gebhart/patrepeval huggingface dataset:
The Relationship between Nurse Work Schedules, Sleep Duration, and Drowsy Driving (2007)

Given the large numbers of nurses who reported struggling to stay awake when driving home from work and the frequency with which nurses reported drowsy driving, greater attention should be paid to increasing nurse awareness of the risks and to implementing strategies to prevent drowsy driving episodes to ensure public safety. Without mitigation, fatigued nurses will continue to put the public and themselves at risk.
Nanotubular Highways for Intercellular Organelle Transport (2004)

Cell-to-cell communication is a crucial prerequisite for the development and maintenance of multicellular organisms. To date, diverse mechanisms of intercellular exchange of information have been documented, including chemical synapses, gap junctions, and plasmodesmata. Here, we describe highly sensitive nanotubular structures formed de novo between cells that create complex networks. These structures facilitate the selective transfer of membrane vesicles and organelles but seem to impede the flow of small molecules. Accordingly, we propose a novel biological principle of cell-to-cell interaction based on membrane continuity and intercellular transfer of organelles.
From retrospect to prospect: Assessing modularity and stability from software architecture (2009)

Architecture level decisions, directly influenced by environmental factors, are crucial to preserve modularity and stability throughout software development life cycle. Tradeoffs of modularization alternatives, such as aspect oriented vs. object-oriented decompositions, thus need to be assessed from architecture models instead of source code. In this paper, we present a suite of architecture level metrics, taking external factors that drive software changes into consideration and measuring how well an architecture produces independently substitutable modules. We formalize these metrics using logical models to automate quantitative stability and modularity assessment. We evaluate the metrics using eight aspect oriented and object-oriented releases of a software product line architecture, driven by a series of heterogeneous changes. By contrasting with an implementation level analysis, we observe that these metrics can effectively reveal which modularization alternative generates more stable, modular design from high-level models.
Spontaneous, elongation factor G independent translocation of Escherichia coli ribosomes. (1983)

In a classical translocation experiment, deacylated RNA is bound to the ribosomal peptidyl-tRNA site (P site) and N-acetyl-phenylalanyl-tRNA (AcPhe-tRNA) to the aminoacyl-tRNA site (A site); upon addition of elongation factor (EF-G) and GTP, AcPhe-tRNA is translocated from the A to the P site. Here, we demonstrate a model reaction for a spontaneous, EF-G independent translocation. If AcPhe-tRNA is bound to the P site and Phe-tRNA to the A site at 15 mM Mg2+, then at 37 degrees C up to 60% of the AcPhe2-tRNA formed is found at the P site without the addition of EF-G. We demonstrate the following: 1) the spontaneous translocation is not merely illusory as a result of Phe-tRNA binding directly to the P site; 2) it is not mimicked by release of AcPhe2-tRNA from an A site and rebinding to a P site of another ribosome; 3) it is not caused by an EF-G contaminant present in the 70 S preparation, since without EF-G the spontaneous translocation works equally well in the presence of guanyl-5'-yl imidodiphosphate or fusidic acid; 4) AcPhe2-tRNA evidently has a higher affinity for the P site than AcPhe-tRNA, thus promoting the spontaneous translocation; and 5) peptide-bond formation favors the subsequent translocation. Addition of EF-G increases the initial rate by a factor of 13. Furthermore, at 15 mM Mg2+, 37 degrees C and in the presence of EF-G and GTP, Phe-tRNA cannot be translocated from the A to the P site, if the P site is occupied by deacylated tRNA. With the spontaneous translocation system, all reactions of the elongation cycle are cooperatively interconnected; i.e. upon binding of aminoacyl-tRNA to the A site, a significant portion of the ribosomes performs a complete round of the elongation cycle without the addition of elongation factor EF-G.
Evaluation of the Datascope Accutorr Plus according to the recommendations of the Association for the Advancement of Medical Instrumentation. (1997)

