gebhart/patrepeval huggingface dataset:
Noninvasive Estimation of Blood Pressure Using Photoplethysmographic Signals in the Period Domain (2005)

In order to detect hypertension at its early stage, blood pressure (BP) of an individual must be carefully monitored. Aiming to monitor BP noninvasively and continuously, this study examines a new feature, normalized harmonic area (NHA), which is extracted from photoplethysmoographic (PPG) signals in the period domain by using the discrete period transform (DPT). BP, pulse transit time (PTT), diastolic time (DT) and NHA were obtained from photoplethysmographic (PPG) signals in the period domain by using the discrete period transform (DPT). BP, pulse transit time (PTI), diastolic time (DT) and NHA were obtained from 28 subjects before and immediately after step-climbing exercise. It was found that NHA has more significant correlation wiith BP than PTT and DT in this study. The mean difference and standard deviation (Mean&#177;SD) between the BP estimated from NHA and the reference BP obtained from a commercial oscillometric BP meter were 0.37&#177;4.3 mmHg and 0.51&#177;4.8 mmHg for SBP and DBP, respectively. The result indicate that NHA is potentially a useful indicator of arterial BP.
Genetically engineered immunoglobulins reveal structural features controlling segmental flexibility. (1988)

We have carried out nanosecond fluorescence polarization studies of genetically engineered immunoglobulins to determine the structural features controlling their segmental flexibility. The proteins studied were hybrids of a relatively rigid isotype (mouse IgG1) and a relatively flexible one (mouse IgG2a). They have identical light chains and heavy chain variable regions and have the same combining sites for epsilon-dansyl-L-lysine, a fluorescent hapten. The fluorescence of the bound dansyl chromophore was excited at 348 nm with subnanosecond laser pulses, and the emission in the nanosecond time range was measured with a single-photon-counting apparatus. The emission anisotropy kinetics of the hybrid antibodies revealed that segmental flexibility is controlled by the heavy chain constant region 1 (CH1) as well as by the hinge. In contrast, the CH2 and CH3 domains did not influence segmental flexibility. The hinge and CH1 domains must be properly matched to allow facile movement of the Fab units. Studies of hybrids of IgG1 and IgG2a within CH1 showed that the loop formed by residues 131-139 is important in controlling segmental flexibility. X-ray crystallographic studies by others of human IgG1 have shown that this loop makes several van der Waals contacts with the hinge.
SCN5A mutation (T1620M) causing Brugada syndrome exhibits different phenotypes when expressed in Xenopus oocytes and mammalian cells (2000)

Brugada syndrome is a hereditary cardiac disease causing abnormal ST segment elevation in the ECG, right bundle branch block, ventricular fibrillation and sudden death. In this study we characterized a new mutation in the SCN5A gene (T1620M), causing the Brugada syndrome. The mutated channels were expressed in both Xenopus leavis oocytes and in mammalian tsA201 cells with and without the beta-subunit and studied using the patch clamp technique. Opposite phenotypes were observed depending on the expression system. T1620M mutation led to a faster recovery from inactivation and a shift of steady-state inactivation to more positive voltages when expressed in Xenopus oocytes. However, using the mammalian expression system no effect on steady-state inactivation was observed, but this mutation led to a slower recovery from inactivation. Our finding supports the idea that the slower recovery from inactivation of the cardiac sodium channels seen in our mammalian expression system could decrease the density of sodium channels during the cardiac cycle explaining the in vivo arrhythmogenesis in patients with Brugada syndrome.
The natural product honokiol preferentially inhibits cellular FLICE-inhibitory protein and augments death receptor–induced apoptosis (2008)

