gebhart/patrepeval huggingface dataset:
Adeno-Associated Viral Vectors for Retinal Gene Transfer and Treatment of Retinal Diseases (2005)

Retinal gene transfer holds big promises for the treatment of inherited and non-inherited blinding diseases, such as retinitis pigmentosa or age-related macular degeneration. Key to the development of successful gene-based therapies for the eye are efficient tools for retinal gene transfer. Vectors based on adeno-associated viruses (AAV) are able to transduce robustly and persistently different retinal cell types of animal models after a single intraocular administration. Recombinant AAV (rAAV) vectors are versatile gene transfer tools in that capsid proteins from dozens of AAV serotypes can be easily interchanged, resulting in the creation of recombinant vectors with unique transduction properties. This has allowed successful proof-of-principle studies using rAAV-mediated gene transfer to restore retinal morphology and function in small and large animal models of retinal diseases. In addition, gene delivery using rAAV vectors in the eye seems to have appropriate biosafety characteristics to rapidly move it from bench to bedside. All the above aspects will be reviewed and discussed in detail below.
Novel components for integrated millimeter -wave front -ends. (2004)

To my father Mohammad-Hossein, and in the loving memory of my mother Nassrin. ii ACKNOWLEDGEMENTS For a real student, education never ends. At least that is the hope. Nevertheless, after nearly a quarter of a century of being “in school”, now I finally find myself at the end of my formal course of education. Although it is too soon to feel the relief, I have already started to feel the void. So my acknowledgement, which is naturally my last stage of thesis writing, is filled with an air of nostalgia. The acknowledgement for a Ph.D. thesis, I believe, must be an acknowledgement to ones entire career of studentship. However, the endless number of people who have been involved in my education during the years makes it impossible to carry out a fair task. So I limit my list to those who have been directly engaged in the last part, namely my years at the University of Michigan. Among all who have contributed to my post graduate education, my greatest
Plasma serine proteinase inhibitors (serpins) exhibit major conformational changes and a large increase in conformational stability upon cleavage at their reactive sites. (1988)

Intact and proteolytically modified human serpins, alpha 1-proteinase inhibitor, antithrombin III, alpha 1-antichymotrypsin, and C1 inhibitor, were compared by circular dichroism, fluorescence spectroscopy, and resistance against unfolding by guanidine HCl. The modified proteins were prepared from the intact and active inhibitors by selective proteolytic cleavage in their reactive site loops and tested for complete loss of activity. Significant differences in the spectral properties between intact and modified inhibitors indicate that a major conformational rearrangement is triggered by the cleavage. This leads to a large increase in conformational stability as demonstrated by large shifts of the transition profiles recorded as a function of guanidine HCl concentration at 20 degrees C by circular dichroism at 220 nm. Intact inhibitors were unfolded in two steps of about equal size centered at 0.8-1.7 and 2.5-3.5 M concentrations of the denaturant, respectively. Under identical conditions modified inhibitors are completely stable, and their denaturation occurs only well above 4 M guanidine HCl in one or two steep transition steps. From the similarity of the spectral changes and shifts in transition profiles for all four serpins studied it is concluded that the conformational changes and stabilization triggered by the modification hit is an important common mechanistic feature of this class of inhibitors. This is supported by the observation that ovalbumin, which is homologous with the serpins but apparently lacks inhibitory activity, exhibits neither spectral changes nor a significant change in stability upon proteolytic modification.
Anti-cyanobacterial activity of Moringa oleifera seeds (2009)

