gebhart/patrepeval huggingface dataset:
Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor (1996)

Indinavir (IDV) (also called CRIXIVAN, MK-639, or L-735,524) is a potent and selective inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease. During early clinical trials, in which patients initiated therapy with suboptimal dosages of IDV, we monitored the emergence of viral resistance to the inhibitor by genotypic and phenotypic characterization of primary HIV-1 isolates. Development of resistance coincided with variable patterns of multiple substitutions among at least 11 protease amino acid residues. No single substitution was present in all resistant isolates, indicating that resistance evolves through multiple genetic pathways. Despite this complexity, all of 29 resistant isolates tested exhibited alteration of residues M-46 (to I or L) and/or V-82 (to A, F, or T), suggesting that screening of these residues may be useful in predicting the emergence of resistance. We also extended our previous finding that IDV-resistant viral variants exhibit various patterns of cross-resistance to a diverse panel of HIV-1 protease inhibitors. Finally, we noted an association between the number of protease amino acid substitutions and the observed level of IDV resistance. No single substitution or pair of substitutions tested gave rise to measurable viral resistance to IDV. The evolution of this resistance was found to be cumulative, indicating the need for ongoing viral replication in this process. These observations strongly suggest that therapy should be initiated with the most efficacious regimen available, both to suppress viral spread and to inhibit the replication that is required for the evolution of resistance.
Phase I Clinical Trial of a HER-2/neu Peptide (E75) Vaccine for the Prevention of Prostate-Specific Antigen Recurrence in High-Risk Prostate Cancer Patients (2005)

The E75 vaccine strategy is safe and effective in eliciting an immune response against the HER-2/neu protein in HRPC patients and may be useful as a preventive strategy against disease recurrence. Vaccination in response to a rising PSA may be too late.
The anatomy of a context-aware application (1999)

We describe a platform for context-aware computing which enables applications to follow mobile users as they move around a building. The platform is particularly suitable for richly equipped, networked environments. The only item a user is required to carry is a small sensor tag, which identifies them to the system and locates them accurately in three dimensions. The platform builds a dynamic model of the environment using these location sensors and resource information gathered by telemetry software, and presents it in a form suitable for application programmers. Use of the platform is illustrated through a practical example, which allows a user's current working desktop to follow them as they move around the environment.
Polysilicon thin layers for photovoltaic applications (2003)

Thin layers of polycrystalline silicon as the optically absorbing material for photovoltaic devices represents a promising way for simultaneously achieving good performances and low manufacturing cost. In this paper, the preparation of polysilicon thin layers together with technological process for a p-i-n type photovoltaic cell fabrication are presented. The crystalline structure, surface morphology and optical properties were investigated by AFM technique, X-ray diffraction and spectrophotometer measurements.
Syndromic surveillance models using Web data: The case of scarlet fever in the UK (2012)

Recent research has shown the potential of Web queries as a source for syndromic surveillance, and existing studies show that these queries can be used as a basis for estimation and prediction of the development of a syndromic disease, such as influenza, using log linear (logit) statistical models. Two alternative models are applied to the relationship between cases and Web queries in this paper. We examine the applicability of using statistical methods to relate search engine queries with scarlet fever cases in the UK, taking advantage of tools to acquire the appropriate data from Google, and using an alternative statistical method based on gamma distributions. The results show that using logit models, the Pearson correlation factor between Web queries and the data obtained from the official agencies must be over 0.90, otherwise the prediction of the peak and the spread of the distributions gives significant deviations. In this paper, we describe the gamma distribution model and show that we can obtain better results in all cases using gamma transformations, and especially in those with a smaller correlation factor.
Enhancing the spectral sensitivity of interferometers using slow-light media (2007)

We demonstrate experimentally that the spectral sensitivity of an interferometer can be greatly enhanced by introducing a slow-light medium into it. The experimental results agree very well with theoretical predictions that the enhancement factor of the spectral sensitivity is equal to the group index n(g) of the slow-light medium.
Bilateral Adversarial Training: Towards Fast Training of More Robust Models Against Adversarial Attacks (2019)

