gebhart/patrepeval huggingface dataset:
CD20-targeted tetrameric interferon-α, a novel and potent immunocytokine for the therapy of B-cell lymphomas (2009)

Interferon-alpha (IFN-alpha) has direct inhibitory effects on some tumors and is a potent stimulator of both the innate and adaptive immune systems. A tumor-targeting antibody-IFN-alpha conjugate (mAb-IFN-alpha) could kill by direct actions of the monoclonal antibody (mAb) and IFN-alpha on tumor cells and also potentiate a tumor-directed immune response. The modular Dock-and-Lock method (DNL) was used to generate 20-2b, the first immunocytokine having 4 cytokine (IFN-alpha2b) groups that are fused to the humanized anti-CD20 mAb, veltuzumab. Additional mAb-IFN-alpha constructs, each retaining potent IFN-alpha2b biologic activity, also were produced by DNL. The 20-2b shows enhanced antibody-dependent cellular cytotoxicity compared with veltuzumab but lacks complement-dependent cytotoxicity. The 20-2b inhibits in vitro proliferation of lymphoma cells and depletes them from whole human blood more potently than the combination of veltuzumab and a nontargeting, irrelevant, mAb-IFN-alpha. The 20-2b demonstrated superior therapeutic efficacy compared with veltuzumab or nontargeting mAb-IFN-alpha in 3 human lymphoma xenograft models, even though mouse immune cells respond poorly to human IFN-alpha2b. Targeting IFN-alpha with an anti-CD20 mAb makes the immunocytokine more potent than either agent alone. These findings suggest that 20-2b merits clinical evaluation as a new candidate antilymphoma therapeutic.
Biologic therapy for psoriasis: an update on the tumor necrosis factor inhibitors infliximab, etanercept, and adalimumab, and the T-cell-targeted therapies efalizumab and alefacept. (2005)

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European population. Over the last several years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. The goal of this article is to update the progress of the tumor necrosis inhibitors which are available, or under investigation, for clinical use in psoriasis: infliximab, etanercept, and adalimumab, as well as the T-cell-targeted therapies efalizumab and alefacept (Table 1).
Idiopathic Pulmonary Fibrosis (2001)

It is hypothesized that the extent and severity of fibrosis and cellularity found on lung biopsy determine the prognosis and response to therapy in idiopathic pulmonary fibrosis (IPF). The objective of this study was to determine which histopathologic features predict survival in IPF. We prospectively studied 87 patients with usual interstitial pneumonia (UIP) confirmed by surgical lung biopsy. Four pathologists independently graded the extent and severity of specific histopathologic features. We used Cox proportional-hazards models to assess the effect of histopathologic patterns on patients' survival. The effects of age, sex, and smoking were also included in the analysis. Sixty-three patients died during the 17-yr study period. Survival was longer in subjects with lesser degrees of granulation/connective tissue deposition (fibroblastic foci). The degree of alveolar space cellularity, alveolar wall fibrosis, and cellularity did not affect survival. A history of cigarette smoking, the level of dyspnea, and the degree of lung stiffness at presentation were also shown to be independent factors predicting survival. The extent of fibroblastic foci present on lung biopsy predicts survival in IPF. These findings support the hypothesis that the critical pathway to end-stage fibrosis is not "alveolitis" but rather the ongoing epithelial damage and repair process associated with persistent fibroblastic proliferation. Controlling these processes, rather than stopping inflammation, appears most important in preventing progressive disease and the fatal outcome common in IPF.
A global spacecraft control network for spacecraft autonomy research (1996)

ABSTRACT. The Stanford Space Systems Development Laboratory (SSDL) has initiated the development and integration of a worldwide space control network. This network will serve as a command and control architecture for scholastic and amateur spacecraft. In addition, it will offer a unique real world testbed for the application and validation of advanced autonomous spacecraft operations strategies. The proposed network will initially consist of globally distributed amateur radio ground stations at locations throughout North America and Europe. These stations will be linked via the Internet to Stanford and alternate control centers. The Stanford control center will be capable of both human and computer based decision making for the purposes of coordinating user experiments, performing satellite and network resource scheduling, and conducting spacecraft and network fault management. The flexible nature of this project promises to promote validation of high risk autonomy strategies that are too extreme for many operational networks. This paper describes the project&amp;apos;s system architecture, its proposed use as a command and control system, its value as a testbed for spacecraft autonomy research, and its current implementation. 1.
Comparison of Gastrofntestinal Transit in Mobile and Non-Ambulant Elderly Inpatients (1998)

Poster and platform presentations minimal supervision technique that could realistically replace the standard BE.
Amide Analogues of Trichostatin A as Inhibitors of Histone Deacetylase and Inducers of Terminal Cell Differentiation (1999)

Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. We have described previously analogues of the complex natural HD inhibitors trapoxin B and trichostatin A with activities in the submicromolar range. Here we report structure-activity relationship analyses of further analogues of trichostatin A with respect to in vitro inhibition of maize HD-2 and their ability to induce terminal cell differentiation in Friend leukemic cells. This is the first report that shows the correlation between HD inhibitory activity and action on cancer cells on a larger series of similar compounds. Only the compounds that inhibit HD induce differentiation and/or exert antiproliferative activities in cell culture. Our studies support the use of in vitro systems as screening tools and provide structure-activity relationships that merit further investigation of this interesting target.
Antineoplastic activity of a novel multimeric gemcitabine-monophosphate prodrug against thyroid cancer cells in vitro. (2000)

Gemcitabine (Gem) is a deoxycytidine analog that is effective against pancreatic cancer and other malignancies following conversion to the 5'-O-mono-, di- and tri-phosphate forms. We evaluated the cytotoxicity of GemMP[10], a novel multimeric form of 2'-deoxy-2',2"-difluorocytidine-5'-O-monophosphate (gemcitabine monophosphate) against three thyroid carcinoma cell lines established from anaplastic (8505C), papillary (B-CPAP) and poorly-differentiated papillary (BHT-101) cancer. GemMP[10] decreased tumor cell growth at concentrations ranging from 1 to 50 nM. These concentrations were 5- to 10-fold lower than those required for inhibition of tumor cell growth by monomeric Gem. GemMP[10] cytotoxicity occurred via induction of apoptosis. Flow cytometric analysis of GemMP[10] treated cells revealed growth arrest in S-phase. Fas-antigen expression was increased in thyroid cancer cells treated with GemMP[10], whereas Fas-L and Bcl-2 expression were not significantly affected. These results demonstrated that GemMP[10] is a potent cytotoxic agent that serves to induce apoptosis in association with increased Fas expression in cultured thyroid cancer cell lines.
Microsoft Windows 2000 Network Architecture Guide (2000)

The purpose of this guide is to inform the reader about the services that are available in the Microsoft Windows 2000 environment and how to integrate these services into their network architecture. This guide is not intended to provide individual security settings for the network devices. Instead, it is designed to provide the reader an idea of what functionality is recommended in each part of the network.
Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma (2009)

Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.
New methodology for the synthesis of functionalized indolizidine and quinolizidine ring systems (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew methodology for the synthesis of functionalized indolizidine and quinolizidine ring systemsEric D. EdstromCite this: J. Am. Chem. Soc. 1991, 113, 17, 6690–6692Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://doi.org/10.1021/ja00017a060Request reuse permissionsArticle Views540Altmetric-Citations83LEARN 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 InReddit PDF (372 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Carbonic Anhydrase Inhibitors. Inhibition of Cytosolic Isozymes I and II and Transmembrane, Cancer-associated Isozyme IX with Lipophilic Sulfonamides (2003)

A series of new compounds was obtained by reaction of aromatic/heterocyclic sulfonamides incorporating amino groups with N,N-diphenylcarbamoyl chloride and diphenylacetyl chloride. These sulfonamides were assayed for the inhibition of three carbonic anhydrase (CA, EC 4.2.1.1) isozymes: the cytosolic CA I and CA II, and the transmembrane, cancer-associated isozyme CA IX. Good inhibitors against all these isoforms were detected, and the inhibition profile of the newly investigated isozyme IX was observed to be different from that of the cytosolic isozymes, I and II. This may lead to the development of novel anticancer therapies based on the selective inhibition of CA IX.
The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. (1991)

Computerized mapping of atrial fibrillation was performed in animals and man. To study atrial fibrillation in a systematic manner, we developed a clinically relevant experimental model of atrial fibrillation. Chronic mitral regurgitation was created surgically in 25 dogs without opening the pericardium. After several months of chronic mitral regurgitation, the atria became enlarged and sustained atrial fibrillation could be induced by standard programmed electrical stimulation techniques. Computerized isochronous activation maps of the atria were recorded during atrial fibrillation from 208 bipolar electrodes simultaneously. In a parallel study, human atrial fibrillation was mapped with a separate 160-channel intraoperative mapping system in patients with paroxysmal atrial fibrillation who were undergoing surgical correction of the Wolff-Parkinson-White syndrome. The canine activation sequence maps demonstrated a spectrum of rhythm abnormalities ranging from simple atrial flutter to complex atrial fibrillation. They also showed that macroreentrant circuits within the atrial myocardium were responsible for the entire spectrum of arrhythmias. Atrial reentry was also documented during human atrial fibrillation. All patients had nonuniform conduction around regions of bidirectional block in both atria resulting in multiple discrete wave fronts. In addition, six patients had a single reentrant circuit in the right atrium in which bidirectional block of the activation wave front occurred along the sulcus terminals between the venae cavae. The left atrium in all patients demonstrated multiple wave fronts and conduction block, but left atrial reentry could not be detected. Both the experimental study and the clinical study demonstrated that multiple wave fronts, nonuniform conduction, bidirectional block, and large (macroreentrant) reentrant circuits occur during atrial fibrillation. The presence of macroreentrant circuits and the absence of either microreentrant circuits or evidence of atrial automaticity suggests that atrial fibrillation should be amenable to surgical ablation.
Repression of bacterial lipoprotein production byFrancisella novicidafacilitates evasion of innate immune recognition (2012)

