gebhart/patrepeval huggingface dataset:
Deep Metric Learning with BIER: Boosting Independent Embeddings Robustly (2018)

Learning similarity functions between image pairs with deep neural networks yields highly correlated activations of embeddings. In this work, we show how to improve the robustness of such embeddings by exploiting the independence within ensembles. To this end, we divide the last embedding layer of a deep network into an embedding ensemble and formulate the task of training this ensemble as an online gradient boosting problem. Each learner receives a reweighted training sample from the previous learners. Further, we propose two loss functions which increase the diversity in our ensemble. These loss functions can be applied either for weight initialization or during training. Together, our contributions leverage large embedding sizes more effectively by significantly reducing correlation of the embedding and consequently increase retrieval accuracy of the embedding. Our method works with any differentiable loss function and does not introduce any additional parameters during test time. We evaluate our metric learning method on image retrieval tasks and show that it improves over state-of-the-art methods on the CUB-200-2011, Cars-196, Stanford Online Products, In-Shop Clothes Retrieval and VehicleID datasets. Therefore, our findings suggest that by dividing deep networks at the end into several smaller and diverse networks, we can significantly reduce overfitting.
An investigation of dose titration with darifenacin, an M 3 ‐selective receptor antagonist (2005)

Darifenacin appears to be an effective, well-tolerated and flexible treatment for patients with OAB, allowing individualized dosing according to patient needs.
The Nucleolin Binding Activity of Hepatitis Delta Antigen Is Associated with Nucleolus Targeting (1998)

Hepatitis delta antigens (HDAgs) are important for the replication and assembly of hepatitis delta virus (HDV). To understand the association between HDAgs and cellular proteins and the mechanism of viral multiplication, we have studied the interaction between HDAgs and nucleolin, a major nucleolar phosphoprotein. The interaction between HDAgs and nucleolin was first demonstrated by immunofluorescence staining studies. HDAgs and endogenous nucleolin were colocalized in the nucleoli of cultured cells transfected with plasmids encoding the small and large HDAg. Coimmunoprecipitation results indicated that the NH2-terminal domain of HDAg was essential for its binding to nucleolin. In vitro ligand binding assays revealed two nucleolin binding sites, NBS1 and NBS2. Each spanned amino acid residues 35-50 and 51-65, respectively, with a conserved core sequence K(K/R)XK. HDV replication was modulated by exogenous human nucleolin. In addition, a small HDAg mutant S-d65/75, which possesses both NBS1 and NBS2, was capable of transactivating HDV replication, whereas the small HDAg mutant S-d50/75, which retained NBS1 but not NBS2, was unable to support the replication of HDV. Thus, the nucleolin binding activity of HDAg is critical for its nucleolar targeting and is involved in the modulation of HDV replication.
Role of Kupffer Cells in Iodized Oil Embolization (1994)

Kupffer cells play an important role in clearing iodized oil from the liver. Iodized oil activates the immune defense system in the liver, which may have a synergistic effect in tumor treatment.
Aeroacoustic Analysis of Fan Noise Reduction with Increased Bypass Nozzle Area (2005)

An advanced model turbofan was tested in the NASA Glenn 9-by 15-Foot Low Speed Wind Tunnel (9x15 LSWT) to explore far field acoustic effects of increased bypass nozzle area. This fan stage test was part of the NASA Glenn Fan Broadband Source Diagnostic Test, second entry (SDT2) which acquired aeroacoustic results over a range of test conditions. The baseline nozzle was sized to produce maximum stage performance at cruise condition. However, the wind tunnel testing is conducted near sea level condition. Therefore, in order to simulate and obtain performance at other operating conditions, two additional nozzles were designed and tested one with +5 percent increase in weight flow (+5.4 percent increase in nozzle area compared with the baseline nozzle), sized to simulate the performance at the stage design point (takeoff) condition, and the other with a +7.5 percent increase in weight flow (+10.9 percent increase in nozzle area) sized for maximum weight flow with a fixed nozzle at sea level condition. Measured acoustic benefits with increased nozzle area were very encouraging, showing overall sound power level (OAPWL) reductions of 2 or more dB while the stage thrust actually increased by 2 to 3 percent except for the most open nozzle at takeoff rotor speed where stage performance decreased. Effective perceived noise levels for a 1500 ft engine flyover and 3.35 scale factor showed a similar noise reduction of 2 or more EPNdB. Noise reductions, principally in the level of broadband noise, were observed everywhere in the far field. Laser Doppler Velocimetry measurements taken downstream of the rotor showed that the total turbulent velocity decreased with increasing nozzle flow, which may explain the reduced rotor broadband noise levels.
Direct isolation of human central nervous system stem cells (2000)

