gebhart/patrepeval huggingface dataset:
Novel Genes Associated with Colorectal Cancer Are Revealed by High Resolution Cytogenetic Analysis in a Patient Specific Manner (2013)

Genomic abnormalities leading to colorectal cancer (CRC) include somatic events causing copy number aberrations (CNAs) as well as copy neutral manifestations such as loss of heterozygosity (LOH) and uniparental disomy (UPD). We studied the causal effect of these events by analyzing high resolution cytogenetic microarray data of 15 tumor-normal paired samples. We detected 144 genes affected by CNAs. A subset of 91 genes are known to be CRC related yet high GISTIC scores indicate 24 genes on chromosomes 7, 8, 18 and 20 to be strongly relevant. Combining GISTIC ranking with functional analyses and degree of loss/gain we identify three genes in regions of significant loss (ATP8B1, NARS, and ATP5A1) and eight in regions of gain (CTCFL, SPO11, ZNF217, PLEKHA8, HOXA3, GPNMB, IGF2BP3 and PCAT1) as novel in their association with CRC. Pathway and target prediction analysis of CNA affected genes and microRNAs, respectively indicates TGF-β signaling pathway to be involved in causing CRC. Finally, LOH and UPD collectively affected nine cancer related genes. Transcription factor binding sites on regions of >35% copy number loss/gain influenced 16 CRC genes. Our analysis shows patient specific CRC manifestations at the genomic level and that these different events affect individual CRC patients differently.
Comparison of efficacy of fluconazole mouthrinse and clotrimazole mouthpaint in the treatment of oral candidiasis (2009)

Candidiasis is by far the most common oral fungal infection in humans and has a variety of clinical features. It is considered to be an opportunistic infection, affecting individuals who are debilitated by another disease. Fluconazole, one of the newer azoles available for systemic use and clotrimazole as a topical ointment are both shown to be effective in the treatment of oral candidiasis and are considered to be well tolerated and useful medications. No study has evaluated the comparison of clinical and mycological response of oral candidiasis to fluconazole mouthrinse and clotrimazole mouthpaint. The aim of this study was to evaluate the efficacy of fluconazole mouthrinse and compare it with clotrimazole mouthpaint in the treatment of oral candidiasis.
Optimization of layout design and OPC by using estimation of transistor properties (2006)

At deep sub-wavelength nodes, it is difficult to transfer accurate mask pattern onto the wafer. However, actual gate pattern is distorted, and timing analysis tools calculates circuit performance on the assumption that the same gate length exists throughout the whole gate width. We calculated the property of the original 2 dimensional distorted transistor by using distribution of gate length. Firstly, in order to evaluate the accuracy of this approach, we have compared them with experimental results that may influence the 65 nm-node design rule. In the conventional method using a rectangular model, results of transistor properties are different from the experimental values, however, results of this approach can reproduce the experimental results. Secondly, this approach is applied to optimization of layout design and OPC. In order to investigate the influence of circuit performance on a layout design and OPC, we calculated the properties (drive current; Ion and leakage current; Ioff) of each transistor contained in standard cell library which is most referred to in a system LSI. We have investigated 2 layouts and 8 OPCs. According to these results, we find out that optimal OPC differs according to the prioritization of Ion and Ioff, whether it is an N-channel or P-channel, and also by layout. Furthermore relaxation of layout decreases variability of Ion caused by defocus. Moreover, since the influence of pattern distortion can be expressed by circuit term such as Ion and Ioff in addition to conventional process terms, it becomes easier for designers to understand manufacturing issues.
NO-Induced Reversible Switching of the Electronic Interaction between a Porphyrin-Coordinated Cobalt Ion and a Silver Surface (2007)

