gebhart/patrepeval huggingface dataset:
Single-molecule detection of biomolecules by surface-enhanced coherent anti-Stokes Raman scattering (2005)

We report on the applicability of combining surface-enhanced Raman scattering (SERS) with coherent anti-Stokes Raman scattering for high-sensitivity detection of biological molecules. We found that this combination of techniques provides more than 3 orders of signal enhancement compared with SERS and permits monitoring of biological molecules such as deoxyguanosine monophosphate (dGMP) and deoxyadenosine monophosphate at the single-molecule level. This combined technique also improved detection sensitivity for angiotensin peptide. As this is believed to be the first report of detection of dGMP at the single-molecule level, we suggest that this approach can serve as a new tool for biological studies.
Headache-related disability in the management of migraine (2001)

Existing barriers to successful migraine care. Migraine is a common neurologic disorder that affects 11% or more of the adult population.1 The past decade has seen huge advances in our understanding of the epidemiology and underlying mechanisms of migraine.2 Several effective new acute and preventive therapies have been introduced. Unfortunately, clinical treatment has not kept pace with scientific advances: Migraine remains relatively under-recognized, under-diagnosed and under-treated.3

Migraine is a heterogeneous condition that results in a spectrum of disability within and among different individuals.4 Disability from migraine can be measured as time lost from paid work, household work, school, and family, and from social and leisure activities. Unlike the long-term disability of stroke or multiple sclerosis, migraine-associated disability can be relieved by successful treatment of the headache. However, during an attack migraine-related disability can be severe and imposes a considerable aggregate burden on the sufferer and on society.

Although severely affected sufferers tend to receive more medical care than those less affected,5 over half of all migraine sufferers deny having received a migraine diagnosis from a physician,5-7⇓⇓ and of those patients who receive an accurate diagnosis, many do not receive suitable therapy.8 Most migraine sufferers rely on over-the-counter medications to the exclusion of prescription …
Synergic Monodeprotonation of Bis(benzene)chromium by Using Mixed Alkali Metal–Magnesium Amide Bases and Structural Characterization of the Heterotrimetallic Products (2004)

Mixed-metal chemical synergy is strikingly exemplified by the clean, selective deprotonation of one benzene ring of bis(benzene)chromium by bimetallic (Na/Mg or K/Mg) amide base mixtures. The bis(benzene)chromium moiety forms high-yielding crystalline trimetallic products (see picture) with the mixed bases, but it is inert towards the non-synergic, parent monometallic amides. Na/K red; Mg green; Cr light blue; N yellow; C black.
Low-threshold quantum dot lasers with 201 nm tuningrange (2000)

A grating-coupled external-cavity quantum dot laser is tuned across a 201 nm range at a maximum bias of 2.87 kA/cm2, one order of magnitude less than the bias required for comparable tuning of quantum well lasers. The tuning range increases for higher cavity losses of the quantum dot laser.
Direct view of stress distribution in solid by mechanoluminescence (1999)

Visualization of stress distribution has been realized by a nondestructive mechanoluminescence (ML) from SrAl2O4:Eu, which can emit three magnitudes higher visible light than that of well-known ML substance of quartz. A simulation result confirms that such a ML image successfully reflects the stress distribution. A kinetic model for ML of SrAl2O4:Eu is proposed.
A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia (2003)

Neoangiogenesis has been shown to play an important role in the pathogenesis of acute myeloid leukemia (AML). Autocrine and paracrine secretion of angiogenic and hematopoietic growth factors such as vascular endothelial growth factor (VEGF) and stem cell factor (SCF) in the bone marrow microenvironment may promote proliferation and survival of leukemic blasts. This concept represented the rationale for the initiation of a multicenter phase 2 trial of SU5416, a small molecule inhibitor of phosphorylation of VEGF receptors 1 and 2, c-kit, the SCF receptor, and fms-like tyrosine kinase-3 (FLT3) in patients with advanced AML. Entered into the study were 43 patients with refractory AML or elderly patients not judged medically fit for intensive induction chemotherapy; 42 patients received at least one dose of study drug. Treatment was generally well tolerated, with nausea, headache, and bone pain the most frequent treatment-related side effects. One patient had a morphologic remission (French-American-British [FAB] criteria of complete response without normalization of blood neutrophil and platelet counts) lasting for 2 months. There were 7 patients who achieved a partial response (reduction of blasts by at least 50% in bone marrow and peripheral blood) lasting 1 to 5 months. Patients with AML blasts expressing high levels of VEGF mRNA by quantitative polymerase chain reaction (PCR) had a significantly higher response rate and reduction of bone marrow microvessel density than patients with low VEGF expression consistent with the antiangiogenic effects of SU5416.
Systemic Administration of Connexin43 Mimetic Peptide Improves Functional Recovery after Traumatic Spinal Cord Injury in Adult Rats (2016)

