gebhart/patrepeval huggingface dataset:
Context-Aware Captions from Context-Agnostic Supervision (2017)

We introduce an inference technique to produce discriminative context-aware image captions (captions that describe differences between images or visual concepts) using only generic context-agnostic training data (captions that describe a concept or an image in isolation). For example, given images and captions of siamese cat and tiger cat, we generate language that describes the siamese cat in a way that distinguishes it from tiger cat. Our key novelty is that we show how to do joint inference over a language model that is context-agnostic and a listener which distinguishes closely-related concepts. We first apply our technique to a justification task, namely to describe why an image contains a particular fine-grained category as opposed to another closely-related category of the CUB-200-2011 dataset. We then study discriminative image captioning to generate language that uniquely refers to one of two semantically-similar images in the COCO dataset. Evaluations with discriminative ground truth for justification and human studies for discriminative image captioning reveal that our approach outperforms baseline generative and speaker-listener approaches for discrimination.
Measuring bottleneck bandwidth of targeted path segments (2004)

Accurate measurement of network bandwidth is crucial for network management applications as well as flexible Internet applications and protocols which actively manage and dynamically adapt to changing utilization of network resources. Extensive work has focused on two approaches to measuring bandwidth: measuring it hop-by-hop, and measuring it end-to-end along a path. Unfortunately, best-practice techniques for the former are inefficient, and techniques for the latter are only able to observe bottlenecks visible at end-to-end scope. In this paper, we develop end-to-end probing methods which can measure bottleneck bandwidth along arbitrary, targeted subpaths of a path in the network, including subpaths shared by a set of flows. We evaluate our technique through extensive ns simulations, then provide a comparative Internet performance evaluation against hop-by-hop techniques. We also describe a number of applications which we foresee as standing to benefit from solutions to this problem, ranging from network troubleshooting and capacity provisioning to optimizing the layout of application-level overlay networks to optimized replica placement.
Scavenger Receptors Class A-I/II and CD36 Are the Principal Receptors Responsible for the Uptake of Modified Low Density Lipoprotein Leading to Lipid Loading in Macrophages (2002)

Modification of low density lipoprotein (LDL) can result in the avid uptake of these lipoproteins via a family of macrophage transmembrane proteins referred to as scavenger receptors (SRs). The genetic inactivation of either of two SR family members, SR-A or CD36, has been shown previously to reduce oxidized LDL uptake in vitro and atherosclerotic lesions in mice. Several other SRs are reported to bind modified LDL, but their contribution to macrophage lipid accumulation is uncertain. We generated mice lacking both SR-A and CD36 to determine their combined impact on macrophage lipid uptake and to assess the contribution of other SRs to this process. We show that SR-A and CD36 account for 75-90% of degradation of LDL modified by acetylation or oxidation. Cholesteryl ester derived from modified lipoproteins fails to accumulate in macrophages taken from the double null mice, as assessed by histochemistry and gas chromatography-mass spectrometry. These results demonstrate that SR-A and CD36 are responsible for the preponderance of modified LDL uptake in macrophages and that other scavenger receptors do not compensate for their absence.
Antiviral Activity of the Proteasome on Incoming Human Immunodeficiency Virus Type 1 (1998)

Following cell surface receptor binding and membrane fusion, human immunodeficiency virus (HIV) virion cores are released in the cytoplasm. Incoming viral proteins represent potential targets for cytosolic proteases. We show that treatment of target cells with the proteasome inhibitors MG132 and lactacystin increased the efficiency of HIV infection. Proteasome inhibitors were active at the early steps of the viral cycle. Incoming p24Gag proteins accumulated in the cytosol, and larger amounts of proviral DNA were synthesized. In vitro, purified 20S proteasome degraded HIV virion components. Thus, degradation of incoming viral proteins by the proteasome represents an early intracellular defense against infection.
Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis (2019)

