gebhart/patrepeval huggingface dataset:
Synthesis and Structure-Activity Relationships of Potent Antitumor Active Quinoline and Naphthyridine Derivatives (2007)

The disease of cancer has been ranked second after cardiovascular diseases and plant-derived molecules have played an important role for the treatment of cancer. Nine cytotoxic plant-derived molecules such as vinblastine, vincristine, navelbine, etoposide, teniposide, taxol, taxotere, topotecan and irinotecan have been approved as anticancer drugs. Recently, epothilones are being emerging as future potential anti-tumor agents. However, targeted cancer therapy has now been rapidly expanding and small organic molecules are being exploited for this purpose. Amongst target specific small organic molecules, quinazoline was found as one of the most successful chemical class in cancer chemotherapy as three drugs namely Gefitinib, Erlotinib and Canertinib belong to this series. Now, quinazoline related chemical classes such as quinolines and naphthyridines are being exploited in cancer chemotherapy and a number of molecules such as compounds EKB-569 (52), HKI-272 (78) and SNS-595 (127a) are in different phases of clinical trials. This review presents the synthesis of quinolines and naphthyridines derivatives, screened for anticancer activity since year 2000. The synthesis of most potent derivatives in each prototype has been delineated. A brief structure activity relationship for each prototype has also been discussed. It has been observed that aniline group at C-4, aminoacrylamide substituents at C-6, cyano group at C-3 and alkoxy groups at C-7 in the quinoline ring play an important role for optimal activity. While aminopyrrolidine functionality at C-7, 2'-thiazolyl at N-1 and carboxy group at C-3 in 1,8-naphthyridine ring are essential for eliciting the cytotoxicity. This review would help the medicinal chemist to design and synthesize molecules for targeted cancer chemotherapy.
Amniotic membrane transplantation (1999)

In 1910 Davis was the first to report the use of fetal membranes as surgical material in skin transplantation.1Since then the use of amniotic membrane in surgery has been expanded.1-9 It is now utilised as a biological dressing for burned skin, skin wounds, and chronic ulcers of the leg,9-16 as an adjunctive tissue in surgical reconstruction of artificial vagina,9 17-19 and for repairing omphaloceles.9 20 It has also been used to prevent tissue adhesion in surgical procedures of the abdomen, head, and pelvis.9 21 22 In the 1940s several authors reported the beneficial role of amniotic membrane in treating a variety of ocular surface disorders.5-7 23 However, its use was abandoned for decades until recently, when it was reintroduced to ophthalmologists. Several studies have addressed this subject and the scope of the application of amniotic membrane transplantation (AMT) in the management of ocular surface disorders is ever increasing.

Certain characteristics make the amniotic membrane ideally suited to its application in ocular surface reconstruction. It can be easily obtained and its availability is nearly unlimited. The tissue can be preserved at −80°C for several months, allowing sufficient time to plan surgery or consider a trial of other options. Amniotic membrane does not express HLA-A, B, or DR antigens and hence immunological rejection after its transplantation does not occur.24-26It is also believed to have antimicrobial properties, reducing the risks of postoperative infection.27 Antifibroblastic activity28-30 and cell migration/growth promoting activity31-33 have also been demonstrated with regard to the amniotic membrane.

The purpose of this paper is to review the characteristics of amniotic membrane that make it potentially useful to treat ocular surface abnormalities and to discuss the current indications, the surgical technique, and the outcome of AMT.

Mammalian embryos lie …
Growth and grazing of a heterotrophic dinoflagellate Gyrodinium dommans, feeding on a red tide flagellate, Chattonella antique (1992)

Growth and grazing of a heterotrophic dinoflagellate, Gyrodinium dominans, were examined in laboratory batch cultures. When ChattoneUa antiqua was used as prey, G. dominans grew at a rate of ca 0.9 d-' (at 25C). Cell division of G. don~inans was not affected by the light: dark period. Growth rate of G. dominans was significantly affected by temperature and was maximal within the range 25 to 2 27.5OC. Rate of ingestion of C. antiqua (at ca 1 x 103 to 2 X lo3 cells ml-l) by G. dominans was 3 8 prey cell-' d-' and growth efficiencies on the basis of carbon and nitrogen were 0.31 and 0.33, respectively. Results suggest the ecological importance of G. dominans In the disappearance of C. antlqua red tides.
Signal Processing in Sequence Analysis: Advances in Eukaryotic Gene Prediction (2008)

