gebhart/patrepeval huggingface dataset:
Intraocular expression of endostatin reduces VEGF‐induced retinal vascular permeability, neovascularization, and retinal detachment (2003)

Endostatin, a proteolytic fragment of collagen XVIII, is an endogenous inhibitor of tumor angiogenesis that also inhibits choroidal neovascularization. In this study, we assessed the effects of increased intraocular expression of endostatin on vascular endothelial growth factor (VEGF)-induced changes in the retina. After subretinal injection of a pair of gutless adenoviral vectors (AGV) designed to provide tamoxifen-inducible expression of endostatin, diffuse endostatin immunoreactivity was induced thoroughout the retina by administration of tamoxifen. Induction of endostatin in double transgenic mice with doxycycline-induced expression of VEGF in the retina resulted in significant suppression of leakage of intravascular [3H]mannitol into the retina. The ability of endostatin to reduce VEGF-induced retinal vascular permeability was confirmed by using [3H]mannitol leakage and two other parameters, fluorescein leakage and retinal thickness, after subretinal injection of a bovine immunodeficiency lentiviral vector coding for endostatin (BIV-vectored endostatin, or BIVendostatin). Subretinal injection of BIVendostatin resulted in more discrete, less intense staining for endostatin in the retina than that seen with the inducible AGV system, which suggested lower levels and allowed visualization of sites where endostatin was concentrated. Endostatin staining outlined retinal blood vessels, which suggested endostatin binding to a component of vessel walls. More prolonged or higher level expression of VEGF in the retina resulted in neovascularization and retinal detachment, both of which were also significantly reduced by BIVendostatin. These data suggest that endostatin may be an endogenous inhibitor of vasopermeability as well as neovascularization. In patients with diabetic retinopathy, endostatin gene transfer may provide a way to decrease the risk of three causes of visual loss: macular edema, neovascularization, and retinal detachment.
Supplementary Figure Legends 1-6 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity (2023)

Supplementary Figure Legends 1-6 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
Calpain-mediated tau fragmentation is altered in Alzheimer’s disease progression (2018)

The aggregation of intracellular tau protein is a major hallmark of Alzheimer's disease (AD). The extent and the stereotypical spread of tau pathology in the AD brain are correlated with cognitive decline during disease progression. Here we present an in-depth analysis of endogenous tau fragmentation in a well-characterized cohort of AD and age-matched control subjects. Using protein mass spectrometry and Edman degradation to interrogate endogenous tau fragments in the human brain, we identified two novel proteolytic sites, G323 and G326, as major tau cleavage events in both normal and AD cortex. These sites are located within the sequence recently identified as the structural core of tau protofilaments, suggesting an inhibitory mechanism of fibril formation. In contrast, a different set of novel cleavages showed a distinct increase in late stage AD. These disease-associated sites are located outside of the protofilament core sequence. We demonstrate that calpain 1 specifically cleaves at both the normal and diseased sites in vitro, and the site selection is conformation-dependent. Monomeric tau is predominantly cleaved at G323/G326 (normal sites), whereas oligomerization increases cleavages at the late-AD-associated sites. The fragmentation patterns specific to disease and healthy states suggest novel regulatory mechanisms of tau aggregation in the human brain.
Seven new planetary nebulae in the direction of Baade's Window (1985)

The authors present seven new planetary nebula candidates that were discovered with interference-filter photographs, and that lie in or near Baade's Window (l = 1°.0, b = -3°.9). Two of them are angularly resolved, and are probably relatively nearby disk objects. All are faint and suffer from high interstellar reddening.
Comparison of BinaxNOW TM and SARS-CoV-2 qRT-PCR detection of the Omicron Variant from Matched Anterior Nares Swabs (2022)

