gebhart/patrepeval huggingface dataset:
7-N-(Mercaptoalkyl)mitomycins:  Implications of Cyclization for Drug Function (2002)

The Kyowa Hakko Kogyo and Bristol-Myers Squibb companies reported that select mitomycin C(7) aminoethylene disulfides displayed improved pharmacological profiles compared with mitomycin C (1). Mechanisms have been advanced for these mitomycins that differ from 1. Central to many of these hypotheses is the intermediate generation of 7-N-(2-mercaptoethyl)mitomycin C (5). Thiol 5 has been neither isolated nor characterized. Two efficient methods were developed for mitomycin (porfiromycin) C(7)-substituted thiols. In the first method, the thiol was produced by a thiol-mediated disulfide exchange process using an activated mixed mitomycin disulfide. In the second route, the thiol was generated by base-mediated cleavage of a porfiromycin C(7)-substituted thiol ester. We selected four thiols, 7-N-(2-mercaptoethyl)mitomycin C (5), 7-N-(2-mercaptoethyl)porfiromycin (12), 7-N-(2-mercapto-2-methylpropyl)mitomycin C (13), and 7-N-(3-mercaptopropyl)porfiromycin (14), for study. Thiols 5 and 12-14 differed in the composition of the alkyl linker that bridged the thiol with the mitomycin (porfiromycin) C(7) amino substituent. Thiol generation was documented by HPLC and spectroscopic studies and by thiol-trapping experiments. The linker affected the structure of the thiol species and the stability of the thiol. We observed that thiols 5 and 12 existed largely as their cyclic isomers. Evidence is presented that cyclization predominantly occurred at the mitomycin C(7) position. Correspondingly, alkyl linker substitution (13) or extension of the linker to three carbons (14) led to enhanced thiol stability and the predominant formation of the free thiol species. The dominant reaction of thiols 5 and 12-14 or their isomers was dimerization, and we found no evidence that thiol formation led to mitosene production and aziridine ring-opening. These findings indicated that thiol generation was not sufficient for mitomycin ring activation. The potential pharmacological advantages of mitomycin C(7) aminoethylene disulfides compared with 1 is discussed in light of the observed thiol cyclization pathway.
A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up (2003)

<b>Background and aims:</b> Mutant tumour derived DNA has been detected in the sera of colorectal cancer patients. We investigated if mutant serum <i>KRAS2</i> was detectable preoperatively in a large group of patients with colorectal neoplasia. A prospective study of 94 patients who underwent putative curative resection for colorectal carcinoma (CRC) was performed to ascertain if serum mutant <i>KRAS2</i> could be used postoperatively as a disease marker. <b>Methods:</b> Preoperative sera from 78 patients were analysed (group A). Sera from 94 patients were obtained three monthly for up to three years during the postoperative period (group B). Codon 12 and 13 <i>KRAS2</i> mutations were analysed in matched tumour and serum samples. <b>Results:</b> In the preoperative group (group A), <i>KRAS2</i> mutation was found in 41/78 (53%) tumours and in 32/78 (41%) preoperative sera. Of 41 tumour <i>KRAS2</i> mutation positive cases, 31/41 (76%) had an identical serum mutation detectable. In group B, the postoperative follow up group, 60/94 cases were primary tumour <i>KRAS2</i> mutation positive. Of these 60, 16/60 (27%) became persistently serum mutant <i>KRAS2</i> positive postoperatively. Ten of 16 (63%) of these developed a recurrence compared with only 1/44 (2%) patients who remained serum mutant negative (odds ratio 71.7 (95% confidence interval 7.7–663.9; p=0.0000). None of 34 tumour mutation negative cases became serum mutant <i>KRAS2</i> positive postoperatively, despite recurrence in 9/34 patients. The relative hazard of disease recurrence in postoperative serum mutant <i>KRAS2</i> positive patients was 6.37 (2.26–18.0; p=0.000). <b>Conclusions:</b> Serum mutant <i>KRAS2</i> can be detected preoperatively in all stages of colorectal neoplasia. Postoperatively, serum mutant <i>KRAS2</i> is a strong predictor of disease recurrence, stronger even than Dukes’ stage of disease, and thus shows potential for use in clinical practice as a marker of preclinical disease recurrence.
A cloned human cDNA determines expression of a mouse stage-specific embryonic antigen and the Lewis blood group alpha(1,3/1,4)fucosyltransferase. (1990)

