gebhart/patrepeval huggingface dataset:
Strategies for Generating Diverse Antibody Repertoires Using Transgenic Animals Expressing Human Antibodies (2018)

Therapeutic molecules derived from antibodies have become a dominant class of drugs used to treat human disease. Increasingly, therapeutic antibodies are discovered using transgenic animal systems that have been engineered to express human antibodies. While the engineering details differ, these platforms share the ability to raise an immune response that is comprised of antibodies with fully human idiotypes. Although the predominant transgenic host species has been mouse, the genomes of rats, rabbits, chickens, and cows have also been modified to express human antibodies. The creation of transgenic animal platforms expressing human antibody repertoires has revolutionized therapeutic antibody drug discovery. The observation that the immune systems of these animals are able to recognize and respond to a wide range of therapeutically relevant human targets has led to a surge in antibody-derived drugs in current development. While the clinical success of fully human monoclonal antibodies derived from transgenic animals is well established, recent trends have seen increasingly stringent functional design goals and a shift in difficulty as the industry attempts to tackle the next generation of disease-associated targets. These challenges have been met with a number of novel approaches focused on the generation of large, high-quality, and diverse antibody repertoires. In this perspective, we describe some of the strategies and considerations we use for manipulating the immune systems of transgenic animal platforms (such as XenoMouse<sup>®</sup>) with a focus on maximizing the diversity of the primary response and steering the ensuing antibody repertoire toward a desired outcome.
“Living” Free Radical Photopolymerization Initiated from Surface-Grafted Iniferter Monolayers (1999)

A method for chemically modifying a surface with grafted monolayers of initiator groups, which can be used for a “living” free radical photopolymerization, is described. By using “living” free radical polymerizations, we were able to control the length of the grafted polymer chains and therefore the layer thickness up to ∼100 nm. Also, single-layer grafted block copolymers were obtained by subsequent polymerizations of styrene and methyl methacrylate monomers. The surface-grafted polymer and block copolymer layers were evidenced by direct imaging methods (transmission and scanning electron microscopy) and by indirect surface characterization methods (contact angle measurements, SFM, XPS, and IR). The ability to control the thickness of the grafted polymer as well as the synthesis of a grafted block copolymer layer in a well-defined manner affirms the “living” character of the surface-initiated free radical photopolymerization.
In vitro cytocidal effect of lytic peptides on several transformed mammalian cell lines. (1992)

Several types of transformed mammalian cells, derived from established cell lines, were found to be lysed in vitro by three novel lytic peptides (SB-37, SB-37*, and Shiva-1). This is in contrast with the behavior of normal cells, where the observed lytic activity of the peptides is greatly reduced. Based on experiments utilizing compounds which disrupt the cytoskeleton (colchicine and cytochalasin-D), it is surmised that alterations in the cytoskeleton of transformed cells increase their sensitivity to the cytolytic activity exerted by the peptides, primarily by causing a loss of osmotic integrity. Thus, a stable and regenerative cytoskeletal system, as that possessed by normal cells, would seem requisite to withstanding the lytic effects of the peptides.
Suppression of Apoptosis by Nitric Oxide via Inhibition of Interleukin-1β–converting Enzyme (ICE)-like and Cysteine Protease Protein (CPP)-32–like Proteases (1997)

