gebhart/patrepeval huggingface dataset:
Differential Regulation of B-Raf Isoforms by Phosphorylation and AutoinhibitoryMechanisms (2006)

The B-Raf proto-oncogene encodes several isoforms resulting from alternative splicing in the hinge region upstream of the kinase domain. The presence of exon 8b in the B2-Raf(8b) isoform and exon 9b in the B3-Raf(9b) isoform differentially regulates B-Raf by decreasing and increasing MEK activating and oncogenic activities, respectively. Using different cell systems, we investigated here the molecular basis of this regulation. We show that exons 8b and 9b interfere with the ability of the B-Raf N-terminal region to interact with and inhibit the C-terminal kinase domain, thus modulating the autoinhibition mechanism in an opposite manner. Exons 8b and 9b are flanked by two residues reported to down-regulate B-Raf activity upon phosphorylation. The S365A mutation increased the activity of all B-Raf isoforms, but the effect on B2-Raf(8b) was more pronounced. This was correlated to the high level of S365 phosphorylation in this isoform, whereas the B3-Raf(9b) isoform was poorly phosphorylated on this residue. In contrast, S429 was equally phosphorylated in all B-Raf isoforms, but the S429A mutation activated B2-Raf(8b), whereas it inhibited B3-Raf(9b). These results indicate that phosphorylation on both S365 and S429 participate in the differential regulation of B-Raf isoforms through distinct mechanisms. Finally, we show that autoinhibition and phosphorylation represent independent but convergent mechanisms accounting for B-Raf regulation by alternative splicing.
Auger coefficients in type-II InAs/Ga1−xInxSb quantum wells (1998)

Two different approaches, a photoconductive response technique and a correlation of lasing thresholds with theoretical threshold carrier concentrations have been used to determine Auger lifetimes in InAs/GaInSb quantum wells. For energy gaps corresponding to 3.1–4.8 μm, the room-temperature Auger coefficients for seven different samples are found to be nearly an order-of-magnitude lower than typical type-I results for the same wavelength. The data imply that at this temperature, the Auger rate is relatively insensitive to details of the band structure.
COOPERATIVE PLANNING BY COORDINATING THE SUPPLY CHANNEL (2006)

Abstract. Cooperation between manufacturing enterprises has recently become widespread in order to cope with newly emerged challenges, such as growing customer expectations, increasing product variety and decreasing product lifecycles. Nowadays the response to these challenges seems to be the formation of tight relations in supply chains and networks, which enables joint handling of market risks and involves sharing benefits and mutual growth. Our current work studies this situation in case of high manufacturing setup costs, which inspire enterprises to produce in large sized lots, which could in turn, lead to obsolete inventories on unstable markets. We propose a method for coordinating supply channels on such markets and a framework for cooperative planning.
Uptake and trafficking of fluorescent conjugates of folic acid in intact kidney determined using intravital two-photon microscopy (2004)

Intravital two-photon microscopy was used to follow the uptake and trafficking of fluorescent conjugates of folic acid in the rat kidney. Intravenously administered folate-linked dye molecules quickly filled the plasma volume but not cellular components of the blood. Glomerular filtration occurred immediately and binding to proximal tubule cells was seen within seconds. Fluorescence from a pH-insensitive conjugate of folic acid, folate Texas red (FTR), was readily observed on the apical surface of the proximal tubules and in multiple cellular compartments, but little binding or uptake could be detected in any other kidney cells. Fluorescence from a pH-sensitive conjugate of folic acid, folate fluorescein, was seen only on the apical surface of proximal tubule cells, suggesting that internalized folate conjugates are localized to acidic compartments. The majority of the FTR conjugate internalized by proximal tubules accumulated within a lysosomal pool, as determined by colocalization studies. However, portions of FTR were also shown by electron microscopy to undergo transcytosis from apical to basal domains. Additional studies with colchicine, which is known to depolymerize microtubules and interrupt transcytosis, produced a marked reduction in endocytosis of FTR, with accumulation limited to the subapical region of the cell. No evidence of cytosolic release of either folate conjugate was observed, which may represent a key difference from the cytosolic deposition seen in neoplastic cells. Together, these data support the argument that folate conjugates (and, by extrapolation, physiological folate) bind to the apical surface of proximal tubule cells and are transported into and across the cells in endocytic compartments.
Interactions between Human C5, C6, and C7 and Their Functional Significance in Complement-Dependent Cytolysis (1973)

