gebhart/patrepeval huggingface dataset:
Isophosphoramide Mustard and Its Mechanism of Bisalkylation (1998)

To investigate the mechanism(s) of bisalkylation by isophosphoramide mustard (IPM), IPM-beta,beta,beta',beta'-d(4) was synthesized and the products of its reaction with thiosulfate (at pD 7.0) were analyzed by NMR. By both (1)H and (13)C NMR, the distribution of deuterium in the products was consistent with bisalkylation through sequential aziridinyl intermediates [(NCH(2)CD(2)S):(NCD(2)CH(2)S) = 53:47]. Under the given reaction conditions, label scrambling as a result of thiosulfate acting as a leaving group was ruled out through control experiments. The data gave a calculated kinetic isotope effect of 0.97 per deuterium. For the initial aziridine species formed from IPM, ab initio quantum chemical calculations gave a hybridization value of sp(2.4)(-)(2.5) for each of the C-H bonds of the reaction centers, and this correlated with the observed inverse isotope effect. Other structure and bond order data were also determined for this aziridine intermediate and related compounds.
The HISS story overview: a novel hepatic neurohumoral regulation of peripheral insulin sensitivity in health and diabetes (1999)

Data are reviewed that are consistent with the following working hypothesis that proposes a novel mechanism regulating insulin sensitivity, which when nonfunctional, leads to severe insulin resistance. Postprandial elevation in insulin levels activates a hepatic parasympathetic reflex release of a putative hepatic insulin-sensitizing substance (HISS), which activates glucose uptake at skeletal muscle. Insulin causes HISS release in fed but not fasted animals. The reflex is mediated by acetylcholine and involves release of nitric oxide in the liver. Interruption of the release of HISS is achieved by surgical denervation of the anterior hepatic nerve plexus, muscarinic receptor blockade, or nitric oxide synthase antagonism and leads to immediate severe insulin resistance. The nitric oxide donor, SIN-1, reverses L-NAME-induced insulin resistance. Denervation-induced insulin resistance is reversed by intraportal but not intravenous administration of acetylcholine or SIN-1. Liver disease is often associated with insulin resistance; the bile duct ligation model of liver disease results in parasympathetic neuropathy and insulin resistance that is reversed by intraportal acetylcholine. Possible relevance of this HISS-dependent control of insulin action to insulin resistance in diabetes, liver disease, and obesity is discussed.Key words: insulin resistance, parasympathetic nerves, liver, obesity, nitric oxide.
Functional soluble CD100/Sema4D released from activated lymphocytes: possible role in normal and pathologic immune responses (2001)

CD100/Sema4D is a 150-kd transmembrane protein that belongs to the semaphorin family. The interaction of CD100 with CD72 is critical for the immune system. In CD100-deficient mice, the production of specific antibodies against T-cell-dependent antigens is severely impaired, but not against T-cell-independent antigens. Here, a functional soluble CD100 protein (sCD100) released from activated lymphocytes is reported. sCD100 was detected in culture supernatants of activated lymphocytes. Either affinity-purified from supernatants of activated T-cells, or produced as a recombinant sCD100 protein consisting of the extracellular region of the mouse CD100 fused to the human IgG1 Fc (CD100-Fc), sCD100 significantly enhanced CD40-induced B-cell responses. Furthermore, sCD100 was detected either in sera of mice immunized with T-cell-dependent antigens, or in sera of MRL/lpr mice, but not in sera of mice immunized with T-cell-independent antigens. A significant correlation was observed between the level of sCD100 and the titer of autoantibodies in the serum of MRL/lpr mice. This study's findings suggest a potential role for sCD100 in immune responses, including production of antibody, and autoimmune diseases. (Blood. 2001;97:3498-3504)
The mitochondrial environment is required for activity of the cholesterol side-chain cleavage enzyme, cytochrome P450scc. (1994)

Steroidogenesis is initiated by the conversion of cholesterol to pregnenolone by mitochondrial cytochrome P450scc [cholesterol, reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving); EC 1.14.15.6]. Several subsequent steroidal conversions occur in the endoplasmic reticulum (ER), but the last step in the production of glucocorticoids and mineralocorticoids again occurs in the mitochondria. Although cellular compartmentalization of steroidogenic enzymes appears to be a feature of all steroidogenic pathways, some reports indicate that cholesterol can be converted to pregnenolone outside the mitochondria. To investigate whether P450scc can function outside the mitochondria, we constructed vectors producing P450scc and various fusion enzymes of P450scc with electron-transport proteins and directed their expression to either the ER or the mitochondria. Whether targeted to mitochondria or to the ER, plasmid vectors encoding P450scc and fusion proteins of P450scc with either mitochondrial or microsomal electron-transport proteins produced immunodetectable protein. When expressed in mitochondria, all of these constructions converted 22-hydroxycholesterol to pregnenolone, but when expressed in the ER none of them produced pregnenolone. These results show that P450scc can function only in the mitochondria. Furthermore, it appears to be the mitochondrial environment that is required, rather than the specific mitochondrial electron-transport intermediates.
Time-Course of Smooth Muscle Cell Proliferation following Balloon Angioplasty and Excimer Laser Treatment in an Experimental Animal Model (1991)

