gebhart/patrepeval huggingface dataset:
Speckle-field digital holographic microscopy (2009)

The use of coherent light in conventional holographic phase microscopy (HPM) poses three major drawbacks: poor spatial resolution, weak depth sectioning, and fixed pattern noise due to unwanted diffraction. Here, we report a technique which can overcome these drawbacks, but maintains the advantage of phase microscopy - high contrast live cell imaging and 3D imaging. A speckle beam of a complex spatial pattern is used for illumination to reduce fixed pattern noise and to improve optical sectioning capability. By recording of the electric field of speckle, we demonstrate high contrast 3D live cell imaging without the need for axial scanning - neither objective lens nor sample stage. This technique has great potential in studying biological samples with improved sensitivity, resolution and optical sectioning capability.
Liberalism in the Theory of Social Choice (1976)

Journal Article Liberalism in the Theory of Social Choice Get access M. J. Farrell M. J. Farrell Gonville and Caius College, Cambridge Search for other works by this author on: Oxford Academic Google Scholar The Review of Economic Studies, Volume 43, Issue 1, February 1976, Pages 3–10, https://doi.org/10.2307/2296595 Published: 01 February 1976 Article history Received: 01 July 1974 Accepted: 01 February 1975 Published: 01 February 1976
Insertion of a pathogenic mutation into a yeast artificial chromosome containing the human amyloid precursor protein gene. (1994)

The genetic modelling of human disease would be considerably facilitated if pathogenic mutations could be inserted into transgenes which were then expressed in an appropriate manner. Yeast artificial chromosomes (YACs), when used as transgenes appear to direct expression with the correct temporal and spatial distribution. Here we demonstrate that it is comparatively straightforward to introduce pathogenic mutations into such YACs by the use of the 'pop-in, pop-out' procedure, by inserting an Alzheimer-causing mutation (APP717Val-->lle) into an APP-containing YAC which has previously been used as a transgene. The significance of these procedures for the modelling of human disease is discussed.
TransTerm: a database of translational signals (1996)

The TransTerm database of sequence contexts of stop and start codons has been expanded to include approximately 50% more species than last year's release. It now contains 148 organisms and >39 500 coding sequences; it is now available on the World Wide Web. The database includes: (i) initiation and termination sequence contexts organized by species; (ii) summary parameters about the individual sequences (sequence length, GC%, GC3, Nc, CAI) in addition to tables of base frequencies for each species' stop and start codon sequence context; (iii) species codon usage tables; and (iv) summary tables of stop signal frequency.
Low-Oxygen-Recovery Assay for High-Throughput Screening of Compounds against Nonreplicating Mycobacterium tuberculosis (2007)

Screening for new antimicrobial agents is routinely conducted only against actively replicating bacteria. However, it is now widely accepted that a physiological state of nonreplicating persistence (NRP) is responsible for antimicrobial tolerance in many bacterial infections. In tuberculosis, the key to shortening the 6-month regimen lies in targeting this NRP subpopulation. Therefore, a high-throughput, luminescence-based low-oxygen-recovery assay (LORA) was developed to screen antimicrobial agents against NRP Mycobacterium tuberculosis. M. tuberculosis H37Rv containing a plasmid with an acetamidase promoter driving a bacterial luciferase gene was adapted to low oxygen conditions by extended culture in a fermentor with a 0.5 headspace ratio. The MICs of 31 established antimicrobial agents were determined in microplate cultures maintained under anaerobic conditions for 10 days and, for comparative purposes, under aerobic conditions for 7 days. Cultures exposed to drugs under anaerobic conditions followed by 28 h of "recovery" under ambient oxygen produced a luminescent signal that was, for most compounds, proportional to the number of CFU determined prior to the recovery phase. No agents targeting the cell wall were active against NRP M. tuberculosis, whereas drugs hitting other cellular targets had a range of activities. The calculated Z' factor was in the range of 0.58 to 0.84, indicating the suitability of the use of LORA for high-throughput assays. This LORA is sufficiently robust for use for primary high-throughput screening of compounds against NRP M. tuberculosis.
Crosstalk Between the Immune and Central Nervous Systems with Special Reference to Drug Development (2011)

