gebhart/patrepeval huggingface dataset:
Innovative strategies for stabilization of therapeutic peptides in aqueous formulations (2012)

Ontwikkeling tropenbestendig medicijn tegen levensbedreigende bloeding kraamvrouw In de tropische ontwikkelingslanden sterven jaarlijks ongeveer 150.000 moeders - waarvan 50 % in Afrika onder de Sahara - vlak na de geboorte van hun kind ten gevolge van een onstelpbare bloeding (post-partum hemorrhage, PPH). De beschikbaarheid van een geschikte vloeibare vorm van het medicijn oxytocine zou mogelijk hun dood kunnen voorkomen. Dankzij oxytocine-injecties, die worden toegediend in geval van hevige post-partumbloedingen, is in de Westerse wereld deze doodsoorzaak sterk teruggedrongen. Het belangrijkste probleem bij vloeibare oxytocine is dat het koel bewaard moet worden. Christina Avanti ging daarom op zoek naar oxytocineformulering die warmtestabiel is. Zij ontwikkelde een formulering gebaseerd op een combinatie van zinkionen en malonaatbuffer, die helaas nog niet voldoet aan de standaardeis van veel farmacopees, zoals stabiliteit van minstens één jaar bij 40 °C of twee jaar bij 30 °C. Haar formuleringen zijn echter wel veelbelovend. Een definitieve conclusie over de geschiktheid van deze formulering kan echter pas worden getrokken na afronding van een real-time stabiliteitsstudie van twee jaar. De resultaten van dit onderzoek zullen in november 2012 beschikbaar komen. Zolang er nog geen warmtestabiele, goedkope en veilige versie van het geneesmiddel op de markt is, is het belangrijk dat gefinancierd wordt dat: 1. Op plaatsen waar geen koelkast beschikbaar is, het opslaan van de huidige conventionele oxytocineformuleringen bij tropische omgevingsomstandigheden mogelijk is, op voorwaarde dat ze elke zes maanden worden vervangen. Of: 2. Er koelkasten op zonne-energie komen waar die op dit moment niet voorhanden zijn.
Implantable Microimagers (2008)

Implantable devices such as cardiac pacemakers, drug-delivery systems, and defibrillators have had a tremendous impact on the quality of live for many disabled people. To date, many devices have been developed for implantation into various parts of the human body. In this paper, we focus on devices implanted in the head. In particular, we describe the technologies necessary to create implantable microimagers. Design, fabrication, and implementation issues are discussed vis-à-vis two examples of implantable microimagers; the retinal prosthesis and in vivo neuro-microimager. Testing of these devices in animals verify the use of the microimagers in the implanted state. We believe that further advancement of these devices will lead to the development of a new method for medical and scientific applications.
Technology evaluation: SELEX, Gilead Sciences Inc. (2000)

Systematic evolution of ligands by exponential enrichment (SELEX) technology has been under development for a decade, and is a general method for identification of oligonucleotide ligands as potential drugs. A pool of randomized RNA or single stranded DNA sequences were selected against certain targets. The sequences of tighter binding with the targets were isolated and amplified. The selection was repeated using the enriched pool derived from the first round selection. Several rounds of this process lead to winning sequences that are called 'aptamers' or 'ligands'. This technology has been applied to a wide range of targets including various enzymes of HIV, growth factors and inflammation-inducing enzymes. The first aptamer that has proceeded to phase I clinical studies is NX-1838, an injectable angiogenesis inhibitor that can be potentially used to treat macular degeneration-induced blindness.
Renal Filtration and Catabolism of Complement Protein D (1985)

