gebhart/patrepeval huggingface dataset:
Data collection strategies for patient-reported information (1994)

The U.S. health care transition demands increased accountability for medical care. This has contributed to increased interest in documenting medical outcomes, including improvements in health-related quality of life and treatment satisfaction. These data can only be obtained by asking patients directly about their current health state, perception of well-being, and satisfaction with care. Systematic collection of patient-reported data is often poorly done because its demands are underestimated and inadequately supported. Rigorous quality assurance is critical in any clinical trial or treatment delivery evaluation program.
Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence (1999)

The synthesis of virulence factors and other extracellular proteins responsible for pathogenicity in Staphylococcus aureus is under the control of the agr locus. A secreted agr-encoded peptide, AgrD, processed from the AgrD gene product, is known to be an effector of self-strain activation and cross-strain inhibition of the agr response. Biochemical analysis of AgrD peptides isolated from culture supernatants has suggested that they contain an unusual thiol ester-linked cyclic structure. In the present work, chemical synthesis is used to confirm that the mature AgrD peptides contain a thiolactone structure and that this feature is absolutely necessary for full biological activity. The AgrD synthetic thiolactone peptides exhibited biological activity in vivo in a mouse protection test. Structure-activity studies have allowed key aspects of the peptide structure involved in the differential activation and inhibition functions to be identified. Accordingly, we propose a model for activation and inhibition of the agr response in which the former, but not the latter, involves specific acylation of the agr transmembrane receptor, AgrC.
Insulin-Like Growth Factor 1 and a Cytosolic Tyrosine Kinase Activate Chloride Outward Transport during Maturation of Hippocampal Neurons (2001)

The development of hyperpolarizing inhibition is an important step in the maturation of neuronal networks. Hyperpolarizing inhibition requires Cl(-) outward transport that is accomplished by KCC2, a K(+)/Cl(-) cotransporter. We show that cultured hippocampal neurons initially contain an inactive form of the KCC2 protein, which becomes activated during subsequent maturation of the neurons. We also show that this process is accelerated by transient stimulation of IGF-1 receptors. Because the transporter can be rapidly activated by coapplication of IGF-1 and an Src kinase and can be deactivated by membrane-permeable protein tyrosine kinase inhibitors, we suggest that activation of K(+)/Cl(-) cotransporter function by endogenous protein tyrosine kinases mediates the developmental switch of GABAergic responses to hyperpolarizing inhibition.
Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure. (1995)

To determine whether additional hypertrophy would be beneficial or maladaptive in cardiac failure, the effects of insulin-like growth factor (IGF-1) were investigated in rats with left ventricular (LV) dysfunction. In normal rats, 3 mg/kg per d of recombinant human IGF-1 for 14 d augmented LV wt (32%) and increased LV/body wt ratio (P < 0.01). 2 d after coronary occlusion, rats were randomized to IGF-1 (3 mg/kg per d) or placebo. After 2 wk, IGF-1-treated rats showed significant increases in LV wt (13%) and LV wt/tibial length ratio, but LV/body wt ratio was unchanged. By microangiography, compared with controls (n = 12) IGF-1-treated rats (n = 16) showed increased LV end-diastolic volume (19%) and stroke volume (31%) (both significant normalized to tibial length, but not to body wt). Average infarct size did not differ between groups. The LV ejection fraction (EF) was not significantly different between groups, but estimated cardiac output was higher in treated rats; there was a significant interaction for the EF between infarct size and treatment (P = 0.029) and a trend for EF to be higher in treated rats with large infarctions (EF 33.4 vs 25.1% in controls). Myocyte cross-sectional areas in noninfarcted LV zones tended to be larger in treated rats (232.1 vs 205.4 microns 2; P = 0.10), but there was no difference in capillary density and collagen content did not differ between groups. In conclusion, IGF-1 administration caused hypertrophy of the normal heart in vivo. When stimulated by IGF-1, the severely dysfunctional heart in evolving myocardial infarction is capable of undergoing additional hypertrophy with evidence of improved function, suggesting a beneficial effect. Further investigation of the potential role of growth factor therapy in heart failure appears warranted.
A practical approach for 'zero' downtime in an operational information system (2003)

