gebhart/patrepeval huggingface dataset:
Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies (2001)

In the early 1990s, 4 randomized studies compared conditioning regimens before transplantation for leukemia with either cyclophosphamide (CY) and total-body irradiation (TBI), or busulfan (Bu) and CY. This study analyzed the long-term outcomes for 316 patients with chronic myeloid leukemia (CML) and 172 patients with acute myeloid leukemia (AML) who participated in these 4 trials, now with a mean follow-up of more than 7 years. Among patients with CML, no statistically significant difference in survival or disease-free survival emerged from testing the 2 regimens. The projected 10-year survival estimates were 65% and 63% with Bu-CY versus CY-TBI, respectively. Among patients with AML, the projected 10-year survival estimates were 51% and 63% (95% CI, 52%-74%) with Bu-CY versus CY-TBI, respectively. At last follow-up, most surviving patients had unimpaired health and had returned to work, regardless of the conditioning regimen. Late complications were analyzed after adjustment for patient age and for acute and chronic graft-versus-host disease (GVHD). CML patients who received CY-TBI had an increased risk of cataract formation, and patients treated with Bu-CY had an increased risk of irreversible alopecia. Chronic GVHD was the primary risk factor for late pulmonary disease and avascular osteonecrosis. Thus, Bu-CY and CY-TBI provided similar probabilities of cure for patients with CML. In patients with AML, a nonsignificant 10% lower survival rate was observed after Bu-CY. Late complications occurred equally after both conditioning regimens (except for increased risk of cataract after CY-TBI and of alopecia with Bu-CY).
Replication of sub-micrometre features using microsystems technology (2005)

AbstractMany fields of industry are looking for growth from miniaturisation. Because competition is increasing, costs are becoming more important in mass production. These are the driving forces for improving and developing micro injection moulding and replication technologies. This experimental study was carried out to replicate sub-micrometre features using the micro injection moulding technique. For the experiments, polycarbonate (PC) was selected because of its flow properties. The effects of processing parameters on the replication properties were observed. The best replication results were achieved when a small injection piston diameter and large shot size were used in micro injection moulding.Keywords: MICRO INJECTION MOULDINGREPLICATIONSUB-MICROMETREPOLYCARBONATE
Structural and biophysical characterization of the tandem substrate-binding domains of the ABC importer GlnPQ (2020)

ABSTRACT The ATP-binding cassette transporter GlnPQ is an essential uptake system that transports glutamine, glutamic acid, and asparagine in Gram-positive bacteria. It features two extracytoplasmic substrate-binding domains (SBDs) that are linked in tandem to the transmembrane domain of the transporter. The two SBDs differ in their ligand specificities, binding affinities and their distance to the transmembrane domain. Here, we elucidate the effects of the tandem arrangement of the domains on the biochemical, biophysical and structural properties of the protein. For this, we determined the crystal structure of the ligand-free tandem SBD1-2 protein from L. lactis in the absence of the transporter and compared the tandem to the isolated SBDs. We also used isothermal titration calorimetry to determine the ligand-binding affinity of the SBDs and single-molecule Förster-resonance energy transfer (smFRET) to relate ligand binding to conformational changes in each of the domains of the tandem. We show that substrate binding and conformational changes are not notably affected by the presence of the adjoining domain in the wild-type protein, and changes only occur when the linker between the domains is shortened. In a proof-of-concept experiment, we combine smFRET with protein-induced fluorescence enhancement and show that a decrease in SBD linker length is observed as a linear increase in donor-brightness for SBD2 while we can still monitor the conformational states (open/closed) of SBD1. These results demonstrate the feasibility of PIFE-FRET to monitor protein-protein interactions and conformational states simultaneously. HIGHLIGHTS Resolved crystal structure of tandem SBD1-2 of GlnPQ from Lactococcus lactis Conformational states and ligand binding affinities of individual domains SBD1 and SBD2 are similar to tandem SBD1-2 No cooperative effects are seen for different ligands for SBDs in the tandem Proof of concept experiments show that PIFE-FRET can monitor SBD conformations and protein-protein interaction simultaneously
Posttreatment Results of Combining Naltrexone with Cognitive-Behavior Therapy for the Treatment of Alcoholism (2001)

Naltrexone, an opiate antagonist medication, has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments. Although the within-treatment efficacy of naltrexone has received primary attention, there has been little published on the outcome of individuals once the medication is discontinued. Animal studies have led to concern regarding a quick rebound to heavy drinking. This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy. Of the 131 subjects evaluated during the treatment phase, 124 (95%) had up to 14 weeks of posttreatment drinking data available for analysis. Measures of craving and blood markers of heavy drinking were also evaluated. By the end of treatment, naltrexone demonstrated significantly greater efficacy than placebo. However, once the medication was discontinued, there was a gradual increase in relapse rates, heavy drinking days, and drinks per drinking day, and fewer days of abstinence were reported. By the end of the 14-week follow-up period, although naltrexone-treated subjects were, on average, still doing better than control subjects, the effectiveness of naltrexone was no longer statistically significant. There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals. These data suggest that, for a number of alcoholic subjects, continued treatment with naltrexone, or perhaps psychosocial intervention, for longer than 3 months is indicated. Future research should identify which alcohol-dependent individuals may need prolonged treatment to improve treatment success in the long term.
Galeazzi fracture dislocation (2008)

