gebhart/patrepeval huggingface dataset:
An Islet-Stabilizing Implant Constructed Using a Preformed Vasculature (2008)

Islet transplantation for the purpose of treating insulin-sensitive diabetes is currently limited by several factors, including islet survival posttransplantation. In the current study, a tissue-engineered prevascularized pancreatic encapsulating device (PPED) was developed. Isolated islets were placed in collagen gels, and they exhibited fourfold more insulin release than islets not in collagen. The insulin released by beta-cells in islets encapsulated in collagen exhibited unobstructed diffusion within the collagen gels. Subsequent studies evaluated the ability to create a sandwich comprised of two layers of prevascularized collagen gels around a central collagen gel containing islets. In vitro characterization of the islets showed that islets are functional and responded to glucose stimulation. The PPEDs were implanted subcutaneously into severe combined immunodeficient mice. Islet survival was assessed after 7, 14, and 28 days. Immunohistochemical analysis was performed on the implants to detect insulin and the presence of intraislet endothelial cells. At all time points, insulin was localized in association with intact and partially dissociated islets. Moreover, cells that exhibited insulin staining were colocalized with intraislet endothelial cells. These data indicate that the PPED enhances islet survival by supporting islet viability and maintaining intraislet endothelial cell structures.
Waveguide Handbook (1986)

The Waveguide Handbook is an unbridged reprint of the book first published in 1951 by McGrawHill as volume 10 of the MIT Radiation Laboratory Series. Although the primary aim of the book is to present the equivalent circuit parameters for a large amount of microwave structures, a brief but coherent account of the fundamental concepts necessary for their proper utilisation is included
Cytotoxic CD4+ T cells from a sporozoite-immunized volunteer recognize the Plasmodium falciparum CS protein (1991)

The present data provide the first evidence that a protozoan parasite, Plasmodium falciparum, can induce CD4+ cytotoxic T cells in man. The CD4+ cytotoxic T lymphocytes (CTL) were derived from a sporozoite-immunized volunteer who was protected against challenge with P. falciparum sporozoites. These T cells recognize an epitope within the circumsporozoite (CS) protein, an immunodominant sporozoite surface antigen, present also in liver stages of the parasite, which has been investigated as a vaccine candidate. The class II restricted T cell clones specifically lyse autologous B cells pulsed with a synthetic peptide representing a C-terminal sequence of the P. falciparum CS protein. The same peptide, as well as recombinant or native CS protein, also stimulates proliferation and gamma-interferon production by the CD4+ CTL. The CTL epitope, KIQNSLSTEW, is recognized in the context of HLA-DR7 and overlaps both a highly conserved, as well as a polymorphic, region of the P. falciparum CS protein.
TWO MUTATIONS IDENTIFIED IN THE ANDROGEN RECEPTOR OF THE NEW HUMAN PROSTATE CANCER CELL LINE MDA PCA 2A (1999)

Two mutations were identified in the AR gene of the MDA PCa 2a cell line that are likely responsible for the decreased androgen sensitivity and altered ligand specificity observed in these cells. Thus, this new cell line with partial androgen responsiveness and PSA expression can serve as a functionally relevant model system of bone metastatic prostate cancer, and can be used to investigate the role of AR mutations in prostate cancer and its progression to androgen independence.
Interferon gamma regulates platelet endothelial cell adhesion molecule 1 expression and neutrophil infiltration into herpes simplex virus-infected mouse corneas. (1996)

In a mouse model of herpes simplex virus (HSV) 1 corneal infection, tissue destruction results from a CD4+ T cell-mediated chronic inflammation, in which interleukin 2 and interferon (IFN) gamma are requisite inflammatory mediators and polymorphonuclear leukocytes (PMN) are the predominant infiltrating cells. In vivo neutralization of IFN-gamma relieved inflammation at least in part through a specific block of PMN extravasation into HSV-1-infected corneas. Intercellular adhesion molecule (ICAM) 1 and platelet endothelial cell adhesion molecule (PECAM) 1 were upregulated on the vascular endothelium of inflamed corneas. Reduced PMN extravasation in anti-IFN-gamma-treated mice was associated with a dramatic reduction of PECAM-1 but not ICAM-1 expression on vascular endothelium. PMN accumulated in the lumen of corneal vessels after in vivo IFN-gamma neutralization. PECAM-1 was readily detectable on PMN inside the vessels but was not detectable on PMN that extravasated into the infected cornea. Moreover, flow cytometric analysis revealed reduced PECAM-1 expression but elevated major histocompatibility complex class I expression on PMN that recently extravasated into the peritoneal cavity when compared with PMN in the peripheral blood. We conclude that IFN-gamma contributes to HSV-1-induced corneal inflammation by facilitating PMN infiltration; this appears to be accomplished through upregulation of PECAM-1 expression on the vascular endothelium; and PMN downregulate PECAM-1 expression during the process of extravasation.
Heat Shock Proteins in Renal Cell Carcinomas (2005)