BACKGROUND: Automatic noninvasive blood pressure measurement devices should be clinically validated prior to marketing using standard criteria such as those published by the Association for the Advancement of Medical Instrumentation and the British Hypertension Society. OBJECTIVE: To assess a new bedside oscillometric device (Accutorr Plus, Datascope Inc., Montvale, New Jersey, USA). METHODS: We compared measurements obtained using the device with mercury column measurements for 90 subjects (448 measurements). In addition to calculation of the limits of agreement for the device versus observers, we determined the impact of age, the blood pressure level, the body mass, and the arm size on the levels of agreement. RESULTS: There was a good agreement between observers, with a mean difference of 0.38 +/- 4.47 mmHg for the systolic and 0.0 +/- 3.7 mmHg for the diastolic blood pressure. The observer-device agreement was -0.04 +/- 7.93 mmHg for the systolic and 0.35 +/- 5.75 mmHg for the diastolic blood pressure. Regression analyses showed that, as the systolic blood pressure and age increased, the level of disagreement for the systolic blood pressure also increased ( P < 0.001 for both). CONCLUSIONS: The Accutorr Plus satisfied the criteria of the Association for the Advancement of Medical Instrumentation for a general adult population with large ranges in age, blood pressure, body mass and arm circumference. Not unlike many oscillometric devices, for systolic blood pressures > 190 mmHg, the device error increased.
Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. (1987)

We investigated the antigen specificity and presentation requirements for inactivation of T lymphocytes in vitro and in vivo. In vitro studies revealed that splenocytes treated with the crosslinker 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (ECDI) and soluble antigen fragments failed to stimulate significant proliferation by normal pigeon cytochrome c-specific T cell clones, suggesting that the chemical treatment inactivated full antigen presentation function. However, T cell clones exposed to ECDI-treated splenocytes and antigen in vitro were rendered unresponsive for at least 8 d to subsequent antigen stimulation with normal presenting cells. As predicted by the in vitro results, specific T cell unresponsiveness was also induced in vivo in B10.A mice injected intravenously with B10.A, but not B10.A(4R), splenocytes coupled with pigeon cytochrome c via ECDI. The antigen and MHC specificity of the induction of this T cell unresponsiveness in vitro and in vivo was identical to that required for T cell activation. These results suggest that nonmitogenic T cell recognition of antigen/MHC on ECDI-modified APCs results in the functional inactivation of T cell clones.
Pre-hospital surgical cricothyroidotomy by advanced paramedics within a UK regional ambulance service: a service evaluation (2017)

Abstract published with permission. Introduction ‐ Surgical cricothyroidotomy, the insertion of a tracheal tube through an incision in the cricothyroid membrane, is a life-saving intervention utilised when other methods of airway management are ineffective. This evaluation aims to examine the procedural success of the intervention when performed by advanced paramedics within the North West Ambulance Service over a 4-year period. Methods ‐ A retrospective database and patient record evaluation were used, utilising internal data from the North West Ambulance Service. Patients who underwent pre-hospital surgical cricothyroidotomy performed by a North West Ambulance Service advanced paramedic between November 2012 and April 2017 were included. Indications for use, patient demographics, time to insertion and overall success rate data were collected. Results ‐ Pre-hospital surgical cricothyroidotomy was performed on a total of 36 occasions. Medical cardiac arrest accounted for 18 (50%) and traumatic cardiac arrest for 12 (33%) of the interventions. The remaining interventions were performed on patients with cardiac output at the time of the intervention: five (14%) traumatic aetiology and one (3%) medical aetiology. Of the patients, 31 (86%) were male and five (14%) female. The median age was 44.5 years old; ages ranged from 9 years to 88 years old (IQR 29.75). Median time from first cut to insertion of the tracheal tube was 1 minute (range < 30 secs‐5 mins; IQR 75 secs). The overall success rate for pre-hospital surgical cricothyroidotomy was 97% (n = 35). An inability to locate anatomical landmarks was attributed to the only unsuccessful attempt secondary to foreign body airway obstruction. Discussion ‐ Surgical cricothyroidotomy was successfully performed autonomously for a variety of pre-hospital emergency aetiologies across a variety of patient demographics. The success rate (97%) of the intervention, defined as successful ventilation via a surgically inserted tracheal tube, when performed by this cohort of North West Ambulance Service advanced paramedics is highly favourable when compared with other professional groups undertaking the intervention in the pre-hospital environment.
Mucoadhesive polymers for buccal drug delivery (2014)