Abstract Two types of complexes were observed between C5, C6 and C7. In their native form these three complement proteins enter into reversible interactions which were demonstrated by zone ultracentrifugation. Interactions between C5 and C6 occurred in absence of C7 and between C5 and C7 in absence of C6. Presence of C6, however, enhanced the association of C5 and C7. Formation of a stable C5–C6 complex was effected by the complement enzyme . This complex () had a sedimentation coefficient of 12 to 14S and exhibited the ability to attach itself firmly to non-sensitized sheep erythrocytes (E) in presence of C7. activity was also generated by trypsin or plasmin, suggesting the existence of a new pathway of complement activation by non-complement enzymes beginning with C5. produced with trypsin or displayed typical ultrastructural membrane lesions and was susceptible to lysis by C8 and C9. Regardless of experimental conditions, C5, C6, and C7 were taken up by the surface of cells in equimolar quantities. The affinity between native C5, C6, and C7 displayed in free solution, and the equimolarity of the cell-bound equivalents, support the concept of a firm trimolecular assembly as the topologic base of the membrane attack mechanism of complement.
Synthesis of 3-Alkenyl-1-azaanthraquinones via Diels-Alder and Electron Transfer Reactions (2002)

A convenient route to 3-alkenyl-1-azaanthraquinones via a hetero Diels-Alder reaction between an azadiene and naphthoquinone, a free radical chlorination and an electron transfer reaction is reported.
Das thermische Verhalten von Isopren‐Styrol‐Zweiblockcopolymeren (1981)

Abstract Investigations by pyrolysis‐gas chromatography (P‐GC) and by thermogravimetry (TG) on styrene‐isoprene two‐block copolymers demonstrated that the thermal behaviour of these copolymers is influenced mainly by the microstructure of the polyisoprene (PI) block. Generally, the PI blocks with a higher content of vinylic 1,2‐microstructures show a lower content of volatile products in P‐GC and a slower weight loss in TG, suggesting an apparent higher thermostability. All copolymers show in P‐GC the main products of the corresponding homopolymers in an amount directly proportional to the respective content of the components in the copolymers. All results suggest an independent degradation of the two different blocks of styrene‐isoprene block copolymers.
Ecotourism: Conserving biocultural diversity and contributing to sustainable development (2016)

This thesis looks at how ecotourists can become aware of biocultural diversity (the intersection of biological and cultural diversity) and help contribute to sustainable development, which considers the needs of both present and future generations. The thesis will address the ecotourism industry and how people who travel with companies that cater to ecotourists can contribute to biocultural diversity and sustainable development. It will utilize a sustainable development framework and a critical theory approach for considering biological and cultural perspectives including human rights and social justice, the contribution of traditional knowledge, community involvement, and the effects of human impact and globalization. The primary audience of my research is people who travel the globe in search of the earth’s natural wonders. I highlight issues related to minimizing environmental impact, respecting local cultures, building environmental awareness, and providing direct financial benefits for conservation. My central research question is: How can travelers help to preserve the environment, be sensitive to local cultures, and contribute to a sustainable future? I ask: By understanding the distinct correlation between biological and cultural diversity, how can we utilize both traditional (and local) knowledge combined with scientific knowledge to help sustain and preserve our natural ecosystems? I conclude with findings that point to the need for shared community authority, management, and decision making; mutual benefits; recognition of the rights, values, norms, power structures, and dynamics of local populations; respect for belief systems as well as traditional and local ecological knowledge; and the importance of contextual adaptation.
Frequency and Bandwidth Agile Pulser for Use in Wideband Applications (2004)

