gebhart/patrepeval huggingface dataset:
Marine and terrestrial records of the Holocene geological history of Sylt and the adjacent Wadden Sea (SE North Sea) (2008)

Sylt is a barrier island at the German-Danish border in the SE North Sea. It consists of a core of Miocene to Pliocene marine and riverine sediments in the central part which forms the source sediment for two spit systems that extend more than 15 km to the south and the north. These protect the backside tidal basins and the mainland against the direct influence of the North Sea. Presently, Sylt is strongly eroded (about 1 m land loss per year at its west coast). Goal of the investigations presented here is to reconstruct the Holocene geological history of the area and to provide data instrumental to build up a scenario for the future development of the area in the light of climate change and sea-level rise.We use the sea-floor classification system RoxAnn to characterize the present state of the sublitoral sedimentary environments, and a parametric echosounder as well as sparker/boomer shallow seismics to reconstruct the Holocene development of the sedimentary environments offshore. Onshore, ground-penetrating radar (GPR), long sediment cores, and surface samples are used to reconstruct the transition from marine to terrestrial environments. West of Sylt and Rømø Sparker data reveal an upper unit with north-directed foreset structures overlying more horizontally bedded sediments. The foreset structures are likely related to the List Deep tidal delta situated between Sylt and Rømø. Under the immediate influence of the recent tidal currents large sandwaves (crest hight up to 7 m) locally occur on the seafloor. Onshore, GPR data reveal alternating processes of swash-bar accretion and severe-storm erosion at the west coast and longshore sediment transport with beach-ridge accretion at the north-facing part of the northern spit. Sediment core granulometric data show the transition from marine via beaches to dune environments. AMS radiocarbon age determinations allow to reconstruct the growth of the spit system whose youngest recurved part became permanently terrestrial about 1000 years ago. Acoustic and sedimentologic data from the recent seafloor west of the coastline show extended alternating zones of coarser and finer sediments that stretch perpendicular to the coastline. Depressions within the otherwise sandy area are being filled with muddy sediments. We will show how the different marine and terrestrial depositional environments are linked to each other and how sediment transport is likely governed. It becomes clear that Sylt is not the result of a retreating coastline as there is clear evidence for periods of extended seaward island growth during the late Holocene. Erosive and accumulative phases of the island appear to be the result of atmospheric forcing and the fluctuating sea level which suggests implications with regard to the future development of this and similar areas.
Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2. (1984)

By using as an experimental system the induction of growth of a cloned, antigen:Ia-reactive helper T cell line by an antigen receptor-specific monoclonal antibody, we demonstrated that growth requires two essential co-factors, exogenously produced IL 1 and endogenously produced IL 2. The primary role of the IL 1 is in the expression of receptors on the T cell surface for IL 2, rather than for promoting the synthesis of IL 2. The use of a clone-specific activating monoclonal antibody at nanogram amounts to activate a cloned helper T cell should allow a detailed characterization of T cell activation via antigen receptor cross-linking.
Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease (2016)

Abstract BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P=4.2×10−10) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P=4.0×10−8), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P=0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P=0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P=2.0×10−4) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P=2.5×10−7). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease. (Funded by the National Institutes of Health and others.)
In Vitro Growth Suppression by Adenoviral Transduction of p21 and p16 in Squamous Cell Carcinoma of the Head and Neck (1998)

Although p21 and p16 are believed to function as cell cycle regulators of cyclin-dependent kinases, we observed no additive or synergistic effect when using them in combination. The expression of transduced p21 and p16 gene products up to days 9 and 12, respectively, was consistent with the growth suppression and cell cycle arrest observed. This work provides information on the previously uncharacterized duration of p21 and p16 transgene product expression and also lends insight into the interaction of these 2 cell cycle regulators in squamous cell carcinoma of the head and neck.
Non-linear PWM control of single-switch quadratic buck converters using internal model (2009)

An internal model control with conditional integrator is proposed for the robust output regulation of single-switch quadratic buck converters. The output regulation problem of a quadratic buck converter is converted to the stabilisation of an augmented system consisting of the buck converter and the internal model. The design procedures include the design of an internal model with conditional integrator and a robust state feedback stabiliser with saturation behaviour. The closed-loop stability of the converter will be theoretically analysed. Finally, the effectiveness of the proposed control scheme for large load and supply variations are also tested. The design of the controller does not require the exact circuit parameters and the stability proof demonstrates the robustness against parameter uncertainties.
Abstract 2642: Identification and characterization of selective inhibitors of ubiquitin specific protease 7 (2010)

