gebhart/patrepeval huggingface dataset:
Potential for personalization (2010)

Current Web search tools do a good job of retrieving documents that satisfy the most common intentions associated with a query, but do not do a very good job of discerning different individuals' unique search goals. We explore the variation in what different people consider relevant to the same query by mining three data sources: (1) explicit relevance judgments, (2) clicks on search results (a behavior-based implicit measure of relevance), and (3) the similarity of desktop content to search results (a content-based implicit measure of relevance). We find that people's explicit judgments for the same queries differ greatly. As a result, there is a large gap between how well search engines could perform if they were to tailor results to the individual, and how well they currently perform by returning results designed to satisfy everyone. We call this gap the potential for personalization . The two implicit indicators we studied provide complementary value for approximating this variation in result relevance among people. We discuss several uses of our findings, including a personalized search system that takes advantage of the implicit measures by ranking personally relevant results more highly and improving click-through rates.
The Many Substrates of Presenilin/γ-Secretase (2011)

The Alzheimer's disease (AD)-associated amyloid-β protein precursor (AβPP) is cleaved by α-, β-, and presenilin (PS)/γ-secretases through sequential regulated proteolysis. These proteolytic events control the generation of the pathogenic amyloid-β (Aβ) peptide, which excessively accumulates in the brains of individuals afflicted by AD. A growing number of additional proteins cleaved by PS/γ-secretase continue to be discovered. Similarly to AβPP, most of these proteins are type-I transmembrane proteins involved in vital signaling functions regulating cell fate, adhesion, migration, neurite outgrowth, or synaptogenesis. All the identified proteins share common structural features, which are typical for their proteolysis. The consequences of the PS/γ-secretase-mediated cleavage on the function of many of these proteins are largely unknown. Here, we review the current literature on the proteolytic processing mediated by the versatile PS/γ-secretase complex. We begin by discussing the steps of AβPP processing and PS/γ-secretase complex composition and localization, which give clues to how and where the processing of other PS/γ-secretase substrates may take place. Then we summarize the typical features of PS/γ-secretase-mediated protein processing. Finally, we recapitulate the current knowledge on the possible physiological function of PS/γ-secretase-mediated cleavage of specific substrate proteins.
The prevalence of agitation and brain injury in skilled nursing facilities: a survey (1996)

All skilled nursing facilities (SNF) in the state of Connecticut were surveyed to determine the number of residents with a primary diagnosis of brain injury, the incidence of agitation among these residents, and management strategies utilized for agitation in these residents, including consultation with brain injury specialists. One hundred and sixty-two, or 64%, of the SNF responded to the survey, and reported on 140 individuals with a primary diagnosis of brain injury. These individuals were residing in 39, or 24%, of the 162 facilities. Forty-five percent of these 39 facilities had brain-injured residents who met the definition of agitation presented in the survey. Management of agitation was equally distributed between environmental manipulation, formal behaviour care plans and medications. The availability of specialist consultation was variable and included physiatrists (38%), psychiatrists (67%), neurologists (41%), and psychologists (36%). This survey study defined the prevalence of brain-injured residents in Connecticut's SNF, and examined management strategies for agitation in this patient population.
Overview on Concepts and Applications of Fab Antibody Fragments (2009)

In this overview, the Fab molecule is introduced and discussed as the first generated antibody fragment, which still dominates basic research and clinical applications. The unit contains a concepts section and an applications section. In the concepts section, the two principal methods for producing Fab, as well as the generation and directed evolution of Fab by phage display, are described. The applications section discusses Fab in clinical applications, as well as their increasingly important role in the determination of the three-dimensional structures of transmembrane proteins.
The Sparc Architecture Manual/Version 9 (1994)