Filtrates from crushed Moringa oleifera seeds were tested for their effects on growth and Photosystem II efficiency of the common bloom-forming cyanobacterium Microcystis aeruginosa. M. aeruginosa populations exhibited good growth in controls and treatments with 4- and 8-mg crushed Moringa seeds per liter, having similar growth rates of 0.50 (+/-0.01) per day. In exposures of 20- to 160-mg crushed Moringa seeds L(-1), growth rates were negative and on average -0.23 (+/-0.05) .day(-1). Presumably, in the higher doses of 20- to 160-mg crushed seeds per liter, the cyanobacteria died, which was supported by a rapid drop in the Photosystem II efficiency (Phi(PSII)), while the Phi(PSII) was high and unaffected in 0, 4, and 8 mg L(-1). High-density populations of M. aeruginosa (chlorophyll-a concentrations of approximately 270 microg L(-1)) were reduced to very low levels within 2 weeks of exposure to >/=80-mg crushed seeds per liter. At the highest dosage of 160 mg L(-1), the Phi(PSII) dropped to zero rapidly and remained nil during the course of the experiment (14 days). Hence, under laboratory conditions, a complete wipeout of the bloom could be achieved. This is the first study that yielded evidence for cyanobactericidal activity of filtrate from crushed Moringa seeds, suggesting that Moringa seed extracts might have a potential as an effect-oriented measure lessening cyanobacterial nuisance.
Estimated source wavelet‐incorporated reverse‐time migration with a virtual source imaging condition (2013)

ABSTRACT Many geophysicists perform reverse‐time migration using a variety of artificial sources to obtain the source wavefield. Upon processing the seismic data, however, it is difficult to recover the original phase and amplitude of the source wavelet used for seismic exploration, regardless of the source. We have therefore used several artificial source wavelets such as Ricker or the first derivative Gauss wavelets expressed by well‐known functions. There are some differences between these artificial source wavelets and the original source wavelets, resulting in imperfect migration images. Artificial source wavelets tend to distort the exact location of subsurface reflectors and they create noise around the boundary of the stratum. To solve this problem, we applied the source estimation technique to the reverse‐time migration algorithm. The source estimation technique approximates the source wavelet to the original exploration source wavelet by a deconvolution method. This technique is used in full waveform inversion and provides better inversion results as demonstrated by other studies. To prove the effect of reverse‐time migration with source estimation, we tested this algorithm on the Sigsbee2a model, SEG/EAGE 3D salt model and 3D real field land data. Using the resulting images of these three models, we found that the source estimation technique can yield better migration images. To suppress the artefacts produced in the migration image, we used a wavenumber filter and Laplacian filter on 2D and 3D examples, respectively. Furthermore, we used the pseudo‐Hessian similar to the source illumination to scale the migration image because the virtual source imaging condition was used for reverse‐time migration.
Control of Immunity by the TNFR-Related Molecule OX40 (CD134) (2010)

TNFR/TNF superfamily members can control diverse aspects of immune function. Research over the past 10 years has shown that one of the most important and prominent interactions in this family is that between OX40 (CD134) and its partner OX40L (CD252). These molecules strongly regulate conventional CD4 and CD8 T cells, and more recent data are highlighting their ability to modulate NKT cell and NK cell function as well as to mediate cross-talk with professional antigen-presenting cells and diverse cell types such as mast cells, smooth muscle cells, and endothelial cells. Additionally, OX40-OX40L interactions alter the differentiation and activity of regulatory T cells. Blocking OX40L has produced strong therapeutic effects in multiple animal models of autoimmune and inflammatory disease, and, in line with a prospective clinical future, reagents that stimulate OX40 signaling are showing promise as adjuvants for vaccination as well as for treatment of cancer.
Altropane, a SPECT or PET imaging probe for dopamine neurons: III. Human dopamine transporter in postmortem normal and Parkinson's diseased brain (1998)

