gebhart/patrepeval huggingface dataset:
Repeatability and reproducibility of corneal thickness measurements by optical coherence tomography. (2002)

Although the commercially available OCT scanner was designed for retinal imaging, with a few minor modifications, the system may be used to image the anterior segment. Previous studies have shown that OCT measurements correlate well with those from conventional techniques, and it has the added advantage of being a noncontact technique. This study further demonstrates that the OCT measurements show a high degree of repeatability and reproducibility. Thus, OCT is emerging as a promising tool for evaluation of CCT in the clinical setting.
A high output mode for submicron M-R memory cells (1992)

A mode which substantially increases the nondestructive read output from submicron magnetoresistive (MR) memory elements has been demonstrated. This mode increases the output for large cells by 50% and the outputs of cells less than a micron wide by 150% to 300%. In this mode, information is stored in the direction of the edge magnetization, and the body of the element serves as a sensor. Outputs of +or-1.2 mV were obtained with cells with an active area of 0.7*3.0 microns. By appropriate use of a step in the field oxide and a word line keeper, the demagnetizing field in the long dimensions of a memory element can be tailored to one desired value to optimize the response characteristics. The mode requires an additional drive strap to write the edge magnetization by coincident selection. For memory application the threshold for switching the edge magnetization must be tightly controlled.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Complete genome sequence of an M1 strain of Streptococcus pyogenes (2001)

The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately one-third of these genes have no identifiable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety of human disease than any other bacterial species, more than 40 putative virulence-associated genes have been identified. Additional genes have been identified that encode proteins likely associated with microbial "molecular mimicry" of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is also present, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential.
Backup reprovisioning to remedy the effect of multiple link failures in WDM mesh networks (2006)

As networks grow in size and complexity, both the probability and the impact of failures increase. The pre-allocated backup bandwidth, which has been widely investigated in the literature, may not be able to provide full protection guarantee when multiple failures occur in a network. In this study, we consider multiple concurrent failures where concurrent means that a new failure occurs before a previous failure is repaired. To combat the effect of multiple concurrent failures, new backups can be reprovisioned after one failure such that the next potential failure can be handled effectively and efficiently. We consider dynamic traffic where a pair of link-disjoint primary and backup paths is provisioned when a new connection request arrives. After a failure occurs, the affected connections switch traffic from their primary paths to backup paths. To protect against next potential failure, we reprovision new backups for connections that become unprotected or vulnerable because of losing their primary or their backup due to the previous failure or due to backup resource sharing. This approach is called Minimal Backup Reprovisioning (MBR). An alternative approach is to globally rearrange backups for all connections after one failure occurs, which is called Global Backup Reprovisioning (GBR). Backup reprovisioning can be performed whenever the network's state changes, e.g., (1) when a new request arrives, (2) when an existing connection terminates, (3) when a network failure occurs, (4) when a failed link/node is repaired, etc., to utilize the available resources more efficiently or to recover quickly from the next failure. In this study, we perform MBR or GBR after one network failure occurs to protect against the next potential failure in a wavelength-convertible WDM mesh network. The link-vector network model which can maximally explore the backup-sharing potential is assumed in this study. We then analyze the complexity of MBR and GBR under such a network model. A reprovisioning algorithm is proposed for MBR which can significantly reduce the connection vulnerability without the knowledge of the location of the next failure. In GBR, both integer linear program (ILP) and heuristic-based approaches are proposed. We compare capacity requirement and computational complexity of MBR to that of GBR through numerical examples. MBR demonstrates a good tradeoff between complexity and capacity efficiency to handle multiple concurrent failures
Microfluidic Immunoassay for Bacterial Toxins with Supported Phospholipid Bilayer Membranes on Poly(dimethylsiloxane) (2004)