The stage-specific embryonic antigen SSEA-1 is a cell-surface oligosaccharide molecule expressed with temporal precision during the murine preimplantation period and implicated in adhesive events involving the process of compaction. We used a mammalian transient expression system to isolate a cloned human cDNA that determines expression of the SSEA-1 molecule. The cDNA sequence predicts a type II transmembrane protein with a domain structure similar to mammalian glycosyltransferases, but without primary sequence similarity to these enzymes. The carboxy-terminal domain of this protein was shown to be catalytically active as a fucosyltransferase when expressed in COS-1 cells as a portion of a secreted protein A fusion peptide. The enzyme is an exceptional glycosyltransferase in that it can use both type I and type II oligosaccharides as acceptor substrates to generate subterminal Fuc alpha(1,4)- and Fuc alpha(1,3)-linkages, respectively, in a manner analogous to the human Lewis blood group fucosyltransferase. Southern blot analysis shows that the cDNA corresponds to sequences syntenic to the Lewis locus on chromosome 19. These results indicate that this cDNA is the product of the human Lewis blood group locus, provide genetic confirmation of the hypothesis that this enzyme can catalyze two distinct transglycosylation reactions, and outline an approach to the isolation of other sequences that determine expression of developmentally regulated oligosaccharide antigens.
Anti-CD22/CD20 Bispecific Antibody with Enhanced Trogocytosis for Treatment of Lupus (2014)

The humanized anti-CD22 antibody, epratuzumab, has demonstrated therapeutic activity in clinical trials of lymphoma, leukemia and autoimmune diseases, treating currently over 1500 cases of non-Hodgkin lymphoma, acute lymphoblastic leukemias, Waldenström's macroglobulinemia, Sjögren's syndrome, and systemic lupus erythematosus. Because epratuzumab reduces on average only 35% of circulating B cells in patients, and has minimal antibody-dependent cellular cytotoxicity and negligible complement-dependent cytotoxicity when evaluated in vitro, its therapeutic activity may not result completely from B-cell depletion. We reported recently that epratuzumab mediates Fc/FcR-dependent membrane transfer from B cells to effector cells via trogocytosis, resulting in a substantial reduction of multiple BCR modulators, including CD22, CD19, CD21, and CD79b, as well as key cell adhesion molecules, including CD44, CD62L, and β7 integrin, on the surface of B cells in peripheral blood mononuclear cells obtained from normal donors or SLE patients. Rituximab has clinical activity in lupus, but failed to achieve primary endpoints in a Phase III trial. This is the first study of trogocytosis mediated by bispecific antibodies targeting neighboring cell-surface proteins, CD22, CD20, and CD19, as demonstrated by flow cytometry and immunofluorescence microscopy. We show that, compared to epratuzumab, a bispecific hexavalent antibody comprising epratuzumab and veltuzumab (humanized anti-CD20 mAb) exhibits enhanced trogocytosis resulting in major reductions in B-cell surface levels of CD19, CD20, CD21, CD22, CD79b, CD44, CD62L and β7-integrin, and with considerably less immunocompromising B-cell depletion that would result with anti-CD20 mAbs such as veltuzumab or rituximab, given either alone or in combination with epratuzumab. A CD22/CD19 bispecific hexavalent antibody, which exhibited enhanced trogocytosis of some antigens and minimal B-cell depletion, may also be therapeutically useful. The bispecific antibody is a candidate for improved treatment of lupus and other autoimmune diseases, offering advantages over administration of the two parental antibodies in combination.
Controlling digital TV set-top box with mobile devices via an IP network (2006)

Digital TV is rolling on with full force recently. Within its capability of transmitting data along with the audiovisual contents, TV program providers can serve their viewers interactively, by offering the customized applications, which run at their viewers' set-top boxes. However, the traditional remote controller, with limited signal transmission distance and designed functionality, restricts the usage scope of applications on DTV within a specific space. In order to defeat this limitation, we devise a novel solution which allows mobile appliances in an IP network, e.g., mobile phones and laptops, to control set-top boxes. Through our special designed system collaborating with a media center responsible for complex multimedia tasks, (such as transcoding and broadcasting digital content), viewers can remotely command their own set-top boxes to record the DTV programs and to watch pre-recorded ones, respectively, by using numerous mobile appliances with the ability to access an IP network. Finally, the experiments proved that our implemented system is very efficient and effectively to control set-top boxes to execute multiple commands in the heterogenous environment combining the DTV network with the IP network
Memapsin 2 (Beta-Secretase) Inhibitors: Drug Development (2008)