Stem cells, which are clonogenic cells with self-renewal and multilineage differentiation properties, have the potential to replace or repair damaged tissue. We have directly isolated clonogenic human central nervous system stem cells (hCNS-SC) from fresh human fetal brain tissue, using antibodies to cell surface markers and fluorescence-activated cell sorting. These hCNS-SC are phenotypically 5F3 (CD133)(+), 5E12(+), CD34(-), CD45(-), and CD24(-/lo). Single CD133(+) CD34(-) CD45(-) sorted cells initiated neurosphere cultures, and the progeny of clonogenic cells could differentiate into both neurons and glial cells. Single cells from neurosphere cultures initiated from CD133(+) CD34(-) CD45(-) cells were again replated as single cells and were able to reestablish neurosphere cultures, demonstrating the self-renewal potential of this highly enriched population. Upon transplantation into brains of immunodeficient neonatal mice, the sorted/expanded hCNS-SC showed potent engraftment, proliferation, migration, and neural differentiation.
Polyphasic identification of yeasts isolated from bark of cork oak during the manufacturing process of cork stoppers (2004)

A two-step protocol was used for the identification of 52 yeasts isolated from bark of cork oak at initial stages of the manufacturing process of cork stoppers. The first step in the identification was the separation of the isolates into groups by their physiological properties and RFLPs of the ITS-5.8S rRNA gene. The second step was the sequencing of the D1/D2 domains of the 26S rRNA gene of selected isolates representing the different groups. The results revealed a predominance of basidiomycetous yeasts (11 species), while only two species represented the ascomycetous yeasts. Among the basidiomycetous yeasts, members representing the species Rhodosporidium kratochvilovae and Rhodotorula nothofagi, that have been previously isolated from plant material, were the most abundant. Yeasts pertaining to the species Debaryomyces hansenii var. fabryii, Rhodotorula mucilaginosa and Trichosporon mucoides were isolated in small numbers.
Selective loss of dopamine D3-type receptor mRNA expression in parietal and motor cortices of patients with chronic schizophrenia. (1993)

The expression of dopamine D3-subtype-receptor mRNA was analyzed in defined anatomic regions of brain obtained postmortem from patients with chronic schizophrenia and from controls. The specific amplification of D3-encoding cDNA by PCR allowed the identification of D3 mRNA expression in a wide variety of anatomic regions in both control brains and brains obtained from schizophrenic patients. However, in the parietal cortex (Brodmann areas 1, 2, 3, and 5) and motor cortex (Brodmann area 4), a selective loss of D3 mRNA expression was found in schizophrenia. A different D3 mRNA species was identified that appears to be widely expressed and that is still found in those regions of schizophrenic brains where D3 mRNA could not be detected. Compared with D3 mRNA this RNA is significantly less abundant, and at present its function (if any) is unclear. Many variables associated with either the course and/or the therapeutic management of the disease may account for the selective loss of D3 mRNA in the motor, somatosensory, and somatosensory association areas of schizophrenic brains.
TCPTP Regulates SFK and STAT3 Signaling and Is Lost in Triple-Negative Breast Cancers (2012)

Tyrosine phosphorylation-dependent signaling, as mediated by members of the epidermal growth factor receptor (EGFR) family (ErbB1 to -4) of protein tyrosine kinases (PTKs), Src family PTKs (SFKs), and cytokines such as interleukin-6 (IL-6) that signal via signal transducer and activator of transcription 3 (STAT3), is critical to the development and progression of many human breast cancers. EGFR, SFKs, and STAT3 can serve as substrates for the protein tyrosine phosphatase TCPTP (PTPN2). Here we report that TCPTP protein levels are decreased in a subset of breast cancer cell lines in vitro and that TCPTP protein is absent in a large proportion of "triple-negative" primary human breast cancers. Homozygous TCPTP deficiency in murine mammary fat pads in vivo is associated with elevated SFK and STAT3 signaling, whereas TCPTP deficiency in human breast cancer cell lines enhances SFK and STAT3 signaling. On the other hand, TCPTP reconstitution in human breast cancer cell lines severely impaired cell proliferation and suppressed anchorage-independent growth in vitro and xenograft growth in vivo. These studies establish TCPTP's potential to serve as a tumor suppressor in human breast cancer.
Cyclin-dependent kinases as cellular targets for antiviral drugs (2002)

