogenic Unit and Inhibits Heregulin-Induced Activation of ErbB3 (2012)

The prevalence of ErbB2 amplification in breast cancer has resulted in the heavy pursuit of ErbB2 as a therapeutic target. Although both the ErbB2 monoclonal antibody trastuzumab and ErbB1/ErbB2 dual kinase inhibitor lapatinib have met with success in the clinic, many patients fail to benefit. In addition, the majority of patients who initially respond will unfortunately ultimately progress on these therapies. Activation of ErbB3, the preferred dimerization partner of ErbB2, plays a key role in driving ErbB2-amplified tumor growth, but we have found that current ErbB2-directed therapies are poor inhibitors of ligand-induced activation. By simulating ErbB3 inhibition in a computational model of ErbB2/ErbB3 receptor signaling, we predicted that a bispecific antibody that docks onto ErbB2 and subsequently binds to ErbB3 and blocks ligand-induced receptor activation would be highly effective in ErbB2-amplified tumors, with superior activity to a monospecific ErbB3 inhibitor. We have developed a bispecific antibody suitable for both large scale production and systemic therapy by generating a single polypeptide fusion protein of two human scFv antibodies linked to modified human serum albumin. The resulting molecule, MM-111, forms a trimeric complex with ErbB2 and ErbB3, effectively inhibiting ErbB3 signaling and showing antitumor activity in preclinical models that is dependent on ErbB2 overexpression. MM-111 can be rationally combined with trastuzumab or lapatinib for increased antitumor activity and may in the future complement existing ErbB2-directed therapies to treat resistant tumors or deter relapse.
Distinct effects of two CD44 isoforms on tumor growth in vivo. (1991)

Tumor growth is dependent in part on interactions between tumor cells and the extracellular matrix of host tissues. Expression of the cell surface glycoprotein CD44/Pgp-1, which mediates cell-substrate interactions is increased in many types of malignancies, but the role of CD44 in tumor growth is largely undefined. Recently, two isoforms of CD44 have been identified: an 80-90 kD form, which has high affinity for cell bound hyaluronate and a 150 kD form which does not mediate attachment to hyaluronate-coated surfaces. In this work, human B cell lymphoma cells stably transfected with cDNA clones encoding either of the two CD44 isoforms were compared for tumorigenicity and metastatic potential in nude mice. Expression of the 80-90 kD form but not the 150 kD form of CD44 greatly enhanced both local tumor formation and metastatic proclivity of the lymphoma cells. Our results suggest that CD44 polypeptides may play an important role in regulating primary and metastatic tumor development in vivo.
Modulated filter banks with arbitrary system delay: efficient implementations and the time-varying case (2000)

We present a new method for the design and implementation of modulated filter banks with perfect reconstruction. It is based on the decomposition of the analysis and synthesis polyphase matrices into a product of two different types of simple matrices, replacing the polyphase filtering part in a modulated filter bank. Special consideration is given to cosine-modulated as well as time-varying filter banks. The new structure provides several advantages. First of all, it allows an easy control of the input-output system delay, which can be chosen in single steps of input sampling rate, independent of the filter length. This property can be used in audio coding applications to reduce pre-echoes. Second, it results in a structure that is nearly twice as efficient as performing the polyphase filtering directly. Perfect reconstruction is a structurally inherent feature of the new formulation, even for nonlinear operations or time-varying coefficients. Hence, the structure is especially suited for the design of time-varying filter banks where both the number of bands as well as the prototype filters can be changed while maintaining perfect reconstruction and critical sampling. Further, a proof of effective completeness is given, and the design of equal magnitude-response analysis and synthesis filter banks is described. Filter design can be performed by nonconstrained optimization of the matrix coefficients according to a given cost function. Design and audio-coding application examples are given to show the performance of the new filter bank.
The c-Src Tyrosine Kinase Regulates Signaling of the Human DF3/MUC1 Carcinoma-associated Antigen with GSK3β and β-Catenin (2001)

