gebhart/patrepeval huggingface dataset:
The IGF/IGFBP system in CNS malignancy (2001)

The insulin-like growth factor (IGF) system includes IGF-I and IGF-II, the type I and type II IGF receptors, and specific IGF binding proteins (IGFBP-1 to IGFBP-6). These factors regulate both normal and malignant brain growth. Enhanced expression of IGF-I and IGF-II mRNA transcripts has been demonstrated in gliomas, meniningiomas, and other tumours. Abnormal imprinting of IGF-II occurs in gliomas, medulloblastomas, and meningiomas. Both types of IGF receptor are expressed in gliomas and, in particular, the type I IGF receptor appears to be upregulated in malignant brain tissue. Antisense IGF-I receptor mRNA induces an antitumour response, resulting in complete brain tumour regression. Clinical trials for the treatment of brain tumours in humans based on a gene transfer protocol using IGF-I receptor antisense are under way. All six IGFBPs are expressed to a variable extent in brain tumours. High concentrations of IGFBP-2 are found in cerebrospinal fluid from patients with malignant central nervous system tumours; therefore, IGFBP-2 might be a useful marker for these tumours. IGFBP-4 appears to be a negative regulator of tumour proliferation. Both in vitro and in vivo experiments suggest that the IGF system represents an important target for the treatment of malignant central nervous system tumours and the ongoing trials should provide valuable information for future therapeutic approaches.
Oncolytic HSV Armed with Platelet Factor 4, an Antiangiogenic Agent, Shows Enhanced Efficacy (2006)

Oncolytic herpes simplex viruses (HSV) have emerged as a promising platform for cancer therapy. However, efficacy as single agents has thus far been unsatisfactory. Tumor vasculature is critical in supporting tumor growth, but successful antiangiogenic approaches often require maintaining constant levels of antiangiogenic products. We hypothesized that oncolytic HSV has the potential to destroy tumor vasculature and that this effect can be enhanced by combination with antiangiogenic gene transfer. We examined the strategy of arming oncolytic HSV with an antiangiogenic transgene, platelet factor 4 (PF4). The PF4 transgene was inserted into oncolytic HSV G47Delta utilizing a bacterial artificial chromosome construction system. Whereas bG47Delta-empty showed robust cell killing and migration inhibition of proliferating endothelial cells (HUVEC and Py-4-1), the effect was further enhanced by PF4 expression. Importantly, enhanced potency did not impede viral replication. In vivo, bG47Delta-PF4 was more efficacious than its nonexpressing parent bG47Delta-empty at inhibiting tumor growth and angiogenesis in both human U87 glioma and mouse 37-3-18-4 malignant peripheral nerve sheath tumor models. Enhancing the antiangiogenic properties of oncolytic HSV through the expression of antiangiogenic factors such as PF4 is a powerful new strategy that targets both the tumor cells and tumor vasculature.
Occult osseous lesions documented by magnetic resonance imaging associated with anterior cruciate ligament ruptures (1992)

Magnetic resonance images (MRI) were performed within three weeks of anterior cruciate ligament (ACL) rupture on 75 skeletally mature patients. Occult bony lesions were documented in 64 (85%) of the patients. Of the 64 patients with bone injuries, 83% had lesions of the lateral compartment. The lateral femoral condyle was involved in 50%, and the lateral tibial plateau was injured in 50% of the patients with changes. Nineteen of the 64 patients had more than one area of bony injury. Although the majority of bony lesions resolve, permanent alterations remained in some cases. This study has implications that may affect rehabilitation and the long-term prognosis in those patients with extensive bony and associated articular cartilage injuries.
Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema (2012)

