gebhart/patrepeval huggingface dataset:
Targeting Established Tumor Vasculature: A Novel Approach to Cancer Treatment (2005)

The selective targeting of established tumor vasculature represents an attractive new anticancer drug strategy, distinct from inhibiting angiogenesis. This is based on the concept that, in contrast to targeting individual tumor cells, the killing of relatively few vascular endothelial cells could result in the death of a large area of tumor (from lack of oxygen and nutrients), drug delivery to vasculature is less challenging than to large solid tumors (which may harbor regions of hypoxia) and, moreover, cells that comprise vasculature (such as endothelial cells) are more genetically stable than tumor cells and hence less likely to acquire changes causing drug resistance. There is accumulating evidence that there are inherent differences in the vasculature of tumors, both morphologic and biochemical, in comparison to normal organs, thus providing a rational basis for this approach. Vascular disrupting agents (VDAs) are now being tested clinically; several are also in late preclinical development. A major class of small molecule VDA is those targeting tubulin, e.g., combretastatin A4 phosphate (CA4P), ZD6126 and AVE8062A. Another distinct non-tubulin based compound, the flavonoid 5,6-dimethyl xanthenone 4-acetic acid (DMXAA, AS1404) induces direct apoptosis of endothelial cells and secondary induction of various vasoactive agents (such as serotonin and tumor necrosis factor a). These agents have all completed Phase I clinical evaluation; dose-limiting toxicities are generally non-overlapping with conventional cytotoxics; there has been evidence of efficacy. A common theme, now being pursued clinically, is that VDAs are expected to show maximum therapeutic benefit when used, intermittently rather than chronically and in combination with either conventional cytotoxics (such as platins or taxanes) or radiotherapy. Thereby, complementary kill of the central compartment of tumors (by VDAs) and the proliferating, well oxygenated, periphery (by cytotoxics or radiotherapy), is predicted. Non-invasive imaging techniques such as dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) have proven useful in the clinical monitoring of VDAs. A variety of additional small molecule anti-tubulin agents, N-cadherin inhibitors and antibody-based products (e.g., delivering effectors such as tissue factor to tumor blood vessels) are in earlier stages of development. The vascular targeting field is entering a particularly exciting phase; the next 1-2 years will be crucial in establishing clinical proof of principle for this approach.
Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast (2000)

The Zap1p transcription factor senses cellular zinc status and increases expression of its target genes in response to zinc deficiency. Previously known Zap1p-regulated genes encode the Zrt1p, Zrt2p, and Zrt3p zinc transporter genes and Zap1p itself. To allow the characterization of additional genes in yeast important for zinc homeostasis, a systematic study of gene expression on the genome-wide scale was used to identify other Zap1p target genes. Using a combination of DNA microarrays and a computer-assisted analysis of shared motifs in the promoters of similarly regulated genes, we identified 46 genes that are potentially regulated by Zap1p. Zap1p-regulated expression of seven of these newly identified target genes was confirmed independently by using lacZ reporter fusions, suggesting that many of the remaining candidate genes are also Zap1p targets. Our studies demonstrate the efficacy of this combined approach to define the regulon of a specific eukaryotic transcription factor.
Search for Cross-Species Transmission of Porcine Endogenous Retrovirus in Patients Treated with Living Pig Tissue (1999)

Pig organs may offer a solution to the shortage of human donor organs for transplantation, but concerns remain about possible cross-species transmission of porcine endogenous retrovirus (PERV). Samples were collected from 160 patients who had been treated with various living pig tissues up to 12 years earlier. Reverse transcription-polymerase chain reaction (RT-PCR) and protein immunoblot analyses were performed on serum from all 160 patients. No viremia was detected in any patient. Peripheral blood mononuclear cells from 159 of the patients were analyzed by PCR using PERV-specific primers. No PERV infection was detected in any of the patients from whom sufficient DNA was extracted to allow complete PCR analysis (97 percent of the patients). Persistent microchimerism (presence of donor cells in the recipient) was observed in 23 patients for up to 8.5 years.
The Value of Noninvasive Measurement of the Compensatory Reserve Index in Monitoring and Triage of Patients Experiencing Minimal Blood Loss (2014)

