gebhart/patrepeval huggingface dataset:
Application of the linear-quadratic model with incomplete repair to radionuclide directed therapy (1991)

The linear-quadratic (LQ) model for fractionated external beam therapy has been modified by previous authors to include the effects due to an exponentially decaying dose rate. However, the LQ model has now been extended to include a general time varying dose rate profile, and the equations can be readily evaluated if an exponential radiation damage repair process is assumed. These equations are applicable to radionuclide directed therapy, including brachytherapy. Kinetic uptake data obtained during radionuclide directed therapy may therefore be used to determine the radiobiological dosimetry of the target and non-target tissues. Also, preliminary tracer studies may be used to pre-plan the radionuclide directed therapy, provided that tracer and therapeutic amounts of the radionuclide carrier are identically processed by the tissues. It is also shown that continuous radionuclide therapy will induce less damage in late-responding tissues than 2 Gy/fraction external beam therapy if the ratio of the maximum dose rate and the sublethal damage repair half-life in the tissue is less than 1.0 Gy. Similar inequalities may be derived for beta-particle radionuclide directed therapy. For example, it can be shown that radionuclide directed therapy will induce less damage to slowly repopulating tissue than 2 Gy/fraction external beam therapy for the same total dose if the maximum percentage initial uptake in tissue is less than 0.046%/g or 0.23%/g for an injected activity of 50 mCi of 90Y or 131I, respectively.
Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion (2007)

Our results identify a second case of the PRKG2-PDGFRB fusion and confirm the unusual PDGFRB breakpoint associated with this fusion. This work also illustrates the use of imatinib for the treatment of specific cases of systemic mastocytosis.
Queue-Dispatch Asynchronous Systems (2013)

To make the development of efficient multi-core applications easier, libraries, such as Grand Central Dispatch (GCD), have been proposed. When using such a library, the programmer writes so-called blocks, which are chunks of codes, and dispatches them, using synchronous or asynchronous calls, to several types of waiting queues. A scheduler is then responsible for dispatching those blocks on the available cores. Blocks can synchronize via a global memory. In this paper, we propose Queue-Dispatch Asynchronous Systems as a mathematical model that faithfully formalizes the synchronization mechanisms and the behavior of the scheduler in those systems. We study in detail their relationships to classical formalisms such as pushdown systems, Petri nets, fifo systems, and counter systems. Our main technical contributions are precise worst-case complexity results for the Parikh coverability problem and the termination question for several subclasses of our model. We give an outlook on extending our model towards verifying input-parametrized fork- join behaviour with the help of abstractions, and conclude with a hands-on approach for verifying GCD programs in practice.
Regulation of mRNA stability by CCCH-type zinc-finger proteins in immune cells (2017)

Current studies using knockout mice have revealed that some Cys-Cys-Cys-His (CCCH)-type zinc-finger proteins, namely tristetraprolin (TTP), Roquin and Regnase-1, play important roles in the immune system. These proteins are closely associated with the fate of their target RNAs in normal immune responses. However, the functions of many RNA-binding proteins have not been characterized precisely. To understand the molecular mechanisms of RNA metabolism in the immune system, investigation of TTP/Roquin/Regnase-1 might provide new knowledge. In this review, we will discuss the current understanding of these proteins in immune regulation and homeostasis and discuss RNA metabolism in the immune system.
Gangliosides of Various Rat Tissues: Distribution of Ganglio-N-Tetraose-Containing Gangliosides and Tissue-Characteristic Composition of Gangliosides1 (1984)

