gebhart/patrepeval huggingface dataset:
Hypoglossal nerve stimulation improves obstructive sleep apnea: 12‐month outcomes (2013)

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty-one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single-arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea-hypopnea index, from in-laboratory polysomnogram) and sleep-related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea-hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h(-1) ) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device-related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.
Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia. (1979)

In the search for the mechanism by which hyperammonemia complicates propionic and methylmalonic acidemia the effects of a series of acyl-coenzyme A (CoA) derivatives were studied on the activity of N-acetylglutamate synthetase in rat liver mitochondria using acetyl-CoA as substrate. Propionyl-CoA was found to be a competitive inhibitor. The inhibition constant of 0.71 mM is in the range of concentrations of propionate found in the serum of patients with propionic and methylmalonic acidemia. Propionyl-CoA was also found to be a substrate for N-acetylglutamate synthetase, forming N-propionylglutamate. This compound was a weak activator of rat liver carbamoylphosphate synthetase; the activation constant was 1.1 mM as compared with 0.12 mM for N-acetylglutamate. A decreased level of N-acetylglutamate in liver mitochondria that would follow inhibition of N-acetylglutamate synthetase by propionyl-CoA would be expected to lead to hyperammonemia. Methylmalonyl-CoA, tiglyl-CoA, and isovaleryl-CoA at a concentration of 3 mM caused 30-70% inhibition of N-acetylglutamate synthetase. 3the latter two compounds are readily detoxified by the formation of N-acylglycine conjugates in liver, which may prevent large accumulations and could explain why hyperammonemia is not characteristic of patients with beta-ketothiolase deficiency or isovaleric acidemia in whom these compounds would be expected to be elevated.
An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells (1994)

P19 cells, a mouse embryonal carcinoma line, can be induced to differentiate into neurons. After induction, however, only a small subpopulation of cells develop as neurons, suggesting that equipotent cells adopt different cell fates. In invertebrate systems, the lin-12-Notch family of genes is thought to control the choice of cell fate. We have therefore asked whether activation of murine Notch (mNotch) regulates neuronal differentiation in P19 cells. We demonstrate that a dominant gain-of-function mutant of mNotch suppresses neurogenesis, as well as myogenesis in P19 cells. Overexpression of the full-length mNotch protein also suppresses neurogenesis. In contrast, the differentiation of glia is not affected by an activated mNotch homologue. These data indicate that mNotch may play a central role in the choice of cell fate in differentiating cells in culture and suggests that mNotch may play a similar role in the choice of fate in the developing mammalian embryo.
Nucleic Acid Nanostructures and Topology (1998)

Knots, polyhedra, and Borromean rings with specific structural and topological features can be made from DNA. Biotechnologists have been exploiting the programmability of DNA intermolecular associations for a quarter of a century. These operations have now been applied successfully to branched DNA species to produce complex target structures (for example, the cube shown in the picture) and a nanomechanical device. The assembly of two-dimensional crystals with programmed topographic characteristics demonstrates the simplicity of translating design into surface structures.
Anoikis: Roadblock to Cell Transplantation? (2002)

Cell therapy, in particular liver cell transplantation, holds great therapeutic potential and is partially hindered by the high rate of apoptosis during cell isolation, cryopreservation, and engraftment. Apoptosis occurring due to cell detachment from the extracellular matrix is a phenomenon termed "anoikis." The purpose of this review is to describe signaling mechanisms pertinent to anoikis in both immortalized cell lines, but particularly in primary normal epithelial cells. The mechanisms described include integrin signaling and survival molecules, caspase activation, and the role of mitochondrial proteins in anoikis. Strategies to prevent anoikis during isolation and cryopreservation of hepatocytes are discussed.
Abstract #4650: Development of human blocking antibodies to \#916;-like ligand-4 (Dll4) in VelocImmune mice for anti-angiogenesis therapy (2009)

