gebhart/patrepeval huggingface dataset:
Clathrin-Mediated Endocytosis Is Impaired in Type A–B Niemann–Pick Disease Model Cells and Can Be Restored by ICAM-1-Mediated Enzyme Replacement (2014)

Drugs often use endocytosis to achieve intracellular delivery, either by passive uptake from the extracellular fluid or by active targeting of cell surface features such as endocytic receptors. An example is enzyme replacement therapy, a clinically practiced treatment for several lysosomal storage diseases where glycosylated recombinant enzymes naturally target the mannose-6-phosphate receptor and are internalized by clathrin mediated endocytosis (CME). However, lysosomal substrate accumulation, a hallmark of these diseases, has been indirectly linked to aberrant endocytic activity. These effects are poorly understood, creating an obstacle to therapeutic efficiency. Here we explored endocytic activity in fibroblasts from patients with type A Niemann-Pick disease, a lysosomal storage disease characterized by acid sphingomyelinase (ASM) deficiency. The uptake of fluid phase markers and clathrin-associated ligands, formation of endocytic structures, and recruitment of intracellular clathrin to ligand binding sites were all altered, demonstrating aberrant CME in these cells. Model polymer nanocarriers targeted to intercellular adhesion molecule-1 (ICAM-1), which are internalized by a clathrin-independent route, enhanced the intracellular delivery of recombinant ASM more than 10-fold compared to free enzyme. This strategy reduced substrate accumulation and restored clathrin endocytic activity to wild-type levels. There appears to be a relationship between lysosomal storage and diminished CME, and bypassing this pathway by targeting ICAM-1 may enhance future therapies for lysosomal storage diseases.
Association of Circulating C1q/TNF-Related Protein 1 Levels with Coronary Artery Disease in Men (2014)

Our data indicate the close association of high CTRP1 levels with CAD prevalence, suggesting that CTRP1 represents a novel biomarker for CAD.
Improved SILAC Quantification with Data-Independent Acquisition to Investigate Bortezomib-Induced Protein Degradation (2021)

Stable isotope labeling by amino acids in cell culture (SILAC) coupled to data-dependent acquisition (DDA) is a common approach to quantitative proteomics with the desirable benefit of reducing batch effects during sample processing and data acquisition. More recently, using data-independent acquisition (DIA/SWATH) to systematically measure peptides has gained popularity for its comprehensiveness, reproducibility, and accuracy of quantification. The complementary advantages of these two techniques logically suggests combining them. Here we develop a SILAC-DIA-MS workflow using free, open-source software. We empirically determine that using DIA achieves similar peptide detection numbers as DDA and that DIA improves the quantitative accuracy and precision of SILAC by an order of magnitude. Finally, we apply SILAC-DIA-MS to determine protein turnover rates of cells treated with bortezomib, an FDA-approved 26S proteasome inhibitor for multiple myeloma and mantle cell lymphoma. We observe that SILAC-DIA produces more sensitive protein turnover models. Of the proteins determined to be differentially degraded by both acquisition methods, we find known proteins that are degraded by the ubiquitin-proteasome pathway, such as HNRNPK, EIF3A, and IF4A1/EIF4A-1, and a slower turnover for CATD, a protein implicated in invasive breast cancer. With improved quantification from DIA, we anticipate that this workflow will make SILAC-based experiments like protein turnover more sensitive.
Homogeneous Diesel Combustion with External Mixture Formation by a Cool Flame Vaporizer (2006)

<div class="htmlview paragraph">The homogeneous Diesel combustion is a way to effect a soot and nitrogen oxide (NO<sub>x</sub>) free Diesel engine operation. Using direct injection of Diesel fuel, the mixture typically ignites before it is fully homogenized. In this study a homogeneous mixture is prepared outside of the combustion chamber by a Cool Flame Vaporizer. At first the specification of the vaporizer is given in this paper. To determine the composition of the vaporizer gas an analysis using gas chromatography/mass spectroscopy (GC/MS) was made. The results give an idea of the effects on engine combustion. Followed by, the vaporizer was adapted to a single-cylinder Diesel engine. To adapt the engine's configuration regarding compression ratio and inlet temperature range a zero dimensional engine process simulation software was utilized. The engine was run in different operating modes. The test results with external mixture formation were compared with two low temperature Diesel combustion strategies based on direct fuel injection: the Premixed Charge Compression Ignition (PCCI) and the Late Low Temperature Combustion (LLTC).</div>
[Radioimmunotargeting: diagnosis and therapeutic use]. (2000)