Blocking of Connexin43 hemichannels, the main gap junction protein located on astrocytes in the central nervous system, has been shown to reduce neural injury in a number of models. We demonstrated previously that local administration of a Connexin43 mimetic peptide, Peptide5, reduces secondary tissue damage after spinal cord injury (SCI). Here, we investigated whether acute systemic delivery of Peptide5 is also protective in a model of SCI. Rats were subjected to a mild spinal cord contusion using the Multicentre Animal Spinal Cord Injury Study impactor and were injected intraperitoneally with Peptide5 or a scrambled peptide immediately and at 2 h and 4 h post-injury. Rats were tested for locomotor recovery and pain hypersensitivity and euthanized at 8 h, 24 h, two weeks, or six weeks post-injury. Compared with control rats, Peptide5 treated rats showed significant improvement in hindlimb locomotor function between three and six weeks post-injury and reductions in at-level mechanical allodynia at weeks one and six post-injury. Immunohistochemistry showed that Peptide5 treatment led to a reduction in total Connexin43 and increased phosphorylated Connexin43 at 8 h compared with scrambled peptide. At two and six weeks, lesion size, the astrocytic and the activated macrophage, and/or microglial response were all decreased in the Peptide5 animals. In addition, neuronal cell numbers were higher in the Peptide5 animals compared with the scrambled peptide treated rats at two and six weeks. These results show for the first time that systemic administration of Peptide5 to block the pathological opening of Connexin43 hemichannels is a feasible treatment strategy in this setting, ameliorating the secondary SCI.
Ley glycolipid-recognizing monoclonal antibody inhibits procoagulant activity and metastasis of human adenocarcinoma (2001)

Tumor procoagulant is associated with cancer at advanced stages of malignancy such as infiltration and metastasis. In the present study, we investigated the role of Ley glycolipid in the mechanism of cancer metastasis. Ley glycolipid acts as an important cofactor in the expression of the blood-coagulating activity of cancer cell-derived coagulating activity 1 (CCA-1), which is one of the known tumor procoagulants. Monoclonal antibody (MoAb) FS01, which serves as the Ley-recognizing epitope, inhibits the procoagulant activity of CCA-1 was found to dose-dependently inhibit the procoagulant activity of normal plasma induced by the human lung adenocarcinoma cell line, HAL8, which shows a high level of Ley expression. It did not, however, inhibit the procoagulant activity of the human colon cancer cell line, RPMI4788, which does not express Ley. Administration of FS01 MoAb inhibited lung metastasis of HAL8 cells, but not that of RPMI4788. The absence of antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity of FS01 MoAb against the HAL8 cell line suggests that the inhibition of HAL8 metastasis by FS01 MoAb derives from the inhibition of blood-coagulating activity of the latter. These findings indicate that Ley glycolipid plays an important role in the mechanism of cancer metastasis via the procoagulant activity of CCA-1.
Sparse MRI: The application of compressed sensing for rapid MR imaging (2007)

The sparsity which is implicit in MR images is exploited to significantly undersample k-space. Some MR images such as angiograms are already sparse in the pixel representation; other, more complicated images have a sparse representation in some transform domain-for example, in terms of spatial finite-differences or their wavelet coefficients. According to the recently developed mathematical theory of compressed-sensing, images with a sparse representation can be recovered from randomly undersampled k-space data, provided an appropriate nonlinear recovery scheme is used. Intuitively, artifacts due to random undersampling add as noise-like interference. In the sparse transform domain the significant coefficients stand out above the interference. A nonlinear thresholding scheme can recover the sparse coefficients, effectively recovering the image itself. In this article, practical incoherent undersampling schemes are developed and analyzed by means of their aliasing interference. Incoherence is introduced by pseudo-random variable-density undersampling of phase-encodes. The reconstruction is performed by minimizing the l(1) norm of a transformed image, subject to data fidelity constraints. Examples demonstrate improved spatial resolution and accelerated acquisition for multislice fast spin-echo brain imaging and 3D contrast enhanced angiography.
IL-21 Up-Regulates the Expression of Genes Associated with Innate Immunity and Th1 Response (2002)

