gebhart/patrepeval huggingface dataset:
Telomerase, checkpoints and cancer. (1997)

Telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state. In particular, the highly specific correlations and early causal relationships between telomere loss in the absence of telomerase activity and replicative senescence or crisis, on the one hand, and telomerase reactivation and cell immortality, on the other, point to a new and important paradigm in the complementary fields of ageing and cancer. Although the signalling pathways between telomeres and transcriptional and cell cycle machinery remain undefined, recently described homologies between telomeric proteins and lipid/protein kinase activities important in chromosome stability provide evidence for the existence of pathways transducing signals originating in chromosome structure to cell cycle regulatory processes. Similarities between cell cycle arrest at senescence and the response of mortal cells to DNA/oxidative damage suggest overlap in the signal transduction mechanisms culminating in irreversible and stable cell cycle arrest. The feasibility of targeting telomeres/telomerase as a strategy for antiproliferative therapeutics has been shown in studies in yeast, in which mutations in specific telomere associated genes result in delayed cell death. Similarly, antisense oligonucleotide inhibition of telomerase activity in human tumour cells (HeLa) results in delayed cell death. The mechanism of cell death and possible escape from this fate require further study. In human cells, however, it would seem reasonable to predict that in these circumstances, apoptosis is induced in the vast majority of cells either directly in response to a DNA damage signal arising from critically shortened telomeres or as a secondary consequence of genetic instability.
A phase Ia study of MPDL3280A (anti-PDL1): Updated response and survival data in urothelial bladder cancer (UBC). (2015)

4501 Background: PD-L1 may contribute to immune escape in UBC, a disease of high mutational complexity and immunogenicity. MPDL3280A was designed to restore T cell–mediated antitumor activity by blocking PD-L1 binding to PD-1 and B7.1 receptors. Methods: Previously treated, metastatic UBC pts were enrolled in an expansion cohort and received 15 mg/kg or 1200 mg IV MPDL3280A q3w. Efficacy-evaluable pts had ≥ 12 wk of follow-up (dosed by Jun 9, 2014; Sep 2, 2014 cutoff). ORR was assessed by RECIST v1.1 (unconfirmed), and archival biopsies were centrally evaluated for PD-L1 tumor-infiltrating immune cell (IC) expression by IHC. In-tumor gene expression and peripheral biomarkers were assessed as exploratory analyses in a subset of pts. Results: Updated analyses include 85 efficacy-evaluable, selectively enrolled UBC pts; 46 were PD-L1 IHC 2/3, 38 were IHC 0/1 and 1 had unknown IHC status. Median age was 66 y (36-89 y), and 75% were male. Baseline visceral mets were present in 77% of pts; 98% received ≥ 1 prior therapy (eg platinum in 93%). The ORR for IHC 2/3 pts was 46% (95% CI 31-61%; 6 CRs, 15 PRs), and for IHC 0/1 pts was 16% (95% CI 6-31%; 6 PRs) with median response durations not yet reached (IHC 2/3 pts, 0+ to 54+ wk; IHC 0/1 pts, 4+ to 33+ wk). Median PFS was 24 wk (95% CI 12-NE) for IHC 2/3 pts and 8 wk (95% CI 6-12 wk) for IHC 0/1 pts. 24-wk OS rates for IHC 2/3 and 0/1 pts were 85% (95% CI 74-96%) and 71% (95% CI 54-88%), respectively, with the medians not yet reached (3 to 72+ wk and 2+ to 51+ wk, respectively). Pts with visceral mets had ORRs of 32% (IHC 2/3: 3 CRs, 7 PRs; n = 31) and 12% (IHC 0/1: 4 PRs; n = 33). Median safety follow-up was 16 wk (3-73 wk). Drug-related AEs occurred in 64% of 87 safety-evaluable pts (most often fatigue, asthenia, nausea); 8% had a related G3-4 AE. 12% of pts had an immune-related AE. No related deaths were seen. Responders had lower myeloid gene expression at baseline (eg Cox-2, IL8; IL1B) and decreased circulating inflammatory and tumor markers (eg CRP; HCG, CA 19-9, CA-125) by cycle 2. Conclusions: MPDL3280A was well tolerated and had durable activity in UBC pts. Response, PFS and OS data are promising for IHC 2/3 and IHC 0/1 UBC pts vs historic controls. Response also correlated with in-tumor and blood-based biomarkers. Clinical trial information: NCT01375842.
1,2,3-Triazoles as versatile directing group for selective sp2 and sp3 C–H activation: cyclization vs substitution (2013)