Division of Cardiology, Department of Medicine, University of Tübingen, FRG Since Grüntzig et al. [2] introduced Percutaneous Transluminal Coronary Angioplasty (PTCA) in 1977, this technique has become a successful method in the treatment of patients with coronary artery disease [3]. The clinical application of PTCA, however, is limited by the occurrence of restenosis in 30–40% of primary successful treated patients [4, 5, 6]. Transluminal angioplasty, performed with an inflatable balloon, is associated with endothelial denudation and early accumulation of platelets and fibrin [7, 8], splitting of the intima and media [9-11], stretching of the medial layer, and overdistention of the adventitia [12, 13]. Platelet adhesion and aggregation induced by endothelial injury following balloon angioplasty has been shown to result in the release of several mitogens [14], including epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). These components, as well as expression of fibroblast growth factor (FGF) and activation of macrophages, are thought to stimulate migration and proliferation of smooth muscle cells (SMC) in the dilated artery [15–18]. In addition, stimulated smooth muscle cells are also capable of producing intrinsic growth factors [19]. Smooth muscle cell proliferation following PTCA was found to be important for the development of restenosis in several experimental and human postmortem studies [20–22] .
Synthese von All‐D‐Val5‐Angiotensin II‐Asp1‐β‐Amid (1965)

Abstract The synthesis of all‐ D ‐Val 5 ‐Angiotensin II‐Asp 1 ‐β‐Amide (Scheme 2), the antipode of the active principle of Hypertensin CIBA®, is carried out according to known schemes in the L ‐series. It showed neither inhibitory nor angiotensin‐like effects up to concentrations of 10 −3 .
Artificial Membrane Fusion Triggered by Strain-Promoted Alkyne–Azide Cycloaddition (2017)

Artificial systems for controlled membrane fusion applicable for drug delivery would ideally use triggers that are orthogonal to biology. To apply the strain-promoted alkyne-azide cycloaddition (SPAAC) to drive membrane fusion, oxo-dibenzocyclooctyne (ODIBO)-lipid 1 was designed, synthesized, and studied alongside azadibenzocyclooctyne (ADIBO)-lipids 2-4 to assess fusion with liposomes containing azido-lipid 5. Lipids 1-2 were first shown to be effective for liposome derivatization. Next, fusion was evaluated using liposomes containing 1 and varying ratios of PC and PE via a FRET dilution fusion assay, and a 1:1 PC-to-PE ratio yielded the greatest signal change attributed to fusion. Finally, lipids 1-4 were compared, and 1 yielded the greatest triggering of fusion, while 2-4 yielded varying efficacies depending on the structural features of each lipid. Fusion was further validated through STEM studies showing larger multilamellar assemblies after liposome mixing, and FRET assay results supporting the mixing of liposome aqueous contents. This work provides a platform for triggered fusion toward drug delivery applications and an understanding of the effects of lipid structure and membrane composition on fusion.
Specific targeting and delivery of virus envelope-coated nanoparticle cargoes into receptor-bearing cells and subcellular compartments (2007)

1 ABSTRACT Viruses are highly efficient nanoscale machines that not only target specific cell types but also penetrate the cell membrane to deliver the virus genome into the cytoplasm. Recently, we described a simple and highly scalable method to modify the surface of nanoparticles with the membranes of murine leukemia viruses (MLV) and showed that these can deliver a simple cargo into receptor bearing cells (Deniger et al., Nano Lett. 2006 Nov;6(11):2414-21). However, the entry route and subcellular destination of the nanocargoes was not determined. Here we use state-of-the-art microscopy techniques on live cells to visualize the penetration and delivery of the cargo to different subcellular compartments. We show that the MLV membrane-coated nanoparticles are specifically captured on the surface of receptor bearing cells from which they are rapidly taken up into early endosomes. We predict that coating of nanoparticle cargoes with virus envelopes will create a biologically compatible capsule to enhance circulation and delivery of nanoscale drug formulations to specific cells and subcellular compartments.
Replication of hepatitis C virus (2000)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Cryptates: the chemistry of macropolycyclic inclusion complexes (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCryptates: the chemistry of macropolycyclic inclusion complexesJean Marie LehnCite this: Acc. Chem. Res. 1978, 11, 2, 49–57Publication Date (Print):February 1, 1978Publication History Published online1 May 2002Published inissue 1 February 1978https://pubs.acs.org/doi/10.1021/ar50122a001https://doi.org/10.1021/ar50122a001research-articleACS PublicationsRequest reuse permissionsArticle Views3426Altmetric-Citations751LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Novel structurally related compounds reactivate latent HIV-1 in a bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation (2011)

