gebhart/patrepeval huggingface dataset:
The role of therapeutic antibodies in drug discovery (2003)

The last 5 years have seen a major upturn in the fortune of therapeutic monoclonal antibodies (mAbs), with nine mAbs approved for clinical use during this period and more than 70 now in clinical trials beyond phase II. Sales are expected to reach $4 billion per annum worldwide in 2002 and $15 billion by 2010. This success can be related to the engineering of mouse mAbs into mouse/human chimaeric antibodies or humanized antibodies, which have had a major effect on immunogenicity, effector function and half-life. The issue of repeated antibody dosing at high levels with limited toxicity was essential for successful clinical applications. Emerging technologies (phage display, human antibody-engineered mice) have created a vast range of novel, antibody-based therapeutics, which specifically target clinical biomarkers of disease. Modified recombinant antibodies have been designed to be more cytotoxic (toxin delivery), to enhance effector functions (bivalent mAbs) and to be fused with enzymes for prodrug therapy and cancer treatment. Antibody fragments have also been engineered to retain specificity and have increased the penetrability of solid tumours (single-chain variable fragments). Radiolabelling of antibodies has now been shown to be effective for cancer imaging and targeting. This article focuses on developments in the design and clinical use of recombinant antibodies for cancer therapy.
Knowledge Adaptation: Teaching to Adapt (2017)

Domain adaptation is crucial in many real-world applications where the distribution of the training data differs from the distribution of the test data. Previous Deep Learning-based approaches to domain adaptation need to be trained jointly on source and target domain data and are therefore unappealing in scenarios where models need to be adapted to a large number of domains or where a domain is evolving, e.g. spam detection where attackers continuously change their tactics. To fill this gap, we propose Knowledge Adaptation, an extension of Knowledge Distillation (Bucilua et al., 2006; Hinton et al., 2015) to the domain adaptation scenario. We show how a student model achieves state-of-the-art results on unsupervised domain adaptation from multiple sources on a standard sentiment analysis benchmark by taking into account the domain-specific expertise of multiple teachers and the similarities between their domains. When learning from a single teacher, using domain similarity to gauge trustworthiness is inadequate. To this end, we propose a simple metric that correlates well with the teacher's accuracy in the target domain. We demonstrate that incorporating high-confidence examples selected by this metric enables the student model to achieve state-of-the-art performance in the single-source scenario.
Pharmacodynamic Studies of the Epidermal Growth Factor Receptor Inhibitor ZD1839 in Skin From Cancer Patients: Histopathologic and Molecular Consequences of Receptor Inhibition (2002)

PURPOSE: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca Pharmaceuticals, Alderley Park, United Kingdom) is under development as an anticancer agent. We studied the pharmacodynamic effects of ZD1839 on EGFR in the skin, an EGFR-dependent tissue, in cancer patients participating in ZD1839 phase I clinical trials. PATIENTS AND METHODS: We studied 104 pre– and/or on–ZD1839 therapy (≈ at day 28 of therapy) skin biopsies from 65 patients receiving escalating doses of daily oral ZD1839. We measured ZD1839 effects on EGFR activation by immunohistochemistry using an antibody specific for the activated (phosphorylated) EGFR. Effects on receptor signaling (activated mitogen-activated protein kinase [MAPK]), proliferation, p27 KIP1 , and maturation were also assessed. RESULTS: Histopathologically, the stratum corneum of the epidermis was thinner during therapy (P &lt; .001). In hair follicles, prominent keratin plugs and microorganisms were found in dilated infundibula. ZD1839 suppressed EGFR phosphorylation in all EGFR-expressing cells (P &lt; .001). In addition, ZD1839 inhibited MAPK activation (P &lt; .001) and reduced keratinocyte proliferation index (P &lt; .001). Concomitantly, ZD1839 increased the expression of p27 KIP1 (P &lt; .001) and maturation markers (P &lt; .001) and increased apoptosis (P &lt; .001). These effects were observed at all dose levels, before reaching dose-limiting toxicities. CONCLUSION: ZD1839 inhibits EGFR activation and affects downstream receptor-dependent processes in vivo. These effects were profound at doses well below the one producing unacceptable toxicity, a finding that strongly supports pharmacodynamic assessments to select optimal doses instead of a maximum-tolerated dose for definitive efficacy and safety trials.
La estrategia estadounidense en Oriente Medio: luchando por evitar el fracaso (2007)

