gebhart/patrepeval huggingface dataset:
Gelatin microspheres crosslinked with genipin for local delivery of growth factors (2010)

A main challenge in tissue engineering and regenerative medicine is achieving local and efficient growth factor release to guide cell function. Gelatin is a denatured form of collagen that cells can bind to and degrade through enzymatic action. In this study, gelatin microspheres were used to release bone morphogenetic protein 2 (BMP2). Spherical microparticles with diameters in the range of 2–6 µm were created by an emulsification process and were stabilized by crosslinking with the small molecule genipin. The degree of crosslinking was varied by controlling the incubation time in genipin solution. Loading rate studies, using soy bean trypsin inhibitor as a model protein, showed rapid protein uptake over the first 24 h, followed by a levelling off and then a further increase after approximately 3 days, as the microspheres swelled. Growth factor release studies using microspheres crosslinked to 20%, 50% and 80% of saturation and then loaded with BMP2 showed that higher degrees of crosslinking resulted in higher loading efficiency and slower protein release. After 24 h, the concentration profiles produced by all microsphere formulations were steady and approximately equal. Microspheres incubated with adult human mesenchymal stem cells accumulated preferentially on the cell surface, and degraded over time in culture. BMP2-loaded microspheres caused a three- to eight-fold increase in expression of the bone sialoprotein gene after 14 days in culture, with more crosslinked beads producing a greater effect. These results demonstrate that genipin-crosslinked gelatin microspheres can be used to deliver growth factors locally to cells in order to direct their function. Copyright © 2010 John Wiley & Sons, Ltd.
CMOS-Based Active Pixel for Low-Light-Level Detection: Analysis and Measurements (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> An analysis of the active pixel sensor (APS), considering the doping profiles of the photodiode in an APS fabricated in a 0.18 <formula formulatype="inline"><tex>$\mu\hbox{m}$</tex></formula> standard CMOS technology, is presented. A simple and accurate model for the junction capacitance of the photodiode is proposed. An analytic expression for the output voltage of the APS obtained with this capacitance model is in good agreement with measurements and is more accurate than the models used previously. A different mode of operation for the APS based on the dc level of the output is suggested. This new mode has better low-light-level sensitivity than the conventional APS operating mode, and it has a slower temporal response to the change of the incident light power. At 1 <formula formulatype="inline"><tex>$\mu\hbox{W/cm}^{2}$</tex></formula> and lower levels of light, the measured signal-to-noise ratio (SNR) of this new mode is more than 10 dB higher than the SNR of previously reported APS circuits. Also, with an output SNR of about 10 dB, the proposed dc level is capable of detecting light powers as low as 20 <formula formulatype="inline"><tex>$\hbox{nW/cm}^{2}$</tex></formula>, which is about 30 times lower than the light power detected in recent reports by other groups. </para>
The Diversity of Neuronal Nicotinic Acetylcholine Receptors (1993)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Hierarchically porous graphene-based hybrid electrodes with excellent electrochemical performance (2013)

A new structure of hierarchically porous graphene–nickel hydroxide (Ni(OH)2) hybrid, which contains both in-plane mesopores and out-of-plane meso/macropores, has been fabricated by a facile one-step method using holey graphene as a framework structure and Ni(OH)2 as a “spacer”. The aforementioned two kinds of pores facilitate the kinetics of processes occurring in an electrode without compromising its conductivity, and assure high charge storage capacity and rate capability. The material displays an excellent rate capability, high stability and its capacitance is among the top values for powder-based supercapacitors. This study paves the way towards the development of feasible strategies for tailoring the porosity of graphene-based structures for advanced energy storage devices.
IL-36 Promotes Myeloid Cell Infiltration, Activation, and Inflammatory Activity in Skin (2014)