Targeting death receptor-mediated apoptosis has emerged as an effective strategy for cancer therapy. However, certain types of cancer cells are intrinsically resistant to death receptor-mediated apoptosis. In an effort to identify agents that can sensitize cancer cells to death receptor-induced apoptosis, we have identified honokiol, a natural product with anticancer activity, as shown in various preclinical studies, as an effective sensitizer of death receptor-mediated apoptosis. Honokiol alone moderately inhibited the growth of human lung cancer cells; however, when combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), greater effects on decreasing cell survival and inducing apoptosis than TRAIL alone were observed, indicating that honokiol cooperates with TRAIL to enhance apoptosis. This was also true to Fas-induced apoptosis when combined with Fas ligand or an agonistic anti-Fas antibody. Among several apoptosis-associated proteins tested, cellular FLICE-inhibitory protein (c-FLIP) was the only one that was rapidly down-regulated by honokiol in all of the tested cell lines. The down-regulation of c-FLIP by honokiol could be prevented by the proteasome inhibitor MG132. Moreover, honokiol increased c-FLIP ubiquitination. These results indicate that honokiol down-regulates c-FLIP by facilitating its degradation through a ubiquitin/proteasome-mediated mechanism. Enforced expression of ectopic c-FLIP abolished the ability of honokiol to enhance TRAIL-induced apoptosis. Several honokiol derivatives, which exhibited more potent effects on down-regulation of c-FLIP than honokiol, showed better efficacy than honokiol in inhibiting the growth and enhancing TRAIL-induced apoptosis as well. Collectively, we conclude that c-FLIP down-regulation is a key event for honokiol to modulate the death receptor-induced apoptosis.
Laparoscopic Primary Repair of Iatrogenic Colon Perforation (2010)

Purpose. Iatrogenic colon perforation is a rare but serious complication of colonoscopy. Surgical intervention is frequently performed using traditional exploratory laparotomy for repair or colectomy; however, the laparoscopic approach may be an alternative option. We report our experience with laparoscopic suture repair and evaluate its effects compared with open surgery.
Methods. We retrospectively analyzed data for eighteen patients who underwent surgical repair after colonoscopy-induced iatrogenic colon perforation between December 2003 and November 2008. Fourteen patients received traditional exploratory laparotomies with primary repair or colectomy. Four patients underwent diagnostic laparoscopy and direct laparoscopic suture repair. The estimated perforation duration, operative time, and length of hospitalization were compared.
Results. In the open surgery group, four patients underwent primary repair of the defect, one of whom added loop T-colostomy for fecal diversion. The others received colectomies, and fecal diversion with loop ileostomy was performed in two. In the laparoscopic group, four patients underwent laparoscopic primary intra-corporeal suture repair. Blood loss was statistically less significant during the laparoscopic approach and the operative times were not different. Although a higher wound infection rate along with more prolonged post-operative ileus and longer hospital stays were noted in the open method, the difference was not statistically significant due to the limited number of cases.
Conclusion. An initial laparoscopic approach for diagnosis of iatrogenic perforations followed by laparoscopic colorraphy of the colon seems safe and efficacious when compared to open surgery. It is reasonable to consider laparoscopic repair of iatrogenic colon perforation as an alternative option.
Macrocyclic aromatic thioether sulfones (1998)

Reaction of 4,4′-sulfonylbis(thiophenol) with 4,4′-dichlorodiphenyl sulfone under pseudo-high-dilution conditions leads to a novel family of all- para macrocyclic thioether sulfones [-SphiSO 2phi-] n (phi = 1,4-phenylene); these include a highly strained [1 + 1] cyclodimer ( n = 2), a cyclotrimer resulting from thioether exchange reactions, and a [2 + 2] cyclotetramer which can adopt two distinctly different conformations, one having molecular D 2 d (‘tennis-ball-seam’) symmetry, in the crystalline state.
Recombinant endotoxin-binding protein (rBPI23) attenuates endotoxin-induced circulatory changes in humans. (1995)

