gebhart/patrepeval huggingface dataset:
Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1α and VEGF (2002)

Acute intensive insulin therapy is an independent risk factor for diabetic retinopathy.Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats.Retinal nuclear extracts from insulin-treated rats contain higher hypoxiainducible factor-1 (HIF-1) levels and demonstrate increased HIF-1-dependent binding to hypoxiaresponsive elements in the VEGF promoter.Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect.The insulin-induced retinal HIF-1 and VEGF increases and the related blood-retinal barrier breakdown are suppressed by inhibitors of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol (PI) 3-kinase, but not inhibitors of p42/p44 MAPK or protein kinase C. Taken together, these findings indicate that acute intensive insulin therapy produces a transient worsening of diabetic blood-retinal barrier breakdown via an HIF-1-mediated increase in retinal VEGF expression.Insulin-induced VEGF expression requires p38 MAPK and PI 3-kinase, whereas hyperglycemia-induced VEGF expression is HIF-1-independent and requires PKC and p42/p44 MAPK.To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy.
A Smartphone-in-the-Loop Active State-of-Charge Manager for Electric Vehicles (2012)

Environmental concerns and the steadily decreasing oil supplies have promoted a significant interest in electric vehicles as a solution for the mobility of the near future, especially in urban environments. The correct handling of the energy behavior on board is one of the most critical problems to be addressed, particularly in urban driving scenarios where the speed profiles - even on fixed routes - are affected by significant unknown disturbances. To address this issue, this paper proposes a novel, spatially distributed and hierarchical control architecture that is capable of regulating the battery state of charge by imposing a desired discharge rate. The effectiveness of the overall control system is assessed by experimental results obtained on a prototype of a light-electric two-wheeled vehicle.
Virology, transmission, and pathogenesis of SARS-CoV-2 (2020)

Peer reviewed
High-transparency superconductor–insulator–normal- metal–insulator–superconductor Josephson junctions for digital electronics (2002)

Nb / Al / AlO x / Al / AlO x / Al / Nb junctions with critical current densities, jc, up to 38 kA/cm2 were fabricated. A critical voltage of Vc=1.25 mV and small hysteresis (about 6% of the critical current) at 4.2 K were obtained for jc=21 kA/cm2. Also, Nb/Al/AlOx/Al/Nb/Al/NbN junctions with jc=33 kA/cm2 and Vc=0.76 mV were fabricated, where it is suggested that a second tunnel barrier at the Al/NbN interface is present as a result of Al nitridation during NbN deposition.
Involvement of BCL-2 in glucocorticoid-induced apoptosis of human pre-B-leukemias. (1992)

To determine the role of BCL-2 in the glucocorticoid-induced apoptosis of lymphocytes, we analyzed the effect of glucocorticoid on two human pre-B-cell lines which express different levels of BCL-2. Glucocorticoid treatment of the 380 cell line which expresses high levels of BCL-2 resulted in inhibition of cellular proliferation without induction of apoptosis. On the other hand, glucocorticoid treatment of the 697 cell line which expresses lower levels of the BCL-2 resulted in both inhibition of cellular proliferation and apoptosis with characteristic internucleosomal DNA cleavage. The glucocorticoid-induced inhibition of cellular proliferation in both cell lines was also associated with repression of the c-myc mRNA expression. Taken together, our data suggest that BCL-2 blocks the glucocorticoid-induced apoptosis of the 380 pre-B-lymphocytes by extending their survival when the level of c-myc expression is repressed. Also by repressing the expression of c-myc, glucocorticoid causes apoptosis of the 697 pre-B-lymphocytes in the absence of high level of BCL-2 expression.
Demonstration of inverse acoustic band gap structures in AlN and integration with piezoelectric contour mode wideband transducers (2009)