IL-21 is a recently characterized T cell-derived cytokine that regulates NK and T cell function. IL-21R shares the common gamma-chain (gamma(c)) with the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Despite the same gamma(c), these cytokines have different effects on diverse cells. In this study, we have studied IL-15- and IL-21-induced gene expression in human primary NK and T cells and the NK-92 cell line. Both IL-15 and IL-21 rapidly induced mRNA synthesis for IFN-gamma, T-bet, IL-2Ralpha, IL-12Rbeta2, IL-18R, and myeloid differentiation factor 88 (MyD88), the genes that are important in activating innate immunity and Th1 response. IL-15 induced STAT5 DNA binding to the IL-2Ralpha IFN-gamma-activated sequence (GAS), MyD88 GAS, and c-cis-inducible elements, whereas IL-21 induced STAT3 DNA binding to MyD88 GAS and c-sis-inducible elements. IL-21-induced STAT3 activation was verified by immunoprecipitation and Western blotting with anti-phosphotyrosine Ab. In addition, pretreatment of NK-92 cells with IL-15 or IL-21 strongly enhanced IL-12-induced STAT4 DNA binding to IL-2Ralpha GAS. The induction of IFN-gamma, T-bet, IL-12Rbeta2, and IL-18R gene expression in NK cells, along with STAT3 activation, suggests that IL-21 is involved in the activation of innate immune responses. Moreover, the enhanced transcription of these genes in T cells establishes a significant role for IL-21 also in the Th1 response.
P-selectin Glycoprotein Ligand-1 Is the Major Counter-receptor for P-selectin on Stimulated T Cells and Is Widely Distributed in Non-functional Form on Many Lymphocytic Cells (1995)

P-selectin glycoprotein ligand-1 (PSGL-1) is the high affinity counter-receptor for P-selectin on myeloid cells (Sako, D., Chang, X.J., Barone, K.M., Vachino, G., White, H.M., Shaw, G., Veldman, G.M., Bean, K.M., Ahern, T.J., Furie, B., Cumming, D. A., and Larsen, G. R. (1993) Cell 75, 1179-1186). Here we demonstrate that PSGL-1 is also widely distributed on T- and B-lymphocytic tumor cell lines, resting peripheral blood T and B cells, and on stimulated peripheral blood T cell and intestinal intraepithelial lymphocyte (IEL) lines. However, the majority of PSGL-1-positive resting peripheral blood lymphocytic cells and lymphoid tumor cell lines do not display significant P-selectin binding. In contrast, in vitro stimulated peripheral blood T cell and IEL lines avidly bind P-selectin, and PSGL-1 is the sole high affinity counter-receptor mediating this binding. During the course of in vitro stimulation, cell surface expression levels of PSGL-1 do not change as P-selectin binding increases. Rather, the activities of two glycosyltransferases reportedly involved in the production of functional PSGL-1 in myeloid cells are substantially higher in the stimulated T-lymphocytic lines than in resting T lymphocytes, consistent with the hypothesis that activation-dependent post-translational events contribute to the expression of functional PSGL-1 on lymphocytes.
Visibility preprocessing for urban scenes using line space subdivision (2002)

We present an algorithm for visibility preprocessing of urban environments. The algorithm uses a subdivision of line space to analytically calculate a conservative potentially visible set for a given region in the scene. We present a detailed evaluation of our method, including a comparison to another recently published visibility preprocessing algorithm. To the best of our knowledge, the proposed method is the first algorithm that scales to large scenes and efficiently handles large view cells.
Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy. (1990)