Lymphedema is a dreaded complication of cancer treatment. However, despite the fact that >5 million Americans are affected by this disorder, the development of effective treatments is limited by the fact that the pathology of lymphedema remains unknown. The purpose of these studies was to determine the role of inflammatory responses in lymphedema pathology. Using mouse models of lymphedema, as well as clinical lymphedema specimens, we show that lymphatic stasis results in a CD4 T-cell inflammation and T-helper 2 (Th2) differentiation. Using mice deficient in T cells or CD4 cells, we show that this inflammatory response is necessary for the pathological changes of lymphedema, including fibrosis, adipose deposition, and lymphatic dysfunction. Further, we show that inhibition of Th2 differentiation using interleukin-4 (IL-4) or IL-13 blockade prevents initiation and progression of lymphedema by decreasing tissue fibrosis and significantly improving lymphatic function, independent of lymphangiogenic growth factors. We show that CD4 inflammation is a critical regulator of tissue fibrosis and lymphatic dysfunction in lymphedema and that inhibition of Th2 differentiation markedly improves lymphatic function independent of lymphangiogenic cytokine expression. Notably, preventing and/or reversing the development of pathological tissue changes that occur in lymphedema may be a viable treatment strategy for this disorder.
Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation. (2000)

Phosphatidylinositol-3 kinase (PI3K) is one of the most important regulatory proteins that is involved in different signaling pathways and controlling of key functions of the cell. The double-enzymatic activity of PI3K (lipid kinase and protein kinase) as well as the ability of this enzyme to activate a number of signal proteins including some oncoproteins determines its fundamental significance in regulation of cell functions such as growth and survival, aging, and malignant transformation. Among the main effectors of PI3K are the mitogen-transducing signal proteins (protein kinase C, phosphoinositide-dependent kinases, small G-proteins, MAP (mitogen activated protein) kinases), which are activated either via their interaction with lipid products of PI3K or through PI3K-dependent phosphorylation of proteins. The anti-apoptotic effect of PI3K is realized by activation of proteins from another signaling pathway--protein kinase B (PKB) and/or PKB-dependent enzymes (GSK-3, ILK). PI3K plays a critical role in malignant transformation. PI3K itself possesses oncogenic activity and also forms complexes with some viral or cellular oncoproteins (src, ras, rac, alb, T-antigen), whose transforming activities are realized only in presence of PI3K. The transforming effect of PI3K is supposed to occur on the basis of complex alterations in cellular signaling pathways: appearance of constitutively generated PI3K-dependent mitogen signal and activation of some protooncogenes (src, ras, rac, etc.), PI3K/PKB-pathway stimulation resulting in delay of apoptosis and increase of cell survival, and actin cytoskeleton reorganization.
Expression of the L14 lectin during mouse embryogenesis suggests multiple roles during pre- and post-implantation development (1992)

Abstract A cDNA encoding L14, the lactose-binding, soluble lectin of relative molecular mass 14 × 103, has been isolated in a differential screen designed to identify genes that are regulated during the differentiation of murine embryonic stem cells in vitro. The expression patterns of the gene and of the encoded protein during mouse embryogenesis are consistent with the lectin playing a role at several stages of development. Firstly, it is initially synthesised in the trophectoderm of expanded blastocysts immediately prior to implantation, suggesting that it may be involved in the attachment of the embryo to the uterine epithelium. Secondly, in the postimplantation embryo, the lectin is abundantly expressed in the myotomes of the somites. This observation, when taken together with data indicating a role for the lectin in myoblast differentiation in culture, suggests that the protein is important in muscle cell differentiation. Finally, within the nervous system expression of this gene is activated early during the differentiation of a particular subset of neurones.
Vaccination with multiple peptides derived from novel cancer‐testis antigens can induce specific T‐cell responses and clinical responses in advanced esophageal cancer (2009)

We previously identified three novel HLA-A24-restricted epitope peptides, which were derived from three cancer-testis antigens, TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3), as targets for cancer vaccination against esophageal squamous cell carcinoma (ESCC). To examine the safety, immunogenicity, and antitumor effect of vaccine treatment using a combination of these three peptides, 10 HLA-A2402-positive advanced ESCC patients who failed to standard therapy were enrolled in a phase I clinical trial. Each of the three peptides (1 mg each) was intradermally administered with 1 mL of incomplete Freund's adjuvant to the neck in three separate regions weekly for 5 weeks. The cancer vaccination therapy was well tolerated without any treatment-associated adverse events of grade 3 or 4. The TTK-, LY6K-, and/or IMP-3-specific T-cell immune responses were observed by enzyme-linked immunospot assay in peripheral blood lymphocytes obtained from nine of the 10 ESCC patients after their vaccination. The median survival time after the vaccination was 6.6 months. The vaccination could induce good clinical responses in 50% of the 10 patients. One patient experienced a complete response in hepatic metastasis lasting 7 months, one showed objective responses in all lung metastasis lesions, and three patients revealed a stable disease condition for at least 2.5 months. The cancer vaccine therapy using these three peptides demonstrated satisfactory safety and good immunogenicity as well as promising disease control rate, and therefore warrants further clinical studies.
Orientation of Asymmetric Stem Cell Division by the APC Tumor Suppressor and Centrosome (2003)

