gebhart/patrepeval huggingface dataset:
Transport of protein toxins into cells: pathways used by ricin, cholera toxin and Shiga toxin (2002)

Ricin, cholera, and Shiga toxin belong to a family of protein toxins that enter the cytosol to exert their action. Since all three toxins are routed from the cell surface through the Golgi apparatus and to the endoplasmic reticulum (ER) before translocation to the cytosol, the toxins are used to study different endocytic pathways as well as the retrograde transport to the Golgi and the ER. The toxins can also be used as vectors to carry other proteins into the cells. Studies with protein toxins reveal that there are more pathways along the plasma membrane to ER route than originally believed.
The Effect of Dexmedetomidine on Oral Mucosal Blood Flow and the Absorption of Lidocaine (2018)

Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2 adrenoreceptor and is associated with reduced anesthetic requirements, as well as attenuated blood pressure and heart rate in response to stressful events. A previous study reported that cat gingival blood flow was controlled via sympathetic alpha-adrenergic fibers involved in vasoconstriction. In the present study, experiment 1 focused on the relationship between the effects of DEX on alpha adrenoreceptors and vasoconstriction in the tissues of the oral cavity and compared the palatal mucosal blood flow (PMBF) in rabbits between general anesthesia with sevoflurane and sedation with DEX. We found that the PMBF was decreased by DEX presumably because of the vasoconstriction of oral mucosal vessels following alpha-2 adrenoreceptor stimulation by DEX. To assess if this vasoconstriction would allow decreased use of locally administered epinephrine during DEX infusion, experiment 2 in the present study monitored the serum lidocaine concentration in rabbits to compare the absorption of lidocaine without epinephrine during general anesthesia with sevoflurane and sedation with DEX. The depression of PMBF by DEX did not affect the absorption of lidocaine. We hypothesize that this is because lidocaine dilates the blood vessels, counteracting the effects of DEX. In conclusion, despite decreased palatal blood flow with DEX infusion, local anesthetics with vasoconstrictors should be used in implant and oral surgery even with administered DEX.
Provider satisfaction: an analysis based on expectation. (1993)

Provider organizations will need to be in closer touch with their medical staffs in order to successfully anticipate and react to the many changes that lie ahead in the financing and delivery of health care services. This will mean understanding both physicians feelings and expectations. If you were asked today how satisfied your physicians are with your HMO, what would be your reply? How would you know? This staff-model HMO conducted a formal survey of its physicians to determine their expectations of the organization and their level of satisfaction with their work and environment. Such a tool is recommended for others interested in maintaining good relations with their physicians.
Performance characterisation of the MCNS DOCSIS 1.0 CATV protocol with prioritised first come first served scheduling (1999)

The Multimedia Cable Networks Systems (MCNS) Data Over Cable Service Interface Specifications (DOCSIS) is established as the primary cable network data communications standard. The head-end scheduling algorithm is not defined within the standard but it is the key function for providing the required performance capability. Computer simulation, using the Common Simulation Framework (CSF) 12 version of the CableLabs DOCSIS 1.0 computer model, has been used to predict the upstream system throughput and mean access delay. A prioritised first come first served scheduling algorithm has been considered to provide a baseline reference set of performance statistics against which other algorithms can be compared. The simulations, with theoretical confirmation, have shown that the maximum sustainable system throughput is 1965 kbps for a channel capacity of 2560 kbps and a packet size of 1500 octets, whereas for packet size of 100 octets the maximum sustainable throughput is only 1550 kbps. The mean access delay is found to vary between 10-900 ms depending on the offered load and assuming that the offered load does not exceed the capacity of the channel. Excess offered load causes service starvation according to the assigned priority.
Studies on polyazaindenes synthesis of several new condensed pyridazine derivatives (1990)

Article without abstract
Prokaryotes: The unseen majority (1998)

The number of prokaryotes and the total amount of their cellular carbon on earth are estimated to be 4-6 x 10(30) cells and 350-550 Pg of C (1 Pg = 10(15) g), respectively. Thus, the total amount of prokaryotic carbon is 60-100% of the estimated total carbon in plants, and inclusion of prokaryotic carbon in global models will almost double estimates of the amount of carbon stored in living organisms. In addition, the earth's prokaryotes contain 85-130 Pg of N and 9-14 Pg of P, or about 10-fold more of these nutrients than do plants, and represent the largest pool of these nutrients in living organisms. Most of the earth's prokaryotes occur in the open ocean, in soil, and in oceanic and terrestrial subsurfaces, where the numbers of cells are 1.2 x 10(29), 2.6 x 10(29), 3.5 x 10(30), and 0. 25-2.5 x 10(30), respectively. The numbers of heterotrophic prokaryotes in the upper 200 m of the open ocean, the ocean below 200 m, and soil are consistent with average turnover times of 6-25 days, 0.8 yr, and 2.5 yr, respectively. Although subject to a great deal of uncertainty, the estimate for the average turnover time of prokaryotes in the subsurface is on the order of 1-2 x 10(3) yr. The cellular production rate for all prokaryotes on earth is estimated at 1.7 x 10(30) cells/yr and is highest in the open ocean. The large population size and rapid growth of prokaryotes provides an enormous capacity for genetic diversity.
T3 glycoprotein is functional although structurally distinct on human T-cell receptor gamma T lymphocytes. (1987)