Physiological levels of shear stress alter the genetic program of cultured endothelial cells and are associated with reduced cellular turnover rates and formation of atherosclerotic lesions in vivo. To test the hypothesis that shear stress (15 dynes/cm2) interferes with programmed cell death, apoptosis was induced in human umbilical venous cells (HUVEC) by tumor necrosis factor-alpha (TNF-alpha). Apoptosis was quantified by ELISA specific for histone-associated DNA-fragments and confirmed by demonstrating the specific pattern of internucleosomal DNA-fragmentation. TNF-alpha (300 U/ml) mediated increase of DNA-fragmentation was completely abrogated by shear stress (446 +/- 121% versus 57 +/- 11%, P <0.05). This anti-apoptotic activity of shear stress decreased after pharmacological inhibition of endogenous nitric oxide (NO)-synthase by NG-monomethyl-L-arginine and was completely reproduced by exogenous NO-donors. The activation of interleukin-1beta-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like cysteine proteases was required to mediate TNF-alpha-induced apoptosis of HUVEC. Endothelial-derived nitric oxide (NO) as well as exogenous NO donors inhibited TNF-alpha-induced cysteine protease activation. Inhibition of CPP-32 enzyme activity was due to specific S-nitrosylation of Cys 163, a functionally essential amino acid conserved among ICE/CPP-32-like proteases. Thus, we propose that shear stress-mediated NO formation interferes with cell death signal transduction and may contribute to endothelial cell integrity by inhibition of apoptosis.
Stability of flucytosine in an extemporaneously compounded oral liquid (1996)

The stability of flucytosine in an oral liquid prepared from capsules was studied. Flucytosine 10-mg/ml oral liquid was prepared from 500-mg capsules (with distilled water as the diluent) and transferred to 10 glass and 10 plastic amber bottles. Five of each type of bottle were stored at 4 degrees C and five of each at 25 degrees C. Samples were taken at 0, 7, 14, 28, 42, 56, 70, and 91 days, and flucytosine concentration was measured by stability-indicating high-performance liquid chromatography. Flucytosine was stable in the liquid formulation for at least 70 days under all the study conditions. The physical appearance of the liquid stored at 4 degrees C did not change during the study period. Flocculation was observed both in glass and in plastic bottles stored at 25 degrees C on day 14 and thereafter. Flucytosine 10 mg/mL in an extemporaneously prepared oral liquid was stable for 70 days in glass or plastic prescription bottles kept at 4 or 25 degrees C.
The Regulation of Angular Momentum During Human Walking (2003)

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Physics, 2003.
A Perspective on Medical Robotics (2006)

This paper provides an overview of medical robotics, from the perspective of a researcher who has been actively involved in the field for 17 years. Like all robot systems, medical robots fundamentally couple information to physical action to significantly enhance humans' ability to perform important tasks-in this case surgical interventions, rehabilitation, or simply helping handicapped people in daily living tasks. Research areas include modeling and analysis of anatomy and task environments, interface technology between the "data world" and the physical world, and study of how complex systems are put together. This paper will discuss these research areas and illustrate their interrelationship with application examples. Although the main focus will be on robotic systems for surgery, it will also discuss the relationship of these research areas to rehabilitation and assistance robots. Finally, it will include some thoughts on the factors driving the acceptance of medical robotics and of how research can be most effectively organized
On the choice of suitable operators and parameters in multigrid methods (1981)

In this report we consider multigrid methods for the solution of elliptic boundary value problems.These methods are described by a simple Algol-like program.By special choices of some operators and parameters almost every multigrid strategy that has been proposed in the literature for linear problems can be recovered.Several possibilities for the restriction, prolongation, coarse grid and smoothing operators are considered.Further1nore, we consider the nuanber of smoothing steps and the number of coarse grid corrections.Some comparitive experiments are described with the Poisson, anisotropic diffusion and the convection-diffusion equations
Benign conditions associated with raised serum CA-125 concentration (2000)

A retrospective audit carried out in the Department of Clinical Biochemistry, covering a period of 42 months, showed 19 benign conditions, that gave rise to elevated serum CA-125 concentrations. These included six patients with non-malignant gynaecological disease, six patients with abdominal disorders, and seven patients with lung disease. These observations confirm that false-positive elevations can occur and that care must be taken before attributing an elevated serum CA-125 as an indicator of ovarian malignancy.
Cross-linking of both Fc gamma RI and Fc gamma RII induces secretion of tumor necrosis factor by human monocytes, requiring high affinity Fc-Fc gamma R interactions. Functional activation of Fc gamma RII by treatment with proteases or neuraminidase. (1990)