Introduction. 1. Overview. 2. Definitions. 3. Architectural Overview. 4. Data Formats. 5. Registers. 6. Instructions. 7. Traps. 8. Memory Models. Annex A: (Normative) Instruction Definitions. Annex B: (Normative) IEEE 754-1985 Requirements for SPARC-V9. Annex C: (Normative) SPARC-V9 Implementation Dependencies. Annex D: (Normative) Formal Specification of the Memory Models. Annex E: (Informative) Opcode Maps. Annex F: (Informative) SPARC-V9 MMU Requirements. Annex G: (Informative) Suggested Assembly Language Syntax. Annex H: (Informative) Software Considerations. Annex I: (Informative) Extending the SPARC-V9 Architecture. Annex J: (Informative) Programming With the Memory Models. Annex K: (Informative) Changes from SPARC-V8 to SPARC-V9. Bibliography. Index.
Correction: Endothelial Membrane Remodeling Is Obligate for Anti-Angiogenic Radiosensitization during Tumor Radiosurgery (2010)

Background: While there is significant interest in combining anti-angiogenesis therapy with conventional anti-cancer treatment, clinical trials have as of yet yielded limited therapeutic gain, mainly because mechanisms of anti-angiogenic therapy remain to a large extent unknown. Currently, anti-angiogenic tumor therapy is conceptualized to either ''normalize'' dysfunctional tumor vasculature, or to prevent recruitment of circulating endothelial precursors into the tumor. An alternative biology, restricted to delivery of anti-angiogenics immediately prior to single dose radiotherapy (radiosurgery), is provided in the present study.
Different modes of stop codon restriction by the Stylonychia and Paramecium eRF1 translation termination factors (2007)

In universal-code eukaryotes, a single-translation termination factor, eukaryote class-1 polypeptide release factor (eRF1), decodes the three stop codons: UAA, UAG, and UGA. In some ciliates, like Stylonychia and Paramecium, eRF1s exhibit UGA-only decoding specificity, whereas UAG and UAA are reassigned as sense codons. Because variant-code ciliates may have evolved from universal-code ancestor(s), structural features should exist in ciliate eRF1s that restrict their stop codon recognition. In omnipotent eRF1s, stop codon recognition is associated with the N-terminal domain of the protein. Using both in vitro and in vivo assays, we show here that chimeric molecules composed of the N-terminal domain of Stylonychia eRF1 fused to the core domain (MC domain) of human eRF1 retained specificity toward UGA; this unambiguously associates eRF1 stop codon specificity to the nature of its N-terminal domain. Functional analysis of eRF1 chimeras constructed by swapping ciliate N-terminal domain sequences with the matching ones from the human protein highlighted the crucial role of the tripeptide QFM in restricting Stylonychia eRF1 specificity toward UGA. Using the site-directed mutagenesis, we show that Paramecium eRF1 specificity toward UGA resides within the NIKS (amino acids 61-64) and YxCxxxF (amino acids 124-131) motifs. Thus, we establish that eRF1 from two different ciliates relies on different molecular mechanisms to achieve specificity toward the UGA stop codon. This finding suggests that eRF1 restriction of specificity to only UGA might have been an early event occurring in independent instances in ciliate evolutionary history, possibly facilitating the reassignment of UAG and UAA to sense codons.
Serological and Clinical Features of Patients with Myasthenia Gravis in North Indian Population (2010)

Myasthenia gravis (MG) is a disorder of neuromuscular junction associated with presence of antibodies against nicotinic acetylcholine receptors (nAChRs). Here, we compared the clinical and serological profile of seropositive myasthenia gravis (SPMG) and seronegative myasthenia gravis (SNMG) patients. Anti-AChR antibody was measured using radio receptor immunoassay and correlated with clinical phenotype in 250 MG patients over 2004 and 2006. Out of 250 MG patients, 161 (64.4%) were males (male:female = 1.8:1). SNMG patients formed 40% (n = 101) of our MG patients which is much higher as compared to Caucasian and Oriental population (15%-20%). The median age of disease onset in SPMG was significantly higher than SNMG patients (43 years; range 8-74 vs. 35 years; range 4-72, p = .022). A bimodal peak of age of disease onset in both genders was observed (first peak in second-third decades and second one in fifth-sixth decades). Among the MG patients with late-onset of disease, male were significantly higher compared to Caucasian and Oriental MG population (p = .047). MG patients with thymoma were significantly older and consisted of higher percent of males. Bulbar symptoms and severe grade (IIB+ III+ IV) at disease onset were more frequent in SPMG than SNMG patients.
An empirical comparison of pie vs. linear menus (1988)