Complement protein D, a serine protease participating in the formation of the C3 convertase of the alternative complement pathway, has the lowest molecular weight (23,750) and serum concentration of all complement proteins. In normal serum, D is the rate-limiting protease of the alternative pathway of complement activation. We report that the serum concentrations of D in 20 patients with chronic renal failure (mean +/- S.D., 0.42 +/- 0.28 mg per deciliter) and in 16 patients on long-term dialysis (1.53 +/- 0.39 mg per deciliter) were significantly higher (P less than 0.001) than in 22 healthy adults (0.18 +/- 0.04 mg per deciliter). In chronic renal failure the serum concentration of D correlated with that of creatinine (r = 0.75, P less than 0.001). The serum concentrations of D found in patients with renal failure reached and in some cases exceeded those at which the protease is no longer rate-limiting. Thus, enhanced activity of the alternative pathway of complement should be expected in patients with advanced renal failure. Urinary D was undetectable (less than 0.2 micrograms per deciliter) in 17 normal adults and either undetectable or below the concentration expected from the degree of proteinuria in 10 patients with nephrotic syndrome. However, in a patient with Fanconi's syndrome the urinary concentration of D (1.3 mg per deciliter) was an order of magnitude higher than the serum concentration, representing 0.5 per cent of the total protein. The urinary D in this patient had normal hemolytic activity, antigenicity, and size. These results indicate that D is filtered through the glomerular membrane and is probably catabolized in the proximal renal tubules.
Planar laterally oxidized vertical-cavity lasers for low-threshold high-density top-surface-emitting arrays (1997)

We introduce a novel device architecture that enables the fabrication of low threshold high density vertical-cavity surface-emitting laser (VCSEL) arrays. Our structure relies on a group of small via holes to access a buried AlGaAs layer for lateral oxidation. In contrast to the conventional method of exposing mesa sidewalls through etched pillars, this technique provides our VCSEL's with the benefits of oxide confinement without sacrificing wafer planarity. Maintaining wafer planarity is essential for the easy fabrication and contacting of densely packed devices. The devices operate at 827 nm, with a minimum threshold current of 200 μA, and a maximum output power of 3.15 mW.
Bone marrow‐derived stromal cell line expressing osteoblastic phenotype in vitro and osteogenic capacity in vivo (1989)

Marrow stroma has been shown to have osteogenic potential. Here we report the characterization of a unique stromal cell line derived from mouse bone marrow (MBA-15), which expresses osteoblastic phenotype in vitro and forms bone in vivo. More than 70% of cells in culture were histochemically positive for alkaline phosphatase. The enzyme levels were enhanced threefold when cultures were treated with dexamethasone. Gel electrophoresis of [3H]-proline-labeled cultures showed that MBA-15 cells produced only type I collagen. These cells were responsive to PTH, as indicated by a 50-fold increase in intracellular cAMP. Prostaglandin E2, but not calcitonin, stimulated cAMP up to 70-fold. When cultures were grown to confluence and fed daily with ascorbic acid and beta-glycerophosphate, the cells formed a Von Kossa positive, thick extracellular matrix, shown to contain hydroxyapatite crystals. MBA-15 cells produced mineralized bone when implanted in diffusion chambers. These results indicate that the MBA-15 cell line possesses osteoblastic features in vitro and osteogenic capacity in vivo.
A Novel Controlled Local Drug Delivery System for Inner Ear Disease (2008)

We report the development of CGP-hydrogel, a biodegradable matrix that achieves local, sustained delivery of dexamethasone to the inner ear. There were no significant complications resulting from the surgical procedure or the administration of CGP-hydrogel to our murine model.
Characterization of the homopolymer tailing reaction catalyzed by terminal deoxynucleotidyl transferase. Implications for the cloning of cDNA. (1982)

Two assays were developed to monitor the efficiency of the terminal transferase-catalyzed tailing reaction and the lengths of the products synthesized on duplex DNA substrates.In assay 1, pBR322 DNA digested with either PstI or HindII served as terminal transferase initiators in the presence of [u-~'P]~GTP or [a-32P]dCTP.The tailed DNA was then subjected to a secondary restriction digest using an enzyme which cuts close to only one of the original ends, and the products were resolved by electrophoresis in urea-polyacrylamide gels.This method permits the direct visualization of the lengths of the polymerized tails, a value which can be compared to that calculated from the acid-precipitable radioactivity at the end of the reaction.It was found that these two estimates were closely correlated for the 3'-extended PstI ends using either dGTP or dCTP as monomer substrate.In contrast, the calculated tail length underestimated that revealed by gel analysis of the blunt HindII termini, suggesting that this reaction is relatively inefficient.The efficiency of the tailing reaction using PstI and Hind11 substrates was measured directly in assay 2. Short restriction fragments labeled at the 5'-end opposite to the PstI or HindII site of interest were tailed with nonradioactive deoxynucleotides and the products were separated by electrophoresis as in assay 1.The efficiency of tailing was then derived from the fraction of radioactivity appearing in the elongated and unreacted molecules.Greater than 90% of the PstI ends reacted in this assay as opposed to less than half of the HindII ends, thus confirming the indications of assay 1.The blunt end tailing efficiency could not be substantially increased by varying the enzyme or monomer substrate concentrations or the incubation temperature.The length distribution of products formed at limiting enzyme Concentration was consistent with a nonprocessive mechanism of polymerization.These results are considered in terms of the practical applications of terminal transferase in the
Bcl6 controls granzyme B expression in effector CD8+ T cells (2006)