Cross-linking of Fc gamma R on human monocytes with human IgG has been shown to induce secretion of the inflammatory and immunoregulatory cytokine TNF. In the present study we examined the role of both constitutively expressed monocyte Fc gamma R, the 72-kDa high affinity Fc gamma R (Fc gamma RI), and the 40-kDa low affinity receptor (Fc gamma RII), in the induction of TNF secretion. On the basis of preferential binding of the Fc moiety of murine mAb of different isotype, Fc gamma RI and Fc gamma RII were selectively cross-linked by using either solid-phase murine (m)IgG2a, or solid-phase mIgG1, respectively. On freshly isolated, untreated monocytes only cross-linking of Fc gamma RI with solid-phase mIgG2a induced TNF secretion. The interaction between Fc gamma RII and mIgG1 could be enhanced by treatment of monocytes with proteases or with the desialylating enzyme neuraminidase. After treatment of monocytes with these enzymes, TNF secretion was effectively induced by solid-phase mIgG1, apparently through cross-linking of Fc gamma RII. However, mIgG1-induced TNF secretion differed between protease-treated monocytes from high responder individuals and monocytes from low responder individuals, TNF secretion being considerably less in the latter population. Protease-treated monocytes and mononuclear cells from individuals with an inherited defect in cell membrane expression of Fc gamma RI were induced to secrete TNF by solid-phase human IgG, confirming the capacity of Fc gamma RII to induce TNF secretion. It was not possible to induce TNF secretion by cross-linking Fc gamma RI or Fc gamma RII with anti-Fc gamma R mAb and soluble or solid-phase anti-mIgG, indicating that high affinity Fc-Fc gamma R interactions are necessary to induce release of this cytokine.
Photothermal image cytometry of human neutrophils (1996)

Photothermal imaging, when applied to the study of living cells, provides morphofunctional information about cell populations. In technical terms, the method is complementary to optical microscopy. The photothermal method was used for cell imaging and quantitative studies. We have developed a dual-laser technique and have constructed an automated image cytometer based on an optical microscope. The theory of the method, the technical equipment, and the computer software are described. With our technique, three types of cell images can be acquired and analyzed: optical, pulsed laser time-domain, and photothermal. The parameters of each kind of image are considered in detail. Preliminary results of studies on living human neutrophils are presented.
Development of the IL‐12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives (2011)

Since the original publication of the article "Development of the IL-12/23 antagonist ustekinumab in psoriasis: Past, present and future perspectives" in March 2011 (see Appendix),(1) there have been several new publications and developments of note. A number of new reports from the ustekinumab psoriasis clinical development program have been published. The analysis of efficacy and safety in the PHOENIX 1 long-term extension demonstrated that continuous stable maintenance dosing of ustekinumab was generally well tolerated and sustained durable efficacy through up to three years of treatment.(2) Pooled safety data from the phase 2 and phase 3 global trials showed that the safety profile of long-term continuous ustekinumab treatment through up to three years(3,4) and four years(5) of follow-up was favorable and comparable to what has been reported previously in the shorter-term ustekinumab psoriasis studies.(6-8) This represents the greatest exposure and longest follow-up of psoriasis patients treated with a biologic published to date. Additional phase 3 trials in Asian populations demonstrated similar high levels of efficacy and favorable safety profiles in Japanese,(9,10) Korean,(11,12) and Taiwanese(11,12) patients as those observed in trials conducted in mostly White populations in North America and Europe.(6-8) These data support the positive benefit:risk profile and consistency of response to ustekinumab over years of usage, and in multiple ethnic groups. Results from up to five years of treatment with ustekinumab in the long-term extensions of the phase 3 trials, and the efficacy, safety, and effect on quality of life in Chinese patients will be available in 2012. In addition to clinical trials of ustekinumab for the treatment of psoriasis, 24-week data from one phase 3 study of ustekinumab for the treatment of psoriatic arthritis has recently been presented(13) and another study is ongoing. A Phase 2b trial in Crohn's disease has also been presented,(14) and three phase 3 studies in Crohn's disease are currently in progress.
Functionally selective peripheral nerve stimulation with a flat interface nerve electrode (2002)