In the present study the protective effect of a recombinant endotoxin-binding protein rBPI23 on the circulatory changes in experimental endotoxemia in humans was investigated. In a controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg body weight), and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). Hemodynamic parameters were obtained non-invasively by means of M-mode, two-dimensional, and Doppler echocardiography. rBPI23 significantly reduced indices of the endotoxin-induced hyperdynamic circulation. rBPI23 treatment significantly reduced increase in cardiac index (P = 0.0156). rBPI23 treatment diminished the endotoxin-induced decrease in systemic vascular resistance index (P = 0.0304). rBPI23 did not prevent the endotoxin-induced rise in body temperature and systolic, diastolic and mean arterial pressure were not significantly different in the rBPI23- and placebo-treatment arm. Both treatment periods showed a small reduction in end diastolic and end systolic volumes. rBPI23 treatment slightly reduced the increase in M-mode ejection fraction and fractional shortening. These results indicate that rBPI23 is capable of attenuating the potentially deleterious circulatory effects of endotoxin in humans.
Biosynthesis Of Peptide Antibiotics (1987)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Cholecystokinin Acts as an Essential Factor in the Exacerbation of Pancreatic Bile Duct Ligation-Induced Rat Pancreatitis Model Under Non-fasting Condition (2000)

We examined the influence of 2 gut hormones involved in the enhancement of pancreatic exocrine secretion, secretin and cholecystokinin (CCK), in the exacerbation of pancreatitis. We also examined the role of the vagal system, which was considered to be a transmission route for these hormones. Our model of pancreatitis in the rat was prepared by pancreatic bile duct ligation (PBDL), which simultaneously ligated the pancreatic duct and the common bile duct. Serum amylase activity and histopathological changes in the pancreas were used as indices of pancreatitis. We also measured the volume of pancreatic juice, as well as the amylase activity and protein level of the pancreatic juice, as indices of increased pancreatic exocrine secretion. Two gut hormones were given 6 times at 1-h intervals. Administration of secretin (1-3 microg/kg, s.c.) did not influence serum amylase activity in rats with PBDL-induced pancreatitis. However, food stimulation and administration of CCK-8 (1 microg/kg, s.c.) increased serum amylase activity and promoted vacuolation of the pancreatic acinar cells in rats with PBDL-induced pancreatitis. Administration of atropine (3 mg/kg, s.c.) or a CCK1-receptor antagonist, Z-203 (0.1 mg/kg, i.v.), inhibited food-stimulated or CCK-8-induced (1 microg/kg, s.c.) enhancement of pancreatic exocrine secretion and exacerbation after the development of PBDL-induced pancreatitis. These results suggest that not secretin, which regulates the volume of pancreatic juice, but CCK, which regulates the secretion of pancreatic enzymes via the vagal system, plays an essential role in food-stimulated exacerbation after the development of pancreatitis.
A new prediction model search algorithm for fast block motion estimation (2002)

Most of the fast block matching algorithms (BMAs) use the origin as the initial center of the search. To improve the accuracy of the fast BMAs, a new prediction model (PM) search algorithm is proposed. Based on the spatial correlation of motion and the fast center-biased BMA, the four causal neighbour blocks are chosen to predict the starting search point and then the center-biased BMA is used to find the final motion vector as the global minimum is closer to the predicted center. Experimental results show that the proposed prediction model improves the performance of most fast BMAs such as the new three-step search and the four-step search, in terms of the motion compensation errors. In addition, the average computational requirement is also reduced.
The human EGF receptor gene: structure of the 110 kb locus and identification of sequences regulating its transcription. (1988)

The human epidermal growth factor receptor (EGFR) proto-oncogene is shown to span 110 kb of DNA divided into 26 exons. Analysis of sequences surrounding exon 1 reveals a highly CG rich region which promotes transcription. The activity of the EGF receptor promoter can be modulated by E1A protein and receptor RNA levels increased by stimulation with phorbol ester or fetal calf serum. Promoter activity is assayed by linkage to the chloramphenicol acetyl transferase gene and transfection in three cell lines, with quantitation of plasmid DNA uptake by isolation of a Hirt supernatent from each transfection. Deletion analysis of the CG rich promoter region of the gene and construction of chimeric EGFR/SV40 promoters are used to demonstrate positive transcription elements located both within exon 1 and 5' to the start of transcription. Negative regulation of transcription by sequences within a -140 to +80 region is suggested. Cotransfection experiments suggest a requirement for the interaction of DNA binding protein Sp1 for maximal activity. Finally, derepression of a positive regulatory sequence located in exon 1 during cotransfection experiments is shown. Results are discussed in reference to the multilevel regulation of EGF receptor expression.
[Selenium, glutathione peroxidase, peroxides and platelet functions]. (1996)

