gebhart/patrepeval huggingface dataset:
Endocytic pathways and biological effects induced by UVB‐dependent or ligand‐dependent activation of the keratinocyte growth factor receptor (2005)

UVB exposure of epidermal cells is known to trigger early and late molecular pathways dependent on receptor tyrosine kinases and reactive oxygen species (ROS). We have recently reported that UVB irradiation induces tyrosine phosphorylation, kinase activation, and internalization of the receptor for the keratinocyte growth factor (KGFR), a paracrine mediator of epithelial growth, differentiation, and survival. Here we analyzed in more detail the UVB-induced endocytic pathway of KGFR and the role of KGFR activation and internalization in regulating UVB-promoted apoptosis and cell cycle arrest. Immunogold electron microscopy and confocal analysis revealed that the UVB-induced endocytosis of KGFR occurs through clathrin-coated pits and that the internalized receptors are sorted to the degradative route and reach the lysosomal compartment with a timing similar to that induced by their ligand KGF. Treatment with the anti-oxidant N-acetylcysteine inhibited KGFR endocytosis, suggesting that the receptor internalization is mediated by the intracellular production of ROS. The ligand-independent KGFR endocytic pathway induced by UVB requires receptor kinase activity and tyrosine phosphorylation and involves transient receptor ubiquitination. Inhibition of KGFR activity reduces both the KGF-mediated proliferative response and the UVB-promoted apoptotic cell death, indicating a different effect of ligand-induced and UVB-induced KGFR triggering. In addition, receptor internalization leads to protection from apoptosis caused by UVB exposure. Finally, we compared directly the behavior of KGFR with that of the epidermal growth factor receptor (EGFR) upon UVB exposure. Surprisingly, biochemical and immunofluorescence analysis showed that EGFR, differently from KGFR, does not undergo UVB-induced tyrosine phosphorylation and internalization. Taken together, our results suggest a differential role of KGFR and EGFR in the response of epidermal cells to UVB possibly because KGFR endocytosis could be crucial for attenuation of survival signals in the suprabasal layers of human skin.
Supplementary Data from The INPP4B Tumor Suppressor Modulates EGFR Trafficking and Promotes Triple-Negative Breast Cancer (2023)

&lt;p&gt;Supplementary figures S1-S7&lt;/p&gt;
Intravenous esomeprazole for prevention of peptic ulcer re‐bleeding: rationale/design of Peptic Ulcer Bleed study (2008)

The carefully designed protocol and quality control measures represent a pragmatic approach to contemporary challenges in peptic ulcer bleeding management and, it is hoped, qualify the Peptic Ulcer Bleed study as a new standard for future interventional studies.
T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire (2017)

Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment.
Recent advances in amyotrophic lateral sclerosis research: perspectives for personalized clinical application (2010)

Treatment of amyotrophic lateral sclerosis (ALS) has been fueled, in part, by frustration over the shortcomings of the symptomatic drugs available, since these do not impede the progression of this disease. Currently, over 150 different potential therapeutic agents or strategies have been tested in preclinical models of ALS. Unfortunately, therapeutic modifiers of murine ALS have failed to be successfully translated into strategies for patients, probably because of differences in pharmacokinetics of the therapeutic agents, route of delivery, inefficiency of the agents to affect the distinct pathologies of the disease or inherent limitations of the available animal models. Given the multiplicity of the pathological mechanisms implicated in ALS, new therapies should consider the simultaneous manipulation of multiple targets. Additionally, a better management of ALS therapy should include understanding the interactions between potential risk factors, biomarkers and heterogeneous clinical features of the patients, aiming to manage their adverse events or personalize the safety profile of these agents. This review will discuss novel pharmacological approaches concerning adjusted therapy for ALS patients: iron-binding brain permeable multimodal compounds, genetic manipulation and cell-based treatment.
Design of a microprocessor‐controlled automated injection system for the analysis of gas phase cigarette smoke using glass capillary columns (1979)

Abstract An automatic injection system for the analysis of gas phase smoke has been designed and evaluated using the microprocessor‐controlled Hewlett‐Packard 5830 gas chromatograph. The cryogenic preconcentration trap was constructed from relatively inexpensive and readily available materials. It was determined that the use of the preconcentration trap, as opposed to condensing the smoke on the head of the cold (‐50°C) chromatographic column, significantly enhanced the resolution of the more volatile gas phase components. Data are presented which illustrate the injection system characteristics. In addition, chromatograms of gas phase smoke are presented which demonstrate the effectiveness of this technique.
Energy-Efficient Service-Aware Multi-Connectivity Scheduler for Uplink Multi-Layer Non-Terrestrial Networks (2023)