Renal cell carcinoma (RCC) represents one of the most common cancer types in the Western World. One third of the RCC patients had metastasis at presentation with a poor 5-year survival. Nephrectomy is the most important treatment modality of this disease, since most of the RCCs are resistant to cytotoxic chemotherapy and radiation therapy. Recent immunotherapeutic approaches have been shown to improve the survival rate of RCC patients. Thus, RCC appears to have an immunogenic basis, and therefore represents an attractive target for immunotherapies. So far, only a few RCC-associated antigens have been characterized. However, with the implementation of ome-based technologies, an increasing number of tumor-associated antigens and tumor markers has been identified that includes various heat shock proteins (HSPs). RCC lesions demonstrate heterogeneous expression patterns for HSPs. In most cases overexpression of certain HSPs, such as HSP27, HSP70 and HSP72, has been detected both in RCC cell lines as well as in the tumor lesions when compared to normal kidney epithelium. Furthermore, HSPs play an important role in apoptotic cell death, in the regulation of cell proliferation and in the augmentation of lysis of RCC by HLA class I-restricted cytotoxic T lymphocytes. In this context, it is noteworthy that wild-type and mutated HSPs have been identified to act as tumor-associated antigens, which consequently resulted in the first clinical phase I and II trials using HSP for vaccination of RCC patients. In this chapter we will briefly present the relevance of HSPs in the pathomechanisms of RCC.
Regional brain stiffness changes across the Alzheimer's disease spectrum (2015)

Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.
Resonant Antidromic Cortical Circuit Activation as a Consequence of High-Frequency Subthalamic Deep-Brain Stimulation (2007)

Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.
Occurence of glycosidically bound fl avour compounds in hops, hop products and beer (2007)

Glycosidically bound fl avour compounds of hops are considered to contribute to the hop fl avour in beer. Therefore, different hop varieties and hop products were analyzed for their glycoside content. During extraction with supercritical CO 2 almost all of the hop glycosides remain in spent hops. After ethanol extraction, glycosides could be detected in both the ethanol tannin extract and the ethanol pure resin extract. In all examined varieties an enrichment of the sensorially important glycosides of monoterpene alcohols (e.g. linalool) and nor-carotenoids could be observed in the ethanol pure resin extracts. Some of these glycosides could be detected in hopped beer, where they could act as precursors for the organoleptically active linalool. This could be confi rmed by a rise in free linalool in a stored beer brewed with a re-extracted ethanol pure resin extract containing linalyl glycoside, compared to a beer brewed with a glycoside-free hop preparation. The strongly fl avouractive s-damascenone could also be liberated from hop glycosides, but hops seem not to be the only source for this ketone.
Decreased Serum Tryptophan Concentration Predicts Poor Prognosis in Malignant Melanoma Patients (2006)

Decreased serum tryptophan concentrations and elevated serum neopterin levels can be used as predictive markers for the future course in melanoma patients. Moreover, our data support previous speculations that a higher degree of IDO expression could play a crucial role for tumor progression.
Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer’s disease brain (2015)

Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development.
Optimizing Compiler for the CELL Processor (2005)

Developed for multimedia and game applications, as well as other numerically intensive workloads, the CELL processor provides support both for highly parallel codes, which have high computation and memory requirements, and for scalar codes, which require fast response time and a full-featured programming environment. This first generation CELL processor implements on a single chip a Power Architecture processor with two levels of cache, and eight attached streaming processors with their own local memories and globally coherent DMA engines. In addition to processor-level parallelism, each processing element has a Single Instruction Multiple Data (SIMD) unit that can process from 2 double precision floating points up to 16 bytes per instruction.
Solubilzation in formamide protects RNA from degradation (1992)

