gebhart/patrepeval huggingface dataset:
Interstitial Lung Disease Induced by Drugs and Radiation (2004)

An ever-increasing number of drugs can reproduce variegated patterns of naturally occurring interstitial lung disease (ILD), including most forms of interstitial pneumonias, alveolar involvement and, rarely, vasculitis. Drugs in one therapeutic class may collectively produce the same pattern of involvement. A few drugs can produce more than one pattern of ILD. The diagnosis of drug-induced ILD (DI-ILD) essentially rests on the temporal association between exposure to the drug and the development of pulmonary infiltrates. The histopathological features of DI-ILD are generally consistent, rather than suggestive or specific to the drug etiology. Thus, the diagnosis of DI-ILD is mainly made by the meticulous exclusion of all other possible causes. Drug dechallenge produces measurable improvement in symptoms and imaging in the majority of patients, whereas corticosteroid therapy is indicated if symptoms are present or drug dechallenge is without an effect. Rechallenge is justified in a minority of patients, and is discouraged for diagnostic purposes only. Pneumotox (www.pneumotox.com) provides updated information on drug-induced respiratory disease.
Regression and Time Series Model Selection (1998)

Introduction to model selection the univariate regression model the univariate autoregressive model the multivariate regression model the vector autoregressive model the cross-validation and bootstrap robust and quasi-likelihood model selections non-parametric regressions and wavelets simulations and case studies.
Delayed Initiation of Adjuvant Chemotherapy Among Patients With Breast Cancer (2015)

For patients with breast cancer, adverse outcomes are associated with delaying initiation of adjuvant chemotherapy 91 or more days. Delayed TTC was particularly detrimental among patients with triple-negative breast cancer. The determinants of delays in chemotherapy initiation appeared to be sociodemographic, and clinicians should provide timelier care to all patients.
Approaching Capacity on Noncoherent Block Fading Channels with Successive Decoding (2006)

A receiver structure that uses decision feedback and successive decoding is proposed for a noncoherent channel with independent block fading. The transceiver employs a block interleaver to decompose the channel into a set of independent fading sub-channels. LDPC codes are used on each sub-channel, and the decoded data are fed back to help in channel estimation. Simulation results indicate that the performance of the proposed system is within 0.7 dB of the Shannon capacity of the binary-input block fading channel.
Protective Effect of rhIL-11 in a Murine Model of Acetaminophen-Induced Hepatotoxicity (2001)

Acetaminophen intoxication results in hepatotoxicity associated with increased serum concentrations of hepatocellular leakage enzymes such as aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase, centrilobular degeneration and necrosis, and activation of Kupffer cells. Recombinant human Interleukin-11 (rhIL-11) downregulates the production of proinflammatory mediators from activated macrophages and has direct effects on hepatocyte gene expression. Based on these biological activities of rhIL-11, the effect of pretreatment with rhIL-11 in a murine model of acetaminophen-induced hepatotoxicity was examined. Administration of 500 microg/kg acetaminophen to B6C3F1 mice resulted in progressive hepatotoxicity as demonstrated by elevated serum concentrations of hepatocellular leakage enzymes and TNFalpha and histopathology. Pretreatment with 250 or 500 microg/kg of subcutaneously administered rhIL-11 2 hours before acetaminophen administration reduced serum concentrations of hepatocellular leakage enzymes and TNFalpha by 40-50%. This was associated with a statistically significant decrease in mean severity score for centrilobular hemorrhage and necrosis from grade 3 to grade 2 for rhIL-11-treated animals compared to vehicle. These results indicate that treatment with rhIL-11 has a protective effect in a model of acetaminophen-induced liver damage.
Identification of ZNF217, hnRNP‐K, VEGF‐A and IPO7 as targets for microRNAs that are downregulated in prostate carcinoma (2012)

In primary prostate cancer (PCa), a major cause of cancer-related death in men, the expression of various microRNAs (miRNAs) is deregulated. We previously detected several miRNAs, for example, miR-24 and miR-22, as significantly downregulated in PCa (Szczyrba et al., Mol Cancer Res 2010;8:529-38). An in silico search predicted that zinc finger protein 217 (ZNF217) and importin 7 (IPO7) were potential target genes of these miRNAs. Additionally, for two genes that are deregulated in PCa (heterogeneous nuclear ribonucleoprotein K, hnRNP-K, and vascular endothelial growth factor A, VEGF-A), we identified two regulatory miRNAs, miR-205 and miR-29b. The regulation of the 3'-untranslated regions of the four genes by their respective miRNAs was confirmed by luciferase assays. As expected, the upregulation of ZNF217, hnRNP-K, VEGF-A and IPO7 could be verified at the protein level in the PCa cell lines LNCaP and DU145. ZNF217 and IPO7, which had not yet been studied in PCa, were analyzed in more detail. ZNF217 mRNA is overexpressed in primary PCa samples, and this overexpression translates to an elevated protein level. However, IPO7 was upregulated at the protein level alone. The inhibition of ZNF217 and IPO7 by siRNA resulted in reduced proliferation of the PCa cell lines. ZNF217 could thus be identified as an oncogene that is overexpressed in PCa and affects the growth of PCa cell lines, whereas the function of IPO7 remains to be elucidated in greater detail.
Ubiquitin-specific protease 22-induced autophagy is correlated with poor prognosis of pancreatic cancer (2014)