Currently available triage and monitoring tools are often late to detect life-threatening clinically significant physiological aberrations and provide limited data in prioritizing bleeding patients for treatment and evacuation. The Compensatory Reserve Index (CRI) is a novel means of assessing physiologic reserve, shown to correlate with central blood volume loss under laboratory conditions. The purpose of this study was to compare the noninvasive CRI device with currently available vital signs in detecting blood loss. Study subjects were soldiers volunteering for blood donation (n = 230), and the control group was composed of soldiers who did not donate blood (n = 34). Data collected before and after blood donation were compared, receiver operator characteristic curves were generated after either donation or the appropriate time interval, and areas under the curves (AUCs) were compared. Compared with pre-blood loss, blood donation resulted in a mean reduction of systolic blood pressure by 3% (before, 123 mmHg; after, 119 mmHg; P < 0.01). The CRI demonstrated a 16% reduction (before, 0.74; after, 0.62; P < 0.01). Heart rate, diastolic blood pressure, and oxygen saturation remained unchanged. The AUC for change in CRI was 0.81, 0.56 for change in heart rate, 0.53 for change in systolic blood pressure, 0.55 and 0.58 for pulse pressure and shock index, respectively. The AUCs for detecting mild blood loss at a single measurement were 0.73 for heart rate, 0.60 for systolic blood pressure, 0.62 for diastolic blood pressure, 0.45 for pulse oximetry, and 0.84 for CRI. The CRI was better than standard indices in detecting mild blood loss. Single measurement of CRI may enable a more accurate triage, and CRI monitoring may allow for earlier detection of casualty deterioration.
SNPs in cancer research and treatment (2004)

Genetic variation in the human genome is an emerging resource for studying cancer, a complex set of diseases characterised by both environmental and genetic contributions. The number of common germ-line variants is great, on the order of 10-15 million per person, and represents a remarkable opportunity to investigate the aetiology, interindividual differences in treatment response and outcomes of specific cancers. The study of genetic variation can elucidate critical determinants in environmental exposure and cancer, which could have future implications for preventive and early intervention strategies. However, we are in the initial stages of characterising the tools (i.e., the single-nucleotide polymorphism, SNP) to rigorously analyse the genetic contributions to complex diseases, such as cancer. If the promise of the genomic era is to be realised, we must integrate this information into new strategies for implementation in both public health measures and, most importantly, provision of individual cancer-related care.
[Induction of retarded exoerythrocytic schizonts by chloroguanide resulting in delayed parasitaemia of Plasmodium inui in Macaca mulatta]. (1990)

Three Rhesus monkeys inoculated with a large number of sporozoites of Plasmodium inui dissected from the salivary glands of infected mosquitoes, Anopheles dirus. Two of the monkeys (inoculated with 8.06 x 10(5) and 1.3 x 10(7) sporozoites, respectively) were treated with chloroguanide base 6 mg/(kg.d) x 4 d starting from 24 h after the inoculations and the other one (inoculated with 5.93 x 10(6) sporozoites) was not treated with chloroguanide as control. The primary parasitaemia attacks occurred in the former 2 monkeys were 31 and 25 d respectively after inoculation, while in the control was 7.5 d. Liver biopsies were done in all of the 3 monkeys, normal schizonts were seen in the control monkey on d 8 after inoculation, while none were detected in the 2 monkeys treated with chloroguanide. However, the retarded exoerythrocytic schizonts were found by indirect fluorescent antibody test (IFAT) in liver sections of the monkey inoculated with 1.3 x 10(7) sporozoites. Therefore, it is evident that moderate doses of chloroguanide retarded the formation of schizonts and thus delayed the primary parasitaemia.
Extracting secret keys from integrated circuits (2005)

Modern cryptographic protocols are based on the premise that only authorized participants can obtain secret keys and access to information systems. However, various kinds of tampering methods have been devised to extract secret keys from conditional access systems such as smartcards and ATMs. Arbiter-based physical unclonable functions (PUFs) exploit the statistical delay variation of wires and transistors across integrated circuits (ICs) in manufacturing processes to build unclonable secret keys. We fabricated arbiter-based PUFs in custom silicon and investigated the identification capability, reliability, and security of this scheme. Experimental results and theoretical studies show that a sufficient amount of inter-chip variation exists to enable each IC to be identified securely and reliably over a practical range of environmental variations such as temperature and power supply voltage. We show that arbiter-based PUFs are realizable and well suited to build, for example, key-cards that need to be resistant to physical attacks.
myo-Inositol Oxygenase Offers a Possible Entry Point into Plant Ascorbate Biosynthesis (2004)