The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in most human carcinomas. The cytoplasmic domain of MUC1 interacts with glycogen synthase kinase 3 beta (GSK3 beta) and thereby decreases binding of MUC1 and beta-catenin. The present studies demonstrate that MUC1 associates with the c-Src tyrosine kinase. c-Src phosphorylates the MUC1 cytoplasmic domain at a YEKV motif located between sites involved in interactions with GSK3 beta and beta-catenin. The results demonstrate that the c-Src SH2 domain binds directly to pYEKV and inhibits the interaction between MUC1 and GSK3 beta. Moreover and in contrast to GSK3 beta, in vitro and in vivo studies demonstrate that c-Src-mediated phosphorylation of MUC1 increases binding of MUC1 and beta-catenin. The findings support a novel role for c-Src in regulating interactions of MUC1 with GSK3 beta and beta-catenin.
Internet Security Association and Key Management Protocol (ISAKMP) (1998)

This memo describes a protocol utilizing security concepts necessary for establishing Security Associations (SA) and cryptographic keys in an Internet environment. A Security Association protocol that negotiates, establishes, modifies and deletes Security Associations and their attributes is required for an evolving Internet, where there will be numerous security mechanisms and several options for each security mechanism. The key management protocol must be robust in order to handle public key generation for the Internet community at large and private key requirements for those private networks with that requirement. The Internet Security Association and Key Management Protocol (ISAKMP) defines the procedures for authenticating a communicating peer, creation and management of Security Associations, key generation techniques, and threat mitigation (e.g. denial of service and replay attacks). All of these are necessary to establish and maintain secure communications (via IP Security Service or any other security protocol) in an Internet environment.
Practical Drug Evaluation Method (1966)

THE EVALUATION of psychopharmacologic agents in an outpatient setting presents special problems. Crossover designs are rarely possible, partly because they take too long and partly because psychiatric status changes too rapidly. Drug-placebo and drugdrug designs are the rule. These designs, however, are most vulnerable to withingroup variability, and psychiatric outpatients tend to be very heterogeneous. There is, therefore, a major need for experimental designs and procedures which minimize withingroup variability. In a recent paper<sup>1</sup>the authors described a method of drug evaluation which was intended to meet these difficulties. The method depended on three critical features: A. In the first two weeks under treatment, psychiatric outpatients typically undergo a marked improvement in Symptomatology.<sup>2-5</sup>Associated with this improvement are large amounts of variability. Some patients improve dramatically while others do not improve at all. In the Florida method all patients are
Drop Mixing in a Microchannel for Lab-on-a-Chip Platforms (2007)

We present theory, simulations, and experiments for discrete drop mixing in microchannels. The drops are placed sequentially in a channel and then moved at a set velocity to achieve mixing. The mixing occurs in three different regimes (diffusion-dominated, dispersion-dominated, and convection-dominated) depending on the Péclet number (Pe) and the drop dimensions. Introducing the modified Péclet number (Pe*), we show asymptotic curves that can be used to predict the mixing time and the required distance for mixing for any of the three regimes. Simulations of the mixing experiments using COMSOL agree with the theoretical limits. In our experimental work, we used a polydimethylsiloxane (PDMS) microchannel with a membrane air bypass valve to remove the air between drops. This approach enables precise control of the mixing and merging site. Experimental, simulation, and theoretical results all agree and show that mixing can occur in fractions of a second to hours, depending on the parameters used.
Discovery of a Potent, Selective, and Orally Active Proteasome Inhibitor for the Treatment of Cancer (2008)

The ubiquitin-proteasome pathway plays a central role in regulation of the production and destruction of cellular proteins. These pathways mediate proliferation and cell survival, particularly in malignant cells. The successful development of the 20S human proteasome inhibitor bortezomib for the treatment of relapsed and refractory multiple myeloma has established this targeted intervention as an effective therapeutic strategy. Herein, the potent, selective, and orally bioavailable threonine-derived 20S human proteasome inhibitor that has been advanced to preclinical development, [(1R)-1-[[(2 S,3 R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]-1-oxobutyl]amino]-3-methylbutyl]boronic acid 20 (CEP-18770), is disclosed.
Expression of epidermal growth factor receptors and c-erbB-2 proteins in human astrocytic tumors. (1997)

