gebhart/patrepeval huggingface dataset:
Oxidized Chondroitin Sulfate-Cross-Linked Gelatin Matrixes:  A New Class of Hydrogels (2005)

A naturally occurring glycosaminoglycan such as chondroitin-6-sulfate was first converted in to its aldehyde derivative by periodate oxidation and used as a cross-linking agent for gelatin giving rise to a new class of hydrogels. Cross-linking was predominantly due to Schiff's base formation between the epsilon-amino groups of lysine or hydroxylysine side groups of gelatin and the aldehyde groups in oxidized chondroitin sulfate. The hydrogels were prepared from chondroitin sulfate with different degrees of oxidation and gelatin. They were characterized for degree of cross-linking, cross-linking density, equilibrium swelling, water vapor transmission rate, internal structure, and blood-compatibility. Degree of cross-linking of the gels determined by trinitrobenzene sulfonic acid assay showed that, the higher the degree of oxidation of the polysaccharide, the higher the degree of cross-linking. Examination of the internal structure by scanning electron microscopy showed that the hydrogels were highly porous in nature with interconnecting pores ranging from 50 to 200 mum. Equilibrium swelling showed that the gels retained about 90% water and did not undergo dehydration rapidly. The hydrogels were nontoxic and blood-compatible. Since an important phase of early wound healing has been shown to involve secretion of glycosaminoglycans such as chondroitin sulfate by fibroblasts which form a hydrophilic matrix suitable for remodeling during healing, this new class of hydrogels prepared from chondroitin sulfate and gelatin without employing any extraneous cross-linking agents are expected to have potential as wound dressing materials.
Non-adiabatic holonomic quantum computation (2012)

We develop a non-adiabatic generalization of holonomic quantum computation in which high-speed universal quantum gates can be realized using non-Abelian geometric phases. We show how a set of non-adiabatic holonomic one- and two-qubit gates can be implemented by utilizing optical transitions in a generic three-level Λ configuration. Our scheme opens up the possibility of realizing universal holonomic quantum computation on qubits characterized by short coherence time.
Decorin Gene Delivery Inhibits Cardiac Fibrosis in Spontaneously Hypertensive Rats by Modulation of Transforming Growth Factor-β/Smad and p38 Mitogen-Activated Protein Kinase Signaling Pathways (2009)

Fibrosis is the response of heart and other organs to injuries. Excessive fibrosis can cause organ dysfunction or even failure. Transforming-growth factor (TGF)-beta is a cytokine that induces fibroblast proliferation and increases the synthesis of a number of extracellular matrix proteins including collagens. Decorin (DCN) is a natural antagonist of TGF-beta. In the current study, we investigated the potential antifibrotic effects of DCN gene delivery by a recombinant adeno-associated viral (rAAV) vector to inhibit cardiac fibrosis in old, spontaneously hypertensive rats (SHRs), which develop severe cardiac and kidney fibrosis if without intervention. The rAAV-DCN vector was injected (at a dose of 1 x 10(11) vector genomes) via the tail vein into 5-month-old male SHRs, resulting in persistent, stable expression of DCN (up to 16 weeks). rAAV-DCN treatment significantly reduced collagen content and fibrosis in the heart and attenuated cardiomyocyte hypertrophy. Hemodynamics data at 16 weeks showed that DCN gene delivery induced a significant increase in left ventricular end-systolic pressure and maximal-minimal rate of pressure increase (+/-dp/dt(max)), but a decrease in left ventricular end-diastolic pressure (p < 0.05), compared with those of control animals. The expression of TGF-beta and alpha-smooth muscle actin, and the phosphorylation levels of Smad2 and p38 MAPK, were markedly reduced by rAAV-DCN treatment as compared with the controls. Thus, these results suggest that rAAV-mediated DCN overexpression led to the inhibition of hypertension-induced cardiac fibrosis and hypertrophy and improved cardiac function, and therefore may have therapeutic potential for organ fibrosis.
Nano-Patterning for Patterned Media using Block-Copolymer. (2002)

Block-copolymers are known to generate nano-scale microdomains by microphase-separation, if they are annealed at a temperature lower than their order-disorder transition temperatures. We tried to transfer microdomains onto substrates by only using the reactive-ion etching method, which is widely used in semiconductor manufacturing processes.Block-copolymers consisting of an aromatic polymer and an acrylic polymer were used since there is a big difference in the dry-etch resistance, and nanometer-scale dot patterns can be easily obtained on the substrates.Regarding the application of this nano-patterning technique, we demonstrated the first circumferential magnetic patterned media for hard disk, which were prepared on a 2.5-inch diameter glass plate.
Differential effect of IFNalpha-2b on the cytochrome P450 enzyme system: a potential basis of IFN toxicity and its modulation by other drugs. (2002)