Raising the concept of mucoadhesion in the 1980s, the use of mucoadhesive polymers for buccal drug delivery has been the subject of interest. Buccal route is one of the non-invasive routes comprising several advantages such as targeting the specific tissue (I), bypassing the first-pass effect (II) as well as higher patient compliance (III) and higher bioavailability (IV) have rendered administration route feasible for a variety of drugs. This review highlights the use of mucoadhesive polymers in buccal drug delivery. An overview of the oral mucosa's anatomy, theories of mucoadhesion as well as mucoadhesive polymers is given within this review. Furthermore, recent advantages in mucoadhesive polymers according to the variety of drug delivery forms are presented.
TCP startup performance in large bandwidth networks (2005)

Next generation networks with large bandwidth and long delay pose a major challenge to TCP performance, especially during the startup period. We evaluate the performance of TCP Reno/Newreno, Vegas and Hoe's modification in large bandwidth delay networks. We propose a modified slow-start mechanism, called adaptive start (Astart), to improve the startup performance in such networks. When a connection initially begins or re-starts after a coarse timeout, Astart adaptively and repeatedly resets the slow-start threshold (ssthresh) based on an eligible sending rate estimation mechanism proposed in TCP Westwood. By adapting to network conditions during the startup phase, a sender is able to grow the congestion window (cwnd) fast without incurring risk of buffer overflow and multiple losses. Simulation experiments show that Astart can significantly improve the link utilization under various bandwidth, buffer size and round-trip propagation times. The method avoids both under-utilization due to premature slow-start termination, as well as multiple losses due to initially setting ssthresh too high, or increasing cwnd too fast. Experiments also show that Astart achieves good fairness and friendliness toward TCP New Reno. Lab measurements using a Free BSD Astart implementation are also reported in this paper, providing further evidence of the gains achievable via Astart.
Thalidomide analogue CC1069 inhibits development of rat adjuvant arthritis (1999)

The cytokine tumour necrosis factor-alpha (TNF-alpha) has been implicated in the aetiology of rheumatoid arthritis in humans as well as of experimental arthritis in rodents. Thalidomide, and to a greater extent the new thalidomide analogue CC1069, inhibit monocyte TNF-alpha production both in vitro and in vivo. The aim of the present study is to establish whether these drugs block production of TNF-alpha as well as IL-2 by rat leucocytes and whether this inhibition affects the development of rat adjuvant arthritis (AA). Cultured splenocytes were stimulated with either lipopolysaccharide (LPS) or concanavalin A (Con A) in the presence of thalidomide, CC1069, or solvent, and the production of TNF-alpha and IL-2 were compared. Next, adjuvant was injected into the base of the tail of rats without or with daily intraperitoneal injections with 100-200 mg/kg per day thalidomide or 50-200 mg/kg per day CC1069. Disease activity, including ankle swelling, hind limb radiographic and histological changes, weight gain, and ankle joint cytokine mRNA levels, were monitored. CC1069, but not the parent drug thalidomide, inhibited in vitro production of TNF-alpha and IL-2 by stimulated splenocytes in a dose-dependent manner. In vivo, a dose-dependent suppression of AA disease activity occurred in the CC1069-treated animals. In contrast, thalidomide-treated rats experienced comparable arthritis severity to placebo-treated animals. There was also a reduction in TNF-alpha and IL-2 mRNA levels in the ankle joints of CC1069-treated rats compared with thalidomide- and placebo-treated arthritic rats. Early initiation of CC1069 treatment suppressed AA inflammation more efficiently than delayed treatment. We conclude that thalidomide, which did not suppress TNF-alpha or IL-2 production in vitro by Lewis rat cells, did not suppress development of rat AA. However, the development of rat AA can be blocked by the thalidomide analogue CC1069, which is an efficient inhibitor of TNF-alpha production and IL-2 in vitro.
The TAK1-NLK Mitogen-Activated Protein Kinase Cascade Functions in the Wnt-5a/Ca2+ Pathway To Antagonize Wnt/β-Catenin Signaling (2002)

