gebhart/patrepeval huggingface dataset:
Fiber-reinforced hydrogel scaffolds for heart valve tissue engineering (2014)

Heart valve-related disorders are among the major causes of death worldwide. Although prosthetic valves are widely used to treat this pathology, current prosthetic grafts cannot grow with the patient while maintaining normal valve mechanical and hemodynamic properties. Tissue engineering may provide a possible solution to this issue through using biodegradable scaffolds and patients' own cells. Despite their similarity to heart valve tissue, most hydrogel scaffolds are not mechanically suitable for the dynamic stresses of the heart valve microenvironment. In this study, we integrated electrospun poly(glycerol sebacate) (PGS)-poly(ɛ-caprolactone) (PCL) microfiber scaffolds, which possess enhanced mechanical properties for heart valve engineering, within a hybrid hydrogel made from methacrylated hyaluronic acid and methacrylated gelatin. Sheep mitral valvular interstitial cells were encapsulated in the hydrogel and evaluated in hydrogel-only, PGS-PCL scaffold-only, and composite scaffold conditions. Although the cellular viability and metabolic activity were similar among all scaffold types, the presence of the hydrogel improved the three-dimensional distribution of mitral valvular interstitial cells. As seen by similar values in both the Young's modulus and the ultimate tensile strength between the PGS-PCL scaffolds and the composites, microfibrous scaffolds preserved their mechanical properties in the presence of the hydrogels. Compared to electrospun or hydrogel scaffolds alone, this combined system may provide a more suitable three-dimensional structure for generating scaffolds for heart valve tissue engineering.
Novel Cosuspension Metered-Dose Inhalers for the Combination Therapy of Chronic Obstructive Pulmonary Disease and Asthma (2011)

Pressurized metered dose inhaler is the most common inhaled dosage form, ideally suited for delivering the highly potent compounds that medicinal chemists typically discover for respiratory therapeutic targets. The clinical benefit of combination therapy for asthma and chronic obstructive pulmonary disease has been well established, and many of the new discovery candidates are likely to be studied in the clinic as combination drugs even at early stages of development. We present a novel pressurized metered dose inhaler formulation approach to enable consistent aerosol performance of a respiratory therapeutic whether it is emitted from a single-, double- or triple-therapy product. This should enable rapid nonclinical and clinical assessment whether alone or in combination with other drugs, without the challenge of in vitro performance dissimilarity across product types.
Fostering collaboration in systems of systems (2002)

Human society is fundamentally a hierarchical set of nested systems with systems. With the exception of the viewpoint of proponents of socio-technical systems, our view of technological systems has tended to treat each system in isolation. The growth of local and wide area networking, and especially the ease of digital communications brought about by the Internet, has allowed many of our technological systems to become more closely integrated than before. The prospects of broad and effective collaboration and cooperation within these large aggregates of distributed systems promises to lower the cost of ownership and increase the effectiveness of the linked systems. This view has come to be called the System of Systems (SoS) view, and has been embraced by numerous data-intensive operational communities, including defense command and control, law enforcement, health care and financial institutions. This paper describes aspects of the Air Traffic Management Partnership, a development effort led by Lockheed Martin with the participation of Applied Systems Intelligence, Inc. and others to define the foundational elements of a distributed collaborative air traffic management system. Particular attention is focused in this paper on the nature of the interactions required to foster collaboration and cooperation within the bounded real-time communications and safety environment of air traffic management.
Robot‐Assisted Stapedotomy: Micropick Fenestration of the Stapes Footplate (2002)

These are the first results showing quantitative improvements in performance during simulated ear surgery using RA and differential effects of RA on performance for users of different experience levels.
Naphthalene, an insect repellent, is produced by Muscodor vitigenus, a novel endophytic fungus (2002)