Genomic sequence processing has been an active area of research for the past two decades and has increasingly attracted the attention of digital signal processing researchers in recent years. A challenging open problem in deoxyribonucleic acid (DNA) sequence analysis is maximizing the prediction accuracy of eukaryotic gene locations and thereby protein coding regions. In this paper, DNA symbolic-to-numeric representations are presented and compared with existing techniques in terms of relative accuracy for the gene and exon prediction problem. Novel signal processing-based gene and exon prediction methods are then evaluated together with existing approaches at a nucleotide level using the Burset/Guigo1996, HMR195, and GENSCAN standard genomic datasets. A new technique for the recognition of acceptor splice sites is then proposed, which combines signal processing-based gene and exon prediction methods with an existing data-driven statistical method. By comparison with the acceptor splice site detection method used in the gene-finding program GENSCAN, the proposed DSP-statistical hybrid technique reveals a consistent reduction in false positives at different levels of sensitivity, averaging a 43% reduction when evaluated on the GENSCAN test set.
Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways (2009)

ER stress-induced apoptosis is implicated in various pathological conditions, but the mechanisms linking ER stress-mediated signaling to downstream apoptotic pathways remain unclear. Using human and mouse cell culture and in vivo mouse models of ER stress-induced apoptosis, we have shown that cytosolic calcium resulting from ER stress induces expression of the Fas death receptor through a pathway involving calcium/calmodulin-dependent protein kinase IIgamma (CaMKIIgamma) and JNK. Remarkably, CaMKIIgamma was also responsible for processes involved in mitochondrial-dependent apoptosis, including release of mitochondrial cytochrome c and loss of mitochondrial membrane potential. CaMKII-dependent apoptosis was also observed in a number of cultured human and mouse cells relevant to ER stress-induced pathology, including cultured macrophages, endothelial cells, and neuronal cells subjected to proapoptotic ER stress. Moreover, WT mice subjected to systemic ER stress showed evidence of macrophage mitochondrial dysfunction and apoptosis, renal epithelial cell apoptosis, and renal dysfunction, and these effects were markedly reduced in CaMKIIgamma-deficient mice. These data support an integrated model in which CaMKII serves as a unifying link between ER stress and the Fas and mitochondrial apoptotic pathways. Our study also revealed what we believe to be a novel proapoptotic function for CaMKII, namely, promotion of mitochondrial calcium uptake. These findings raise the possibility that CaMKII inhibitors could be useful in preventing apoptosis in pathological settings involving ER stress-induced apoptosis.
Data level inference detection in database systems (2002)

Existing work on inference detection for database systems mainly employ functional dependencies in the database schema to detect inferences. It has been noticed that analyzing the data stored in the database may help to detect more inferences. We describe our effort in developing a data level inference detection system. We have identified five inference rules that a user can use to perform inferences. They are "subsume", "unique characteristic", "overlapping", "complementary", and "functional dependency" inference rules. The existence of these inference rules confirms the inadequacy of detecting inferences using just functional dependencies. The rules can be applied any number of times and in any order. These inference rules are sound. They are not necessarily complete, although we have no example that demonstrates incompleteness. We employ a rule based approach so that future inference rules can be incorporated into the detection system. We have developed a prototype of the inference detection system using Perl on a Sun SPARC 20 workstation. The preliminary results show that on average it takes seconds to process a query for a database with thousands of records. Thus, our approach to inference detection is best performed offline, and would be most useful to detect subtle inference attacks.
The Mechanism of alpha-Helix Formation by Peptides (1992)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More
Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes. (1988)