An operational information system (OIS) supports a real-time view of an organization's information critical to its logistical business operations. A central component of an OIS is an engine that integrates data events captured from distributed, remote sources in order to derive meaningful real-time views of current operations. This event derivation engine (EDE) continuously updates these views and also publishes them to a potentially large number of remote subscribers. The paper first describes a sample OIS and EDE in the context of an airline's operations. It then defines the performance and availability requirements to be met by this system, specifically focusing on the EDE component. One particular requirement for the EDE is that subscribers to its output events should not experience downtime due to EDE failures, crashes or increased processing loads. Toward this end, we develop and evaluate a practical technique for masking failures and for hiding the costs of recovery from EDE subscribers. This technique utilizes redundant EDEs that coordinate view replicas with a relaxed synchronous fault tolerance protocol. A combination of pre- and post-buffering of replicas is used to attain a solution that offers low response times (i.e., 'zero' downtime) while also preventing system failures in the presence of deterministic faults like 'ill-formed' messages. Parallelism realized via a cluster machine and application-specific techniques for reducing synchronization across replicas are used to scale a 'zero' downtime EDE to support the large number of subscribers it must service.
Characteristic Physical Properties and Structural Fragments of Marketed Oral Drugs (2003)

An increasingly competitive pharmaceutical market demands improvement in the efficiency and probability of drug candidate discovery. Usually these new drug candidates are targeted for oral administration, so a detailed understanding of the molecular-level properties that relate to optimal pharmacokinetics is a critical step toward improving the probability of selecting successful clinical candidates. Although the characteristics of druglike molecules have been previously discussed in the literature, the importance of this topic sustains a continued interest for additional perspective and further detailed statistical analyses. In this contribution, we approach the analysis from the perspective of profiling distinguishing features of orally administered drugs. We have compiled both structural and route-administration information for a total of 1729 marketed drugs to provide a solid basis for developing a new perspective on the characteristics of over 1000 orally administered drugs. The molecular properties and most commonly occurring structural elements are statistically analyzed to capture the differences between routes of administration, as well as between marketed drugs and SAR or clinical compounds. We find that, with respect to other routes of administration, oral drugs tend to be lighter and have fewer H-bond donors, acceptors, and rotatable bonds than drugs with other routes of administration. These differences are particularly pronounced when comparing the mean values for oral vs injectable drugs. We also demonstrate that the mean property values for oral drugs do not vary substantially with respect to launch date, suggesting that the range of acceptable oral properties is independent of synthetic complexity or targeted receptor. Finally, we note that, while these properties are descriptive of each class, they are not necessarily predictive of what class any particular drug will reside in, since there is significant overlap in the acceptable ranges found for each drug class.
In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). (2000)

Phosphatidylinositol 3-kinase (PI3-K) induces mitogenesis, cell growth, and cell transformation. Amplification of the gene encoding the P110alpha subunit likely is an important event in ovarian cancer progression, and PI3-K inhibitors are possible therapeutic agents for this disease. We evaluated effects of LY294002, a potent inhibitor of PI3-K, on growth of ovarian carcinoma in vivo and in vitro, and on ascites formation in vivo. Athymic mice were inoculated i.p. with the ovarian cancer cell line OVCAR-3. Seven days after inoculation, mice were treated with or without LY294002 (100 mg/kg of body weight) for 3 weeks. Body weight and abdominal circumference were measured twice weekly. At the end of the experiment, mice were sacrificed, ascites volume was measured, and tumors were excised. Mean tumor burden in the LY294002-treated group was reduced by approximately 65% versus controls. Virtually no ascites developed in the treatment group; mean volume of ascites in controls was 3.3 +/- 0.38 ml. OVCAR-3 cells also were cultured in vitro without and with LY294002 (1, 5, and 10 microM) for 24 h. The number of cells in 1, 5, and 10 microM LY294002-treated wells was reduced by 27, 56, and 75%, respectively, versus controls. In vivo and in vitro morphological studies demonstrated that LY294002 induced marked nuclear pyknosis and diminished cytoplasmic volume in the tumor cells, confirmed as apoptosis. Thus, LY294002 significantly inhibits growth and ascites formation of ovarian carcinoma in vivo and markedly inhibits ovarian cancer cell proliferation in vitro, suggesting an important role of PI3-K inhibitors as a potentially useful treatment for women with ovarian carcinoma.
Heteroaromatic Boron Compounds (1964)