Abstract Regulated protein turnover is primarily controlled by the ubiquitin-proteasome system. The only marketed drug related to the ubiquitin-proteasome system, bortezomib, is acting as a proteasome inhibitor and has been approved for the treatment of some hematological cancers. Targeting the upstream ubiquitin conjugation/deconjugation system carries out promises of therapeutics with increased specificity and selectivity. Ubiquitin-specific proteases (USP) are involved in the deubiquitination of specific target substrates regulating their stability, subcellular localization and/or activation status. USP represent a drugable target class due to their thiol-protease catalytic core which is amenable to pharmacological inhibition by small molecules. A genome-wide RNAi screen of the catalytically active human USPs in cancer-relevant cellular models and phenotypic assays allowed us to identify USP7/HAUSP as promising cancer target. Fluorescence-based screening assays using optimized USP substrates including various ubiquitin derivatives (ubiquitin precursor, branched ubiquitin chains) as well as specific, physiological substrates were developed. High-throughput screening performed on our chemically diverse library followed by different optimization programs resulted in the discovery of several series as novel USP7 inhibitors. Our progress made towards the specificity issue will be presented here with the identification of the first USP7-specific series. These will help further validate this novel class of molecular targets and may provide a structural basis for the development of new anticancer drugs. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2642.
Second Primary Malignancies in Chronic Lymphocytic Leukaemia; Skin, Solid Organ, Haematological, and Richter’s Syndrome (2021)

Abstract Chronic lymphocytic leukaemia (CLL) is invariably accompanied by some degree of immune failure. CLL patients have a high rate of second primary malignancy (SPM) compared to the general population. We comprehensively documented the incidence of all forms of SPM including skin cancer (SC), solid organ malignancy (SOM), second haematological malignancy (SHM), and separately Richter’s Syndrome (RS) across all therapy eras. Among the 517 CLL/SLL patients, the overall incidence of SPMs with competing risks were SC 31.07%, SOM 25.99%, SHM 5.19% and RS 7.55%. Melanoma accounted for 30.3% of SC. Squamous cell carcinoma (SCC), including 8 metastatic SCCs, was 1.8 times more than basal cell carcinoma (BCC), a reversal of the typical BCC:SCC ratio. The most common SOM were prostate (6.4%) and breast (4.5%). SHM included 7 acute myeloid leukaemia and 5 myelodysplasia of which 8 were therapy-related. SPMs are a major health burden with 44.9% of CLL patients with at least one, and apart from SC, associated with significantly reduced overall survival. Dramatic improvements in CLL treatment and survival have occurred with immunochemotherapy and targeted therapies but mitigating SPM burden will be important to sustain further progress.
Locomotion- and mechanics-mediated tactile sensing: antenna reconfiguration simplifies control during high-speed navigation in cockroaches (2013)

Animals can expend energy to acquire sensory information by emitting signals and/or moving sensory structures. We propose that the energy from locomotion itself could permit control of a sensor, whereby animals use the energy from movement to reconfigure a passive sensor. We investigated high-speed, antenna-mediated tactile navigation in the cockroach Periplaneta americana. We discovered that the passive antennal flagellum can assume two principal mechanical states, such that the tip is either projecting backward or forward. Using a combination of behavioral and robotic experiments, we demonstrate that a switch in the antenna's state is mediated via the passive interactions between the sensor and its environment, and this switch strongly influences wall-tracking control. When the tip of the antenna is projected backward, the animals maintain greater body-to-wall distance with fewer body collisions and less leg-wall contact than when the tip is projecting forward. We hypothesized that distally pointing mechanosensory hairs at the tip of the antenna mediate the switch in state by interlocking with asperities in the wall surface. To test this hypothesis, we performed laser ablation of chemo-mechanosensory hairs and added artificial hairs to a robotic antenna. In both the natural and artificial systems, the presence of hairs categorically increased an antenna's probability of switching state. Antennal hairs, once thought to only play a role in sensing, are sufficient for mechanically reconfiguring the state of the entire antenna when coupled with forward motion. We show that the synergy between antennal mechanics, locomotion and the environment simplifies tactile sensing.
Linking interfacial work of deformation from deconvoluted macro-rheological spectrum to early stage healing in selected polyurethanes (2020)