On comparison with the unaffected side, the ulnar head will be prominent with associated soft-tissue swelling.
Abstract 5345: Heterogeneous tumor PSMA expression represents a resistance mechanism to PSMA-targeted radioligand therapy (2020)

Abstract Radioligand therapy (RLT) with prostate-specific membrane antigen (PSMA)-targeting ligands is effective in ~50% of patients with advanced prostate cancer (PC). Causes for RLT failure are not well understood. The prevalent PSMA heterogeneity in PC might contribute to RLT failure. Here we investigate the relationship between RLT efficacy and PSMA levels per cell, and PSMA heterogeneity. PC cells expressing different levels of PSMA (RM1-PSMA low, medium, high, or RM1-YFP that do not express PSMA), or a mix of PSMA− and PSMA+ cells (RM1-YFP/ RM1-PSMA-high; PC3/ PC3-PIP) at various ratios were subcutaneously injected into NSG mice. Mice were treated with 177Lu- or 225Ac-PSMA617 (RLT) and tumor growth was monitored. In a subset of mice, radioligand uptake (γ-counting), DNA damage and PSMA expression (anti-53BP1 and -PSMA immunohistochemistry, respectively) were quantified in tumors resected 2 days after RLT. Increasing PSMA levels and fractions of PSMA+ cells improved RLT efficacy in both, the RM1 and PC3 model. PSMA expression correlated with radioligand uptake into the tumor and the degree of DNA damage and. Treatment with 225Ac-PSMA617 (vs. 177Lu-PSMA617) improved RLT outcomes and tended to enhance the differences in therapeutic efficacy between experimental groups. Taken together, we demonstrate in mouse models of PC that optimal anti-tumor efficacy of RLT hinges on homogenously high target expression. Although PSMA-RLT is effective even in tumors with low PSMA levels or with a small number of PSMA+ cells, low or heterogeneous PSMA expression might result in undertreatment and selection of treatment resistant clones. Systematic assessment of intra- and inter-lesion PSMA heterogeneity is currently not feasible clinically; however, this issue might be addressed by individual patient dosimetry to optimize safely delivered maximal tumor doses. Clinical studies designed to determine intra- and inter-lesion PSMA heterogeneity and to optimize PSMA-RLT for each patient are highly warranted. Citation Format: Katharina Lueckerath, Kyle Current, Catherine Meyer, Clara Magyar, Christine E. Mona, Joel Almajano, Roger Slavik, Andreea D. Stuparu, Chloe Cheng, David Dawson, Caius Radu, Johannes Czernin. Heterogeneous tumor PSMA expression represents a resistance mechanism to PSMA-targeted radioligand therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5345.
C70-based aqueous-soluble fullerene for the water composition-tolerant performance of eco-friendly polymer solar cells (2020)

Our work highlights the development of eco-PSCs based on newly developed C<sub>70</sub>-based water/alcohol soluble fullerene with enhanced light absorption, aggregation properties and highly solvent composition-tolerant eco-friendly solvent processes.
An analysis of constant modulus receivers (1999)

This paper investigates connections between (non-blind) Wiener receivers and blind receivers designed by minimizing the constant modulus (CM) cost. Applicable to both T-spaced and fractionally spaced FIR equalization, the main results include (1) a test for the existence of CM local minima near Wiener receivers; (2) an analytical description of CM receivers in the neighborhood of Wiener receivers; (3) mean square error (MSE) bounds for CM receivers. When the channel matrix is invertible, we also show that the CM receiver is approximately colinear with the Wiener receiver and provide a quantitative measure of the size of neighborhoods that contain the CM receivers and the accuracy of the MSE bounds.
On the Use of Hidden Markov Modeling and Time-frequency Features for Damage Classification in Composite Structures (2009)

A novel approach based on hidden Markov models (HMMs) is proposed for damage classification in composite structures. Time-frequency damage features are first extracted from the measured signals using the matching pursuit decomposition algorithm. The features are then incorporated as observation sequences to be modeled statistically by the HMMs. Once built, the HMMs are integrated very efficiently into a Bayesian framework for the classification of structural damage. Both discrete and continuous observation density HMMs are considered; continuous HMMs are shown to yield better accuracy, but at the cost of added computational complexity. A decision fusion procedure is employed to combine the local classification results at each sensor, significantly enhancing the overall classification performance. The utility of the proposed technique is demonstrated by its application to the classification of delamination damage, impact damage, and progressive tensile damage in laminated composites.
A transaction-based unified simulation/emulation architecture for functional verification (2001)