This paper introduces the concept of energy efficiency (EE) in the uplink with the capability of multi-connectivity (MC) in a multi-orbit non-terrestrial network (NTN), where user terminals (UTs) can be simultaneously served by more than one satellite to achieve higher peak throughput at reduced energy consumption. This concept also considers the service classification of the users, so that network dimensioning is performed in order to satisfy the quality of service (QoS) requirement of users. MC can increase throughput, but this entails increased power consumption at user terminal for uplink transmissions. To this end, an energy-efficient service-aware multi-connectivity (EE-SAMC) scheduling algorithm is developed in this paper to improve the EE of uplink communications. EE-SAMC uses available radio resources and propagation information to intelligently define a dynamic resource allocation pattern, that optimally routes traffic so as to reduce the energy consumption at the UT while ensuring QoS is maximized. EE-SAMC is designed based on the formulation of a non-convex combinatorial problem, it is solved in two ways involving firstly an optimization solution and secondly a heuristic approach. The effectiveness of EE-SAMC is compared with random allocation, round robin and heuristic schedulers in terms of EE, throughput and delay; EE-SAMC outperforms all schedulers.
The Cystic Transverse Limb of the Articular Branch: a Pathognomonic Sign Forperoneal Intraneural Ganglia Atthe Superior Tibiofibular Joint (2006)

This article demonstrates reproducible magnetic resonance imaging features that will easily allow one to identify the joint connection (the tail sign) in paraarticular cysts and also to distinguish between peroneal intraneural and extraneural ganglia (the transverse limb sign and the signet ring sign) at the superior tibiofibular joint with accuracy and confidence and with subsequent improvement in treatment and patient outcomes.
The mechanical response of commercially pure copper under multiaxial loading at low and high strain rates (2022)

In this paper, we present the dynamic response of commercially pure copper subjected to combined tension-torsion loads representative of real case impact scenarios. Experiments were conducted both quasi statically, at a strain rate equal to 10−3 s−1, and dynamically at strain rates in the region between 500 s−1 and 1000 s−1. All high rate experiments were conducted using a novel Split Hopkinson Tension-Torsion Bar instrumented with high-speed photographic equipment. The dynamic combined loading experiments demonstrate the capability of the apparatus to generate longitudinal and torsional stress waves which are synchronised upon loading of the specimen. The presented data show that dynamic equilibrium conditions and nearly steady strain rates were achieved during the experiments. Additionally, the analyses of the loading paths show that nearly proportional strain loading was attained during testing. The measured experimental results illustrate, for the first time, the failure stress locus of the material over a wide range of stress states including pure torsion, shear-dominated combined tension-shear, tension-dominated combined tension-shear and plain tension. The quasi-static and dynamic failure envelopes are herein presented in the normal stress vs shear stress space to motivate the development of accurate and effective constitutive models. To conclude, the Drucker-Prager criterion was employed to approximate the failure loci and to assess the rate sensitivity of the material. A moderate asymmetry of the uniaxial ultimate stresses in tension and compression is predicted both at quasi-static and dynamic strain rates.
Expression of β‐glucosidase increases trichome density and artemisinin content in transgenic Artemisia annua plants (2015)

Artemisinin is highly effective against multidrug-resistant strains of Plasmodium falciparum, the aetiological agent of the most severe form of malaria. However, a low level of accumulation of artemisinin in Artemisia annua is a major limitation for its production and delivery to malaria endemic areas of the world. While several strategies to enhance artemisinin have been extensively explored, enhancing storage capacity in trichome has not yet been considered. Therefore, trichome density was increased with the expression of β-glucosidase (bgl1) gene in A. annua through Agrobacterium-mediated transformation. Transgene (bgl1) integration and transcript were confirmed by molecular analysis. Trichome density increased up to 20% in leaves and 66% in flowers of BGL1 transgenic plants than Artemisia control plants. High-performance liquid chromatography, time of flight mass spectrometer data showed that artemisinin content increased up to 1.4% in leaf and 2.56% in flowers (per g DW), similar to the highest yields achieved so far through metabolic engineering. Artemisinin was enhanced up to five-fold in BGL1 transgenic flowers. This study opens the possibility of increasing artemisinin content by manipulating trichomes' density, which is a major reservoir of artemisinin. Combining biosynthetic pathway engineering with enhancing trichome density may further increase artemisinin yield in A. annua. Because oral feeding of Artemisia plant cells reduced parasitemia more efficiently than the purified drug, reduced drug resistance and cost of prohibitively expensive purification process, enhanced expression should play a key role in making this valuable drug affordable to treat malaria in a large global population that disproportionally impacts low-socioeconomic areas and underprivileged children.
Society for Anti-infective Pharmacology--Ninth International Symposium. 3-4 July 1999, Birmingham, UK. (1999)