Increasing evidence suggests that the dopamine transporter is situated almost exclusively on dopamine neurons. Accordingly, it is an valuable marker for Parkinson's disease and other pathological states of dopamine neurons. We previously demonstrated that the potent dopamine transport inhibitor [125I]altropane (IACFT:E-N-iodoallyl-2β-carbomethoxy-3β-(4-fluorophenyl)tropane) is a high affinity selective probe for the dopamine transporter in monkey brain and an effective SPECT imaging agent in nonhuman primate brain. We now report the binding properties of [125I]altropane in postmortem tissue of normal human brain and compare the findings to Parkinson's diseased brain. In homogenates of human brain putamen, [125I]altropane bound with high affinity (KD: 4.96 ± 0.38 nM, n = 4) and site density (BMAX: 212 ± 41.1 pmol/g original wet tissue weight) well within the density range reported previously for the dopamine transporter in this brain region. Drugs inhibited [125I]altropane binding with a rank order of potency that corresponded closely to their rank order for blocking dopamine transport (r 0.98, P < 0.001). In postmortem Parkinson's diseased brain, bound [125I]altropane (1 nM) was markedly reduced (89%, 99% in putamen, depending on measures of nonspecific binding) compared with normal aged-matched controls (normal putamen: 49.2 ± 8.1 pmol/g; Parkinson's diseased putamen: 0.48 ± 0.33 pmol/g; n = 4). In vitro autoradiography, conducted in tissue sections at a single plane of the basal ganglia, revealed high levels of [125I]altropane binding the caudate nucleus and putamen, but lower levels (73% of the caudate-putamen) in the nucleus accumbens (n = 7). In Parkinson's diseased brains (n = 4), [125I]altropane binding was 13% of the levels detected in normal putamen, 17% of normal values in the caudate nucleus, and 25% of normal levels in nucleus accumbens. The association of [125I]altropane to the dopamine transporter in human postmortem tissue, the marked reduction of [125I]altropane binding in Parkinson's diseased brains, its rapid entry into brain and highly localized distribution in dopamine-rich brain regions, support its use as a probe for monitoring the dopamine transporter in vitro and in vivo by SPECT imaging. Synapse 29:116–127, 1998. © 1998 Wiley-Liss, Inc.
Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages (2004)

Experimental injury is useful to induce tissue stem cells, which may exist in small numbers under normal conditions. The salivary glands originate from the endoderm and consist of acinar and ductal epithelial cells, which have exocrine function. After salivary gland duct ligation, acinar cells disappear as a result of apoptosis, and duct epithelium subsequently proliferates. In this study, we analyzed the tissue stem cells induced by salivary gland duct ligation in mice using immunohistochemistry and flow cytometry. We sorted the Sca-1(+)/c-Kit(+) fraction from adult mice salivary glands by way of fluorescence-activated cell sorting. The sorted cells were apparently homogeneous and were designated mouse salivary gland-derived progenitors (mSGPs). mSGP cells differentiated into a hepatic lineage when cultured in matrigel. In spherical culture in the presence of glucagon-like peptide-1 (GLP-1), these cells differentiated into a pancreatic endocrine lineage. When spheroidal bodies of mSGP, 20 to 30 microm in diameter, were transplanted into liver via the portal vein, the cells integrated into hepatic cords and expressed albumin and alpha1-antitrypsin, suggesting that they had differentiated into hepatic-type cells. Moreover, ductlike structures formed by mSGP cells also appeared, epithelial cells of which were positive for cytokeratin 19. In conclusion, fluorescence-activated cell sorting (FACS) based on histologic evidence is efficient in isolating adult tissue stem cells of the salivary gland. Tissue stem cells of endodermal origin (e.g., hepatic oval cells, pancreatic epithelial progenitor cells, and salivary gland progenitor cells) have similarities in their molecular markers and tissue location. Our findings suggest the existence of common tissue stem cells in endoderm-derived organs.
Chronic Cerebellar Stimulation in Epilepsy (1976)

Ten of 15 patients subjected to chronic cerebellar stimulation have had previously intractable seizures modified or inhibited up to periods of three years. Stimulation of anterior lobe appears to be more efficacious than stimulation of posterior lobe. Cerebellar biopsies, obtained in five patients at the time of stimulator placement, revealed in every instance a reduction in the molecular layer, decreased or absent Purkinje cells, and decreased stellate cells. One unimproved patient died during a seizure 17 months after stimulation was initiated. Histological examination of the brain did not reveal tissue damage attributable to the stimulator. There is no evidence of any adverse effect of chronic cerebellar stimulation in humans who have undergone stimulation for periods up to three years.
A Particle Filtering Approach To Constrained Motion Estimation In Tracking Multiple Targets (2006)