The COVID-19 pandemic has increased the use of rapid antigen tests such as the Abbott BinaxNOWTM COVID-19 Antigen Self-Test. In winter of 2021-2022, the omicron variant surge made it quickly apparent that although rapid diagnostic tests (RDTs) are less sensitive than qRT-PCR, the accessibility, ease of use, and rapid read-outs of RDTs made them a sought after and often sold-out item at local suppliers. Here, we sought to qualify the BinaxNOWTM test for use in our university testing program as a method to rule-in positive or rule-out negative individuals quickly when they seek care at our priority qRT-PCR testing site. To perform this qualification study, we collected matched additional swabs from individuals attending this test site for standard of care qRT-PCR testing. All matched swabs were tested using the BinaxNOWTM RDT. Initially as part of a feasibility study, test period 1 (n=110) samples were put in cold storage prior to testing. In follow-on test period (n=209), we tested samples real-time at the test facility. Combined, 102 of 319 samples tested positive for SARS-CoV-2. All samples for which genome sequence could be collected were omicron (n=92). We observed a calculated sensitivity of 53.9%, specificity of 100%, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 82.2% for the BinaxNOWTM tests (n=319). Sensitivity improved (75.3%) by changing the qRT-PCR positivity threshold from a CT of 40 to a CT of 30. The ROC curve shows that for qRT-PCR positive CT values between 24-40, the BinaxNOWTM test is of limited value diagnostically. Our results suggest that RDT tests could be used in our setting to confirm SARS-CoV-2 infection in individuals with substantial viral load, but that a significant fraction of infected individuals would be missed if we used RDT tests exclusively to rule out infection.
Differential Role of Plasma and Platelet-Derived Factor V In Vivo (2017)

Abstract Coagulation factor V (FV) has a profound effect on coagulation and deficiency states lead to bleeding. In blood, there are two pools of FV with 80% found in plasma and 20% contained in the α-granules of platelets. The biological basis for this separation is not clear; however, structural distinctions between the pools have been identified suggesting they may have unique effects or play different roles following injury. Broadly however, in vivo evidence for this is lacking. Transgenic mice with synthesis limited to liver or megakaryocytes have been generated to study the role of plasma and platelet FV (Sun et al, Blood 102:2856, 2003). Either pool is sufficient for basal hemostasis and tail-bleeding times were only slightly prolonged compared to wild-type (wt) mice. The impact of the two pools following different hemostatic challenges in different vessels is not known. To expand our in vivo understanding of the FV pools on clot formation, we further studied mice with only platelet FV (platelet-FV+) or plasma FV (plasma-FV+). As a control, we also generated mice with essentially little to no total FV (FV-low). To generate platelet-FV+ mice, wt mice were treated with a single dose of a liver targeted antisense oligonucleotide (ASO) to knockdown plasma FV (ASO-FV; 40 mg/kg). After 3 weeks of ASO-FV treatment, the plasma FV levels assessed with a murine FV-specific ELISA were at the lower limits of detection while platelet FV levels were normal. This confirms prior work showing platelet FV originates from megakaryocyte synthesis in mice, which is different from humans. To generate plasma-FV+ mice, we used previously established transgenic mice only expressing FV (~30% of wt) from the liver with no platelet FV. To create FV-low mice, plasma-FV+ mice were treated with ASO-FV; this resulted in mice with markedly reduced ( Disclosures Ivanciu: Bayer: Research Funding; Novo Nordisk: Research Funding. Crosby: Ionis Pharmaceuticals: Employment, Research Funding. Revenko: Ionis Pharmaceuticals: Employment, Research Funding. MacLeod: Ionis Pharmaceuticals: Employment. Monia: Ionis Pharmaceuticals: Employment. Davidson: Spark Therapeutics: Consultancy. Camire: Bayer: Consultancy, Research Funding; Pfizer: Consultancy, Patents & Royalties, Research Funding; Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Research Funding.
Erratum to: Biomechanical comparison of graft structures in anterior cruciate ligament reconstruction (2016)