Monoclonal antibodies labeled with a radionuclide make feasible the in vivo radioimmunotargeting of tumor cells. This targeting could be performed for diagnosis, using gamma emitters, or for therapeutic purpose when antibodies are labeled with beta- and in the future alpha-emitters. Diagnosis applications (tumor detection and caracterization), i.e. immunoscintigraphy, have been widely investigated during 20 last years. This technic appeared quite interesting, complementary of morphological imaging, and clinically useful, but difficult on a practical point of view because of several pharmacological and immunological limitations. For these reasons, despite several consequent improvements (especially two-steps or pre-targeting methods), immunoscintigraphy is currently not widely used; furthermore, other scintigraphic methods, mainly positron emission tomography with 18F-fluorodeoxyglucose, are efficient and easier to perform. On the other hand, knowledge of the biodistribution of radiolabeled antibodies allows the development of their therapeutic use, i.e. radioimmunotherapy, which represents a new method of cancer treatment. Radioimmunotherapy has several particular radiobiological and dosimetric aspects, which remain widely under investigation. Understanding of these aspects, together with a better delineation of the indications, allow to be really optimist concerning this new way of cancer treatment, as shown by clinical results that have been obtained in non Hodgkin's lymphoma. Radiolabeled immunoconjugates appears as a growing field in nuclear medicine, which sustains numerous preclinical and clinical studies.
Inhibitory effects of antiherpesviral thymidine analogs against varicella-zoster virus (1982)

Thymidine analogs highly active against herpes simplex virus were compared in their inhibitory action against seven strains of varicella-zoster virus by a plaque reduction assay. E-5-Bromovinyl-arabinosyluracil (BV-ara-U) was most active, followed by E-5 chlorovinyl-arabinosyluracil, E-5-bromovinyl-2'-deoxyuridine (BV-dUrd), 2'-fluoro-5-methyl-arabinosyluracil, 2'-fluoro-5-iodo-arabinosylcytosine, arabinosylthymine, 5-vinyl-arabinosyluracil, acycloguanosine, and 5-iodo-2'-deoxyuridine, in order to decreasing activity. BV-ara-U was more than 10 times as active as BV-dUrd and almost completely inhibited plaque development of five strains of varicella-zoster virus at a concentration as low as 1 ng/ml.
Assessment of tissue blood flow following small artery welding with an intraluminal dissolvable stent (1999)

Using the technique of radioactive 51Cr-labeled biological microspheres, this study evaluated arterial blood flow following small vessel anastomosis by CO2 laser welding and a dissolvable stent in the lumen. A total of 30 Sprague-Dawley rats were divided into two groups. Group A: 11 rats had their femoral arteries ligated on one side. The contralateral side served as a control, with the artery transected and repaired using conventional microsuturing. Group B: 19 rats had their femoral arteries transected and repaired using CO2 laser welding and an intraluminal dissolvable stent technique. The contralateral side was again used as a control using conventional microsuturing. At 1 hr postoperatively, 51Cr-labeled biological microspheres were injected centripetally into the left common carotid artery and the legs and thighs immediately harvested for measurement of radioactivity. All repaired arteries were patent (30/30 in the microsuturing group and 19/19 in the stented welding group), with no detectable stenosis or dilation at the repaired site. Statistical analysis showed that tissue radioactivity (cpm/g) in the ligated group (3,972 +/- 384 in thighs and 3,142 +/- 742 in legs) was significantly lower than in the microsuturing group (7,132 +/- 1,723 in thighs and 6,557 +/- 1,469 in legs) (P < 0.01). In the ligated group, a significant reduction of blood flow was seen in the legs when compared with the thighs (P < 0.05). There was no significant difference in radioactivity when comparing the microsuturing control with the stented welding group, in both thighs (7,064 +/- 2,599 and 7,006 +/- 2,406, respectively; P > 0.05) and legs (6,386 +/- 1,703 and 6,288 +/- 1,757, respectively; P > 0.05). This study provided evidence that the dissolvable stent placed intraluminally does not impair blood circulation and that when coupled with CO2 laser welding offers a high-quality alternative to conventional small vessel anastomosis.
Human movement activity classification approaches that use wearable sensors and mobile devices (2013)