Menus are largely formatted in a linear fashion listing items from the top to bottom of the screen or window. Pull down menus are a common example of this format. Bitmapped computer displays, however, allow greater freedom in the placement, font, and general presentation of menus. A pie menu is a format where the items are placed along the circumference of a circle at equal radial distances from the center. Pie menus gain over traditional linear menus by reducing target seek time, lowering error rates by fixing the distance factor and increasing the target size in Fitts's Law, minimizing the drift distance after target selection, and are, in general, subjectively equivalent to the linear style.
Short message service based applications in the GSM network (2005)

Mobile data services represents a new frontier in the benefits that can be offered to the mobile customer, which have hitherto included voice only in addition to the characteristic terminal mobility. In view of the limitations and costs of mobile communication, the most interesting data services appear to be the "virtual circuit" services, i.e. those in which the mobile radio network assigns radio resources dynamically and only during the actual transmission. A further aspect to be borne in mind is the user coverage conditions, as inadequate coverage would limit connectivity prerogatives and preclude the use of the service by customers such as vehicle fleet operators for whom mobility is a basic, if not indeed overriding consideration. An answer to this kind of demand is provided by the pan-European GSM network with the voice integrated short message service, or SMS. The article introduces the SMS architecture and shows, using the SMS facilities, how to provide services, which includes transmission of location information, credit cards authentication, computer-based messaging and remote monitoring to mobile customers within GSM coverage area.
Axin, an inhibitor of the Wnt signalling pathway, interacts with β‐catenin, GSK‐3β and APC and reduces the β‐catenin level (1998)

Axin interacts with beta-catenin, GSK-3beta and APC, and negatively regulates the Wnt signalling pathway, presumably by regulating the level of beta-catenin.
Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients (2012)

The development and optimization of immune therapies in patients has been hampered by the lack of preclinical models in which their effects on human immune cells can be studied. As a result, observations that have been made in preclinical studies have suggested mechanisms of drug action in murine models that have not been confirmed in clinical studies. Here, we used a humanized mouse reconstituted with human hematopoietic stem cells to study the mechanism of action of teplizumab, an Fc receptor nonbinding humanized monoclonal antibody to CD3 being tested in clinical trials for the treatment of patients with type 1 diabetes mellitus. In this model, human gut-tropic CCR6(+) T cells exited the circulation and secondary lymph organs and migrated to the small intestine. These cells then produced interleukin-10 (IL-10), a regulatory cytokine, in quantities that could be detected in the peripheral circulation. Blocking T cell migration to the small intestine with natalizumab, which prevents cellular adhesion by inhibiting α(4) integrin binding, abolished the treatment effects of teplizumab. Moreover, IL-10 expression by CD4(+)CD25(high)CCR6(+)FoxP3 cells returning to the peripheral circulation was increased in patients with type 1 diabetes treated with teplizumab. These findings demonstrate that humanized mice may be used to identify novel immunologic mechanisms that occur in patients treated with immunomodulators.
Topoisomerase I inhibitors in the combined-modality therapy of lung cancer. (2004)

Locally advanced non-small-cell lung cancer represents 30% to 40% of all pulmonary malignancies. Most patients will die of the disease after aggressive contemporary treatments. Therefore, significant improvement in therapeutic methods must be implemented to improve overall survival rates. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar) and topotecan (Hycamtin)--offers the hope of significant advances in the treatment of lung cancer. Irinotecan and topotecan are camptothecin derivatives that inhibit topoisomerase I enzyme. It is believed that topoisomerase I inhibitors stabilize a DNA/topoisomerase I complex and interact with replication machinery to cause cell death. A significant amount of data demonstrates that these topoisomerase I inhibitors also act as radiosensitizers. With the increasing data that support concurrent chemoradiation treatment for malignancies, including lung cancer and head and neck cancers, there is an impetus to pursue the additional drugs that may potentially improve local control and survival. Irinotecan is undergoing early clinical trials in the combined-modality setting in several different disease sites. This paper will review the data on the role of camptothecin derivatives as a radiosensitizer and as a component of combined-modality therapy for lung cancer. It is hoped that newer treatment strategies, like the combination of radiation and topoisomerase I inhibitors, will have a significant impact on cure rates in the future.
Photosensitizers in photodynamic therapy. (1994)