Cyclin-dependent kinases (cdks) are required for replication of viruses that replicate only in dividing cells, such as adeno- and papillomaviruses. Recently, cdks have been shown to be required also for replication of viruses that can replicate in non-dividing cells, such as HIV-1 and herpes simplex virus types 1 and 2 (HSV-1 and -2). In these experiments, pharmacological cdk inhibitors (PCIs) were shown to have potent antiviral activity in vitro against HIV-1, HSV-1 and -2, human cytomegalovirus, varicella-zoster virus, and to inhibit specific functions of other viruses. Since two PCIs, flavopiridol and roscovitine, are proving to be non-toxic in human clinical trials against cancer, PCIs may be useful as antivirals. As significant advantages, PCIs are active in vitro against many viruses, including drug-resistant strains of HIV-1 and HSV-1, and mutant strains of HIV-1 or HSV-1 resistant to PCIs have not been identified in spite of intense efforts. Furthermore, the antiviral effects of a PCI and a conventional antiviral drug are additive. The aetiopathogenesis of several diseases, such as Kaposi's sarcoma, HPV-induced cervical carcinoma and HIV-associated nephropathy (HIVAN), among others, includes replication or expression of proteins by viruses that require cdks. Thus, PCIs could target both the aetiological agent (the virus) and the pathogenic mechanisms (cell replication). Two important questions regarding the antiviral activities of PCIs are the focus of current research efforts, (i) the identity of the specific cdks that mediate the antiviral activities of PCIs, and (ii) whether PCIs have antiviral activity in vivo at non-toxic doses.
M4T: a comparative protein structure modeling server (2007)

Multiple Mapping Method with Multiple Templates (M4T) (http://www.fiserlab.org/servers/m4t) is a fully automated comparative protein structure modeling server. The novelty of M4T resides in two of its major modules, Multiple Templates (MT) and Multiple Mapping Method (MMM). The MT module of M4T selects and optimally combines the sequences of multiple template structures through an iterative clustering approach that takes into account the 'unique' contribution of each template, its sequence similarity to other template sequences and to the target sequences, and the quality of its experimental resolution. MMM module is a sequence-to-structure alignment method that is aimed at improving the alignment accuracy, especially at lower sequence identity levels. The current implementation of MMM takes inputs from three profile-to-profile-based alignment methods and iteratively compares and ranks alternatively aligned regions according to their fit in the structural environment of the template structure. The performance of M4T was benchmarked on CASP6 comparative modeling target sequences and on a larger independent test set and showed a favorable performance to current state-of-the-art methods.
Topotecan as a radiosensitizer in the treatment of children with malignant diffuse brainstem gliomas (2005)

The findings of the current study regarding newly diagnosed brainstem glioma patients treated with topotecan given as a radiosensitizing agent did not reproduce the encouraging results obtained in preclinical studies. Therefore, the concomitant combination of topotecan and radiotherapy at this schedule and these doses cannot be recommended for the treatment of patients with brainstem gliomas.
A pilot study of the CY-1899 T-cell vaccine in subjects chronically infected with hepatitis B virus (1999)

Clinical observations suggest that eradication of the hepatitis B virus (HBV) is immune-mediated. Vigorous cytotoxic T lymphocyte (CTL) activity directed at HLA class I-bound viral epitopes are detected during acute hepatitis B, but not in chronic hepatitis B carriers. A CTL epitope derived from the hepatitis B core protein amino acids 18-27 has been incorporated into a vaccine also comprised of a T-helper cell epitope and 2 palmitic acid residues (CY-1899). The aim of this study was to determine whether repeated doses of CY-1899 given to patients with chronic hepatitis B could initiate in vivo CTL activity and viral clearance. Patients with chronic hepatitis B received up to 4 doses (ranging from 0.05 mg to 15 mg) 6 weeks apart. Following vaccination, patients were monitored for hepatitis B surface antigen and "e" status, HBV-DNA levels, liver biochemistry, CTL activity, and any adverse events. Ninety patients with chronic hepatitis B infection received CY-1899. Mean CTL responses were all low but were maximal following vaccination with 5 mg CY-1899. Peak CTL responses never exceeded 10 lytic units (LU) regardless of vaccine dose, this value being well below that seen following resolution of acute hepatitis B. No significant changes in liver biochemistry or viral serology were observed during follow-up. No serious adverse events were noted. Administration of the single-epitope vaccine, CY-1899, initiated CTL activity, but of a magnitude lower than that observed during spontaneous HBV clearance. This low-level CTL activity was not associated with viral clearance.
Analyzing Optimal Marketing Strategies Over Customers' Networks (2011)