Bcl6, a sequence-specific transcriptional repressor, is important for generation and maintenance of memory CD8(+) T cells. Although memory CD8(+) T cells are generated from effector CD8(+) T cells, a role for Bcl6 in effector CD8(+) T cells is largely unknown. We show here that Bcl6 expression was transiently induced in activated CD8(+) T cells and continuously up-regulated in effector CD8(+) T cells. The amount of granzyme B mRNA among effector molecules produced by effector CD8(+) T cells inversely correlated with the amount of Bcl6 mRNA in CD8(+) T cells. Overexpression of Bcl6 in CD8(+) T cells resulted in lower killing activity at their effector phase, supporting the reduction of granzyme B expression in effector CD8(+) T cells by Bcl6. We identified a putative Bcl6-binding DNA sequence in the promoter region of the granzyme B gene. Binding of Bcl6 to the Bcl6-binding sequence was detected in naive CD8(+) T cells but not in activated CD8(+) T cells by chromatin immunoprecipitation assay. Furthermore, the Bcl6-binding sequence was required for Bcl6 to repress the luciferase reporter gene expression controlled by the granzyme B promoter. Thus, the granzyme B gene is a molecular target of Bcl6 in effector CD8(+) T cells.
Resonance response of scanning force microscopy cantilevers (1994)

A variational method is used to calculate the deflection and the fundamental and harmonic resonance frequencies of commercial V-shaped and rectangular atomic force microscopy cantilevers. The effective mass of V-shaped cantilevers is roughly half that calculated for the equivalent rectangular cantilevers. Damping by environmental gases, including air, nitrogen, argon, and helium, affects the frequency of maximum response and to a much greater degree the quality factor Q. Helium has the lowest viscosity, resulting in the highest Q, and thus provides the best sensitivity in noncontact force microscopy. Damping in liquids is dominated by an increase in effective mass of the cantilever due to an added mass of the liquid being dragged with that cantilever.
Displacement Estimation By Hierarchical Blockmatching (1988)

A hierarchical blockmatching algorithm for the estimation of displacement vector fields in digital television sequences is presented. Known blockmatching techniques fail frequently as a result of using a fixed measurement window size. Using distinct sizes of measurement windows at different levels of a hierarchy, the presented blockmatching technique yields reliable and homogeneous displacement vector - fields, which are close to the true displacements, rather than only a match in the sense of a minimum mean absolute luminance difference. In the environment of a low bit rate hybrid coder for image sequences, the hierarchical blockmatching algorithm is well suited for both, motion compensating prediction, and motion compensating interpolation. Compared to other high sophisticated displacement estimation techniques, the computational effort is decreased drastically. Due to the regularity and the very small number of necessary operations, the presented hierarchical blockmatching algorithm can be implemented in hardware very easily.
Human embryonic germ cell derivatives express a broad range of developmentally distinct markers and proliferate extensively in vitro (2000)

Human pluripotent stem cells (hPSCs) have been derived from the inner cell mass cells of blastocysts (embryonic stem cells) and primordial germ cells of the developing gonadal ridge (embryonic germ cells). Like their mouse counterparts, hPSCs can be maintained in culture in an undifferentiated state and, upon differentiation, generate a wide variety of cell types. Embryoid body (EB) formation is a requisite step in the process of in vitro differentiation of these stem cells and has been used to derive neurons and glia, vascular endothelium, hematopoietic cells, cardiomyocytes, and glucose-responsive insulin-producing cells from mouse PSCs. EBs generated from human embryonic germ cell cultures have also been found to contain a wide variety of cell types, including neural cells, vascular endothelium, muscle cells, and endodermal derivatives. Here, we report the isolation and culture of cells from human EBs as well as a characterization of their gene expression during growth in several different culture environments. These heterogeneous cell cultures are capable of robust and long-term [>70 population doublings (PD)] proliferation in culture, have normal karyotypes, and can be cryopreserved, clonally isolated, and stably transfected. Cell cultures and clonal lines retain a broad pattern of gene expression including simultaneous expression of markers normally associated with cells of neural, vascular/hematopoietic, muscle, and endoderm lineages. The growth and expression characteristics of these EB-derived cells suggest that they are relatively uncommitted precursor or progenitor cells. EB-derived cells may be suited to studies of human cell differentiation and may play a role in future transplantation therapies.
Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee. (1980)