Purpose: Double-bundle (DB) anterior cruciate ligament (ACL) reconstruction may offer kinematic restoration superior to anatomic single bundle (SB), but it remains technically challenging. The femoral attachment site has the most effect on ACL graft isometry, so a simplified three-socket (3S) construct which still uses two sockets to cover the femoral ACL attachment is attractive. It was hypothesised that ACL reconstruction using three- and four-socket techniques would more closely restore native knee kinematics compared to anatomic two-socket (SB) surgery. Methods: Nine cadaveric knees were used to evaluate the kinematics of ACL-intact, ACL-deficient, anatomic SB, three-socket, and DB arthroscopic ACL reconstructions. Suspensory fixation was used, and grafts were tensioned to match the anterior draw of the intact knee at 20°. A six-degree-of-freedom robotic system measured knee laxity under 90 N anterior tibial force and rotational laxity under 5 N-m torque. Combined moments were applied to simulate the pivot-shift subluxation: 4 N-m internal rotation and 8 N-m valgus. Results: Significant differences between reconstructions were not found during anterior tibial loading, apart from SB being more lax than DB at 60° flexion. All reconstructions produced comparable laxity to the intact state, apart from SB at 60°. Significant differences between reconstructions were not found at any flexion angle during tibial internal/external applied torques. Under combined loading, DB produced significantly less laxity than SB constructs apart from anterior tibial translation at 0° and internal rotation at 45°. 3S and DB were comparable to the native knee throughout. Conclusion: Although 3S restored laxities to a similar extent to DB, significant superiority over SB surgery was not observed. Although statistically significant differences were found between SB and DB surgery during anterior tibial and simulated pivot-shift loading, both remained similar to the native knee. The clinical relevance is that this study did not support an ACL graft construct more complex than an anatomic single bundle.
Neuron-MOS Temporal Winner Search Hardware for Fully-Parallel Data Processing (1995)

A unique architecture of winner search hardware has been developed using a novel neuron-like high functionality device called Neuron MOS transistor (or vMOS in short) [1,2] as a key circuit element. The circuits developed in this work can find the location of the maximum (or minimum) signal among a number of input data on the continuous-time basis, thus enabling real-time winner tracking as well as fully-parallel sorting of multiple input data. We have developed two circuit schemes. One is an ensemble of self-loop-selecting vMOS ring oscillators finding the winner as an oscillating node. The other is an ensemble of vMOS variable threshold inverters receiving a common ramp-voltage for competitive excitation where data sorting is conducted through consecutive winner search actions. Test circuits were fabricated by a double-polysilicon CMOS process and their operation has been experimentally verified.
ChemInform Abstract: Microporous Crystal 12CaO×7Al2O3 Encaging Abundant O‐ Radicals. (2002)

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.
Plasma β-amyloid as potential biomarker of Alzheimer disease: possibility of diagnostic tool for Alzheimer disease (2010)

Alzheimer disease (AD), which is characterized by progressive cognitive and behavioral deficit, is the most common form of dementia. The incidence of AD is increasing at an alarming rate, and has become a major public health concern in many countries. It is well known that the onset of AD is preceded by a long preclinical period. It is thus critical to establish diagnostic biomarkers that can predict the risk of developing AD prior to clinical manifestation of dementia, for effective prevention and early intervention. With the emergence of potential promising approaches to treat AD targeting the beta-amyloid (Abeta) pathway, such as gamma-secretase inhibitors and vaccine therapy, there is an urgent need for such diagnostic markers. Although cerebrospinal fluid (CSF) Abeta and tau protein levels are candidate biomarkers for AD, the invasive sampling procedure with associated complications limits their use in routine clinical practice. Plasma Abeta has been suggested as an inexpensive and non-invasive biomarker for AD. Although most previous cross-sectional studies on plasma Abeta level in humans failed to show a significant difference between individuals with AD compared to healthy older adults, many strategies are under investigation to improve the diagnostic potential of plasma Abeta. One promising approach is to modify the plasma Abeta level using some potential modulators. It is possible that a difference in plasma Abeta level might be unmasked by evaluating the response to stimulation by a modulator. Anti-Abeta antibody and Abeta binding proteins have been reported to be such modulators of plasma Abeta. In addition, the glucometabolic or hormonal status appears to modulate the plasma Abeta level. Our recent study has shown the possibility that glucose loading could be a novel simple strategy to modulate the plasma Abeta level, making it better suited for early diagnosis. This review summarizes the utility and limitations of current biomarkers of AD and discusses future strategies to improve the diagnostic potential of plasma Abeta.
AutoTune: Improving End-to-end Performance and Resource Efficiency for Microservice Applications (2021)