Se avecinan desafíos para Estados Unidos con respecto a Irán, Líbano y Palestina. La suerte del declarado empeño de la Administración Bush de promover la reforma política y la democracia en Oriente Medio pende de un hilo. En este documento se analizan el laberinto al que se enfrenta EEUU en Irak y la evolución de la estrategia en Irán.
Incremental Surface Extraction from Sparse Structure-from-Motion Point Clouds (2013)

In this paper we propose a new method to incrementally extract a surface from a consecutively growing Structure-from-Motion (SfM) point cloud in real-time. Our method is based on a Delaunay triangulation (DT) on the 3D points. The core idea is to robustly label all tetrahedra into freeand occupied space using a random field formulation and to extract the surface as the interface between differently labeled tetrahedra. For this reason, we propose a new energy function that achieves the same accuracy as state-of-the-art methods but reduces the computational effort significantly. Furthermore, our new formulation allows us to extract the surface in an incremental manner, i. e. whenever the point cloud is updated we adapt our energy function. Instead of minimizing the updated energy with a standard graph cut, we employ the dynamic graph cut of Kohli et al. [1] which enables efficient minimization of a series of similar random fields by re-using the previous solution. In such a way we are able to extract the surface from an increasingly growing point cloud nearly independent of the overall scene size. Energy Function for Surface Extraction Our method formulates surface extraction as a binary labeling problem, with the goal of assigning each tetrahedron either a free or occupied label. For this reason, we model the probabilities that a tetrahedron is free- or occupied space analyzing the set of rays that connect all 3D points to image features. Following the idea of the truncated signed distance function (TSDF), which is known from voxel-based surface reconstructions, a tetrahedron in front of a 3D point X has a high probability to be free space, whereas a tetrahedron behind X is presumably occupied space. We further assume that it is very unlikely that neighboring tetrahedra obtain different labels, except for pairs of tetrahedra that have a ray through the face connecting both. Such a labeling problem can be elegantly formulated as a pairwise random field and since our priors are submodular, we can efficiently find a global optimal labeling solution e. g. using graph cuts. In contrast to existing methods like [2], our energy depends only on the visibility information that is directly connected to the four 3D points that span the tetrahedraVi. Hence a modification of the tetrahedral structure by inserting new points has only limited effect on the energy function. This property enables us to easily adopt the energy function to a modified tetrahedral structure. Incremental Surface Extraction To enable efficient incremental surface reconstruction, our method has to consecutively integrate new scene information (3D points as well as visibility information) in the energy function and to minimize the modified energy efficiently. Integrating new visibility information, i. e. adding rays for newly available 3D points, affects only those terms of the energy function that relate
Ionic Strength-Controlled Virtual Area of Mesoporous Platinum Electrode (2004)

Mesoporous electrodes provide an unusual opportunity to observe the dramatic transition of the electrochemical potential distribution in vicinity to mesoporous surfaces as the ionic strength varies. The experimental results were in accordance with what the classical Gouy-Chapman theory predicts on the basis of the correlation between Debye length (kappa-1) and the diameter of mesopores. Using the phenomenon that the electrochemically effective area of mesoporous electrode depends on the ionic strength, the faradaic current density of dioxygen reduction could be controlled by the electrolyte concentration.
Transport of Molecules, Particles, and Cells in Solid Tumors (1999)