Ubiquitin‑specific protease 22 (USP22) is a component of the transcription regulatory histone acetylation complex SAGA, which broadly regulates gene transcription and correlates with cancer progression, metastasis and prognosis. Autophagy is a cell pathway with dual functions that promotes cell survival or death. However, it is not known whether USP22 can regulate autophagy in pancreatic cancer. In the present study, we first identified that USP22 was overexpressed in a large number of pancreatic cancer patient samples, concomitant with the increased expression of LC3, a marker of autophagy. Statistical analysis revealed that the increase in USP22 and autophagy was positively correlated with poor prognosis of pancreatic cancer patients. Further investigation using a human pancreatic cancer cell (Panc‑1) identified that the overexpression of USP22 increased the processing of LC3 into the active form LC3‑II and the number of autophagosomes, thus leading to enhanced autophagy. Activation of ERK1/2 kinase rather than AKT1 by USP22 was found to be one of the mechanisms promoting LC3 processing. USP22‑induced autophagy was also found to enhance cell proliferation and resistance to starvation and chemotherapeutic drugs in Panc‑1 cells, therefore expressing an overall effect that promotes cell survival. Collectively, the present study demonstrated a new function of USP22 that induces autophagy, thus leading to the poor prognosis of pancreatic cancer.
Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue. (1991)

It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF). The levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P less than 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN gamma than the sera of healthy children (P less than 0.001 for sIL-2R, IL-2, and IFN gamma; P less than 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P less than 0.05), sCD4 (P less than 0.001), and sCD8 (P less than 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN gamma in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma among grades 1, 2, and 3 of DHF. These results indicate (a) T lymphocytes are activated and produce IL-2 and IFN gamma in vivo during DHF and DF, (b) CD4+ T lymphocytes are activated in DHF and DF, and the level of activation is higher in DHF than in DF, and (c) activation of CD8+ T lymphocytes is evident in DHF, but not in DF.
Definition of specific peptide motifs for four major HLA-A alleles. (1994)

Allele-specific motifs for the human MHC class I molecules, HLA-A1, A3, A11, and A24 were characterized by three complementary approaches. First, amino acid sequence analysis of acid eluted peptide pools from affinity purified class I molecules defined putative motifs 9 or 10 amino acids in length and bearing critical anchor residues at position 2 and at the COOH-terminal. These motifs were distinct, with the exception of the HLA-A3 and A11 motifs that were very similar to each other. Second, the correctness of these putative motifs was verified by analyzing the binding capacity of polyalanine peptide analogues to purified HLA-A molecules. Several alternative anchor residues that were not obvious from the pooled peptide sequencing analysis were identified. Third, sequences of individual peptides eluted from HLA-A1, A11, and A24 were determined by tandem mass spectrometry. Nonamers were the predominant species, although peptides of 8, 10, 11, and 12 amino acids in length were also identified. These peptides displayed anchor residues predicted by the specific motifs at position 2 and at the COOH-terminal, regardless of peptide length. Synthetic versions of the naturally processed peptides were shown to bind to the appropriate HLA-A alleles with IC50 values in the 0.3- to 200-nM range. A rational approach to search Ags with known amino acid sequences for epitopes restricted by some of the most common HLA-A types and of potential clinical importance is now feasible.
A Novel Algorithm for Defending Path-Based Denial of Service Attacks in Sensor Networks (2010)

Existing end-to-end security mechanisms are vulnerable to path-based denial of service attacks (PDoS). If checking integrity and authenticity of a message is done only at the final destination, the intermediate nodes are going to forward bogus packets injected by an adversary many hops before they are detected. Therefore, the adversary can easily overwhelm intermediate nodes by bogus or replayed packets. This attack exhausts the nodes along the path. In addition, other downstream nodes that depend on the exhausted nodes as intermediate nodes will be isolated, and they have to find alternative paths. Regarding broadcast traffic that originated from the base station, if packets were injected by an adversary, the whole network's nodes will be exhausted. Therefore, there is a need to enable intermediate nodes to filter out bogus packets. We adopted a link layer security scheme to enable en route intermediate nodes to filter out any bogus or replayed packet as soon as it is injected into the network. Our scheme can handle different types of traffic. Simulation results show that our algorithm outperforms the one-way hash chain (OHC) algorithm and that it is more scalable.
Transformed mammalian cells are deficient in kinase-mediated control of progression through the G1 phase of the cell cycle. (1991)