Selective cyclization and substitution was achieved with designated 1,2,3-triazole acid auxiliary groups under Pd catalyzed C–H activation conditions. Both sp2 and sp3 C–H bonds were effectively activated, giving the desired products in good yields. This result revealed the first successful example of exclusive substitution using 1,2,3-triazole ligands, while another triazole-containing directing group dominantly gave cyclization under identical conditions.
IGOR: a system for program debugging via reversible execution (1988)

Typical debugging tools are insufficiently powerful to find the most difficult types of program misbehaviors. We have implemented a prototype of a new debugging system, IGOR, which provides a great deal more useful information and offers new abilities that are quite promising. The system runs fast enough to be quite useful while providing many features that are usually available only in an interpreted environment. We describe here some improved facilities (reverse execution, selective searching of execution history, substitution of data and executable parts of the programs) that are needed for serious debugging and are not found in traditional single-thread debugging tools. With a little help from the operating system, we provide these capabilities at reasonable cost without modifying the executable code and running fairly close to full speed. The prototype runs under the DUNE distributed operating system.The current system only supports debugging of single-thread programs. The paper describes planned extensions to make use of extra processors to speed the system and for applying the technique to multi-thread and time dependent executions.
Melting and flowing of viscous volumes (2004)

We present a simple, linear 3D cellular automata approach for animating the melting process of solid volumetric models. Accurate modelling of object melting usually requires complicated physical simulations of heat transfer and phase transition from solid to liquid. Instead, we propose a simplified model to describe the melting behaviors of highly viscous objects, such as wax, lava, plastic, metal and chocolate. We simulate the process by which a volumetric solid transforms into a viscous liquid as the amount of heat it accumulates on its surface reaches a certain temperature. We then animate smooth fluid behavior using a cellular automata. The dynamic volume data is rendered directly on texture mapping hardware to achieve an interactive speed.
Pain Relief and Opioid Requirements in the First 24 Hours after Surgery in Patients Taking Buprenorphine and Methadone Opioid Substitution Therapy (2013)

The number of patients in buprenorphine opioid substitution therapy (BOST) or methadone opioid substitution therapy (MOST) programs is increasing. If these patients require surgery, it is generally agreed that methadone should be continued perioperatively. While some also recommend that buprenorphine is continued, concerns that it may limit the analgesic effectiveness of full mu-opioid agonists have led others to suggest that it should cease before surgery. However, no good evidence exists for either course of action. Therefore, we undertook a retrospective cohort study comparing pain relief and opioid requirements in the first 24 hours after surgery in 22 BOST and 29 MOST patients prescribed patient-controlled analgesia. There were no significant differences in pain scores (rest and movement), incidence of nausea or vomiting requiring treatment, or sedation between the BOST and MOST patient groups overall, or between those patients within each of these groups who had and had not received their methadone or buprenorphine the day after surgery. There were also no significant differences in patient-controlled analgesia requirements between BOST and MOST patient groups overall, or between patients who did or did not receive MOST on the day after surgery. BOST patients who were not given their usual buprenorphine the day after surgery used significantly more patient-controlled analgesia opioid (P=0.02) compared with those who had received their dose. These results confirm that continuation of buprenorphine perioperatively is appropriate.
Integrated optical measurement system for fluorescence spectroscopy in microfluidic channels (2001)