In this paper, we study fast training of adversarially robust models. From the analyses of the state-of-the-art defense method, i.e., the multi-step adversarial training [34], we hypothesize that the gradient magnitude links to the model robustness. Motivated by this, we propose to perturb both the image and the label during training, which we call Bilateral Adversarial Training (BAT). To generate the adversarial label, we derive an closed-form heuristic solution. To generate the adversarial image, we use one-step targeted attack with the target label being the most confusing class. In the experiment, we first show that random start and the most confusing target attack effectively prevent the label leaking and gradient masking problem. Then coupled with the adversarial label part, our model significantly improves the state-of-the-art results. For example, against PGD100 white-box attack with cross-entropy loss, on CIFAR10, we achieve 63.7% versus 47.2%; on SVHN, we achieve 59.1% versus 42.1%. At last, the experiment on the very (computationally) challenging ImageNet dataset further demonstrates the effectiveness of our fast method.
Normalization of depressed natural killer activity after interferon-alpha therapy is associated with a low frequency of relapse in patients with chronic hepatitis C. (1993)

In the present study, we found that human recombinant interferon-alpha (rIFN-alpha) given at a dose of 3 x 10(6) units thrice weekly for three months, and 1.5 x 10(6) units thrice weekly for the next three months, was able to restore depressed natural-killer (NK) activity to normal values in 12 out of 21 chronic hepatitis C patients positive for anti-HCV antibodies. In all of these patients, NK normalization was still sustained after three months from suspension of therapy. Eighteen patients also showed a normalization of the alanine aminotransferase (ALT) level by the end of treatment (responder patients), independently of changes in NK activity. No significant improvement in either NK activity or aminotransferase levels was seen among 20 untreated patients. In 8 responder patients (1 with normalized and 7 with low NK activity), ALT levels returned to pre-therapy values within three months after suspension of rIFN-alpha administration (relapse). We found that patients who normalized NK activity had a lower frequency of relapse as compared to patients with low NK activity by the end of treatment (p > 0.01). Immunofluorescence analysis of biopsy-derived liver tissue revealed that rIFN-alpha was able to induce strong MHC class I antigen expression on hepatocytes of treated patients, but this was not related to the clinical course.
A tumor-expressed inhibitor of the early but not late complement lytic pathway enhances tumor growth in a rat model of human breast cancer. (2002)

Membrane-bound complement inhibitors protect host cells from inadvertent complement attack, and complement inhibitors are often up-regulated on tumors, possibly representing a selective adaptation by tumors to escape elimination by a host antitumor immune response. Relevant in vivo studies using rodent models of human cancer have been hampered by the fact that human complement inhibitors are not effective against rodent complement. Using nude rats and MCF7 cells expressing different rat complement inhibitors, a model of human breast cancer was established to investigate the role of complement and complement inhibitors in tumor progression. Expression of rat CD59, an inhibitor of the terminal cytolytic membrane attack complex of complement, had no effect on the incidence or growth rate of MCF7 tumors. In contrast, expression of rat Crry, an inhibitor of complement activation, dramatically enhanced the tumorigenicity of MCF7 cells. The expression of rat Crry on MCF7 inhibited the in vivo deposition of complement C3 fragments that serve as opsonins for receptors on phagocytes and natural killer cells. These data provide direct in vivo evidence that an inhibitor of complement activation can facilitate tumor growth by modulating C3 deposition. These data indicate an important role for complement opsonization in promoting cell-mediated antitumor immune function, a conclusion further supported by the demonstration that expression of rat Crry, but not rat CD59, on MCF7 cells inhibits rat cell-mediated cytotoxicity in vitro. Rat complement activation on MCF7 tumors was mediated by tumor-reactive antibodies present in the serum of naïve nude rats, but there was also an IgM response to MCF7 tumors, a situation with similarities to some human cancers. These data support a hypothesis that blocking complement inhibitor function on tumor cells will not only enhance monoclonal antibody-mediated immunotherapy but may also be effective at enhancing a normally ineffective humoral immune response in the absence of administered antitumor antibody.
Cell Atlas technologies and insights into tissue architecture (2020)