We report a heterogeneous immunoassay for cholera toxin (CT) using supported bilayer membranes (SBMs) in a poly(dimethylsiloxane) (PDMS) microfluidic device. Phosphatidylcholine membranes assembled on plasma-oxidized PDMS by vesicle fusion bring about favorable surface properties, such as improved wettability and protein resistance. Contact angle measurements show that the lipid membranes can preserve hydrophilic surfaces for hours, whereas untreated substrates rapidly undergo hydrophobic recovery. Fluorescence recovery after photobleaching performed in situ reveals that the membranes have relatively high lateral mobility. Experimental data-fitting to theoretical models yields diffusion coefficients of 1.8 +/- 0.7 microm(2)/s on PDMS and 3.4 +/- 0.8 microm(2)/s on glass. Fluorescence studies utilizing tagged proteins show that SBMs reduce nonspecific adsorption of avidin and BSA on PDMS by 2-3 orders of magnitude, as compared to that on plasma oxidized surfaces. SBMs and their protein-resistant properties are not significantly affected by long flow times, indicating good membrane stability. These studies increase our understanding of the relationship between molecular level interactions and membrane properties, allowing for development of a rapid heterogeneous immunoassay for CT in PDMS microchips with cell surface receptor molecules. Using optimized sample injection and buffer washing conditions, microfluidic immunoassay of CT is complete within 25 min, and a dynamic range over 3 orders of magnitude with a detection limit of 8 fmol of toxin is achieved.
Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers (2001)

Exendin-4 is a long-acting potent agonist of the glucagon-like peptide 1 (GLP-1) receptor and may be useful in the treatment of type 2 diabetes and obesity. We examined the effects of an intravenous infusion of exendin-4 (0.05 pmol. kg(-1). min(-1)) compared with a control saline infusion in healthy volunteers. Exendin-4 reduced fasting plasma glucose levels and reduced the peak change of postprandial glucose from baseline (exendin-4, 1.5 +/- 0.3 vs. saline, 2.2 +/- 0.3 mmol/l, P < 0.05). Gastric emptying was delayed, as measured by the paracetamol absorption method. Volunteers consumed 19% fewer calories at a free-choice buffet lunch with exendin-4 (exendin-4, 867 +/- 79 vs. saline 1,075 +/- 93 kcal, P = 0.012), without reported side effects. Thus our results are in accord with the possibility that exendin-4 may be a potential treatment for type 2 diabetes, particularly for obese patients, because it acts to reduce plasma glucose at least partly by a delay in gastric emptying, as well as by reducing calorie intake.
Crystal Structure of Phenylalanine Ammonia Lyase:  Multiple Helix Dipoles Implicated in Catalysis, (2004)

The first three-dimensional structure of phenylalanine ammonia lyase (PAL) has been determined at 2.1 A resolution for PAL from Rhodosporidium toruloides. The enzyme is structurally similar to the mechanistically related histidine ammonia lyase (HAL), with PAL having an additional approximately 160 residues extending from the common fold. We propose that catalysis (including lowering the pK(a) of nonacidic C3 of l-phenylalanine for an E1cb mechanism) is potentially governed by dipole moments of seven alpha helices associated with the PAL active site (six positive poles and one negative pole). Cofactor 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) resides atop the positive poles of three helices, for increasing its electrophilicity. The helix dipoles appear fully compatible with a model of phenylalanine docked in the active site of PAL having the first covalent bond formed between the amino group of substrate and the methylidene group of MIO: 12 highly conserved residues (near the N termini of helices for enhancing function) are poised to serve roles in substrate recognition, MIO activation, product separation, proton donation, or polarizing electrons from the phenyl ring of substrate for activation of C3; and a highly conserved His residue (near the C terminus of the one helix that directs its negative pole toward the active site to increase the residue's basicity) is positioned to act as a general base, abstracting the pro-S hydrogen from C3 of substrate. A similar mechanism is proposed for HAL, which has a similar disposition of seven alpha helices and similar active-site residues. The helix dipoles appear incompatible with a proposed mechanism that invokes a carbocation intermediate.
Effects of Daily Iron Supplementation in 2- to 5-Year-Old Children: Systematic Review and Meta-analysis (2013)