A transportable miniaturized fiber-pigtailed measurement system is presented which allows quantitative fluorescence detection in microliquid handling systems. The microliquid handling chips are made in silica on silicon technology and the optical functionality is monolithically integrated with the microfluidic channel system. This results in inherent stability and photolithographic alignment precision. Permanently attached optical fibers provide a rugged connection to the light source, detection, and data processing unit, which potentially allows field use of such systems. Fluorescence measurements with two dyes, fluorescein, and Bodipy 650/665 X, showed good linear behavior over a wide range of concentrations. Minimally detected concentrations were 250 pM for fluorescein and 100 nM for Bodipy.
<i>PLA2G6</i> mutations in PARK14‐linked young‐onset parkinsonism and sporadic Parkinson's disease (2011)

Mutations of PLA2G6 gene have been lately proposed to be the causative gene for PARK14 in patients with autosomal recessive young-onset parkinsonism (YOPD). The role of PLA2G6 mutations as a risk factor for Parkinson's disease is not clear. To study the PLA2G6 mutations in PARK14-linked patients and its association with the onset of sporadic Parkinson's disease (sPD), sequencing and gene dosage analyses were carried out in 25 patients (onset age ≦30 years) then the identified variants were assessed in 956 sporadic PD (sPD) patients and 802 age-matched healthy controls. Four genetic variants were identified; one patient had homozygous c.991G > T (p.Asp331Tyr) mutation, two had compound heterozygous c.991G > T/c.1077G > A (p.Met358IlefsX) mutation, one had single c.1976A > G (p.Asn659Ser) mutation, and one patient had an exon 1 hetero-deletion. The c.1077G > A mutation resulted in a 4-bp deletion in leukocyte mRNA by activating a cryptic splice site in exon 7. Only p.Asp331Tyr was identified in four sPD patients and four controls. The onset age for PLA2G6 mutation carriers was younger than that for sPD (29.86 ± 8.59 vs. 56.84 ± 11.33 years, P = 0.0002). The analysis of previously reported PARK14 patients revealed that those who carried a truncated mutation tended to have a complicated phenotype and atrophies of cortex and cerebellum. In conclusion, PLA2G6 mutation was the second common genetic cause after PRKN mutation in our YOPD patients and might be a risk factor for early-onset PD in Han Chinese. Additionally, mutation data should be interpreted carefully because even a synonymous mutation could cause abnormal mRNA splicing.
Magnetographic assessment of fetal hiccups and their effect on fetal heart rhythm (2007)

Fetal hiccups emerge as early as nine weeks post-conception, being the predominant diaphragmatic movement before 26 weeks of gestation. They are considered as a programmed isometric inspiratory muscle exercise of the fetus in preparation for the post-natal respiratory function, or a manifestation of a reflex circuitry underlying the development of suckling and gasping patterns. The present paper provides the first evidence of non-invasive biomagnetic measurements of the diaphragm spasmodic contractions associated with fetal hiccups. The magnetic field patterns generated by fetal hiccups exhibit well-defined morphological features, consisting of an initial high frequency transient waveform followed by a more prolonged low frequency component. This pattern is consistent across recordings obtained from two fetal subjects, and it is confirmed by signals recorded in a neonatal subject. These results demonstrate that fetal biomagnetometry can provide insights into the electrophysiological mechanisms of diaphragm motor function in the fetus. Additionally, we study the correlation between hiccup events and fetal cardiac rhythm and provide evidence that hiccups may modulate the fetal heart rate during the last trimester of pregnancy.
Substituent Effects on Xenon Binding Affinity and Solution Behavior of Water-Soluble Cryptophanes (2009)

A water-soluble triacetic acid cryptophane-A derivative (TAAC) was synthesized and determined by isothermal titration calorimetry and fluorescence quenching assay to have a xenon association constant of 33,000 M(-1) at 293 K, which is the largest value measured for any host molecule to date. Fluorescence lifetime measurements of TAAC in the presence of varying amounts of xenon indicated static quenching by the encapsulated xenon and the presence of a second non-xenon-binding conformer in solution. Acid-base titrations and aqueous NMR spectroscopy of TAAC and a previously synthesized tris(triazole propionic acid) cryptophane-A derivative (TTPC) showed how solvation of the carboxylate anions can affect the aqueous behavior of the large, nonpolar cryptophane. Specifically, whereas only the crown-crown conformer of TTPC was observed, a crown-saddle conformer of TAAC was also assigned in aqueous solution.
Performic acid (PFA): tests on an advanced primary effluent show promising disinfection performance (2009)