To investigate the role of kinase-mediated mechanisms in regulating mammalian cell proliferation, we determined the effects of the general protein kinase inhibitor staurosporine on the proliferation of a series of nontransformed and transformed cultured rodent and human cells. Levels of staurosporine as low as 1 ng/ml prevented nontransformed cells from entering S phase (i.e., induced G1 arrest), indicating that kinase-mediated processes are essential for commitment to DNA replication in normal cells. At higher concentrations of staurosporine (50-75 ng/ml), nontransformed mammalian cells were arrested in both G1 and G2. The period of sensitivity of nontransformed human diploid fibroblasts to low levels of the drug commenced 3 hr later than the G0/G1 boundary and extended through the G1/S boundary. Interference with activity of the G1-essential kinase(s) caused nontransformed human cells traversing mid-to-late G1 at the time of staurosporine addition to be "set back" to the initial staurosporine block point, suggesting the existence of a kinase-dependent "G1 clock" mechanism that must function continuously throughout the early cycle in normal cells. The initial staurosporine block point at 3 hr into G1 corresponds to neither the serum nor the amino acid restriction point. In marked contrast to the behavior of nontransformed cells, neither low nor high concentrations of staurosporine affected G1 progression in transformed cultures; high drug concentrations caused transformed cells to be arrested solely in G2. These results indicate that kinase-mediated regulation of DNA replication is lost as the result of neoplastic transformation, but the G2-arrest mechanism remains intact.
The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation (2002)

Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT-PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in hTERC silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. hTERC methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between hTERC expression and proliferation, telomere length or hTERT expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerase negative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression.
Indigenous Ecological Knowledges: editorial (2016)

PAN: Philosophy Activism Nature, vol. 11, p. 1 urn:ISSN:1443-6124
Suppressor T Cells in Human Diseases (2004)

Although central and peripheral tolerance are important for the regulation of human immune responses to self- and microbial antigens, an important role of suppressor CD4(+) CD25(+) T cells is suggested from the recent investigations of human autoimmune diseases and HIV. These new data provide increasing evidence that altered function of CD4(+) CD25(+) T cells may be an important factor in a wide range of human inflammatory and infectious diseases.
Molecular analysis of Huntington's disease and linked polymorphisms in the Indian population (2003)

The distribution of CAG repeats in the normal population suggests a higher prevalence of HD, closer to that seen in Western Europe. Haplotype analysis suggests the presence of a founder mutation in a subset of families and provides evidence for multiple and geographically distinct origins for the HD mutation in India.
Changes in Cellular mRNA Stability, Splicing, and Polyadenylation through HuR Protein Sequestration by a Cytoplasmic RNA Virus (2013)

The impact of RNA viruses on the post-transcriptional regulation of cellular gene expression is unclear. Sindbis virus causes a dramatic relocalization of the cellular HuR protein from the nucleus to the cytoplasm in infected cells. This is due to the expression of large amounts of viral RNAs that contain high affinity HuR binding sites in their 3â UTRs effectively serving as a sponge for the HuR protein. Sequestration of HuR by Sindbis virus is associated with destabilization of cellular mRNAs that normally bind HuR and rely on it to regulate their expression. Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs due to sequestration of HuR protein by the 3â UTR of transcripts of this cytoplasmic RNA virus. These studies suggest a new molecular mechanism of virus-host interaction that likely has significant impact on virus replication, cytopathology and pathogenesis.
Polymorphonuclear leukocyte-induced vasocontraction and endothelial dysfunction. Role of selectins. (1994)