The use of rheology and terminal flow relaxation times to predict healing behavior at long healing times is by now quite well accepted. In this work we go one step further and explore the use of macro-rheology (in particular the stored work of deformation) to predict the early stage interfacial healing properties (fracture resistance) of a set of self-healing polyurethanes. The interfacial healing is measured by single edge notch fracture experiments, using short healing times and a low healing temperature to exclude the effect of long range molecular motion on mechanical properties restoration. The systems based on aromatic diisocyanates show high fracture resistance after healing, while very limited restoration of the mechanical properties is observed for aliphatic and cycloaliphatic based polyurethanes. Linear sweep rheology and time-temperature-superposition allow obtaining the macro-rheological master curve and the mechanical relaxation spectra (H(t)). The application of a recently established deconvolution protocol to the H(t) gives the characteristic relaxation times and stored works of deformation associated to individual dynamic processes such as segmental motion, reversible bonds, and terminal flow. It is found that the calculated stored works of deformation related to the reversible bond relaxation reproduce the trend observed by fracture resistance at healed interfaces and reveal a qualitative correspondence between reversible bonds work of deformation and interfacial healing fracture resistance. Moreover, the method seems to point to the existence of a threshold interfacial work of deformation below which no efficient load transfer can be observed.
ChemInform Abstract: Activity‐Based Probes for the Study of Proteases: Recent Advances and Developments (2012)

Abstract Review: ca. 150 refs.
Crystal Structure Determination of Glycerol-Containing Lipids from Electron Diffraction Data. Use of Analog Compounds Based upon Configurational Isomers of Cyclopentane-1, 2, 3-TRIOL (1977)

Lipids containing long polymethylene chains were among the first compounds subjected to electron diffraction structure analysis. It was only recently realized, however, that various distortions of thin lipid microcrystal plates, e.g. bends, polar group and methyl end plane disorders, etc. (1-3), restrict coherent scattering to the methylene subcell alone, particularly if undistorted molecular layers have well-defined end planes. Thus, ab initio crystal structure determination on a given single uncharacterized natural lipid using electron diffraction data can only hope to identify the subcell packing and the chain axis orientation with respect to the crystal surface. In lipids based on glycerol, for example, conformations of long chains and polar groups about the C-C bonds of this moiety still would remain unknown. One possible means of surmounting this difficulty is to investigate structural analogs of the material of interest in conjunction with the natural compound itself. Suitable analogs to the glycerol lipids are compounds based on the three configurational isomers of cyclopentane-1,2,3-triol shown in Fig. 1, in which three rotameric forms of the natural glycerol derivatives are fixed by the ring structure (4-7).
Performance of PAHs emission from bituminous coal combustion (2004)

Carcinogenic and mutagenic polycyclic aromatic hydrocarbons (PAHs) generated in coal combustion have caused great environmental health concern. Seventeen PAHs (16 high priority PAHs recommended by USEPA plus Benzo[e]pyrene) present in five raw bituminous coals and released during bituminous coal combustion were studied. The effects of combustion temperature, gas atmosphere, and chlorine content of raw coal on PAHs formation were investigated. Two additives (copper and cupric oxide) were added when the coal was burned. The results indicated that significant quantities of PAHs were produced from incomplete combustion of coal pyrolysis products at high temperature, and that temperature is an important causative factor of PAHs formation. PAHs concentrations decrease with the increase of chlorine content in oxygen or in nitrogen atmosphere. Copper and cupric oxide additives can promote PAHs formation (especially the multi-ring PAHs) during coal combustion.
Understanding the formation of bulk- and surface-active layered (oxy)hydroxides for water oxidation starting from a cobalt selenite precursor (2020)

Starting from a cobalt selenite precatalyst, we obtained a bulk and a near-surface active oxygen evolution catalyst and connected their structural properties to the precatalyst structure, the transformation conditions, and the catalytic activity.
Circadian Changes of Left Ventricular Ejection Fraction in Normal Subjects (1994)

Sleep has a specific physiology with related cardiovascular changes. We have previously found in respiratory patients [chronic obstructive pulmonary disease (COPD) and sleep apnea syndrome (OSAS)] an unexpected decrease in left ventricular ejection fraction (LVEF) at waking in the morning when compared with the rest period during the day. Whether this observation was linked to the consequences of the respiratory abnormalities or reflected physiological fluctuations related to the changes in autonomic nervous system tone remained unknown. Thus, we have set out to analyze the changes in LVEF with sleep in normal individuals. Eight healthy young men had LVEF measured before and after submaximal exercise, at rest before bedtime, and on waking in the morning. Technetium-99m with in vivo red cell labelling was used. Sleep parameters were assessed using classical polysomnography. In order to detect any influence of autonomic nervous system stimulation on LVEF, sympathovagal tone (SVT) was also assessed during night-time LVEF measurements using spectral analysis of RR intervals. LVEF at rest was within the normal limits for all the subjects (range 51-62%). On submaximal exercise, the LVEF increased in four subjects, was unchanged in two, and decreased in two. The main result concerns the changes in LVEF overnight. In the morning, LVEF decreased dramatically in three subjects and reached a level of < 30% in four. These decreases in LVEF were not related to changes in SVT or sleep structure. LVEF values returned to normal in 30 min. The LVEF changes during exercise are in accordance with previous data in the literature. The dramatic decrease in LVEF observed in the morning could be related either to vascular resistance changes or to nocturnal variations in cardiac contractility, which both need further studies to be established.
PI-3K and Akt are mediators of AP-1 induction by 5-MCDE in mouse epidermal Cl41 cells (2004)

