gebhart/patrepeval huggingface dataset:
Activity of Entrectinib in a Patient With the First Reported <i>NTRK</i> Fusion in Neuroendocrine Cancer (2017)

Despite advances in genomic analysis, the molecular origin of neuroendocrine tumors (NETs) is complex and poorly explained by described oncogenes. The neurotrophic TRK family, including <i>NTRK</i>1, 2, and 3, encode the proteins TRKA, TRKB, TRKC, respectively, involved in normal nerve development. Because NETs develop from the diffuse neuroendocrine system, we sought to determine whether <i>NTRK</i> alterations occur in NETs and whether TRK-targeted therapy would be effective. A patient with metastatic well-differentiated NET, likely of the small intestine, was enrolled on the STARTRK2 trial (ClinicalTrials.gov identifier: NCT02568267) and tissue samples were analyzed using an RNA-Seq next-generation sequencing platform. An <i>ETV6:NTRK3</i> fusion was identified and therapy was initiated with the investigational agent entrectinib, a potent oral tyrosine kinase inhibitor of TRKA, TRKB, and TRKC. Upon treatment with entrectinib, the patient experienced rapid clinical improvement; his tumor response was characterized by initial tumor growth and necrosis. This is the first report of an <i>NTRK</i> fusion in NETs. Our patient's response to entrectinib suggests that <i>NTRK</i> fusions can be important in the pathogenesis of NETs. Recent DNA-based genomic analyses of NETs may have missed <i>NTRK</i> fusions due its large gene rearrangement size and multiple fusion partners. The tumor's initial pseudoprogression may represent a unique response pattern for TRK-targeted therapies. An effort to characterize the prevalence of <i>NTRK</i> fusions in NETs using optimal sequencing technology is important.
A Transient Vanadium Flow Battery Model Incorporating Vanadium Crossover and Water Transport through the Membrane (2012)

This paper presents a 2-D transient, isothermal model of a vanadium redox flow battery that can predict the species crossover and related capacity loss during operation. The model incorporates the species transport across the membrane due to convection, diffusion, and migration, and accounts for the transfer of water between the half-cells to capture the change in electrolyte volume. The model also accounts for the side reactions and associated changes in species concentration in each half-cell due to vanadium crossover. A set of boundary conditions based on the conservations of flux and current are incorporated at the electrolyte|membrane interfaces to account for the steep gradients in concentration and potential at these interfaces. In addition, the present model further improves upon the accuracy of existing models by incorporating a more complete version of the Nernst equation, which enables accurate prediction of the cell potential without the use of a fitting voltage. A direct comparison of the model predictions with experimental data shows that the model accurately predicts the measured voltage of a single charge/discharge cycle with an average error of 1.83%, and estimates the capacity loss of a 45 cycle experiment with an average error of 4.2%.
Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages (1991)

Thrombomodulin is an essential cofactor for the activation of the anticoagulant protein C by thrombin. We have identified the expression of thrombomodulin messenger RNA (mRNA) and protein in peripheral blood monocytes. While untreated monocytes expressed thrombomodulin mRNA by Northern blot analysis, lipopolysaccharide-treated cells had decreased mRNA expression. Thrombomodulin antigen was shown in the cytoplasm and on the surface of monocytes by immunohistochemical staining, and thrombomodulin activity was shown on the surface of intact monocytes. One population of synovial lining cells that normally expressed mononuclear phagocyte antigens also expressed thrombomodulin in both noninflamed osteoarthritic synovium and in inflamed rheumatoid arthritis synovium. However, these cells did not express another endothelial protein, von Willebrand factor. We conclude that both circulating and tissue mononuclear phagocytes are capable of expressing thrombomodulin.
Chimeric cytochromes P450 engineered by domain swapping and random mutagenesis for producing human metabolites of drugs (2014)