In the last five years, there has been a renewal of interest in the protective role of selenium in vascular disorders, inspired by experimental evidence that this trace element could modulate leukotriene and prostaglandin synthesis in both endothelial cells and platelets. In people living in low-selenium areas, a relationship has been established between a decrease in plasma selenium and an increase in the risk of coronary disease, atherosclerosis, platelet hyperaggregability and synthesis of proaggregant and proinflammatory compounds like thromboxane A2 and leukotrienes. Selenium, as an essential part of glutathione peroxidase, takes part in the reduction of hydrogen peroxides and lipid peroxides. The concentration of these peroxides, in turn, regulates the activities of cyclooxygenase and lipooxygenase pathways, ultimately influencing the production of eicosanoids and modulating the balance between a proaggregatory and antiaggregatory state. Recent evidence shows that selenium, via its action on glutathione peroxidase activity, may be primarily responsible for the regulation of the endogenous hydroperoxide level. In human platelets, the activity of glutathione peroxidase is particularly high and is very sensitive to the requirement of selenium. This sensitivity could explain why platelets of selenium-deficient subjects show increased aggregation, thromboxane B2 production and synthesis of the lipoxygenase-derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. These results support the hypothesis that selenium supplementation has a positive effect on platelet aggregation in selenium-deficient subjects. In France, more than 10% of the population is selenium-deficient and long-term supplementation with low doses of selenium could have a beneficial effect on the prevention of both thrombosis and coronary heart disease in these subjects.
Synthesis of 1,2,5-Thiadiazolidin-3-one 1,1-Dioxide Derivatives and Evaluation of Their Affinity for MHC Class-II Proteins (1999)

1,2,5-Thiadiazolidin-3-one 1,1-dioxide derivatives (±)-1a – d and (±)-2 were designed by molecular modeling as MHC (major histocompatibility complex) class-II inhibitors. They were prepared from the unsymmetrically N,N′-disubstituted acyclic sulfamides (±)-4a – d (Scheme 1) and (±)-11 (Scheme 2). These N-alkyl-N′-arylsulfamide precursors were synthesized by nucleophilic substitution of either a sulfamoyl-chloride or a N-sulfamoyloxazolidinone. Extension of base-induced cyclization methods from aliphatic to aromatic sulfamides gave access to the desired target molecules. The N-alkyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide derivatives (±)-3a – c were also prepared by the oxazolidinone route (Scheme 4) for coupling to a tetrapeptide fragment. The X-ray crystal structure of 1,2,5-thiadiazolidin-3-one 1,1-dioxide (±)-21a was solved, and the directionality of the H-bond donor (N−H) and acceptor (SO2) groups of the cyclic scaffold determined (Figs. 1 and 2). The pKa value of the N−H group in (±)-21a was determined by 1H-NMR titration as 11.9 (Fig. 3). Compounds (±)-1a – d were shown to inhibit competition peptide binding to HLA-DR4 molecules in the single-digit millimolar concentration range.
Discovery of Endothelial to Mesenchymal Transition as a Source for Carcinoma-Associated Fibroblasts (2007)