A transaction-based layered architecture providing for 100% portability of a C-based testbench between simulation and emulation is proposed. Transaction-based communication results in performance which is commensurate with emulation without a hardware target. Testbench portability eliminates duplicated effort when combining system level simulation and emulation. An implementation based on the IKOS VStation emulator validates these architectural claims on real designs.
Coupling next-generation sequencing to dominant positive screens for finding antibiotic cellular targets and resistance mechanisms in Escherichia coli (2018)

In order to expedite the discovery of genes coding for either drug targets or antibiotic resistance, we have developed a functional genomic strategy termed Plas-Seq. This technique involves coupling a multicopy suppressor library to next-generation sequencing. We generated an Escherichia coli plasmid genomic library that was transformed into E. coli. These transformants were selected step by step using 0.25× to 2× minimum inhibitory concentrations for ceftriaxone, gentamicin, levofloxacin, tetracycline or trimethoprim. Plasmids were isolated at each selection step and subjected to Illumina sequencing. By searching for genomic loci whose sequencing coverage increased with antibiotic pressure we were able to detect 48 different genomic loci that were enriched by at least one antibiotic. Fifteen of these loci were studied functionally, and we showed that 13 can decrease the susceptibility of E. coli to antibiotics when overexpressed. These genes coded for drug targets, transcription factors, membrane proteins and resistance factors. The technique of Plas-Seq is expediting the discovery of genes associated with the mode of action or resistance to antibiotics and led to the isolation of a novel gene influencing drug susceptibility. It has the potential for being applied to novel molecules and to other microbial species.
Arg-Gingipain Inhibition and Anti-bacterial Activity Selective forPorphyromonas gingivalisby Malabaricone C (1999)

Effects of malabaricon C, isolated from nutmeg (Myristica fragrans), on Arg-gingipain activity and growth of several kinds of anaerobic and aerobic microorganisms were investigated. Malabaricone C irreversibly inhibited Arg-gingipain by 50% at a concentration of 0.7 microgram/ml and selectively suppressed Porphyromomas gingivalis growth.
Aminobenzole, XIII. Isomerisierung, Enthalogenierung und Entalkylierung von Brom‐N,N‐dialkylanilinen mit Mineralsäuren (1977)

Abstract Brom‐ N , N ‐dialkylanilinium‐halogenide reagieren beim Erhitzen in Chloroform zu Gemischen aus Isomerisierungs‐, Enthalogenierungs‐ und Entalkylierungsprodukten. — Die Abhängigkeit der Produktbildung von Reaktionszeit und ‐temperatur, von sterischen und elektronischen Einflüssen im Substrat sowie von der Nucleophilie der Anionen der eingesetzten Protonensäuren wurde untersucht: Die Bildung der erhaltenen Verbindungen ist über die Reversibilität der Kernbromierung und die Entalkylierung der Aniliniumsalze zu deuten. — Für die Entalkylierung wird ein S N 2‐Mechanismus nachgewiesen, für die Isomerisierung — mittels 82 Brommarkierter Verbindungen — ein intermolekularer Verlauf.
Testing the efficacy of rotenone as a piscicide for New Zealand pest fish species. (2003)

The first South Island populations of Gambusia affinis and Koi carp were discovered in the Nelson region in May and July (2000), respectively. A delimitation survey using a standardised rapid sampling protocol was undertaken to determine how widespread these species were within the Nelson/Marlborough region. A total of 219 ponds and 54 waterways were surveyed over the warmer summer months and Gambusia were located in a further 19 farm ponds, and koi in one. In addition, illegally liberated populations of rudd, tench and red finned perch were also detected. These latter species were previously absent from the region. Survey data suggested that Gambusia and koi were restricted to farm ponds, although there was potential that they could spread from these into natural waterways. Under a pesticides board experimental licence, rotenone was applied to 17 ponds in an effort to eradicate these founding populations. Initial observations suggest that this was successful in killing all koi and Gambusia within these ponds. We discuss the results of these trials, efficacy of the application techniques used, rate of breakdown and variable responses of the different fish poisoned. Results of preliminary trials to resuscitate non-target fish species are also reported. 1 . I N T R O D U C T I O N Rotenone has been used extensively by fisheries managers in North America since the 1930s (Finlayson et al. 2000) and is recognised as the most environmentally benign of the commonly used fish poisons (Ling 2003). Its use in New Zealand has been limited to a few small water bodies with the only significant reported application being the 1981 removal of fish from Lake Parkinson, a small 1.9-ha dune lake south of Auckland (Rowe & Champion 1994). Rotenone has also been used extensively as a marine fish sampling tool, principally applied by taxonomist from the Museum of New Zealand (Paulin & Roberts 1993).
Recent Advances in Intraoperative Neuromonitoring of Spinal Cord Function: Pedicle Screw Stimulation Techniques (1997)