Muscodor vitigenus is a recently described endophytic fungus of Paullinia paullinioides, a liana growing in the understorey of the rainforests of the Peruvian Amazon. This fungus produces naphthalene under certain cultural conditions. Naphthalene produced by M. vitigenus was identified by gas chromatography/mass spectrometry. Its chromatographic and mass spectral properties were identical to authentic naphthalene. Agar plugs supporting growth of the fungus and producing known amounts of naphthalene effectively repelled the adult stage of the wheat stem sawfly, Cephus cinctus, in Y-tube bioassay tests. Authentic naphthalene, at comparable concentrations to those in tests involving the fungus itself, mimicked the insect repellency of the fungus. Although other Muscodor spp. produce volatile antimicrobials, M. vitigenus is unique in its ability to produce naphthalene almost exclusively. This report also describes the potential practical implications of M. vitigenus.
Identification by mass spectrometry of threonine 97 in bovine myelin basic protein as a specific phosphorylation site for mitogen-activated protein kinase. (1990)

Bovine myelin basic protein (MBP) was found to be an excellent in vitro substrate (apparent Km = 50 microM) for MAP (mitogen-activated protein) kinase and can be used in lieu of microtubule-associated protein 2 for purification and functional studies of the enzyme. MBP phosphotransferase activity co-purified with MAP kinase during sequential DE52, phenyl-Superose, and gel filtration chromatography, and kinase activities for the two substrates were co-regulated by mitogen stimulation. MAP kinase phosphorylated MBP exclusively on threonine, and only one major phosphopeptide was generated by digestion with trypsin or endoproteinase Lys-C. Using mass spectrometry, we determined that the phosphorylation site is threonine 97, present in the conserved triproline loop of MBP, with (partial) sequence -Thr-Pro-Arg-Thr97-Pro-Pro-Pro-. Thr97 is a known in vivo phosphorylation site in MBP although enzymes capable of phosphorylating this site have not been identified previously. MAP kinase phosphorylated peptide 88-109 from rabbit MBP and a synthetic peptide 91-109 from human MBP but did not phosphorylate either the histone H1 peptide, utilized by p34cdc2, or the peptide substrate for the recently described proline-directed kinase. Thus, the sequence surrounding threonine 97 in bovine MBP may contain essential features of a recognition sequence for MAP kinase.
Combined Parenteral and Enteral Nutrition in Severe Trauma (1992)

Early enteral feeding is increasingly advocated for the nutrition support of severely stressed patients. The successful use of this modality in critical illness is often limited by the patient's condition, the availability of access for feeding, and the patient's tolerance of the enteral formula. Factors such as abdominal injury or constraints on fluid volume also complicate nutrition support in this setting. Attention to a secure and well-maintained small bowel access tube and appropriate formula selection allow safe tube feeding in these patients. This case report describes the clinical course of a patient with severe chest and abdominal trauma who received enteral nutrition despite a large, open abdominal wound.
Absence of insulinotropic glucagon‐like peptide‐I(7–37) receptors on isolated rat liver hepatocytes (1991)

The effects of glucagon and the glucagon-like peptide GLP-1(7-37) were compared in rat liver hepatocytes. Glucagon elevated cAMP, elevated intracellular free calcium ([Ca2+]i), activated phosphorylase and stimulated gluconeogenesis, whereas GLP-1(7-37) was without effect on any of these parameters. GLP-1(7-37) did not block any of the actions of glucagon. The glucagon analog, des His1[Glu9] glucagon amide, was a partial agonist in liver, but also was an effective antagonist of glucagon actions in liver but not those of GLP-1(7-37) in islet B cells. It was concluded that in the rat, GLP-1(7-37) is a potent insulin secretagogue [1] but is without effect on liver.
A new immunobiological view of radiation-promoted lymphomagenesis (1997)