Photodynamic therapy (PDT) is based on the use of light-sensitive molecules called photosensitizers. Photoactivation causes the formation of singlet oxygen, which produces peroxidative reactions that can cause cell damage and death. Porfimer sodium (Photofrin, manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, BC, Canada) is the photosensitizer that has been studied most extensively. Patients generally have to be hospitalized for 2 days prior to light treatment after administration of porfimer sodium; it takes approximately 48 hours after injection to reach optimal concentration in tumor tissue. The tumoricidal capacity of PDT with porfimer sodium is determined in part by the maximum depth of penetration of light having a wavelength of 630 nm. Porfimer sodium causes cutaneous photosensitivity that may last for up to 6 weeks. Benzoporphyrin derivative (BPD verteporfin; BPD-Quadra Logic Technologies, Inc, Vancouver, BC, Canada), another photosensitizer, accumulates more rapidly in tumor tissue, permitting optimal PDT 30 to 150 minutes following intravenous administration. It is rapidly cleared from the body, and skin photosensitivity does not extend beyond a few days. The primary mechanism of action of PDT is related to the selective accumulation of photosensitizers in cancer tissue. Photodynamic therapy also shows promise in the treatment of a number of nonneoplastic conditions, including psoriasis, macular degeneration of the retina, atherosclerotic plaque and restenosis, bone marrow purging for treatment of leukemias with autologous bone marrow transplantation, inactivation of viruses in blood or blood products, and several autoimmune conditions, including rheumatoid arthritis. Physiologic characteristics shared by this disparate group of diseases, and the mechanisms by which they may mediate photoactivation, are discussed.
Leukocyte‐depleted blood A comparison of filtration techniques (1983)

Febrile transfusion reactions due to leukoagglutinins are commonly seen in multitransfused patients. It has been suggested that reduction of the number of leukocytes per transfusion to 0.5 x 10(9) or less would prevent nonhemolytic febrile transfusion reactions in the majority of patients. Therefore, we have compared the ability of several filters to reduce the leukocyte content of stored whole blood drawn into citrate-phosphate-dextrose. The leukocyte absorption filters, Imugard IG500 and Erypur, produced 98.3 +/- 2.4 and 98.3 +/- 1.7 percent leukocyte depletion, respectively. The leukocyte adherence filter, Leuko-Pak, produced a depletion of 54.6 +/- 14.7 percent. The microaggregate filters, Biotest MF10B Microfiltration set, Ultipor Blood Transfusion Filter SQ40S, and Travenol 20 micron High Capacity Transfusion Filter, produced 37.5 +/- 10.8, 13.3 +/- 11.2, and 44.5 +/- 11.3 percent leukocyte depletion, respectively. It would appear that of the filters tested, the Imugard IG500 and the Erypur are the only filters which can invariably reduce the absolute number of leukocytes in a unit of stored whole blood to below 0.5 x 10(9).
Protease Nexin-2/Amyloid β-Protein Precursor Inhibits Factor Xa in the Prothrombinase Complex (1995)