The electronic interaction between a porphyrin-coordinated Co ion and a silver surface was switched by an axial nitric oxide (NO) ligand on the Co ion. This process is reversible and was monitored with X-ray and UV-photoelectron spectroscopy (XPS and UPS). The Co−Ag interaction leads to an electron transfer from the Ag surface to the Co ion and to a new electronic state close to the Fermi level. Both effects vanish if an axial NO ligand coordinates to the Co ion, indicating that the Co−Ag interaction is suppressed. As a possible explanation, we discuss a competition, similar to the trans effect, between the two axial ligands on the Co ion: the NO molecule and the Ag surface. These findings have important implications for sensor technology and for catalysis on supported metalloporphyrins, in which the catalytic activity of the metal center is controlled by the interaction with the underlying surface.
On some challenges and design choices in ad-hoc communications (2002)

Ad-hoc networks are network architectures that can be rapidly (ideally immediately) deployed and that do not need to rely on pre-existing infrastructure. The salient feature of this breed of networks is that they can operate in different and differing propagation and network operational conditions, which cannot be predicted during the network design stage. We discuss some of the challenges and choices that need to be made while designing an ad-hoc network. In particular, we address the following three issues: hierarchical vs. flat network architectures, proactive vs. reactive (on demand) routing protocols vs. a hybrid approach, and sensing-based vs. dialog-based medium access control.
The colorectal microRNAome (2006)

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. These studies suggest that the human genome contains many more miRNAs than currently identified and provide an approach for the large-scale experimental cloning of novel human miRNAs in human tissues.
Tumor αvβ3 Integrin Is a Therapeutic Target for Breast Cancer Bone Metastases (2007)

In breast cancer bone metastasis, tumor cells stimulate osteoclast-mediated bone resorption, and bone-derived growth factors released from resorbed bone stimulate tumor growth. The alphavbeta3 integrin is an adhesion receptor expressed by breast cancer cells and osteoclasts. It is implicated in tumor cell invasion and osteoclast-mediated bone resorption. Here, we hypothesized that the therapeutic targeting of tumor alphavbeta3 integrin would prevent bone metastasis formation. We first showed that, compared with mock-transfected cells, the i.v. inoculation of alphavbeta3-overexpressing MDA-MB-231 breast cancer cells in animals increased bone metastasis incidence and promoted both skeletal tumor burden and bone destruction. The direct inoculation of alphavbeta3-overexpressing transfectants into the tibial bone marrow cavity did not however enhance skeletal tumor burden and bone destruction, suggesting that alphavbeta3 controls earlier events during bone metastasis formation. We next examined whether a nonpeptide antagonist of alphavbeta3 (PSK1404) exhibits meaningful antitumor effects in experimental breast and ovarian cancer bone metastasis. A continuous PSK1404 treatment, which inhibited osteoclast-mediated bone resorption in an animal model of bone loss, substantially reduced bone destruction and decreased skeletal tumor burden. Importantly, a short-term PSK1404 treatment that did not inhibit osteoclast activity also decreased skeletal tumor burden and bone destruction. This dosing regimen caused a profound and specific inhibition of bone marrow colonization by green fluorescent protein, alphavbeta3-expressing tumor cells in vivo and blocked tumor cell invasion in vitro. Overall, our data show that tumor alphavbeta3 integrin stands as a therapeutic target for the prevention of skeletal metastases.
HFE gene knockout produces mouse model of hereditary hemochromatosis (1998)