Cell phones and other mobile devices become part of human culture and change activity and lifestyle patterns. Mobile phone technology continuously evolves and incorporates more and more sensors for enabling advanced applications. Latest generations of smart phones incorporate GPS and WLAN location finding modules, vision cameras, microphones, accelerometers, temperature sensors etc. The availability of these sensors in mass-market communication devices creates exciting new opportunities for data mining applications. Particularly healthcare applications exploiting build-in sensors are very promising. This paper reviews different approaches of human activity recognition.
Photodynamic therapy update 2007. (2007)

The use of photodynamic therapy (PDT) in the US has shown record growth in 2007 with more clinicians utilizing PDT for more clinical entities than ever before. Research endeavors utilizing PDT in published clinical manuscripts have been slow in 2007 and yet the use continues to rise significantly. This manuscript will highlight the state of PDT in the US as 2007 comes to a close and focus on the future of PDT as we move toward 2008.
Organising pneumonia mimicking invasive fungal disease in patients with leukaemia (2010)

Clinical charts from 63 consecutive highly immunocompromised haematologic patients presenting with pulmonary nodular lesions on CT scan, classified as either probable or possible invasive fungal disease (IFD) according to the revised EORTC/MSG classification, were retrospectively studied. Histopathological analysis of lung tissues, available for 23 patients, demonstrated proven IFD in 17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar damage in one and organising pneumonia (OP) in five cases. In the OP cases, three of which have been defined as probable IFD according to EORTC/MSG classification, extensive immunohistochemical, molecular and immunological analyses for fungi were negative. Our case descriptions extend the notion that OP may be encountered as a distinct histopathological entity in pulmonary nodular lesions in patients with leukaemia with probable/possible IFD.
Multiphase separation of copper nanowires (2016)

This communication reports a new method to purify copper nanowires with nearly 100% yield from undesired copper nanoparticle side-products formed during batch processes of copper nanowire synthesis. This simple separation method can yield large quantities of long, uniform, high-purity copper nanowires to meet the requirements of nanoelectronics applications as well as provide an avenue for purifying copper nanowires in the industrial scale synthesis of copper nanowires, a key step for commercialization and application of nanowires.
Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins (2007)

Transcription factors and other allosteric cell signaling proteins contain a disproportionate number of domains or segments that are intrinsically disordered (ID) under native conditions. In many cases folding of these segments is coupled to binding with one or more of their interaction partners, suggesting that intrinsic disorder plays an important functional role. Despite numerous hypotheses for the role of ID domains in regulation, a mechanistic model has yet to be established that can quantitatively assess the importance of intrinsic disorder for intramolecular site-to-site communication, the hallmark property of allosteric proteins. Here, we present such a model and show that site-to-site allosteric coupling is maximized when intrinsic disorder is present in the domains or segments containing one or both of the coupled binding sites. This result not only explains the prevalence of ID domains in regulatory proteins, it also calls into question the classical mechanical view of energy propagation in proteins, which predicts that site-to-site coupling would be maximized when a well defined pathway of folded structure connects the two sites. Furthermore, in showing that the coupling mechanism conferred by intrinsic disorder is robust and independent of the network of interactions that physically link the coupled sites, unique insights are gained into the energetic ground rules that govern site-to-site communication in all proteins.
Characterization of an Exo‐β‐d‐Fructosidase from <i>Streptococcus mutans</i> Ingbritt (1992)

An extracellular enzyme beta-D-fructosidase was purified from the culture supernatant of Streptococcus mutans Ingbritt and characterized. The molecular weight of the enzyme was 127,000 as determined by SDS-polyacrylamide gel electrophoresis. The enzyme was specific for levan which mainly consists of beta-(2,6)-linked D-fructose and was also able to hydrolyze inulin, sucrose and raffinose at the activities of 13, 9 and 5% of that hydrolyzing levan, respectively. The pH optima for levan, inulin and sucrose were approximately 5.5, 6.0 and 5.0, respectively. The enzyme was optimally reactive at 55 C for levan. The enzyme was inhibited by Fe3+, Hg2+ and Zn2+ and not by either anionic or non-ionic detergents. Paper chromatographic analysis revealed that the enzyme attacked levan by an exo-type mechanism.
G-quadruplexes in promoters throughout the human genome (2006)