One of the important goals of peripheral nerve electrode development is to design an electrode for selective recruitment of the different functions of a common nerve trunk. A challenging task is gaining selective access to central axon populations. In this paper, a simple electrode that takes advantage of the neural plasticity to reshape the nerve is presented. The flat interface nerve electrode (FINE) reshapes the nerve into a flat geometry to increase the surface area and move central axon populations close to the surface. The electrode was implanted acutely on the sciatic nerve of eight cats. The FINE can significantly reshape the nerve and fascicles (p < 0.0001) while maintaining the same total nerve cross-sectional area. The stimulation thresholds were 2.89 nC for pulse amplitude modulation and 10.2 nC for pulse-width modulation. Monopolar, square-pulse stimulation with single contacts on the FINE selectively recruited each of the four main branches of the sciatic nerve. Simultaneous stimulation with two contacts produced moments about the ankle joint that were a combination of the moments produced by the individual contacts when stimulated separately.
LDL receptor‐related protein: a multiligand receptor for lipoprotein and proteinase catabolism (1995)

The accumulation of excessive cholesterol-rich lipoproteins within vascular cells, the proliferation of vascular cells, and fibrin deposition are hallmark features of atherosclerosis. Evidence accumulated over the past few years supports the hypothesis that one member of the LDL receptor family, the low density lipoprotein receptor-related protein (LRP), affects the dynamics of each of these processes. LRP is expressed in several vascular cell types, including smooth muscle cells, and in macrophages, and is also expressed in these cells in atherosclerotic lesions. This receptor is a large endocytotic receptor that mediates the catabolism of a number of molecules known to be important in vascular biology, including apolipoprotein E- and lipoprotein lipase-enriched lipoproteins, thrombospondin, and plasminogen activators. The capacity of LRP to mediate lipoprotein catabolism may be a factor in the development of the lesion by contributing to the formation of foam cells. LRP has recently been shown to mediate the catabolism of thrombospondin, a molecule that has potent biological effects on cells of the vasculature. The regulation of its extracellular accumulation by LRP might modulate the dynamic processes of tissue remodeling associated with the response to vascular injury. In addition, LRP regulates the expression of plasmin activity by directly binding and mediating the cellular internalization of urokinase- and tissue-type plasminogen activators. The cellular removal of these two enzymes decreases the local profibrinolytic potential, possibly leading to a thrombotic state at lesion sites.
Content Based Image Retrieval at the End of the Early Years (2000)

AbstractÐThe paper presents a review of 200 references in content-based image retrieval. The paper starts with discussing the working conditions of content-based retrieval: patterns of use, types of pictures, the role of semantics, and the sensory gap. Subsequent sections discuss computational steps for image retrieval systems. Step one of the review is image processing for retrieval sorted by color, texture, and local geometry. Features for retrieval are discussed next, sorted by: accumulative and global features, salient points, object and shape features, signs, and structural combinations thereof. Similarity of pictures and objects in pictures is reviewed for each of the feature types, in close connection to the types and means of feedback the user of the systems is capable of giving by interaction. We briefly discuss aspects of system engineering: databases, system architecture, and evaluation. In the concluding section, we present our view on: the driving force of the field, the heritage from computer vision, the influence on computer vision, the role of similarity and of interaction, the need for databases, the problem of evaluation, and the role of the semantic gap. Index TermsÐReview, content based, retrieval, semantic gap, sensory gap, narrow domain, broad domain, weak segmentation, accumulative features, salient features, signs, structural features, similarity, semantic interpretation, query space, display space,
Oxytocin and Oxytocin Receptors in Cancer Cells and Proliferation (2004)