Memapsin 2 (beta-secretase, BACE 1) processing of beta-amyloid precursor protein is the first step in the pathway leading to the production of amyloid-beta, thus, it is a major target for the development of inhibitor drug for the treatment of Alzheimers's Disease. Although there are distinctive advantages of this protease as a drug target, the development of drug-like memapsin 2 inhibitors has been somewhat slow since the cloning of the protease seven years ago. Here we review the progress of memapsin 2 inhibitor development using crystal structure-based design cycles. Recent progress has evolved the inhibitors into sizes sufficiently small to penetrate cell membranes and the blood-brain barrier yet retain potency for the inhibition of Abeta production in cultured cells and experimental animals. Such progress lends optimism that clinically useful memapsin 2 inhibitors will eventually be developed.
Reconstructing spatio-temporal activities of neural sources using an MEG vector beamformer technique (2001)

We have developed a method suitable for reconstructing spatio-temporal activities of neural sources by using magnetoencephalogram (MEG) data. The method extends the adaptive beamformer technique originally proposed by Borgiotti and Kaplan to incorporate the vector beamformer formulation in which a set of three weight vectors are used to detect the source activity in three orthogonal directions. The weight vectors of the vector-extended version of the Borgiotti-Kaplan beamformer are then projected onto the signal subspace of the measurement covariance matrix to obtain the final form of the proposed beamformer's weight vectors. Our numerical experiments show that both spatial resolution and output signal-to-noise ratio of the proposed beamformer are significantly higher than those of the minimum-variance-based vector beamformer used in previous investigations. We also applied the proposed beamformer to two sets of auditory-evoked MEG data, and the results clearly demonstrated the method's capability of reconstructing spatio-temporal activities of neural sources.
Graphene Oxide–Polyethylenimine Nanoconstruct as a Gene Delivery Vector and Bioimaging Tool (2011)

Graphene oxide (GO) has attracted an increasing amount of interest because of its potential applications in biomedical fields such as biological imaging, molecular imaging, drug/gene delivery, and cancer therapy. Moreover, GO could be fabricated by modifying its functional groups to impart specific functional or structural attributes. This study demonstrated the development of a GO-based efficient gene delivery carrier through installation of polyethylenimine, a cationic polymer, which has been widely used as a nonviral gene delivery vector. It was revealed that a hybrid gene carrier fabricated by conjugation of low-molecular weight branched polyethylenimine (BPEI) to GO increased the effective molecular weight of BPEI and consequently improved DNA binding and condensation and transfection efficiency. Furthermore, this hybrid material facilitated sensing and bioimaging because of its tunable and intrinsic electrical and optical properties. Considering the extremely high transfection efficiency comparable to that of high-molecular weight BPEI, high cell viability, and its application as a bioimaging agent, the BPEI-GO hybrid material could be extended to siRNA delivery and photothermal therapy.
Evaluation of Seminal Plasma Parameters in Patients With Chronic Prostatitis or Leukocytospermia (1999)

No AccessJournal of UrologyUrological Survey: Abstracts: Urinary Tract Infection1 Apr 1999Evaluation of Seminal Plasma Parameters in Patients With Chronic Prostatitis or Leukocytospermia M. Ludwig, C. Kummel, I. Schroeder-Printzen, R.-H. Ringert, and W. Weidner M. LudwigM. Ludwig More articles by this author , C. KummelC. Kummel More articles by this author , I. Schroeder-PrintzenI. Schroeder-Printzen More articles by this author , R.-H. RingertR.-H. Ringert More articles by this author , and W. WeidnerW. Weidner More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)61748-8AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Evaluation of Seminal Plasma Parameters in Patients With Chronic Prostatitis or Leukocytospermia." The Journal of Urology, 161(4), pp. 1418–1419 Departments of Urology, Justus-Liebig-Universitat, Giessen and Medical School, Georg-August-Universitat, Gottingen, Germany© 1999 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 161Issue 4April 1999Page: 1418-1419 Advertisement Copyright & Permissions© 1999 by American Urological Association, Inc.MetricsAuthor Information M. Ludwig More articles by this author C. Kummel More articles by this author I. Schroeder-Printzen More articles by this author R.-H. Ringert More articles by this author W. Weidner More articles by this author Expand All Advertisement PDF downloadLoading ...
Graph-based mining of multiple object usage patterns (2009)