Gangliosides were extracted from various tissues of rat (Wistar strain, male, 3 months old) and their structures were elucidated by enzymatic and chemical procedures including the analysis by negative ion fast atom bombardment mass spectrometry. All tissues analyzed contained gangliosides in various but characteristic concentrations. GD1a was detected in the various extraneural tissues (erythrocytes, buffy coat, bone marrow, testis, spleen, and liver) in amounts corresponding to more than 30% of total lipid-bound sialic acid, and surprisingly, it was the sole ganglioside found in buffy coat. The extraneural tissues were classified into several categories according to the nature of the asialo-oligosaccharides of gangliosides as follows: (1) gangliosides with ganglio-N-tetraose were exclusively present (buffy coat and erythrocytes), (2) the concentration of ganglio-N-tetraose-containing gangliosides was higher than that of lactose-containing gangliosides (testis and bone marrow), (3) ganglio-N-tetraose-containing gangliosides amounted to 25-30% of lactose-containing gangliosides (liver and spleen), (4) ganglio-N-tetraose-containing gangliosides amounted to 7-11% of lactose-containing gangliosides (lung and stomach), (5) more than 90% of gangliosides were lactose-containing gangliosides (heart, intestine, and kidney). In addition, the following gangliosides were characteristically detected in high concentration in the following tissues: GM4 in kidney. GM2 in bone marrow, fucosyl GM1 and GM1 in erythrocytes and GM3 with 2-hydroxy fatty acid, phytosphingosine and N-glycolylneuraminic acid in intestine.
Application of 16S rDNA‐DGGE to examine the microbial ecology associated with a social wasp Vespula germanica (2003)

Invertebrates host numerous bacteria, with interactions ranging from pathogenesis to symbiosis. While certain symbiotic relationships have been well studied, little is known about the dynamics of these bacterial communities. Denaturing gradient gel electrophoresis (DGGE) was used to examine the bacterial microflora associated with the eusocial wasp Vespula germanica. DGGE profiles of larval guts revealed a variable microflora, suggesting that V. germanica is not dependent on a particular suite of mutualists. The variation in profiles was not related to season, nest size or macrohabitat. Sequences corresponding to Lactococcus, Lactobacillus, a novel Leuconostoc and two Rickettsiella grylli strains were obtained. DGGE proved to be a useful technique for characterizing the wasp microflora. Given the importance of microbial communities to invertebrates, there is much to be gained from the application of such techniques.
Against amnesia: representations of memory in Algerian cinema (2010)

Remembering and forgetting in their most extreme forms are crucial factors in the negotiation of a modern Algerian national identity. Algeria's history since gaining independence from French rule in 1962 has made questions of memory particularly acute. This article explores how the Algerian cinema of the last twenty years or so has attempted to counter official history working against both enforced amnesia and a state-sanctioned monolithic memory fixated on the liberation struggle to celebrate the transmission of corporeal gendered memory, of marginalized cultural identities, and of neglected historical origins. In the context of October 1988 and the so-called civil war of the 1990s, close readings are offered of films by Merzak Allouache, Mohamed Chouikh, Nadir Mokneche, Amor Hakkar and Tariq Teguia. Theoretical underpinning comes from readings of Fanon, Freud, cultural history and trauma theory.
Robustness of adiabatic quantum computation (2001)

We study the fault tolerance of quantum computation by adiabatic evolution, a quantum algorithm for solving various combinatorial search problems. We describe an inherent robustness of adiabatic computation against two kinds of errors, unitary control errors and decoherence, and we study this robustness using numerical simulations of the algorithm.
Structural and Functional Characterization of Mycobacterium tuberculosis CmtR, a PbII/CdII-Sensing SmtB/ArsR Metalloregulatory Repressor (2005)