Whole-body irradiation produces T-cell leukaemias/ lymphomas (TCL) in some strains of inbred mice in an X-ray dose-related manner. Radiation biologists have related the rapid "initiation' and early appearance of preleukaemic cells in these mice to unrepaired DNA damage inflicted by radiation. Following initiation, radiation-altered thymic differentiation fosters multi-step transformation changes in proto-oncogenes and suppressor gene expression in individual clones of non-invasive preleukaemia cells as they progress to malignancy. The malignant clones arising from small numbers of initiated preleukaemia thymocytes become fully transformed only after several more months to a year after irradiation in those strains of mice which develop T-cell lymphomas. When the RFM mouse was subjected to sublethal whole-body X-ray, only 50% of the mice developed TCL by 6 months, yet nearly all developed preleukaemia thymocytes. The T-cell-mediated immune response of the irradiated host has never been substantiated to contribute to malignant TCL development. Until recently, X-ray-induced TCL were not known to carry common tumour rejection antigens TATA. However, several studies have revealed that both preleukaemia cells and fully malignant TCL express an immunogenic, common oncofoetal glycoprotein, termed 44kD OFA. OFA-activated memory CD4 Tm and CD8 Ten. T-effector cells in irradiated mice expressing OFA. As most irradiated RFM mice exhibit preleukaemia thymocytes yet only half develop tumours, this finding implicates active host T-cell effector responses in X-ray-initiated tumorigenesis. Further, the recent discovery of OFA-specific CD8 Ts clones in irradiated mice, which inhibited cytotoxicity of CD8 clones to OFA or TSTA, may explain which mice develop T-cell lymphomas.
New Pathologic Classification of Lung Cancer: Relevance for Clinical Practice and Clinical Trials (2013)

We summarize significant changes in pathologic classification of lung cancer resulting from the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. The classification was developed by an international core panel of experts representing IASLC, ATS, and ERS with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. Because 70% of patients with lung cancer present with advanced stages, a new approach to small biopsies and cytology with specific terminology and criteria focused on the need for distinguishing squamous cell carcinoma from adenocarcinoma and on molecular testing for EGFR mutations and ALK rearrangement. Tumors previously classified as non-small-cell carcinoma, not otherwise specified, because of the lack of clear squamous or adenocarcinoma morphology should be classified further by using a limited immunohistochemical workup to preserve tissue for molecular testing. The terms "bronchioloalveolar carcinoma" and "mixed subtype adenocarcinoma" have been discontinued. For resected adenocarcinomas, new concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma define patients who, if they undergo complete resection, will have 100% disease-free survival. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic, acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype with poor prognosis. Former mucinous bronchioloalveolar carcinomas are now called "invasive mucinous adenocarcinoma." Because the lung cancer field is now rapidly evolving with new advances occurring on a frequent basis, particularly in the molecular arena, this classification provides a much needed standard for pathologic diagnosis not only for patient care but also for clinical trials and TNM classification.
A deblocking filter with two separate modes in block-based video coding (1999)

This paper presents a method to remove blocking artifacts in low bit-rate block-based video coding. The proposed algorithm has two separate filtering modes, which are selected by pixel behavior around the block boundary. In each mode, proper one-dimensional filtering operations are performed across the block boundary along the horizontal and vertical directions, respectively. In the first mode, corresponding to flat regions, a strong filter is applied inside the block as well as on the block boundary because the flat regions are more sensitive to the human visual system (HVS) and the artifacts propagated from the previous frame due to motion compensation are distributed inside the block. In the second mode, corresponding to other regions, a sophisticated smoothing filter which is based on the frequency information around block boundaries, is used to reduce blocking artifacts adaptively without introducing undesired blur. Even though the proposed deblocking filter is quite simple, it improves both subjective and objective image quality for various image features.
Frequency-varying sinusoidal modeling of speech (1989)

A sinusoidal model is presented where the nonstationary nature of speech is considered by using a time-varying frequency and amplitude for each sinusoid. The proposed model generalizes other sinusoidal models while still having an analytically tractable short-time spectrum. The estimation of the parameters of the sinusoids is done in the frequency domain by a suboptimal linear estimator. The experimental results obtained with the proposed model illustrate its ability to represent nonstationary speech frames.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
PCR Site-Directed Mutagenesis Using Pyrococcus sp GB-D Polymerase Coupled to a Rapid Screening Procedure: Application to a β-Glucanase Gene (2003)