Although the understanding of disease mechanisms becomes rapidly progressed in recent years, there remain a lot of unmet medical needs in a number of disease fields. Especially in the degenerative diseases of the central nervous system (CNS) such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke and traumatic brain injury, currently available drugs only manage the symptoms, and there exist few disease-modifying therapies. Therefore, novel therapeutic interventions that modify and delay the disease progression are highly demanded. Drug development for the CNS diseases is particularly challenging (Kola I and Landis J, 2004). One of the hurdles to develop drugs for the CNS diseases is poor translation from animal models to human diseases (Pritchard JF, 2008). One strategy to overcome this hurdle is to examine therapeutic potential of a target molecule in a number of experimental settings, assuming that a molecule that modulates pathophysiologic mechanisms underlying a range of neurodegenerative disease has a higher chance to work in human disease (Mehal WZ, Iredale J & Friedman SL 2011). Although this strategy requires much resource, it enables us to eliminate candidates that act only in a particular experimental setting that might have a lower chance to be effective in humans. One example for this strategy is a kynurenine 3-monooxygenase that catalyzes the conversion of kynurenine to 3-hydroxykynurenine in the kynurenine pathway of tryptophan degradation (Stone TW & Darlington LG, 2002; Schwarcz R, 2004). A small molecule inhibitor of kynurenine 3-monooxygenase increased the levels of neuroprotective kynurenic acid and decreased the levels of neurotoxic quinolinic acid/3-hydroxykynurenine in mice. Furthermore, the treatment with the kynurenine 3-monooxygenase inhibitor ameliorated neurodegeneration in two types of mouse neurodegenerative models for Alzheimer’s disease and Huntington’s disease (Reinhart PH & Kelly JW, 2011; Zwilling D et al., 2011). These observations suggest that the kynurenine 3-monooxygenase would be more promising therapeutic target than conventional therapeutic ones that are effective in animal models of a single disease. Another strategy to increase the probability of success of drug development in the CNS diseases is to target a molecule that possess multiple pharmacological actions and hence
A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21 in patients with advanced lung adenocarcinoma (2018)

The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses). A two-stage minimax design was used. During phase I, no dose-limiting toxicities were shown in three patients who received GM.CD40L.CCL21. During phase II, of evaluable patients, 5/33 patients (15.2%) randomized for GM.DCD40L (p = .023) and 3/32 patients (9.4%) randomized for GM.DCD40L.CCL21 (p = .20) showed 6-month progression-free survival. Median overall survival was 9.3 versus 9.5 months with GM.DCD40L versus GM.DCD40L.CCL21 (95% CI 0.70-2.25; p = .44). For GM.CD40L versus GM.CD40L.CCL21, the most common treatment-related adverse events (TRAEs) were grade 1/2 injection site reaction (51.4% versus 61.1%) and grade 1/2 fatigue (35.1% versus 47.2%). Grade 1 immune-mediated TRAEs were isolated to skin. No patients showed evidence of pseudo-progression or immune-related TRAEs of grade 1 or greater of pneumonitis, endocrinopathy, or colitis, and none discontinued treatment due to toxicity. Although we found no significant associations between vaccine immunogenicity and outcomes, in limited biopsies, one patient treated with GMCD40L.CCL21 displayed abundant tumor-infiltrating lymphocytes. This possible effectiveness warrants further investigation of GM.CD40L in combination approaches.
Size-Dependent Optical Properties ofVO2Nanoparticle Arrays (2004)