Extraordinary advances in molecular biology and biotechnology have led to the development of a vast number of therapeutic anti-cancer agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle, or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, which it then must migrate through. Unfortunately, tumors often develop in ways that hinder these steps. The goal of research in this area is to analyze each of these steps experimentally and theoretically and integrate the resulting information into a unified theoretical framework. This paradigm of analysis and synthesis has fostered a better understanding of physiological barriers in solid tumors and aided in the development of novel strategies to exploit and/or overcome these barriers for improved cancer detection and treatment.
Searching for the 1 in 2,400,000: A review of dystrophin gene point mutations (1994)

The past few years have seen a rapid increase in our knowledge of naturally occurring mutations in the dystrophin gene. Although earlier studies were limited to gross rearrangement mutations, we are now in a position to draw lessons on the molecular etiology of the remaining one-third of cases of Duchenne and Becker muscular dystrophy (DMD, BMD) which are associated with small mutations. This paper reviews 70 published and unpublished small mutations in the dystrophin gene and asks what we can learn about their nature, their distribution, and approaches to their characterisation. Strikingly for such a well-conserved gene, missense mutations are extremely rare, and the vast majority of DMD point mutations, like the gross rearrangements, result in premature translational termination. It seems increasingly likely that almost all cases of DMD arise solely as a result of a reduction in the level of dystrophin transcripts, and we argue that > 95% of DMD mutations contribute nothing to the functional dissection of the dystrophin protein. Most of the few BMD point mutations presented here are missense mutations in the N-terminal or C-terminal domains or are splice-site mutations that probably act, like BMD deletions, via the production of in-frame, interstitially deleted transcripts.
Human chemotaxis receptor genes cluster at 19q13.3-13.4. Characterization of the human C5a receptor gene (1993)

The human C5a anaphylatoxin and formyl peptide receptor genes, as well as two genes with high sequence identity to the formyl peptide receptor, FPRH1 and FPRH2, have been mapped to chromosome 19 (Lu et al., 1992). Further analysis reveals that these genes are present in the 19q13.3 band adjacent to the 13.3-13.4 interface. MRNAs for the C5a and formyl peptide receptors, as well as for FPRH1, are expressed in cAMP differentiated U937 cells and human eosinophils, while all four transcripts are expressed in human lung. This observation opens the possibility for coordinate regulation of these genes. In order to initiate the mapping of fine structure at this locus, genomic clones have been analyzed. All four of the genes have a similar structure, with the receptor protein encoded in a single exon. Detailed characterization of the C5a receptor gene reveals a two exon structure, with the 5' untranslated sequence and initiating methionine located in the first exon. An intron of approximately 9 kb separates exon 1 from the receptor-encoding exon 2. The region of genomic DNA flanking the 5' untranslated sequence possesses promoter activity when transfected into the myeloid-derived rat basophilic leukemia RBL-1 cells, but the same region is inactive when transfected into nonmyeloid cells. Deletional analyses indicate that C5a receptor 5' flanking region contains both cell-specific suppressor and promoter regions.
Chemotherapeutic agents and hepatotoxicity. (1992)

T HERE ARE THREE major questions to be addressed regarding chemotherapeutic agents and hepatotoxicity. What is the spectrum of hepatotoxicity? Which drugs should be avoided in patients with pre-existing liver disease? And what dosage modifications should be made when faced with abnormal liver function tests? Several recent articles have reviewed this subject.1-5 In the population being considered for chemotherapy, there are multiple other potential causes of abnormal liver function tests that must be considered (Table 1). Patients with metastatic disease may have known or occult hepatic metastases. All patients may have been exposed to hepatotoxins, including other medications, alcohol, chemicals. They may have other coexisting medical conditions that affect the liver or, because of their immunocompromised state, be prone to infectious complications, including the several forms of viral hepatitis. Baseline evaluation of patients about to undergo chemotherapy should therefore always include liver function tests, and when clinically indicated, hepatic imaging.6 The spectrum of hepatic toxicities ranges from the (usually) incidental elevations of transaminases observed with the nitrosoureas to life-threatening massive hepatic necrosis observed with dacarbazine. For the most part, pure single-drug toxicity is observed less often as the emphasis in chemotherapy shifts to combination regimes. Furthermore, the increased use of high-dose regimens with autologous bone marrow or stem-cell support has complicated the picture by revealing toxicities at very high doses that are not observed with conventional doses. Combination chemotherapy has been implicated in the development of fatal hepatic necrosis after haloalkane anesthesia.7 Allopurinol, frequently administered before chemotherapy to prevent urate nephropathy and secondary gout, has also been linked to fulminant hepatic failure, presumably caused by a hypersensitivity reaction.8,9 There is also a report of allopurinol hepatotoxicity potentiated by tamoxifen, a possible drug interaction. lo Several instances of
Heterogeneous tissue distribution of a mitochondrial DNA polymorphism in heteroplasmic subjects without mitochondrial disorders (2001)