Hereditary hemochromatosis (HH) is a common autosomal recessive disease characterized by increased iron absorption and progressive iron storage that results in damage to major organs in the body. Recently, a candidate gene for HH called HFE encoding a major histocompatibility complex class I-like protein was identified by positional cloning. Nearly 90% of Caucasian HH patients have been found to be homozygous for the same mutation (C282Y) in the HFE gene. To test the hypothesis that the HFE gene is involved in regulation of iron homeostasis, we studied the effects of a targeted disruption of the murine homologue of the HFE gene. The HFE-deficient mice showed profound differences in parameters of iron homeostasis. Even on a standard diet, by 10 weeks of age, fasting transferrin saturation was significantly elevated compared with normal littermates (96 +/- 5% vs. 77 +/- 3%, P < 0.007), and hepatic iron concentration was 8-fold higher than that of wild-type littermates (2,071 +/- 450 vs. 255 +/- 23 microg/g dry wt, P < 0.002). Stainable hepatic iron in the HFE mutant mice was predominantly in hepatocytes in a periportal distribution. Iron concentrations in spleen, heart, and kidney were not significantly different. Erythroid parameters were normal, indicating that the anemia did not contribute to the increased iron storage. This study shows that the HFE protein is involved in the regulation of iron homeostasis and that mutations in this gene are responsible for HH. The knockout mouse model of HH will facilitate investigation into the pathogenesis of increased iron accumulation in HH and provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload.
Prevention of Kidney Ischemia/Reperfusion-induced Functional Injury, MAPK and MAPK Kinase Activation, and Inflammation by Remote Transient Ureteral Obstruction (2002)

Protection against ischemic kidney injury is afforded by 24 h of ureteral obstruction (UO) applied 6 or 8 days prior to the ischemia. Uremia or humoral factors are not responsible for the protection, since unilateral UO confers protection on that kidney but not the contralateral kidney. Prior UO results in reduced postischemic outer medullary congestion and leukocyte infiltration. Prior UO results in reduced postischemic phosphorylation of c-Jun N-terminal stress-activated protein kinase 1/2 (JNK1/2), p38, mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and MKK3/6. Very few cells stain positively for proliferating cell nuclear antigen after obstruction, indicating that subsequent protection against ischemia is not related to proliferation with increased numbers of newly formed daughter cells more resistant to injury. UO increases the expression of heat shock protein (HSP)-25 and HSP-72. The increased HSP-25 expression persists for 6 or 8 days, whereas HSP-72 does not. HSP-25 expression is increased in the proximal tubule cells in the outer stripe of the outer medulla postobstruction, prior to, and 24 h after ischemia. In LLC-PK(1) renal epithelial cells, adenovirus-expressed human HSP-27 confers resistance to chemical anoxia and oxidative stress. Increased HSP-27 expression in LLC-PK(1) cells results in reduced H(2)O(2)-induced phosphorylation of JNK1/2 and p38. In conclusion, prior transient UO renders the kidney resistant to ischemia. This resistance to functional consequences of ischemia is associated with reduced postischemic activation of JNK, p38 MAP kinases, and their upstream MAPK kinases. The persistent increase in HSP-25 that occurs as a result of UO may contribute to the reduction in phosphorylation of MAPKs that have been implicated in adhesion molecule up-regulation and cell death.
Development and optimization of a cell‐based assay for the selection of synthetic compounds that potentiate bone morphogenetic protein‐2 activity (2009)

The requirement of large amounts of the recombinant human bone morphogenetic protein-2 (BMP-2) produces a huge translational barrier for its routine clinical use due to high cost. This leads to an urgent need to develop alternative methods to lower costs and/or increase efficacies for using BMP-2. In this study, we describe the development and optimization of a cell-based assay that is sensitive, reproducible, and reliable in identifying reagents that potentiate the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. The assay is based on a BMP-responsive Smad1-driven luciferase reporter gene. LIM mineralization protein-1 (LMP-1) is a novel intracellular LIM domain protein that has been shown by our group to enhance cellular responsiveness to BMP-2. Our previous report elucidated that the binding of LMP-1 with the WW2 domain in Smad ubiquitin regulatory factor-1 (Smurf1) rescues the osteogenic Smads from degradation. Here, using the optimized cell-based assay, we first evaluated the activity of the recombinantly prepared proteins, LMP-1, and its mutant (LMP-1DeltaSmurf1) that lacks the Smurf1-WW2 domain-binding motif. Both the wild type and the mutant proteins were engineered to contain an 11-amino acid HIV-TAT protein derived membrane transduction domain to aid the cellular delivery of recombinant proteins. The cell-based reporter assay confirmed that LMP-1 potentiates the BMP-induced stimulation of C2C12 cells towards the osteoblastic phenotype. The potentiating effect of LMP-1 was significantly reduced when a specific-motif known to interact with Smurf1 was mutated. We validated the results obtained in the reporter assay by also monitoring the expression of mRNA for osteocalcin and alkaline phosphatase (ALP) which is widely accepted osteoblast differentiation marker genes. Finally, we provide further confirmation of our results by measuring the activity of alkaline phosphatase in support of the accuracy and reliability of our cell-based assay. Direct delivery of synthesized protein can be limited by high cost, instability or inadequate post-translational modifications. Thus, there would be a clear benefit for a low cost, cell penetrable chemical compound. We successfully used our gene expression-based assay to choose an active compound from a select group of compounds that were identified by computational screenings as the most likely candidates for mimicking the function of LMP-1. Among them, we selected SVAK-3, a compound that showed a dose-dependent potentiation of BMP-2 activity in inducing osteoblastic differentiation of C2C12 cells. We show that either the full length LMP-1 protein or its potential mimetic compound consistently exhibit similar potentiation of BMP-2 activity even when multiple markers of the osteoblastic phenotype were parallely monitored.
Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity (2015)