The SmtB/ArsR family of prokaryotic metalloregulators are winged-helix transcriptional repressors that collectively provide resistance to a wide range of both biologically required and toxic heavy-metal ions. CmtR is a recently described Cd(II)/Pb(II) regulator expressed in Mycobacterium tuberculosis that is structurally distinct from the well-characterized SmtB/ArsR Cd(II)/Pb(II) sensor, Staphylococcus aureus plasmid pI258-encoded CadC. From functional analyses and a multiple sequence alignment of CmtR paralogs, M. tuberculosis CmtR is proposed to bind Pb(II) and Cd(II) via coordination by Cys57, Cys61, and Cys102 [Cavet et al. (2003) J. Biol. Chem. 278, 44560-44566]. We establish here that both wild-type and C102S CmtR are homodimers and bind Cd(II) and Pb(II) via formation of cysteine thiolate-rich coordination bonds. UV-vis optical spectroscopy, (113)Cd NMR spectroscopy (delta = 480 ppm), and (111m)Cd perturbed angular correlation (PAC) spectroscopy suggest two or three thiolate donors in the wild-type protein. Cys57 and Cys61 anchor the coordination complex, while Cys102 plays only an accessory role in stabilizing the metal chelate in the free protein because C102S CmtR binds Cd(II) and Zn(II) with only approximately 10-20-fold lower affinity relative to wild-type CmtR but approximately 100-1000-fold lower for Pb(II). Quantitative investigation of CmtR-cmt O/P binding equilibria using fluorescence anisotropy, however, reveals that Cys102 functions as a key allosteric metal ligand, because substitution of Cys102 abrogates disassembly of oligomeric CmtR-cmt O/P oligomeric complexes. The implications of these findings on the evolution of distinct metal-sensing sites in a family of homologous proteins are discussed.
Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine (2015)

The communesin alkaloids are a diverse family of Penicillium-derived alkaloids. Their caged-polycyclic structure and intriguing biological profiles have made these natural products attractive targets for total synthesis. Similarly, the ascidian-derived alkaloid, perophoramidine, is structurally related to the communesins and has also become a popular target for total synthesis. This review serves to summarize the many elegant approaches that have been developed to access the communesin alkaloids and perophoramidine. Likewise, strategies to access the communesin ring system are reviewed.
Usefulness of AgNOR Score in Differentiating Benign from Malignant Pulmonary Aspiration Cytology (1997)

The AgNOR technique may be of considerable value in aiding a diagnosis of malignancy, especially when the score is > 6.
300 GHz microfabricated waveguide slotted arrays (2014)

We present a computationally efficient and accurate design technique for waveguide slotted arrays. The design technique is verified through measurements of a frequency-scanned antenna operating over the 275 to 295 GHz frequency range that has been fabricated using the PolyStrata® microfabrication process. Distribution Statement “A” (Approved for public release, Distribution Unlimited).
Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007)

We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.
Amantadine Small-Particle Aerosol: Generation and Delivery to Man (1979)

An aerosol generator suitable for administration of a small-particle aerosol of amantadine for treatment of influenza A infection in man is described. As currently operated, the usual daily recommended oral dose of amantadine of 120 to 200 mg can be given in 8 to 10 hr of inhalation of the aerosol. Limited clinical study indicates the safety and probable efficacy of this method of treatment.
Utility of various commercially available human immunodeficiency virus (HIV) antibody diagnostic kits for use in conjunction with efficacy trials of HIV-1 vaccines (1995)

There is a need for human immunodeficiency virus (HIV) screening assays which will distinguish uninfected HIV vaccine recipients from HIV-infected individuals. Commercial screening kits were used to test serum samples from low- and high-risk participants in clinical trials before and after immunization with various recombinant HIV type 1 (HIV-1) envelope glycoprotein 120 (gp120) candidate vaccines. All kits were 100% sensitive in detecting HIV infection. Both Murex Single Use Diagnostic System and United Biomedical, Inc., HIV type 1 or 2 (HIV-1/2) enzyme immunoassay (EIA) kits, which detect antibodies to HIV-1 gp41, were 98 to 100% specific when used to screen baseline or recombinant gp120-vaccinated populations as vaccine-induced antibodies to gp120 were nonreactive in these tests. The Abbott HIVAB HIV-1 EIA (lysate of whole infected cells, reactive with anti-gp120 antibodies) gave high levels of reactivity due to vaccine-induced antibodies and a high baseline rate of false positives (12 of 83) among nonvaccinated high-risk volunteers. Assays containing only gp41 and p24 solid-phase components are compatible with gp120-based vaccines but are unlikely to be useful in a similar role for vaccines containing gp160, gp41, or gp120 plus p24 antigens. Efficacy trials must be designed in concert with available diagnostic screening assays to avoid problems caused by vaccine-induced seroconversion in high-risk populations.
All‐trans retinoic acid regulates adhesion mechanism and transmigration of the acute promyelocytic leukaemia cell line NB‐4 under physiologic flow (1999)