The IL-1 family members IL-36α (IL-1F6), IL-36β (IL-1F8), and IL-36γ (IL-1F9) and the receptor antagonist IL-36Ra (IL-1F5) constitute a novel signaling system that is poorly understood. We now show that these cytokines have profound effects on the skin immune system. Treatment of human keratinocytes with IL-36 cytokines significantly increased the expression of CXCL1, CXCL8, CCL3, CCL5, and CCL20, potent chemotactic agents for activated leukocytes, and IL-36α injected intradermally resulted in chemokine expression, leukocyte infiltration, and acanthosis of mouse skin. Blood monocytes, myeloid dendritic cells (mDC), and monocyte-derived DC (MO-DC) expressed IL-36R and responded to IL-36. In contrast, no direct effects of IL-36 on resting or activated human CD4(+) or CD8(+) T cells, or blood neutrophils, could be demonstrated. Monocytes expressed IL-1A, IL-1B, and IL-6 mRNA and IL-1β and IL-6 protein, and mDC upregulated surface expression of CD83, CD86, and HLA-DR and secretion of IL-1β and IL-6 after treatment with IL-36. Furthermore, IL-36α-treated MO-DC enhanced allogeneic CD4(+) T cell proliferation, demonstrating that IL-36 can stimulate the maturation and function of DC and drive T cell proliferation. These data indicate that IL-36 cytokines actively propagate skin inflammation via the activation of keratinocytes, APC, and, indirectly, T cells.
A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor (2000)

The mechanisms responsible for the low factor VIII (fVIII) activity in the plasma of patients with mild/moderate hemophilia A are poorly understood. In such patients, we have identified a series of fVIII mutations (Ile2098Ser, Ser2119Tyr, Asn2129Ser, Arg2150His, and Pro2153Gln) clustered in the C1 domain and associated with reduced binding of fVIII to von Willebrand factor (vWf). For each patient plasma, the specific activity of mutated fVIII was close to that of normal fVIII. Scatchard analysis showed that the affinity for vWf of recombinant Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII mutants was reduced 8-fold, 80-fold, and 3-fold, respectively, when compared with normal fVIII. Given the importance of vWf for the stability of fVIII in plasma, these findings suggested that the reduction of fVIII binding to vWf resulting from the above-mentioned mutations could contribute to patients' low fVIII plasma levels. We, therefore, analyzed the effect of vWf on fVIII production by Chinese hamster ovary (CHO) cells transfected with expression vectors for recombinant B domain-deleted normal, Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII. These 3 mutations impaired the vWf-dependent accumulation of functional fVIII in culture medium. Analysis of fVIII production by transiently transfected CHO cells indicated that, in addition to the impaired stabilization by vWf, the secretion of functional Ile2098Ser and Arg2150His fVIII was reduced about 2-fold and 6-fold, respectively, by comparison to Ser2119Tyr and normal fVIII. These findings indicate that C1-domain mutations resulting in reduced fVIII binding to vWf are an important cause of mild/moderate hemophilia A.
RNA Interference Inhibits DUX4-induced Muscle Toxicity In Vivo: Implications for a Targeted FSHD Therapy (2012)

No treatment exists for facioscapulohumeral muscular dystrophy (FSHD), one of the most common inherited muscle diseases. Although FSHD can be debilitating, little effort has been made to develop targeted therapies. This lack of focus on targeted FSHD therapy perpetuated because the genes and pathways involved in the disorder were not understood. Now, more than 2 decades after efforts to decipher the root cause of FSHD began, this barrier to translation is finally lowering. Specifically, several recent studies support an FSHD pathogenesis model involving overexpression of the myopathic DUX4 gene. DUX4 inhibition has therefore emerged as a promising therapeutic strategy for FSHD. In this study, we tested a preclinical RNA interference (RNAi)-based DUX4 gene silencing approach as a prospective treatment for FSHD. We found that adeno-associated viral (AAV) vector-delivered therapeutic microRNAs corrected DUX4-associated myopathy in mouse muscle. These results provide proof-of-principle for RNAi therapy of FSHD through DUX4 inhibition.
T-cell Clonal Anergy (1989)

Chemical fixation of splenic antigen-presenting cells (APC) with paraformaldehyde or 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (ECDI) destroys their ability to stimulate a proliferative response from interleukin-2 (IL-2)-producing T-cell clones (Jenkins and Schwartz 1987). In addition, exposure of the clones to antigen in the presence of the chemically fixed APC induces in them a hyporesponsive state to subsequent stimulation by normal APC and antigen (Fig. 1A). This induction of proliferative nonresponsiveness requires the correct allelic form of the major histocompatibility complex (MHC) class II molecule and the precise peptide recognized by the antigen receptor of the T-cell clone. These observations suggest that antigen-receptor occupancy is qualitatively normal and that the delivery of some other signal required for T-cell activation has been damaged by the fixation.
Soluble type II transforming growth factor-beta (TGF-beta) receptor inhibits TGF-beta signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation. (2001)