Human drug metabolites produced by cytochrome P450 enzymes are critical for safety testing and may themselves act as drugs or leads in the drug discovery and development process. Here, highly active chimeric fusion proteins (chimeras) were obtained by reductase domain swapping of mutants at key catalytic residues of the heme domain with that of a natural variant (CYP102A1.2) of P450 BM3 (CYP102A1.1) from Bacillus megaterium. Random mutagenesis at the heme domain of the chimera was also used to generate chimeric mutants that were more active and diverse than the chimeras themselves. To determine whether the chimeras and several mutants of the highly active chimera displayed enhanced catalytic activity and, more importantly, whether they acquired activities of biotechnological importance, we measured the oxidation activities of the chimeras and chimeric mutants toward human P450 substrates, mainly drugs. Some of the chimeric mutants showed high activity toward typical human P450 substrates including drugs. Statin leads, especially chiral products, with inhibitory effects toward HMG-CoA reductase could be obtained from metabolites of statin drugs generated using these chimeric mutants. This study reveals the critical role of the reductase domain for the activity of P450 BM3 and shows that chimeras generated by domain swapping can be used to develop industrial enzymes for the synthesis of human metabolites from drugs and drug leads.
Efficient approach to Normalization of Multimodal Biometric Scores (2011)

Information fusion at the matching score level is widely used, due to the simplicity in combining the scores generated by different matchers. Since the matching scores output by various modalities are diverse in numerical range, score normalization is needed first, to transform these scores into a common domain. Then score fusion is to be carried out on the normalized scores. In this paper, we have studied the performance of different normalization techniques and fusion rules in the context of a multimodal biometric system based on iris and palm print traits of a user. The conventional normalization techniques used for testing are min-max, median-MAD, double-sigmoid and tanh. These normalized results are combined using tanh, mean, sum, product, min, max and median fusion methods. Also, we propose two novel normalization methods namely modified tanh normalization and max normalization as well as a new modified min-max fusion technique for biometric verification. The experimental results on CASIA iris and palm print databases show that the application of proposed max and modified tanh normalization schemes followed by mean and tanh fusion methods result in better recognition performance compared to all other methods.
Development and Evaluation of an Instrumented Linkage System for Total Knee Surgery (2007)

The principles and application of total knee surgery using optical tracking have been well demonstrated, but electromagnetic tracking may offer further advantages. We asked whether an instrumented linkage that attaches directly to the bone can maintain the accuracy of the optical and electromagnetic systems but be quicker, more convenient, and less expensive to use. Initial testing using a table-mounted digitizer to navigate a drill guide for placing pins to mount a cutting guide demonstrated the feasibility in terms of access and availability. A first version (called the Mark 1) instrumented linkage designed to fix directly to the bone was constructed and software was written to carry out a complete total knee replacement procedure. The results showed the system largely fulfilled these goals, but some surgeons found that using a visual display for pin placement was difficult and time consuming. As a result, a second version of a linkage system (called the K-Link) was designed to further develop the concept. User-friendly flexible software was developed for facilitating each step quickly and accurately while the placement of cutting guides was facilitated. We concluded that an instrumented linkage system could be a useful and potentially lower-cost option to the current systems for total knee replacement and could possibly have application to other surgical procedures.
Ruby Optical Maser as a Raman Source (1962)

The successful use of the ruby optical maser for excitation of Raman spectra is described. The conditions of the experiment are discussed, and the utility of the ruby maser for this purpose is evaluated.
Multiple Serotypes and Strains of<i>Streptococcus Suis</i>in Naturally Infected Swine Herds (1996)