This paper reviews the chemistry of a new class of heteroaromatic compounds containing boron atoms as components of six-membered aromatic rings; over twenty ring systems of this kind have been reported during the last five years. These compounds are of a different order of stability to any previously known organic compounds of boron and their discovery has opened up a whole new field of heteroaromatic chemistry. Boron can now be regarded as a respectable "organic" element.
TimeWarp (2008)

Mobile location-aware applications have become quite popular across a range of new areas such as pervasive games and mobile edutainment applications. However it is only recently, that approaches have been presented which combine gaming and education with mobile Augmented Reality systems. However they typically lack a close crossmedia integration of the surroundings, and often annotate or extend the environment rather than modifying and altering it.
FOLFIRI® and Bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms (2014)

Clinicaltrials.gov: NCT00467142 (registration date: April 25, 2007).
Surface-Enhanced Resonance Raman Scattering as a Novel Method of DNA Discrimination (2000)

DNA analysis often requires a separation step; this step is avoided if surface-enhanced resonance Raman scattering (SERRS) is used. SERRS is shown to differentiate between two labeled oligonucleotide strands, in varying proportions, in a mixture, and at low concentration levels. The method is discriminatory, sensitive, and requires only commonly available equipment.
Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia. (2000)

Despite achieving complete remission with retinoic acid (RA), most patients with acute promyelocytic leukemia (APL) have minimal residual disease detectable by reverse transcription-PCR (RT-PCR) amplification. HuM195, a humanized monoclonal antibody reactive with the cell surface antigen CD33, specifically targets and kills myeloid leukemia cells. We studied whether HuM195 could eliminate minimal residual disease in patients with APL by using RT-PCR. After attaining clinical complete remission with RA and/or chemotherapy, patients received HuM195 twice weekly for 3 weeks. Patients in first remission were given consolidation chemotherapy, generally with three cycles of idarubicin and cytarabine. Patients in second or greater remission did not receive chemotherapy. All patients received six monthly courses of maintenance with two doses of HuM195. Twenty-five of 27 patients treated in first remission had positive RT-PCR determinations before HuM195 treatment. Of the 22 patients evaluable for conversion of positive RT-PCR assays, 11 (50%) became RT-PCR negative after HuM195 treatment without additional therapy. Within the subset of patients who received RA alone as induction, 8 of 18 evaluable patients (44%) had negative RT-PCR determinations after HuM195 treatment but before chemotherapy. Among similar patients treated on earlier studies, 7 of 34 patients (21%) induced into remission with RA and then maintained on the drug for 1 month were RT-PCR negative before chemotherapy (P = 0.07). Twenty-five of 27 patients with newly diagnosed APL (93%) remain in clinical complete remission for 7+ to 58+ months, with median follow-up of 29 months. Seven patients in second or third remission and one patient in molecular relapse were also treated. Only one of these patients became RT-PCR negative after treatment with HuM195. These data suggest that HuM195 has activity against minimal residual disease in APL, particularly in newly diagnosed patients.
Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs (2004)

Dendritic cells (DCs) are known to induce the growth and function of natural killer (NK) cells. Here, we address the capacity of DCs to interact with NK cells in human lymphoid organs and identify the role of specific DC-derived cytokines. We demonstrate that DCs colocalize with NK cells in the T cell areas of lymph nodes. In culture, DCs from either blood or spleen primarily stimulate the CD56(bright)CD16- NK cell subset, which is enriched in secondary lymphoid tissues. Blocking of IL-12 abolished DC-induced IFN-gamma secretion by NK cells, whereas membrane-bound IL-15 on DCs was essential for NK cell proliferation and survival. Maturation by CD40 ligation promoted the highest IL-15 surface presentation on DCs and led to the strongest NK cell proliferation induced by DCs. These results identify secondary lymphoid organs as a potential DC/NK cell interaction site and identify the distinct roles for DC-derived IL-12 and IL-15 in NK cell activation.
QSAR − How Good Is It in Practice? Comparison of Descriptor Sets on an Unbiased Cross Section of Corporate Data Sets (2006)