Two biosynthetic pathways for ascorbate (l-ascorbic acid [AsA]; vitamin C) in plants are presently known, the mannose/l-galactose pathway and an l-GalUA pathway. Here, we present molecular and biochemical evidence for a possible biosynthetic route using myo-inositol (MI) as the initial substrate. A MI oxygenase (MIOX) gene was identified in chromosome 4 (miox4) of Arabidopsis ecotype Columbia, and its enzymatic activity was confirmed in bacterially expressed recombinant protein. Miox4 was primarily expressed in flowers and leaves of wild-type Arabidopsis plants, tissues with a high concentration of AsA. Ascorbate levels increased 2- to 3-fold in homozygous Arabidopsis lines overexpressing the miox4 open reading frame, thus suggesting the role of MI in AsA biosynthesis and the potential for using this gene for the agronomic and nutritional enhancement of crops.
Ultrawide-band/high-frequency photodetectors (1999)

The two main trends in the progress of ultrawide-band/high-frequency photodetectors (PD's), improving the bandwidth-efficiency product and obtaining a high saturation current, are reviewed. With respect to achieving large bandwidth-efficiency, the limiting factors and potentials of edge-coupled (waveguide, waveguide-fed, traveling-wave, periodic-traveling-wave), resonant-cavity, and refracting-facet photodiodes, as well as the avalanche photodiode are discussed. Regarding high-saturation current, the author estimated how much the space-charge effect limits the saturation current and two ways to reduce the space-charge effect are outlined. One way is to distribute the photocarriers along the edge-coupled PD's and the other is to increase the carrier velocity using a uni-traveling carrier structure. The waveguide-photodiode-based technologies that we have developed are also presented; namely the design and fabrication of a 100-GHz waveguide photodiode (WGPD), uni-traveling carrier WGPD, 60-GHz packaging, and a 20-GHz large-core WGPD for planar lightwave circuit integration. A 50-Gb/s receiver opto-electronic integrated circuit technology based on the WGPD is also presented.
Regulation of Macrophage Recognition through the Interplay of Nanoparticle Surface Functionality and Protein Corona (2016)

Using a family of cationic gold nanoparticles (NPs) with similar size and charge, we demonstrate that proper surface engineering can control the nature and identity of protein corona in physiological serum conditions. The protein coronas were highly dependent on the hydrophobicity and arrangement of chemical motifs on NP surface. The NPs were uptaken in macrophages in a corona-dependent manner, predominantly through recognition of specific complement proteins in the NP corona. Taken together, this study shows that surface functionality can be used to tune the protein corona formed on NP surface, dictating the interaction of NPs with macrophages.
Documenting the NICU design dilemma: comparative patient progress in open-ward and single family room units (2010)

This study showed the SFR to be more conducive to family-centered care, and to enhance infant medical progress and breastfeeding success over that of an open ward.
The Worldwide Prevalence of ADHD: A Systematic Review and Metaregression Analysis (2007)

Our findings suggest that geographic location plays a limited role in the reasons for the large variability of ADHD/HD prevalence estimates worldwide. Instead, this variability seems to be explained primarily by the methodological characteristics of studies.
Magnetic resonance elastography reveals altered brain viscoelasticity in experimental autoimmune encephalomyelitis (2012)

Cerebral magnetic resonance elastography (MRE) measures the viscoelastic properties of brain tissues in vivo. It was recently shown that brain viscoelasticity is reduced in patients with multiple sclerosis (MS), highlighting the potential of cerebral MRE to detect tissue pathology during neuroinflammation. To further investigate the relationship between inflammation and brain viscoelasticity, we applied MRE to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EAE was induced and monitored by MRE in a 7-tesla animal MRI scanner over 4 weeks. At the peak of the disease (day 14 after immunization), we detected a significant decrease in both the storage modulus (G') and the loss modulus (G″), indicating that both the elasticity and the viscosity of the brain are reduced during acute inflammation. Interestingly, these parameters normalized at a later time point (day 28) corresponding to the clinical recovery phase. Consistent with this, we observed a clear correlation between viscoelastic tissue alteration and the magnitude of perivascular T cell infiltration at both day 14 and day 28. Hence, acute neuroinflammation is associated with reduced mechanical cohesion of brain tissues. Moreover, the reduction of brain viscoelasticity appears to be a reversible process, which is restored when inflammation resolves. For the first time, our study has demonstrated the applicability of cerebral MRE in EAE, and showed that this novel imaging technology is highly sensitive to early tissue alterations resulting from the inflammatory processes. Thus, MRE may serve to monitor early stages of perivascular immune infiltration during neuroinflammation.
Single-dose pharmacokinetics of sublingual versus oral administration of micronized 17-estradiol (1997)