Wnt signaling controls a variety of developmental processes. The canonical Wnt/beta-catenin pathway functions to stabilize beta-catenin, and the noncanonical Wnt/Ca(2+) pathway activates Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). In addition, the Wnt/Ca(2+) pathway activated by Wnt-5a antagonizes the Wnt/beta-catenin pathway via an unknown mechanism. The mitogen-activated protein kinase (MAPK) pathway composed of TAK1 MAPK kinase kinase and NLK MAPK also negatively regulates the canonical Wnt/beta-catenin signaling pathway. Here we show that activation of CaMKII induces stimulation of the TAK1-NLK pathway. Overexpression of Wnt-5a in HEK293 cells activates NLK through TAK1. Furthermore, by using a chimeric receptor (beta(2)AR-Rfz-2) containing the ligand-binding and transmembrane segments from the beta(2)-adrenergic receptor (beta(2)AR) and the cytoplasmic domains from rat Frizzled-2 (Rfz-2), stimulation with the beta-adrenergic agonist isoproterenol activates activities of endogenous CaMKII, TAK1, and NLK and inhibits beta-catenin-induced transcriptional activation. These results suggest that the TAK1-NLK MAPK cascade is activated by the noncanonical Wnt-5a/Ca(2+) pathway and antagonizes canonical Wnt/beta-catenin signaling.
Immunoradioactive agent against cancer. (1967)

Dextromoramide-Seymour-Shove and Wilson Ml for non-therapeutic reasons is recognized to be of increasing importance among younger people in Britain (Connell, 1964; Bewley, 1965). Dependence on an extensive range of other drugs is also becoming more common (Wilson, 1965 ; Madden and Wilson, 1966). This alarming increase in non-therapeutically-induced dependence must not be allowed to with- draw attention from the possibility of causing dependence in patients as a result of unwise or ignorant prescription of dependence-producing drugs for therapeutic reasons.
A unique view on male infertility around the globe (2015)

This study demonstrates a novel and unique way to calculate the distribution of male infertility around the world. According to our results, at least 30 million men worldwide are infertile with the highest rates in Africa and Eastern Europe. Results indicate further research is needed regarding etiology and treatment, reduce stigma & cultural barriers, and establish a more precise calculation.
Mitochondrial medicine (1995)

Abstract. In the mitochondrion, inherited defects have been identified in the electron transport system by which ATP is formed, as well as in the transport and metabolism of fuels. Clinical findings in diseases due to these defects can be related to abnormal accumulations of metabolic intermediates and inadequate or inefficient ATP generation. In the oxidative process within the mitochondrion, chemical oxidants are generated, which can cause cellular damage. As the body's defences against the oxidants decline, oxidative damage appears to contribute to the ageing process itself as well as to age‐related degenerative diseases. Understanding in this area has accelerated with knowledge of the synthesis, structure and function of the mitochondrion and its specific DNA. The frontier is expected to advance rapidly as causal relationships between these diseases and mitochondrial dysfunction, and the potential role of antioxidants in therapy, are better defined.
A New Monoclonal Anti-CD3∊ Antibody Reactive on Paraffin Sections (2000)

We generated a new monoclonal antibody (MAb), F7.2.38, by immunizing mice with CD3varepsilongammadelta/CD3omega complexes purified from human T-cells by OKT3 MAb-Sepharose affinity chromatography. Immunoprecipitation experiments and Western blotting analysis showed that MAb F7.2.38 recognized the CD3varepsilon chain in CD3varepsilon cDNA-transfected FOX B-cells and in various T-cell lines. Using flow cytometry on permeabilized or intact cells, the epitope was found to be located in the cytoplasmic tail of the CD3varepsilon chain. Immunohistochemical staining on paraffin-embedded sections showed that the reactivity of MAb F7.2.38 was comparable to that of the commercially available anti-CD3varepsilon polyclonal antibody. Of the 52 well-characterized T-cell lymphomas, 41 were positive for F7. 2.38 (79%), whereas all 37 B-cell lymphomas and 69 non-lymphoid tumors were unreactive. This new anti-CD3varepsilon antibody would be particularly useful for phenotyping T-cell lymphomas on routinely processed paraffin-embedded tissue sections.
Antitubulin agents for the treatment of cancer – a medicinal chemistry update (2006)