The observed interperson differences can be explained by somatic segregation, which occurs randomly at various developmental stages. Besides tissue specific selection, this process might participate in the distribution of pathogenic mtDNA mutations.
Monitoring Serial Changes in Circulating Human Breast Cancer Cells in Murine Xenograft Models (2008)

Circulating tumor cells (CTC) are emerging as a powerful prognostic and predictive biomarker in several types of cancer, including breast, colon, and prostate. Studies of CTC in metastasis and further development of CTC as a biomarker in cancer have been limited by the inability to repetitively monitor CTC in mouse models of cancer. We have validated a method to enumerate CTC in blood samples obtained from living mice using a modified version of an in vitro diagnostic system for quantifying CTC in patients. Different routes of blood collection were tested to identify a method to reproducibly recover CTC from tumor-bearing mice without interference from contaminating normal murine epithelial cells. CTC are present in blood samples from mice bearing orthotopic xenografts of several different breast cancer cell lines and primary breast cancer cells from patient biopsies. We also show that this technology can be used for serial monitoring of CTC in mouse xenograft models of human breast cancer. These results establish a new method for studying CTC in mouse models of epithelial cancer, providing the foundation for studies of molecular regulation of CTC in cancer and CTC as biomarker for therapeutic efficacy.
New Strategies in Engineering T-cell Receptor Gene-Modified T cells to More Effectively Target Malignancies (2015)

The immune system, T cells in particular, have the ability to target and destroy malignant cells. However, antitumor immune responses induced from the endogenous T-cell repertoire are often insufficient for the eradication of established tumors, as illustrated by the failure of cancer vaccination strategies or checkpoint blockade for most tumors. Genetic modification of T cells to express a defined T-cell receptor (TCR) can provide the means to rapidly generate large numbers of tumor-reactive T cells capable of targeting tumor cells in vivo. However, cell-intrinsic factors as well as immunosuppressive factors in the tumor microenvironment can limit the function of such gene-modified T cells. New strategies currently being developed are refining and enhancing this approach, resulting in cellular therapies that more effectively target tumors and that are less susceptible to tumor immune evasion.
Frontline: IL‐7 does not prevent pro‐B/pre‐B cell maturation to the immature/sIgM+ stage (2004)

IL-7 plays many fundamental roles during murine B lineage development. One reported function is to maintain progenitors in a developmentally immature state by preventing differentiation to the surface IgM (sIgM)(+) stage. Withdrawal of IL-7 from cultures has been shown to lead to increases in mature traits such as RAG expression, IgL rearrangements and expression of sIgM. These observations have been interpreted as an inductive event promoting the differentiation of progenitor cells. In contrast to this, we reproducibly observe sIgM(+) cells that have differentiated in cultures containing IL-7. We find that sIgM(+) cells arise as a normal consequence when B lineage cells are cultured in the presence of IL-7. However, these cells are short-lived and are quickly replaced by newly emerging sIgM(+) cells that differentiate from sIgM(-) progenitors. Withdrawal of IL-7 from these cultures only prevents the survival and proliferation of CD2(-)sIgM(-) pro-B cells but does not change the number of cells that differentiate to the sIgM(+) stage. This changes the ratio of sIgM(-):sIgM(+) cells and results only in an apparent maturation of the culture as a whole. Therefore withdrawal of IL-7 from these cultures acts as a selection event, not an induction event, for populations that are normally present.
Distal Digital Replantation (2013)