Procedures capable of inducing the differentiation of authentic articular cartilage to resurface degenerated human joints would be invaluable. Surgical methods, such as drilling through to subchondral bone, are often attempted. It is not known, however, whether the cartilage that forms is true articular cartilage or, for example, fibrocartilage. The present experimental study in rabbits compared the properties of such repair cartilage with those of normal articular cartilage.
Identification and Characterization of a Ligand-independent Oligomerization Domain in the Extracellular Region of the CD95 Death Receptor (1999)

The CD95 death receptor plays an important role in several physiological and pathological apoptotic processes involving in particular the immune system. CD95 ligation leads to clustering of the receptor cytoplasmic "death domains" and recruitment of the zymogen form of caspase-8 to the cell surface. Activation of this protease through self-cleavage, followed by activation of downstream effector caspases, culminates in cleavage of a set of cellular proteins resulting in apoptosis with disassembly of the cell. It is very well known that the extracellular region of the CD95 receptor is required for CD95L interaction and that the death domain is necessary for the induction of the apoptotic signaling. Here, we identified and characterized a novel CD95 ligand- and death domain-independent oligomerization domain mapping to the NH(2)-terminal extracellular region of the CD95 receptor. In vitro and in vivo studies indicated that this domain, conserved among all soluble CD95 variants, mediates homo-oligomerization of the CD95 receptor and of the soluble CD95 proteins, as well as hetero-oligomerization of the receptor with the soluble variants. These results offer new insight into the mechanism of apoptosis inhibition mediated by the soluble CD95 proteins and suggest a role of the extracellular oligomerization domain in the regulation of the non-signaling state of the CD95 receptor.
Telomerase activity and human telomerase reverse transcriptase mRNA expression in soft tissue tumors: correlation with grade, histology, and proliferative activity. (1999)

Telomerase activity (TA) is detected in most human cancers but, with few exceptions, not in normal somatic cells. Little is known about TA in soft tissue tumors. We have examined a series of benign and malignant soft tissue tumors for TA using the telomerase repeat amplification protocol assay. Analysis of the expression of the human telomerase reverse transcriptase was also carried out using RT-PCR. TA was undetectable in benign lesions (15 of 15) and low-grade sarcomas (6 of 6) and was detectable in 50% (19 of 38) of intermediate-/high-grade sarcomas. Although the presence of TA in soft tissue tumors is synonymous with malignancy, it is neither a reliable method in making the distinction between reactive/benign and malignant (especially low-grade) lesions nor a reliable marker of tumor aggressiveness. Leiomyosarcomas and storiform/pleomorphic malignant fibrous histiocytomas rarely showed TA, irrespective of their grade. A strong correlation between human telomerase reverse transcriptase mRNA expression and TA was observed, supporting the close relationship between both parameters. No significant relationship was observed between proliferative activity (as assessed by MIB-1 immunolabeling) and TA. We verified that the absence of telomerase expression was not due to the presence of telomerase inhibitors and therefore alternative mechanism(s) for cell immortalization, yet to be determined, seem to be involved in the development and/or maintenance of some soft tissue sarcomas.
Hedonics in Consumer Behavior (2007)

To maximize happiness, one could either improve desired external outcomes (e.g., wealth) or optimize the relationship between desired external outcome and happiness without improving the outcome per se. Economics focuses on the first method. The present chapter advocates a science about the second method, which we term hedonomics. With its objective to help individuals, including consumers and policymakers, make decisions that maximize their happiness with external outcomes, hedonomics focuses on the relationships (a) between external outcomes and happiness, and (b) between decision and happiness.
Demonstration and study of a discharge-pumped, table-top soft-x-ray laser (1996)