Performic acid, or PFA (CH(2)O(3)), is a well-known oxidizing agent and disinfectant in the medical field and food industry. It has recently become available on a commercial scale for potential use in wastewater disinfection. This study investigated its application to an advanced primary effluent which is recalcitrant to disinfection by UV and peracetic acid (PAA). Methods were developed for determining PFA concentrations in stock solutions as well as in residual concentrations in the wastewater. Batch and continuous-flow pilot studies showed a correlation between log fecal coliform removals and PFA doses. A PFA dose of approximately 3.4 mg/L and a contact time of 45 minutes could achieve 3-logs removal, and almost total disinfection could be achieved using a dose of 6 mg/L. The by-products of PFA addition are hydrogen peroxide and formic acid (CHOOH), neither of which is considered to be toxic to aquatic fauna at the doses required for disinfection.
Evaluation of a Cell Selection Framework for Radio Access Networks considering Backhaul Resource Limitations (2007)

Cell selection in mobile radio access networks is mainly driven by efficient resource usage of the air interface. In this paper we add a new dimension to the cell selection problem by considering also the current occupancy of transport resources in the backhaul part of the network since, it is believed that, with the introduction of high speed services, this backhaul network can be a limiting factor. In such cases, we demonstrate that a cell selection algorithm using transport status information provides significant benefits over traditional schemes exclusively based on radio criteria, even under those scenarios where the selection of a cell other than the best radio server can be thought as not adequate in terms of radio resource management (e.g. single-layer/single-RAT deployments). The cell selection problem is analytically formulated and developed by means of a multidimensional Markov chain.
Cervical cancer vaccines: Emerging concepts and developments (2001)

Certain human cancers are linked to infection by oncogenic viruses that are able to cause transformation of the normal host cell into a cancerous cell. Human papillomavirus (HPV) DNA and expression of viral transforming proteins are found in virtually all cervical cancer cells, indicating an important role of this virus in the pathogenesis of the disease. Evidence exists that the immune response to cancer cells can play a major role in determining the outcome of disease. The fact that HPV is a necessary cause for cervical cancer provides a clear opportunity to develop a therapeutic vaccine against the virus to treat patients with cervical cancer at its early and late stages. Development of a prophylactic vaccine for HPV would also reduce the incidence of cervical neoplasias by preventing virus infection. Various candidate HPV vaccines are being developed and tested in animal models and/or in human clinical trials. These HPV vaccines, both preventive and therapeutic, are the subjects of this review.
Photodynamic detection of diseased axillary sentinel lymph node after oral application of aminolevulinic acid in patients with breast cancer (2004)