The size effects on the optical properties of vanadium dioxide nanoparticles in ordered arrays have been studied. Contrary to previous VO2 studies, we observe that the optical contrast between the semiconducting and metallic phases is dramatically enhanced in the visible region, presenting size-dependent optical resonances and size-dependent transition temperatures. The collective optical response as a function of temperature presents an enhanced scattering state during the evolving phase transition. The effects appear to arise because of the underlying VO2 mesoscale optical properties, the heterogeneous nucleation behind the phase transition, and the incoherent coupling between the nanoparticles undergoing an order-disorder-order transition. Calculations that support these interpretations are presented.
Charged Residues in the Transmembrane Domains of Hepatitis C Virus Glycoproteins Play a Major Role in the Processing, Subcellular Localization, and Assembly of These Envelope Proteins (2000)

For most membrane proteins, the transmembrane domain (TMD) is more than just an anchor to the membrane. The TMDs of hepatitis C virus (HCV) envelope proteins E1 and E2 are extreme examples of the multifunctionality of such membrane-spanning sequences. Indeed, they possess a signal sequence function in their C-terminal half, play a major role in endoplasmic reticulum localization of E1 and E2, and are potentially involved in the assembly of these envelope proteins. These multiple functions are supposed to be essential for the formation of the viral envelope. As for the other viruses of the family Flaviviridae, these anchor domains are composed of two stretches of hydrophobic residues separated by a short segment containing at least one fully conserved charged residue. Replacement of these charged residues by an alanine in HCV envelope proteins led to an alteration of all of the functions performed by their TMDs, indicating that these functions are tightly linked together. These data suggest that the charged residues of the TMDs of HCV glycoproteins play a key role in the formation of the viral envelope.
Genomic alterations inBCL2L1andDLC1contribute to drug sensitivity in gastric cancer (2015)

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Recent high-throughput analyses of genomic alterations revealed several driver genes and altered pathways in GC. However, therapeutic applications from genomic data are limited, largely as a result of the lack of druggable molecular targets and preclinical models for drug selection. To identify new therapeutic targets for GC, we performed array comparative genomic hybridization (aCGH) of DNA from 103 patients with GC for copy number alteration (CNA) analysis, and whole-exome sequencing from 55 GCs from the same patients for mutation profiling. Pathway analysis showed recurrent alterations in the Wnt signaling [APC, CTNNB1, and DLC1 (deleted in liver cancer 1)], ErbB signaling (ERBB2, PIK3CA, and KRAS), and p53 signaling/apoptosis [TP53 and BCL2L1 (BCL2-like 1)] pathways. In 18.4% of GC cases (19/103), amplification of the antiapoptotic gene BCL2L1 was observed, and subsequently a BCL2L1 inhibitor was shown to markedly decrease cell viability in BCL2L1-amplified cell lines and in similarly altered patient-derived GC xenografts, especially when combined with other chemotherapeutic agents. In 10.9% of cases (6/55), mutations in DLC1 were found and were also shown to confer a growth advantage for these cells via activation of Rho-ROCK signaling, rendering these cells more susceptible to a ROCK inhibitor. Taken together, our study implicates BCL2L1 and DLC1 as potential druggable targets for specific subsets of GC cases.
Physiologically active hydrogel (in situ gel) of sparfloxacin and its evaluation for ocular retention using gamma scintigraphy (2015)

Objective: Due to the structure and physiological barrier of eye, only 1% of instilled dose is available for action on the corneal surface. In this work, we developed and evaluated chitosan (pH sensitive) and gellan gum (ion sensitive) in situ gel of sparfloxacin to improve precorneal residence time. Materials and Methods: A protocol for radiolabeling of sparfloxacin with Tc-99m was optimized to study the ocular retention using gamma scintigraphy technique. Results: The clear formulation was developed. In vitro release showed a sustained and prolonged release compared to plain eye drop solution. Dynamic and static gamma scintigraphy showed better retention than plain eye drops. The ocular tolerance test (hen's egg test-chorioallantoic membrane test and infra-red study) showed that the formulation is nonirritant and can be used as ocular vehicle. Conclusion: Radiolabel protocol for sparfloxacin was successfully developed and evaluated on ocular retention studies of developed in situ gel. The developed in situ gel is non irritant and can go further with clinical evaluation.
A multisubunit particle implicated in membrane fusion. (1992)