Certain G-rich DNA sequences readily form four-stranded structures called G-quadruplexes. These sequence motifs are located in telomeres as a repeated unit, and elsewhere in the genome, where their function is currently unknown. It has been proposed that G-quadruplexes may be directly involved in gene regulation at the level of transcription. In support of this hypothesis, we show that the promoter regions (1 kb upstream of the transcription start site TSS) of genes are significantly enriched in quadruplex motifs relative to the rest of the genome, with >40% of human gene promoters containing one or more quadruplex motif. Furthermore, these promoter quadruplexes strongly associate with nuclease hypersensitive sites identified throughout the genome via biochemical measurement. Regions of the human genome that are both nuclease hypersensitive and within promoters show a remarkable (230-fold) enrichment of quadruplex elements, compared to the rest of the genome. These quadruplex motifs identified in promoter regions also show an interesting structural bias towards more stable forms. These observations support the proposal that promoter G-quadruplexes are directly involved in the regulation of gene expression.
Hybrid Collaborative Filtering with Neural Networks (2016)

Collaborative Filtering aims at exploiting the feedback of users to provide personalised recommendations. Such algorithms look for latent variables in a large sparse matrix of ratings. They can be enhanced by adding side information to tackle the well-known cold start problem. While Neu-ral Networks have tremendous success in image and speech recognition, they have received less attention in Collaborative Filtering. This is all the more surprising that Neural Networks are able to discover latent variables in large and heterogeneous datasets. In this paper, we introduce a Collaborative Filtering Neural network architecture aka CFN which computes a non-linear Matrix Factorization from sparse rating inputs and side information. We show experimentally on the MovieLens and Douban dataset that CFN outper-forms the state of the art and benefits from side information. We provide an implementation of the algorithm as a reusable plugin for Torch, a popular Neural Network framework.
DT-SSIM: A Decentralized Trustworthy Self-Sovereign Identity Management Framework (2021)

In a ubiquitous environment enclosing cooperative Internet-of-Things (IoT) devices, individuals, and entities, digital identity management (DIM) becomes critical and challenging. DIM pertains to device identities authentication and verification to enable trustworthy service exchange, data collection, and decision making. DIM is the supporting pillar for all online services and the foundation for security and authentication mechanisms. Due to the extreme heterogeneity, scale, and configuration complexity of such environments, enabling trustworthy DIM is crucial and seriously challenging. In an IoT context, devices use local digital identities stored within a tamper-proof unit and verified by a centralized authority for authentication. The recent attacks on IoT systems showed how vulnerable such a design is. It is also an inherent problem that influences humans. From that, self-sovereign identity (SSI) has emerged as a decentralized DIM approach embracing the concept of portable self-possession identity. SSI was presented to couple the digital identity from the owner to enable large-scale cooperation. However, digital identity storage and verification still occur on the device and in a centralized manner. Utilizing a local single-point-of-failure storage memory for verifiable credentials is one of the considerable drawbacks in contemporary SSI. In this regard, this article introduces decentralized trustworthy-self-sovereign identity management (DT-SSIM), a novel decentralized trustworthy SSI management framework. DT-SSIM integrates the secret share scheme with the blockchain-based smart contracts technologies to provide transparent and trustworthy SSI-based DIM services for IoT. Storing IoT identity credentials outside the devices’ local storage preserves the identity credentials from being tampered with or misused. Evaluations and discussions show the resiliency assessment of the system and the cost and estimated running times for verification processes in DT-SSIM.
DNA Damage in Oocytes Induces a Switch of the Quality Control Factor TAp63α from Dimer to Tetramer (2011)