In this report, we describe a novel activation antigen that appears very early after T cell activation and is absent in resting lymphocytes, through which agonistic proliferative signals can be triggered by mAb binding. It has been designated as activation inducer molecule (AIM) and is a disulphide-linked heterodimeric structure containing two polypeptide chains of Mr 33,000 and 27,000. The expression of AIM can be induced by different activation stimuli such as PMA, PHA, or anti-CD3 mAb, but not by the Ca2+ ionophore A23187, and it precedes the expression of other activation molecules such as 4F2 or the IL-2-R. Once AIM antigens are expressed on lymphocytes after stimulation with submitogenic doses of PMA, the binding of anti-AIM mAbs triggers a strong proliferative response. Furthermore, a comitogenic effect of the anti-AIM mAbs is exerted in the presence of either PHA or anti-CD3 mAb. The activation of lymphocytes through AIM antigens induces both IL-2 and IL-2-R receptor synthesis and is inhibited by anti-IL-2-R mAbs.
Abstract 71: Novel Bach1 Modulators Increase HMOX1 and Suppress Hypertension in the Goldblatt Model of Renovascular Hypertension (2013)

We report for the first time a novel class of compounds that specifically modulate the Bach1 transcriptional repressor pathway. In cellula, the compounds selectively inhibit the activity of the transcriptional repressor Bach1 resulting in transcription of a network of antioxidant and cytoprotective genes including HMOX1. HPP-1971, a member of this class, is a potent and selective Bach1 inhibitor that induces HMOX1 &gt; 40-fold with a potency of 408 nM in human lung fibroblasts. To assess activity in vivo, we tested HPP-1971 in the Goldblatt model of renovascular hypertension. Sprague Dawley rats were implanted with in dwelling pressure telemeter probes and subsequently underwent sham surgery or placement of a 0.25 mm silver clip around the left renal artery. HPP-1971 treatment, dosed orally at 1,3,10 and 30 mpk, commenced three days following clip surgery, and continued for 18 days. At study completion, blood pressure, clipped kidney weight, renal HMOX1 enzyme activity and plasma aldosterone levels were measured (see Table). HPP-1971 attenuated both kidney atrophy and the increase in blood pressure in a dose dependent manner with significant differences seen at 3, 10 and 30 mpk (p&lt;.0001). HMOX1 enzyme activity in the clipped kidney increased with treatment, reaching a maximum of 5.7 ± 0.9 nM/hr/mg at 30 mpk relative to sham operated animals (p&lt;.0001). Plasma aldosterone levels increased in 2K1C animals compared to sham controls but were reduced by HPP-1971 treatment. These findings define a novel role for Bach1 suppressors in counteracting the influence of the RAAS system on hypertension and kidney atrophy in the 2K1C model of renovascular hypertension.
Differential Regulation of the Dopamine D2and D3 Receptors by G Protein-coupled Receptor Kinases and β-Arrestins (2001)

The D(2) and D(3) receptors (D(2)R and D(3)R), which are potential targets for antipsychotic drugs, have a similar structural architecture and signaling pathway. Furthermore, in some brain regions they are expressed in the same cells, suggesting that differences between the two receptors might lie in other properties such as their regulation. In this study we investigated, using COS-7 and HEK-293 cells, the mechanism underlying the intracellular trafficking of the D(2)R and D(3)R. Activation of D(2)R caused G protein-coupled receptor kinase-dependent receptor phosphorylation, a robust translocation of beta-arrestin to the cell membrane, and profound receptor internalization. The internalization of the D(2)R was dynamin-dependent, suggesting that a clathrin-coated endocytic pathway is involved. In addition, the D(2)R, upon agonist-mediated internalization, localized to intracellular compartments distinct from those utilized by the beta(2)-adrenergic receptor. However, in the case of the D(3)R, only subtle agonist-mediated receptor phosphorylation, beta-arrestin translocation to the plasma membrane, and receptor internalization were observed. Interchange of the second and third intracellular loops of the D(2)R and D(3)R reversed their phenotypes, implicating these regions in the regulatory properties of the two receptors. Our studies thus indicate that functional distinctions between the D(2)R and D(3)R may be found in their desensitization and cellular trafficking properties. The differences in their regulatory properties suggest that they have distinct physiological roles in the brain.
Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Hepatocyte Antioxidative Enzymes (2002)

