gebhart/patrepeval huggingface dataset:
Selective delivery of therapeutic agents for the diagnosis and treatment of cancer (2005)

Research activity aimed towards achieving specific and targeted delivery of cancer therapeutics has expanded tremendously in the last decade, resulting in new ways of directing drugs to tumours, as well as new types of drugs. The available strategies exploit differences in the nature of normal and cancer cells and their microenvironment. The discovery and validation of cancer-associated markers, as well as corresponding ligands, is pivotal for developing selective delivery technology for cancer. Although most current clinical trials are either monoclonal antibody- or gene-based, methodological advances in combinatorial libraries of peptides, single chain variable fragments and small organic molecules are expected to change this scenario in the near future. Nanotechnology platforms today allow systematic and modular combinations of therapeutic agents and tumour-binding moieties that may generate novel, personalised agents for selective delivery in cancer. This paper discusses recent developments and future prospects of targeted delivery technologies in the management of cancer.
Evidence Against Altered Expression of GLUT1 or GLUT4 in Skeletal Muscle of Patients With Obesity or NIDDM (1990)

Studies of experimental diabetes in rodents induced by the beta-cell toxin streptozocin have shown that the insulin-resistant glucose transport of peripheral tissues (muscle and adipose) in these animals can be ascribed in part to a pretranslational reduction of the major insulin-sensitive glucose transporter (GLUT4) in these tissues. Because a central feature of non-insulin-dependent diabetes mellitus (NIDDM) is an imparied ability of insulin to enhance glucose disposal in skeletal muscle, we examined the hypothesis that reduced expression of GLUT4 is a characteristic finding in the skeletal muscle of subjects with NIDDM. Biopsies of skeletal muscles were obtained from 17 patients with NIDDM and 10 lean and 9 obese nondiabetic subjects. Among the diabetic subjects, 7 were newly diagnosed and untreated. Compared with age-matched and body-weight-matched healthy control subjects, there was no significant alteration in the level of GLUT4 mRNA demonstrated by Northern blot and slot blot or GLUT4 protein determined by immunoblotting muscle membranes. Neither GLUT4 mRNA nor protein concentration correlated with the degree of glycemic control, fasting plasma insulin or glucose, diabetes duration, body mass index, sex, or age. GLUT1 mRNA and protein levels were also not significantly different between diabetic and matched control subjects. Thus, unlike streptozocin-induced diabetes in rodents, there is no evidence that impaired expression of the major insulin-responsive glucose transporter is responsible for insulin-resistant glucose transport in the skeletal muscle of these lean and moderately obese NIDDM patients.
Concentrations of 9-Tetrahydrocannabinol and 11-Nor-9-Carboxytetrahydrocannabinol in Blood and Urine After Passive Exposure to Cannabis Smoke in a Coffee Shop (2010)

Cannabinoid concentrations in blood and urine after passive exposure to cannabis smoke under real-life conditions were investigated in this study. Eight healthy volunteers were exposed to cannabis smoke for 3 h in a well-attended coffee shop in Maastricht, Netherlands. An initial blood and urine sample was taken from each volunteer before exposure. Blood samples were taken 1.5, 3.5, 6, and 14 h after start of initial exposure, and urine samples were taken after 3.5, 6, 14, 36, 60, and 84 h. The samples were subjected to immunoassay screening for cannabinoids and analyzed using gas chromatography-mass spectrometry (GC-MS) for Delta(9)-tetrahydrocannabinol (THC), 11-nor-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH). It could be demonstrated that all volunteers absorbed THC. However, the detected concentrations were rather small. None of the urine samples produced immunoassay results above the cutoff concentration of 25 ng/mL. THC-COOH concentrations up to 5.0 and 7.8 ng/mL before and after hydrolysis, respectively, were found in the quantitative GC-MS analysis of urine. THC could be detected in trace amounts close to the detection limit of the used method in the first two blood samples after initial exposure (1.5 and 3.5 h). In the 6 h blood samples, THC was not detectable anymore. THC-COOH could be detected after 1.5 h and was still found in 3 out of 8 blood samples after 14 h in concentrations between 0.5 and 1.0 ng/mL.
Base-stacking and base-pairing contributions into thermal stability of the DNA double helix (2006)