Distal replantation performed at institutions that specialize in microsurgery and specifically tailored to the level of injury is associated with good survival, function, and patient satisfaction and superior aesthetic outcome. More prospective data are needed to evaluate the cost of treatment, psychological outcomes, and functional outcomes of distal replantation compared with revision amputation.
Vagal Tone and Meal-Induced Abdominal Symptoms in Healthy Subjects (2002)

Epigastric discomfort in response to rapid ingestion of a test meal in healthy subjects was not related to vagal tone as indexed by RSA. Vagal tone varied with breathing pattern and body position. It is possible that increasing vagal tone by such measures can be beneficial in the treatment of patients with functional dyspepsia.
<title>Intraoperative MR-guided DBS implantation for treating PD and ET</title> (2001)

Deep brain stimulator (DBS) implantation is a promising treatment alternative for suppressing the motor tremor symptoms in Parkinson disease (PD) patient. The main objective is to develop a minimally invasive approach using high spatial resolution and soft-tissue contrast MR imaging techniques to guide the surgical placement of DBS. In the MR-guided procedure, the high spatial resolution MR images were obtained intra-operatively and used to target stereotactically a specific deep brain location. The neurosurgery for craniotomy was performed in the front of the magnet outside of the 10 Gauss line. Aided with positional registration assembly for the stereotactic head frame, the target location (VIM or GPi or STN) in deep brain areas was identified and measured from the MR images in reference to the markers in the calibration assembly of the head frame before the burrhole prep. In 20 patients, MR- guided DBS implantations have been performed according to the new methodology. MR-guided DBS implantation at high magnetic field strength has been shown to be feasible and desirable. In addition to the improved outcome, this offers a new surgical approach in which intra-operative visualization is possible during intervention, and any complications such as bleeding can be assessed in situ immediately prior to dural closure.
ThinSight (2009)

research-article Share on ThinSight: a thin form-factor interactive surface technology Authors: Shahram Izadi Microsoft Research Cambridge, U.K. Microsoft Research Cambridge, U.K.View Profile , Steve Hodges Microsoft Research Cambridge, U.K. Microsoft Research Cambridge, U.K.View Profile , Alex Butler Microsoft Research Cambridge, U.K. Microsoft Research Cambridge, U.K.View Profile , Darren West Microsoft Research Cambridge, U.K. Microsoft Research Cambridge, U.K.View Profile , Alban Rrustemi Microsoft Research Cambridge, U.K. Microsoft Research Cambridge, U.K.View Profile , Mike Molloy Microsoft Research Cambridge, U.K. Microsoft Research Cambridge, U.K.View Profile , William Buxton Microsoft Research Cambridge, U.K. Microsoft Research Cambridge, U.K.View Profile Authors Info & Claims Communications of the ACMVolume 52Issue 12December 2009pp 90–98https://doi.org/10.1145/1610252.1610277Published:01 December 2009Publication History 6citation4,849DownloadsMetricsTotal Citations6Total Downloads4,849Last 12 Months10Last 6 weeks1 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 Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Synthesis and Characterization of Oligo(9,9-dihexyl-2,7-fluorene ethynylene)s:  For Application as Blue Light-Emitting Diode (2001)

[reaction: see text] Highly soluble and strongly blue fluorescent oligo(9,9-dihexyl-2,7-fluorene ethynylene)s (OFEs) were synthesized by a Pd/Cu-catalyzed Sonogashira coupling reaction. An organic light-emitting diode using pentamer 15 as the emitting material was successfully fabricated and emitted a bright blue light.