These results indicate that endogenous TGF-betas can confer a growth advantage in vivo to a pancreatic cancer cell line that is growth inhibited in vitro and suggest that a soluble receptor approach can be used to block these tumorigenic effects of TGF-betas.
Internal cleavage of the inhibitory 7B2 carboxyl-terminal peptide by PC2: a potential mechanism for its inactivation. (1996)

The neuroendocrine protein 7B2 contains two domains, a 21-kDa protein required for prohormone convertase 2 (PC2) maturation and a carboxyl-terminal (CT) peptide that inhibits PC2 at nanomolar concentrations. To determine how the inhibition of PC2 is terminated, we studied the metabolic fate of the 7B2 CT peptide in RinPE-7B2, AtT-20/PC2-7B2, and alphaTC1-6 cells. Extracts obtained from cells labeled for 6 h with [3H]valine were subjected to immunoprecipitation using an antibody raised against the extreme carboxyl terminus of r7B2, and immunoprecipitated peptides were separated by gel filtration. All three cell lines yielded two distinct peaks at about 3.5 kDa and 1.5 kDa, corresponding to the CT peptide and a smaller fragment consistent with cleavage at an interior Lys-Lys site. These results were corroborated using a newly developed RIA against the carboxyl terminus of the CT peptide which showed that the intact CT peptide represented only about half of the stored CT peptide immunoreactivity, with the remainder present as the 1.5-kDa peptide. Both peptides could be released upon phorbol 12-myristate 13-acetate stimulation. We investigated the possibility that PC2 itself could be responsible for this cleavage by performing in vitro experiments. When 125I-labeled CT peptide was incubated with purified recombinant PC2, a smaller peptide was generated. Analysis of CT peptide derivatives for their inhibitory potency revealed that CT peptide 1-18 (containing Lys-Lys at the carboxyl terminus) represented a potent inhibitor, but that peptide 1-16 was inactive. Inclusion of carboxypeptidase E (CPE) in the reaction greatly diminished the inhibitory potency of the CT peptide against PC2, in line with the notion that the CT peptide cleavage product is not inhibitory after the removal of terminal lysines by CPE. In summary, our data support the idea that PC2 cleaves the 7B2 CT peptide at its internal Lys-Lys site within secretory granules; deactivation of the cleavage product is then accomplished by CPE, thus providing an efficient mechanism for intracellular inactivation of the CT peptide.
In vivo stimulation and restoration of the immune response by the noninflammatory fragment 163-171 of human interleukin 1 beta. (1988)

The synthetic nonapeptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, showed in vivo immunomodulatory capacities qualitatively and quantitatively comparable to those of the mature human IL-1 beta protein. In fact, both IL-1 beta and the 163-171 fragment stimulated the immune response of normal mice and restored immune reactivities of immunocompromised animals. In addition, the synthetic IL-1 peptide was as efficient as the entire protein in inducing tumor rejection and radioprotection. On the other hand, the 163-171 fragment did not cause any of several inflammation-associated metabolic changes inducible by the whole IL-1 beta molecule in vivo: hypoferremia, hypoglycemia, hyperinsulinemia, increase in circulating corticosterone, SAA and fibrinogen, decrease in hepatic drug-metabolizing enzymes. Furthermore, at variance with IL-1 beta, the 163-171 peptide did not show the toxic effects causing shock and death in adrenalectomized mice. Thus, these results confirm our previous in vitro observations that functional domains are identifiable within the multipotent cytokine IL-1 beta, and demonstrate the biological relevance of this finding in a variety of in vivo systems. The identification of a selectively active fragment of a cytokine may thus represent a significant step towards a better directed and more rational immunotherapeutic approach.
Canine hemophilia B resulting from a point mutation with unusual consequences. (1989)