The roles of selectin adhesion molecules (P- and L-selectin) and their counterreceptor sialyl Lewisx were investigated in polymorphonuclear leukocyte (PMN)-induced cat coronary vasocontraction and endothelial dysfunction. Unstimulated autologous PMNs (10(6) cells/mL) were added to organ chambers containing cat coronary artery rings stimulated with either thrombin (2 U/mL) or hydrogen peroxide (100 mumol/L). PMNs elicited a significant vasocontraction in thrombin- (119 +/- 14 mg) and hydrogen peroxide- (132 +/- 15 mg) stimulated coronary rings. This PMN-induced vasocontraction was significantly attenuated by pretreatment with either an anti-P-selectin, an anti-L-selectin monoclonal antibody (ie, MAb PB 1.3 and MAb DREG-200), or a sialyl Lewis(x)-containing oligosaccharide (SLe(x)-OS). Endothelial function as assessed by endothelium-dependent vasorelaxation to acetylcholine was also significantly attenuated after PMN-induced vasocontraction in stimulated coronary rings. This endothelial dysfunction was significantly prevented by either PB 1.3, DREG-200, or SLe(x)-OS. In contrast, endothelium-independent relaxation to acidified sodium nitrite was not altered by PMN incubation, indicating that vascular smooth muscle function was unaffected. Adherence of PMNs to coronary endothelium also significantly increased following stimulation of endothelium with either thrombin or hydrogen peroxide, but this was significantly attenuated by PB 1.3, DREG-200, or SLe(x)-OS. Thus, PMN-endothelial interaction mediated by either selectin adhesion molecules (ie, P-selectin and L-selectin) or sialyl Lewis(x) may play an important role in PMN-induced vasocontraction and endothelial dysfunction. This mechanism may be important in the early endothelial dysfunction observed following reperfusion of an ischemic coronary vasculature.
Distinct Roles for Tsg101 and Hrs in Multivesicular Body Formation and Inward Vesiculation (2006)

In mammalian cells, epidermal growth factor (EGF) stimulation promotes multivesicular body (MVB) formation and inward vesiculation within MVB. Annexin 1 is required for EGF-stimulated inward vesiculation but not MVB formation, demonstrating that MVB formation (the number of MVBs/unit cytoplasm) and inward vesiculation (the number of internal vesicles/MVB) are regulated by different mechanisms. Here, we show that EGF-stimulated MVB formation requires the tumor susceptibility gene, Tsg101, a component of the ESCRT (endosomal sorting complex required for transport) machinery. Depletion of Tsg101 potently inhibits EGF degradation and MVB formation and causes the vacuolar domains of the early endosome to tubulate. Although Tsg101 depletion inhibits MVB formation and alters the morphology of the early endosome in unstimulated cells, these effects are much greater after EGF stimulation. In contrast, depletion of hepatocyte growth factor receptor substrate (Hrs) only modestly inhibits EGF degradation, does not induce tubulation of the early endosome, and causes the generation of enlarged MVBs that retain the ability to fuse with the lysosome. Together, these results indicate that Tsg101 is required for the formation of stable vacuolar domains within the early endosome that develop into MVBs and Hrs is required for the accumulation of internal vesicles within MVBs and that both these processes are up-regulated by EGF stimulation.
Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors (2001)

Angiogenesis is the development of blood vessels from an existing vasculature. This process is fundamental to both physiological wound healing and the growth of malignant tumors, as it restores or creates a blood supply to growing tissue. In both cases, the release of angiogenic molecules by macrophages recruited to the wound or tumor site is central to the formation of these neovessels. Reduced vascular perfusion in tissues generates tissue ischemia and a marked reduction in local levels of oxygen (hypoxia) and glucose. Cells adapt by switching to anaerobic metabolic pathways, with a concomitant increase in lactate production and reduction in extracellular pH. In tumors, these microenvironmental "stress" factors stimulate tumor cells to secrete a wide array of proangiogenic cytokines and enzymes, promoting the re-establishment of a local vascular supply. Here we review the evidence that these stress factors, in particular hypoxia and high lactate levels, stimulate macrophages to perform similar proangiogenic functions in both tumors and wounds. The resolution of wounds results in restoration of tissue integrity and perfusion, and macrophage presence is reduced to preinjury levels. However, in tumors a high number of macrophages persists and might contribute to the ongoing growth, neovascularization, and metastasis of malignant cells.
World-Wide Web: a distributed hypermedia paradigm for global networking (1994)

The World-Wide Web (WWW) provides a unified client image to an enormous range and variety of information services on the Internet. WWW use presently undergoes a spectacular growth and seems set to surpass that of all other Internet services. WWW combines extreme power with maximal simplicity and ease of use through its metaphor of distributed hypermedia. A WWW document provides formatted text with possibilities of embedded graphics, sound, animation, and hyperlinks. The hyperlinks when selected provide automatic access to other WWW-documents, files or services (FTP, Gopher, News, Telnet, WAIS, Email...) available anywhere on the Internet. This paper reviews some of the freely available WWW software: browsers, servers, and editors. An elementary introduction is given to the underlying protocols: HTML (HyperText Mark-up Language) for the formatting of hyperdocuments, HTTP (Hypertext Transfer Protocol) for the communication between WWW browsers and servers, and URL (Uniform Resource Locators) as a universal addressing scheme for Internet files and services.