This paper presents the first design and demonstration of a novel inverse acoustic band gap (IABG) structure in aluminum nitride (AlN) and its direct integration with contour-mode wideband transducers in the Very High Frequency (VHF) range. This design implements an efficient approach to co-fabricate in-plane AlN electro-acoustic transducers with bulk acoustic waves (BAWs) IABG arrays (10 times 10). The IABG unit cell consists of a cylindrical high acoustic velocity (V) media, which is held by four thin tethers, surrounded by a low acoustic velocity matrix (air). The center media is formed by 2-mum-thick AlN, which is sandwiched by 200-nm-thick top and bottom platinum (Pt) layers. The experimental results indicate that the designed IABG has a stop band from 185 MHz to 240 MHz and is centered at 218 MHz in the Gamma-X direction. This demonstration not only confirms the existence of the frequency band gap in the IABG structure, but also opens possibilities for the integration of ABG structures with RF MEMS devices.
ChemInform Abstract: A 1,3‐Dipolar Cycloaddition Route to 3‐Acyl‐4‐hydroxy‐pyridin‐2‐ones and ‐pyran‐2‐ones. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Overview of Gene Silencing by RNA Interference (2009)

The potential of harnessing RNA interference (RNAi) for sequence-specific gene silencing has generated much excitement and progress in the field. Recent advances in RNAi technology suggest that RNAi-based approaches may soon become an effective therapeutic strategy against a myriad of diseases. This overview provides a brief description of important considerations when designing an RNAi-based method for gene silencing and therapeutic development: (a) mechanistic aspects of RNAi-mediated gene silencing in mammalian cells; (b) structural requirements for potent siRNA duplexes; (c) off-target effects and interferon responses; and (d) effective delivery of RNAi-inducing agents. Promising therapeutic applications of RNAi that are currently in the developmental pipeline are also described.
A Palpation System for Artery Localization in Laparoscopic Surgery (1994)

This paper describes a system for finding hidden arteries in remote and inaccessible locations. A tactile array sensor is located in the end of a long, 10 mm diameter probe. In a surgical application, the surgeon presses the sensor against the tissue of interest, and electronics read out the pressure distribution across the contact area at a high rate. A computer captures this information and processes the signal to find the periodic pressure variations due to the pulsatile arterial blood flow. The results are then displayed on a video monitor for the surgeon's use. This device is the first part of a complete remote palpation system that will convey tactile information to the surgeon's finger tips using shape, pressure, and vibration displays.
TIGA: target illumination GWAS analytics (2021)

Supplementary data are available at Bioinformatics online.
Detection of Micrometastases Using SPECT/Fluorescence Dual-Modality Imaging in a CEA-Expressing Tumor Model (2017)

Intraoperative dual-modality imaging can help the surgeon distinguish tumor from normal tissue. This technique may prove particularly valuable if small tumors need to be removed that are difficult to detect with the naked eye. The humanized anticarcinoembryonic antigen (anti-CEA) monoclonal antibody, labetuzumab, can be used as a tumor-targeting agent in colorectal cancer, since CEA is overexpressed in approximately 95% of colorectal cancer. Dual-labeled labetuzumab, labeled with both a near-infrared fluorescent dye (IRDye800CW) and a radioactive label (<sup>111</sup>In), can be used as a tracer for dual-modality imaging. This study aimed to assess whether dual-modality imaging using <sup>111</sup>In-diethylenetriaminepentaacetic acid (DTPA)-labetuzumab-IRDye800CW can detect pulmonary micrometastases in a mouse model. <b>Methods:</b> Pulmonary GW-39 human colonic carcinoma microcolonies were induced in athymic BALB/c mice by intravenous injection of 100 μL of a GW-39 cell suspension. After 1, 2, 3, and 4 wk of tumor growth, dual-modality imaging was performed 3 d after intravenous injection of <sup>111</sup>In-DTPA-labetuzumab-IRDye800CW (10 μg, 25 MBq). Small-animal SPECT images and optical images were acquired, and image-guided surgery was performed. Finally, the biodistribution of the dual-labeled tracer was determined. Formalin-fixed sections of the lungs were analyzed using fluorescence imaging, autoradiography, and immunohistochemistry. <b>Results:</b> Submillimeter pulmonary tumor colonies could be visualized with both small-animal SPECT and fluorescence imaging from the first week of tumor growth, before they became visible to the naked eye. Furthermore, dual-modality imaging could be used to guide resection of tumors. Mean uptake (percentage injected dose per gram) of the dual-labeled tracer in tumors was 17.2 ± 5.4 and 16.5 ± 4.4 at weeks 3 and 4, respectively. Immunohistochemical analysis of the tumorous lungs showed that the distribution of the radioactive and fluorescent signal colocalized with CEA-expressing tumors. <b>Conclusion:</b> Dual-modality imaging after injection of <sup>111</sup>In-labetuzumab-IRDye800CW can be used to detect submillimeter CEA-expressing pulmonary tumors before they become visible to the naked eye, supporting the added value of this technique in the resection of small tumors.
Possible role for thymine glycol in the selective inhibition of DNA synthesis on oxidized DNA templates. (1985)