We review results of the first demonstration of large soft‐x‐ray amplification in a discharge‐created plasma. A fast compressive capillary discharge was utilized to create elongated plasma columns with length‐to‐diameter ratios in excess of 500:1 having the required density and temperature for soft‐x‐ray amplification by collisional excitation of Ne‐like ions. The most recent measurements, conducted in capillary discharges up to 20 cm in length, have yielded an amplification of ∼exp(14) in the 46.9 nm line of Ne‐like argon. The dependence of the laser line intensity with discharge parameters and the dynamics of the capillary discharge plasma column under lasing conditions are reported. Prospects for laser operation at shorter wavelengths are discussed.
Reactions of 4‐Chloro‐9H‐xanthene‐9‐thione with Tetrachloro‐o‐benzoquinone (1984)

Reaktionen von 4‐Chlor‐9 H ‐xanthen‐9‐thion mit Tetrachlor‐ O ‐benzochinon 4‐Chlor‐9 H ‐xanthen‐9‐thion ( 1 ) reagiert mit Tetrachlor‐ o ‐benzochinon zu dem cyclischen Acetal 2 . Zur Struktursicherung wurde 2 auf unabhängigen Wegen aus Tetrachlor‐ o ‐benzochinon und 4‐Chlor‐9‐diazo‐9 H ‐xanthen oder 4‐Chlor‐9 H ‐xanthen‐9‐on‐hydrazon sowie aus Tetrachlorbrenzcatechin und 4,9,9‐Trichlor‐9 H ‐xanthen synthetisiert. Die Spaltung der Acetalgruppe in 2 mit Salzsäure, Malononitril, Cyanessigsäure‐ethylester und Hydrazinhydrat wurde studiert.
Noninvasive fluid flow measurements in microfluidic channels with backscatter interferometry (2004)

The ability to measure fluid velocity within picoliter volumes or on-chip noninvasively, is important toward fully realizing the potential of microfluidics and micrototal analysis systems, particularly in applications such as micro-high-performance liquid chromatography (HPLC) or in metering mixing where the flow rate must be quantified. Additionally, these measurements need to be performed directly on moving fluids in a noninvasive fashion. We presented here the proof of principle experiments showing nonintrusive fluid flow measurements can be accomplished on-chip using a pump and probe configuration with backscattering interferometry. The on-chip interferometric backscatter detector (OCIBD) is based on a fiber-coupled HeNe laser that illuminates a portion of an isotropically etched 40 microm radius channel and a position sensitive transducer to measure fringe pattern shifts. An infrared laser with a mechanical shutter is used to heat a section of a flowing volume and the resulting refractive index (RI) change is detected with the OCIBD downstream as a time-dependent RI perturbation. Fluid velocity is quantified as changes in the phase difference between the shutter signal and the OCIBD detected signal in the Fourier domain. The experiments are performed in the range of 3-6 microL/h with 3sigma detection limits determined to be 0.127 nL/s. Additionally, the RI response of the system is calibrated using temperature changes as well as glycerol solutions.
An amino-bisphosphonate targets MMP-9–expressing macrophages and angiogenesis to impair cervical carcinogenesis (2004)

A mouse model involving the human papillomavirus type-16 oncogenes develops cervical cancers by lesional stages analogous to those in humans. In this study the angiogenic phenotype was characterized, revealing intense angiogenesis in high-grade cervical intraepithelial neoplasias (CIN-3) and carcinomas. MMP-9, a proangiogenic protease implicated in mobilization of VEGF, appeared in the stroma concomitant with the angiogenic switch, expressed by infiltrating macrophages, similar to what has been observed in humans. Preclinical trials sought to target MMP-9 and angiogenesis with a prototypical MMP inhibitor and with a bisphosphonate, zoledronic acid (ZA), revealing both to be antiangiogenic, producing effects comparable to a Mmp9 gene KO in impairing angiogenic switching, progression of premalignant lesions, and tumor growth. ZA therapy increased neoplastic epithelial and endothelial cell apoptosis without affecting hyperproliferation, indicating that ZA was not antimitotic. The analyses implicated cellular and molecular targets of ZA’s actions: ZA suppressed MMP-9 expression by infiltrating macrophages and inhibited metalloprotease activity, reducing association of VEGF with its receptor on angiogenic endothelial cells. Given its track record in clinical use with limited toxicity, ZA holds promise as an “unconventional” MMP-9 inhibitor for antiangiogenic therapy of cervical cancer and potentially for additional cancers and other diseases where MMP-9 expression by infiltrating macrophages is evident.