These data suggest that strategies to minimize the impairment of CYP enzymes could alter the toxicity profile of HDI and augment its therapeutic utility, and that recognition of these potential interactions is important in the therapeutic application of IFNs.
Development of Cell-Cycle Inhibitors for Cancer Therapy (2009)

The cell cycle governs the transition from quiescence through cell growth to proliferation. The key parts of the cell cycle machinery are the cyclin-dependent kinases (CDKS) and the regulatory proteins called cyclins. The CDKS are rational targets for cancer therapy because their expression in cancer cells is often aberrant and their inhibition can induce cell death. Inhibitors of CDKS can also block transcription.Several drugs targeting the cell cycle have entered clinical trials. These agents include flavopiridol, indisulam, AZD5438, SNS-032, bryostatin-1, seliciclib, PD 0332991, and SCH 727965. Phase i studies have demonstrated that these drugs can generally be administered safely. Phase ii studies have shown little single-agent activity in solid tumors, but combination studies with cytotoxic chemotherapy have been more promising. In hematologic malignancies, reports have shown encouraging single-agent and combination activity. Pharmacodynamic studies show that the dose and schedule of these drugs are crucial to permit maximum therapeutic effect.
Expression and structural analysis of a novel highly inducible gene encoding alpha 1-antitrypsin in rabbit. (1994)

alpha 1-Antitrypsin is a major plasma proteinase inhibitor whose primary function is to control the proteolytic activity of neutrophil elastase that hydrolyzes structural proteins. This protein, in rabbit is expressed as three isoforms designated as F, S-1, and S-2. An inducible form of this protein has been cloned from an acute-phase cDNA library of rabbit liver. Structural study has revealed that the cloned cDNA is the S-2 isoform previously identified by partial peptide sequence analysis. The amino acid sequence of the reactive center of the S-2 form is not conserved and thus can be categorized as of unorthodox type. mRNA analysis has indicated that the transcription of the S-2 isoform which is normally present at a very low concentration increases more than 100-fold under inflammatory conditions while the expression of the F and S-1 isoforms changes about 1.5-fold under similar conditions. The S-2 isoform is biologically active and capable of inhibiting both elastase and chymotrypsin. The high level of induction of this active isoform of alpha 1-antitrypsin under inflammatory conditions and its apparent resistance to oxidation-mediated inactivation, common to the orthodox forms of alpha 1-antitrypsin, make the S-2 isoform suitable for gene therapy in diseases associated with alpha 1-antitrypsin deficiency.
Class I MHC-peptide interactions: structural requirements and functional implications. (1995)

In this chapter, we have defined the structural motifs that dictate the capacity of peptides to bind to five different HLA-A alleles that represent some of the most common alleles found in different ethnic populations. In general, these peptide motifs were very specific for the individual HLA-A alleles, with the exception of HLA-A degree 0301 and HLA-A degree 1101, for which the motifs were very similar. When these motifs were tested against an unbiased and complete set of nonamer peptides derived from human papillomavirus E6 and E7 proteins, it was found that the vast majority of high and intermediate binding peptides contained the appropriate motif. Furthermore, using the dominant anchor residues, together with the amino acid positions that interact with secondary anchor residues, it was possible to predict high and intermediate binders. Finally, the finding that there is a direct correlation between binding affinity for MHC and immunogenicity suggests a practical application of being able to predict those peptides that have a high affinity binding for a particular MHC allele--that is, in the design of peptide based vaccines for prophylactic or therapeutic use.
The role of hypoxia in inflammatory disease (Review) (2015)

Mammals have developed evolutionarily conserved programs of transcriptional response to hypoxia and inflammation. These stimuli commonly occur together in vivo and there is significant crosstalk between the transcription factors that are classically understood to respond to either hypoxia or inflammation. This crosstalk can be used to modulate the overall response to environmental stress. Several common disease processes are characterised by aberrant transcriptional programs in response to environmental stress. In this review, we discuss the current understanding of the role of the hypoxia-responsive (hypoxia-inducible factor) and inflammatory (nuclear factor-κB) transcription factor families and their crosstalk in rheumatoid arthritis, inflammatory bowel disease and colorectal cancer, with relevance for future therapies for the management of these conditions.
Real-time eye gaze direction classification using convolutional neural network (2016)