In 2 to 5 year olds, daily iron supplementation increases hemoglobin and ferritin. There is a concerning lack of data on the effect of iron supplementation on clinically important outcomes including anemia, ID anemia, ID, and cognitive development. Additional interventional studies in this age group are needed.
Long-term Idiotype Vaccination Combined with Interleukin-12 (IL-12), or IL-12 and Granulocyte Macrophage Colony-Stimulating Factor, in Early-Stage Multiple Myeloma Patients (2007)

These results indicate that idiotype immunization of myeloma patients with GM-CSF and IL-12 may induce specific T-cell response more frequently than with IL-12 alone and that immune response may correlate with time to progression and nonresponse with increased numbers of regulatory T cells.
The Identification of a Succinyl-CoA Thioesterase Suggests a Novel Pathway for Succinate Production in Peroxisomes (2005)

Dicarboxylic acids are formed by omega-oxidation of fatty acids in the endoplasmic reticulum and degraded as the CoA ester via beta-oxidation in peroxisomes. Both synthesis and degradation of dicarboxylic acids occur mainly in kidney and liver, and the chain-shortened dicarboxylic acids are excreted in the urine as the free acids, implying that acyl-CoA thioesterases (ACOTs), which hydrolyze CoA esters to the free acid and CoASH, are needed for the release of the free acids. Recent studies show that peroxisomes contain several acyl-CoA thioesterases with different functions. We have now expressed a peroxisomal acyl-CoA thioesterase with a previously unknown function, ACOT4, which we show is active on dicarboxylyl-CoA esters. We also expressed ACOT8, another peroxisomal acyl-CoA thioesterase that was previously shown to hydrolyze a large variety of CoA esters. Acot4 and Acot8 are both strongly expressed in kidney and liver and are also target genes for the peroxisome proliferator-activated receptor alpha. Enzyme activity measurements with expressed ACOT4 and ACOT8 show that both enzymes hydrolyze CoA esters of dicarboxylic acids with high activity but with strikingly different specificities. Whereas ACOT4 mainly hydrolyzes succinyl-CoA, ACOT8 preferentially hydrolyzes longer dicarboxylyl-CoA esters (glutaryl-CoA, adipyl-CoA, suberyl-CoA, sebacyl-CoA, and dodecanedioyl-CoA). The identification of a highly specific succinyl-CoA thioesterase in peroxisomes strongly suggests that peroxisomal beta-oxidation of dicarboxylic acids leads to formation of succinate, at least under certain conditions, and that ACOT4 and ACOT8 are responsible for the termination of beta-oxidation of dicarboxylic acids of medium-chain length with the concomitant release of the corresponding free acids.
Synthesis of oligonucleotides on cellulose by a phosphotriester method (1980)

The synthesis of oligothymidilic acids, (dT)m (where m = 4, 7, 10, 13, 16, 19, 22, and 25), was carried out using a solid phase approach in combination with the modified phosphotriester methodology developed in solution. Cellulose was used as the solid support after its functionalization with a specially featured dinucleoside diphosphate, 5'-0-p-chlorophenylphospho-2'(3')-0-acetyluridilyl-[2'(3')-3']-5'-0-dimethoxytritylthymidine p-chlorophenylester. The fully protected trideoxynucleoside triphosphate containing only thymidine was repeatedly used to elongate the oligonucleotide chain in the 3'-5' direction. Individual coupling yields ranged from 45% to 75%. The total time needed to prepare (dT)25 was four days. Similarly, the tridecanucleotide d(AGAAGGTACTTTT) was synthesized in good yield. The results show that this approach can be used for a fast and economic way to synthesize oligodeoxynucleotides.
Epidermal growth factor receptor inhibitors in colorectal cancer treatment: What’s new? (2007)