The N-ethylmaleimide sensitive fusion protein (NSF) is required for fusion of lipid bilayers at many locations within eukaryotic cells. Binding of NSF to Golgi membranes is known to require an integral membrane receptor and one or more members of a family of related soluble NSF attachment proteins (alpha-, beta-, and gamma-SNAPs). Here we demonstrate the direct interaction of NSF, SNAPs and an integral membrane component in a detergent solubilized system. We show that NSF only binds to SNAPs in the presence of the integral receptor, resulting in the formation of a multisubunit protein complex with a sedimentation coefficient of 20S. Particle assembly reveals striking differences between members of the SNAP protein family; gamma-SNAP associates with the complex via a binding site distinct from that used by alpha- and beta-SNAPs, which are themselves equivalent, alternative subunits of the particle. Once formed, the 20S particle is subsequently able to disassemble in a process coupled to the hydrolysis of ATP. We suggest how cycles of complex assembly and disassembly could help confer specificity to the generalized NSF-dependent fusion apparatus.
A new targeted blue light phototherapy for the treatment of acne (2007)

Targeted blue light phototherapy with MultiClear is effective for the treatment of inflammatory acne lesions. This new irradiation device offers some advantages over previous blue light systems.
Laser pointer interaction (2001)

Group meetings and other non-desk situations require that people be able to interact at a distance from a display surface. This paper describes a technique using a laser pointer and a camera to accomplish just such interactions. Calibration techniques are given to synchronize the display and camera coordinates. A series of interactive techniques are described for navigation and entry of numbers, times, dates, text, enumerations and lists of items. The issues of hand jitter, detection error, slow sampling and latency are discussed in each of the interactive techniques.
βIII-Tubulin Regulates Breast Cancer Metastases to the Brain (2015)

Brain metastases occur in about 10% to 30% of breast cancer patients, which culminates in a poor prognosis. It is, therefore, critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII-tubulin, Nestin, and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII-tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2, and MDA-MB-468), which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells.
Receptor-mediated transcellular transport of immunoglobulin: synthesis of secretory component as multiple and larger transmembrane forms. (1980)

We have characterized the early biosynthetic forms of secretory component (SC). SC is synthesized in various glandular epithelial cells and functions in transepithelial transport of certain polymeric immunoglobulins. In rabbit, mature SC is known to be heterogeneous, consisting of two or three immunologically related glycoproteins. Using translation of mRNA from rabbit mammary gland or liver in a wheat germ cell-free system supplemented with dog pancreas microsomal vesicles, we discovered that the translation products of SC mRNA include at least four distinct polypeptides. Moreover, we found that all four polypeptides are synthesized not as soluble secretory forms but as considerably larger transmembrane forms that are core-glycosylated and asymmetrically integrated into the dog pancreas microsomal vesicles in a translation-coupled manner. We therefore conclude that the mature secreted forms of SC are endoproteolytic fragments derived from and comprising the ectoplasmic portion of the transmembrane precursor forms. The detection of transmembrane precursor forms for mature SC provides a protein structural basis for their function as receptors mediating transepithelial transport of immuno-globulin molecules.
VCAP-AMP-VECP Compared With Biweekly CHOP for Adult T-Cell Leukemia-Lymphoma: Japan Clinical Oncology Group Study JCOG9801 (2007)

The longer OS at 3 years and higher CR rate with VCAP-AMP-VECP compared with biweekly CHOP suggest that VCAP-AMP-VECP might be a more effective regimen at the expense of higher toxicities, providing the basis for future investigations in the treatment of ATLL.
CADASIL with a Novel Mutation in Exon 7 of NOTCH3 (C388Y) (2006)

We report a 38-year-old Japanese woman who had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with a novel mutation (TGT to TAT) at nucleotide position 1241 (C388Y) in exon 7 of the Notch3 gene (NOTCH3). Immunostaining of a skin biopsy with a Notch3 monoclonal antibody is a beneficial method for the screening of CADASIL, particularly in the case of rare mutations outside the mutation hotspots in NOTCH3 as shown in this patient.
Magnetic recording properties of magneto-optical media by merge type GMR head (2000)