A state of T-cell activation, reflected by a marked degree of spontaneous proliferation in vitro, exists among patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) but not in those with retroviral-induced adult T-cell leukemia (ATL). We wished to define the mechanism by which the immune activation of circulating cells from HAM/TSP is driven, thus gaining insight into the pathogenesis of this HTLV-I-associated disease. By using a modification of the polymerase chain reaction, we compared the levels of interleukin 2 (IL-2) and IL-2 receptor alpha chain (IL-2R alpha) mRNA expression to the transcription of the HTLV-I transactivator gene, pX, in peripheral blood mononuclear cells of HAM/TSP and ATL patients as well as seropositive carriers. Up-regulation of IL-2 and IL-2R alpha transcripts was detected in HAM/TSP and seropositive carriers that paralleled the coordinate mRNA expression of the pX transactivator. In addition, IL-2 and soluble IL-2R alpha serum levels in HAM/TSP and seropositive carriers were elevated. Despite markedly elevated levels of soluble IL-2R alpha in ATL, transcripts for IL-2 and pX were not demonstrable in the circulating cells. Finally, the marked degree of in vitro spontaneous proliferation present in HAM/TSP was profoundly inhibited by specific anti-IL-2R or anti-IL-2 blocking antibodies. Collectively, these results suggest that immune activation in HAM/TSP, in contrast to ATL, is virally driven by the transactivation and coordinate expression of IL-2 and IL-2R alpha. This deregulated autocrine process may contribute to the evolution of inflammatory nervous system damage in HAM/TSP.
Distal ileum and colon: targeted sites for 5-ASA release. (1991)

Sulphasalazine, used in the treatment of ulcerative colitis, is cleaved in the colon by the metabolic action of colonic bacteria on the diazo bond to release 5-Aminosalicylic acid (5-ASA) and sulpharidine. Whilst the former has been demonstrated to be active moiety, the latter is reputed to be responsible for toxicity associated with sulphasalazine therapy. A new multi-particulate formulation of 5-ASA has been designed (Asalan) to achieve targeted release of the drug in both the distal small intestine and colon and hence may be beneficial in the treatment of not only Ulcerative Colitis but also Crohn's disease. An imaging study was performed with beads formulated with barium sulphate using the same procedure employed to prepare 5-ASA beads. This study suggested 5-ASA capsule disintegration and bead dispersal in both the distal ileum and colon. This targetting was confirmed in two further in vivo studies using the 5-ASA formulation itself. In the first study comparison of plasma ASA levels following treatment with sulphasalazine treatment confirmed that 5-ASA release was occurring proximal to the colon. Despite this earlier release, the percentage of administered dose that was unabsorbed (dose-urinary recovery) was approximately 90%. In a second study a comparison was made with a single unit tablet of 5-ASA. A greater consistency and accuracy of targetting, as revealed by the appearance of plasma ASA levels, was confirmed for the capsule formulation. These separate studies were undertaken to evaluate the in vivo intestinal release characteristics of this new 5-ASA formulation in healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Proteomics for Cancer Biomarker Discovery and Therapeutic Targeting (2002)

As we emerge into the post-genome era, proteomics finds itself as the driving force field as we translate the nucleic acid information archive into understanding how the cell actually works and how disease processes operate. Even so, the traditionally held view of proteomics as simply cataloging and developing lists of the cellular protein repertoire of a cell are now changing, especially in the sub-discipline of clinical proteomics. The most relevant information archive to clinical applications and drug development involves the elucidation of the information flow of the cell; the "software" of protein pathway networks and circuitry. The deranged circuitry of the cell as the drug target itself as well as the effect of the drug on not just the target, but also the entire network, is what we now are striving towards. Clinical proteomics, as a new and most exciting sub-discipline of proteomics, involves the bench-to-bedside clinical application of proteomic tools. Unlike the genome, there are potentially thousands of proteomes: each cell type has its own unique proteome. Moreover, each cell type can alter its proteome depending on the unique tissue microenvironment in which it resides, giving rise to multiple permutations of a single proteome. Since there is no polymerase chain reaction equivalent to proteomics- identifying and discovering the "wiring diagram" of a human diseased cell in a biopsy specimen remains a daunting challenge. New micro-proteomic technologies are being and still need to be developed to drill down into the proteomes of clinically relevant material. Cancer, as a model disease, provides a fertile environment to study the application of proteomics at the bedside. The promise of clinical proteomics and the new technologies that are developed is that we will detect cancer earlier through discovery of biomarkers, we will discover the next generation of targets and imaging biomarkers, and we can then apply this knowledge to patient-tailored therapy.
SAR by MS:  Discovery of a New Class of RNA-Binding Small Molecules for the Hepatitis C Virus:  Internal Ribosome Entry Site IIA Subdomain (2005)