The growth of solid tumors depends on the growth of a functional tumor vasculature. Recent studies have shown that blockade of the Dll4-Notch pathway in established tumors results in increased tumor vessel density, but paradoxically, increased tumor hypoxia and decreased tumor growth, even in tumors that are resistant to VEGF blockade. These anti-tumor actions of Dll4 blockade are a result of aberrant non-productive tumor angiogenesis. To exploit Dll4 as a target for the treatment of cancer, we sought to develop and characterize fully human antibodies that block the Dll4-Notch pathway. By immunizing VelocImmune mice, which express the full repertoire of human antibody variable domains in the endogenous locus of the mouse immunoglobin gene, we discovered an array of antibodies that bind to various domains of Dll4 and efficiently block the interaction of Dll4 with Notch receptors. Further characterization was performed on 40 of these antibodies, which represent significant diversity of repertoire and bind Dll4 with an affinity of less than 1 nM, in cell-based and biochemical assays. A subset of these antibodies was further tested using in vivo assays. To better evaluate the effects of these antibodies in pre-clinical tumor models, we used Velocigene technology to generate a genetically engineered mouse in which the region of the murine Dll4 gene that encodes the extracellular portion of Dll4 was replaced with the equivalent human genetic region (~7 kB). This \#8216;humanized\#8217; Dll4 allele expresses Dll4 mRNA and protein at approximately the same levels as the endogenous allele and has yielded viable homozygous mice. Initial studies in these humanized Dll4 mice demonstrate that VelocImmune Dll4 antibodies potently inhibit tumor growth and produce aberrant tumor vasculature. These novel reagents will allow for detailed evaluation of the role of Dll4 in tumor angiogenesis, as well as meaningful characterization of fully human Dll4 antibodies for pre-clinical development. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4650.
The Geometry of Algorithms with Orthogonality Constraints (1998)

In this paper we develop new Newton and conjugate gradient algorithms on the Grassmann and Stiefel manifolds. These manifolds represent the constraints that arise in such areas as the symmetric eigenvalue problem, nonlinear eigenvalue problems, electronic structures computations, and signal processing. In addition to the new algorithms, we show how the geometrical framework gives penetrating new insights allowing us to create, understand, and compare algorithms. The theory proposed here provides a taxonomy for numerical linear algebra algorithms that provide a top level mathematical view of previously unrelated algorithms. It is our hope that developers of new algorithms and perturbation theories will benefit from the theory, methods, and examples in this paper.
Rapid Detection of Necrosis in Breast Cancer with Desorption Electrospray Ionization Mass Spectrometry (2016)

Identification of necrosis in tumors is of prognostic value in treatment planning, as necrosis is associated with aggressive forms of cancer and unfavourable outcomes. To facilitate rapid detection of necrosis with Mass Spectrometry (MS), we report the lipid MS profile of necrotic breast cancer with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) imaging validated with statistical analysis and correlating pathology. This MS profile is characterized by (1) the presence of the ion of m/z 572.48 [Cer(d34:1) + Cl]<sup>-</sup> which is a ceramide absent from the viable cancer subregions; (2) the absence of the ion of m/z 391.25 which is present in small abundance only in viable cancer subregions; and (3) a slight increase in the relative intensity of known breast cancer biomarker ions of m/z 281.25 [FA(18:1)-H]<sup>-</sup> and 303.23 [FA(20:4)-H]<sup>-</sup>. Necrosis is accompanied by alterations in the tissue optical depolarization rate, allowing tissue polarimetry to guide DESI-MS analysis for rapid MS profiling or targeted MS imaging. This workflow, in combination with the MS profile of necrosis, may permit rapid characterization of necrotic tumors from tissue slices. Further, necrosis-specific biomarker ions are detected in seconds with single MS scans of necrotic tumor tissue smears, which further accelerates the identification workflow by avoiding tissue sectioning and slide preparation.
MyoD expression marks the onset of skeletal myogenesis in Myf-5 mutant mice (1994)

The expression pattern of myogenic regulatory factors and myotome-specific contractile proteins was studied during embryonic development of Myf-5 mutant mice by in situ hybridization and immunohistochemistry. In contrast to somites in wild-type embryos, no expression of myogenin and Myf-6 (MRF4), or any other myotomal markers was detected in mutant animals at E9.0 and E10.0 indicating that Myf-5 plays a crucial role during this developmental period. Significantly, the onset of MyoD expression in rostral somites of E10.5 embryos was unaffected by the Myf-5 mutation suggesting that the activation of the MyoD gene occurs independently of Myf-5 at the correct developmental time. Immediately after the activation of MyoD myogenin transcripts and protein accumulated within the myotome. The first contractile proteins of the sarcomeric apparatus appeared slightly later. By E11.5 the expression of muscle markers were indistinguishable between wild-type and Myf-5 mutant mice. The migration of muscle precursor cells that leave the somites to form limb musculature was monitored in Myf-5-mutant mice by Pax-3 expression. Pax-3-positive cells were equally found in somites and limbs of E10.0 wild-type and mutant mice indicating that myogenic factor expression at the level of somites is not a prerequisite for determination and subsequent migration of limb precursor cells.
Specific labelling by peanut agglutinin of the outer acrosomal membrane of the human spermatozoon (1991)