We have developed an architecture to produce a wideband pulser that is tunable in the important parameters of pulsewidth, bandwidth, and center frequency. The pulser is based on a parallel plate Blumlein pulse-forming network (PFN) with a movable center (charge) conductor. When the center conductor is displaced from the ideal Blumlein position, the balance in the PFN is lost, resulting in a slightly ringing waveform that can be tuned. By selecting the amount of ringing, the output bandwidth of the PFN can be adjusted. Furthermore, by simply sliding the center conductor out of the PFN, the effective electrical length can be adjusted, allowing the fundamental period of the ringing waveform to be altered, thereby changing the center frequency of the output waveform. Our pulser is designed to operate in the range of 300 MHz to 2 GHz, but the architecture is scalable outside this range. In this paper, we present design and simulation results, low-voltage tests, and preliminary high-voltage (15-kV) data that is obtained with a pressurized gas trigatron designed specifically for this test fixture. The pulser is being designed for laboratory use in testing the effects of interaction of high-intensity wideband electromagnetic fields with small-scale electrical and biological systems.
Torsional Rigidity of Positively and Negatively Supercoiled DNA (1992)

Time-correlated single-photon counting of intercalated ethidium bromide was used to measure the torsion constants of positively supercoiled, relaxed, and negatively supercoiled pBR322 DNA, which range in superhelix density from +0.042 to -0.123. DNA behaves as coupled, nonlinear torsional pendulums under superhelical stress, and the anharmonic term in the Hamiltonian is approximately 15 percent for root-mean-square fluctuations in twist at room temperature. At the level of secondary structure, positively supercoiled DNA is significantly more flexible than negatively supercoiled DNA. These results exclude certain models that account for differential binding affinity of proteins to positively and negatively supercoiled DNA.
Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma (2016)

The p21-activated kinase 4 (PAK4) is a key downstream effector of the Rho family GTPases and is found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC) cells but not in normal human pancreatic ductal epithelia (HPDE). Gene copy number amplification studies in PDAC patient cohorts confirmed PAK4 amplification making it an attractive therapeutic target in PDAC. We investigated the antitumor activity of novel PAK4 allosteric modulators (PAM) on a panel of PDAC cell lines and chemotherapy-resistant flow-sorted PDAC cancer stem cells (CSC). The toxicity and efficacy of PAMs were evaluated in multiple subcutaneous mouse models of PDAC. PAMs (KPT-7523, KPT-7189, KPT-8752, KPT-9307, and KPT-9274) show antiproliferative activity in vitro against different PDAC cell lines while sparing normal HPDE. Cell growth inhibition was concurrent with apoptosis induction and suppression of colony formation in PDAC. PAMs inhibited proliferation and antiapoptotic signals downstream of PAK4. Co-immunoprecipitation experiments showed disruption of PAK4 complexes containing vimentin. PAMs disrupted CSC spheroid formation through suppression of PAK4. Moreover, PAMs synergize with gemcitabine and oxaliplatin in vitro KPT-9274, currently in a phase I clinical trial (clinicaltrials.gov; NCT02702492), possesses desirable pharmacokinetic properties and is well tolerated in mice with the absence of any signs of toxicity when 200 mg/kg daily is administered either intravenously or orally. KPT-9274 as a single agent showed remarkable antitumor activity in subcutaneous xenograft models of PDAC cell lines and CSCs. These proof-of-concept studies demonstrated the antiproliferative effects of novel PAMs in PDAC and warrant further clinical investigations. Mol Cancer Ther; 16(1); 76-87. ©2016 AACR.
Lymphatic MAFB regulates vascular patterning during developmental and pathological lymphangiogenesis (2020)

MAFB is a transcription factor involved in the terminal differentiation of several cell types, including macrophages and keratinocytes. MAFB is also expressed in lymphatic endothelial cells (LECs) and is upregulated by VEGF-C/VEGFR-3 signaling. Recent studies have revealed that MAFB regulates several genes involved in lymphatic differentiation and that global Mafb knockout mice show defects in patterning of lymphatic vessels during embryogenesis. However, it has remained unknown whether this effect is LEC-intrinsic and whether MAFB might also be involved in postnatal lymphangiogenesis. We established conditional, lymphatic-specific Mafb knockout mice and found comparable lymphatic patterning defects during embryogenesis as in the global MAFB knockout. Lymphatic MAFB deficiency resulted in increased lymphatic branching in the diaphragm at P7, but had no major effect on lymphatic patterning or function in healthy adult mice. By contrast, tumor-induced lymphangiogenesis was enhanced in mice lacking lymphatic MAFB. Together, these data reveal that LEC-expressed MAFB is involved in lymphatic vascular morphogenesis during embryonic and postnatal development as well as in pathological conditions. Therefore, MAFB could represent a target for therapeutic modulation of lymphangiogenesis.
In Vitro Comparison of 4 Ultrasound Lithotripsy Devices (2003)