The physiological decline that occurs in aging is thought to result, in part, from accumulation of oxidative damage generated by reactive oxygen species during normal metabolic processes. Elevated levels of antioxidative enzymes in liver tissues are present in the Ames dwarf, a growth hormone (GH)-deficient mouse that lives more than 1 year longer than wild-type mice from the same line. In contrast, transgenic mice that overexpress GH exhibit depressed hepatic levels of catalase and have significantly shortened life spans. In this study, we evaluated the in vitro effects of GH and insulin-like growth factor 1 (IGF-1) on antioxidative enzymes in mouse hepatocytes. Hepatocytes were isolated from wild-type mice following perfusion of livers with a collagenase-based buffer. Dispersed cells were plated on Matrigel and treated with rat GH (0.1, 1.0, or 10 microg/ml) or IGF-1 (0.5, 5.0, or 50 nM) for 24 hr. Hepatocytes were recovered and protein was extracted for immunoblotting and enzyme activity assays of catalase (CAT), glutathione peroxidase (GPX), and manganese superoxide dismutase (MnSOD). A 41% and 27% decrease in catalase activity was detected in cells treated with GH, whereas IGF-1 reduced CAT activity levels to a greater extent than GH (P < 0.0001). The activity and protein levels of GPX were also significantly depressed in cells treated with GH, whereas activity alone was decreased in cells treated with IGF-1 (P < 0.04). GH significantly suppressed MnSOD levels by 40% and 66% in 1.0 and 0.1 microg/ml concentrations, respectively. Similarly, IGF-1 decreased MnSOD protein levels (5 nM; P < 0.05). These results suggest that GH and IGF-1 may decrease the ability of hepatocytes to counter oxidative stress. In addition, these experiments provide an explanation for the differing antioxidative defense capacity of GH-deficient versus GH-overexpressing mice, and they suggest that GH is directly involved in antioxidant regulation and the aging process.
Cotonoates A and B, New Aromatic Esters from Cotoneaster racemiflora (2008)

Abstract Phytochemical investigation of the chloroform soluble fraction of the methanolic extract of Cotoneaster racemiflora resulted in the isolation of two new aromatic esters named cotonoates A (1) and B (2) along with the known compound methyl 3,4-dihydroxy-5-methoxybenzoate (3). The structures of the new compounds have been assigned on the basis of spectral analysis including 1D and 2D NMR techniques. Compound 3 shows significant antioxidant and lipoxygenase inhibitory activities.
The long QT syndrome. Prospective longitudinal study of 328 families. (1991)

Among 232 probands and 1,264 family members with prospective follow-up, three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years, whichever occurred first (Cox hazard ratio; 95% confidence limits): 1) QTc (1.052; 1.017, 1.088), 2) history of cardiac event (3.1; 1.3, 7.2), and 3) heart rate (1.017; 1.004, 1.031). The findings from this prospective longitudinal study highlight the clinical features, risk factors, and course of LQTS.
Elastin‐like polypeptides: Biomedical applications of tunable biopolymers (2010)

Artificial repetitive polypeptides have grown in popularity as a bioinspired alternative to synthetic polymers. The genetically encoded synthesis, monodispersity, potential lack of toxicity, and biocompatibility are attractive features of these biopolymers for biological applications. Elastin-like polypeptides (ELPs) are one such class of biopolymers that are of particular interest because of their "smart"-stimuli responsive-properties. Herein, we discuss the genetically encoded design and recombinant synthesis of ELPs that enable precise control of their physicochemical properties and which have led to a wide range of biomedical applications of these biopolymers in the last decade.
Androgenic Action of Dehydroepiandrosterone (DHEA) on Nerve Density in the Ovariectomized Rat Vagina (2013)

Considering that the antiestrogen acolbifene had no inhibitory effect on the effect of DHEA in rat vagina while blocking the stimulatory effect of premarin, the present data indicate that DHEA exerts its stimulatory effect on the fiber density through an androgenic action.
Vancomycin-resistant enterococcal bacteremia: comparison of clinical features and outcome between Enterococcus faecium and Enterococcus faecalis. (2008)

Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial pathogens. This study was conducted to clarify the clinical features and outcome of patients with vancomycin-resistant enterococcal bacteremia.Patients with vancomycin-resistant enterococcal bacteremia treated at a medical center in northern Taiwan between November 1998 and July 2006 were reviewed. Clinical and bacteriological characteristics of Enterococcus faecium and Enterococcus faecalis were compared.Twelve patients (6 males and 6 females) were included for analyses. The mean age was 69.3 years (range, 40 to 86 years), and 8 cases (66.7%) were older than 65 years. All patients had underlying disease. Two patients received total hip replacement before development of VRE bacteremia. Twelve patients had prior exposure to broad-spectrum antimicrobial therapy. Ten patients had prior intensive care unit stay and prior mechanical ventilation before VRE bacteremia. All of the patients (n = 12) had an intravascular catheter in place. Bacteremia was caused by E. faecalis in 4 patients and by E. faecium in eight. The portals of entry included urinary tract (8.3%), skin, soft tissue and bone (41.7%) and unknown sources (50.0%). E. faecium showed a higher rate of resistance to ampicillin and teicoplanin than E. faecalis (87.5% vs 0.0%, p=0.01). The 60-day mortality rate was higher in patients with E. faecium bacteremia than E. faecalis bacteremia (62.5% vs 0.0%), although statistical significance was not obtained (p=0.08).VRE bacteremia may have an impact on the mortality and morbidity of hospitalized patients. Patients with bacteremia caused by vancomycin-resistant E. faecium had a grave prognosis, especially immunosuppressed patients. The prudent use of antibiotics and strict enforcement of infection control may prevent further emergence and spread of VRE.
Treating patients with the NPTC accelerator based proton treatment facility (2004)

The Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital has been treating patients with proton beams since November 2001. Over 200 patients were treated in the first year of operation. This facility has replaced the program at the Harvard Cyclotron Laboratory (HCL) where proton treatments had been underway for over three decades. Features such as rotating gantries and deeper proton penetration allow a wider range of clinical applications at this new facility. The requirements of accelerator reproducibility and availability are perhaps at a higher level than those required at an accelerator based physics facility. These requirements and the system performance will be highlighted in this paper. Operation of a proton cyclotron produced by industry (Ion Beam Applications) and the four operating beam lines along with the Gantries and patient-positioning systems will be discussed. Of particular interest in addition to the required availability is the systematic approach to safety and accuracy in the design and implementation.
Low-loss parallel-plate waveguide at 10.6 μm (1974)

A slightly curved parallel-plate waveguide made of metal or dielectric material is proposed for a low-loss and self-focusing optical guide for CO2 laser beams. The minimum-loss TE1 mode in a copper guide with a separation of 0.5 mm has a transmission loss as low as 0.02 dB/m, and the loss is 6 times less than that of the TE01 mode in the hollow circular guide of diameter equal to the separation. Theoretical prediction of the low-loss and self-focusing characteristics of the waveguide has been experimentally confirmed.
Currie and 1st Canadian Division at Second Ypres, April 1915: Controversy, Criticism and Official History (1996)

22 April1915, 1st Canadian Division was stationed in the Ypres salient, when the first gas attack of the war took place.To the left of the Canadians was the French 45th Algerian Division, which hastily retired in the face of the unexpected chlorine gas.It was left, therefore, to 1st Canadian Division to fill the gap and restore the situation, which was basically achieved by 23 April.However, severe German attacks over the next two days, 24 and 25 April, tested 1st Canadian Division to the limit.The critical problems of these two days caused Brigadier-General Arthur Currie (General Officer Commanding (GOC), 2nd Brigade, in 1st Canadian Division) to order two of his battalions to retire during the morning of 24 April, but the retirement did not take place.Further difficulties at midday on 24 April caused Currie to again issue retirement orders, and to leave his headquarters and seek reinforcements to fill a gap on his left.This entailed a visit by Currie to the headquarters of the neighbouring British 27th
Signaling Through Scaffold, Anchoring, and Adaptor Proteins (1997)

The process by which extracellular signals are relayed from the plasma membrane to specific intracellular sites is an essential facet of cellular regulation. Many signaling pathways do so by altering the phosphorylation state of tyrosine, serine, or threonine residues of target proteins. Recently, it has become apparent that regulatory mechanisms exist to influence where and when protein kinases and phosphatases are activated in the cell. The role of scaffold, anchoring, and adaptor proteins that contribute to the specificity of signal transduction events by recruiting active enzymes into signaling networks or by placing enzymes close to their substrates is discussed.