Tumorigenesis is the result of sequential or multiple genetic alterations. The overexpression or amplification of various oncogenes in diverse human brain tumors have been observed. While numerous studies on the immunohistochemical demonstration of EGFR-overexpression have been reported, little has been found in the literature about the c-erbB-2 protein in human astrocytic tumors. In the present study, we evaluated the expression of EGFR and c-erbB-2 protein in 33 astrocytic tumors with immunohistochemistry. According to the World Health Organization brain tumor classification, the study included 9 low-grade astrocytomas (grade 2), 15 anaplastic astrocytomas (grade 3), and 9 glioblastomas multiforme (grade 4). The positive EGFR immunoreactivity was detected in 28 (85%) of 33 tumors. The expression of EGFR increased with the grade of malignancy in low-grade astrocytomas (67%), anaplastic astrocytomas (87%), and glioblastomas (100%). For the expression of c-erbB-2 protein, 17 (51.5%) of 33 tumors were positive immunostain, including 3 low-grade astrocytomas (37.5%), 9 anaplastic astrocytomas (81.8%), and 5 glioblastomas (62.5%). Different degrees of immunoreactivity for c-erbB-2 protein were found in variant grades of astrocytomas. However, the positive immunostain of EGFR displayed moderate or strong reactivity. The coexpression of EGFR and c-erbB-2 protein was found in 17 (15.5%) of 33 tumors. The results emphasize that the overexpression of EGFR parallels astrocytoma progession and higher frequency of c-erbB-2 immunoreactivity was seen in snaplastic astrocytomas and glioblastomas than in low-grade astrocytomas.
The Moderating Effect of Age on Self-Care (1996)

The study examined the moderating effect of age on the relations between symptom severity, self-care and others' care, patients' perception of the extent of problem solution, their satisfaction with the solution, and their perception of control over their health. Participating in the study were 121 female and 167 male chronically ill patients. Results indicated that age did play a major role in the relations between self-care and others' care and self-care outcomes. The young population sought maximum relief of symptoms with minimum effort from the self. The elderly, in contrast, could be said fo maximize control because what was important for them was not to depend on others but to be self-sufficient in solving their health problems.
CCR3 blockade as a new therapy for asthma (2000)

Among the inflammatory cells infiltrating the lungs of asthmatic patients, eosinophils and Th2 cells are thought to play a central role in the pathogenesis of this disease. Several studies have implicated that chemokines are prime candidates for being responsible for the selective recruitment of the leukocyte subsets found in atopic diseases. Regulated upon activation, normal T-cell-expressed and secreted (RANTES), monocyte chemoattractant protein-3 (MCP-3), MCP-4 and the eotaxins, for example, have been shown in vitro to potently induce eosinophil chemotaxis as well as initiate several other pro-inflammatory activities such as integrin activation, lipid mediator biosynthesis and degranulation. Ligand binding and chemotaxis experiments with these chemokines demonstrated that a G-protein coupled-receptor (GPCR) cloned from eosinophils, termed CCR3, was responsible for producing a chemokine selectivity profile identical to that of eosinophils. In addition, blocking CCR3 on eosinophils, with a monoclonal antibody, completely abolished eosinophil responses to these chemokines. Together these studies strongly suggest a central role for this receptor in eosinophil trafficking. CCR3 has also been found on in vitro derived Th2 cells and on T-cells co-localising with eosinophils in diseased tissue, thus revealing a possible pathogenic mechanism for T-cell recruitment into the airways. Therefore, blockade of CCR3 represents a highly attractive and innovative strategy for asthma therapy.
Spatial and Temporal Expression Patterns of the Epithelial Cell Adhesion Molecule (EpCAM/EGP-2) in Developing and Adult Kidneys (2007)