Colorectal cancer constitutes one of the most common malignancies and the second leading cause of death from cancer in the western world representing one million new cases and half a million deaths annually worldwide. The treatment of patients with metastatic colon cancer comprises different regimens of chemotherapeutic compounds (fluoropyrimidines, irinotecan and oxaliplatin) and new targeted therapies. Interestingly, most recent trials that attempt to expose patients to all five-drug classes (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and cetuximab) achieve an overall survival well over 2 years. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit for colorectal cancer mainly cetuximab, panitumumab, erlotinib and gefitinib. We will also describe briefly the molecular steps that lie beneath them and the different clinical or molecular mechanisms that are reported for resistance and response.
Immunopathogenesis of IBD: insufficient suppressor function in the gut? (2006)

The intestinal immune system is in a constant state of controlled inflammation, and there is substantial evidence that loss of control is an important pathogenic mechanism in inflammatory bowel diseases (IBD). A major current working hypothesis defines Crohn’s disease as a dysregulated immune response towards components of the intestinal flora, leading to chronic intestinal inflammation.1 The causes for this inappropriate response can be attributed to (a combination of) defects in the epithelial barrier, the innate immune response or the adaptive immune response.

Animal experiments as well as clinical data indicate that the immunopathogenesis of Crohn’s disease and ulcerative colitis differ at the level of T cell differentiation and activation although the governing mechanisms responsible for these differences have been incompletely defined. In both diseases, activation of T cells is evident but pathogenic T cells in Crohn’s disease predominantly produce interferon γ (membrane bound), tumour necrosis factor (TNF)α and interleukin (IL)-23 whereas ulcerative colitis is characterised by production of IL-5 and IL-13.2,3

The increased production of “Th1” type cytokines in Crohn’s disease is probably related to increased activation of mucosal dendritic cells and macrophages, and the pivotal function of membrane associated (Toll-like receptor (TLR)) and intracellular (nucleotide oligomerisation domain (NOD) family) receptors in the activation of these antigen presenting cells (APC) has now been well established. Both receptors are key mediators of innate host defence, crucially involved in maintaining intestinal homeostasis.4 In healthy subjects, the colonic mucosa harbours “non-inflammatory” dendritic cells, expressing low levels of TLR2 and TLR4 and producing cytokines such as IL-10, contributing to a non-inflammatory environment,5,6 but in the mucosa of patients with Crohn’s disease the production of IL-12 is greatly increased.7–9 Dendritic cells in both ulcerative colitis and Crohn’s disease have an activated phenotype with higher levels of the …
Effect of classic preconditioning on the gene expression pattern of rat hearts: a DNA microarray study (2003)

To profile gene expression patterns involved in ischemic preconditioning, we monitored global gene expression changes by DNA microarray analysis of 3200 rat-specific genes and by real-time quantitative polymerase chain reaction in rat hearts. Forty-nine genes with altered expression were found after ischemia/reperfusion as compared to control non-ischemic hearts and 31 genes were characteristic for classic preconditioning followed by ischemia/reperfusion as compared to ischemia/reperfusion without preconditioning. Genes with altered expression due to ischemia and/or preconditioning included those controlling protein degradation, stress responses, apoptosis, metabolic enzymes, regulatory proteins, and several unknown cellular functions. Metallothionein, natriuretic peptides, coagulation factor VII, cysteine proteinase inhibitor, peroxisome proliferator activator receptor gamma and myosin light chain kinase genes were previously suspected to be related to several cardiovascular diseases, however, most of these genes have not previously been shown to be related to myocardial ischemia/reperfusion. Some genes were observed to change specifically in response to preconditioning: oligoadenylate synthase, chaperonin subunit epsilon, a cGMP phosphodiesterase (PDE9A1), a secretory carrier membrane protein, an amino acid transporter, and protease 28 subunit. None of these genes has previously been shown to be involved in the mechanism of preconditioning.
Processing of in vitro-synthesized gag precursor proteins of human immunodeficiency virus (HIV) type 1 by HIV proteinase generated in Escherichia coli (1988)