5-Methylchrysene has been found to be a complete carcinogen in laboratory animals. However, the tumor promotion effects of (±)-anti-5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE) remain unclear. In the present work, we found that 5-MCDE induced marked activator protein-1 (AP-1) activation in Cl41 cells. 5-MCDE also induced a marked activation of phosphatidylinositol 3-kinase (PI-3K). Inhibition of PI-3K impaired 5-MCDE–induced AP-1 transactivation, suggesting that PI-3K is an upstream kinase involved in AP-1 activation by 5-MCDE. Furthermore, we found that Akt is a PI-3K downstream mediator for 5-MCDE–induced AP-1 transactivation, whereas another PI-3K downstream kinase, p70S6K, was not involved in AP-1 activation by 5-MCDE. Moreover, inhibition of Akt activation blocked 5-MCDE–induced activation of extracellular signal–regulated protein kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs), whereas it did not affect p38K activation. Consistently, overexpression of a dominant-negative mutant of ERK2 or JNK1 blocked the AP-1 activation by 5-MCDE. These results demonstrate that 5-MCDE is able to induce AP-1 activation, and the AP-1 induction is specifically through a PI-3K/Akt–dependent and p70S6K-independent pathway.
Large‐gap peripheral nerve repair using xenogeneic transplants in rhesus macaques (2023)

Surgical intervention is required to successfully treat severe, large-gap (≥4 cm) peripheral nerve injuries. However, all existing treatments have shortcomings and an alternative to the use of autologous nerves is needed. Human and porcine nerves are physiologically similar, with comparable dimensions and architecture, presence and distribution of Schwann cells, and conserved features of the extracellular matrix (ECM). We report the repair of fully transected radial nerves in 10 Rhesus Macaques using viable, whole sciatic nerve from genetically engineered (GalT-KO), designated pathogen free (DPF) porcine donors. This resulted in the regeneration of the transected nerve, and importantly, recovery of wrist extension function, distal muscle reinnervation, and recovery of nerve conduction velocities and compound muscle action potentials similar to autologous controls. We also demonstrate the absence of immune rejection, systemic porcine cell migration, and detectable residual porcine material. Our preliminary findings support the safety and efficacy of viable porcine nerve transplants, suggest the interchangeable therapeutic use of cross-species cells, and highlight the broader clinical potential of xenotransplantation.
Tolerance to Noninherited Maternal MHC Antigens in Mice (2003)

The phenomenon of tolerance to noninherited maternal Ags (NIMA) is poorly understood. To analyze the NIMA effect C57BL/6 (H-2(b/b)) males were mated with B6D2F(1) (H-2(b/d)) females, whereby 50% of the offspring are H-2(b/b) mice that have been exposed to maternal H-2(d) alloantigens. Controls were H-2(b/b) offspring of C57BL/6 mothers, either inbred C57BL/6 mice or F(1) backcross mice from breedings with H-2(b/d) fathers. We found that 57% of the H-2(b/b) offspring of semiallogeneic (H-2(b/d)) mothers accepted fully allogeneic DBA/2 (H-2(d/d)) heart grafts for >180 days, while similar transplants were all rejected by day 11 in controls (p < 0.0004). Foster nursing studies showed that both oral and in utero exposure to NIMA are required for this tolerogenic effect. An effect of NIMA was also found to extend the survival of skin grafts from a semiallogeneic donor (p < 0.02). Pretransplant analysis of splenocytes showed a 40-90% reduction of IL-2-, IL-5-, and IFN-gamma-producing T cells responding to H-2(d)-expressing APC in NIMA(d)-exposed vs control mice. Injection of pregnant BALB/c-dm2 (H-2L(d)-negative) female mice i.v. with H-2L(d)(61-80) peptide profoundly suppressed the offspring's indirect pathway alloreactive CD4(+) T cell response to H-2L(d). These results suggest that the natural exposure of the fetus and newborn to maternal cells and/or soluble MHC Ags suppresses NIMA-allospecific T cells of the offspring, predisposing to organ transplant tolerance in adult mice.