We discovered a group of quinolin-8-ol derivatives that can induce latent HIV-1 in a primary cell model without causing global T cell activation. This work expands the number of latency-reversing agents and provides new possible scaffolds for further drug development research.
Activation of Clotting Factors XI and IX in Patients With Acute Myocardial Infarction (2000)

In acute coronary events, plaque rupture and the subsequent formation of the catalytic tissue factor-factor VIIa complex is considered to initiate coagulation. It is unknown whether clotting factors XI and IX are activated in acute coronary events. Therefore, we prospectively investigated the activation of clotting factors XI and IX as well as activation of the contact system and the common pathway in 50 patients with acute myocardial infarction (AMI), in 50 patients with unstable angina pectoris (UAP), and in 50 patients with stable angina pectoris (SAP). Factor XIa-C1 inhibitor complexes, which reflect acute activation of factor XI, were detected in 24% of the patients with AMI, 8% of the patients with UAP, and 4% of the patients with SAP (P<0.05), whereas factor XIa-alpha(1)-antitrypsin complexes, which reflect chronic activation, were observed equally in all 3 study groups. Factor IX peptide levels were significantly higher in the patients with AMI and UAP compared with the patients with SAP (P<0.01). No differences regarding markers of the common pathway were demonstrated. Fibrinopeptide A levels were elevated in patients with AMI compared with patients with UAP and those with SAP (P<0.01). Factor XIIa- or kallikrein-C1 inhibitor complexes were not increased. In conclusion, this is the first demonstration of the activation of clotting factors XI and IX in patients with acute coronary syndromes. Because these clotting factors are considered to be important for continuous thrombin generation and clot stability, their activation might have clinical and therapeutic consequences.
Novel mutations associated with carnitine palmitoyltransferase II deficiency (1999)

The most common form of carnitine palmitoyltransferase II (CPT II) deficiency occurs in adults and is characterized by muscle pain, stiffness, and myoglobinuria, triggered by exercise, fasting, or other metabolic stress. This study reports the molecular heterogeneity of CPT2 mutations and their biochemical consequences among a series of 59 individuals who were suspected of having CPT II deficiency based on the decreased CPT activity observed in muscle or leukocytes samples, clinical findings, or referral for mutation analysis from other laboratories. Only 19 subjects were considered to be at particularly high risk of CPT II deficiency based on review of their clinical symptoms and residual CPT activity. The samples were initially screened for 11 mutations with allele-specific oligonucleotides (ASO). Extensive sequence analysis was subsequently performed on 14 samples which either had a CPT2 mutation detected by ASO screening or the residual CPT activity was below that observed in ASO positive samples. Three known (P50H, S113L, and F448L) and three novel mutations were identified among 13 individuals in this study. A single nucleotide polymorphism was also identified 11 bp distal to the CPT2 polyadenylation site that will be useful for linkage analysis. Two of the new mutations were single nucleotide missense mutations, R503C and G549D, that occurred in highly conserved regions of the CPT isoforms, and the third was a frameshift mutation, 413 delAG, caused by a 2-bp deletion upstream of a previously identified missense mutation, F448L. The 413 delAG mutation was the second most common mutation identified in our study (20% of mutant alleles) and all individuals with the mutation were of Ashkenazi Jewish ancestry suggesting a defined ethnic origin for the mutation. Despite rigorous mutation analysis, six of 13 individuals identified with CPT2 mutations remained as heterozygotes. We propose that heterozygosity for certain CPT2 mutations, S113L and R503C, is sufficient to render individuals at risk of clinical symptoms.
Disposable Microfluidic Devices: Fabrication, Function, and Application (2005)

This review article describes recent developments in microfluidics, with special emphasis on disposable plastic devices. Included is an overview of the common methods used in the fabrication of polymer microfluidic systems, including replica and injection molding, embossing, and laser ablation. Also described are the different methods by which on-chip operations—such as the pumping and valving of fluid flow, the mixing of different reagents, and the separation and detection of different chemical species—have been implemented in a microfluidic format. Finally, a few select biotechnological applications of microfluidics are presented to illustrate both the utility of this technology and its potential for development in the future.
Decision Making Regarding Smith-Petersen vs. Pedicle Subtraction Osteotomy vs. Vertebral Column Resection for Spinal Deformity (2006)