Benign as well as malignant tumour tissues of the breast demonstrate higher fluorescence intensity (FI) than normal breast tissue after application of a photosensitiser. As a follow-up study, we evaluated the FI of metastatic sentinel lymph nodes and metastatic axillary lymph nodes compared to nonmetastatic sentinel and axillary lymph nodes in patients with breast cancer. In all, 11 patients received 30 mg 5-aminolevulinic acid (ALA) kg(-1) bodyweight orally 3 h prior to surgery. The sentinel lymph node was marked with Nanocoll preoperatively and with a blue dye intraoperatively. Tumour excision, excision of the sentinel lymph node and an axillary lymph node dissection were performed during the same surgical session. The operation site was illuminated with blue light (400 nm) to obtain macroscopic tissue characterisation of fluorescence. Tissue samples were stored protected from light, and analysed using a fluorescence microscope. Results were correlated with histopathology. In all, 14 sentinel lymph nodes, seven axillary lymph nodes and seven primary tumours were analysed. Metastatic sentinel lymph nodes demonstrated a statistically significant higher FI than nonmetastatic sentinel lymph nodes (2630 vs 526, P<0.0001). The FI of metastatic sentinel lymph nodes, of metastatic axillary lymph nodes and of the primary tumour were comparably high, and were statistically significantly higher compared to the normal mammary tissue. Intraoperatively, only in a few cases, it was possible to recognise the metastatic sentinel lymph node macroscopically with blue light. Our study indicates that photodynamic diagnosis with ALA has a potential in the diagnosis and detection of the sentinel lymph node in patients with breast cancer, and is worth to be further investigated and developed for intraoperative photodynamic diagnosis and possibly therapy.
Imidazo[1,2-a]pyridines - novel substitution reactions (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImidazo[1,2-a]pyridines - novel substitution reactionsElli S. Hand and William W. PaudlerCite this: J. Org. Chem. 1976, 41, 22, 3549–3556Publication Date (Print):October 1, 1976Publication History Published online1 May 2002Published inissue 1 October 1976https://pubs.acs.org/doi/10.1021/jo00884a013https://doi.org/10.1021/jo00884a013research-articleACS PublicationsRequest reuse permissionsArticle Views381Altmetric-Citations17LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Radiation Sensitivity of Human Bone Marrow Cells Measured by a Cell Culture Method (1970)

Abstract A culture technique for measuring the proliferative capacity of a class of human hemopoietic cells is presented. This method is used to assess the radio-sensitivity of this class of human hemopoietic cells, and to compare them directly to mouse hemopoietic cells tested in the same system. We conclude that the sensitivity of human bone marrow to irradiation as measured directly is of the same order as that predicted on the basis of experiments in mice.
ConvoKit: A Toolkit for the Analysis of Conversations (2020)

Jonathan P. Chang, Caleb Chiam, Liye Fu, Andrew Wang, Justine Zhang, Cristian Danescu-Niculescu-Mizil. Proceedings of the 21th Annual Meeting of the Special Interest Group on Discourse and Dialogue. 2020.
Decisions (2015)

Maggie didn't make her trip to Weill Cornell Medical College to participate in studies of patients with severe brain injury. Left partially paralyzed and perhaps even permanently unconscious more than a year after a brainstem stroke during her senior year at Smith College, she was now fighting her third bout of pneumonia in succession. Her mother Nancy called to tell us she had to cancel the visit. Maggie was just too sick and the doctors at Good Samaritan Medical Center in Brockton, Massachusetts, wanted to reinsert a tracheostomy tube to help her breathe.
Nitric oxide and bone (2001)

Nitric oxide (NO) is a free radical which has important effects on bone cell function. The endothelial isoform of nitric oxide synthase (eNOS) is widely expressed in bone on a constitutive basis, whereas inducible NOS is only expressed in response to inflammatory stimuli. It is currently unclear whether neuronal NOS is expressed by bone cells. Pro-inflammatory cytokines such as IL-1 and TNF cause activation of the iNOS pathway in bone cells and NO derived from this pathway potentiates cytokine and inflammation induced bone loss. These actions of NO are relevant to the pathogenesis of osteoporosis in inflammatory diseases such as rheumatoid arthritis, which are characterized by increased NO production and cytokine activation. Interferon gamma is a particularly potent stimulator of NO production when combined with other cytokines, causing very high concentrations of NO to be produced. These high levels of NO inhibit bone resorption and formation and may act to suppress bone turnover in severe inflammation. The eNOS isoform seems to play a key role in regulating osteoblast activity and bone formation since eNOS knockout mice have osteoporosis due to defective bone formation. Other studies have indicated that the NO derived from the eNOS pathway acts as a mediator of the effects of oestrogen in bone. eNOS also mediates the effects of mechanical loading on the skeleton where it acts along with prostaglandins, to promote bone formation and suppress bone resorption. Pharmacological NO donors have been shown to increase bone mass in experimental animals and preliminary evidence suggests that these agents may also influence bone turnover in man. These data indicate that the L-arginine/NO pathway represents a novel target for therapeutic intervention in the prevention and treatment of bone diseases.