Stem cell self-renewal can be specified by local signals from the surrounding microenvironment, or niche. However, the relation between the niche and the mechanisms that ensure the correct balance between stem cell self-renewal and differentiation is poorly understood. Here, we show that dividing Drosophila male germline stem cells use intracellular mechanisms involving centrosome function and cortically localized Adenomatous Polyposis Coli tumor suppressor protein to orient mitotic spindles perpendicular to the niche, ensuring a reliably asymmetric outcome in which one daughter cell remains in the niche and self-renews stem cell identity, whereas the other, displaced away, initiates differentiation.
Effects of Medium Perfusion Rate on Cell-Seeded Three-Dimensional Bone Constructs in Vitro (2003)

Cellular activity at the center of tissue-engineered constructs in static culture is typically decreased relative to the construct periphery because of transport limitations. We have designed a tissue culture system that perfuses culture medium through three-dimensional (3D) porous cellular constructs to improve nutrient delivery and waste removal within the constructs. This study examined the effects of medium perfusion rate on cell viability, proliferation, and gene expression within cell-seeded 3D bone scaffolds. Human trabecular bone scaffolds were seeded with MC3T3-E1 osteoblast-like cells and perfused for 1 week at flow rates of 0.01, 0.1, 0.2, and 1.0 mL/min. Confocal microscopy after 1 week of culture indicated that a flow rate of 1.0 mL/min resulted in substantial cell death throughout the constructs whereas lowering the flow rate led to an increasing proportion of viable cells, particularly at the center of the constructs. DNA analysis showed increases in cell proliferation at a flow rate of 0.01 mL/min relative to 0.2 mL/min and static controls. Conversely, mRNA expressions of Runx2, osteocalcin, and alkaline phosphatase were upregulated at 0.2 mL/min compared with lower flow rates as quantified by real-time RT-PCR. These data suggest that medium perfusion may benefit the development of 3-D tissues in vitro by enhancing transport of nutrients and waste within the constructs and providing flow-mediated mechanical stimuli.
A tuneable, switchable dielectric grating (1993)

Electromagnetic scattering characteristics of dielectric gratings are examined numerically using the finite-element method. The gratings are created by introducing pressurized dielectric fluid into periodic tubes within a dielectric sheet. A structure is presented which has an extremely narrow stop-band (total power reflection) immediately adjacent to a passband (total transmission). It is shown that the critical bands can be shifted by changing the fluid pressure, at a cost of only slightly less than perfect passband transmission (97%), while the rejection band remains perfect (100%). Thus, a unique tuneable, switchable frequency selective surface can be easily realized.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Fc binding site for streptococcal protein G is in the C gamma 2-C gamma 3 interface region of IgG and is related to the sites that bind staphylococcal protein A and human rheumatoid factors. (1989)

Abstract The isolated 35 kDa fragment of protein G obtained by papain digestion of group G streptococci was found to bind solid phase intact IgG, Fc (2C gamma 2 + 2C gamma 3 domains), F(ab')2 and F(acb)2 (F(ab')2 + 2C gamma 2 domains) fragments but not pFc' (2C gamma 3 domains) fragments. The level of binding to rabbit F(acb)2 and rabbit F(ab')2 fragments was similar. Protein G binding to solid phase Fc fragments was inhibited by IgG, Fc, staphylococcal protein A and its monovalent fragment D, but was enhanced by F(ab')2 fragments. Chemical modification of tyrosine but not histidine residues of IgG abrogated its ability to inhibit the binding of protein G to solid phase Fc fragments. Protein G was found to strongly inhibit the binding of a monoclonal and a polyclonal human rheumatoid factor to IgG. These findings indicate that protein G binds with separate sites to the Fc and F(ab')2 fragments of IgG, that the interaction with the Fc fragment occurs at the C gamma 2-C gamma 3 domain interface region and that tyrosine but not histidine residues in this area are likely involved. The relationship of the Fc fragment-binding site specificity of protein G to that of other microbial IgG binding proteins and human rheumatoid factors is discussed.
The Gut Microbiome and Individual-Specific Responses to Diet (2020)