Particle filtering has been successfully used in complex target tracking applications such as multiple target tracking. The particle filter can be used to incorporate constraints on target motion to improve tracking performance; this can be achieved using likelihood functions and sampling distributions. In this paper, we propose the constraint likelihood function independent partitions (CLIP) algorithm that uses constraints on target motion. This is achieved by incorporating a constraint likelihood function with the particle weights. As demonstrated by our simulations, a higher increase in tracking performance is obtained with our proposed constrained motion proposal (COMP) algorithm that incorporates target kinematic constraint information directly into the proposal density of the particle filter
HKUST‐1 Membranes Anchored on Porous Substrate by Hetero MIL‐110 Nanorod Array Seeds (2013)

Great anchors and seeds: Hetero-seeding growth processes and anchored nanorod arrays were successfully utilized in the synthesis of HKUST-1 membranes. These arrays were firmly anchored on porous substrates by using a MIL-110 nanorod array as both the anchor and seed. The resulting HKUST-1 membranes demonstrated good separation factors for binary gases exceeding the Knudson selectivity.
High-Frequency Scalable Electrical Model and Analysis of a Through Silicon Via (TSV) (2011)

We propose a high-frequency scalable electrical model of a through silicon via (TSV). The proposed model includes not only the TSV, but also the bump and the redistribution layer (RDL), which are additional components when using TSVs for 3-D integrated circuit (IC) design. The proposed model is developed with analytic <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">RLGC</i> equations derived from the physical configuration. Each analytic equation is proposed as a function of design parameters of the TSV, bump, and RDL, and is therefore, scalable. The scalability of the proposed model is verified by simulation from the 3-D field solver with parameter variations, such as TSV diameter, pitch between TSVs, and TSV height. The proposed model is experimentally validated through measurements up to 20 GHz with fabricated test vehicles of a TSV channel, which includes TSVs, bumps, and RDLs. Based on the proposed scalable model, we analyze the electrical behaviors of a TSV channel with design parameter variations in the frequency domain. According to the frequency-domain analysis, the capacitive effect of a TSV is dominant under 2 GHz. On the other hand, as frequency increases over 2 GHz, the inductive effect from the RDLs becomes significant. The frequency dependent loss of a TSV channel, which is capacitive and resistive, is also analyzed in the time domain by eye-diagram measurements. Due to the frequency dependent loss, the voltage and timing margins decrease as the data rate increases.
Preparation and characterization of rf sputtered indium tin oxide films (1985)

Indium tin oxide films have been grown by rf sputtering at various Ar-O2 mixtures, at low substrate temperatures (200 °C), and deposition rates (25 Å/min), followed by post deposition annealing (at 350 °C) in different ambients (O2, N2, and cracked ammonia). Influence of a reactive gas (oxygen) on the sputtering rate of a metallic (indium/tin) alloy target has been investigated. Growth parameters and annealing conditions have been optimized. The films were characterized by electron and x-ray diffraction, scanning electron microscopy, and transmittance as a function of wavelength. The effect of heat treatment in various environments on the structural, electrical, and optical properties has been investigated. Effect of a new annealing ambient, cracked ammonia (reducing atmosphere), on the reactively sputtered oxide films is being reported for the first time. Cracked ammonia was found to be very effective and cheap and resulted in films of high quality (electrical and optical) with good structural properties. Films with low sheet resistances (Rs=30 Ω/⧠ at film thicknesses of 800 Å and Rs=8.5 Ω/⧠ at film thicknesses of 5000 Å) with high visible transmission (∼95%) have been achieved by annealing in cracked ammonia.
Therapeutic Targeting of the CBP/p300 Bromodomain Blocks the Growth of Castration-Resistant Prostate Cancer (2017)

Resistance invariably develops to antiandrogen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here, we report that the transcriptional coactivator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth <i>in vitro</i> and <i>in vivo</i> Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression. Our findings offer a preclinical proof of concept for small-molecule therapies to target the CBP/p300 bromodomain as a strategy to treat castration-resistant prostate cancer. <i>Cancer Res; 77(20); 5564-75. ©2017 AACR</i>.
Pathologic Characteristics of Transplanted Kidney Xenografts (2011)