The interplay of multiple objects in object-oriented programming often follows specific protocols, for example certain orders of method calls and/or control structure constraints among them that are parts of the intended object usages. Unfortunately, the information is not always documented. That creates long learning curve, and importantly, leads to subtle problems due to the misuse of objects.
Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity. (1994)

A costimulatory signal through B7 to its counter-receptor CD28 on T cells enhances T cell activation. We have generated recombinant retroviruses containing cDNA for murine B7 and transduced a panel of murine tumor lines with varying immunogenicity to study the effect of B7 costimulation on antitumor immunity. In contrast to the progressive outgrowth of all wild-type (B7-) tumors in unimmunized syngeneic mice, four immunogenic tumors, lymphoma RMA, EL4, mastocytoma P815, and melanoma E6B2, regressed completely when transduced with the B7 gene. In contrast, four nonimmunogenic tumors, sarcomas MCA101, MCA102, and Ag104, and melanoma B16, remained tumorigenic after transduction of the B7 gene. Immunization with B7-transduced immunogenic tumors enhanced protective immunity and increased specific cytotoxic T lymphocyte (CTL) activity against the respective wild-type tumors as compared to immunization with nontransduced or mock-transduced tumors. Moreover, cocultivation of CTL with B7-transduced EL4 cells augmented the specificity of tumor-reactive CTL in long-term cultures. Treatment by injection of B7-transduced tumor cells cured 60% of mice with established wild-type EL4 lymphoma. In contrast, immunization with nonimmunogenic tumors transduced with B7 did not provide protective immunity and did not increase specific CTL activity. Our results show that tumor immunogenicity is critical to the outcome of costimulation of T cell-mediated tumor immunity by B7.
Tumor associated macrophage in pancreatic cancer (2014)

Pancreatic cancer is a highly malignant tumor.It is of great importance to improve the effectiveness of treatment by studying the mechanisms which lead to invasion and metastasis in pancreatic cancer.In some malignant tumors,tumor associated macrophage (TAM) plays an important role in tumor progression and invasion.TAM also plays an important role in pancreatic cancer which consists mainly of stromal elements.Research into the mechanisms for occurrence and development of pancreatic cancer,the role played by TAM as well as TAM transformation between the different phenotypes may bring a breakthrough in the treatment of pancreatic cancer.

Key words: 
Tumor associated macrophage;  Pancreatic cancer;  Tumor microenvironment
Radiation characteristics of high repetition rate capillary Z-pinch EUV source (2004)

An extreme ultraviolet (EUV) source as a candidate for a light source in next generation lithography systems has been studied. A xenon capillary Z-pinch source was coupled with an all-solid-state magnetic pulse compression (MPC) generator. In order to evaluate the source performance, radiation characteristics such as radiation energy, spectrum and angular radiation distribution were observed, as well as the energy stability at high repetition rate operation. The xenon Z-pinch load was driven by a pulsed current of which peak current and pulse duration were approximately 20 kA and 275 ns, respectively. Changing the pressure condition in the capillary, it was understood that the highest on-axis EUV energy was 4.2 mJ/sr within 2 % bandwidth around 13.5 nm at low-repetition rate. Knowing the effective, usable solid angle of radiation at 34.5 W of EUV power was confirmed at 7 kHz
Differential regulation of indoleamine 2,3-dioxygenase expression by nitric oxide and inflammatory mediators in IFN-γ-activated murine macrophages and microglial cells (1997)