Nutritional content and timing are increasingly appreciated to constitute important human variables collectively impacting all aspects of human physiology and disease. However, person-specific mechanisms driving nutritional impacts on the human host remain incompletely understood, while current dietary recommendations remain empirical and nonpersonalized. Precision nutrition aims to harness individualized bodies of data, including the human gut microbiome, in predicting person-specific physiological responses (such as glycemic responses) to food. With these advances notwithstanding, many unknowns remain, including the long-term efficacy of such interventions in delaying or reversing human metabolic disease, mechanisms driving these dietary effects, and the extent of the contribution of the gut microbiome to these processes. We summarize these conceptual advances, while highlighting challenges and means of addressing them in the next decade of study of precision medicine, toward generation of insights that may help to evolve precision nutrition as an effective future tool in a variety of "multifactorial" human disorders.
Presence of CpG DNA and the Local Cytokine Milieu Determine the Efficacy of Suppressive DNA Vaccination in Experimental Autoimmune Encephalomyelitis (1999)

We here study the adjuvant properties of immunostimulatory DNA sequences (ISS) and coinjected cytokine-coding cDNA in suppressive vaccination with DNA encoding an autoantigenic peptide, myelin basic protein peptide 68-85, against Lewis rat experimental autoimmune encephalomyelitis (EAE). EAE is an autoaggressive, T1-mediated disease of the CNS. ISS are unmethylated CpG motifs found in bacterial DNA, which can induce production of type 1 cytokines in vertebrates through the innate immune system. Because ISS in the plasmid backbone are necessary for efficient DNA vaccination, we studied the effect of one such ISS, the 5'-AACGTT-3' motif, in our system. Treatment with a DNA vaccine encoding myelin basic protein peptide 68-85 and containing three ISS of 5'-AACGTT-3' sequence suppressed clinical signs of EAE, while a corresponding DNA vaccine without such ISS had no effect. We further observed reduced proliferative T cell responses in rats treated with the ISS-containing DNA vaccine, compared with controls. We also studied the possible impact of coinjection of plasmid DNA encoding rat cytokines IL-4, IL-10, GM-CSF, and TNF-alpha with the ISS-containing DNA vaccine. Coinjection of IL-4-, IL-10-, or TNF-alpha-coding cDNA inhibited the suppressive effect of the DNA vaccine on EAE, whereas GM-CSF-coding cDNA had no effect. Coinjection of cytokine-coding cDNA with the ISS-deficient DNA vaccine failed to alter clinical signs of EAE. We conclude that the presence of ISS and induction of a local T1 cytokine milieu is decisive for specific protective DNA vaccination in EAE.
New Photolabile Protecting Groups in Nucleoside and Nucleotide Chemistry—Synthesis, Cleavage Mechanisms and Applications (1998)

Abstract New photolabile protecting groups have been found in the 2-(2-nitrophenyl)ethoxycarbonyl and the 2-(2-nitrophenyl)ethylsulfonyl group, respectively. The influence of substituents at the phenyl ring as well as the side-chain has been investigated regarding the photolysis rates on irradiation at 365 mn. β-Branching in the side-chain leads to highly increased rates of photodeprotection. A new type of photocleavage mechanism consisting of a photoinduced β-elimination process is proposed.
PROTEOMICS Reviews 2016 (2016)