Most large web-scale applications are now built by composing collections (from a few up to 100s or 1000s) of microservices. Operators need to decide how many resources are allocated to each microservice, and these allocations can have a large impact on application performance. Manually determining allocations that are both cost-efficient and meet performance requirements is challenging, even for experienced operators. In this paper we present AutoTune, an end-to-end tool that automatically minimizes resource utilization while maintaining good application performance.
Permeabilizing millions of cells with single pulses of an excimer laser. (1993)

Poration of millions of cells with single laser pulses of an argon fluoride excimer laser is developed and demonstrated on plant cells. The essence of the technique is to use the large beam size (10 x 25 mm) of the excimer laser and to split it using an appropriate mask into millions of micron- or submicron-sized beams of 193-nm radiation with enough energy to perforate cell membranes and walls. The extremely small depth of penetration of the 193-nm radiation in biological tissue (< 1 microns) is used to great advantage in this technique to provide for a gentle method that does not lead to cell death. This is the first laser-based method that has enough throughput to make it viable for biotechnological applications. Of considerable significance is that the method is applicable not only in the case of the single cells in suspension, but also for cells growing on the leaves of living plants.
Development and characterization of rabbit antisera to human MHC‐linked transporters associated with antigen processing (1996)

The limited availability of sera to human MHC-linked transporters associated with antigen processing (TAP) has hampered the analysis of the role of these molecules in the reduced HLA Class I antigen expression by normal and transformed cells. To overcome these limitations, anti-human TAP1 and anti-human TAP2 xenoantisera have been generated and characterized. To this end rabbits have been immunized with TAP1-specific or TAP2-specific peptides which correspond to nonhomologous, hydrophilic regions of each transporter subunit. The immunized rabbits developed high titer IgG antibodies which displayed specific reactivity with the immunizing peptides in ELISA. Both anti-TAP1 and anti-TAP2 antisera immunoprecipitated the 70-76 kDa TAP complex from TAP(+)-TAP2+ cell lines WALK and Colo 38, but precipitated no component from TAP(-)-TAP2- cell lines T2 and SK-MEL-19. Furthermore, in immunodepletion experiments anti-TAP1 and anti-TAP2 antisera removed the molecules recognized by each of them in a lymphoid cell extract. Lastly, in Western blotting assays anti-TAP1 and anti-TAP2 antisera reacted specifically with isolated TAP1 and TAP2, respectively. The latter results in conjunction with those of the immunodepletion experiments indicate that TAP1 and TAP2 are not detectable as isolated subunits in a cell extract and that TAP heterocomplex is the major, if not the only detectable molecular species in cells. Anti-TAP1 and anti-TAP2 antisera were evaluated in immunohistochemical staining of both frozen and formalin fixed sections of skin and primary malignant melanoma lesions. Both antisera stained the cytoplasm of keratinocytes in normal skin and of melanoma cells in malignant lesions. The antisera we have elicited with TAP1- and TAP2-specific peptides appear to be useful reagents to characterize the role of TAP in abnormalities of HLA Class I antigen expression.
Multi-crystal native SAD analysis at 6 keV (2014)

Anomalous diffraction signals from typical native macromolecules are very weak, frustrating their use in de novo structure determination. Here, native SAD procedures are described to enhance signal to noise in anomalous diffraction by using multiple crystals in combination with synchrotron X-rays at 6 keV. Increased anomalous signals were obtained at 6 keV compared with 7 keV X-ray energy, which was used for previous native SAD analyses. A feasibility test of multi-crystal-based native SAD phasing was performed at 3.2 Å resolution for a known tyrosine protein kinase domain, and real-life applications were made to two novel membrane proteins at about 3.0 Å resolution. The three applications collectively serve to validate the robust feasibility of native SAD phasing at lower energy.
Phase aberration correction with ultrasonic time reversal mirrors (1994)