Induction of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) is involved in the immunomodulatory roles of IFN-gamma and evidence suggests that these pathways are functionally cross-regulated. We report here that nitric oxide (NO) negatively modulates the expression of IDO activity in IFN-gamma-primed macrophages, but not in microglial cells from mouse. In MT2 macrophages, the induction of IDO activity by IFN-gamma was further increased by the presence of NOS inhibitors, whereas culturing of IFN-gamma-activated MT2 cells with NO generators produced a marked reduction of IDO activity expression. Conversely, neither NOS inhibitors nor exogenous NO affected the induction of the enzyme activity in N11 microglial cells after IFN-gamma activation. LPS and picolinic acid, two costimulatory agents that up-regulate inducible NOS in activated cells, regulated IDO induction differently in the two cell lines. LPS and picolinic acid caused a significant decrease of IDO activity in IFN-gamma-activated MT2 cells. This effect, however, did not appear to be mediated by the ability of LPS and picolinic acid to stimulate NO production. In N11 cells, LPS further stimulated the enzyme activity and picolinic acid had no effect. Northern blot analysis revealed that, in MT2 macrophages, NOS inhibitors increased the levels of IDO mRNA, while a reduction was observed with picolinic acid. No changes in IDO mRNA levels were detected in N11 cells. Consistent with the functional heterogeneity of phagocytes, the reported results indicate the existence of marked differences in the regulation of IDO expression between murine macrophages and microglial cells.
An Efficient Homomorphic Encryption Protocol for Multi-User Systems. (2012)

Abstract. The homomorphic encryption problem has been an open one for three decades. Recently, Gentry has proposed a full solution. Subsequent works have made improvements on it. However, the time complexities of these algorithms are still too high for practical use. For example, Gentry’s homomorphic encryption scheme takes more than 900 seconds to add two 32 bit numbers, and more than 67000 seconds to multiply them. In this paper, we develop a non-circuit based symmetric-key homomorphic encryption scheme. It is proven that the security of our encryption scheme is equivalent to the large integer factorization problem, and it can withstand an attack with up to � � ln poly����� � chosen plaintexts for any predetermined ��, where � � is the security parameter. Multiplication, encryption, and decryption are almost linear in ����, and addition is linear in ����. Performance analyses show that our algorithm runs multiplication in 108 milliseconds and addition in a tenth of a millisecond for � � = 1024 and � � = 16. We further consider practical multiple-user data-centric applications. Existing homomorphic encryption schemes only consider one master key. To allow multiple users to retrieve data from a server, all users need to have the same key. In this paper, we propose to transform the master encryption key into different user keys and develop a protocol to support correct and secure communication between the users and the server using different user keys. In order to prevent collusion between some user and the server to derive the master key, one or more key agents can be added to mediate the interaction.
Oxygen Pressure in Urine and Its Relation to Intrarenal Blood Flow (1958)

Oxygen tensions in renal pelvic urine, renal venous blood and arterial blood ( P u , P v , P a ) were measured in anesthetized dogs breathing oxygen tensions of 150, 760 and 1900 mm Hg. In dogs having high Diodrast extraction ratios, the respective values for P u were 27, S.E. ± 3; 49 ± 5 and 120 ± 7 mm Hg. Corresponding values for P v were 50 ± 3, 96 ± 8 and 858 ± 47 mm Hg. Renal O 2 consumption was unaffected by oxygen tension; therefore, the increasing P v – P u cannot be interpreted as a gradient across tubule cells. In dogs having low Diodrast extraction ratios, P u was higher (e.g. 72 ± 6 mm Hg in contrast to 49 ± 5 at 1 atm. O 2 ). These results, which are difficult to explain by classical renal hemodynamics, can be accounted for by the cell-separation theory. Assuming that urine oxygen is equilibrated with peritubular capillary blood it is possible to calculate peritubular relative to arterial hematocrit ( H T / H a ). H T / H a , so calculated, averages 0.52 ± .06 for high extraction kidneys and 0.96 ± .06 for low extraction kidneys, thus relating low Diodrast extraction to failure of cell-separation. An alternative mechanism, involving equilibration of urine oxygen with medullary, rather than peritubular, blood could also explain the facts provided that the hematocrit of medullary blood is low. Further work is required to localize the region of low oxygen tension within the kidney: the present results indicate, however, that the region concerned is supplied with blood of low red cell concentration. Oxygen in human bladder urine is largely determined by gaseous equilibration with ureteral walls and cannot be used as a measure of intrarenal oxygen pressure.