The quality of QSAR (Quantitative Structure-Activity Relationships) predictions depends on a large number of factors including the descriptor set, the statistical method, and the data sets used. Here we study the quality of QSAR predictions mainly as a function of the data set and descriptor type using partial least squares as the statistical modeling method. The study makes use of the fact that we have access to a large number of data sets and to a variety of different QSAR descriptors. The main conclusions are that the quality of the predictions depends both on the data set and the descriptor used. The quality of the predictions correlates positively with the size of the data set and the range of biological activities. There is no clear dependence of the quality of the predictions on the complexity of the data set. All of the descriptors tested produced useful predictions for some of the data sets. None of the descriptors is best for all data sets; it is therefore necessary to test in each individual case, which descriptor produces the best model. In our tests, 2D fragment based descriptors usually performed better than simpler descriptors based on augmented atom types. Possible reasons for these observations are discussed.
Endothelin Receptor Type B Counteracts Tenascin-C–Induced Endothelin Receptor Type A–Dependent Focal Adhesion and Actin Stress Fiber Disorganization (2007)

Tenascin-C, an extracellular matrix molecule of the tumor-specific microenvironment, counteracts the tumor cell proliferation-suppressing effect of fibronectin by blocking the integrin alpha(5)beta(1)/syndecan-4 complex. This causes cell rounding and stimulates tumor cell proliferation. Tenascin-C also stimulates endothelin receptor type A (EDNRA) expression. Here, we investigated whether signaling through endothelin receptors affects tenascin-C-induced cell rounding. We observed that endothelin receptor type B (EDNRB) activation inhibited cell rounding by tenascin-C and induced spreading by restoring expression and function of focal adhesion kinase (FAK), paxillin, RhoA, and tropomyosin-1 (TM1) via activation of epidermal growth factor receptor, phospholipase C, c-Jun NH(2)-terminal kinase, and the phosphatidylinositol 3-kinase pathway. In contrast to EDNRB, signaling through EDNRA induced cell rounding, which correlated with FAK inhibition and TM1 and RhoA protein destabilization in the presence of tenascin-C. This occurred in a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-dependent manner. Thus, tumorigenesis might be enhanced by tenascin-C involving EDNRA signaling. Inhibition of tenascin-C in combination with blocking both endothelin receptors could present a strategy for sensitization of cancer and endothelial cells toward anoikis.
Catalysis of liquid phase organic reactions using chemically modified mesoporous inorganic solids (1998)

The modification of silicas and related materials by attachment of organic functionalities to their surface is an important area of research in heterogeneous catalysis and green chemistry. The methods available for the preparation of these hybrid organic–inorganic materials are reviewed, as are their applications as catalysts in a range of reactions.
Prorenin and Renin-Induced Extracellular Signal-Regulated Kinase 1/2 Activation in Monocytes Is Not Blocked by Aliskiren or the Handle-Region Peptide (2008)

