gebhart/patrepeval huggingface dataset:
The Effects of Multiple Doses of Lomecel‐B, Longeveron’ s Cell‐based Therapy, on Alzheimer’s disease: Study Design and Rationale of this Phase 2a Multi‐ center Clinical trial. (2022)

Abstract Background Lomecel‐B is an allogeneic medicinal signaling cell (MSC) formulation under clinical investigation for Alzheimer’s disease (AD). We have successfully completed a double‐blinded, placebo‐controlled Phase 1 safety trial, in which Lomecel‐B was found to be safe and tolerable in patients with mild AD, and yielded preliminary evidence supporting potential efficacy. Mechanistically, this included evidence of pro‐vascular and anti‐inflammatory activities. Extending upon these promising results, we present the rationale and design of the next‐phase 2a trial in this program. Method The primary objective of this double‐blinded, randomized, and placebo‐controlled Phase 2a trial is to evaluate the safety of multiple doses of Lomecel‐B versus a single dose or placebo. Forty‐eight participants will be equally randomized to four study arms, and will receive intravenous infusions at Weeks 0, 4, 8, and 12, and followed up through Week 39 post‐first infusion. Arm 1 will receive four intravenous infusions of placebo. Arm 2 will receive one infusion of low‐dose Lomecel‐B (2.5×10 7 cells) followed by three infusions of Placebo. Arm 3 will receive four infusions of low‐dose Lomecel‐B. Arm 4 will receive four infusions of high‐dose Lomecel‐B (10 8 cells). Enrolled subjects will undergo a multi‐tiered screening process (clinical evaluation, blood‐work, MRI, and PET). Major enrollment criteria are mild AD with confirmatory beta‐amyloid tracer PET, 60‐85 years of age, and a MMSE score of 18‐24. Safety will be monitored by examining vital signs, physical and neurological exams, laboratory tests (hematology, coagulation, blood chemistry, and urinalysis), and neuroimaging. The secondary objectives are to assess the effects of Lomecel‐B on the cognitive function, and pro‐vascular and anti‐inflammatory biomarkers. Exploratory objectives include neurocognitive, neuropsychiatric, quality‐of‐life, activities‐of‐daily‐living, frailty status, and biomarkers assessments. Result This multicenter phase 2a trial has been allowed to proceed by FDA, is IRB approved, and actively enrolling. Conclusion This trial is designed to obtain safety and preliminary efficacy data on the effects of a multiple doses of Lomecel‐B on mild AD, with an emphasis on biomarkers related to proposed mechanisms of action (MOAs). We anticipate this trial will have complete enrollment by early 2023, and preliminary safety findings available soon thereafter.
Morphological control in inorganic nanostructured material (2010)

Control of the particle morphology and particle outer diameter (from nano and submicron sizes) has increasingly captured the attention of researchers for decades. The exploration of unique sizes and shapes as they relate to various properties has become a great quest for large field applications. To meet these demands, this study covered our recent developments in an aerosol-assisted self-assembly technique (a spray method) for particle processing. The particle processing of several morphologies (sphere, doughnut, encapsulated, porous, hollow, raspberry, and hairy shapes) was discussed in terms of the selection of material types, the addition of supporting materials, and the change of process conditions. Controllable particle outer diameter was discussed in terms of the adjustment of the droplet size and concentration, and the addition of specific techniques. A theoretical mechanism was also simplified described, especially to describe how particles are designed with various sizes and morphologies. The performance of various particle morphologies was also demonstrated, which was essential for an understanding of the importance that shape could exert on practical use. Because the method outlined here can be broadly applied to the production of various types of functional materials, we believe that this report contributes new information to the field of chemical, material, environmental, and medical engineering.
Adsorber Particles with Magnetically‐Supported Improved Electrochemical Conversion Behavior for Waste Water Treatment Processes (2020)

Abstract Micron‐sized supraparticles, consisting of a plurality of discrete nano‐ and microscale functional units, are assembled and fused by means of a droplet extrusion process. By combining nano magnetite, activated carbon, and conductive carbon with a polymeric binder matrix, particles are obtained which unite good magnetic properties, electrical conductivity, and adsorber activity through the high accessible surface area of the incorporated activated carbon of about 570 m 2 g −1 , thereby enabling a new approach toward sustainable water treatment processes. Due to the interplay of the components, it is possible to adsorb target substances, dissolved in the water which is demonstrated by the adsorption of the model dye methylene blue. A very fast adsorption kinetic and an adsorption capacity of about 400 mg g −1 is determined. By using the developed composite particles, it is also possible to electrochemically alter substances flowing through a magnetically‐stabilized fluidized‐bed reactor by electrochemically charging/discharging, significantly supported by the magnetic field enabling alternatingly optimum mobility/adsorption phases with contact/charging intervals. The electrochemical conversion can be increased up to 151% depending on the applied flow‐rate and electrical voltage. By applying an external magnetic field, a further increase of electrochemical conversion of up to 70% can be observed.
Superconducting Single Photon Detector Enables Time-Resolved Emission Testing of Low Voltage Scaled ICs (2016)