The spatiotemporal expression pattern of EpCAM changes during nephrogenesis. In the adult kidney, the expression varies markedly along the nephron. These data provide a basis for further studies on EpCAM in developing and adult kidneys.
Dual-specific Chimeric Antigen Receptor T Cells and an Indirect Vaccine Eradicate a Variety of Large Solid Tumors in an Immunocompetent, Self-antigen Setting (2016)

<b>Purpose:</b> While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model.<b>Experimental Design:</b> In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including orthotopic breast tumors and large liver tumors.<b>Results:</b> ACTIV therapy induced durable complete remission of a variety of Her2<sup>+</sup> tumors, some in excess of 150 mm<sup>2</sup>, in immunocompetent mice expressing Her2 in normal tissues, including the breast and brain. Vaccinia virus induced extensive proliferation of T cells, leading to massive infiltration of T cells into tumors. Durable tumor responses required the chemokine receptor CXCR3 and exogenous IL2, but were independent of IFNγ. Mice were resistant to tumor rechallenge, indicating immune memory involving epitope spreading. Evidence of limited neurologic toxicity was observed, associated with infiltration of cerebellum by T cells, but was only transient.<b>Conclusions:</b> This study supports a view that it is possible to design a highly effective combination immunotherapy for solid cancers, with acceptable transient toxicity, even when the target antigen is also expressed in vital tissues. <i>Clin Cancer Res; 23(10); 2478-90. ©2016 AACR</i>.
Spot‐blot analysis of sorted chromosomes assigns a fructose intolerance disease locus to chromosome 9 (1985)

The aldolase B gene was mapped to chromosome 9 using a rapid gene mapping system. This system uses a dual-laser sorter to identify and separate metaphase human chromosomes stained with either DIPI-chromomycin or Hoechst-chromomycin. Chromosome panels were constructed from a normal cell line by sorting 22 chromosome fractions directly onto nitrocellulose filters. Twelve labeled gene probes hybridized to the sorted chromosomal DNA fractions predicted by previous chromosome assignments. Eighteen newly cloned genes have been mapped using the same protocol.
Digital's Alpha project (1993)

article Free Access Share on Digital's Alpha project Author: Robert M. Supnik Digital Equipment Corp. Digital Equipment Corp.View Profile Authors Info & Claims Communications of the ACMVolume 36Issue 2Feb. 1993pp 30–32https://doi.org/10.1145/151220.151223Published:01 February 1993Publication History 3citation241DownloadsMetricsTotal Citations3Total Downloads241Last 12 Months15Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Publisher SiteeReaderPDF
Ligand−Receptor Interactions in Chains of Colloids:  When Reactions Are Limited by Rotational Diffusion (2007)

We discuss the theory of ligand receptor reactions between two freely rotating colloids in close proximity to one other. Such reactions, limited by rotational diffusion, arise in magnetic bead suspensions where the beads are driven into close contact by an applied magnetic field as they align in chainlike structures. By a combination of reaction-diffusion theory, numerical simulations, and heuristic arguments, we compute the time required for a reaction to occur in a number of experimentally relevant situations. We find in all cases that the time required for a reaction to occur is larger than the characteristic rotation time of the diffusion motion tau(rot). When the colloids carry one ligand only and a number n of receptors, we find that the reaction time is, in units of tau(rot), a function simply of n and of the relative surface alpha occupied by one reaction patch alpha = pirC2/(4pir2), where rC is the ligand receptor capture radius and r is the radius of the colloid.
[The changing trends of expression of VEGF and its relationship with the levels of NO in rat corpus luteum of pseudopregnant]. (2005)

There is a intimate temporal relationship between the expression of VEGF and angiogenesis in corpus luteum, VEGF may play a role in luteum formation by improving angiogenesis mediated by NO, NO may play a role in luteum regression as a luteolytic during the late luteal phase.
Loss of Oocytes in Dazl Knockout Mice Results in Maintained Ovarian Steroidogenic Function but Altered Gonadotropin Secretion in Adult Animals (2000)