We have used the polymerase chain reaction to amplify the entire coding region of canine factor IX from a hemophilia B animal. When the sequence was compared to that which codes for normal canine factor IX, a single missense mutation was identified. This mutation (G----A at nucleotide 1477) results in the substitution of glutamic acid for glycine-379 in the catalytic domain of the molecule. The mutation creates a new restriction site that allowed confirmation of the abnormal sequence in both hemophilic and carrier animals. Amino acid 379 in canine factor IX corresponds to position 381 in human factor IX, a location at which no human mutations have been described. Moreover, it occurs at one of the few amino acids that have been rigorously conserved among the trypsin-like serine proteases throughout evolution. The mutation responsible for canine hemophilia B results in a complete lack of circulating factor IX in the affected animals. As it is unusual for a missense mutation to result in a complete absence of protein product, structural modeling of the mutant and normal proteins was pursued. These studies suggest that the observed mutation would have major adverse effects on the tertiary structure of the aberrant factor IX molecule. The elucidation of this mutation sheds light on structure-function relationships in factor IX and should facilitate future experiments directed toward gene therapy of this disease.
Synthese, Struktur und Oxotransferreaktionen von Dioxomolybdän(VI)‐Komplexen mit mehrzähnigen Aminoalkoholen als Liganden (1997)

Abstract Die dreibasigen, fünfzähnigen Aminoalkohole l,l‐Bis(2‐hydroxyethyl)‐4‐(2‐hydroxybenzyl)4,4‐diaza‐butan (H 3 hebab) und N ‐Salicyliden‐2‐(bis(2‐hydroxyethyl)‐amino)ethylamin (H 3 sabhea) reagieren mit [MoO 2 (acac)2] in Methanol als Lösungsmittel zu den cis ‐Dioxomolybdän(VI)‐Komplexen [MoO 2 (Hsabhea)] ( 1 ) und [MoO 2 (Hhebab)] ( 2 ). Die Komplexe wurden mit Hilfe von 1 H‐NMR‐, 13 C‐NMR‐, Schwingungs‐ (IR, Raman) und UV/Vis‐Spektroskopie sowie Kristallstrukturanalysen ( 1 ): monokline Raumgruppe P2 1 / c ; a = 1583,6(5); b = 681,2(3); c = 1332,8(5) pm; β = 101,42(3)°; Z = 4; 2 : monokline Raumgruppe P2 1 / c ; a = 2096,5(4); b = 755,5(1); c = 2000,4(4) pm; β = 112.26(1)°; Z = 8) charakterisiert. In beiden Komplexen besitzt das Molybdän(VI)‐Zentrum eine verzerrt oktaedrische Umgebung, dabei sind die Oxo‐Liganden jeweils trans ‐ständig zu den beiden Stickstoffdonorzentren der Ligandgerüste. Für 1 führt dies zu einer sterisch gespannten facialen Koordination der üblicherweise meridional koordinierten Imino‐Chelateinhcit des Ligandgerüsts, bestehend aus Phenolatsauerstoff‐ bzw. Imin‐ und tertiärem Aminstickstoffdonor. Die Reaktivität der Komplexe 1 und 2 bezüglich der Sauerstoffübertragung wird am Beispiel der Modellreaktion zwischen DMSO und Triphenylphosphan untersucht. Beide Komplexe katalysieren diese Reaktion, wobei 1 jedoch deutlich reaktiver ist. Die beobachtete Reaktivitätsabstufung läßt sich im wesentlichen auf die strukturellen Unterschiede der Komplexe 1 und 2 zurückführen.
Next-generation sequencing for HLA typing of class I loci (2011)

Next-generation sequencing on the 454 FLX Titanium platform is a reliable, efficient, and scalable technology for HLA typing.
Low dielectric constant films prepared by plasma-enhanced chemical vapor deposition from tetramethylsilane (1999)

Dielectric films have been prepared by radio-frequency plasma-enhanced chemical vapor deposition from mixtures of tetramethylsilane with oxygen. The films have been characterized as-deposited and after annealing at 400 °C to determine the thermal stability of their properties. Rutherford backscattering and forward recoil elastic scattering have been used for determination of the composition of the films. Optical properties were characterized by Fourier transform infrared spectroscopy and measurements of the index of refraction and optical gap. The electrical properties were measured in a Si/insulator/metal configuration. It has been found that the index of refraction decreases and the optical gap and dielectric constant increase with increasing oxygen concentration in the gas feed. While the materials did not show a mass or composition loss after annealing, the annealing resulted in a reduction of the dielectric constant of the films. Dielectric constants as low as 3.1 have been obtained after annealing the film deposited from pure tetramethylsilane.
Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement (2000)