The success of all-trans retinoic acid (ATRA) in the therapy of acute promyelocytic leukaemia (APL) has received increased attention. Unfortunately, life-threatening multiorgan failure commonly occurs, i.e. retinoic acid syndrome, and is thought to be the result of organ infiltration by leukaemic cells. We hypothesized that ATRA-induced differentiation of APL cells leads to adhesion receptor alterations responsible for leucocyte extravasation from the blood into tissue. Changes in adhesive properties of the APL cell line NB-4 in response to ATRA were investigated using a parallel plate flow chamber under conditions that recapitulate physiologic flow conditions. Untreated NB-4 cells initially tether and roll on activated human umbilical vein endothelial cell monolayers using a combination of E-selectin, P-selectin and alpha4 integrin. After ATRA treatment, > 80% of initial NB-4 cell attachment to endothelial cells was E-selectin dependent. Stable arrest (firm adherence) of NB-4 cells on activated endothelium was also altered by ATRA treatment. Untreated NB-4 cells used alpha4 integrin to arrest on endothelium, but beta2 integrin dependent arrest was induced by ATRA. With the acquisition of beta2 integrin function, ATRA-treated cells acquired the ability to transmigrate through activated endothelium. Thus, ATRA dramatically altered the adhesion phenotype on NB-4 cells: ATRA induced rolling largely attributable to E-selectin, abrogated alpha4 integrin dependent rolling, and promoted acquisition of beta2 integrin dependent firm adherence and transmigration. These findings represent novel cellular and differentiation effects of ATRA, and, to our knowledge, are the first demonstration that a therapeutic agent differentially regulates alpha4 and beta2 integrin on the same leucocyte.
A nonlinear filter for estimating a sinusoidal signal and its parameters in white noise: on the case of a single sinusoid (1997)

A nonlinear filter is proposed for estimating a complex sinusoidal signal and its parameters (frequency, amplitude, and phase) from measurements corrupted by white noise. This filter is derived by applying an extended complex Kalman filter (ECKF) to a nonlinear stochastic system whose state variables are a function of its frequency and a sample of an original signal, and then, proof of the stability is given in the case of a single complex sinusoid. Simulations demonstrate that the proposed nonlinear filter is effective as a method for estimating a single complex sinusoid and its frequency under a low signal-to-noise ratio (SNR). In addition, the effect of the initial condition in the filter on frequency estimation is also discussed.
Physiological and molecular insights into drought tolerance (2002)

&nbsp; Water is a major limiting factor in world agriculture. In general, most crop plants are highly sensitive to even a mild dehydration stress. There are however, a few genera of plants unique to Southern Africa, called &ldquo;resurrection plants&rdquo; which can tolerate extreme water loss or desiccation. We have used&nbsp;Xerophyta viscosa, a representative of the monocotyledonous resurrection plants to isolate genes that are associated with osmotic stress tolerance. Several genes that are differentially expressed, and that confer functional sufficiency to osmotically-stressed&nbsp;Escherichia coli&nbsp;are being studied at the molecular and biochemical levels. In this review, we use this as a basis to discuss the physiological and molecular insights into drought tolerance. &nbsp; Key words:&nbsp;Drought stress, reactive oxygen species, osmoprotectants, abscisic acid, transcription factors.
Electrical Characterization of Printed Nanocrystalline Silicon Films, Cooperative Research and Development Final Report, CRADA Number CRD-07-00241 (2011)

This CRADA helped Innovalight characterize and quantify their ink-based selective emitter technology. Controlled localized doping of selective emitter structures via Innovalight Silicon Ink technology was demonstrated. Both secondary ion mass spectrometry and scanning capacitance microscopy revealed; abrupt lateral dopant profiles at ink-printed boundaries. Uniform doping of iso- and pyramidalsurfaces was also verified using scanning electron microscopy dopant contrast imaging.
Cancer Immunotherapy (2013)