.The evolution of internal spinal instrumentation is grounded in the therapeutic constructs and spinal biomechanics associated with spinal deformities. Newer instrumentation methods for spinal fusion, which involve placing screws into the vertebral pedicles to hold the rods, have evolved for the treatment of degenerative spinal disease and traumatic insult to the lumbosacral spine. Two significant advantages of spinal instrumentation using segmental, transpedicular, screw fixation are enhanced rigidity and stability of the spine, and greater flexibility for the surgeon to accommodate a patient's individual anatomy. Despite these advances in instrumentation design, neurological deficits from improper screw placement may occur. The determination of screw placement using traditional methods like anatomical identification of bony landmarks and radiographic techniques have significant limitations. An alternative method for monitoring pedicle screw placement involves an electrophysiological approach called pedicle screw stimulation technique. Evoked electromyographic activity is recorded from muscle groups innervated by the spinal nerve roots at risk. Either constant current or voltage stimulation applied through the hardware used to form the pedicle holes, inside the pedicle holes, and through the implanted screws is performed to determine the stimulation threshold needed to produce a compound muscle action potential. These threshold values for evoked EMG are then used for evaluating the success or failure of screw placement. A relatively high EMG threshold suggests proper pedicle screw placement with an intact pedicle wall surrounding the screw; a relatively low threshold indicates a malposed screw resulting in a possible cracked or breached pedicle.
Thermodynamics of active-site ligand binding to Escherichia coli glutamine synthetase (1987)

Active-site ligand interactions with dodecameric glutamine synthetase from Escherichia coli have been studied by calorimetry and fluorometry using the nonhydrolyzable ATP analogue 5'-adenylyl imidodiphosphate (AMP-PNP), L-glutamate, L-Met-(S)-sulfoximine, and the transition-state analogue L-Met-(S)-sulfoximine phosphate. Measurements were made with the unadenylylated enzyme at pH 7.1 in the presence of 100 mM KCl and 1.0 mM MnCl2, under which conditions the two catalytically essential metal ion sites per subunit are occupied and the stoichiometry of active-site ligand binding is equal to 1.0 equiv/subunit. Thermodynamic linkage functions indicate that there is strong synergism between the binding of AMP-PNP and L-Met-(S)-sulfoximine (delta delta G' = -6.4 kJ/mol). In contrast, there is a small antagonistic effect between the binding of AMP-PNP and L-glutamate (delta delta G' = +1.4 kJ/mol). Proton effects were negligible (less than or equal to 0.2 equiv of H+ release or uptake/mol) for the different binding reactions. The binding of AMP-PNP (or ATP) to the enzyme is entropically controlled at 303 K with delta H = +5.4 kJ/mol and delta S = +150 J/(K.mol). At 303 K, the binding of L-glutamate (delta H = -22.2 kJ/mol) or L-Met-(S)-sulfoximine [delta H = -45.6 kJ/mol with delta Cp approximately equal to -670 +/- 420 J/(K.mol)] to the AMP-PNP.Mn.enzyme complex is enthalpically controlled with opposing delta S values of -29 or -46 J/(K.mol), respectively. The overall enthalpy change is negative and the overall entropy change is positive for the simultaneous binding of AMP-PNP and L-glutamate or of AMP-PNP and L-Met-(S)-sulfoximine to the enzyme. For the binding of the transition-state analogue L-Met-(S)-sulfoximine phosphate (which inactivates the enzyme by blocking active sites), both enthalpic and entropic contributions also are favorable at 303 K [delta G' approximately equal to -109 and delta H = -54.8 kJ/mol of subunit and delta S approximately equal to +180 J/(K.mol)].
The response of the cross-bridge cycle model to oscillations in intracellular calcium: A mathematical analysis (2005)

The response of smooth muscle cells to changes in blood pressure is a large component of the processes that regulate blood flow. Models of the mechanical behaviour of smooth muscle cells normally assume that the mechanical properties of the cell are dependent upon the state of attached myosin, this being determined by a four state kinetic model. An analysis of the behaviour of this kinetic model is presented here, in particular the response to oscillations in intracellular calcium. It is shown that the amplitudes of oscillation of the states in the kinetic model drop off rapidly with frequency and that at 1 Hz are of negligible magnitude. This is found to be true for a number of different combinations of model parameters, indicating that at the cardiac driving frequency the smooth muscle cell response is solely determined by the mechanical behaviour of the cells, without any influence of the biochemical processes, i.e. the response is purely passive.