In a costumers’ network obtained, for example, from social networks, modeling influences among buyers is useful to estimate a buyer’s decision to buy an item. This kind of influences is sometimes modeled with submodular functions and the problem of finding the marketing strategies to offer items to buyers that maximize the revenues of other buyers can be formulated as submodular maximization. In this paper, we address the problem of analyzing optimal and near-optimal solutions (strategies) to this problem and investigate numerically with real social network data.
Characteristics of a terahertz photomixer based on a high-electron mobility transistor structure with optical input through the ungated regions (2004)

We develop a device model for a terahertz photomixer that utilizes the excitation of plasma oscillations in the channel of a device similar to a high-electron mobility transistor (HEMT). The device design assumes vertical optical input through the ungated source–gate and gate–drain regions. Using this model, we calculate the characteristics of the HEMT photomixer: the responsivity as a function of the signal frequency for devices with different geometrical and physical parameters, and the dependence of resonant frequency on the length of the gated and ungated portions of the channel and the gate voltage. We compare also the performance of the HEMT photomixer with that of a similar device but one in which the optical input is through the substrate.
BRAF and RAS mutations in human lung cancer and melanoma. (2002)

BRAF encodes a RAS-regulated kinase that mediates cell growth and malignant transformation kinase pathway activation. Recently, we have identified activating BRAF mutations in 66% of melanomas and a smaller percentage of many other human cancers. To determine whether BRAF mutations account for the MAP kinase pathway activation common in non-small cell lung carcinomas (NSCLCs) and to extend the initial findings in melanoma, we screened DNA from 179 NSCLCs and 35 melanomas for BRAF mutations (exons 11 and 15). We identified BRAF mutations in 5 NSCLCs (3%; one V599 and four non-V599) and 22 melanomas (63%; 21 V599 and 1 non-V599). Three BRAF mutations identified in this study are novel, altering residues important in AKT-mediated BRAF phosphorylation and suggesting that disruption of AKT-induced BRAF inhibition can play a role in malignant transformation. To our knowledge, this is the first report of mutations documenting this interaction in human cancers. Although >90% of BRAF mutations in melanoma involve codon 599 (57 of 60), 8 of 9 BRAF mutations reported to date in NSCLC are non-V599 (89%; P < 10(-7)), strongly suggesting that BRAF mutations in NSCLC are qualitatively different from those in melanoma; thus, there may be therapeutic differences between lung cancer and melanoma in response to RAF inhibitors. Although uncommon, BRAF mutations in human lung cancers may identify a subset of tumors sensitive to targeted therapy.
Minireview: 11β-Hydroxysteroid Dehydrogenase Type 1— A Tissue-Specific Amplifier of Glucocorticoid Action1 (2001)

11beta-hydroxysteroid dehydrogenases (11beta-HSDs) catalyze the interconversion of active glucocorticoids (cortisol, corticosterone) and inert 11-keto forms (cortisone, 11-dehydrocorticosterone). 11beta-HSD type 2 has a well recognized function as a potent dehydrogenase that rapidly inactivates glucocorticoids, thus allowing aldosterone selective access to otherwise nonselective mineralocorticoid receptors in the distal nephron. In contrast, the function of 11beta-HSD type 1 has, until recently, been little understood. 11beta-HSD1 is an ostensibly reversible oxidoreductase in vitro, which is expressed in liver, adipose tissue, brain, lung, and other glucocorticoid target tissues. However, increasing data suggest that 11beta-HSD1 acts as a predominant 11beta-reductase in many intact cells, whole organs, and in vivo. This reaction direction locally regenerates active glucocorticoids within expressing cells, exploiting the substantial circulating levels of inert 11-keto steroids. While the biochemical determinants of the reaction direction are not fully understood, insights to its biological importance have been afforded by use of inhibitors in vivo, including in humans, and the generation of knockout mice. Such studies suggest 11beta-HSD1 effectively amplifies glucocorticoid action at least in the liver, adipose tissue, and the brain. Inhibition of 11beta-HSD1 represents a potential target for therapy of disorders that might be ameliorated by local reduction of glucocorticoid action, including type 2 diabetes, obesity, and age-related cognitive dysfunction.
Associations of human leukocyte antigen DRB with resistance or susceptibility to HIV-1 infection in the Pumwani Sex Worker Cohort (2008)