Cellular senescence entails a stable cell-cycle arrest and a pro-inflammatory secretory phenotype, which contributes to aging and age-related diseases. Obesity is associated with increased senescent cell burden and neuropsychiatric disorders, including anxiety and depression. To investigate the role of senescence in obesity-related neuropsychiatric dysfunction, we used the INK-ATTAC mouse model, from which p16<sup>Ink4a</sup>-expressing senescent cells can be eliminated, and senolytic drugs dasatinib and quercetin. We found that obesity results in the accumulation of senescent glial cells in proximity to the lateral ventricle, a region in which adult neurogenesis occurs. Furthermore, senescent glial cells exhibit excessive fat deposits, a phenotype we termed "accumulation of lipids in senescence." Clearing senescent cells from high fat-fed or leptin receptor-deficient obese mice restored neurogenesis and alleviated anxiety-related behavior. Our study provides proof-of-concept evidence that senescent cells are major contributors to obesity-induced anxiety and that senolytics are a potential new therapeutic avenue for treating neuropsychiatric disorders.
Globally optimum ML estimation of timing and frequency offset in OFDM systems (2002)

We present a globally optimum maximum likelihood estimator for carrier frequency and symbol timing synchronization of orthogonal frequency division modulation (OFDM) systems. The approach proposed here is an extension of the previously proposed estimation method given by Van de Beek, Sandel and Borjesson (see IEEE Trans. on Signal Processings, vol.45, no.3, p. 1800-05, 1997). Our research indicates that the previously proposed likelihood metric does not globally characterize the estimation problem. Based on this observation, a new likelihood function for the joint timing and frequency offset estimation is derived. The resulting probabilistic measure is used to develop an unbiased ML estimator. Furthermore, a moment estimator for carrier frequency offset estimation under uncertain symbol timing is proposed and the statistical property of this estimator is analyzed. In comparison to the previously proposed methods, the proposed estimator is computationally and statistically efficient which makes the estimator more attractive for real time applications. The performance of the proposed estimator is assessed through computer simulations.
Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases (1995)

B-cell precursor (BCP) leukemia is the most common form of childhood cancer and the second most common form of acute leukemia in adults. Human BCP leukemia was treated in a severe combined immunodeficient mouse model by targeting of the tyrosine kinase inhibitor Genistein (Gen) to the B cell-specific receptor CD19 with the monoclonal antibody B43. The B43-Gen immunoconjugate bound with high affinity to BCP leukemia cells, selectively inhibited CD19-associated tyrosine kinases, and triggered rapid apoptotic cell death. At less than one-tenth the maximum tolerated dose more than 99.999 percent of human BCP leukemia cells were killed, which led to 100 percent long-term event-free survival from an otherwise invariably fatal leukemia. The B43-Gen immuno-conjugate might be useful in eliminating leukemia cells in patients who have failed conventional therapy.
Suppression of Cell-Mediated Immunity following Recognition of Phagosome-Confined Bacteria (2009)

Listeria monocytogenes is a facultative intracellular pathogen capable of inducing a robust cell-mediated immune response to sub-lethal infection. The capacity of L. monocytogenes to escape from the phagosome and enter the host cell cytosol is paramount for the induction of long-lived CD8 T cell-mediated protective immunity. Here, we show that the impaired T cell response to L. monocytogenes confined within a phagosome is not merely a consequence of inefficient antigen presentation, but is the result of direct suppression of the adaptive response. This suppression limited not only the adaptive response to vacuole-confined L. monocytogenes, but negated the response to bacteria within the cytosol. Co-infection with phagosome-confined and cytosolic L. monocytogenes prevented the generation of acquired immunity and limited expansion of antigen-specific T cells relative to the cytosolic L. monocytogenes strain alone. Bacteria confined to a phagosome suppressed the production of pro-inflammatory cytokines and led to the rapid MyD88-dependent production of IL-10. Blockade of the IL-10 receptor or the absence of MyD88 during primary infection restored protective immunity. Our studies demonstrate that the presence of microbes within a phagosome can directly impact the innate and adaptive immune response by antagonizing the signaling pathways necessary for inflammation and the generation of protective CD8 T cells.
MEMS Based True Time Delay Technology for Phased Antenna Array Systems (2007)

Phased antenna array (PAA) systems play an important role in modern radar and communication technologies. In order to satisfy the broadband requirement of future PAA systems, a true time delay approach is preferred over phase delay approaches. Several true time delay methods for PAA beam steering and beam shaping are compared at K-Band and Ka-Band frequencies. Fabrication details and test results for Ka- Band micro-electro-mechanical systems (MEMS) based true time delay lines are presented.
Pharmacokinetics of a new carbapenem, DA-1131, after intravenous administration to rats with alloxan-induced diabetes mellitus (1998)