As the magnitude of resection increases, the ability to correct deformity improves, but also the risk of complication increases. Therein, an understanding of potential applications and complications is helpful.
Viability and survival of hNT neurons determine degree of functional recovery in grafted ischemic rats (1998)

We recently reported behavioral improvements following intrastriatal transplantation of cryopreserved cultured human neuroteratocarcinoma-derived cells (hNT neurons) in rats with cerebral ischemia induced by occlusion of the middle cerebral artery. In the present study, the viability and survival of hNT neurons were evaluated immediately prior to the transplantation surgery and at 3 months post-transplantation in ischemic rats. Cryopreserved hNT neurons were routinely thawed, and trypan blue exclusion viability counts revealed 52-95% viable hNT neurons before transplantation. Monthly behavioral tests, starting at 1 month and extending to 3 months post-transplantation, revealed that ischemic animals that were intrastriatally transplanted with hNT neurons (approximately 40000) and treated with an immunosuppressive drug displayed normalization of asymmetrical motor behavior compared with ischemic animals that received medium alone. Within-subject comparisons of cell viability and subsequent behavioral changes revealed that a high cell viability just prior to transplantation surgery correlated highly with a robust and sustained functional improvement in the transplant recipient. Furthermore, histological analysis of grafted brains revealed a positive correlation between number of surviving hNT neurons and degree of functional recovery. In concert with similar reports on fetal tissue transplantation, we conclude that high cell viability is an important criterion for successful transplantation of cryopreserved neurons derived from cell lines to enhance graft-induced functional effects.
Characterization of New Estrogen Receptor Destabilizing Compounds: Effects on Estrogen-Sensitive and Tamoxifen-Resistant Breast Cancer (2004)

ZK-703 and ZK-253 are potent, long-term inhibitors of growth in both tamoxifen-sensitive and tamoxifen-resistant breast cancer models.
Retiming and clock skew for synchronous systems (1994)

Retiming and clock skew are both timing optimization methods for synchronous circuitry but are usually applied separately. We use the concept of scheduling to form a common background in the formulation of retiming and clock skew, and to study the interplay between, retiming and clock skew. A methodology to optimise synchronous circuitry with both retiming and clock skew is proposed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. (1985)

Although vasodilator therapy has been shown to improve functional capacity in patients with congestive heart failure, there is no evidence that such therapy can prolong survival. Coronary artery ligation in the rat was used to produce a wide range of myocardial infarct sizes and a resultant spectrum of left ventricular dysfunction. To determine the relationship between size of myocardial infarction and long-term survival and to test the hypothesis that long-term therapy with captopril could improve survival after myocardial infarction, 302 rats were randomly assigned to either placebo or captopril therapy 14 days after coronary artery ligation. The animals were kept in a laminar flow unit and followed daily for a 1 year period or until spontaneous death. Size of myocardial infarction was determined by planimetry of serial histologic sections of the left ventricle. One year survival in placebo-treated rats decreased markedly in direct relation to increasing size of infarction (from 71% in noninfarcted rats to only 8% in rats with large infarcts). Long-term captopril therapy prolonged the survival of rats with infarcts (p less than .02). The most marked improvement in survival was noted in the animals with infarcts of moderate size, in which 1 year survival was 21% in the placebo-treated rats and 48% in the captopril-treated rats. Thus, in this experimental preparation of myocardial infarction and left ventricular dysfunction, survival was inversely related to size of infarction. Long-term therapy with captopril, which we had previously shown to improve left ventricular function and lessen dilatation in the chronic phase of infarction, also had a pronounced effect on prolonging survival in this preparation of chronic infarction.
Diet and breast cancer in causation and therapy (1986)

The major macronutrient associated with increased breast cancer risk is dietary fat. Evidence for this association is based on epidemiologic, clinical, and laboratory animal studies. In addition, there is suggestive epidemiologic evidence that differences in postmastectomy survival rates in Japan and the United States may be attributable to differences in dietary fat intake. The importance of the type of fat consumed, as well as its amount, has emerged as an issue of major importance. Some oils, including those rich in monounsaturates, medium chain fatty acids, or omega-3 (n-3) fatty acids appear to lack tumor-promoting effects despite their presence in the diet at high levels. Possible mechanisms by which dietary fat may exert its effects could be either direct or indirect. Direct mechanisms involve dietary modification of membrane structure and function; indirect mechanisms involve alterations in the endocrine system, and/or the metabolism of essential fatty acids to biologically active eicosanoids such as prostaglandins, and suppression of immune responses. Dietary guidelines and dietary intervention trials for the primary and secondary prevention of breast cancer are discussed.