Two factors are mainly responsible for the stability of the DNA double helix: base pairing between complementary strands and stacking between adjacent bases. By studying DNA molecules with solitary nicks and gaps we measure temperature and salt dependence of the stacking free energy of the DNA double helix. For the first time, DNA stacking parameters are obtained directly (without extrapolation) for temperatures from below room temperature to close to melting temperature. We also obtain DNA stacking parameters for different salt concentrations ranging from 15 to 100 mM Na+. From stacking parameters of individual contacts, we calculate base-stacking contribution to the stability of A*T- and G*C-containing DNA polymers. We find that temperature and salt dependences of the stacking term fully determine the temperature and the salt dependence of DNA stability parameters. For all temperatures and salt concentrations employed in present study, base-stacking is the main stabilizing factor in the DNA double helix. A*T pairing is always destabilizing and G*C pairing contributes almost no stabilization. Base-stacking interaction dominates not only in the duplex overall stability but also significantly contributes into the dependence of the duplex stability on its sequence.
Assembly of Nanoparticles into Opaline Structures over Large Areas (1999)

A simple technique for crystallizing spherical nanoparticles into 3D opaline structures, which can be of use as diffractive elements in the fabrication of optical or electro-optical devices, is presented. Both polystyrene beads and silica colloids within the size range 50–100 nm have been successfully ordered and it is thought that the technique can also be applied to monodisperse particles of other materials and to particles of even smaller size.
Manipulation of Microalgal Lipid Production Using Genetic Engineering (1996)

Genetic transformation of two species of diatoms has been accomplished by introducing chimeric plasmid vectors containing a bacterial antibiotic resistance gene driven by regulatory sequences from the acetyl-CoA carboxylase (ACCase) gene from the diatom Cyclotella cryptica. The recombinant DNA integrated into one or more random sites within the algal genome and the foreign protein was produced by the algal transformants. This is the first report of genetic transformation of any chlorophyll c-containing microalgal strain. We are using this system to introduce additional copies of the ACCase gene into diatoms in an attempt to manipulate lipid accumulation in transformed strains.
Diagnosis of Huntington Disease (2003)

Conscientious laboratory work, knowledgeable interpretation of genetic test results, and the availability of pre- and posttest counseling are essential components of HD diagnosis.
Non-equivalence of different evaluation algorithms to derive mean particle size from dynamic light scattering data (2019)

Different manufacturers of dynamic light scattering (DLS) instruments implement various evaluation algorithms. Users often implicitly assume that the various algorithms yield the same mean value and deliver results of the same precision. This assumption was tested using results obtained by cumulants analysis, CONTIN and Non-Negative Least Squares fitting (NNLS) of distributions, and frequency analysis on near-spherical silica and polystyrene latex particles obtained in one laboratory and results on near-spherical silica obtained in other laboratories. Particles have been measured in the size range of 10 to 200 nm. The results show that the average particle diameters from different algorithms differ significantly and that these differences increase with an increasing polydispersity of the material. Also, precision, both within-laboratory (repeatability) as well as between-laboratory standard deviations (reproducibility), differs between the algorithms investigated, especially for the more polydisperse silica materials. The results obtained from the cumulants method usually show the best repeatability and the lowest between-laboratory standard deviation. The results also show that the conversion of intensity-weighted results to volume-weighted results increase the between-laboratory standard deviation, confirming the theoretical expectations that conversion increases the variation significantly.
Control of extracellular matrix remodelling within ovarian tissues: localization and regulation of gene expression of plasminogen activator inhibitor type-1 within the ovine corpus luteum (1997)