Degradation by RNase is a major concern when handling RNA samples. The omnipresent enzyme (fingertips, dust etc.) is heat- stable and does not require cofactors for its enzymatic activity. This makes it difficult to inactivate RNase in RNA samples. Although there are several isolation methods yielding RNase-free RNA (1, 2), precautions have to be undertaken to avoid RNase contamination at the final step of isolation, i.e. solubilization of RNA. The common practice is to solubilize RNA in diethyl pyrocarbonate (DEPC)-treated water (1, 2). The solubilized RNA is susceptible, however, to accidental contamination with RNase during handling and storage of samples. In addition, long-term storage of water-solubilized RNA samples requires temperature as low as -70C to prevent degradation of RNA (1, 2).
Comparative analysis of proteins with a mucus-binding domain found exclusively in lactic acid bacteria (2005)

Lactic acid bacteria (LAB) are frequently encountered inhabitants of the human intestinal tract. A protective layer of mucus covers the epithelial cells of the intestine, offering an attachment site for these bacteria. In this study bioinformatics tools were used to identify and characterize proteins containing one type of mucus-binding domain, called MUB, that is postulated to play an important role in the adherence of LAB to this mucus layer. By searching in all protein databases 48 proteins containing at least one of these MUB domains in nine LAB species were identified. These MUB domains varied in size, ranging from approximately 100 to more than 200 residues per domain. Complete MUB domains were found exclusively in LAB. The number of MUB domains present in a single protein varied from 1 to 15. In some cases, orthologous proteins in closely related species contained a different number of domains, indicating that repeats of the domain undergo rapid duplication and deletion. Proteins containing the MUB domain were often encoded by gene clusters that encode multiple extracellular proteins. In addition to one or more copies of the MUB domain, many of these proteins contained other domains that are predicted to be involved in binding to and degradation of extracellular components. These findings strongly suggest that the MUB domain is an LAB-specific functional unit that performs its task in various domain contexts and could fulfil an important role in host-microbe interactions in the gastrointestinal tract.
Meniere's disease and middle ear pressure – vestibular function after transtympanic tube placement (2009)

Most patients (68.2%) reported an improvement of vertigo. Before surgery 63.6% of patients did not show VEMPs, whereas vestibulo-collic reflexes were measured in 36.4% of all cases compared with 68.2% of patients without and 31.8% with recorded VEMPs after surgery. No statistically different findings in gain and phase lag of SHA testing were seen postoperatively compared to preoperative findings.
Parkville virus: A novel genetic variant of human calicivirus in the Sapporo virus clade, associated with an outbreak of gastroenteritis in adults (1997)

This report describes the characterization of Parkville virus, the etiologic agent of an outbreak of foodborne gastroenteritis, that has the morphology of a calicivirus and genetic properties that distinguish it from previously identified strains in the Sapporo/Manchester virus clade. Sequence analysis of the Parkville virus genome showed it contained the RNA-dependent RNA polymerase motifs GLPSG and YGDD characteristic of members of the family Caliciviridae with an organization identical to that reported for the Manchester virus where the capsid region of the polyprotein is fused to the RNA polymerase. Parkville virus however, demonstrates considerable sequence divergence from both the Manchester and Sapporo caliciviruses, providing the first indications that genetic diversity exists within caliciviruses of this previously homogeneous clade. On the basis of recent advances in the genetic characterization of members of the family Caliciviridae, we propose a new interim phylogenetic classification system in which Parkville virus would be included with Manchester and Sapporo virus as a separate group distinct from the small round-structured viruses (Norwalk-like viruses) that also cause diarrhea in humans.
The Origins of Enhanced Activity in Factor VIIa Analogs and the Interplay between Key Allosteric Sites Revealed by Hydrogen Exchange Mass Spectrometry (2008)