Our findings indicate that human leukocyte antigen DRB-specific CD4+ T-cell responses are an important factor in resistance/susceptibility to HIV-1 infection.
Cell‐free protein synthesis enables high yielding synthesis of an active multicopper oxidase (2015)

Multicopper oxidases (MCOs) are broadly distributed in all kingdoms of life and perform a variety of important oxidative reactions. These enzymes have potential biotechnological applications; however, the applications are impeded by low expression yields in traditional recombinant hosts, solubility issues, and poor copper cofactor assembly. As an alternative to traditional recombinant protein expression, we show the ability to use cell-free protein synthesis (CFPS) to produce complex MCO proteins with high soluble titers. Specifically, we report the production of MCOs in an Escherichia coli-based cell-free transcription-translation system. Total yields as high as 1.2 mg mL(-1) were observed after a 20-h batch reaction. More than 95% of the protein was soluble and activity was obtained by simple post-CFPS addition of copper ions in the form of CuSO4 . Scale-up reactions were achieved from 15 to 100 µL without a decrease in productivity and solubility. CFPS titers were higher than in vivo expression titers and more soluble, avoiding the formation of inclusion bodies. Our work extends the utility of the cell-free platform to the production of active proteins containing copper cofactors and demonstrates a simple method for producing MCOs.
Conformational modification of muscle phosphofructokinase from Jaculus orientalis upon ligand binding (1989)

Phosphofructokinase from Jaculus orientalis muscle is an allosteric enzyme regulated by substrates and nucleotide effectors. The conformational modifications upon ligand binding were probed by UV difference spectra and reactivities of thiol groups towards dithiobisnitrobenzoate and N-ethylmaleimide. The binding of Fru-6-P induced significant perturbations in the environment of the aromatic residues and buried the most reactive on the three accessible cysteines per protomer. The same effect on thiol reactivity was observed upon binding of the activator AMP. Various perturbations of both difference spectra and thiol reactivity were detected in the presence of either Mg-ATP, an allosteric inhibitor, or Mg-ITP which is not an effector.
Micro/nanorobots for biomedicine: Delivery, surgery, sensing, and detoxification (2017)

Micro- and nanoscale robots that can effectively convert diverse energy sources into movement and force represent a rapidly emerging and fascinating robotics research area. Recent advances in the design, fabrication, and operation of micro/nanorobots have greatly enhanced their power, function, and versatility. The new capabilities of these tiny untethered machines indicate immense potential for a variety of biomedical applications. This article reviews recent progress and future perspectives of micro/nanorobots in biomedicine, with a special focus on their potential advantages and applications for directed drug delivery, precision surgery, medical diagnosis and detoxification. Future success of this technology, to be realized through close collaboration between robotics, medical and nanotechnology experts, should have a major impact on disease diagnosis, treatment, and prevention.
Development of a [3+3] Cycloaddition Strategy toward Functionalized Piperidines (2003)

This paper describes a novel route to functionalized piperidines via a formal [3+3] cycloaddition reaction of activated aziridines and palladium-trimethylenemethane (Pd-TMM) complexes. The cycloaddition reaction generally proceeds enantiospecifically with ring opening at the least hindered site of the aziridine. Therefore, readily available enantiomerically pure 2-substituted aziridines can be utilized to prepare enantiomerically pure 2-substituted piperidines in good to excellent yield. The N-substituent on the aziridine proved to be crucial to the success of this reaction with only 4-toluenesulfonyl (Ts) and 4-methoxybenzenesulfonyl (PMBS) aziridines permitting smooth cycloaddition to take place. Additionally, spirocyclic aziridines have been found to participate in the [3+3] cycloaddition reaction, whereas 2,3-disubstituted aziridines can be applied to provide fused bicyclic piperidines, albeit in low yield.