Extensive extracellular matrix remodelling occurs within the lifespan of the corpus luteum, particularly during corpus luteum formation and regression. A major mechanism for the regulation of extracellular matrix remodelling is via local production of specific proteinase inhibitors, such as the serine proteinase inhibitor plasminogen activator inhibitor type-1 (PAI-1). The objective of the present study was to characterize the localization, ontogeny and regulation of PAI-1 expression within ovine corpora lutea. Urokinase binding activity was detected within medium conditioned by ovine luteal cells. Production of PAI-1 by ovine luteal cells was confirmed by immunoprecipitating it from labelled proteins in culture medium. mRNA encoding PAI-1 was present within developing (day 3), mature (day 10) and regressing (30 h after prostaglandin F2 alpha injection on day 10 after the onset of oestrus) corpora lutea as demonstrated by in situ hybridization. The ontogeny of PAI-1 mRNA expression was characterized within corpora lutea collected on days 3, 7, 10, 13 and 16 after the onset of oestrus (n = 4, 4, 4, 3 and 4, respectively). Expression of PAI-1 mRNA did not differ during the luteal phase (P = 0.06), although a trend for an increase in the amount of PAI-1 mRNA was observed on day 16. Expression of PAI-1 mRNA was also examined during luteal regression in corpora lutea collected 0, 6, 12, 24 and 36 h after injection of prostaglandin F2 alpha on day 10 after the onset of oestrus (n = 4 at each time). Relative PAI-1 mRNA concentrations changed significantly during luteolysis induced by prostaglandin F2 alpha (P = 0.0002). Administration of prostaglandin F2 alpha resulted in a transient sevenfold increase in PAI-1 mRNA 6 h after injection (P = 0.0001) but by 12 h the amounts had returned to values similar to those detected on day 10. We conclude that PAI-1 is a major secretory product of ovine luteal cells and that a transient increase in PAI-1 mRNA occurs during luteolysis induced by prostaglandin F2 alpha. PAI-1 probably plays a key local role in the control of extracellular proteolysis during the luteal phase.
Computational Analyses of Propulsion Aeroacoustics for Mixed Flow Nozzle Pylon Installation at Takeoff (2001)

A CFD analyses is presented for a set of baseline and noise suppression mixed flow nozzles with and without a pylon installation. The five model configurations are as follows; a baseline core/fan dual-stream nozzle with an external plug, a chevron mixer nozzle with a peak on the symmetry plane with external plug, both of the above nozzles with an installed bifurcating pylon and lastly a clocked chevron mixer nozzle such that a trough is aligned with the center of the pylon. The fluid flow is simulated by solving the asymptotically steady, compressible, Reynolds-averaged Navier-Stokes equations using an implicit, up-wind, flux-difference splitting finite volume scheme and standard two equation k-epsilon turbulence model with a linear stress representation. All computations are performed using the multiblock, parallel, structured code PAB3D. Results indicate that the clocked chevron with pylon case achieves the most optimal levels of average and peak turbulence kinetic energy and vorticity and therefore is expected to be the quietest of the five configurations tested. Further study is required to refine expressions which are indicative of noise and mate these with rigorous noise prediction models.
Trastuzumab-Based Photoimmunotherapy Integrated with Viral HER2 Transduction Inhibits Peritoneally Disseminated HER2-Negative Cancer (2016)

Peritoneal dissemination is the most frequent metastasis in gastric cancer and is associated with poor prognosis. The lack of particular target antigens in gastric cancer other than HER2 has hampered the development of treatments for peritoneal dissemination of gastric cancer. We hypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumab-based photoimmunotherapy (PIT) might provide excellent and selective antitumor effects for peritoneal dissemination of gastric cancer. In vitro, adenovirus/HER2-ECD (Ad/HER2-ECD) efficiently transduced HER2-ECD into HER2-negative gastric cancer cells. Trastuzumab-IR700 (Tra-IR700)-mediated PIT induced selective cell death of HER2-ECD-transduced tumor cells. Ad/HER2-ECD also induced homogenous expression of HER2 in heterogeneous gastric cancer cells, resulting in uniform sensitivity of the cells to Tra-IR700-mediated PIT. Anti-HER2 PIT integrated with adenoviral HER2-ECD gene transfer was applied in mice bearing peritoneal dissemination of HER2-negative gastric cancer. Intraperitoneal administration of Ad/HER2-ECD and Tra-IR700 with PIT inhibited peritoneal metastasis and prolonged the survival of mice bearing MKN45. Furthermore, minimal side effects allowed the integrated therapy to be used repeatedly, providing better control of peritoneal dissemination. In conclusion, the novel therapy of molecular-targeted PIT integrated with gene transfer technology is a promising approach for the treatment of peritoneal dissemination in gastric cancer.
The efficacy of current rabies vaccines and novel Nanobody®-based antivirals against highly pathogenic phylogroup -1 and -2 members of the Lyssavirus genus (2010)