Since Robert Hooke first described the existence of 'cells' in 1665, scientists have sought to identify and further characterise these fundamental units of life. While our understanding of cell location, morphology and function has expanded greatly; our understanding of cell types and states at the molecular level, and how these function within tissue architecture, is still limited. A greater understanding of our cells could revolutionise basic biology and medicine. Atlasing initiatives like the Human Cell Atlas aim to identify all cell types at the molecular level, including their physical locations, and to make this reference data openly available to the scientific community. This is made possible by a recent technology revolution: both in single-cell molecular profiling, particularly single-cell RNA sequencing, and in spatially resolved methods for assessing gene and protein expression. Here, we review available and upcoming atlasing technologies, the biological insights gained to date and the promise of this field for the future.
Long-Term In Vivo Gene Expression via Delivery of PEI–DNA Condensates from Porous Polymer Scaffolds (2005)

Nonviral delivery vectors are attractive for gene therapy approaches in tissue engineering, but suffer from low transfection efficiency and short-term gene expression. We hypothesized that the sustained delivery of poly(ethylenimine) (PEI)-condensed DNA from three-dimensional biodegradable scaffolds that encourage cell infiltration could greatly enhance gene expression. To test this hypothesis, a PEI-condensed plasmid encoding beta-galactosidase was incorporated into porous poly(lactide-co-glycolide) (PLG) scaffolds, using a gas foaming process. Four conditions were examined: condensed DNA and uncondensed DNA encapsulated into PLG scaffolds, blank scaffolds, and bolus delivery of condensed DNA in combination with implantation of PLG scaffolds. Implantation of scaffolds incorporating condensed beta-galactosidase plasmid into the subcutaneous tissue of rats resulted in a high level of gene expression for the entire 15-week duration of the experiment, as exemplified by extensive positive staining for beta-galactosidase gene expression observed on the exterior surface and throughout the cross-sections of the explanted scaffolds. No positive staining could be observed for the control conditions either on the exterior surface or in the cross-section at 8- and 15-week time points. In addition, a high percentage (55-60%) of cells within scaffolds incorporating condensed DNA at 15 weeks demonstrated expression of the DNA, confirming the sustained uptake and expression of the encapsulated plasmid DNA. Quantitative analysis of beta-galactosidase gene expression revealed that expression levels in scaffolds incorporating condensed DNA were one order of magnitude higher than those of other conditions at the 2- week time point and nearly two orders of magnitude higher than those of the control conditions at the 8- and 15-week time points. This study demonstrated that the sustained delivery of PEI-condensed plasmid DNA from PLG scaffolds led to an in vivo long-term and high level of gene expression, and this system may find application in areas such as bone tissue engineering.
NAC-1 Controls Cell Growth and Survival by Repressing Transcription of Gadd45GIP1, a Candidate Tumor Suppressor (2007)

Cancer mortality and morbidity are primarily related to recurrent tumors, and characterization of recurrence-associated genes should illuminate fundamental properties of tumor progression and provide new therapeutic targets. We have previously identified NAC-1, a member of the BTB/POZ gene family and a transcription repressor, as a gene associated with recurrent ovarian carcinomas after chemotherapy. We further showed that homodimerization of NAC-1 proteins is essential for tumor growth and survival. In this study, we applied serial analysis of gene expression and identified growth arrest and DNA-damage-inducible 45-gamma interacting protein (Gadd45GIP1) as one of the downstream genes negatively regulated by NAC-1. NAC-1 knockdown in both SKOV3 and HeLa cells that expressed abundant endogenous NAC-1 induced Gadd45GIP1 expression transcriptionally; on the other hand, engineered expression of NAC-1 in NAC-1-negative RK3E and HEK293 cells suppressed endogenous Gadd45GIP1 expression. In NAC-1-expressing tumor cells, induction of dominant negative NAC-1 conferred a growth-inhibitory effect that can be partially reversed by Gadd45GIP1 knockdown. Induced Gadd45GIP1 expression resulted in growth arrest in SKOV3 and HeLa cells both in vitro and in vivo. In summary, NAC-1 contributes to tumor growth and survival by at least inhibiting Gadd45GIP1 expression, which has a tumor suppressor effect in cancer cells.
The cyanelle genome ofCyanophora paradoxa, unlike the chloroplast genome, codes for the ribosomal L3 protein (1990)