For xenotransplantation to become a clinical reality, we need to better understand the mechanisms of graft rejection or acceptance. We examined pathologic changes in α1,3-galactosyltransferase gene-knockout pig kidneys transplanted into baboons that were treated with a protocol designed to induce immunotolerance through thymic transplantation (n=4) or were treated with long-term immunosuppressants (n=3). Hyperacute rejection did not occur in α1,3-galactosyltransferase gene-knockout kidney xenografts. By 34 days, acute humoral rejection led to xenograft loss in all three xenografts in the long-term immunosuppression group. The failing grafts exhibited thrombotic microangiopathic glomerulopathy with multiple platelet-fibrin microthrombi, focal interstitial hemorrhage, and acute cellular xenograft rejection. Damaged glomeruli showed IgM, IgG, C4d, and C5b-9 deposition. They also demonstrated endothelial cell death, diffuse endothelial procoagulant activation with high expression of tissue factor and vWF, and low expression of the ectonucleotidase CD39. In contrast, in the immunotolerance group, two of four grafts had normal graft function and no pathologic findings of acute or chronic rejection at 56 and 83 days. One of the remaining kidneys had mild but transient graft dysfunction with reversible, mild microangiopathic glomerulopathy, probably associated with preformed antibodies. The other kidney in the immunotolerance group developed unstable graft function at 81 days and developed chronic xenograft glomerulopathy. In summary, the success of pig-to-primate xenotransplantation may necessitate immune tolerance to inhibit acute humoral and cellular xenograft rejection.
&lt;title&gt;New 0.54 aperture i-line wafer stepper with field-by-field leveling combined with global alignment&lt;/title&gt; (1991)

i-line wafer steppers are evolving as established production tools, and it is evident that they will be used to realize features in the sub-half-micron region. Consequently, i-line steppers can be expected to be the equipment of choice for volume production of 16 MBit DRAMs and possibly the first generation of 64 Mbit devices, before the introduction of DUV lithography. However, for this sub-half-micron resolution, lenses with higher apertures and large field sizes will be required. In this paper a new family of wafer steppers is introduced, with a new mechanical frame design and modular architecture which can accommodate a family of large field i-line and deep UV lenses. Results from the first lens type with NAequals0.54 and a field diameter of 25.5 mm are described. To overcome the anticipated depth of focus problems on production wafers, a field-by-field leveling system is introduced, ensuring optimum focus over the whole image field. A challenging problem of wafer steppers using this option is the alignment accuracy during stepping of stage and active leveling of the wafer chuck. The stepper concept introduced here is able to realize the field-by-field leveling without the need for the throughput consuming field-by-field alignment. For that purpose a wafer stage with a new metrology system and improved accuracy has been designed, resulting in an overlay accuracy better than 85 nm in the global alignment mode. Simultaneously a throughput of more than 80 150 mm wafers per hour is realized. Along with the new lens and metrology concept, the stepper contains local environmental control systems performing better than class 1, to ensure clean handling of 8-inch wafers without the need for space consuming environmental enclosures. This paper reports practical results from the new stepper, including resist features below 0.4 micrometers , overlay measurements, particle control, as well as a general description of the new stepper architecture.
Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs (2009)

Deep sequencing technologies such as Illumina, SOLiD, and 454 platforms have become very powerful tools in discovering and quantifying small RNAs in diverse organisms. Sequencing small RNA fractions always identifies RNAs derived from abundant RNA species such as rRNAs, tRNAs, snRNA, and snoRNA, and they are widely considered to be random degradation products. We carried out bioinformatic analysis of deep sequenced HeLa RNA and after quality filtering, identified highly abundant small RNA fragments, derived from mature tRNAs that are likely produced by specific processing rather than from random degradation. Moreover, we showed that the processing of small RNAs derived from tRNA(Gln) is dependent on Dicer in vivo and that Dicer cleaves the tRNA in vitro.