PCR methodology is one of the fastest available procedures for site-directed mutagenesis (1,2). However, it has been criticized for a lack of reliability because of unwanted mismatches produced during the PCR reaction (3,4). In the present protocol, we describe an improvement on the efficiency of site-directed mutagenesis by PCR using the Pyrococcus species GB-D polymerase instead of the commonly used Thermus aquatiqus (Taq) polymerase. Taq polymerase lacks a 3′→5′ proofreading exonuclease activity that is not crucial for several PCR applications, but is advisable for site-directed mutagenesis experiments. Some thermophilic DNA polymerases have this activity, among them the Thermococcus litoralis and the Pyrococcus species GB-D enzymes. A 10-fold higher efficiency has been reported for these enzymes over that observed for Taq polymerase (5). PCR site-directed mutagenesis is specially suitable for protein engineers when it is coupled to a screening procedure directly performed on the transformant plates. In such cases the procedure is rapid (3 d from mutagenic primers to selection of clones) and efficient (98–100% of successful mutagenesis).
The meaning and management of yield in hotels (1995)

Definitions of yield management vary in terms of their content and focus. Develops a “best fit” definition of yield management of the hotel sector by reviewing the literature in this area and extracting the key words and central meanings used. In addition, produces a list of eight features using a comparison and analysis of the views of London‐based front office managers and features of yield management applications promoted through vendors′ sales literature. Together these eight features illustrate what an ideal yield management application would offer. While all of the applications currently for sale within the UK offer some of these features, none of them are capable of performing the complete range.
Plasma levels of interleukin-1 receptor antagonist (IL-1ra) and severity of illness in patients with burns. (1996)

The present study was conducted to determine whether a plasma interleukin-1 receptor antagonist (IL-1ra) would reflect the severity of burn injury and to examine the relation between IL-1ra and the cytokines. We studied 24 burn patients in whom the total burn surface area (TBSA) accounted for at least 20% of the body surface, and in whom serial blood samples could be obtained beginning immediately after the burn injury. Plasma levels of IL-1ra were determined by enzyme-linked immunosorbent assay (ELISA). Plasma levels of tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 were also determined by ELISA. Endotoxin was measured by an endotoxin-specific synthetic substrate method. There was a significant correlation between the plasma levels of IL-1ra and TBSA during the first week following burn injury. The IL-1ra level was the highest immediately after the burn injury. The level decreased markedly thereafter, and again rose when infection occurred. The IL-1ra level was extraordinarily elevated in patients who developed concomitant sepsis, septic shock or the septic multiple organ dysfunction syndrome. The IL-1ra level on admission and the maximum IL-1ra level during the observation period were significantly higher in the patients who eventually died than in the survivors. There was a significant correlation between the level of IL-1ra and that of TNF-alpha, IL-6 or IL-8 during the observation period. No correlation was found between IL-1ra and endotoxin. The plasma IL-1ra level was closely correlated with the severity of inflammation and the clinical status of the burn patients, regardless of the infection. Results suggest that IL-1ra can serve as an index of the systemic inflammatory response syndrome (SIRS).
Wavelength beam combining of mid-IR semiconductor lasers (2002)

Semiconductor lasers operating in the mid-infrared between /spl lambda//spl sim/3-5 /spl mu/m are of interest for a variety of commercial and military applications. Some applications, such as infrared countermeasures, require multiwatt-class beams with near-diffraction-limited beam quality. Achieving such a high brightness beam from a single semiconductor laser has proven to be challenging at any wavelength. To achieve this goal, we are pursuing the approach of wavelength beam combining (WBC) to scale the brightness of a single laser element, which has relatively low power, by the number of elements in an array. With WBC, the beam quality of the combined beam is close to that of a single element while the power is that of the array. This is achieved by superimposing the beams from individual elements of a laser array, each operating at a different wavelength, both in the near field and far field by means of a dispersive element such as a diffraction grating. We describe the application of WBC to an array of /spl lambda//spl sim/4 /spl mu/m, broad-area, optically-pumped semiconductor lasers.
Glu496 to Ala Polymorphism in the P2X7 Receptor Impairs ATP-Induced IL-1β Release from Human Monocytes (2004)