Because physiological changes occurring in diabetes patients could alter the pharmacokinetics of drugs used to treat the disease, the pharmacokinetics and tissue distribution of DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous (i.v.) administration of the drug, 50 mg kg-1, to control and alloxan-induced diabetes mellitus (AIDM) rats. The impaired kidney function was observed by pretreatment with alloxan based on physiological parameters of plasma, creatinine clearance, and the kidney microscopy. After 1-min i.v. infusion of DA-1131, the plasma concentrations of DA-1131 and the total area under the plasma concentration-time curve of DA-1131 from time zero to time infinity (AUC) increased significantly in the AIDM rats (7350 versus 4400 micrograms min mL-1) when compared with those in control rats. This was due to significantly slower total body clearance (Cl) of DA-1131 (6.80 versus 11.4 mL min-1 kg-1) in AIDM rats than that in control rats. The significantly slower Cl of DA-1131 in AIDM rats was due to significantly slower renal (2.62 versus 4.95 mL min-1 kg-1, because of the considerably decreased glomerular filtration rate of DA-1131) and nonrenal (3.99 versus 6.34 mL min-1 kg-1, possibly because of the considerably slower metabolism in rat liver and kidney) clearance in AIDM rats. The amount of DA-1131 recovered from each rat tissue studied was significantly higher in AIDM rats than that in control rats, however, the tissue to plasma ratios were not significantly different between the two groups of rats.
A Prospective Study of Periodontal Disease and Pancreatic Cancer in US Male Health Professionals (2007)

Two previous cohort studies reported positive associations between tooth loss or periodontitis and pancreatic cancer risk. Data on periodontal disease were obtained at baseline and every other year thereafter in a cohort of 51,529 male health professionals aged 40-75 years. A total of 216 patients were diagnosed with incident pancreatic cancer during 16 years of follow-up. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models controlling for potential confounders, including detailed smoking history. All statistical tests were two-sided. Compared with no periodontal disease, history of periodontal disease was associated with increased pancreatic cancer risk (overall, multivariable RR = 1.64, 95% CI = 1.19 to 2.26; P = .002; crude incidence rates: 61 versus 25 per 100,000 person-years; among never smokers, multivariable RR = 2.09, 95% CI = 1.18 to 3.71; P = .01; crude incidence rates: 61 versus 19 per 100,000 person-years). In contrast, baseline number of natural teeth and cumulative tooth loss during follow-up were not strongly associated with pancreatic cancer. The association between periodontal disease and increased risk of pancreatic cancer may occur through plausible biologic mechanisms, but confirmation of this association is necessary.
A Pharmacokinetic Interaction Study Between Butorphanol and Sumatriptan Nasal Sprays in Healthy Subjects: Importance of the Timing of Butorphanol Administration (2002)

Sumatriptan and butorphanol nasal sprays are commonly used agents for the management of migraine headaches. Under certain circumstances, these two agents may be administered closely in time. However, the possibility of a pharmacokinetic interaction and the safety of this regime have not been examined. In this crossover design study, 24 healthy subjects received the following four treatments, each separated by at least 7 days: 1 mg butorphanol (Stadol NS7); 20 mg sumatriptan (Imitrex Nasal Spray); or both formulations together with butorphanol administered either 1 or 30 min after sumatriptan. Serial plasma samples were collected for 24 h post-dose and analysed for butorphanol and/or sumatriptan by HPLC-MS/MS. Butorphanol plasma concentrations were reduced when it was administered 1 min (mean 28.6% decrease in AUC(0-infinity)), but not 30 min, after sumatriptan. The pharmacokinetics of sumatriptan were not substantially altered by butorphanol. The combination of nasally administered sumatriptan and butorphanol appeared safe. However, if butorphanol nasal spray is administered <30 min after sumatriptan nasal spray, the analgesic effect of butorphanol may be diminished due to reduced nasal absorption resulting from probable transient vasoconstriction of nasal blood vessels by sumatriptan.
Antibody 9D5 Recognizes Oligomeric Pyroglutamate Amyloid-β in a Fraction of Amyloid-β Deposits in Alzheimer's Disease without Cross-Reactivity with other Protein Aggregates (2012)