Abstract Advancements in photodetector technology are revitalizing time-resolved emission (TRE) techniques in semiconductor failure analysis. In this article, the authors explain how superconducting single-photon detectors improve the capabilities of TRE measurements as demonstrated on 14 nm FinFET technology and an inverter chain with power supply voltages down to 0.4 V.
Diacylfuroxans Are Masked Nitrile Oxides That Inhibit GPX4 Covalently (2019)

GPX4 represents a promising yet difficult-to-drug therapeutic target for the treatment of, among others, drug-resistant cancers. Although most GPX4 inhibitors rely on a chloroacetamide moiety to modify covalently the protein's catalytic selenocysteine residue, the discovery and mechanistic elucidation of structurally diverse GPX4-inhibiting molecules have uncovered novel electrophilic warheads that bind and inhibit GPX4. Here, we report our discovery that diacylfuroxans can act as masked nitrile oxide prodrugs that inhibit GPX4 covalently with unique cellular and biochemical reactivity compared to existing classes of GPX4 inhibitors. These observations illuminate a novel molecular mechanism of action for biologically active furoxans and also expand the collection of reactive groups capable of targeting GPX4.
The role of IgE, IgG, and IgA in tolerance, sensitization, and targeted treatment of allergic disease (2021)

Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. In genetically-predisposed subjects exposure to minute quantities of allergens leads to the production of IgE antibodies which is termed allergic sensitization and mainly occurs in early childhood. Allergen-specific IgE then binds to the high (FcRI) and low affinity receptors (FcRII, also called CD23) for IgE on effector cells and antigen-presenting cells, respectively. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE-facilitated allergen presentation perpetuates T cell-mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared to IgE, and do not efficiently interfere with allergen-induced inflammation. However IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mastcells and basophils. Here we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.
Dynamic Evaluation and Implementation Guidelines for a Nonproprietary W-Beam Guardrail Trailing-End Terminal (2013)

Most state departments of transportation use simple adaptations of crashworthy guardrail end terminals, which typically include breakaway posts and an anchor cable, for downstream anchorage systems. The guardrail safety performance for vehicular impacts occurring in close proximity to these simplified, downstream anchorage systems is not well known. Further, the length of need (LON) for the downstream end of these systems has yet to be adequately determined. This research project assessed the safety performance of the Midwest Guardrail System (MGS) for impacts occurring in close proximity to a nonproprietary, trailing-end guardrail terminal under the Test Level 3 conditions of the Manual for Assessing Safety Hardware. The two research objectives were to (a) determine the end of the LON for impacts with light pickup trucks and (b) investigate potential risks for a small passenger car to become unstable when striking the downstream end of the MGS anchored by the nonproprietary, trailing-end terminal. Numerical simulations were carried out to identify the most critical impact location for the 1100C small car and the end of the LON for the 2270P pickup truck. In full-scale crash tests, considerable snag of the 1100C vehicle occurred; however, occupant risk values and vehicle stability were within acceptable limits. The crash test with the 2270P pickup indicated that the end of the LON was located at the sixth post from the downstream-end post. Guidelines were proposed for installing the MGS to shield hazards in close proximity to the tested nonproprietary, trailing-end terminal.
Termination Structures for Diamond Schottky Barrier Diodes (2006)

A comprehensive study on the off-state performance of synthetic single crystal (SSC) diamond Schottky barrier diodes (SBDs) is the subject of this paper. Three termination structures suitable for unipolar diamond power devices are numerically investigated. Comparisons between the three terminations, based on blocking performance and area consumption are presented. Optimum design parameters derived from simulations are included for each structure. Experimental results of reverse-biased diamond SBDs for the first time with ramp angle termination are also presented
Possible Polaron Effect in Complex Terahertz Conductivity of Electron-Doped Nanoporous Crystal 12CaO·7Al2O3 (2006)

We have measured the temperature dependence of the complex THz conductivity \(\tilde{\sigma}(\omega)\) of electron-doped 12CaO·7Al 2 O 3 (C12A7) (carrier concentration, 5×10 18 cm -3 ) showing the DC conductivity of Mott variable-range hopping. The complex dielectric constant of electron-doped C12A7 gradually decreases to that of undoped C12A7 with decreasing temperature, which is caused by the freeze-out of hopping carriers. The extracted \(\tilde{\sigma}(\omega)\) stemming from the electrons was found to obey the Jonscher law between 0.3 and 1.2 THz in the measured temperature range, 50–300 K. Detailed discussions are presented by employing several pair-approximation models generally describing the frequency and temperature dependences of the power s in the Jonscher law up to GHz range, from which it has been revealed that the most plausible model is one taking into account a polaron effect. A distribution of relaxation time conjectured from the model is presented. Our results significantly suggest the extension of the use of the Jonscher law and the pair-approximation model beyond the GHz range, although some modifications may be needed for the latter.
FACTORS AFFECTING PRODUCTION OF TRANSGENIC MICE BY ICSI-MEDIATED DNA TRANSFER (2007)