The recently cloned (pro)renin receptor [(P)RR] mediates renin-stimulated cellular effects by activating mitogen-activated protein kinases and promotes nonproteolytic prorenin activation. In vivo, (P)RR is said to be blocked with a peptide consisting of 10 amino acids from the prorenin prosegment called the "handle-region" peptide (HRP). We tested whether human prorenin and renin induce extracellular signal-regulated kinase (ERK) 1/2 activation and whether the direct renin inhibitor aliskiren or the HRP inhibits the receptor. We detected the (P)RR mRNA and protein in isolated human monocytes and in U937 monocytes. In U937 cells, we found that both human renin and prorenin induced a long-lasting ERK 1/2 phosphorylation despite angiotensin II type 1 and 2 receptor blockade. In contrast to angiotensin II-ERK signaling, renin and prorenin signaling did not involve the epidermal growth factor receptor. A mitogen-activated protein kinase kinase 1/2 inhibitor inhibited both renin and prorenin-induced ERK 1/2 phosphorylation. Neither aliskiren nor HRP inhibited binding of (125)I-renin or (125)I-prorenin to (P)RR. Aliskiren did not inhibit renin and prorenin-induced ERK 1/2 phosphorylation and kinase activity. Fluorescence-activated cell sorter analysis showed that, although fluorescein isothiocyanate-labeled HRP bound to U937 cells, HRP did not inhibit renin or prorenin-induced ERK 1/2 activation. In conclusion, prorenin and renin-induced ERK 1/2 activation are independent of angiotensin II. The signal transduction is different from that evoked by angiotensin II. Aliskiren has no (P)RR blocking effect and did not inhibit ERK 1/2 phosphorylation or kinase activity. Finally, we found no evidence that HRP affects renin or prorenin binding and signaling.
Amiloride reduces the taste intensity of Na+ and Li+ salts and sweeteners. (1983)

The diuretic amiloride, a potent inhibitor of sodium transport in a variety of epithelial systems, was applied to the human tongue. Application of amiloride reduced the taste intensity of sodium and lithium salts and of sweeteners ranging widely in chemical structure. The sweeteners included saccharides, glycosides, dipeptides, proteins, and amino acids. Amiloride did not affect perception of potassium or calcium salts, bitter and sour tastes, or amino acids without a sweet or salty component. These findings were supported by neurophysiological studies in rat, which showed that amiloride diminished the NaCl response relative to KCl. The results are consistent with the position that an amiloride-sensitive transport mechanism is involved in taste perception of sodium and lithium salts and of sweeteners.
COVID-19 Testing (2020)

We demonstrate the value of reporting probability of false-positive results, probability of false-negative results, and costs to patients and health care. These risk metrics can be calculated from the risk drivers of PPA and PNA combined with estimates of prevalence, cost, and Reff number (people infected by 1 positive SARS-CoV-2 carrier).
Fiber-optic ladder networks for inverse decoding coherent CDMA (1992)

Coherent fiber-optic networks are used to improve upon incoherent CDMA schemes. If a single-channel network is used between transmitters and receivers, standard coherent correlation takes place. If several parallel spatial channels (fibers and/or polarizations) are used, ideal inverse decoding can be implemented, with perfect delta -function response of the matched decoder. The two-channel case is studied in detail. The rules for finding inverses of a given coding network and the relationship between matched networks for one-channel decoding and two-channel inverse decoding are given. Phase and frequency differences among stations imply that unwanted signals add up incoherently. The ideal two-channel network with inverse decoding has no loss due to encoding/decoding, only inevitable loss due to the broadcast network. In experiments using a single fiber between a transmitter and a receiver by orthogonal polarizations, delta -function inverse response was observed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia coli O157:H7 cleaves human coagulation factor V (1997)

In this study, we identified and characterized a novel secreted protein, the extracellular serine protease EspP, which is encoded by the large plasmid of enterohaemorrhagic Escherichia coli (EHEC) O157:H7. The corresponding espP gene consists of a 3900 bp open reading frame that is able to encode a 1300-amino-acid protein. EspP is synthesized as a large precursor which is then processed at the N- and C-termini during secretion. It can be grouped into the autotransporter protein family. The deduced amino acid sequence of EspP showed homology to several secreted or surface-exposed proteins of pathogenic bacteria, in particular EspC of enteropathogenic E. coli and IgA1 proteases from Neisseria spp. and Haemophilus influenzae. Hybridization experiments and immunoblot analysis of clinical EHEC isolates showed that EspP is widespread among EHEC of the serogroup O157 and that it also exists in serogroup 026. A specific immune response against EspP was detected in sera from patients suffering from EHEC infections. Functional analysis showed that EspP is a protease capable of cleaving pepsin A and human coagulation factor V. Degradation of factor V could contribute to the mucosal haemorrhage observed in patients with haemorrhagic colitis.