Innate recognition systems, including the Toll-like receptors (TLRs), play a critical role in activating host defences and proinflammatory pathways in response to infection. Pathogens have developed strategies to subvert TLRs in order to survive and replicate within the host. The model intracellular pathogen, Francisella novicida, modulates host defences to promote survival and replication in macrophages. TLR2, which recognizes bacterial lipoproteins (BLPs), is critical for activating host defences and proinflammatory cytokine production in response to Francisella infection. Here we show that the F. novicida protein FTN_0757 acts to repress BLP production, dampening TLR2 activation. The ΔFTN_0757 mutant strain induced robust TLR2-dependent cytokine production in macrophages compared with wild-type bacteria, and produced increased amounts of BLPs. The deletion of one BLP (FTN_1103) from ΔFTN_0757 decreased the total BLP concentration to near wild-type level sand correlated with a decrease in the inductionof TLR2 signalling. The overproduction of BLPs also contributed to the in vivo attenuation of the ΔFTN_0757 mutant, which was significantly rescued when FTN_1103 was deleted. Taken together, these data reveal a novel mechanism of immune evasion by the downregulation of BLP expression to subvert TLR2 activation, which is likely used by numerous other intracellular bacterial pathogens.
The Hartley transform (1986)

The author describes the fast algorithm he discovered for spectral analysis and indeed any purpose to which Fourier Transforms and the Fast Fourier Transform are normally applied.
Antigen‐specific immunotherapy of cervical and ovarian cancer (2008)

We contrast the efforts to treat ovarian cancer and cervical cancer through vaccination because of their different pathobiology. A plethora of approaches have been developed for therapeutic vaccination against cancer, many of which target defined tumor-associated antigens (TAAs). Persistent infection with oncogenic human papillomavirus (HPV) types causes cervical cancer. Furthermore, cervical cancer patients frequently mount both humoral and T-cell immune responses to the HPV E6 and E7 oncoproteins, whose expression is required for the transformed phenotype. Numerous vaccine studies target these viral TAAs, including recent trials that may enhance clearance of pre-malignant disease. By contrast, little is known about the etiology of epithelial ovarian cancer. Although it is clear that p53 mutation or loss is a critical early event in the development of epithelial ovarian cancer, no precursor lesion has been described for the most common serous histotype, and even the location of its origin is debated. These issues have complicated the selection of appropriate ovarian TAAs and the design of vaccines. Here we focus on mesothelin as a promising ovarian TAA, because it is overexpressed and immunogenic at high frequency in patients, is displayed on the cell surface, and potentially contributes to ovarian cancer biology.
Identification of an outer membrane protein involved in utilization of hemoglobin-haptoglobin complexes by nontypeable Haemophilus influenzae (1996)

A recombinant plasmid containing a 6.5-kb fragment of nontypeable Haemophilus influenzae (NTHI) chromosomal DNA was shown to confer a hemoglobin-haptoglobin-binding phenotype on Escherichia coli. Use of a mini-Tn10kan transposon for random insertion mutagenesis of this recombinant plasmid allowed localization of the NTHI DNA responsible for this hemoglobin-haptoglobin-binding phenotype to a 3.5-kb PstI-XhoI fragment within the 6.5-kb NTHI DNA insert. When this mutagenized NTHI DNA fragment was used to transform the wild-type NTHI strain, the resultant kanamycin-resistant mutant exhibited significantly decreased abilities to bind hemoglobin-haptoglobin and utilize it as a source of heme for aerobic growth in vitro. This mutant also lacked expression of a 115-kDa outer membrane protein that was present in the wild-type parent strain. Transformation of this mutant with wild-type NTHI chromosomal DNA restored the abilities to bind and utilize hemoglobin-haptoglobin and to express the 115-kDa outer membrane protein. Nucleotide sequence analysis of the relevant NTHI DNA revealed the presence of a gene, designated hhuA, that encoded a predicted 117,145-Da protein. The HhuA protein exhibited features typical of a TonB-dependent outer membrane receptor and had significant identity with the hemoglobin receptors of both Haemophilus ducreyi and Neisseria meningitidis.
Correlation of Diffusion Tensor Imaging with Histology in the Developing Human Frontal Cerebrum (2009)