Summary form only given. The complete presentation was not made available for publication as part of the conference proceedings.
An automated visual inspection of solder joints using 2D and 3D features (2002)

In this paper, efficient techniques for solder joint inspection have been described. Using three layers of ring shaped LED's with different illumination angles, three frames of images are sequentially obtained. From these images the regions of interest (soldered regions) are segmented, and their characteristic features including the average gray level and the percentage of highlights-referred to as 2D features-are extracted. Based on the backpropagation algorithm of neural networks, each solder joint is classified into one of the pre-defined types. If the output value is not in the confidence interval, the distribution of tilt angles-referred to as 3D features-is calculated, and the solder joint is classified based on the Bayes classifier. The second classifier requires more computation while providing more information and better performance. The proposed inspection system has been implemented and tested with various types of solder joints in SMDs. The experimental results have verified the validity of this scheme in terms of speed and recognition rate.
Comparative Profiling of Triple-Negative Breast Carcinomas Tissue Glycoproteome by Sequential Purification of Glycoproteins and Stable Isotope Labeling (2016)

This work provides potential glycoprotein markers to function as a novel tissue-based biomarker for TNBC.
Hop (Humulus lupulus)-Derived Bitter Acids as Multipotent Bioactive Compounds (2009)

Hop acids, a family of bitter compounds derived from the hop plant (Humulus lupulus), have been reported to exert a wide range of effects, both in vitro and in vivo. They exhibit potential anticancer activity by inhibiting cell proliferation and angiogenesis, by inducing apoptosis, and by increasing the expression of cytochrome P450 detoxification enzymes. Furthermore, hop bitter acids are effective against inflammatory and metabolic disorders, which makes them challenging candidates for the treatment of diabetes mellitus, cardiovascular diseases, and metabolic syndrome. This review summarizes the current knowledge on hop bitter acids, including both phytochemical aspects, as well as the biological and pharmacological properties of these compounds.
Multiple dermatofibromas: Dermoscopic patterns (2013)

Dermatofibromas are benign skin lesions that consist of pigmented papules or nodules. They produce the dimple sign when laterally squeezed and are usually found on the legs. These clinical features lead to the diagnosis in most cases. However, the differential diagnosis with other lesions, such as atypical nevi and melanoma can be difficult, and the dermoscopy may help the diagnosis. There are several dermoscopic patterns associated with dermatofibromas, the most common being a central white scar like patch with delicate pigment network at the periphery. This article describes the case of a patient who had eleven clinically similar dermatofibromas, with four distinct patterns when submitted to dermoscopic examination.
Cbl-b, a RING-type E3 Ubiquitin Ligase, Targets Phosphatidylinositol 3-Kinase for Ubiquitination in T Cells (2001)

Cbl-b is implicated in setting the threshold of T lymphocyte activation. In Cbl-b-deficient T cells, the activation of Vav, a guanine nucleotide exchange factor, is significantly enhanced. The molecular mechanism underlying Cbl-b-regulated Vav activation was unclear. Here it is shown that Cbl-b interacts with and induces ubiquitin conjugation to the p85 regulatory subunit of phosphatidylinositol 3-kinase, an upstream regulator of Vav. A functional RING finger of Cbl-b was essential for p85 ubiquitination. However, a loss of function mutation at the well-conserved amino-terminal variant src homology (SH) 2 domain of Cbl-b did not affect its ligase activity. A distal carboxyl-terminal proline-rich region in Cbl-b was mapped to contain the primary binding sequences for the SH3 domain of p85. Deletion of either the distal proline-rich region in Cbl-b or the SH3 domain of p85 severely reduced ubiquitin conjugation to p85. The data suggest a molecular link for Cbl-b-mediated negative regulation of Vav, with phosphatidylinositol 3-kinase as a direct target for Cbl-b E3 ubiquitin ligase.