We expressed the gag and proteinase regions of human immunodeficiency virus (HIV) type 1 by transcription and translation in vitro. A synthetic RNA spanning the gag and pro domains gave primarily the unprocessed capsid precursor pr53. Efficient cleavage of this precursor was observed when the gag and pro domains were placed in the same translational reading frame, yielding equimolar amounts of the gag protein and of proteinase (PR). Expression of HIV type 1 PR in Escherichia coli as a fusion protein gave rapid autocatalytic processing to an HIV-specific protein of approximately 11 kilodaltons. HIV PR generated in E. coli specifically induced cleavage of the HIV capsid precursor, whereas deletion of the carboxy-terminal 17 amino acids of the proteinase rendered it inactive. Inhibitor studies showed that the enzyme was insensitive to inhibitors of serine and cysteine proteinases and metalloproteinases and was inhibited only by a very high concentration (1 mM) of pepstatin A.
Control of the intracellular levels of prostaglandin E2 through inhibition of the 15-hydroxyprostaglandin dehydrogenase for wound healing (2013)

Excessive scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Much experimental data suggests that prostaglandin E₂ (PGE₂) plays a role in the prevention of excessive scarring. However, it has a very short half-live in blood, its oxidization to 15-ketoprostaglandins is catalyzed by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, we reported that 15-PGDH inhibitors significantly increased PGE₂ levels in A549 cells. In our continuing attempts to develop highly potent 15-PGDH inhibitors, we newly synthesized various thiazolidine-2,4-dione derivatives. Compound 27, 28, 29, and 30 demonstrated IC₅₀ values of 0.048, 0.020, 0.038 and 0.048 μM, respectively. They also increased levels of PGE₂ in A549 cells. Especially, compound 28 significantly increased level of PGE₂ at 260 pg/mL, which was approximately fivefold higher than that of control. Scratch wounds were analyzed in confluent monolayers of HaCaT cells. Cells exposed to compound 28 showed significantly improved wound healing with respect to control.
Plasma Soluble P-Selectin in Acute Myocardial Infarction: Effects of Coronary Recanalization Therapy (1998)

P-selectin is translocated from platelets and endothelial cells to initiate the first step in a sequence of events leading to the adherence of leukocytes, possibly inducing reperfusion injury and the no-reflow phenomenon in acute myocardial infarction (AMI). This study was undertaken to investigate plasma P-selectin in AMI patients undergoing coronary recanalization therapy. A total of 40 patients were studied: 20 patients with AMI who underwent coronary recanalization by direct percutaneous transluminal coronary angioplasty (PTCA), 10 patients with AMI who underwent thrombolytic therapy by tissue-type plasminogen activator (TPA), and 10 patients with stable angina pectoris who underwent elective PTCA. Blood samples were obtained from systemic arteries before and immediately after PTCA or thrombolytic therapy. Plasma-soluble P-selectin was measured by enzyme immunoassay. Plasma P-selectin was significantly higher in AMI than in stable angina pectoris (176.6 +/- 12.9 ng/mL vs 91.4 +/- 9.5 ng/mL, p<0.001). Plasma P-selectin did not change significantly as a result of elective PTCA in patients with stable angina (from 91.4 +/- 9.5 ng/mL to 87.9 +/- 7.9 ng/mL). Plasma P-selectin was decreased by direct PTCA in all of the 20 patients with AMI (from 176.2 +/- 17.7 ng/mL to 141.7 +/- 12.6 ng/mL; p<0.001, paired t-test), whereas it was increased by thrombolysis using TPA in nine of the 10 AMI patients (from 177.4 +/- 17.2 ng/mL to 248.8 +/- 17.3 ng/mL, p<0.005). Increased P-selectin activity in AMI appeared to be attenuated by direct PTCA, but augmented by thrombolysis, possibly due to direct stimulatory effects of TPA on P-selectin expression. This may lead to less favorable results in salvaging the ischemic myocardium by thrombolytic than mechanical coronary recanalization therapy in AMI.