We describe a 1132 bp sequence of the cyanelle genome of Cyanophora paradoxa containing the rpl3 gene. This gene, which is not chloroplast encoded in plants, is the first of a long cyanelle ribosomal operon whose organization resembles that of the S10 operon of E. coli. We have shown that the rpl3 gene is transcribed in cyanelles as a 7500 nucleotide precursor and that the 5'-end of the mRNA starts approximately 90 nucleotides upstream from the initiation codon. However, no typical procaryotic promoter could be found for this gene. We have detected, using anti E. coli L3 antibodies, the cyanelle L3 protein in cyanelle extracts and in E. coli cells transformed with the cyanelle rpl3 gene.
Effect of vagal stimulation on the overflow of norepinephrine into the coronary sinus during cardiac sympathetic nerve stimulation in the dog. (1976)

In anesthetized dogs with the chest open, supramaximal stimulation of the left cardiac sympathetic nerves at 2 and 4 Hz produced an increase of 40-50% in ventricular contractile force (CF) and of 40-65% in coronary sinus blood flow. At these frequencies of stimulation, norepinephrine (NE) overflow into the coronary sinus was 29.8 +/- 5.1 (SE) and 54.9 +/- 13.2 ng/min, respectively. Concurrent, supramaximal vagal stimulation, at a frequency of 15 Hz, had no significant effect on coronary sinus blood flow, but caused a 25% reduction in CF and a 30% decrease in NE overflow. The changes in CF and NE overflow evoked by vagal stimulation were prevented by atropine. These results are consistent with the hypothesis that there are muscarinic receptors on the postganglionic sympathetic terminals in the walls of the ventricles. Acetylcholine released during vagal stimulation combines with these receptors, causes a reduction in the liberation of NE, and thereby attenuates the positive inotropic response.
MR Imaging of the Knee (1989)

A new examination protocol for patients with suspected meniscal or hyaline cartilage disorders is presented. Knees were imaged with a fast gradient echo imaging sequence with subsequent three-dimensional transformation. Data were transferred to an image processing system that allows reconstruction in any plane desired. Approximately 200 interactively positioned reconstructions are displayed and reviewed in approximately 10 min. Thirty-five patients with suspected meniscal or hyaline cartilage disorders were examined prospectively. All underwent subsequent arthroscopy. The magnetic resonance (MR) diagnosis showed an accuracy of 91.4% compared with arthroscopic findings. Owing to the short imaging time, the proposed procedure permits screening of knee joint disorders with MR.
Dose calculation for photon beams with intensity modulation generated by dynamic jaw or multileaf collimations (1994)

A dose calculation algorithm has been developed for photon beams with intensity modulation generated by dynamic jaw or multileaf collimations. First, an in-air fluence distribution is constructed based on the dynamic motion of the jaws or leaves, taking into account the variation of output with field size defined by the jaws. The fluence distribution is then convolved with the appropriate pencil beam kernel to give correction factors which are used to calculate the dose distribution for an intensity-modulated photon field. The proposed algorithm is strictly valid in homogeneous media only, patient heterogeneity correction is accounted for in an approximate manner. Dose distributions at several depths and for several field sizes were calculated for 6- and 15-MV x-ray beams for a set of standard wedges produced by dynamic jaws. Measurements were made with film and an ion chamber. Comparisons between calculated and measured data show good agreement (within 2%) for both dose profiles and wedge factors. Similar calculations and measurements were also made for a 25-MV intensity-modulated photon field produced by dynamic motion of a multileaf collimator. Agreement between calculations and measurements is also good (within 3%). The "tongue-and-groove" effect associated with a multileaf collimator design is also examined using a ring-shaped field produced by matching two component fields. The computation time for a dynamic-collimated field is the same as that for an irregular field shaped by conventional blocks. The algorithm is applicable to any pattern of jaw or multileaf motions. The strengths and remaining problems of the algorithm are discussed.
The optimal number of major histocompatibility complex molecules in an individual. (1992)