This meeting, organized as a 'self-contained' pre-symposium to the 21st International Congress of Chemotherapy, was introduced by Paul Tulkens (Université Catholique de Louvain, Brussels, Belgium), the outgoing president of the society, who reviewed the progress of pharmacodynamics (PD) and pharmacokinetics (PK) in anti-infective research over the past ten years. It was noted that, hitherto, the factors driving therapeutic regimens have been largely 'irrational' with a concentration on achieving the lowest dosage, PK being used principally to establish drug presence and PD considerations largely 'terra incognita'. In contrast, through recent PK/PD studies, we now know that the dose effect of different classes of anti-infectives varies widely, with some showing time-dependence, some a post-antibiotic effect and some co-operating with host defenses. By integrating these factors, we should be in a better position to predict the success or failure of potential new antibiotics at an earlier stage. The focus of the meeting was, therefore, the use of PD and PK to accelerate drug discovery, development and registration. Two particular factors were stressed: the need to establish dosing regimens which avoided or minimized the development of resistance and the role of PD/PK in the discovery process for novel classes of antibiotics that are emerging from genomic programs. The conference was attended by approximately 50 participants, from academia and industry, with representatives from several regulatory authorities also present.
Testing Functional Fields Of View With The Multi-screen Text Display Device RSG (2005)

Wearers of Progressive lenses, which have differing power as a function of the eyes' position, must sometimes make head movements in order to clearly see a target in space. The progressive lenses thus induce a "modified gaze field" which changes the required tradeoff between head and eye movement in shifts of gaze. This paper reports experiments using a multi-screen microcomputer text display device to test the effects of various modifications of the gaze field on reading performance. Subjects were asked to repeat aloud 3-word groups presented one word at a time on three CRTs separated by one of several visual angles. The number of words reported incorrectly as presentation rate is increased is a measure of the impairment of gaze-directed reading. Results of preliminary experiments describe the drop in performance under normal vision conditions as a function of target eccentricity. This data is the basis for comparison with the measured performance of subject wearing progressive lenses and illustrates the different gaze shift strategies among subjects.
Atypical interactions between GCPII and hydroxamate-based inhibitors (2014)

Human glutamate carboxypeptidase II (GCPII) is a zinc-dependent metallopeptidase implicated in diverse pathologies. GCPII-specific ligands can be used in diagnostic and therapeutic applications in prostate cancer and various neurological disorders [1]. Such ligands typically consist of a glutamate moiety linked to a zinc-binding group to ensure high specificity and affinity, respectively [2]. Hydroxamate functionality is one of the prominent zinc-binding functions used in the field, however, there are no structural data describing interactions between hydroxamates and GCPII. Here we report X-ray structures of six complexes between GCPII and hydroxamate-based inhibitors. Our structures reveal unexpected positioning of hydroxamates in the internal GCPII pocket that differs markedly from binding modes of matching prototypical GCPII inhibitors featuring different zinc-binding groups. They provide mechanistic explanation for prior structure-activity relationship studies and can be exploited for the structure-assisted design of novel GCPII-specific compounds.
Only three driver gene mutations are required for the development of lung and colorectal cancers (2014)

Cancer arises through the sequential accumulation of mutations in oncogenes and tumor suppressor genes. However, how many such mutations are required for a normal human cell to progress to an advanced cancer? The best estimates for this number have been provided by mathematical models based on the relation between age and incidence. For example, the classic studies of Nordling [Nordling CO (1953) Br J Cancer 7(1):68-72] and Armitage and Doll [Armitage P, Doll R (1954) Br J Cancer 8(1):1-12] suggest that six or seven sequential mutations are required. Here, we describe a different approach to derive this estimate that combines conventional epidemiologic studies with genome-wide sequencing data: incidence data for different groups of patients with the same cancer type were compared with respect to their somatic mutation rates. In two well-documented cancer types (lung and colon adenocarcinomas), we find that only three sequential mutations are required to develop cancer. This conclusion deepens our understanding of the process of carcinogenesis and has important implications for the design of future cancer genome-sequencing efforts.
Ant-based adaptive trust evidence distribution in MANET (2004)