All ultrasound devices are effective for lithotripsy. Changes in the ultrasound setup and integration of modern technical knowledge into ultrasound devices increase efficacy.
Lambda Interferon (IFN-λ) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-γ-Induced Nitric Oxide Production (2007)

Hantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), are known to be sensitive to nitric oxide (NO) and to pretreatment with type I and II interferons (alpha interferon [IFN-alpha]/IFN-beta and IFN-gamma, respectively). Elevated serum levels of NO and IFN-gamma have been observed in HFRS patients, but little is known regarding the systemic levels of other IFNs and the possible effects of hantaviruses on innate antiviral immune responses. In Puumala virus-infected HFRS patients (n = 18), we report that the levels of IFN-alpha and IFN-beta are similar, whereas the level of IFN-lambda (type III IFN) is significantly decreased, during acute (day of hospitalization) compared to the convalescent phase. The possible antiviral effects of IFN-lambda on the prototypic hantavirus Hantaan virus (HTNV) replication was then investigated. Pretreatment of A549 cells with IFN-lambda alone inhibited HTNV replication, and IFN-lambda combined with IFN-gamma induced additive antiviral effects. We then studied the effect of postinfection treatment with IFNs. Interestingly, an already-established HTNV infection was insensitive to subsequent IFN-alpha, -beta, -gamma, and -lambda stimulation, and HTNV-infected cells produced less NO compared to noninfected cells when stimulated with IFN-gamma and IL-1beta. Furthermore, less phosphorylated STAT1 after IFN treatment was observed in the nuclei of infected cells than in those of noninfected cells. The results suggest that hantavirus can interfere with the activation of antiviral innate immune responses in patients and inhibit the antiviral effects of all IFNs. We believe that future studies addressing the mechanisms by which hantaviruses interfere with the activation and shaping of immune responses may bring more knowledge regarding HFRS and HCPS pathogenesis.
DXOMARK Objective Video Quality Measurements (2020)

Video capture is becoming more and more widespread. The technical advances of consumer devices have led to improved video quality and to a variety of new use cases presented by social media and artificial intelligence applications. Device manufacturers and users alike need to be able to compare different cameras. These devices may be smartphones, automotive components, surveillance equipment, DSLRs, drones, action cameras, etc. While quality standards and measurement protocols exist for still images, there is still a need of measurement protocols for video quality. These need to include parts that are non-trivially adapted from photo protocols, particularly concerning the temporal aspects. This article presents a comprehensive hardware and software measurement protocol for the objective evaluation of the whole video acquisition and encoding pipeline, as well as its experimental validation.
Intraperitoneal Paclitaxel Is a Safe and Effective Therapeutic Strategy for Treating Mucinous Appendiceal Adenocarcinoma (2023)

The activity and safety of intraperitoneal paclitaxel in orthotopic PDX models of mucinous appendiceal adenocarcinoma supports the evaluation of intraperitoneal paclitaxel in a prospective clinical trial of this rare tumor type.
Obtaining precise parameter estimates for nonlinear catalytic rate models (1966)

Abstract A method is reviewed which allows data points to be chosen in such a fashion that precise estimates of the parameters in nonlinear reaction rate models can be obtained. This method allows each future data point to be selected such that the confidence region of the estimated parameters is smaller with it than with any other possible data point within the region of experimentation. This procedure is applied for Hougen‐Watson models with hypothetical experimental data which were generated with the guidance of an example from the current chemical engineering literature. It is found that, for the same number of data points, the parameters in the model can be estimated eighteen times more precisely by using this suggested experimental design than by another commonly used design. Confidence regions are presented for the parameters of the Hougen‐Watson models with two types of designs. It is found that the positions of the data points in the well‐designed experiments are more sensitive to the functional form of the model than to the current estimates of the magnitudes of the parameter values.
Factors Associated with Stent Change and Prognosis in Patients with Malignant Ureteral Obstruction (2022)