Current rabies virus (RABV) vaccines and RABV immunoglobulins (RIG) confer protection against phylogroup 1 lyssaviruses. However, they offer partial or no protection against phylogroup 2 lyssaviruses and the high costs of such treatments, especially RIG, can result in poor availability/coverage. Therefore, alternative intervention strategies are required to address these issues. Using a pseudotype-based neutralisation assay (PNA) we first evaluated the efficacy of commercial RABV vaccines against each lyssavirus species. Existing RABV vaccines stimulated high neutralising serum antibody titres against RABV isolates but did not confer protection against antigenically divergent lyssaviruses. Subsequently, selection of anti-rabies llama (Lama glama) heavy chain antibody fragments (VHH/Nanobody®) was undertaken from immune libraries and tested for neutralising potency against a panel of geographically divergent RABV isolates and a range of lyssaviruses using live virus (RFFIT) and PNA. Strong neutralisation of all RABV isolates and the majority of lyssavirus species tested were observed (in the nanomolar range). Bivalent constructs greatly improved neutralising potency. Improved biologicals are required to counter the public health threat posed by these highly pathogenic viruses and Nanobodies® offer an attractive alternative.
Atomic Layer Deposition of the Solid Electrolyte LiPON (2015)

We demonstrate an atomic layer deposition (ALD) process for the solid electrolyte lithium phosphorousoxynitride (LiPON) using lithium tert-butoxide (LiO<sup>t</sup>Bu), H<sub>2</sub>O, trimethylphosphate (TMP), and plasma N<sub>2</sub> (<sup>P</sup>N<sub>2</sub>) as precursors. We use in-situ spectroscopic ellipsometry to determine growth rates for process optimization to design a rational, quaternary precursor ALD process where only certain substrate–precursor chemical reactions are favorable. We demonstrate via in-situ XPS tunable nitrogen incorporation into the films by variation of the <sup>P</sup>N<sub>2</sub> dose and find that ALD films over approximately 4.5% nitrogen are amorphous, whereas LiPON ALD films with less than 4.5% nitrogen are polycrystalline. Lastly, we characterize the ionic conductivity of the ALD films as a function of nitrogen content and demonstrate their functionality on a model battery electrode—a Si anode on a Cu current collector.
Composition of wheat‐flour lipids (1970)

Abstract Lipids were extracted from a single sample of wheat flour using three solvent systems: ethanol–diethyl ether–water (2:2:1 by vol.); chloroform–methanol (2:1 by vol.); and water‐saturated n‐butanol. Analysis of the extracts and of residual lipid in the extracted flour showed that water‐saturated n‐butanol was the most efficient solvent. Wheat‐flour lipids were extracted with water‐saturated n‐butanol and separated by chromatographic procedures into individual components. The lipid classes which were isolated and studied were steryl ester, free sterol, 6‐ O ‐acyl steryl glucoside, steryl glucoside, triglyceride, diglyceride, monoglyceride, free fatty acid, monogalactosyl diglyceride, 6‐ O ‐acyl monogalactosyl diglyceride, digalactosyl diglyceride, digalactosyl monoglyceride, monoglycosyl ceramide, diglycosyl ceramide, N ‐acyl phosphatidyl ethanolamine, N ‐acyl lysophosphatidyl ethanolamine, phosphatidyl ethanolamine, lysophosphatidyl ethanolamine, phosphatidyl choline, lysophosphatidyl choline, phosphatidyl serine and phosphatidyl inositol. Monogalactosyl monoglyceride was also tentatively identified. The quantitative distributions of the lipid classes were determined. Monoglycosyl ceramide contained small amounts of normal fatty acids (12:0–24:0) and large amounts of 2‐hydroxy fatty acids (principally 16:0 and 20:0), with similar amounts of dihydroxy long‐chain bases (18:0 and 18:1) and trihydroxy long‐chain bases (18:0, 18:1, 19:0, 19:1, 20:0, 22:0). The principal sterols were identified as β‐sitosterol, campesterol, and C 28 and C 29 saturated sterols. The fatty acids in the sterol lipids were principally 16:0 (50–60%) and 18:2 (28–30%) with small amounts of 16:1, 18:0, 18:1 and 18:3. The fatty acids in all the glycerides were principally 18:2 (51–84%) with lesser amounts of 16:0, 18:0, 18:1 and 18:3.
Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia (2013)

We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.).
Synthesis of a New Conformation-Constrained l-Tyrosine Analogue as a Potential Scaffold for SH2 Domain Ligands (2003)