Factor VIIa (FVIIa) circulates in the blood in a zymogen-like state. Only upon association with membrane-bound tissue factor (TF) at the site of vascular injury does FVIIa become active and able to initiate blood coagulation. Here we used hydrogen exchange monitored by mass spectrometry to investigate the conformational effects of site-directed mutagenesis at key positions in FVIIa and the origins of enhanced intrinsic activity of FVIIa analogs. The differences in hydrogen exchange of two highly active variants, FVIIa(DVQ) and FVIIa(VEAY), imply that enhanced catalytic efficiency was attained by two different mechanisms. Regions protected from exchange in FVIIa(DVQ) include the N-terminal tail and the activation pocket, which is a subset of the regions of FVIIa protected from exchange upon TF binding. FVIIa(DVQ) appeared to adopt an intermediate conformation between the free (zymogen-like) and TF-bound (active) form of FVIIa and to attain enhanced activity by partial mimicry of TF-induced activation. In contrast, exchange-protected regions in FVIIa(VEAY) were confined to the vicinity of the active site of FVIIa. Thus, the changes in FVIIa(VEAY) appeared to optimize the active site region rather than imitate the TF-induced effect. Hydrogen exchange analysis of the FVIIa(M306D) variant, which was unresponsive to stimulation by TF, correlated widespread reductions in exchange to the single mutation in the TF-binding region. These results reveal the delicate interplay between key allosteric sites necessary to achieve the transition of FVIIa into the active form.
Identification of retinoids with nuclear receptor subtype-selective activities. (1991)

Retinoic acid (RA) and its synthetic analogues, retinoids, have shown promising results in the prevention of epithelial carcinogenesis and in the treatment of acute promyelocytic leukemia and various proliferative skin disorders. Retinoid action on gene regulation is mediated by three distinct nuclear retinoic acid receptor subtypes, RA receptors alpha, beta, and gamma. The existence of multiple RA receptors has raised the possibility that receptor subtype-specific retinoids with reduced side effects can be developed. To analyze the activity of retinoids at the molecular level, we used a receptor activation assay. RA and 22 retinoids were compared on the three receptor subtypes. We found the alpha receptor to be least sensitive to activation by RA and the gamma receptor to be most sensitive. Compared with RA, one of the retinoids showed increased activity for the alpha and beta receptors. Three retinoids revealed no gene activation activity and showed no antagonistic effects when assayed in the presence of RA. Surprisingly, several of the retinoids were efficient activators of the beta and gamma receptors but poor activators or nonactivators of the alpha receptor. Our data demonstrate that the three RA receptor subtypes have differential ligand activation specificities and that the design of receptor subtype-selective retinoids is possible.
Implications of the serine protease HtrA1 in amyloid precursor protein processing (2005)

The defining features of the widely conserved HtrA (high temperature requirement) family of serine proteases are the combination of a catalytic protease domain with one or more C-terminal PDZ domains and reversible zymogen activation. Even though HtrAs have previously been implicated in protein quality control and various diseases, including cancer, arthritis, and neuromuscular disorder, the biology of the human family members is not well understood. Our data suggest that HtrA1 is directly involved in the beta-amyloid pathway as it degrades various fragments of amyloid precursor protein while an HtrA1 inhibitor causes accumulation of Abeta in astrocyte cell culture supernatants. Furthermore, HtrA1 colocalizes with beta-amyloid deposits in human brain samples. Potential implications in Alzheimer's disease are discussed.
Human-ovine xenogenic transplantation of stem cells in utero. (1992)

The preimmune status of the early gestational age fetus provides a permissive environment that bypasses the immunological barrier and permits the engraftment and expression of hemopoietic stem cells (HSC). We used in utero approach to establish long term (greater than 2 years) engraftment and expression of human fetal liver HSC in sheep. Engraftment occurred in 40% (13 of 33) of the recipients. Of 5 live born sheep, all were chimeric. Engraftment was multilineage, involving lymphoid, myeloid and erythroid donor (human) cells. Interestingly, these progenitors have continued to exhibit responsiveness to human specific growth factors both in vitro and in vivo. Therefore, the integration of human HSC into the hemopoietic framework of the host appeared to be incomplete, with donor progenitors retaining certain phenotypic characteristics that may be exploited to preferentially manipulate the donor (human) cell population in these animals. Donor HSC primarily seeded the host bone marrow. Since the donor cells were of liver origin and the host liver at the time of transplantation was the major hemopoietic organ, this near exclusive seeding to the marrow indicates the greater affinity of marrow for the homing HSC. Nonetheless, no cells of donor origin appeared in the host circulation until the perinatal period, suggesting that donor HSC expand with the developing marrow spaces, but do not undergo terminal differentiation. The absence of a significant immunological barrier and the availability of expanding marrow homing sites render the fetus an excellent host (and donor) for HSC transplantation.