Despite the beneficial therapeutic effects of intravenous immunoglobulin (IVIg) in inflammatory diseases, consistent therapeutic efficacy and potency remain major limitations for patients and physicians using IVIg. These limitations have stimulated a desire to generate therapeutic alternatives that could leverage the broad mechanisms of action of IVIg while improving therapeutic consistency and potency. The identification of the important anti-inflammatory role of fragment crystallizable domain (Fc) sialylation has presented an opportunity to develop more potent Ig therapies. However, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for clinical use. Therefore, we set out to develop the first, to our knowledge, robust and scalable process for generating a well-qualified sialylated IVIg drug candidate with maximum Fc sialylation devoid of unwanted alterations to the IVIg mixture. Here, we describe a controlled enzymatic, scalable process to produce a tetra-Fc-sialylated (s4-IVIg) IVIg drug candidate and its qualification across a wide panel of analytic assays, including physicochemical, pharmacokinetic, biodistribution, and in vivo animal models of inflammation. Our in vivo characterization of this drug candidate revealed consistent, enhanced anti-inflammatory activity up to 10-fold higher than IVIg across different animal models. To our knowledge, this candidate represents the first s4-IVIg suitable for clinical use; it is also a valuable therapeutic alternative with more consistent and potent anti-inflammatory activity.
Plane Waves in a Thermoelastic Solid (1957)

In an isotropic, thermoelastic solid shear waves are unaltered by thermal effects. However, two distinct dilatational waves exist, both of which are dispersed and attenuated by the medium. One of the waves (denoted the E wave) is close in character to the pure elastic wave, the other wave (denoted the T wave) is similar in nature to the pure thermal wave. The properties of the two dilatational motions are studied and relations are given expressing the variation, in each, of phase velocity, amplitude attenuation, and specific loss with impressed frequency. For the E wave the result is verified that this disturbance propagates at the adiabatic velocity at low frequencies and at the isothermal velocity at very high frequencies. An explanation based on physical considerations is offered to account for this generally overlooked phenomenon. It is further found that the amplitude is attenuated exponentially as the square of the frequency at relatively low frequencies, but approaches finite value as the frequency increases without limit. The specific loss reaches maximum for the E wave, a minimum for the T wave, near the frequency whose period is equal to the relaxation time due to thermal currents. Finally, the ratios are computed of the amplitude of the temperature to the amplitude of the displacement in each of the two modes of motion. Numerical work indicates that, for metals at room temperature, the effect of coupling between elastic and thermal motions is very small.
Carbon Nanotube/Polymer Composites as a Highly Stable Hole Collection Layer in Perovskite Solar Cells (2014)