We present a brief description of the epidemiology, clinical signs, and lesions in 21 accessions in which multiple serotypes of S. suis or multiple distinct isolates (strains) of the same capsular serotype of S. suis were identified. Isolates of the same capsular serotype that had different antibiogram profiles were considered to be distinct isolates or “strains” for the purposes of this study. Streptococcus suis isolates of the same capsular serotype and identical antibiogram profiles were considered to be identical organisms. These cases were selected to determine whether or not herds infected with multiple serotypes (or strains) of S. suis had unique features that might serve to distinguish these herds from those infected with a single serotype and strain of S. suis and to provide additional information on the development of this disease in swine. Selected cases were limited to those in which isolates were identified by capsular serotyping. Untypeable isolates of S. suis were not included in this study. Case selection criteria, data collection procedures, etc., were as previously described. 12 Of 277 accessions in which S. suis was identified, 21 accessions (7.6%) involving 37 pigs were cases in which 46 different isolates of S. suis were identified. The distribution of these isolates is shown in Tables 1 and 2. Because of the small sample size, statistical analyses were not performed. Although there was a slight increase in recovery of S. suis in the fall and winter months for all serotypes, S. suis was readily isolated throughout the year. In this study, there was a slight increase (approximately 5%) in the prevalence of serotypes 3, 7, and 8 and a decrease (approximately 10%) in the prevalence of serotype 2 from those reported previously. 12
Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress‐induced apoptosis and enhance proliferation of MSCs via Toll‐like receptor(TLR)‐4 and PI3K/Akt (2009)

Apoptosis of implanted mesenchymal stem cells (MSCs) limits the efficiency of MSC therapy. Recent studies showed the ligands of Toll-like receptors (TLRs) could control the function of these cells. We have investigated the effect of lipopolysaccharides (LPS), a ligand of TLR4, on the survival of MSCs and explored the roles of TLR4 and PI3K/Akt. H(2)O(2)/serum deprivation(H(2)O(2)/SD) induced apoptosis of MSCs but LPS-preconditioning (1.0microg/ml) protected MSCs from H(2)O(2)/SD-induced apoptosis and promoted their proliferation. Western blotting showed that 1.0microg/ml LPS enhanced phosphorylation of both Akt at Ser 473 and nuclear factor-kappa B (NF-kappaB) p65 at Ser 536. However, the protective effects of LPS on survival were not observed in TLR4(lps-del) MSCs. The results suggest appropriate treatments with LPS can protect MSCs from oxidative stress-induced apoptosis and improve the survival of MSCs via the TLR4 and PI3K/Akt pathway.
Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure (2012)

Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (α-synuclein). AS fibrillation follows a nucleation polymerization pathway involving diverse transient prefibrillar species varying in size and morphology. Similar to other neurodegenerative diseases, cytotoxicity is currently attributed to these prefibrillar species rather than to the insoluble aggregates. Nevertheless, the underlying molecular mechanisms responsible for cytotoxicity remain elusive and structural studies may contribute to the understanding of both the amyloid aggregation mechanism and oligomer-induced toxicity. It is already recognized that soluble oligomeric AS species adopt β-sheet structures that differ from those characterizing the fibrillar structure. In the present study we used ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy, a technique especially sensitive to β-sheet structure, to get a deeper insight into the β-sheet organization within oligomers and fibrils. Careful spectral analysis revealed that AS oligomers adopt an antiparallel β-sheet structure, whereas fibrils adopt a parallel arrangement. The results are discussed in terms of regions of the protein involved in the early β-sheet interactions and the implications of such conformational arrangement for the pathogenicity associated with AS oligomers.
Protective effect of O6-methylguanine-DNA methyltransferase (MGMT) on the cytotoxic and recombinogenic activity of different antineoplastic drugs (1996)