The hypothalamic nonapeptide oxytocin plays a crucial role in many reproductive and behavioural functions. However, in recent years, an additional new role for oxytocin has been identified in neoplastic pathology. In tumours, oxytocin acts as a growth regulator, through the activation of a specific G-coupled transmembrane receptor, the oxytocin receptor. In vitro, oxytocin inhibits proliferation of neoplastic cells of either epithelial (mammary and endometrial), nervous or bone origin, all expressing oxytocin receptor. Furthermore, an oxytocin growth-inhibiting effect was also tested and confirmed in vivo in mouse and rat mammary carcinomas. In neoplastic cells derived from two additional oxytocin target tissues, trophoblast and endothelium, oxytocin was found to promote cell proliferation, an effect opposite to that previously described in all other neoplastic oxytocin-responsive cells. The signal transduction pathways coupled to the biological effects of oxytocin are different in oxytocin growth-inhibited or growth-stimulated cells, and may depend on the membrane localization of the oxytocin receptor itself. The inhibitory effect of oxytocin is apparently mediated by activation of the cAMP-protein kinase A pathway, a nonconventional oxytocin signalling pathway, whereas the mitogenic effect is coupled to the increase of intracellular [Ca(2+)] and tyrosine phosphorylation, 'classical' oxytocin transducers. Moreover, the oxytocin receptor localization in lipid rafts enriched in caveolin-1 turns the inhibition of cell growth into a proliferative response, eliciting different epidermal growth factor receptor/mitogen-activated protein kinase activation patterns. This unexpected role of oxytocin (and oxytocin analogues) in regulating cell proliferation, as well as the widespread expression of oxytocin receptors in neoplastic tissues of different origin, opens up new perspectives on the biological role of the oxytocin-oxytocin receptor system in cancer.
Synthesis of Proteins by Native Chemical Ligation (1994)

A simple technique has been devised that allows the direct synthesis of native backbone proteins of moderate size. Chemoselective reaction of two unprotected peptide segments gives an initial thioester-linked species. Spontaneous rearrangement of this transient intermediate yields a full-length product with a native peptide bond at the ligation site. The utility of native chemical ligation was demonstrated by the one-step preparation of a cytokine containing multiple disulfides. The polypeptide ligation product was folded and oxidized to form the native disulfide-containing protein molecule. Native chemical ligation is an important step toward the general application of chemistry to proteins.
In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices. (1983)

We have studied the behavior of cloned capillary endothelial cells grown inside a three dimensional collagen matrix. Cell monolayers established on the surface of collagen gels were covered with a second layer of collagen. This induced the monolayers of endothelial cells to reorganize into a network of branching and anastomosing capillary-like tubes. As seen by electron microscopy, the tubes were formed by at least two cells (in transverse sections) delimiting a narrow lumen. In addition, distinct basal lamina material was present between the abluminal face of the endothelial cells and the collagen matrix. These results showed that capillary endothelial cells have the capacity to form vessel-like structures with well-oriented cell polarity in vitro. They also suggest that an appropriate topological relationship of endothelial cells with collagen matrices, similar to that occurring in vivo, has an inducive role on the expression of this potential. This culture system provides a simple in vitro model for studying the factors involved in the formation of new blood vessels (angiogenesis).
A Kalman-Based Coordination for Hierarchical State Estimation: Agorithm and Analysis (2008)

Hierarchical state estimation algorithms are usually employed in large-scale interconnected power systems, where state estimation usually involves very tedious communications and computations. This paper presents 1) a modified coordination technique that is based on Kalman filtering, derived from hierarchical state estimation; and 2) a time complexity analysis and experimental implementation to compare central, distributed, and hierarchical state estimation algorithms in terms of computation power and communication bandwidth requirements. Analytical and experimental results on the IEEE 118-bus test bed show that the presented approach, i.e., hierarchical Kalman filtering (HKF), needs about 34% communication bandwidth and O(1/N <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> ) computation power in subsystems compared to central state estimation, while giving approximately the same level of estimation precision.
A Novel Selective PPARα Modulator (SPPARMα), K-877 (Pemafibrate), Attenuates Postprandial Hypertriglyceridemia in Mice (2017)

K-877 may attenuate PHTG by suppressing the postprandial increase of chylomicrons and the accumulation of chylomicron remnants more effectively than fenofibrate.