Single-stranded DNA of coliphage M13mp8 was treated with the oxidizing agent, KMnO4, under conditions that selectively form cis-5,6-dihydro-5,6-dihydroxythymine (thymine glycol). Treatment of DNA with 0.7 and 1.4 mM KMnO4 introduced approximately 200 and 400 thymine glycol residues, respectively, per genome. When these DNAs were used to transform Escherichia coli, it was observed that phage survival was reduced in a dose-dependent manner. In studies designed to investigate the effect of DNA oxidation products on replication in vitro, a complementary 15-mer oligodeoxynucleotide was annealed to the oxidized template and extended with the Klenow fragment of DNA polymerase I from E. coli. It was observed that lesions in oxidized DNA strongly inhibited DNA elongation and that DNA synthesis was stopped opposite thymine residues. This is taken as suggestive evidence that the thymine glycol is inhibitory to DNA replication.
A Systems Approach for Tumor Pharmacokinetics (2011)

Recent advances in genome inspired target discovery, small molecule screens, development of biological and nanotechnology have led to the introduction of a myriad of new differently sized agents into the clinic. The differences in small and large molecule delivery are becoming increasingly important in combination therapies as well as the use of drugs that modify the physiology of tumors such as anti-angiogenic treatment. The complexity of targeting has led to the development of mathematical models to facilitate understanding, but unfortunately, these studies are often only applicable to a particular molecule, making pharmacokinetic comparisons difficult. Here we develop and describe a framework for categorizing primary pharmacokinetics of drugs in tumors. For modeling purposes, we define drugs not by their mechanism of action but rather their rate-limiting step of delivery. Our simulations account for variations in perfusion, vascularization, interstitial transport, and non-linear local binding and metabolism. Based on a comparison of the fundamental rates determining uptake, drugs were classified into four categories depending on whether uptake is limited by blood flow, extravasation, interstitial diffusion, or local binding and metabolism. Simulations comparing small molecule versus macromolecular drugs show a sharp difference in distribution, which has implications for multi-drug therapies. The tissue-level distribution differs widely in tumors for small molecules versus macromolecular biologic drugs, and this should be considered in the design of agents and treatments. An example using antibodies in mouse xenografts illustrates the different in vivo behavior. This type of transport analysis can be used to aid in model development, experimental data analysis, and imaging and therapeutic agent design.
94 Risk factors for lymph node metastasis of ovarian, fallopian tube and primary peritoneal cancer in hereditary breast and ovarian cancer syndrome (2020)