Recent evidence suggests that soluble oligomeric amyloid-β (Aβ) assemblies are critically involved in the pathogenesis of Alzheimer's disease (AD). We have generated a conformation-dependent monoclonal antibody (9D5) that selectively recognizes low-molecular weight AβpE3 oligomers, and demonstrated its diagnostic and therapeutic potential. Here, we further characterize the specificity of this antibody by evaluating a spectrum of neurodegeneration-related protein deposits for cross-reactivity, and by comparing the staining pattern of 9D5 with a generic Aβ antibody that targets a linear epitope (mAb NT244), and with another conformation-dependent Aβ antibody that selectively labels amyloid fibrils of various molecular weights (pAb OC). The 9D5 antibody does not cross-react with other aggregated protein deposits in brains of progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, Pick's disease, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, frontotemporal lobar degeneration or amyotrophic lateral sclerosis with TDP-43 inclusions, Creutzfeldt-Jakob disease, and vessel changes in Binswanger encephalopathy, demonstrating the specificity of 9D5 for Aβ deposits. While NT244 and OC showed a comparable plaque load, 9D5 detected only approximately 15% of the total Aβ plaque load in the entorhinal cortex, the CA1 region, and the temporal neocortex. Our study further supports a possible therapeutic advantage of 9D5 by the highly specific recognition of an epitope found only in oligomeric assemblies of AβpE3 of AD patients. Moreover, selective binding to only a pathogenetically relevant fraction of Aβ deposits serves as rationale for passive immunization with 9D5-derivatives by limiting potential side effects of vaccination due to dissolvement of existing amyloid deposits.
Secretion Modification Region-Derived Peptide Disrupts HIV-1 Nef's Interaction with Mortalin and Blocks Virus and Nef Exosome Release (2011)

Nef is secreted from infected cells in exosomes and is found in abundance in the sera of HIV-infected individuals. Secreted exosomal Nef (exNef) induces apoptosis in uninfected CD4⁺ T cells and may be a key component of HIV pathogenesis. The exosomal pathway has been implicated in HIV-1 virus release, suggesting a possible link between these two viral processes. However, the underlying mechanisms and cellular components of exNef secretion have not been elucidated. We have previously described a Nef motif, the secretion modification region (SMR; amino acids 66 to 70), that is required for exNef secretion. In silico modeling data suggest that this motif can form a putative binding pocket. We hypothesized that the Nef SMR binds a cellular protein involved in protein trafficking and that inhibition of this interaction would abrogate exNef secretion. By using tandem mass spectrometry and coimmunoprecipitation with a novel SMR-based peptide (SMRwt) that blocks exNef secretion and HIV-1 virus release, we identified mortalin as an SMR-specific cellular protein. A second set of coimmunoprecipitation experiments with full-length Nef confirmed that mortalin interacts with Nef via Nef's SMR motif and that this interaction is disrupted by the SMRwt peptide. Overexpression and microRNA knockdown of mortalin revealed a positive correlation between exNef secretion levels and mortalin protein expression. Using antibody inhibition we demonstrated that the Nef/mortalin interaction is necessary for exNef secretion. Taken together, this work constitutes a significant step in understanding the underlying mechanism of exNef secretion, identifies a novel host-pathogen interaction, and introduces an HIV-derived peptide with antiviral properties.
Cell-Free Protein Expression (2007)

Following its inception in the 1950s, cell-free protein synthesis made a tremendous impact on the basic life sciences. The use of cell-free systems was key to understanding molecular mechanisms underlying one of the most complicated processes found in nature: protein translation. Since this time, aggressive cutting-edge research and stiff commerica
Antiangiogenic Activity of Tumor Necrosis Factor-.ALPHA. Production Regulators Derived from Thalidomide. (1999)

Recently, we developed novel tumor necrosis factor (TNF)-alpha production regulators with a phthalimide skeleton derived from thalidomide. We show here that some of these compounds are more potent inhibitors than thalidomide of angiogenesis induced by basic fibroblast growth factor in a murine angiogenesis assay.
Solubilization of DNA−Cationic Lipid Complexes in Hydrophobic Solvents. A Single-Molecule Visualization by Fluorescence Microscopy (1999)