Sublingual administration of micronized 17 beta-estradiol results in a rapid, burst-like absorption into the systemic circulation, yielding high E2 levels that fall rapidly over the first 6 hours.
Mesenchymal Progenitors Able to Differentiate into Osteogenic, Chondrogenic, and/or Adipogenic Cells In Vitro Are Present in Most Primary Fibroblast‐Like Cell Populations (2007)

MSCs and mesenchymal progenitor cells (MPCs) are studied for their potential in regenerative medicine. MSCs in particular have great potential, because various reports have shown that they can differentiate into many different cell types. However, the difference between mesenchymal stem/progenitor cells and so-called fibroblasts is unclear. In this study, we found that most of the distinct populations of primary fibroblast-like cells derived from various human tissues, including lung, skin, umbilical cord, and amniotic membrane, contained cells that were able to differentiate into at least one mesenchymal lineage, including osteoblasts, chondrocytes, and adipocytes. We therefore propose that primary fibroblast-like cell populations obtained from various human tissues do not comprise solely fibroblasts, but rather that they also include at least MPCs and possibly MSCs, to some extent. Disclosure of potential conflicts of interest is found at the end of this article.
Immunogenicity and Immunomodulatory Properties of Hepatocyte-like Cells Derived from Human Amniotic Epithelial Cells (2013)

Hepatocyte transplantation is being trialled as an alternative to whole organ transplant for patients with acute liver failure and liver specific metabolic diseases. Due to the scarcity of human hepatocytes, hepatocyte-like cells (HLC) generated from stem cells may become a viable alternative to hepatocyte transplantation. Human amniotic epithelial cells (hAEC) from the placenta have stem cell-like properties and can be differentiated into HLC. Naïve hAEC have low immunogenicity and exert immunomodulatory effects that may facilitate allogeneic transplantation. However, whether the immunogenicity and immunomodulatory properties alter with differentiation into HLC are unknown. We further characterized HLC generated from hAEC, examined changes in human leucocyte antigens (HLA) and co-stimulatory molecules and effects exerted by the HLC on human peripheral blood mononuclear cells (PBMC). HLC derived from hAEC expressed proteins found in hepatocytes, had CYP3A4 drug metabolizing enzyme activity and secreted urea. IFN-γ treatment increased HLA Class IA, Class II and co-stimulatory molecule CD40 expression in the HLC. IFN-γ treated HLC stimulated proliferation of PBMC in one-way mixed lymphocyte reactions and were more immunogenic than undifferentiated hAEC. However, the HLC showed immunomodulatory properties and inhibited mitogen induced PBMC proliferation in vitro. PBMC proliferation may have been inhibited by IL-6, TGF-β1, PGE2 and HLA-G secreted by the HLC. The retention of immunomodulatory properties may enable HLC grafts to survive for longer periods despite the immunogenicity of the HLC.
Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. (1995)

The inhibitor protein I kappa B alpha controls the nuclear import of the transcription factor NF-kappa B. The inhibitory activity of I kappa B alpha is regulated from the cytoplasmic compartment by signal-induced proteolysis. Previous studies have shown that signal-dependent phosphorylation of serine residues 32 and 36 targets I kappa B alpha to the ubiquitin-proteasome pathway. Here we provide evidence that lysine residues 21 and 22 serve as the primary sites for signal-induced ubiquitination of I kappa B alpha. Conservative Lys-->Arg substitutions at both Lys-21 and Lys-22 produce dominant-negative mutants of I kappa B alpha in vivo. These constitutive inhibitors are appropriately phosphorylated but fail to release NF-kappa B in response to multiple inducers, including viral proteins, cytokines, and agents that mimic antigenic stimulation through the T-cell receptor. Moreover, these Lys-->Arg mutations prevent signal-dependent degradation of I kappa B alpha in vivo and ubiquitin conjugation in vitro. We conclude that site-specific ubiquitination of phosphorylated I kappa B alpha at Lys-21 and/or Lys-22 is an obligatory step in the activation of NF-kappa B.
Sigma antagonists potentiate opioid analgesia in rats (1995)