The enantioselective synthesis of a new tricyclic tyrosine analogue is reported. This conformation-constrained SH2 domain ligand scaffold 2 was designed on the basis of the natural ligand, whose structure contains the elements of a tyrosine moiety having chi(1) and chi(2) angles constrained to values observed for a phosphotyrosyl (pTyr) residue bound to the p56(lck) SH2 domain. It represents a unique, highly constrained amino acid, which may be of value in signal transduction studies. Three key steps, an asymmetric tandem Michael addition, an intramolecular Friedel-Crafts reaction, and an intramolecular Mannich reaction, were successfully applied in the presented synthetic route.
Selective Inhibition of CYP17 With Abiraterone Acetate Is Highly Active in the Treatment of Castration-Resistant Prostate Cancer (2009)

CYP17 blockade by abiraterone acetate results in declines in PSA and CTC counts and radiologic responses, confirming that CRPC commonly remains hormone driven.
Closed-form solution of absolute orientation using unit quaternions (1987)

Finding the relationship between two coordinate systems using pairs of measurements of the coordinates of a number of points in both systems is a classic photogrammetric task. It finds applications in stereophotogrammetry and in robotics. I present here a closed-form solution to the least-squares problem for three or more points. Currently various empirical, graphical, and numerical iterative methods are in use. Derivation of the solution is simplified by use of unit quaternions to represent rotation. I emphasize a symmetry property that a solution to this problem ought to possess. The best translational offset is the difference between the centroid of the coordinates in one system and the rotated and scaled centroid of the coordinates in the other system. The best scale is equal to the ratio of the root-mean-square deviations of the coordinates in the two systems from their respective centroids. These exact results are to be preferred to approximate methods based on measurements of a few selected points. The unit quaternion representing the best rotation is the eigenvector associated with the most positive eigenvalue of a symmetric 4 × 4 matrix. The elements of this matrix are combinations of sums of products of corresponding coordinates of the points.
Myocardial signaling defects and impaired cardiac function of a human beta 2-adrenergic receptor polymorphism expressed in transgenic mice. (1996)

A threonine to isoleucine polymorphism at amino acid 164 in the fourth transmembrane spanning domain of the beta 2-adrenergic receptor (beta 2AR) is known to occur in the human population. The functional consequences of this polymorphism to catecholamine signaling in relevant cells or to end-organ responsiveness, however, are not known. To explore potential differences between the two receptors, site-directed mutagenesis was carried out to mimic the polymorphism. Transgenic FVB/N mice were then created overexpressing wild-type (wt) beta 2AR or the mutant Ile-164 receptor in a targeted manner in the heart using a murine alpha myosin heavy chain promoter. The functional properties of the two receptors were then assessed at the level of in vitro cardiac myocyte signaling and in vivo cardiac responses in intact animals. The expression levels of these receptors in the two lines chosen for study were approximately 1200 fmol/mg protein in cardiac membranes, which represents a approximately 45-fold increase in expression over endogenous beta AR. Myocyte membrane adenylyl cyclase activity in the basal state was significantly lower in the Ile-164 mice (19.5 +/- 2.7 pmol/min/mg) compared with wt beta 2AR mice (35.0 +/- 4.1 pmol/min/mg), as was the maximal isoproterenol-stimulated activity (49.8 +/- 7.8 versus 77.1 +/ 7.3 pmol/min/mg). In intact animals, resting heart rate (441 +/- 21 versus 534 +/- 17 bpm) and dP/dtmax (10,923 +/- 730 versus 15,308 +/- 471 mmHg/sec) were less in the Ile-164 mice as compared with wt beta 2AR mice. Similarly, the physiologic responses to infused isoproterenol were notably less in the mutant expressing mice. Indeed, these values, as well as other contractile parameters, were indistinguishable between Ile-164 mice and nontransgenic littermates. Taken together, these results demonstrate that the Ile-164 polymorphism is substantially dysfunctional in a relevant target tissue, as indicated by depressed receptor coupling to adenylyl cyclase in myocardial membranes and impaired receptor mediated cardiac function in vivo. Under normal homeostatic conditions or in circumstances where sympathetic responses are compromised due to diseased states, such as heart failure, this impairment may have important pathophysiologic consequences.
Modified technique of suction blistering for epidermal grafting in vitiligo (1999)

The technique is inexpensive and easy and obviates the need of cumbersome and heavy equipment.