Experiments to bind fluorescein-conjugated Arachis hypogea (peanut) agglutinin (FITC-PNA) to washed human spermatozoa demonstrated that this lectin binds to the acrosome region in air-dried preparations. Since there was no binding when labelling was performed in suspension, and comparable labelling to that seen in air-dried preparations was seen when spermatozoa treated with saponin (to lyse the plasma membrane) were labelled in suspension, the lectin must bind to an intracellular structure, probably the outer acrosomal membrane. This was confirmed by ultrastructural localization of colloidal gold-conjugated lectin in saponin-treated spermatozoa. Treatment of spermatozoa with the detergent Nonidet P-40 caused a marked change in the binding pattern: more spermatozoa showed binding in the equatorial segment of the acrosome with no binding in the anterior cap region. A comparable, less marked, change was seen when spermatozoa were incubated overnight under conditions known to support the capacitation and spontaneous acrosome reactions. Treatment with the calcium ionophore A23187 for 1 h to induce acrosome reactions artificially in uncapacitated spermatozoa resulted in the appearance of patchy acrosome fluorescence. From these experiments it is concluded that PNA binds specifically to the outer acrosomal membrane, and that FITC-PNA-labelling may be used to monitor the human sperm acrosome reaction.
Correlation of cytogenetic patterns and clinicobiological features in adult acute myeloid leukemia expressing lymphoid markers [see comments] (1992)

Cytogenetic, biomolecular, and clinicopathologic features were retrospectively studied in 34 adult patients with acute myelogenous leukemia expressing one or more of the following lymphoid-associated markers (LMs): CD7, CD2, CD10, CD19, CD22, TdT. Six patients showed 11q23 rearrangements (group I); three patients had the classic Ph chromosome (group II); 15 patients had aberrations of the myeloid type (group III), including four patients with structural aberrations of 13q or trisomy 13, three patients with 7q and 1q anomalies, and two patients with trisomy 11q. Ten patients had a normal karyotype (group IV). Anomalies exclusively associated with lymphoid malignancies were not seen. Ig H and/or T-cell receptor genes were found to be rearranged in 50% and 66% of patients in cytogenetic groups I and II, respectively, versus 8% in group III and 12% in group IV. Likewise, more than one LM was more frequently detected in groups I and II. In group III, two of four patients with aberrations of chromosome 13 expressed two or more lymphoid features. Clinically, patients belonging to cytogenetic groups I and II were generally young, presented with a high white blood cell (WBC) count, and had a low complete remission rate. Survival in Ph chromosome-positive cases was uniformly short. We conclude that although there is no cytogenetic anomaly specifically associated with acute myelogenous leukemia expressing LM, a Morphologic, Immunologic, and Cytogenetic classification may constitute a working basis for further studies aimed at a better definition of clinicopathologic features and optimal treatment strategies for these leukemias.
Absorption flattening in the optical spectra of liposome‐entrapped substances (1994)

Measuring optical spectra of chromophore molecules entrapped in liposomes can lead to considerable distortion because of absorption flattening. This phenomenon is analyzed theoretically, and it is shown that the deviation from the Beer-Lambert law becomes larger as the molar absorptivity of the chromophore increases and as the number of entrapped molecules becomes larger. The theoretical equations are tested experimentally with intermediate-sized phospholipid vesicles containing entrapped cytochrome c. It is shown that considerable absorption flattening is observed with vesicles containing about 50 chromophore molecules. The equation given can be used to correct the spectrum.
Safety and efficacy of neonatal vaccination (2008)

Newborns have an immature immune system that renders them at high risk for infection while simultaneously reducing responses to most vaccines, thereby posing challenges in protecting this vulnerable population. Nevertheless, certain vaccines, such as BCG and Hepatitis B vaccine, do demonstrate safety and some efficacy at birth, providing proof of principal that certain antigen-adjuvant combinations are able to elicit protective neonatal responses. Moreover, birth is a major point of healthcare contact globally meaning that effective neonatal vaccines achieve high population penetration. Given the potentially significant benefit of vaccinating at birth, availability of a broader range of more effective neonatal vaccines is an unmet medical need and a public health priority. This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination.
Functionalization and patterning of monolayers on silicon(111) and polydicyclopentadiene (2010)