<h3>Introduction/Background</h3> To establish an individualized surgical strategy for ovarian cancer in patients with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+), we investigated the clinicopathological characteristics that are involved in the increased risk of lymph node metastasis (LNM). <h3>Methodology</h3> We retrospectively reviewed the data of 509 Japanese women who underwent BRCA1 and BRCA2 genetic testing and were registered in the database of the Japanese HBOC Consortium. <h3>Results</h3> BRCA1+ and BRCA2+ were found in 232 (45.6%) of patients in our database, while other patients had no pathogenic variant (BRCA-). The prevalence of LNM was not markedly different between BRCA- (19.5%), BRCA1+ (18.4%) and BRCA2+ (26.2%). Multivariate analysis revealed an absence of a family history of ovarian cancer as an independent predictor for an increased risk of LNM in BRCA1+, and the prevalence of LNM was 11.7% and 42.0% in the groups with and without a family history of ovarian cancer, respectively. This subgroup without a family history of ovarian cancer did not show any correlation with a particular variant of BRCA1. <h3>Conclusion</h3> This study suggested that the existence of a subgroup in which the absence of a family history of ovarian cancer was an independent predictor for an increased risk of lymph node metastasis and certain genetic factors related to the penetrance of hereditary breast and ovarian cancer syndrome might alter the frequency of LNM in BRCA1+ ovarian cancer. We will need to investigate whether or not the same surgical strategy for lymphadenectomy as BRCA- is suitable for this BRCA1+ subgroup. <h3>Disclosures</h3> There are no conflict of interest disclosures from any authors.
Influence of BMI on Gait Characteristics of Young Adults: 3D Evaluation Using Inertial Sensors (2019)

Overweight/obesity is a physical condition that affects daily activities, including walking. The main purpose of this study was to identify if there is a relationship between body mass index (BMI) and gait characteristics in young adults. 12 normal weight (NW) and 10 overweight/obese (OW) individuals walked at a self-selected speed along a 14 m indoor path. H-Gait system, combining seven inertial sensors (fixed on pelvis and lower limbs), was used to record gait data. Walking speed, spatio-temporal parameters and joint kinematics in 3D were analyzed. Differences between NW and OW and correlations between BMI and gait parameters were evaluated. Conventional spatio-temporal parameters did not show statistical differences between the two groups or correlations with the BMI. However, significant results were pointed out for the joint kinematics. OW showed greater hip joint angles in frontal and transverse planes, with respect to NW. In the transverse plane, OW showed a greater knee opening angle and a shorter length of knee and ankle trajectories. Correlations were found between BMI and kinematic parameters in the frontal and transverse planes. Despite some phenomena such as soft tissue artifact and kinematics cross-talk, which have to be more deeply assessed, current results show a relationship between BMI and gait characteristics in young adults that should be looked at in osteoarthritis prevention.
Vertical Interconnection by ASET (2008)

This chapter contains sections titled: Introduction Fabrication Process Overview Via Filling by Cu Electrodeposition Handling of Thin Wafer 3D Chip Stacking Thermal Performance of Chip Stack Module Electric Performance of Vertical Interconnection Practical Application of Through-vias Conclusion References
Religion, Identity and Politics in Northern Ireland (2017)

Has conflict in Northern Ireland kept political dimensions of religion alive, and has religion played a role in fuelling conflict? Conflict in Northern Ireland is not and never will be a holy war. Yet religion is more socially and politically significant than many commentators presume. In fact, religion has remained a central feature of social identity and politics throughout conflict as well as recent change. There has been an acceleration of interest in the relationship between religion, identity and politics in modern societies. Building on this debate, Claire Mitchell presents a challenging analysis of religion in contemporary Northern Ireland, arguing that religion is not merely a marker of ethnicity and that it continues to provide many of the meanings of identity, community and politics. In light of the multifaceted nature of the conflict in Northern Ireland, Mitchell explains that, for Catholics, religion is primarily important in its social and institutional forms, whereas for many Protestants its theological and ideological dimensions are more pressing. Even those who no longer go to church tend to reproduce religious stereotypes of 'them and us'. Drawing on a range of unique interview material, this book traces how individuals and groups in Northern Ireland have absorbed religious types of cultural knowledge, belonging and morality, and how they reproduce these as they go about their daily lives. Despite recent religious and political changes, the author concludes that perceptions of religious difference help keep communities in Northern Ireland socially separate and often in conflict with one another.
TESTING OF ADDITIVELY MANUFACTURED SMALL SCALE RC SPECIMENS FOR STATISTICAL VALIDATION OF STRUCTURAL MODELS IN EARTHQUAKE ENGINEERING (2020)

TESTING OF ADDITIVELY MANUFACTURED SMALL SCALE RC SPECIMENS FOR STATISTICAL VALIDATION OF STRUCTURAL MODELS IN EARTHQUAKE ENGINEERING - XI International Conference on Structural Dynamics - 23-26 November 2020, Athens, Greece
Toxicogenomic Response of Staphylococcus aureus to Triclosan (2008)