This year marks a turning point in cancer, as long-sought efforts to unleash the immune system against tumors are paying off—even if the future remains a question mark.
EGFR and MEK Blockade in Triple Negative Breast Cancer Cells (2015)

Although evidence suggests that the RAF/MEK/ERK pathway plays an important role in triple negative breast cancer (TNBC), resistance to MEK inhibitors has been observed in TNBC cells. Different mechanisms have been hypothesized to be involved in this phenomenon, including receptor tyrosine kinase-dependent activation of the PI3K/AKT pathway. In this study, we analyzed the effects of the MEK1/2 inhibitor selumetinib in combination with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in a panel of TNBC cell lines that showed different levels of sensitivity to single-agent selumetinib: SUM-149 and MDA-MB-231 cells resulted to be sensitive, whereas SUM-159, MDA-MB-468 and HCC70 cells were relatively resistant to the drug. Treatment of TNBC cells with selumetinib produced an increase of the phosphorylation of the EGFR both in selumetinib-sensitive SUM-149, MDA-MB-231 and in selumetinib-resistant MDA-MB-468 TNBC cells. The combination of selumetinib and gefitinib resulted in a synergistic growth inhibitory effect in all the TNBC cell lines, although the IC50 was not reached in SUM-159 and MDA-MB-468 cells. This effect was associated with an almost complete suppression of ERK1/2 activation and a reduction of selumetinib-induced AKT phosphorylation. In addition, in selumetinib-sensitive TNBC cells the combination of selumetinib and gefitinib induced a significant G0/G1 cell cycle arrest and apoptosis. Taken together, our data demonstrated that blockade of the EGFR might efficiently increase the antitumor activity of selumetinib in a subgroup of TNBC and that this phenomenon might be related to the effects of such combination on both ERK1/2 and AKT activation.
PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations (2015)

Oncogenic c-ros oncogene1 (ROS1) fusion kinases have been identified in a variety of human cancers and are attractive targets for cancer therapy. The MET/ALK/ROS1 inhibitor crizotinib (Xalkori, PF-02341066) has demonstrated promising clinical activity in ROS1 fusion-positive non-small cell lung cancer. However, emerging clinical evidence has shown that patients can develop resistance by acquiring secondary point mutations in ROS1 kinase. In this study we characterized the ROS1 activity of PF-06463922, a novel, orally available, CNS-penetrant, ATP-competitive small-molecule inhibitor of ALK/ROS1. In vitro, PF-06463922 exhibited subnanomolar cellular potency against oncogenic ROS1 fusions and inhibited the crizotinib-refractory ROS1(G2032R) mutation and the ROS1(G2026M) gatekeeper mutation. Compared with crizotinib and the second-generation ALK/ROS1 inhibitors ceritinib and alectinib, PF-06463922 showed significantly improved inhibitory activity against ROS1 kinase. A crystal structure of the PF-06463922-ROS1 kinase complex revealed favorable interactions contributing to the high-affinity binding. In vivo, PF-06463922 showed marked antitumor activity in tumor models expressing FIG-ROS1, CD74-ROS1, and the CD74-ROS1(G2032R) mutation. Furthermore, PF-06463922 demonstrated antitumor activity in a genetically engineered mouse model of FIG-ROS1 glioblastoma. Taken together, our results indicate that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation.
β1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol (2003)

Our data suggest that beta(1)-adrenergic receptor polymorphisms are important determinants of antihypertensive response to metoprolol. In the future, codon 49 and 389 genotypes or beta(1)-adrenergic receptor haplotypes might be used to predict the diastolic blood pressure response to metoprolol in patients with hypertension.
ChemInform Abstract: μ3‐SILYLIDYNE HETEROMETAL CLUSTERS (1985)

Abstract Die wie aufgezeigt gewonnenen Silylidin‐ Tricobalt‐Cluster (III)erweisen sich als zu empfindlich, um sich mit den bereits beschriebenen Metallaustauschverfahren in Heterometall‐Cluster umwandeln zu lassen.