The formation of a functional surface combines the properties of a substrate and monolayer to produce a new hybrid that can combine aspects of each. Monolayers can be made on many surfaces, and well defined functionalized monolayers were assembled on silicon(111) and polydicyclopentadiene (PDCPD). Acid terminated monolayers were assembled on silicon(111) and their functionalization chemistry explored. It was shown that using trifluoroacetic anhydride to generate an intermediate reactive anhydride, the surface could be functionalized with amines. It was further shown that using soft lithography these functionalized surfaces could be patterned. Mixed monolayers of methyl and olefin terminated surfaces on silicon(111) were used to develop a new soft lithographic technique with polydimethylsiloxane (PDMS). PDMS can be controllably etched using fluoride species. The surface is first activated by the attachment of the Grubbs’ 1 generation catalyst. A PDMS microfluidic device is then placed on the surface. By using a cross metathesis reaction, the exposed channel can be pacified. The next step, a fluoride etchant is used to remove PDMS, exposing an unreacted surface. Polymer brushes were then grown by ring opening metathesis polymerization (ROMP) in this region. Functionalization of the emerging polymer PDCPD was conducted through two different routes. ROMP formed PDCPD has double bonds that can be functionalized. In the first process, the double bonds were reacted with bromine. This is a rapid reaction and proceeds to a significant depth in the material. Bromines can then be displaced with amines in a substitution reaction. This was demonstrated with a fluorinated amine that when examined by XPS were shown to be present only at the surface, further more we were able to pattern this surface too. Secondly, a process using epoxides was developed. The epoxidation reaction could not be quantified, but formation in the second step of an
Chemistry of β‐Emitting Compounds Based on 18F (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Design Alternatives for Process Group Membership and Multicast (1991)

Process groups are a natural tool for distributed programming, and are increasingly important in distributed computing environments. However, there is little agreement on the most appropriate semantics for process group membership and group communication. These issues are of special importance in the Isis system, a toolkit for distributed programming. Isis supports several styles of process group, and a collection of group communication protocols spanning a range of atomicity and ordering properties. This flexibility makes Isis adaptable to a variety of applications, but is also a source of complexity that limits performance. This paper reports on a new architecture that arose from an effort to simplify Isis process group semantics. Our findings include a refined notion of how the clients of a group should be treated, what the properties of a multicast primitive should be when systems contain large numbers of overlapping groups, and a new construct called the casuality domain. As an illustration, we apply the architecture to the problem of converting processes into fault-tolerant process groups in a manner that is 'transparent' to other processes in the system.
Current Sensing Circuit of MOSFET Switch for Boost Converter (2010)

In this paper, a high voltage current sensing circuit for boost converter is designed and verified by Cadence SPECTRE simulations. The current mirror pair, power and sensing metal-oxide semiconductor field effect transistors (MOSFETs) with size ratio of K, is used in our on-chip current sensing circuit. Very low drain voltages of the current mirror pair should be matched to give accurate current sensing, so a folded-cascode opamp with a PMOS input pair is used in our design. A high voltage high side lateral-diffused MOS transistor (LDMOST) switch is used between the current sensing circuit and power MOSFET to protect the current sensing circuit from the high output voltage. Simulation results using 0.35 <TEX>${\mu}m$</TEX> BCD process show that current sensing is accurate and the pulse frequency modulation (PFM) boost converter using the proposed current sensing circuit satisfies with the specifications.
Cytokine pattern in cystic fibrosis patients during antibiotic therapy and gene therapy using adenoviral vector. (2003)

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite improvements in treatment, pulmonary disease still remains the primary cause of death among these patients. In order to introduce a normal CFTR gene copy into airway epithelial cells, adenoviral vectors (AV) have been developed. AV are known to induce an inflammatory reaction that limits transgene expression, and can be potentially harmful. No human study has clearly monitored simultaneously, systemic and local inflammatory reaction, during AV administration. We report here the levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) in plasma and bronchoalveolar lavage fluid (BALF) from six cystic fibrosis patients receiving AV encoding CFTR (AdCFTR). AdCFTR was administered to three cohorts of two patients into the nose on day 0, at doses ranging from 105 to 4 x 108 plaque-forming units (pfu), followed, on day 1, by aerosolization of 107 to 5.4 x 108 pfu. In order to ensure that patients were in the best clinical condition, and to further attenuate the broncho-pulmonary inflammation secondary to bacterial infection, they received antibiotic therapy, two weeks prior to AdCFTR administration, until 9 to 11 days after. We found that antibiotics markedly decreased CRP, TNF-alpha, IL-6, IL-1Ra levels in blood. In BALF, antibiotics slightly decreased TNF-alpha levels but had no effect on IL-8 and IL-1Ra, while IL-6 levels increased. AdCFTR administration did not induce any systemic or local cytokine release. In both blood and BALF, CRP, IL-8, IL-1Ra, TNF-alpha decreased, while IL-6 levels increased between day -7 and day 3. One patient presented an asymptomatic increase of all parameters in the BALF on day 7. Twenty one days later, he displayed a clinical deterioration suggestive of an exacerbation. In conclusion, this study demonstrates that antibiotic administration tends to attenuate systemic but not local broncho-pulmonary inflammation in CF patients. In the setting of our study, AdCFTR administration did not induce cytokine release. Further studies are necessary to investigate other inflammatory markers and the mechanisms involved during AV-mediated gene transfer for a better understanding of the immune reaction, which continues to hamper the development of gene therapy for CF patients.