In mice, activation of sigma1 receptors antagonizes opioid analgesia. Sigma antagonists potentiate opioid analgesia, implying that the anti-opioid sigma system is tonically active. Co-administration of haloperidol with the mu opioid morphine, the kappa 1 analgesic U50,488H or the kappa 3 agonist naloxone benzoylhydrazone enhances the analgesic activity of all agents. The effect results from sigma receptor blockade since (-)sulpiride, a selective D2 antagonist which does not block sigma receptors, is inactive.
Lipopolysaccharide Induction of the Tumor Necrosis Factor-α Promoter in Human Monocytic Cells (1997)

Biosynthesis of tumor necrosis factor-alpha (TNF-alpha) is predominantly by cells of the monocytic lineage. This study examined the role of various cis-acting regulatory elements in the lipopolysaccharide (LPS) induction of the human TNF-alpha promoter in cells of monocytic lineage. Functional analysis of monocytic THP-1 cells transfected with plasmids containing various lengths of TNF-alpha promoter localized enhancer elements in a region (-182 to -37 base pairs (bp)) that were required for optimal transcription of the TNF-alpha gene in response to LPS. Two regions were identified: region I (-182 to -162 bp) contained an overlapping Sp1/Egr-1 site, and region II (-119 to -88) contained CRE and NF-kappaB (designated kappaB3) sites. In unstimulated THP-1, CRE-binding protein and, to a lesser extent, c-Jun complexes were found to bind to the CRE site. LPS stimulation increased the binding of c-Jun-containing complexes. In addition, LPS stimulation induced the binding of cognate nuclear factors to the Egr-1 and kappaB3 sites, which were identified as Egr-1 and p50/p65, respectively. The CRE and kappaB3 sites in region II together conferred strong LPS responsiveness to a heterologous promoter, whereas individually they failed to provide transcriptional activation. Furthermore, increasing the spacing between the CRE and the kappaB3 sites completely abolished LPS induction, suggesting a cooperative interaction between c-Jun complexes and p50/p65. These studies indicate that maximal LPS induction of the TNF-alpha promoter is mediated by concerted participation of at least two separate cis-acting regulatory elements.
Sporting bodies (2010)

Are pain and injury managed appropriately in the environment of professional sport?Is sports medicine a tool to empower or to disempower athletes? David Howe considers these and other pertinent concerns and questions whether, in the world of modern sport, it is the participants themselves or the sport's administrators who exert more control over athletes' well being. Exploring the historical transformation of sports medicine and the relationships between medicine, body and culture, Sport, Professionalism and Pain bridges a perceived space in the literature between medical anthropology, medical sociology and sport studies.
Reactivation of proliferin gene expression is associated with increased angiogenesis in a cell culture model of fibrosarcoma tumor progression (2001)

Proliferin (PLF) is an angiogenic placental hormone. We now report that PLF gene expression can also occur in a progressive fibrosarcoma mouse tumor cell model. PLF mRNA and protein are detectable at very low levels in cell lines derived from the mild noninvasive stage of tumor development. Expression is greatly augmented in cell lines from the aggressively invasive stage of development, a stage at which the tumor becomes highly angiogenic, and PLF expression remains high in cell lines from the end stage of fibrosarcoma. Activator protein 1 factors present at high levels in the more invasive stages of the tumor may in part allow for increased PLF expression, as cells from the mild stage in which c-jun and junB are stably expressed secrete levels of PLF comparable to that of the advanced stages. Secreted PLF protein is functionally important in tumor cell angiogenic activity, as demonstrated by the reduction of angiogenic activity in fibrosarcoma cell culture medium by immunodepletion of PLF. These results suggest that an extraembryonic genetic program, which has evolved to support fetal growth, may be reactivated in certain tumors and contribute to tumor growth.