The T-cell receptor (TCR) gamma gene product occurs in association with T3 (CD3) polypeptides on the surface of human T lymphocytes. TCR gamma lymphocytes express arrays of T3 polypeptides distinct from those typically observed on TCR alpha beta lymphocytes. This report demonstrates that identical T3 gamma, delta, and epsilon polypeptides are synthesized by TCR gamma lymphocytes and TCR alpha beta lymphocytes. However, the processing of T3 delta oligosaccharides is distinct in the two cell types. This observation may suggest distinct quaternary structures of these receptor complexes. Despite these structural differences, the T3 molecule on TCR gamma lymphocytes is functional. It is associated with and comodulates with TCR gamma and it serves as a substrate for protein kinase C-mediated phosphorylation. Anti-T3 monoclonal antibodies induce a rapid increase in cytoplasmic free calcium, indicating that the receptor complex is involved in signal transduction and triggering of TCR gamma lymphocytes.
A system for fleet management using differential GPS and VHF data transmission mobile networks (1993)

In a number of industries and services, communication with the land vehicles of the fleet has been done through VHF radio systems. This mode of operation brings into question the possibility of using this same VHF equipment to transmit and receive data for position fleet management due to this fundamental advantage. It is possible, although there are a number of limitations and disadvantages in these communication systems, mainly because of the limited propagation properties and the limited availability of channels. These problems can be reduced by means of appropriate system design and data format.
Discovery of Novel and Highly Selective Inhibitors of Calpain for the Treatment of Alzheimer’s Disease: 2-(3-Phenyl-1H-pyrazol-1-yl)-nicotinamides (2017)

Calpain overactivation has been implicated in a variety of pathological disorders including ischemia/reperfusion injury, cataract formation, and neurodegenerative diseases such as Alzheimer's disease (AD). Herein we describe our efforts leading to the identification of ketoamide-based 2-(3-phenyl-1H-pyrazol-1-yl)nicotinamides as potent and reversible inhibitors of calpain with high selectivity versus related cysteine protease cathepsins, other proteases, and receptors. Broad efficacy in a set of preclinical models relevant to AD suggests that inhibition of calpain represents an attractive approach with potential benefit for the treatment of AD.
E-cadherin Negatively Regulates CD44-Hyaluronan Interaction and CD44-mediated Tumor Invasion and Branching Morphogenesis (2003)

CD44 is a principal cell-surface receptor for hyaluronan (HA). Up-regulation of CD44 is often associated with morphogenesis and tumor invasion. On the contrary, reduction of cell-cell adhesion due to down-regulation of E-cadherin is associated with the invasive and metastatic phenotype of carcinomas. In our current study, we investigated the functional relationship between CD44 and E-cadherin. We established an inverse correlation between CD44 and E-cadherin indicating that the cells expressing higher levels of E-cadherin display weaker binding affinity between CD44 and HA. By using TA3 murine mammary carcinoma (TA3) cells, which display CD44-dependent HA binding, branching morphogenesis, and invasion, we demonstrated an inverse functional relationship between CD44 and E-cadherin by transfecting exogenous E-cadherin into the cells. Our results showed that increased expression of E-cadherin in TA3 cells, but not ICAM-1, weakens the binding between CD44 and HA and blocks spreading of the cells on HA substratum and CD44-mediated branching morphogenesis and tumor cell invasion. The results reported here demonstrated for the first time that E-cadherin negatively regulated CD44-HA interaction and CD44 function and suggested that balanced function of CD44 and E-cadherin may be essential for normal epithelial cell functions, and imbalanced up-regulation of CD44 function and/or down-regulation of E-cadherin function likely contributes to tumor progression.
Technical Report: Precautions Regarding the Use of Aerosolized Antibiotics (2000)