Transgenesis in mice is currently most-efficiently performed using pronuclear injection. In the current study, we sought to evaluate whether optimization of intracytoplasmic sperm injection (ICSI)-mediated DNA transfer could increase the efficiency of transgenesis in mice. Competency of B6D2F1-derived epididymal spermatozoa was achieved by freeze and storage in two kinds of medium (NIM, Tris-EGTA). The sperm heads were then exposed for 1 min to different concentrations (2.5 to 7.5 μg/ml) of an isolated DNA linear fragment containing an enhanced green fluorescent protein (EGFP) gene expression cassette, and then microinjected into oocytes. We found that processing of sperm in Tris-EGTA medium was improved from that of NIM. The optimal concentration of EGFP DNA was 2.5–5.0 μg/ml, as determined by the in vitro developmental competence to blastocysts and the extent of EGFP expression in the resultant embryos. Following adoptive transfer of ICSI embryos, we observed optimal transgenesis efficiencies of 4.9% (N= 101 embryos). EGFP positive founder transgenic mice transmitted the transgene to their progeny demonstrating it was indeed integrated into the mouse germ line. Interesting, one founder contained multiple integration sites giving rise to offspring with different levels of EGFP expression. (poster)
Preparation of La-modified PbTiO3 thin films on the oxide buffer layers with NaCl-type structure (1994)

La-modified PbTiO3(PLT: Pb0.9La0.1Ti0.975O3) thin films by rf magnetron sputtering were prepared on the preferred (100)-oriented oxide buffer layers with NaCl-type structure, which were prepared by plasma-enhanced metalorganic chemical vapor deposition. Fused silica, (111)Si, soda-lime glass, and stainless steel were used as the substrates to prepare the oxide buffer layers. The c-axis and a-axis preferred oriented PLT thin films were obtained on the buffer layer, independent of the kind of substrate. Further, highly c-axis oriented PLT thin films were obtained when the substrate had a large thermal expansion coefficient. Significant pyroelectric currents were detected without a poling treatment. The NiCr/PLT/(100)Pt/(100)MgO/stainless steel structure had a dielectric constant of 250, a dielectric loss factor tan δ of 0.8%, and a pyroelectric coefficient of 3.8×10−4 C/m2 K.
Developmental Changes of Catecholamine-mediating Enzyme - Dopamine-β- Hydroxylase and Its Cofactors in Central and Peripheral Tissues and Serum of Long-Evans Rats. (2012)

Dopoamine-β-hydroxylase (DBH) is a catecholamine-synthesizing enzyme which catalyzes the formation of norepinephrine from dopamine. Fifty nine Long-Evans rats of 1 week-old were used to grow on normal diets in 7 different developmental stages, viz., 15 rats in 1 week-old group, 9 rats in 2 weeks-old group, and the remaining 35 rats were divided equally into five groups, 7 rats in each group of 5-, 8-, 12-, 15- and 27-weeks old for systematic developmental studies of DBH. At the end of each developmental period, weights of rats were recorded for that specific group and they were sacrificed. The brain tissues (caudate nucleus, hypothalamus, brain stem, colliculi, cerebral cortex and cerebellum) and peripheral tissues (liver, heart, kidney, adrenal, spleen, pancreas, lung and small intestine) and serum were collected. The brain tissues had the highest activity (expressed as nmole/min/g of wet weight tissue) of DBH at 5 weeks of age. The hypothalamus had the highest activities (11.5 ± 2.2) and the lowest activities were found in the cerebellum (5.7 ± 0.9). The peripheral tissues also showed the peak DBH activities at 5 weeks of age and adrenals had the highest activities (59.2 ± 7.0) among the central and peripheral tissues. The serum DBH activities were relatively low (1.3 ± 0.2) as compared to those in all other tissues. The highest serum DBH activities (1.28 ± 21 nmole/min/ml of serum) were also found in the 5- weeks-old rats. The specific activities of DBH were also measured in various developmental stages and the results were found to be in agreement with the DBH activities expressed in terms of gram of tissues or milliliter of serum. The Km and Vmax values for DBH were measured in the serum samples of each group and the highest Vmax values (78.3 ± 21.2 pmol/min/mg protein) were obtained at 5 weeks of age; while the lowest Km values (0.52 ± 0.04 mM) were obtained at this stage of age.
Early Results of Nidek Customized Aspheric Transition Zones (CATz) in Laser in situ Keratomileusis (2003)