Priming of monocytes with LPS produces large quantities of intracellular, biologically inactive IL-1beta that can be processed and released by subsequent activation of the P2X7 receptor by extracellular ATP. We examined whether a loss-of-function polymorphism of the human P2X7 receptor (Glu496Ala) impairs this process. Both ATP-induced ethidium+ uptake and ATP-induced shedding of L-selectin (CD62L) were nearly absent in monocytes from four subjects homozygous for Glu496Ala confirming that this polymorphism impairs P2X7 function. The level of ATP-induced IL-1beta released in 2 h from LPS-activated whole blood from homozygous subjects was 50% of that from wild-type samples. A more marked defect in IL-1beta release was observed from LPS-activated monocytes of homozygous subjects which was only 22% of that released from wild-type monocytes after a 30-min incubation with ATP. However, after a 60-min incubation with ATP, the amount of IL-1beta released from homozygous monocytes was 70% of that released from wild-type monocytes. Incubation of monocytes of either genotype with nigericin resulted in a similar release of IL-1beta. Western blotting demonstrated that ATP induced the release of mature 17-kDa IL-1beta from monocytes, and confirmed that this process was impaired in homozygous monocytes. Finally, ATP-induced 86Rb+ efflux was 9-fold lower from homozygous monocytes than from wild-type monocytes. The results indicate that ATP-induced release of IL-1beta is slower in monocytes from subjects homozygous for the Glu496Ala polymorphism in the P2X7 receptor and that this reduced rate of IL-1beta release is associated with a lower ATP-induced K+ efflux.
Internal ribosome entry site-mediated translation of Smad5 in vivo: requirement for a nuclear event (2002)

Smad5 is thought to relay signals of the bone morphogenetic protein pathway. The 5' untranslated region (5'UTR) of human Smad5 mRNA is long, has the potential to form secondary structures and contains five AUG codons. Here we show that the 5'UTR of Smad5 contains an internal ribosome entry site (IRES) located within 100 nt of the 3' end of the 5'UTR. The Smad5 IRES was 4-8-fold more active than the poliovirus IRES in C2C12 cells, which have osteoblastic differentiation ability, but was 5-10-fold less active than the poliovirus IRES in 293T cells. When an in vitro transcript of a dicistronic Smad5 IRES construct was transfected into C2C12 cells, the Smad5 IRES was not able to stimulate the translation of the downstream cistron, although the cap-dependent translation of the upstream cistron was efficient. In contrast, the poliovirus IRES in a dicistronic in vitro transcript was able to stimulate the translation of the downstream cistron to a similar extent as in the case of transfection of the corresponding dicistronic DNA construct. These results suggest that Smad5 IRES activity displays cell specificity and that some as yet unidentified nuclear event may be required for efficient Smad5 IRES-driven translation initiation.
The Dietary Treatment of Phenylketonuria (1958)

It was Dr. Bickel who undertook the laborious task of preparing the charcoal-treated casein hydrolysate, now commercially available, and who courageously first gave it to a phenylketonuric patient.
Chemical kinetics: The study of reaction rates in solution (1990)

Introduction to chemical kinetics simple rate equations complicated rete equations fast reactions theory of chemical kinetics phenomena for study structure-reactivity relationships medium effects appendices.
Mechanism of alteration of poly(adenosine diphosphate-ribose) metabolism by hyperthermia. (1988)

The effects of hyperthermia on adenine nucleotide metabolism including NAD and poly(ADP-ribose) have been studied in confluent cultures of C3H10T1/2 cells. Cells replated immediately following hyperthermic treatment showed only 9% survival relative to controls while after a 24-h recovery period at 37 degrees C survival was 87% of control. Hyperthermic treatment caused no detectable effect on total cellular levels of either NAD or ATP but produced a prolonged increase in cellular content of poly(ADP-ribose). Studies of the mechanism of this effect show that a major alteration of poly(ADP-ribose) metabolism caused by hyperthermia involves a decrease in the rate of turnover of polymers of ADP-ribose. Normal polymer turnover rates were restored during recovery at 37 degrees C even in the presence of cyclohexamide. The results argue that poly(ADP-ribose) glycohydrolase activity is reversibly altered by hyperthermia. Inhibition of poly(ADP-ribose) synthesis following hyperthermia delays recovery of normal rates of protein synthesis and recovery of the ability of the cells to plate and form colonies.