To examine the influence of chronic mechanical stretch on functional behavior of cardiac myocytes, we reconstituted embryonic chick or neonatal rat cardiac myocytes to a 3-dimensional engineered heart tissue (EHT) by mixing freshly isolated cells with neutralized collagen I and culturing them between two Velcro-coated silicone tubes, held at a fixed distance with a metal spacer. After 4 days, EHTs were subjected to a phasic unidirectional stretch for 6 days in serum-containing medium. Compared to unstretched controls, RNA/DNA and protein/cell ratios increased by 100% and 50%, respectively. ANF mRNA and alpha-sarcomeric actin increased by 98% and 40%, respectively. Morphologically, stretched EHTs exhibited improved organization of cardiac myocytes into parallel arrays of rod-shaped cells, increased cell length and width, longer myofilaments, and increased mitochondrial density. Thus, stretch induced phenotypic changes, generally referred to as hypertrophy. Concomitantly, force of contraction was two- to fourfold higher both under basal conditions and after stimulation with calcium or the beta-adrenergic agonist isoprenaline. Contraction kinetics were accelerated with a 14-44% decrease in twitch duration under all those conditions. In summary, we have developed a new in vitro model that allows morphological, molecular, and functional consequences of stretch to be studied under defined conditions. The main finding was that stretch of EHTs induced cardiac myocyte hypertrophy, which was accompanied by marked improvement of contractile function.
Antiaggregatorische und Anticoagulante Eigenschaften von Oligoaminen, 1. Mitt. 4‐Piperidinylmethanamine (1986)

Abstract Geeignet in 1‐Stellung aralkylierte 4‐Aminomethyl‐4‐phenyl‐piperidine hemmen in vitro die durch Collagen induzierte Thrombocytenaggregation in Konzentrationen von einigen μmol/1 ( 10 : IC50 = 5,5 · 10 −6 M). In höheren Konzentrationen wird auch die durch Thromboplastin ausgelöste Fibrinbildung behindert ( 10 : 25 % der Norm bei 1 · 10 ‐4 M). Der Arachidonsäuremetabolismus von Thrombocyten wird nicht beeinflußt.
The Growth of Microorganisms in Propofol and Mixtures of Propofol and Lidocaine (1999)

Local anesthetics such as lidocaine have antimicrobial activity. Propofol supports the growth of bacteria responsible for infection. Bacteria were added to propofol and propofol mixed with lidocaine. The addition of lidocaine to propofol in clinically relevant concentrations did not prevent the growth of bacteria. The addition of lidocaine to propofol cannot prevent infection from contaminated propofol.
Two Novel Thioesterases Are Key Determinants of the Bimodal Distribution of Acyl Chain Length of Cuphea palustris Seed Oil (1996)

The seed oil of Cuphea palustris has an unusual fatty-acyl composition, whereby the principal fatty-acyl groups, myristate (64%) and caprylate (20%), differ by more than two methylenes. We have isolated two thioesterase (TE) cDNAs from C. palustris, encoding proteins designated Cp FatB1 and Cp FatB2, which, when expressed in Escherichia coli, have TE activities specific for 8:0/10:0- and 14:0/16:0-acyl carrier protein substrates, respectively. The specific activities of the recombinant affinity-purified enzymes indicate that Cp FatB2 is kinetically superior to Cp FatB1. This result is consistent with the predominance of 14:0 in the seed oil, despite apparently equal mRNA abundance of the two transcripts in the seed. In C. palustris the expression of both sequences is confined to the seed tissues. Based on these findings we propose that these two enzymes are major factors determining the bimodal chain-length composition of C. palustris oil. Analysis of the immature and mature seed oil by reverse-phase high-performance liquid chromatography confirmed that the principal triglycerides contain both 8:0 and 14:0. This result indicates that both fatty acids are synthesized at the same time and in the same cells at all developmental stages during oil deposition, suggesting that the two TEs act together in the same fatty acid synthesis system.