Estimation eye gaze direction is useful in various human-computer interaction tasks. Knowledge of gaze direction can give valuable information regarding users point of attention. Certain patterns of eye movements known as eye accessing cues are reported to be related to the cognitive processes in the human brain. We propose a real-time framework for the classification of eye gaze direction and estimation of eye accessing cues. In the first stage, the algorithm detects faces using a modified version of the Viola-Jones algorithm. A rough eye region is obtained using geometric relations and facial landmarks. The eye region obtained is used in the subsequent stage to classify the eye gaze direction. A convolutional neural network is employed in this work for the classification of eye gaze direction. The proposed algorithm was tested on Eye Chimera database and found to outperform state of the art methods. The computational complexity of the algorithm is very less in the testing phase. The algorithm achieved an average frame rate of 24 fps in the desktop environment.
DNA Binding of AD-Lysine-Based Chiral PNA: Direction Control and Mismatch Recognition (2000)

Peptide nucleic acids (PNAs) are oligonucleotide analogues with a skeleton made up of N-(2-aminoethyl)glycine units; they bind to complementary DNA and RNA with high stability and specificity. In order to improve the binding specificity, solubility and uptake into cells, many modifications have been introduced, some concerning the introduction of stereogenic centres. With the aim of achieving a selective antiparallel binding with DNA, we report in this paper the synthesis and binding abilities of a chiral PNA decamer (H-GTAGATCACT-NH2) bearing three D-Lys-based monomers (a “chiral box”) in the middle of the strand. Indeed, the antiparallel PNA-DNA duplex showed a melting point of 43 °C (determined both by CD and UV spectroscopy), whereas the parallel PNA-DNA duplex failed to form, as shown by the absence of temperature dependence in the UV and CD spectra. Moreover, hybridization experiments carried out with antiparallel DNA strands bearing single mismatches showed that this PNA was excellent in discriminating between mismatched and matched targets. These results indicate that a high chiral constraint in the middle of a PNA sequence strongly affects the direction selectivity, i.e. the antiparallel/parallel preference in the DNA complexation. In particular, a “D-chiral box” favours a highly specific antiparallel DNA binding, thus allowing possible diagnostic applications for the screening of single-point mutations.
A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words. (2004)

The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.
Head Related Transfer Function Personalization Based on Multiple Regression Analysis (2006)

The synthesis of personalization virtual auditory space (VAS) is an important and challenging task in virtual reality. One of the key factors for personalization VAS is to obtain a set of proper head related transfer functions (HRTFs). In this paper, a customization method is presented by applying multiple linear regression analysis to HRTFs and some anthropometric parameters chosen by correlation analysis. Experiments show that the estimated HRTF has small mean square error, and has similar perception effect as the measured HRTF. Furthermore, the localization accuracy of personalized HRTF is increased compared to the non-individual HRTF
An adaptive acceleration structure for screen-space ray tracing (2015)

We propose an efficient acceleration structure for real-time screen-space ray tracing. The hybrid data structure represents the scene geometry by combining a bounding volume hierarchy with local planar approximations. This enables fast empty space skipping while tracing and yields exact intersection points for the planar approximation. In combination with an occlusion-aware ray traversal our algorithm is capable to quickly trace even multiple depth layers. Compared to prior work, our technique improves the accuracy of the results, is more general, and allows for advanced image transformations, as all pixels can cast rays to arbitrary directions. We demonstrate real-time performance for several applications, including depth-of-field rendering, stereo warping, and screen-space ray traced reflections.
Liver dysfunction in sepsis (2018)

Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1.5. The lack of specificity and ability to distinguish acute liver failure from previous liver dysfunction disqualifies bilirubin as a single parameter reflecting the complex liver function. Clinical manifestations of sepsis-associated liver dysfunction include hypoxic hepatitis, sepsis-induced cholestasis and dysfunction of protein synthesis manifesting with, e.g., coagulopathies. Detoxifying liver dysfunction, which is associated with an increase in serum ammonia concentration, manifesting with e.g., confusion, loss of consciousness and hepatic encephalopathy, may be disguised by analgosedation used in the intensive care unit. To determine a liver dysfunction in a critically ill patient, the concept of shock liver may be used. It is a complex syndrome of hemodynamic, cellular, molecular and immunologic changes leading to severe liver hypoxia. In clinical practice, there is no standardized diagnostic panel that would allow for an early, clear diagnosis of acute liver dysfunction, and there is no therapeutic panel enabling the full restoration of damaged liver function. The aim of the article is to present the pathophysiology and clinical manifestations of sepsis-associated liver dysfunction.
A novel integrated optical dissolved oxygen sensor for cell culture and micro total analysis systems (2003)