A new class of small molecules that bind the HCV RNA IRES IIA subdomain with sub-micromolar affinity is reported. The benzimidazole 'hit' 1 with a KD approximately 100 microM to a 29-mer RNA model of Domain IIA was identified from a 180000-member library using mass spectrometry-based screening methods. Further MS-assisted SAR (structure-activity relationships) studies afforded benzimidazole derivatives with sub-micromolar binding affinity for the IIA RNA construct. The optimized benzimidazoles demonstrated activity in a cellular replicon assay at concentrations comparable to their KD for the RNA target.
3′-Azidothymidine (Zidovudine) Inhibits Glycosylation and Dramatically Alters Glycosphingolipid Synthesis in Whole Cells at Clinically Relevant Concentrations (1995)

Recent in vitro work with Golgi-enriched membranes showed that 3'-azidothymidine-5'-monophosphate (AZTMP), the primary intracellular metabolite of 3'-azidothymidine (AZT), is a potent inhibitor of glycosylation reactions (Hall et al. (1994) J. Biol. Chem. 269, 14355-14358) and predicted that AZT treatment of whole cells should cause similar inhibition. In this report, we verify this prediction by showing that treatment of K562 cells with AZT inhibits lipid and protein glycosylation. AZT treatment dramatically alters the pattern of glycosphingolipid biosynthesis, nearly abolishing ganglioside synthesis at clinically relevant concentrations (1-5 microM), and suppresses the incorporation of both sialic acid and galactose into proteins. Control experiments demonstrate that these changes do not result from nonspecific effects on either the secretory apparatus or protein synthesis. On the other hand, studies using isolated nuclei as a model system for chromosomal DNA replication show that AZTTP is a very weak inhibitor of DNA synthesis. These observations strongly suggest that the myelosuppressive effects of AZT in vivo are due to inhibition of protein and/or lipid glycosylation and not to effects on chromosomal DNA replication.
On-chip integrated lensless microscopy module for optical monitoring of adherent growing mammalian cells (2010)

Lab-on-a-chip systems are increasingly applied in cell-based assays for toxicology and drug testing. In this paper, an on-chip integrated lensless microscopy module using a direct projection method for optical monitoring of the shadow images of adherent growing mammalian cells is presented. The biological cells are conserved and interfaced by a microfabricated cavity chip with a 1 microm thick silicon nitride (Si(3)N(4)) substrate onto the surface of a 5 megapixel CMOS image sensor with 2.2 microm pixel size. The optical resolution of the assembly is estimated by the contact/proximate printing theory from optical lithography. Further characterization is made by imaging microbeads in chips with the Si(3)N(4)-membrane as well as in cavity chips with membranes made from dry film resist (DFR, thickness 20, 40 and 60 microm). The module represents a 3 × optical microscope for cell morphology imaging. The function is demonstrated by the growth monitoring of L929 cells cultured in cavity chips with Si(3)N(4) substrate for 2 days and by checking the colorimetric staining of cells with a compromised membrane.
Perturbation of the chromosomal binding of RCC1, Mad2 and survivin causes spindle assembly defects and mitotic catastrophe (2008)

Mitotic catastrophe is a form of cell death that results from aberrant mitosis. Currently, the mechanisms involved in this form of cell death remain poorly understood. We found that actinomycin D induces mitotic catastrophe with severe spindle assembly defects. We have studied the nature of three groups of chromosome binding proteins in mitotic cells treated with actinomycin D. We found that actinomycin D reduced the binding affinity of RCC1 to the mitotic chromosome, which led to a reduction of RanGTP level. In addition, Mad2 was not concentrated at the kinetochores, indicating that the mitotic spindle checkpoint was affected. Furthermore, the localization of survivin was altered in cells. These data suggested that chromosomal binding of the mitotic regulators such as RCC1, Mad2 and survivin is essential for mitotic progression. Mitotic chromosomes not only carry the genetic material needed for the newly synthesized daughter cells, but also serve as docking sites for some of the mitotic regulators. Perturbation of their binding to the mitotic chromosome by actinomycin D could affect their functions in regulating mitotic progression thus leading to severe spindle defects and mitotic catastrophe.