Adaptive time delay focusing techniques allow an efficient correction of the effects due to an inhomogeneous layer close to the transducer array. We have developed in our laboratory a time reversal process able to compensate for all distortion effects in the transmit mode. This process has been extended by developing in the transmit-receive mode a spatiotemporally matched filter approach that focuses optimally on a reflective target whatever the distance between the layer and the transducer array. In this technique, a set of focusing signals perfectly matched to the reflector are built and stored. This set of signals is used to focus in both transmit and receive modes, yielding the maximal signal for the reflector location with a very low side lobe level. We present in this paper an extension of this technique to focus, not only on the reflector, but also around the reflector in order to image the surrounding zone. From the knowledge of the signals needed to focus on the initial reflector, we calculate the new signals matched to the new point of interest. The algorithm uses the concept of time reversal propagation
Passive Pre-Chamber Spark Plug for Future Gasoline Combustion Systems with Direct Injection (2018)

The challenge of using a pre-chamber spark plug for future gasoline combustion processes with direct injection is, on the one hand, to realize an ignitable mixture in the pre-chamber at low load and speed. On the other hand, at high speed and high load, keeping component temperatures have to be kept low in order to prevent irregular combustions (pre-ignition, glow ignition). With increasing requirements regarding fuel consumption and emissions, the challenges to modern combustion strategies are growing steadily. Measures to further increase the efficiency of the combustion engine are required for this purpose. There are different approaches to increase efficiency. These include increasing the compression ratio and diluting the air-fuel mixture. The latter can be generally classified into two broad categories: Dilution with air and dilution with residual gas. In both cases, it turns out that the highest possible dilution is to be preferred with respect to combustion efficiency. Increasing dilution, however, leads in both cases to a deterioration in flammability and a decrease in the flame velocity of combustion. In the resulting requirements for the ignition system, the passive pre-chamber spark plug is an interesting alternative to the conventional spark plug. Due to its functional principle, it can simultaneously improve the ignition and shorten the burn duration. In the present work, the focus is on the behavior of the pre-chamber spark plug while diluting the cylinder charge with air. A particular challenge for the passive pre-chamber spark plug is to safely ignite the mixture at idling and in the low to medium part load with a correspondingly high internal residual gas content. Dilution of the cylinder charge with air also complicates the possibility to have a good air-fuel mixture within the pre-chamber. In order to ensure a reliably ignitable mixture in the pre-chamber even under these boundary conditions, it is necessary to design a suitable pre-chamber geometry in conjunction with the direct injection. This work describes the behavior of different passive pre-chamber spark plugs when using lean mixtures at low and medium part load with CFD simulation. Criteria such as residual gas content and air-fuel ratio at start of ignition at the ignition point as well as other flow parameters such as temperature, velocity and turbulent kinetic energy are examined in detail. The effect of the torch coming out of the pre-chamber is finally assessed by combustion simulation.
Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection (2022)

A successful HIV-1 vaccine will require induction of a polyclonal neutralizing antibody (nAb) response, yet vaccine-mediated induction of such a response in primates remains a challenge. We found that a stabilized HIV-1 CH505 envelope (Env) trimer formulated with a Toll-like receptor 7/8 agonist induced potent HIV-1 polyclonal nAbs that correlated with protection from homologous simian-human immunodeficiency virus (SHIV) infection. The serum dilution that neutralized 50% of virus replication (ID<sub>50</sub> titer) required to protect 90% of macaques was 1:364 against the challenge virus grown in primary rhesus CD4<sup>+</sup> T cells. Structural analyses of vaccine-induced nAbs demonstrated targeting of the Env CD4 binding site or the N156 glycan and the third variable loop base. Autologous nAb specificities similar to those elicited in macaques by vaccination were isolated from the human living with HIV from which the CH505 Env immunogen was derived. CH505 viral isolates were isolated that mutated the V1 to escape both the infection-induced and vaccine-induced antibodies. These results define the specificities of a vaccine-induced nAb response and the protective titers of HIV-1 vaccine-induced nAbs required to protect nonhuman primates from low-dose mucosal challenge by SHIVs bearing a primary transmitted/founder Env.