<b><i>Purpose:</i></b> To identify factors associated with stent changes and prognosis in patients with malignant ureteral obstruction (MUO) undergoing <i>de novo</i> retrograde ureteral stenting. <b><i>Materials and Methods:</i></b> A retrospective cohort study was conducted at a tertiary referral center for consecutive MUO patients referred and initially managed with a ureteral stent. Multivariable regression models evaluated factors associated with the following outcomes: number of stent changes, time to first stent change, and overall survival. <b><i>Results:</i></b> A total of 120 patients from May 2009 to December 2019 were included; mean age was 63 years, majority (76.7%) were women, median duration of follow-up was 6.1 months. Majority (75%) of patients did not require a stent change at 3 months follow-up. Patients with a history of pelvic radiation (subdistribution hazard rate [sHR] 2.12, 95% confidence interval [CI] 1.23-3.67, <i>p</i> = 0.007) and with a history of bowel resection (sHR 2.06, 95% CI 1.05-4.03, <i>p</i> = 0.036) were independently associated with earlier stent changes. Patients with gastrointestinal (GI) malignancy (hazard rate [HR] 14.1, 95% CI 2.66-74.19, <i>p</i> = 0.0019) and proximal ureter obstruction (HR 2.49, 95% CI 1.21-5.14, <i>p</i> = 0.0136) were associated with higher rate of all-cause mortality. <b><i>Conclusions:</i></b> The majority of patients did not require stent change at their first stent surveillance cystoscopy at 3 months follow-up. Patients with a history of pelvic radiation or bowel resection were more likely to require stent change during their stent surveillance visits. GI malignancy and proximal ureter obstruction were associated with higher rates of mortality.
Arginylation Regulates Cytoskeleton Organization and Cell Division and Affects Mitochondria in Fission Yeast (2022)

Protein arginylation mediated by arginyltransferase Ate1 is a posttranslational modification of emerging importance implicated in the regulation of mammalian embryogenesis, the cardiovascular system, tissue morphogenesis, cell migration, neurodegeneration, cancer, and aging. <i>Ate1</i> deletion results in embryonic lethality in mice but does not affect yeast viability, making yeast an ideal system to study the molecular pathways regulated by arginylation. Here, we conducted a global analysis of cytoskeleton-related arginylation-dependent phenotypes in Schizosaccharomyces pombe, a fission yeast species that shares many fundamental features of higher eukaryotic cells. Our studies revealed roles of Ate1 in cell division, cell polarization, organelle transport, and interphase cytoskeleton organization and dynamics. We also found a role of Ate1 in mitochondria morphology and maintenance. Furthermore, targeted mass spectrometry analysis of the total Sc. pombe arginylome identified a number of arginylated proteins, including those that play direct roles in these processes; lack of their arginylation may be responsible for <i>ate1</i>-knockout phenotypes. Our work outlines global biological processes potentially regulated by arginylation and paves the way to unraveling the functions of protein arginylation that are conserved at multiple levels of evolution and potentially constitute the primary role of this modification <i>in vivo</i>.
Analyzing Plasma HIV-1 RNA Measurements as Multiple Recurrent Events in Clinical Trials (2006)

Primary endpoints based on levels of HIV-1 RNA are currently used to evaluate efficacy of antiretroviral therapy in AIDS/HIV clinical trials. These endpoints, however, are generally based on few HIV-1 RNA measurements. More specifically, when the endpoint is the time to virologic failure (usually defined as two consecutive HIV-1 RNA levels above a threshold value), viral load measurements recorded after failure are simply ignored in the analysis. Instead of one virologic failure used in a classical survival analysis, we suggest that a failure be defined as any plasma HIV-1 RNA level above a predefined threshold value. This then becomes an analysis of multiple events of the same type, that is, recurrent virologic failures. Many survival models based on the Cox proportional hazards model have been proposed to handle multiple event data. The two distinct classes of models (marginal and conditional) answer two distinct types of clinical question and should be considered as complementary rather than competing models. We applied the different models to data from a clinical trial in HIV-1-infected patients.