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes alkyl groups from the O6 position of guanine in DNA and thus may protect cells against genotoxic effects of agents inducing this lesion. To analyze quantitatively the level of protection mediated by MGMT against antineoplastic drugs, we determined the cytotoxic and recombinogenic (sister-chromatid exchange inducing) effects of various chemotherapeutic agents in a pair of isogenic Chinese hamster cell lines deficient and proficient for MGMT, generated upon transfection with human MGMT cDNA. Furthermore, we compared the responses of the human cell lines HeLa MR (MGMT deficient) and HeLa S3 (MGMT proficient) to the various agents. It is shown that: (1) MGMT proficient cells are resistant in cell killing to the methylating drug streptozotocin and all the chloroethylating nitrosoureas tested. There was a marked agent specificity in protection. The level of resistance provoked by MGMT increased in the order BCNU < CCNU < ACNU < HeCNU < streptozotocin. (2) MGMT did not protect cells against killing induced by chlorambucil, cisplatin, melphalan, activated cyclophosphamide (malosfamide) and activated ifosfamide (4-hydroperoxy-ifosfamide). (3) MGMT caused protection against the recombinogenic effect of all nitrosoureas tested. The lowest level of protection was again observed for BCNU, followed by CCNU, ACNU < HeCNU < streptozotocin. (4) MGMT proficient cells did not exhibit resistance in SCE induction towards cyclophosphamide (activated by microsomes), 4-hydroperoxy-ifosfamide, mafosfamide, chlorambucil and melphalan. Some protection was afforded, however, against cisplatin (and transplatin). This effect was abolished by pretreatment of cells with O6-benzylguanine, which depletes MGMT, indicating that some lesion(s) induced by cisplatin giving rise to SCEs can be repaired by MGMT. Taken together, these results indicate that streptozotocin, HeCNU and ACNU are more selective than CCNU and BCNU in killing MGMT deficient cells, and that in the cases of cyclophosphamide, ifosfamide, chlorambucil, cisplatin and melphalan MGMT is not involved in mediating cytotoxic drug resistance.
VLSI architecture and FPGA prototyping of a digital camera for image security and authentication (2006)

Two fundamental operations performed by a digital camera are image capturing and storing. The images are subsequently transmitted in various forms over appropriate media. These images are always vulnerable to various forms of copyright attacks and ownership issues. This paper introduces a digital camera with built-in copyright protection and security mechanism for images produced by it. Since the proposal of the trustworthy digital camera by Friedman [1], significant research has been done in developing algorithms for watermarking and encryption with the aim of using them in digital cameras. However, only few of these efforts are involved with the architectural development of the entire digital camera. Incorporation of encryption and watermarking together in the digital camera will assist in protecting and authenticating image files. In this paper, we present an architecture and a hardware efficient FPGA based watermark module towards the development of the complete digital camera.
Evolution of Water Lifting Devices (Pumps) over the Centuries Worldwide (2015)

The evolution of the major achievements in water lifting devices with emphasis on the major technologies over the centuries is presented and discussed. Valuable insights into ancient water lifting technologies with their apparent characteristics of durability, adaptability, and sustainability are provided. A comparison of the relevant technological developments in several early civilizations is carried out. These technologies are the underpinning of modern achievements in water engineering. They represent the best paradigm of probing the past and facing the future. A timeline of the historical development of water pumps worldwide through the last 5500 years of the history of mankind is presented. A chronological order is followed with emphasis on the major civilizations.
NATIONAL TRANSPORTATION SAFETY BOARD: PROFILE OF AN ORGANIZATION (1998)

This article profiles the National Transportation Safety Board (NTSB), an independent federal agency charged with determining the probable causes of transportation accidents and promoting transportation safety through its recommendation process. Although it is among the smallest of government agencies, it has a huge job. The United States transportation network rivals those of other continents and is matched by those of few other nations in size and complexity. NTSB was founded in 1967 and its current charter is the Independent Safety Board Act of 1974. Since 1967 it has investigated more than 100,000 aviation accidents and incidents, as well as about 10,000 surface transportation accidents involving highways, marine and rail transport, and pipelines. NTSB also investigates accidents involving the transportation of hazardous materials and is the sole U.S. accredited representative at foreign accident investigations under provisions of the International Civil Aviation Organization (ICAO). When notified of a major accident, the NTSB launches a Go-Team that varies in size depending on the severity of the accident and the complexity of the issues involved. NTSB also sponsors public forums to promote safe transportation practices, and conducts safety studies that focus public attention on major national safety issues. The NTSB's laboratories are world renowned. During the past 30 years, accident rates have been dropping, while capacity and usage have remained steady or grown, sometimes dramatically, in every mode of transportation. NTSB is accomplishing its job of making the nation's notably safe transportation system even safer.
Density‐dependent endothelial cell production of an inhibitor of smooth muscle cell growth (1993)