The antitubulin agents taxanes and Vinca alkaloids form the first-line of treatment in clinical oncology for many cancers. The crucial role of microtubules in cell division has made antitubulin agents the focus of research, with sustained efforts to find new agents and to improve the profile of known agents by overcoming multi-drug resistance (MDR) and improving the druggability. The present review updates the medicinal chemistry of antitubulin agents covering the patents and literature published from May 2002 to November 2005. The antitubulin agents have been broadly classified into microtubule-destabilising agents, microtubule-stabilising agents and kinesin-like spindle protein inhibitors. This review provides an insight into the diversity of the chemical classes with antitubulin mechanisms of anticancer activity.
Impact of water‐dispersible beadlets as a vehicle for the delivery of carotenoids to cultured cells (2002)

Water-dispersible beadlets of carotenoids were used as supplements for human umbilical vein endothelial cells (HUVECs), human peripheral blood mononuclear cells (PBMCs) and human monocytes. Stability, cellular association and cytotoxicity of the carotenoid beadlets were compared with carotenoids delivered with tetrahydrofuran (THF). Incubations with lycopene, beta-carotene, lutein and astaxanthin dissolved in THF resulted in a lower stability in the medium, lower cellular association, and a higher standard deviation. Beadlets provided 60, 4, 6, and 2 times greater accumulation of lycopene, beta-carotene, lutein and astaxanthin, respectively, by PBMCs than THF. The cellular association of carotenoids delivered by THF seems to be more carotenoid-specific than when carotenoids are delivered by beadlets. After 48 h of incubation under cell culture conditions all of the four carotenoids (1 microM) delivered by beadlets to the medium showed a reduction less than 30%. In addition, no cytotoxic effect of the carotenoid beadlets or the vehicle alone was detected in a concentration range of 0.5-5 microM. The results show that beadlets are a non-toxic vehicle for supplementing and stabilizing carotenoids in culture media offering a reasonable compromise in term of cell accumulation efficiency.
Flow cytometric analysis of DNA stemline heterogeneity in primary and metastatic breast cancer (1991)

Flow cytometric DNA-ploidy analysis was used to investigate intratumor DNA stemline heterogeneity in primary breast carcinomas and lymph node metastases (LNM). The study was done in tumor specimens from 44 patients 35 of whom had LNM. In all, measurements were done in 214 different samples of primary tumors and 211 lymph nodes. Sixty-one percent (27/44) of the primary tumors were found to have multiple DNA aneuploid stemlines when the data of the separate samples per tumor (mean 4.9) were compared. Only five of 44 (11%) primary tumors were DNA diploid; two of these had DNA aneuploid metastases. Statistical analysis of these results indicated that, on average, four samples are needed for reliable determination of the DNA ploidy status of primary tumors by flow cytometry. In the majority of the cases (26/35), distinct tumor DNA stemlines found in LNM were also present in the primary tumor, which suggests that the generation of DNA ploidy diversity may have taken place prior to metastasis. Multiploidy was not related to tumor size but, particularly for LNM, was significantly correlated with age (r = 0.40, P = 0.02). The results of this study support the view that breast cancer is an extremely heterogeneous disease and that underestimation of this factor might account for the disagreement in literature about the prognostic value of DNA ploidy determinations.
Global DNA Methylation Level in Whole Blood as a Biomarker in Head and Neck Squamous Cell Carcinoma (2007)

DNA hypomethylation in nontarget tissue was independently associated with HNSCC and had a complex relationship with the known risk factors associated with the genesis of HNSCC.