TAp63α, a homolog of the p53 tumor suppressor, is a quality control factor in the female germline. Remarkably, already undamaged oocytes express high levels of the protein, suggesting that TAp63α's activity is under tight control of an inhibitory mechanism. Biochemical studies have proposed that inhibition requires the C-terminal transactivation inhibitory domain. However, the structural mechanism of TAp63α inhibition remains unknown. Here, we show that TAp63α is kept in an inactive dimeric state. We reveal that relief of inhibition leads to tetramer formation with ∼20-fold higher DNA affinity. In vivo, phosphorylation-triggered tetramerization of TAp63α is not reversible by dephosphorylation. Furthermore, we show that a helix in the oligomerization domain of p63 is crucial for tetramer stabilization and competes with the transactivation domain for the same binding site. Our results demonstrate how TAp63α is inhibited by complex domain-domain interactions that provide the basis for regulating quality control in oocytes.
Determination of Proton Affinities and Acidity Constants of Sugars (2013)

Proton transfer reactions play a key role in the conversion of biomass derived sugars to chemicals. In this study, we employ high level ab initio theoretical methods, in tandem with solvation effects to calculate the proton affinities (PA) and acidity constants (pKa) of various d-glucose and d-fructose tautomers (protonation-deprotonation processes). In addition, we compare the theoretically derived pH values of sugar solutions against experimentally measured pH values in our lab. Our results demonstrate that the protonation of any of the O atoms of the sugars is thermodynamically preferred without any significant variation in the PA values. Intramolecular hydrogen transfers, dehydration reactions, and ring-opening processes were observed, resulting from the protonation of specific hydroxyl groups on the sugars. Regarding the deprotonation processes (pKa), we found that the sugars' anomeric hydroxyls exhibit the highest acidity. The theoretically calculated pH values of sugar solutions are in excellent agreement with experimental pH measurements at low sugar concentrations. At higher sugar concentrations the calculations predict less acidic solutions than the experiments. In this case, we expect the sugars to act as solvents increasing the proton solvation energy and the acidity of the solutions. We demonstrated through linear relationships that the pKa values are correlated with the relative stability of the conjugate bases. The latter is related to hydrogen bonding and polarization of the C-O(-) bond. A plausible explanation for the good performance of the direct method in calculating the pKa values of sugars can be the presence of intramolecular hydrogen bonds on the conjugate base. Both theory and experiments manifest that fructose is a stronger acid than glucose, which is of significant importance in self-catalyzed biomass-relevant dehydration reactions.
Wireless Solar Water Splitting Device with Robust Cobalt-Catalyzed, Dual-Doped BiVO<sub>4</sub> Photoanode and Perovskite Solar Cell in Tandem: A Dual Absorber Artificial Leaf (2015)

A stand-alone, wireless solar water splitting device without external energy supply has been realized by combining in tandem a CH3NH3PbI3 perovskite single junction solar cell with a cobalt carbonate (Co-Ci)-catalyzed, extrinsic/intrinsic dual-doped BiVO4 (hydrogen-treated and 3 at% Mo-doped). The photoanode recorded one of the highest photoelectrochemical water oxidation activity (4.8 mA/cm(2) at 1.23 VRHE) under simulated 1 sun illumination. The oxygen evolution Co-Ci co-catalyst showed similar performance to best known cobalt phosphate (Co-Pi) (5.0 mA/cm(2) at 1.23 VRHE) on the same dual-doped BiVO4 photoanode, but with significantly better stability. A tandem artificial-leaf-type device produced stoichiometric hydrogen and oxygen with an average solar-to-hydrogen efficiency of 4.3% (wired), 3.0% (wireless) under simulated 1 sun illumination. Hence, our device based on a D4 tandem photoelectrochemical cell represents a meaningful advancement in performance and cost over the device based on a triple-junction solar cell-electrocatalyst combination.
Symbolic manipulation of transfer functions and state space realizations (1996)

In this paper several applications on the use of symbolic computation to control system design are discussed. These applications are of educational value to control engineering courses. The routines developed here provide a quick way to formulate control design problems, ranging from calculating elementary transfer functions to automating the construction of state space realization. This paper also gives detailed discussion on the symbolic computational process of the programs being developed. Examples of symbolic calculation of generalized plant state space realization for use in H/sub /spl infin///H/sub 2/ optimal control are presented.