Customized aspheric transition zones may help reduce induction of spherical aberration in refractive surgical correction of myopia and myopic astigmatism.
Cross-band flexible UWB multiple access for high-rate multi-piconet WPANs (2005)

Emerging technologies including wireless multimedia and personal area networks (WPANs) call for high-rate systems capable of supporting multiple users (piconets) with variable rates. These requirements motivate multi-band ultra-wideband (UWB) radios with low-cost, short time-to-market transceivers. Relative to baseband UWB radios, multi-band systems offer certain advantages, but special multiple access (MA) schemes are needed. To this end, we introduce a cross-band flexible UWB MA scheme for multi-piconet WPANs. The resultant so termed FLEX-UWB design offers resilience against multi-user interference (MUI), can accommodate various spreading alternatives, enables full multipath diversity, and can affect scalable spectral efficiency (from low, to medium and high data rates).
Higher Permittivity Rare Earth-Doped HfO2 and ZrO2 Dielectrics for Logic and Memory Applications (2007)

We demonstrate electrical properties of rare earth (RE)-doped HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> and ZrO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> for application as higher permittivity (k) dielectrics in logic and memory devices. X-ray diffraction (XRD) results show that Dy, Er, and Gd doping stabilizes the higher-k tetragonal phase rather than the lower-k monoclinic phase. This preferred tetragonal phase results in a k~30. Initial electrical results show ~3 nm higher-k enables an equivalent oxide thickness (EOT) of 0.93 nm. Alternatively, ~7nm higher-k reduces leakage currents 1000x relative to HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> achieving <10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-8</sup> A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at an EOT of 2 nm. Capacitance-voltage (C-V) data show increasing amounts of RE dopants shift flatband voltage (Vft) in the negative direction vs. pure HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> .
Dendritic−Linear Miktoarm Star Polymers from Orthogonal Protected Initiators (2002)

The synthesis of miktoarm dendritic−linear star copolymers in a tandem “core-in”/“core-out” approach is described. This synthetic approach is enabled by rational design and synthesis of an orthogonal protected compound containing six sites arranged in an alternating fashion for attachment of dendrimers and atom transfer radical polymerization of linear polymer chains. The judicious choice of the dendrimer surface functionality coupled with the properties of the monomer used in the linear chain allows the creation of amphiphilic molecules capable of supramolecular assembly. 1H NMR and SEC studies of the block copolymers confirmed that the targeted polymer structures were achieved with low polydispersities and good yields. The nature and the size of the arms and dendrons had a significant influence on the hydrodynamic radii (Rh) measured by dynamic light scattering. Some of these macromolecules microphase-separated after annealing.
A Time-Triggered Ethernet (TTE) Switch (2006)

This paper presents the design of a time-triggered Ethernet (TTE) switch, which is one of the core units of the time-triggered Ethernet system. Time-triggered Ethernet is a communication architecture intended to support event-triggered and time-triggered traffic in a single communication system. The TTE switch distinguishes between two classes of traffic. The event-triggered (ET) traffic is handled in conformance with the existing Ethernet standard, while the time-triggered (TT) traffic is transmitted with temporal guarantees. A TTE switch is used in the time-triggered Ethernet system for exchanging time-triggered messages in a time-predictable way while continuing the support of standard Ethernet traffic in order to use existing networking protocols such as IP, UDP or IPX without any modifications. In this paper we present the mechanisms the TTE switch uses to guarantee a constant transmission delay for time-triggered traffic. Also an experimental validation of these mechanisms is given
Integrated Design and Management of a Sustainable Data Center (2009)

The environmental impact of data centers is significant and is growing rapidly. However, there are many opportunities for greater efficiency through integrated design and management of data center components. To that end, we propose a sustainable data center that replaces conventional services in the physical infrastructures with more environmentally friendly IT services. We have identified five principles for achieving this vision: data center scale lifecycle design, flexible and configurable building blocks, pervasive sensing, knowledge discovery and visualization, and autonomous control. We describe these principles and present specific use cases for their application. Successful implementation of the sustainable data center vision will require multi-disciplinary collaboration across various research and industry communities.
HIV evolution and escape. (2004)

Human immunodeficiency virus (HIV) exemplifies the principles of Darwinian evolution with a telescoped chronology. Because of its high mutation rate and remarkably high rates of replication, evolution can be appreciated over periods of days in contrast to the durations conceived of by Darwin. Certain selective pressures that drive the evolution of HIV include chemotherapy, anatomic compartmentalization and the immune response. Examples of these selective forces on HIV evolution are described.