Due to the lack of infrastructure and vulnerability of wireless links, security in ad hoc networks is considered to be much more difficult than in traditional hierarchical networks. Building the trust relationship between entities is a fundamental problem in ad hoc networks, since the availability of servers, which distribute trust certificates, is not guaranteed. Furthermore, the existence of any trusted server might not be assumed either. Therefore, the commonly used key distribution center (KDC) and certification authority (CA) are not applicable in such highly autonomous environments. We propose a scheme for the distribution of trust certificates, which is completely distributed and adaptive to mobility. Our scheme is based on the swarm intelligence paradigm, which has been used for routing both in wired and wireless networks. Our simulations in ns-2 show that it performs very well in ad hoc environments.
Comprehensive multi-cohort transcriptional meta-analysis of muscle diseases identifies a signature of disease severity (2022)

Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: (i) immobility, (ii) inflammatory myopathies, (iii) intensive care unit (ICU) acquired weakness (ICUAW), (iv) congenital muscle diseases, (v) chronic systemic diseases, (vi) motor neuron disease. Patient cohorts were separated in discovery and validation cohorts retaining roughly equal proportions of samples for the disease categories. To remove bias towards a specific muscle disease category we repeated the meta-analysis five times by removing data sets corresponding to one muscle disease class at a time in a "leave-one-disease-out" analysis. We used 636 muscle tissue samples from 30 independent cohorts to identify a 52 gene signature (36 up-regulated and 16 down-regulated genes). We validated the discriminatory power of this signature in 657 muscle biopsies from 12 additional patient cohorts encompassing five categories of muscle diseases with an area under the receiver operating characteristic curve of 0.91, 83% sensitivity, and 85.3% specificity. The expression score of the gene signature inversely correlated with quadriceps muscle mass (r = -0.50, p-value = 0.011) in ICUAW and shoulder abduction strength (r = -0.77, p-value = 0.014) in amyotrophic lateral sclerosis (ALS). The signature also positively correlated with histologic assessment of muscle atrophy in ALS (r = 0.88, p-value = 1.62 × 10<sup>-3</sup>) and fibrosis in muscular dystrophy (Jonckheere trend test p-value = 4.45 × 10<sup>-9</sup>). Our results identify a conserved transcriptional signature associated with clinical and histologic muscle disease severity. Several genes in this conserved signature have not been previously associated with muscle disease severity.
Snow Infiltration Tests on the Shinglevent II Ridge Vent Configuration (1996)

The present study addresses the performance of the ridge vent Shinglevent II,&#13;\na product of Air Vent Inc., in regard to the possible entry of snow into the attic space&#13;\nunder strong wind conditions. The Shinglevent II configuration made available by Air&#13;\nVent Inc. was tested for snow infiltration. To simulate field conditions as closely as&#13;\npossible, actual natural dry snow was used. The tests were conducted during winter&#13;\nusing the open circuit mode of operation of the St. Anthony Falls Laboratory&#13;\nboundary layer wind tunnel.&#13;\nTests 'have been carried out to date at a wind approach angle of 0 degrees&#13;\n(wind direction perpendicular to the roof ridge). The model was constructed in three&#13;\npieces (a central piece and two angle pieces) so that, by omitting the two angle&#13;\npieces, it can be fitted in the tunnel in a rotated 45 degree position for additional&#13;\ntesting with 45 degree approach winds.
Limited sampling strategies for the estimation of atazanavir daily exposure in HIV‐infected patients (2011)

Stepwise multiple regression analyses were applied to 44 atazanavir pharmacokinetic profiles from 44 HIV-1 infected patients concomitantly treated with raltegravir with the goal of identifying limited sampling strategies for the prediction of drug AUC(0-12) . Atazanavir trough-based equations failed to reliably predict daily drug exposure in patients with low drug bioavailability. Conversely, different algorithms based on few samples and associated with good correlation, acceptable bias and imprecision with the measured atazanavir AUC(0-12) were identified. These models could be used to predict atazanavir exposure for clinic or research purposes.
Structural and electronic properties of metastable epitaxialFeSi1+xfilms on Si(111) (1992)

We have investigated the epitaxial growth and the electronic properties of a metallic metastable FeSi phase crystallizing with the CsCl structure on Si(111). Upon annealing below 500 \ifmmode^\circ\else\textdegree\fi{}C the stoichiometry of thin films (20 \AA{}) evolves towards ${\mathrm{FeSi}}_{2}$ with no change of symmetry, i.e., the defect CsCl structure with a statistical occupation of metal sites remains epitaxially stable for all ${\mathrm{FeSi}}_{1+\mathit{x}}$ (0\ensuremath{\le}x\ensuremath{\le}1). Films thicker than -20 \AA{} exhibit a transition to the cubic \ensuremath{\epsilon}-FeSi phase. The electronic band structure of FeSi (CsCl) has been calculated self-consistently using the full-potential linear augmented--plane-wave method.