Protease nexin-2/amyloid beta-protein precursor (PN-2/A beta PP) is a Kunitz-type protease inhibitor which has been shown to be a tight-binding inhibitor of coagulation factors XIa and IXa. Here we show that PN-2/A beta PP and its KPI domain also inhibited isolated factor Xa with a Ki of 10(-8) M. On a solid phase binding assay, PN-2/A beta PP formed a complex with factor Xa. Incubation of molar excess factor Xa to PN-2/A beta PP produced a single cleavage within PN-2/A beta PP's heparin binding domain liberating a 8.2-kDa amino-terminal peptide. PN-2/A beta PP and its KPI domain equally inhibited factor Xa in the prothrombinase complex with a Ki of 1.9 x 10(-8) M and 1.3 x 10(-8) M, respectively. A beta PP695 which does not contain the KPI domain was a substrate of factor Xa but did not inhibit it, indicating the PN-2/A beta PP inhibition of factor Xa was not substrate inhibition. All of the factor Xa inhibition in the prothrombinase complex by PN-2/A beta PP and its KPI domain on the chromogenic assay was accounted for by inhibition of release of prothrombin fragment F1+2 as determined on immunochemical assay. In the prothrombinase complex, PN-2/A beta PP inhibited factor Xa with a kassoc = 1.8 +/- 0.7 x 10(6) M-1 min-1 similar to antithrombin III and heparin inhibition (kassoc of 3.0 +/- 0.2 x 10(6) M-1 min-1). These studies indicated that PN-2/A beta PP in the assembled prothrombinase complex inhibited factor Xa comparable to antithrombin III in the presence of heparin. PN-2/A beta PP's factor Xa inhibitory activity along with its known inhibition of factors XIa and IXa suggest that this protease inhibitor and related proteins could be regulators of hemostatic reactions on membranes of cells in the intravascular compartment.
Increasing DNA repair methyltransferase levels via bone marrow stem cell transduction rescues mice from the toxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, a chemotherapeutic alkylating agent. (1996)

The chloroethylnitrosourea (CNU) alkylating agents are commonly used for cancer chemotherapy, but their usefulness is limited by severe bone marrow toxicity that causes the cumulative depletion of all hematopoietic lineages (pancytopenia). Bone marrow CNU sensitivity is probably due to the inefficient repair of CNU-induced DNA damage; relative to other tissues, bone marrow cells express extremely low levels of the O6-methylguanine DNA methyltransferase (MGMT) protein that repairs cytotoxic O6-chloroethylguanine DNA lesions. Using a simplified recombinant retroviral vector expressing the human MGMT gene under control of the phosphoglycerate kinase promoter (PGK-MGMT) we increased the capacity of murine bone marrow-derived cells to repair CNU-induced DNA damage. Stable reconstitution of mouse bone marrow with genetically modified, MGMT-expressing hematopoietic stem cells conferred considerable resistance to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a CNU commonly used for chemotherapy. Bone marrow harvested from mice transplanted with PGK-MGMT-transduced cells showed extensive in vitro BCNU resistance. Moreover, MGMT expression in mouse bone marrow conferred in vivo resistance to BCNU-induced pancytopenia and significantly reduced BCNU-induced mortality due to bone marrow hypoplasia. These data demonstrate that increased DNA alkylation repair in primitive hematopoietic stem cells confers multilineage protection from the myelosuppressive effects of BCNU and suggest a possible approach to protecting cancer patients from CNU chemotherapy-related toxicity.
Intelligent multi-shot visualization interfaces for dynamic 3D worlds (1998)

In next-generation virtual 3D simulation, training, and entertainment environments, intelligent visualization interfaces must respond to user-specified viewing requests so users can follow salient points of the action and monitor the relative locations of objects. Users should be able to indicate which object(s) to view, how each should be viewed, cinematic style and pace, and how to respond when a single satisfactory view is not possible. When constraints fail, weak constraints can be relaxed or multi-shot solutions can be displayed in sequence or as composite shots with simultaneous viewports. To address these issues, we have developed CONSTRAINTCAM, a real-time camera visualization interface for dynamic 3D worlds. It has been studied in an interactive testbed in which users can issue viewing goals to monitor multiple autonomous characters navigating through a virtual cityscape. CONSTRAINTCAM’s real-time performance in this testbed is encouraging.
Self‐Cleavable Bioluminogenic Luciferin Phosphates as Alkaline Phosphatase Reporters (2008)

After glow. Reactive chemical adaptors were used to stabilize bioluminogenic phosphates for monitoring alkaline phosphatase (AP) activity (see scheme). The 1,6-elimination based luciferin phosphate exhibited ultrasensitive ability to detect ∼10−22 mol of AP enzyme in a homogeneous solution, and picograms of protein in an immunoassay. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2008/z700644_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.