Organic-inorganic perovskite solar cells have recently emerged at the forefront of photovoltaics research. Power conversion efficiencies have experienced an unprecedented increase to reported values exceeding 19% within just four years. With the focus mainly on efficiency, the aspect of stability has so far not been thoroughly addressed. In this paper, we identify thermal stability as a fundamental weak point of perovskite solar cells, and demonstrate an elegant approach to mitigating thermal degradation by replacing the organic hole transport material with polymer-functionalized single-walled carbon nanotubes (SWNTs) embedded in an insulating polymer matrix. With this composite structure, we achieve JV scanned power-conversion efficiencies of up to 15.3% with an average efficiency of 10 ± 2%. Moreover, we observe strong retardation in thermal degradation as compared to cells employing state-of-the-art organic hole-transporting materials. In addition, the resistance to water ingress is remarkably enhanced. These are critical developments for achieving long-term stability of high-efficiency perovskite solar cells.
Immunotactoid glomerulopathy: clinicopathologic and proteomic study (2012)

Hematologic malignancy, particularly lymphoma, is not uncommon in ITG. ITG appears to have a better prognosis than other paraprotein-related renal lesions, with a half of patients expected to recover kidney function with immunosuppressive therapy or chemotherapy. The proteomic profile of ITG is consistent with deposition of monotypic immunoglobulins and activation of the classical and terminal pathway of complement.
A quantitative and qualitative comparative analysis of collagen fibers to determine the role of connective tissue stroma on biological behavior of odontogenic cysts: A histochemical study (2012)

Quality, organization and packing of collagen fibers is different in 3 cystic lesions which accounts for difference in biological behavior of these lesions and it justifies that neoplastic growth requires a functional stroma and the ability of neoplastic cells to induce the formation of such a stroma is of great importance.
The potential supply of organ donors. An assessment of the efficacy of organ procurement efforts in the United States (1992)

<h3>Objectives.</h3> —To estimate the potential supply of organ donors and to measure the efficiency of organ procurement efforts in the United States. <h3>Methods.</h3> —A geographic database has been developed consisting of multiple cause of death and sociodemographic data compiled by the National Center for Health Statistics. All deaths are evaluated as to their potential for organ donation. Two classes of potential donors are identified: class 1 estimates are restricted to causes of death involving significant head trauma only, and class 2 estimates include class 1 estimates as well as deaths in which brain death was less probable. <h3>Results.</h3> —Over 23000 people are currently awaiting a kidney, heart, liver, heart-lung, pancreas, or lung transplantation. Donor supply is inadequate, and the number of donors remained unchanged at approximately 4000 annually for 1986 through 1989, with a modest 9.1% increase in 1990. Between 6900 and 10700 potential donors are available annually (eg, 28.5 to 43.7 per million population). Depending on the class of donor considered, organ procurement efforts are between 37% and 59% efficient. Efficiency greatly varies by state and organ procurement organization. <h3>Conclusions.</h3> —Many more organ donors are available than are being accessed through existing organ procurement efforts. Realistically, it may be possible to increase by 80% the number of donors available in the United States (up to 7300 annually). It is conceivable, although unlikely, that the supply of donor organs could achieve a level to meet demand. (<i>JAMA</i>. 1992;267:239-246)
Experimental demonstration of time-aware software defined networking for OpenFlow-based optical interconnect in intra-datacenter networks (2013)

Due to the high burstiness and high-bandwidth characteristics of the services, optical interconnect in intra-datacenter networks has attracted much attention. Many datacenter applications in the environment require lower delay and higher availability with the end-to-end guaranteed quality of service. In this paper, we propose a novel time-aware software defined networking (TaSDN) architecture for OpenFlow-based optical interconnect in intra-datacenter networks, by introducing a time-aware service scheduling (TaSS) strategy. TaSDN can arrange and accommodate the applications with required QoS considering the time factor, and enhance the responsiveness to quickly provide for intra-datacenter demand. The overall feasibility and efficiency of the proposed architecture are experimentally verified on our testbed with real OpenFlow-enabled tunable optical modules.