The solubilization of DNA−lipid complexes in low-polar organic solvents was studied with the use of the fluorescence microscopy technique. It was demonstrated that the transfer of large T4 DNA complexed with cetyltrimethylammonium bromide (CTAB) and didodecyldimethylammonium bromide (DDAB) is not possible from the aqueous DNA−CTAB and DNA−DDAB solutions. On the other hand, dry DNA−CTAB and DNA−DDAB complexes were successfully dissolved and visualized in some of the studied organic solvents. DNA−DDAB complexes were found to be better soluble, compared to the DNA−CTAB complexes, due to the higher hydrophobicity of DDAB. The ability of the organic solvents to solubilize DNA−lipid complexes was also found to be different, as follows: chlorobenzene > toluene > chloroform, cyclohexane. It was shown that an increase of temperature enhances the solubilization of DNA−lipid complexes. The hydrodynamic radii of T4 DNA−lipid complexes in organic solvents were calculated from the corresponding translational diffusion constants. The obtained data implied that T4 DNA−lipid complexes in hydrophobic liquids have a highly compacted globular conformation and consist of a single T4 DNA macromolecule.
Fatty Acids in Serum Cholesteryl Esters as Quantitative Biomarkers of Dietary Intake in Humans (1997)

The fatty acid composition of serum cholesteryl esters is used as a qualitative biomarker of fatty acid intake, but quantitative data are scarce. Between 1987 and 1992, the authors fed various fatty acids in four controlled trials to 232 healthy Dutch volunteers and measured the proportion of fatty acids in participants' cholesteryl esters. Each 10% of energy fed as linoleic acid (18:2) raised the proportion of linoleic acid in cholesteryl esters by 9.3 g per 100 g of fatty acids (standard deviation (SD) 3.1). For oleic acid (cis-18:1), this figure was 6.5 g/100 g (SD 1.7); for trans fatty acids (trans-18:1), it was 1.1 (SD 0.5); for stearic acid (18:0), 1.0 (SD 0.4); for palmitic acid (16:0), 1.7 (SD 0.5); for myristic acid (14:0), 2.1 (SD 0.7); and for a mixture of saturated fatty acids (12:0, 14:0, and 16:0), it was 2.2 g/100 g (SD 1.0). The coefficient of variation of the responses was fairly constant, indicating that changes in intake for each of these fatty acids can be monitored with similar precision. These data can be used to estimate the degree of compliance in experimental studies involving exchanges of single dietary fatty acids. Most fatty acids in cholesteryl esters may also be used in observational studies to estimate differences in intake. However, because of multiple simultaneous differences in fatty acid intake between free-living individuals and between populations, such data cannot provide information on absolute intake of fatty acids.
Asymmetric Transformation of Enones with Synechococcus sp. PCC 7942 (2004)

Abstract Asymmetric transformation of enones was investigated with cultured cells of Synechococcus sp. PCC 7942 (a cyanobacterium). The cells reduced both the endocyclic C–C double bond of s-trans enones and the exocyclic C–C double bond of s-cis enones with high enantioselectivity to afford optically active α-substituted (S)-ketones under illumination. In addition, the reduction of the double bond of these enones was accompanied by the formation of saturated alcohols. The cells preferentially reduced simple aliphatic ketones rather than cyclic ones to the corresponding (S)-alcohols with excellent enantioselectivity.
Neural stem cells (2002)

Neural stem cells (NSCs) have the ability to self-renew, and are capable of differentiating into neurones, astrocytes and oligodendrocytes. Such cells have been isolated from the developing brain and more recently from the adult central nervous system. This review aims to provide an overview of the current research in this evolving area. There is now increasing knowledge of the factors controlling the division and differentiation of NSCs during normal brain development. In addition, the cues for differentiation in vitro, and the possibility of transdifferentiation are reviewed. The discovery of these cells in the adult brain has encouraged research into their role during neurogenesis in the normal mature brain and after injury. Lastly other sources of neural precursors are discussed, and the potential for stem cells to be used in cell replacement therapy for brain injury or degenerative brain diseases with a particular emphasis on cerebral ischaemia and Parkinson's disease.