Michael J. Dunn This issue of PROTEOMICS contains Part 1 of the 2016 collection of review articles covering various aspects of proteomics technologies and their application in the biosciences. Part 2, containing the remainder of the 2016 collection of review articles, will be published in PROTEOMICS Volume 16, Issue 5. We firmly believe that such an annual collection of review articles is an excellent way for both relative newcomers and experts to keep abreast of developments in the field, and we hope that you will find this year's collection of 27 review articles interesting, informative and stimulating. Please remember that the Proteomics Clinical Applications Reviews 2016 issue will also be published soon (Issue 4, Volume 10). You should certainly not miss this issue in order to keep up-to-date with exciting recent developments in the field of biomedical proteomics! Finally, we are already planning the next collection of review articles that will be published in February 2017 as the PROTEOMICS Reviews 2017 (Issue 4, Volume 17). More information can be found in the Call for Papers, also in this issue. Michael J. Dunn Founding Editor
Ex ova chick chorioallantoic membrane as a novel in vivo model for testing biosensors (2003)

A major problem with implantable sensors is their short in vivo lifetime, due to strong tissue reactions (i.e., inflammation and fibrosis) caused by the implant and the failure of sensor components. The tissue reactions to the sensor, the biocompatibility of components, and the function of the sensor must be evaluated by using in vivo models. Current methods of in vivo biosensor testing are time- and labor- intensive and expensive. In addition, the results often vary on the basis of the surgical skills of the investigator. The in ova chorioallantoic membrane (CAM) of the developing chicken embryo was previously developed in our laboratory as a novel in vivo system to test biomaterials. In this new article, we describe a novel approach for testing biosensors in vivo using the ex ova CAM model as an alternative to the traditional mammalian models. Fertilized chicken eggs were incubated for 3 days in ova and then transferred into a petri dish (ex ova) for further incubation at 37 degrees C and 80% humidity. After 1 week of incubation, acetaminophen biosensors, used as model sensors, were placed on top of the CAM and allowed to incorporate for 1 week. Biosensors were then tested for their sensitivity to acetaminophen. CAM venules were injected with 0.2 mL of a 3.6 mM acetaminophen solution. The current produced by the sensor reflected the change in blood acetaminophen levels. Sensors were also assessed by using gross and histological evaluations. We previously reported on the similarity of the tissue response of the CAM with the mammalian models. The low cost, simplicity, and possibility to continuously visualize the sensor test site through a cell culture dish make this animal model particularly attractive for the rapid in vivo screening of biosensors.
130 Gsample/s photonic analog to digital converter (2004)

Digital processing of the received signals in radar systems leads to higher performance and the ability to rapidly reconfigure such systems. Typically, the analog-to-digital converter (ADC) is the major bottleneck in realizing the digital receiver. Time stretch (TS) preprocessing is a new photonic based approach that can potentially boost the capability of the available electronic ADCs (Coppinger et al, 1999; Bhushan et al, 2000). In this approach, the analog signal is imposed on a chirped optical carrier using an electro-optic modulator. This time to wavelength mapped signal is then dispersed and hence stretched in time prior to digitization by the electronic ADC. Time stretching increases the effective sampling rate and input bandwidth of the ADC. We demonstrate a photonic ADC with a time stretch preprocessor. The system has a sampling rate of 130 GSa/s and a signal-to-noise ratio exceeding 7 effective number of bits.
Electrical impedance tomography/applied potential tomography (1993)

A survey of recent work on electrical impedance tomography as presented at a recent IEE colloquium.
Internetworking with Xinu (1987)

The first volume of this important two-volume series described each step of the design and decision making process, while Volume Two, Internetworking with XINU--covers internetworking and user interface software. Professional software programmers can learn how protocol software fits into an operating system and how VAX software works as well.
Brain renin-angiotensin system in cognitive function: pre-clinical findings and implications for prevention and treatment of dementia. (2009)

Biochemical, physiological and functional studies suggest that the brain renin-angiotensin system (RAS) is regulated independently of the peripheral RAS. Also, all enzymes and peptides necessary for the biosynthesis of various angiotensins have been recognized within the central nervous system. There are divergent opinions concerning the localization of the different components of this system which is not fully understood. It is believed that central actions of angiotensins are not exclusively associated with their traditional roles, many studies showing that central angiotensins are also involved in learning and memory processes. Moreover, clinical trials and studies on animal models suggest that pharmacological manipulation of angiotensin ligands may be of clinical importance in slowing or even stopping the cognitive deterioration seen in vascular dementia and Alzheimer's disease.