Within 2 days of birth, the mouse ovary is mainly composed of oocytes surrounded by a few pregranulosa cells forming primordial follicles that remain quiescent until they are recruited by intraovarian or other unknown factors to initiate growth of the oocyte and proliferation of the attendant granulosa cells. However, the role of the oocyte in this early development and organization of the follicle is poorly understood. The Dazl knockout (-/-) mouse in which there is total ablation of oocytes in fetal life has allowed us to address this issue. Ovaries from -/- females lack any follicular structure and have no cells positive for either Mullerian inhibiting factor or sulfated glycoprotein-1, indicating a lack of small follicles or corpora lutea. However, by immunocytochemistry, there are cells positive for 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase, and aromatase, indicating the presence of steroidogenically active cells capable of producing estrogen. This was confirmed by the presence of hypertrophied uterine endometrium expressing both estrogen receptor alpha (ER alpha) and ER beta together with normal levels of plasma estradiol. In addition, these steroidogenically active cells contain ER beta, inhibin alpha, and betaB-subunits, and -/- mice have low measurable plasma inhibin A and B levels. The ovarian steroids and inhibins had no significant effect on either plasma or pituitary gonadotropin levels, with significantly (P < 0.01) lower LH and FSH in intact +/+ and +/- females. However, significantly (P < 0.05) increased plasma inhibin B together with significantly (P < 0.05) lower FSH were observed in the +/- females. In conclusion, our data showed that despite oocyte loss in fetal life, the adult ovaries contained steroidogenically active cells capable of producing estradiol and inhibin. Furthermore, in the +/- mice, the enhanced plasma inhibin B implies a role for Dazl protein within the oocyte either from more small follicles or increased inhibin B production from each follicle.
Interleukin-32 induces the differentiation of monocytes into macrophage-like cells (2008)

After emigration from the bone marrow to the peripheral blood, monocytes enter tissues and differentiate into macrophages, the prototype scavenger of the immune system. By ingesting and killing microorganisms and removing cellular debris, macrophages also process antigens as a first step in mounting a specific immune response. IL-32 is a cytokine inducing proinflammatory cytokines and chemokines via p38-MAPK and NF-kappaB. In the present study, we demonstrate that IL-32 induces differentiation of human blood monocytes as well as THP-1 leukemic cells into macrophage-like cells with functional phagocytic activity for live bacteria. Muramyl dipepide (MDP), the ligand for the intracellular nuclear oligomerization domain (NOD) 2 receptor, has no effect on differentiation alone but augments the monocyte-to-macrophage differentiation by IL-32. Unexpectedly, IL-32 reversed GM-CSF/IL-4-induced dendritic cell differentiation to macrophage-like cells. Whereas the induction of TNFalpha, IL-1beta, and IL-6 by IL-32 is mediated by p38-MAPK, IL-32-induced monocyte-to-macrophage differentiation is mediated through nonapoptotic, caspase-3-dependent mechanisms. Thus, IL-32 not only contributes to host responses through the induction of proinflammatory cytokines but also directly affects specific immunity by differentiating monocytes into macrophage-like cells.
Drilling technology/GDO (1985)

The Geothermal Technology Division of the US Department of Energy is sponsoring two programs related to drilling technology. The first is aimed at development of technology that will lead to reduced costs of drilling, completion, and logging of geothermal wells. This program has the official title ''Hard Rock Penetration Mechanics.'' The second program is intended to share with private industry the cost of development of technology that will result in solutions to the near term geothermal well problems. This program is referred to as the ''Geothermal Drilling Organization''. The Hard Rock Penetration Mechanics Program was funded at $2.65M in FY85 and the GDO was funded at $1.0M in FY85. This paper details the past year's activities and accomplishments and projects the plans for FY86 for these two programs.
Vector Targeting Makes 5-Fluorouracil Chemotherapy Less Toxic and More Effective in Animal Models of Epithelial Neoplasms (2004)

Replacement of 5-FU in 5-FU-based combination chemotherapy with the Ad-LpCDIRESE1A vector and 5-FU reduces toxicity and increases efficacy. This is a concept that could be potentially applied widely for many forms of cancer treatment.