A straightforward argument is presented to calculate the number of different major histocompatibility complex (MHC) molecules in an individual that maximizes the probability of mounting immune responses against a large number of foreign peptides. It is assumed that increasing the number of MHC molecules per individual, n, has three different effects: (i) it increases the number of foreign peptides that can be presented; (ii) it increases the number of different T-cell receptors (TCRs) positively selected in the thymus; but (iii) it reduces the number of TCRs by negative selection. The mathematical analysis shows that n = 1/f maximizes the number of different TCRs that pass through positive and negative selection and that n = 2/f maximizes the probability to mount immune responses against a large fraction of foreign peptides. Here f is the fraction of TCRs deleted by one MHC molecule. Both results depend on approximations that are discussed in the paper. The model presented has implications for our understanding of the evolutionary forces acting on the MHC.
Leaves, Flowers and Garbage Bags: Making Waves (2004)

the world’s most durable mysteries. Some patterns—clouds, snowflakes— form in space. Others—the ebb and flow of tides, seasonal wet and dry spells—are patterns that form in time. Natural patterns are mysterious because they are complex, organized and interconnected, even though the laws of physics on which they rest—Newton’s classical laws of motion—are simple. The living world presents the ultimate examples of pattern formation. The patterns in biological systems are the most stunningly complex of any we encounter. Consider: In order to form a complex organism from an initial featureless collection of identical cells, a system must undergo myriad transitions that break its spatial symmetries and trigger the differentiation of cells at selected sites. How are these sites selected? How complex and controlled must a growth process be to direct that particular things happen in sequence and at the right sites? It is difficult to imagine how the impersonal interactions of atoms can lead to the growth of a plant or an animal from inanimate matter. Yet in fact this is what happens with the birth and development of every living thing. Some of the simplest features of biological shapes can be explained by basic physical laws. We will describe here an elegant example: the edges of flowers and leaves, where complex rippled shapes give the impressions of ruffles and frills. We suspected that very simple growth processes might provide the mechanism that shapes thin membranes and sheets into complex shapes in space, and indeed we have found that they do. By themselves, these processes do not break
A Newly Identified Member of Tumor Necrosis Factor Receptor Superfamily (TR6) Suppresses LIGHT-mediated Apoptosis (1999)

TR6 (decoy receptor 3 (DcR3)) is a new member of the tumor necrosis factor receptor (TNFR) family. TR6 mRNA is expressed in lung tissues and colon adenocarcinoma, SW480. In addition, the expression of TR6 mRNA was shown in the endothelial cell line and induced by phorbol 12-myristate 13-acetate/ionomycin in Jurkat T leukemia cells. The open reading frame of TR6 encodes 300 amino acids with a 29-residue signal sequence but no transmembrane region. Using histidine-tagged recombinant TR6, we screened soluble forms of TNF-ligand proteins with immunoprecipitation. Here, we demonstrate that TR6 specifically binds two cellular ligands, LIGHT (herpes virus entry mediator (HVEM)-L) and Fas ligand (FasL/CD95L). These bindings were confirmed with HEK 293 EBNA cells transfected with LIGHT cDNA by flow cytometry. TR6 inhibited LIGHT-induced cytotoxicity in HT29 cells. It has been shown that LIGHT triggers apoptosis of various tumor cells including HT29 cells that express both lymphotoxin β receptor (LTβR) and HVEM/TR2 receptors. Our data suggest that TR6 inhibits the interactions of LIGHT with HVEM/TR2 and LTβR, thereby suppressing LIGHT- mediated HT29 cell death. Thus, TR6 may play a regulatory role for suppressing in FasL- and LIGHT-mediated cell death.
Oligooxopiperazines as Nonpeptidic α-Helix Mimetics (2010)

A new class of nonpeptidic alpha-helix mimetics derived from alpha-amino acids and featuring chiral backbones is described. NMR and circular dichroism spectroscopies, in combination with molecular modeling studies, provide compelling evidence that oligooxopiperazine dimers adopt stable conformations that reproduce the arrangement of i, i+4, and i+7 residues on an alpha-helix.