In 1998, the Food and Drug Administration (FDA) approved the licensure of tobramycin solution for inhalation (TOBI). Although a number of additional antibiotics, including other aminoglycosides, beta-lactams, antibiotics in the polymyxin class, and vancomycin, have been administered as aerosols for many years, none are approved by the FDA for administration by inhalation. TOBI was approved by the FDA for the maintenance therapy of patients 6 years or older with cystic fibrosis (CF) who have between 25% and 75% of predicted forced expiratory volume in 1 second (FEV(1)), are colonized with Pseudomonas aeruginosa, and are able to comply with the prescribed medical regimen. TOBI was not approved for the therapy of acute pulmonary exacerbations in patients with CF nor was it approved for use in patients without CF. Currently, no other antibiotics are approved for administration by inhalation to patients with or without CF. The purpose of this statement is to briefly summarize the data that supported approval for licensure of TOBI and to provide recommendations for its safe use. The pharmacokinetics of inhaled aminoglycosides and problems associated with aerosolized antibiotic treatment, including environmental contamination, selection of resistant microbes, and airway exposure to excipients in intravenous formulations, will be discussed.
Spin effects on the luminescence yield of organic light emitting diodes (1998)

The influence of the excitation spectrum on the quantum yield is investigated for organic molecules used in light emitting diodes (LEDs). The significance of the competition between radiative and nonradiative recombination channels is pointed out. A system of master equations is proposed to describe the relaxation of lower levels of the excited molecule, and the solution for the fluorescence yield is obtained assuming relatively weak vibronic coupling. The results are used to interpret the experimental data in oligothiophenes, and general approaches are proposed to increase the relative weight of the radiative decay channel and correspondingly enhance the working properties of organic light emitting diodes. In particular, the fluorescence quantum yield can exceed the simple estimate of 0.25.
A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation (2005)

Gab proteins amplify and integrate signals stimulated by many growth factors. In culture and animals, retinoic acid (RA) induces neuronal differentiation. We show that Gab2 expression is detected in neurons in three models of neuronal differentiation: embryonic carcinoma (EC) stem cells, embryonic stem cells, and primary neural stem cells (NSCs). RA treatment induces apoptosis, countered by basic FGF (bFGF). In EC cells, Gab2 silencing results in hypersensitivity to RA-induced apoptosis and abrogates the protection by bFGF. Gab2 suppression reduces bFGF-dependent activation of AKT but not ERK, and constitutively active AKT, but not constitutively active MEK1, reverses the hypersensitization. Thus, Gab2-mediated AKT activation is required for bFGF's protection. Moreover, Gab2 silencing impairs the differentiation of EC cells to neurons. Similarly, in NSCs, Gab2 suppression reduces bFGF-dependent proliferation as well as neuronal survival and production upon differentiation. Our findings provide the first evidence that Gab2 is an important player in neural differentiation, partly by acting downstream of bFGF to mediate survival through phosphoinositide 3 kinase-AKT.
Abdominal aortic aneurysms: CT evaluation of renal artery involvement. (1995)

CT can help predict whether an initial aortic clamp can be placed caudal to the main renal artery orifices. Its use can be predicted with 100% certainty only when an aneurysm appears to originate at least 3 cm caudal to the origin of the main renal artery.
Heterozygous Missense Mutations in the Insulin Gene Are Linked to Permanent Diabetes Appearing in the Neonatal Period or in Early Infancy (2008)

We identified three missense mutations in the INS gene in four probands. Two of four mutations were inherited in a dominant manner, and the familial description evidenced a marked variability in age of diagnosis and disease progression. In our cohort, the INS mutations may represent approximately 10% of all permanent neonatal diabetes cases, having a later presentation of diabetes and no associated symptoms compared with cases with K(ATP) channel mutations. CONCLUSIONS; Heterozygous INS gene mutations can cause isolated permanent early-infancy diabetes and should be assessed in neonatal as well as in childhood diabetes appearing like type 1, when autoimmune markers are absent. New pharmacogenomic strategies may be applicable, since residual beta-cell function is still present in some patients.
In-cell Selectivity Profiling of Serine Protease Inhibitors by Activity-based Proteomics (2008)

Activity-based proteomics is a methodology that is used to quantify the catalytically active subfraction of enzymes present in complex mixtures such as lysates or living cells. To apply this approach for in-cell selectivity profiling of inhibitors of serine proteases, we designed a novel activity-based probe (ABP). This ABP consists of (i) a fluorophosphonate-reactive group, directing the probe toward serine hydrolases or proteases and (ii) an alkyne functionality that can be specifically detected at a later stage with an azide-functionalized reporter group through a Cu(I)-catalyzed coupling reaction ("click chemistry"). This novel ABP was shown to label the active site of several serine proteases with greater efficiency than a previously reported fluorophosphonate probe. More importantly, our probe was cell-permeable and achieved labeling of enzymes within living cells with efficiency similar to that observed for the corresponding lysate fraction. Several endogenous serine hydrolases whose activities were detected upon in-cell labeling were identified by two-dimensional gel and MS analyses. As a proof of principle, cell-permeable inhibitors of an endogenous serine protease (prolyl endopeptidase) were assessed for their potency and specificity in competing for the in situ labeling of the selected enzyme. Altogether these results open new perspectives for safety profiling studies in uncovering potential cellular "side effects" of drugs (unanticipated off-target inhibition or activation) that may be overlooked by standard selectivity profiling methods.
Transcriptional and functional profiling defines human small intestinal macrophage subsets (2017)

Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos.
Pomegranate (2000)

Pomegranate is a parallel hardware architecture for polygon rendering that provides scalable input bandwidth, triangle rate, pixel rate, texture memory and display bandwidth while maintaining an immediate-mode interface. The basic unit of scalability is a single graphics pipeline, and up to 64 such units may be combined. Pomegranate's scalability is achieved with a novel “sort-everywhere” architecture that distributes work in a balanced fashion at every stage of the pipeline, keeping the amount of work performed by each pipeline uniform as the system scales. Because of the balanced distribution, a scalable network based on high-speed point-to-point links can be used for communicating between the pipelines.
The World Is Still Flat (2007)

The author of the book 'The World is Flat: A Brief History of the 21st Century' delivered The Sydney Institute's Annual Dinner Lecture. He discusses the ideas in the book - that the global economic playing field is being levelled or flattened. The ten forces, events, technologies and companies that he identifies as having created this flat-world platform are outlined. These include the fall of the Berlin Wall, the September 11 attacks and the first Internet browser. The forms of collaboration that the Internet allowed (including the opportunities for companies in Brazil, China and India) are discussed. The vote of thanks is presented by David Mortimer.
RANKL-Mediated Osteoclast Formation from Murine RAW 264.7 Cells (2003)

Osteoclasts (OCs) are the cells uniquely responsible for dissolving both the organic and inorganic components of bone during bone development and remodeling throughout life. These cells originate from hematopoietic precursors of the monocyte/macrophage lineage that are present both in the bone marrow and peripheral circulation, and their numbers and/or activity are frequently increased in a wide array of clinical disorders that are associated with excessive bone loss and affect millions of people (). For many years, investigations into how OCs develop and function have been hampered by the considerable difficulties associated with isolating and culturing these normally rare cells. Whereas cell lines have frequently provided an invaluable research tool and are widely used to decipher mechanisms involved in osteoblast (OB) differentiation and bone formation, no immortalized cell lines for mature OCs exist and the few pre-OC cell lines that have been reported either do not undergo full OC differentiation (,) or involve coculture systems and cells that may not be readily available to all researchers (, , ). To compound the problem further, it has proven difficult or impossible until recently to generate reliably bone-resorptive OCs expressing mature OC characteristics from primary bone marrow or circulating precursor cells in vitro. However, recent breakthroughs have now made the latter possible owing to the identification of the key signal, receptor activator of nuclear factor κB ligand (RANKL), that is responsible for the full development and activation of OCs both in vitro and in vivo (, , ).
The human cathelicidin, hCAP-18, is processed extracellularly to the antimicrobial peptide LL-37 by proteinase 3. (2000)

The human cathelicidin, hCAP-18, is processed extracellularly to the antimicrobial peptide LL-37 by proteinase 3.
Synthesis of a material with high juvenile hormone activity. (1966)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Pathogenic aquaporin-4 reactive T cells are sufficient to induce mouse model of neuromyelitis optica (2015)

In summary, we show that AQP4-reactive T cells are sufficient to trigger an NMO-like disease in mice, independent of antibodies, indicating that pathogenic AQP4-reactive T cells may play a similar role in humans.
ABodyBuilder: Automated antibody structure prediction with data–driven accuracy estimation (2016)

Computational modeling of antibody structures plays a critical role in therapeutic antibody design. Several antibody modeling pipelines exist, but no freely available methods currently model nanobodies, provide estimates of expected model accuracy, or highlight potential issues with the antibody's experimental development. Here, we describe our automated antibody modeling pipeline, ABodyBuilder, designed to overcome these issues. The algorithm itself follows the standard 4 steps of template selection, orientation prediction, complementarity-determining region (CDR) loop modeling, and side chain prediction. ABodyBuilder then annotates the 'confidence' of the model as a probability that a component of the antibody (e.g., CDRL3 loop) will be modeled within a root-mean square deviation threshold. It also flags structural motifs on the model that are known to cause issues during in vitro development. ABodyBuilder was tested on 4 separate datasets, including the 11 antibodies from the Antibody Modeling Assessment-II competition. ABodyBuilder builds models that are of similar quality to other methodologies, with sub-Angstrom predictions for the 'canonical' CDR loops. Its ability to model nanobodies, and rapidly generate models (∼30 seconds per model) widens its potential usage. ABodyBuilder can also help users in decision-making for the development of novel antibodies because it provides model confidence and potential sequence liabilities. ABodyBuilder is freely available at http://opig.stats.ox.ac.uk/webapps/abodybuilder .