Transient early cerebral laminar organization resulting from normal developmental events has been revealed in human beings through histology and imaging studies. DTI studies have postulated that the fractional anisotropy (FA)-based differentiation of different laminar structures reflects both differing cellular density over the glial fibers and fiber alignment in respective regions. The aim of this study was to correlate FA values in these transient zones with histology. Brain DTI was performed on 50 freshly aborted human fetuses with gestational ages (GA) ranging from 12 to 42 weeks. Regions of interest were placed on the cortical plate, subplate, intermediate and germinal matrix (GMx) zones of the frontal lobe to quantify FA values. Glial fibrillary acidic protein (GFAP), neurofilament (NF) and neuron-specific enolase (NSE) immunohistochemical analyses were performed for the cortical plate, intermediate zone and GMx. In the cortical plate, a significant positive correlation was observed between FA values and percentage area of GFAP expression in fetuses <or=28 weeks of GA (r = 0.56, p = 0.01). FA values showed a significant positive correlation with the percentage area of NF expression in the intermediate zone (r = 0.54, p = 0.05). A significant positive correlation was also observed between FA and the number of NSE-positive cells per mm(2) in the GMx (r = 0.76, p < 0.01) and subplate (r = 0.59, p = 0.03) zones. The results of our study suggest that the FA can be used as noninvasive marker of neurodevelopmental events in the frontal lobe of human fetal brain.
Protein kinase C--a novel target for rational anti-cancer drug design? (1989)

Chemical structures and some properties of activators and inhibitors of PKC are reviewed with the aim of answering the question: is PKC a plausible target for potential pharmacological intervention with benefit in the treatment of malignant disease?
Recent advances in silicon-based passive and active optical interconnects (2015)

Silicon photonics has experienced phenomenal transformations over the last decade. In this paper, we present some of the notable advances in silicon-based passive and active optical interconnect components, and highlight some of our key contributions. Light is also cast on few other parallel technologies that are working in tandem with silicon-based structures, and providing unique functions not achievable with any single system acting alone. With an increasing utilization of CMOS foundries for silicon photonics fabrication, a viable path for realizing extremely low-cost integrated optoelectronics has been paved. These advances are expected to benefit several application domains in the years to come, including communication networks, sensing, and nonlinear systems.
Cardiovascular and systemic responses to inhaled pollutants in rodents: effects of ozone and particulate matter. (2001)

Striking similarities have been observed in a number of extrapulmonary responses of rodents to seemingly disparate ambient pollutants. These responses are often characterized by primary decreases in important indices of cardiac and thermoregulatory function, along with secondary decreases in associated parameters. For example, when rats are exposed to typical experimental concentrations of ozone (O(3), they demonstrate robust and consistent decreases in heart rate (HR) ranging from 50 to 100 beats per minute, whereas core temperature (T(co) often falls 1.5-2.5 degrees C. Other related indices, such as metabolism, minute ventilation, blood pressure, and cardiac output, appear to exhibit similar deficits. The magnitudes of the observed decreases may be modulated by changes in experimental conditions and appear to vary inversely with both ambient temperature and body mass. More recent studies in which both healthy and compromised rats were exposed to either particulate matter or its specific components yielded similar results. The agents studied included representative examples of ambient, combustion, and natural source particles, along with individual or combined exposures to their primary metallic constituents. In addition to the substantial decreases in HR and T(co), similar to those seen with the O(3)-exposed rats, these animals also displayed numerous adverse changes in electrocardiographic waveforms and cardiac rhythm, frequently resulting in fatal outcomes. Although there is only limited experimental evidence that addresses the underlying mechanisms of these responses, there is some indication that they may be related to stimulation of pulmonary irritant receptors and that they may be at least partially mediated via the parasympathetic nervous system.
Poly(ethylene-co-propylene macromonomer)s:  Synthesis and Evidence for Starlike Conformations in Dilute Solution (2008)

By use of two sequential coordination−insertion polymerizations, a series of ethylene-co-propylene-based comb polymers was synthesized. First, poly(ethylene-co-propylene) macromonomers featuring one unsaturated chain end were synthesized using a titanium bis(phenoxyimine) catalyst. The macromonomers were then homopolymerized using a living nickel α-diimine catalyst. The molecular weights and corresponding number of arms for each poly(macromonomer) were determined using size-exclusion chromatography with viscometry detection and universal calibration. Viscosity−molecular weight conformation plots for the poly(macromonomer)s revealed compact solution structures. Furthermore, viscometric radii for each poly(macromonomer) (Rv) and corresponding linear macromonomer (Rv)a were determined and the ratio (Rv)/(Rv)a for each pair was compared to those of a variety of polyisoprene-based star polymers with similar functionality. The comparison revealed that despite the obvious comb topology of the poly(macromonomer)s their dilute solution conformations correspond reasonably well to the bona fide polyisoprene stars.