Embryonic data and ultrastructural analyses suggest that the primitive endothelium signals undifferentiated mesenchymal cells to migrate to the forming blood vessel and subsequently regulates mural cell growth and behavior. Upon maturation of the blood vessel, chemotactic and mitogenic signals are apparently diminished and differentiated smooth muscle cells normally remain quiescent. This homeostasis is seemingly upset in conditions which lead to pathologies characterized by smooth muscle cell hyperplasia such as atherosclerosis. By culturing endothelial cells at different densities, we attempted to re-create the various stages of vascular development. Whereas media conditioned by sparse endothelial cells stimulate smooth muscle cells, media conditioned by dense endothelial cell cultures are inhibitory. Culture of sparse smooth muscle cells in media conditioned for 3 days by postconfluent endothelial cell cultures leads to dose-dependent and reversible smooth muscle cell inhibition. Furthermore, in the presence of the endothelial cell-derived inhibitor, smooth muscle cells are rendered refractory to mitogens such as fibroblast growth factor and platelet-derived growth factor. The inhibitory activity is not attributable to the well-characterized inhibitors of smooth muscle cell growth, transforming growth factor type-beta, prostaglandin I2, or heparan sulfate proteoglycan. Partial characterization of the inhibitory conditioned media suggests that the active molecule is smaller than 1,000 da, and stable to boiling as well as proteinase K and heparinase digestion. These findings support the concept that there is intercellular communication between endothelial cells and smooth muscle cells and provide evidence for a novel endothelial cell-derived smooth muscle cell growth inhibitor.
The neurobiology of love (2007)

Romantic and maternal love are highly rewarding experiences. Both are linked to the perpetuation of the species and therefore have a closely linked biological function of crucial evolutionary importance. The newly developed ability to study the neural correlates of subjective mental states with brain imaging techniques has allowed neurobiologists to learn something about the neural bases of both romantic and maternal love. Both types of attachment activate regions specific to each, as well as overlapping regions in the brain's reward system that coincide with areas rich in oxytocin and vasopressin receptors. Both deactivate a common set of regions associated with negative emotions, social judgment and 'mentalizing' that is, the assessment of other people's intentions and emotions. Human attachment seems therefore to employ a push-pull mechanism that overcomes social distance by deactivating networks used for critical social assessment and negative emotions, while it bonds individuals through the involvement of the reward circuitry, explaining the power of love to motivate and exhilarate. Yet the biological study of love, and especially romantic love, must go beyond and look for biological insights that can be derived from studying the world literature of love, and thus bring the output of the humanities into its orbit.
First-Principles, Data-Based, and Hybrid Modeling and Optimization of an Industrial Hydrocracking Unit (2006)

The first-principles, data-based, and hybrid modeling strategies are employed to simulate an industrial hydrocracking unit, to make a comparative performance assessment of these strategies, and to do optimization. A first-principles model (FPM) based on the pseudocomponent approach (Bhutani, N.; Ray, A. K.; Rangaiah, G. P. Ind. Eng. Chem. Res. 2006, 45, 1354) is coupled with neural network(s) in different hybrid architectures. Data-based and hybrid models are promising for important predictions in the presence of variations in operating conditions, feed quality, and catalyst deactivation. Data-based models are purely empirical and are developed using neural networks, whereas the neural-network component of a hybrid model is used to obtain either updated model parameters in the FPM connected in series or to correct predictions of the FPM. This article presents data-based models and three hybrid models, their implementation and evaluation on an industrial hydrocracking unit for predicting steady-state performance, and finally the optimization of the hydrocracking unit using the data-based model and a genetic algorithm.