Activated fibroblasts are associated with many different tumors. Myofibroblasts, activated fibroblasts, and perivascular mesenchymal cells such as pericytes play a role in cancer progression. Many studies suggest that myofibroblasts facilitate tumor growth and cancer progression. The source for myofibroblasts and other activated fibroblasts within the tumors is still debated. Although de novo activation of quiescent fibroblasts into alpha-smooth muscle actin (alpha SMA)-positive myofibroblasts is one likely source, epithelial to mesenchymal transition and bone marrow recruitment are also evolving as possible mechanisms for the emergence of a heterogeneous population of carcinoma-associated fibroblasts. Here, we show that transforming growth factor-beta1 could induce proliferating endothelial cells to undergo a phenotypic conversion into fibroblast-like cells. Such endothelial to mesenchymal transition (EndMT) is associated with the emergence of mesenchymal marker fibroblast-specific protein-1 (FSP1) and down-regulation of CD31/PECAM. Additionally, we show EndMT in tumors using the B16F10 melanoma model and the Rip-Tag2 spontaneous pancreatic carcinoma model. Crossing Tie2-Cre mice with R26Rosa-lox-Stop-lox-LacZ mice allows for irreversible tagging of endothelial cells. We provide unequivocal evidence for EndMT at the invasive front of the tumors in these transgenic mice. Collectively, our results show that EndMT is a unique mechanism for the accumulation of carcinoma-associated fibroblasts and suggest that antiangiogenic treatment of tumors may have a direct effect in decreasing activated fibroblasts that likely facilitate cancer progression.
Biopharmaceutical drug targeting to the brain (2010)

Biopharmaceuticals are large molecule drugs that do not cross the blood-brain barrier (BBB). The limiting factor in the drug development of biopharmaceuticals as new drugs for the human brain is the engineering of effective brain drug targeting technology platforms. Recombinant proteins, enzymes, and monoclonal antibodies can be re-engineered for transport across the human BBB with the molecular Trojan horse technology. The most active BBB molecular Trojan horse is a monoclonal antibody to the human insulin receptor. The genetic engineering of IgG fusion proteins has been demonstrated for neurotrophic factors, decoy receptors, therapeutic enzymes, single chain Fv antibodies, and avidin. The IgG fusion proteins are not toxic on repeated administration in high doses to primates and do not interfere with glycemic control in plasma or brain. IgG fusion proteins contain amino acid sequences that induce immune tolerance, and show low immunogenicity in primates. The IgG fusion proteins are new bifunctional biopharmaceuticals that are both targeted to brain via transport on endogenous BBB receptors, and exert pharmacological effects in brain at the cognate receptor, ligand, or enzyme substrate.
Network Control and Data Transport for C<sup>3</sup>I Applications (1987)

In this paper, communication networks that serve military C <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> I applications are considered. Such networks must operate under highly dynamic conditions, both in terms of network topology and in the volume and distribution of their traffic. The nodes in these networks have to adapt, therfore, to frequent changes while using their scarce resources efficiently and delivering reliable data transport at all times. To help with this, algorithms that provide some of the required functionality, namely, adaptive routing and network reconfiguration schemes are presented. Specifically, two distributed routing algorithms are considered: (1) a shortest-path algorithm that converges after a number of cycles in the order of the network's diameter, and that is almost loop free, and (2) a quasi-static algorithm that confines the message exchange following a link failure to a small set of nodes in order to yield a routing that is close to optimal. We next describe a random node interconnection procedure that enables the nodes to control the neighborhood they communicate directly with. This procedure yields a connected network with high probability if the nodal degree is above some threshold. Efficient scheduling of transmissions over radio channels is essential for high network throughput. An algorithm for optimum scheduling is described and its complexity, which is the best known so far, is discussed. Finally, we discuss a side effect of the requirement for efficient, reliable packet delivery, that is, packets that arrive out of order, and present performance models of the resequencing required at the receiver.
Cellular Responses to Photoreceptor Death in therd1Mouse Model of Retinal Degeneration (2007)

All retinal cell types responded during the process of retinal degeneration, as revealed by changes in gene expression. Genes that showed changes in the in situ hybridization signals during the period of cone death were typically higher in the mutant, with many of them expressed in both the ganglion cell layer and the inner nuclear layer.