Production of accurate microscale oxygen sensors has been conventionally attempted using amperometric methods, which prove to be difficult to miniaturize, mainly due to the requirement of a bulky reference electrode. This paper details the design and fabrication process for an optically based oxygen sensor using an oxygen-sensitive fluorescent dye combined with microfabricated Cytop/spl trade/ waveguides that are monolithically integrated into the sensing substrate. Application of the dye to the optical waveguides was accomplished using a unique electrostatic layer-by-layer deposition process that has allowed us to deposit ultrathin dye layers to specific areas of the substrate. Testing of the oxygen sensitivity of the immobilized dye was carried out.
Reaction Pathway and Free Energy Profile for Prechemical Reaction Step of Human Butyrylcholinesterase-Catalyzed Hydrolysis of (−)-Cocaine by Combined Targeted Molecular Dynamics and Potential of Mean Force Simulations (2010)

Combined targeted molecular dynamics (TMD) and potential of mean force (PMF) simulations have been carried out to uncover the detailed pathway and determine the corresponding free energy profile for the structural transformation from the nonprereactive butyrylcholinesterase (BChE)-(-)-cocaine binding to the prereactive BChE-(-)-cocaine binding associated with the (-)-cocaine rotation in the binding pocket of BChE. It has been shown that the structural transformation involves two transition states (TS1(rot) and TS2(rot)). TS1(rot) is mainly associated with the deformation of the nonprereactive complex, whereas TS2(rot) is mainly associated with the formation of the prereactive complex. It has also been demonstrated that the A328W/Y332G mutation significantly reduces the steric hindrance for (-)-cocaine rotation in the binding pocket of BChE and, thus, decreases the free energy barrier for the structural transformation from the nonprereactive binding to the prereactive binding. The calculated relative free energy barriers are all consistent with available experimental kinetic data. The new mechanistic insights obtained and the novel computational protocol tested in this study should be valuable for future computational design of high-activity mutants of BChE. The general computational strategy and approach based on the combined TMD and PMF simulations may be also valuable in computational studies of detailed pathways and free energy profiles for other similar mechanistic problems involving ligand rotation or another type of structural transformation in the binding pocket of a protein.
Human autoreactive and foreign antigen-specific T cells resist apoptosis induced by soluble recombinant CD95 ligand (1997)

Mature T cells are susceptible to activation-induced cell death in the periphery. Activation-induced cell death is thought to involve CD95/CD95 ligand interactions in vivo. Here we report that stimulated, CD45RO+ human T cell lines specific for myelin basic protein or tetanus toxoid from multiple sclerosis patients and healthy individuals resist apoptosis induced by soluble recombinant CD95 ligand in vitro. In contrast, the same CD95 ligand effectively kills Jurkat T lymphoma and human malignant glioma cells. The resistance of the T cell lines is not due to a lack of CD95 expression at the cell surface and is not overcome by coexposure to CD95 ligand and inhibitors of RNA or protein synthesis. The expression level of BCL-2 is lower in Jurkat than in Ag-specific T cells. After exposure to soluble CD95 ligand, Jurkat T cells, but not Ag-specific T cells, exhibit loss of BCL-2 and BCL-X expression whereas BAX expression is not affected. Surprisingly, Ag-specific T cells are rather sensitive to CD95 ligand expressed at the cell surface of N2A neuroblastoma cells. Accessory molecules expressed by the CD95 ligand-expressing effector cell are dispensable for apoptosis since the T cells are equally sensitive to agonistic APO-1 Ab. Further studies are required to determine whether resistance to soluble CD95 ligand-mediated apoptosis is a possible escape mechanism for T cells from peripheral deletion that may have relevance for autoimmune disorders.
Neonatal meningitis. A clinical and pathological study of 29 cases. (1966)

The case histories of 29 infants in whom purulent meningitis developed during the first month of life were reviewed. There was a high incidence of maternal perinatal infections, and identical organisms were frequently isolated from both the mother and offspring. Gram-negative intestinal organisms were the most frequent etiologic agents. Because signs suggesting meningeal and nervous system involvement developed only late in the course of the illness, the diagnosis was frequently not made until the spinal fluid was examined. The course of the illness was usually fulminant; death occurred within 4 days from the onset of symptoms in the majority of infants. Of the five infants who recovered from the meningitis, four died from neurologic complications within a few months. Postmortem examinations were performed on 25 infants. Although the inflammatory reaction was essentially limited to the spinal fluid pathways and their contents, a wide-spread, at times devastating, non-infectious encephalopathy occurred in every case. Our observations emphasize the paucity and subtlety of the clinical manifestations of meningitis in the neonate and the remarkably high mortality that seems to be little influenced by standard methods of therapy. The pathological features of a meningitis in the newborn are similar to those in the more mature individuals, except for the sparsity of lymphocytes in the subacute stage of the meningeal reaction, the prominence of bacteria in the meningeal exudate long after appropriate antibiotics have been employed, and the high frequency of sequelae in the survivors. The sparsity and delay in appearance of lymphocytes and plasma cells in the inflammatory response may be an important factor in the inadequate defense of the newborn to this infection.