For the first time a genome‐wide transcriptional analysis was performed to elucidate the cellular response of S. aureus to triclosan. Our results indicate that triclosan effects are widespread on the metabolism, affecting many vital cellular processes. Triclosan downregulated the transcription of genes involved in virulence factor and energy metabolism such as amino acid, carbohydrate, lipid transport and metabolism, while multidrug resistance genes, coenzyme transport and metabolism and transcription genes were upregulated. Furthermore, triclosan downregulated transcription of genes encoding major lipid metabolism enzymes such as 3‐hydroxyacyl‐CoA dehydrogenase, acetyl‐CoA acetyltransferase, acetyl‐CoA synthetase, and acetyl‐CoA carboxylase, which all play essential roles in S. aureus lipid metabolism. Interestingly, the expression of enoyl‐ACP reductase gene, fabI, was not changed after exposure of S. aureus with 0.05μM triclosan at 10 and 60min in our study. This work also implies that triclosan may kill S. aureus, by interfering with the ability to form cell wall membrane the same as penicillin. Another important implication of our result is that S. aureus may generate resistance factors under triclosan stress.
The Impact of Regulations, Safety Considerations and Physical Limitations on Research Progress at Maximum Biocontainment (2012)

We describe herein, limitations on research at biosafety level 4 (BSL-4) containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT) are highly regulated due to their potential to pose a severe threat to public health and safety. All federal, state, city, and local regulations must be followed to obtain and maintain registration for the institution to conduct research involving BSAT. These include initial screening and continuous monitoring of personnel, controlled access to containment laboratories, accurate and current BSAT inventory records. Safety considerations are paramount in BSL-4 containment laboratories while considering the types of research tools, workflow and time required for conducting both in vivo and in vitro experiments in limited space. Required use of a positive-pressure encapsulating suit imposes tremendous physical limitations on the researcher. Successful mitigation of these constraints requires additional time, effort, good communication, and creative solutions. Test and evaluation of novel vaccines and therapeutics conducted under good laboratory practice (GLP) conditions for FDA approval are prioritized and frequently share the same physical space with important ongoing basic research studies. The possibilities and limitations of biomedical research involving microbial pathogens of biodefense concern in BSL-4 containment laboratories are explored in this review.
A novel chromatin‐forming histone H1 homologue is encoded by a dispensable and growth‐regulated gene in Bordetella pertussis (1995)

We report the identification of a protein homologous to a histone H1 in Bordetella pertussis. The B. pertussis histone homologue, BpH1, varies in size in different strains from 182 to 206 amino acids. The variability of the size of the protein is due to gene variability by insertion or deletion of DNA modules. Insertion of a kanamycin cassette into the bpH1 gene generates a BpH1 null mutant with phenotypic properties and growth rate similar to those of the wild-type strain, showing that this gene is dispensable. In vitro, the BpH1 protein prevents chromosomal DNA degradation from DNase I and constrains supercoiled DNA. Transcription of the bpH1 gene is activated during exponential growth of the bacteria, whereas it is repressed during the stationary phase of growth. It is proposed that BpH1 plays a role in chromatin formation and condensation during DNA replication and that repression of transcription depends upon a reduced rate of DNA replication.
Haptic exploration of spheres: Techniques and initial experiments (2010)

Haptic perception of properties of objects in the hand is not fully understood. One aspect is the precision with which subjects can detect geometrical features. In this experiment, subjects discriminated between pairs of steel spheres in which one was a precisely manufactured ball bearing and the other was distorted by various degrees. Precise distortions of spheres provide a very sensitive but practical way to create controlled experiments. In one experiment, we reduced the diameter along a single axis and smoothed and polished the resulting shape. In another, the reduced diameter was held constant, and local curvature was varied. Using these spheres, subjects were able to detect subtle changes in sphere diameter along one axis, but were not as sensitive to changes in local curvature. For diameter, a just-noticable-difference (JND) between 2% and 5% was measured.