gebhart/patrepeval huggingface dataset:
Inducible gene deletion in astroglia and radial glia—A valuable tool for functional and lineage analysis (2006)

Astrocytes are thought to play a variety of key roles in the adult brain, such as their participation in synaptic transmission, in wound healing upon brain injury, and adult neurogenesis. However, to elucidate these functions in vivo has been difficult because of the lack of astrocyte-specific gene targeting. Here we show that the inducible form of Cre (CreERT2) expressed in the locus of the astrocyte-specific glutamate transporter (GLAST) allows precisely timed gene deletion in adult astrocytes as well as radial glial cells at earlier developmental stages. Moreover, postnatal and adult neurogenesis can be targeted at different stages with high efficiency as it originates from astroglial cells. Taken together, this mouse line will allow dissecting the molecular pathways regulating the diverse functions of astrocytes as precursors, support cells, repair cells, and cells involved in neuronal information processing.
LRRK2 G2019S as a Cause of Parkinson's Disease in Ashkenazi Jews (2006)

To the Editor: Most cases of Parkinson's disease are considered sporadic and idiopathic, although there is evidence of familial aggregation, and several monogenic forms have been identified.1 Recen...
Thiol‐Click Chemistries for Responsive Neural Interfaces (2013)

Neural interfaces provide an electrical connection between computers and the nervous system: current penetrating devices are orders-of-magnitude stiffer than surrounding tissue. In this work, recent efforts in softening electronics and utilize thiol-ene and thiol-epoxy "click" reactions are built upon to incorporate fluid-sensitive hydrogen bonding into smart substrates for high electrode density neural interfaces. The modulus of these substrates drops more than two orders of magnitude in response to physiological conditions, despite fluid uptake of less than 6%, and can be tuned by the covalent crosslink density and degree of hydrogen bonding in the polymer network. Intracortical and intrafascicular electrode arrays are fabricated and characterized with impedance spectroscopy and cyclic voltammetry.
N-WASP and the Arp2/3 Complex Are Critical Regulators of Actin in the Development of Dendritic Spines and Synapses (2008)

Changes in the number, size, and shape of dendritic spines are associated with synaptic plasticity, which underlies cognitive functions such as learning and memory. This plasticity is attributed to reorganization of actin, but the molecular signals that regulate this process are poorly understood. In this study, we show neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the formation of dendritic spines and synapses in hippocampal neurons. N-WASP localized to spines and active, functional synapses as shown by loading with FM4-64 dye. Knock down of endogenous N-WASP expression by RNA interference or inhibition of its activity by treatment with a specific inhibitor, wiskostatin, caused a significant decrease in the number of spines and excitatory synapses. Deletion of the C-terminal VCA region of N-WASP, which binds and activates the actin-related protein 2/3 (Arp2/3) complex, dramatically decreased the number of spines and synapses, suggesting activation of the Arp2/3 complex is critical for spine and synapse formation. Consistent with this, Arp3, like N-WASP, was enriched in spines and excitatory synapses and knock down of Arp3 expression impaired spine and synapse formation. A similar defect in spine and synapse formation was observed when expression of an N-WASP activator, Cdc42, was knocked down. Thus, activation of N-WASP and, subsequently, the Arp2/3 complex appears to be an important molecular signal for regulating spines and synapses. Arp2/3-mediated branching of actin could be a mechanism by which dendritic spine heads enlarge and subsequently mature. Collectively, our results point to a critical role for N-WASP and the Arp2/3 complex in spine and synapse formation.
Decomposition Approach for Low-Rank Matrix Completion and Its Applications (2014)

In this paper, we describe a low-rank matrix completion method based on matrix decomposition. An incomplete matrix is decomposed into sub-matrices which are filled with a proposed trimming step and then are recombined to form a low-rank completed matrix. The divide-and-conquer approach can significantly reduce computation complexity and storage requirement. Moreover, the proposed decomposition method can be naturally incorporated into any existing matrix completion methods to attain further gain. Unlike most existing approaches, the proposed method is not based on norm minimization nor on SVD decomposition. This makes it possible to be applied beyond real domain and can be used in arbitrary fields, including finite fields. The effectiveness of our proposed method is demonstrated through extensive numerical results on randomly generated and real matrix completion problems and a concrete application-video denoising. The numerical experiments show that the algorithm can reliably solve a wide range of problems at a speed significantly faster than recent algorithms. In the proposed denoising approach, we present a patch-based video denoising algorithm by grouping similar patches and then formulating the problem of removing noise using a decomposition approach for low-rank matrix completion. Experiments show that the proposed approach robustly removes mixed noise such as impulsive noise, Poisson noise, and Gaussian noise from any natural noisy video. Moreover, our approach outperforms state-of-the-art denoising techniques such as VBM3D and 3DWTF in terms of both time and quality. Our technique also achieves significant improvement over time against other matrix completion methods.
Polyethylene Glycol-Based Synthetic Hydrogel Sealant for Closing Vitrectomy Wounds: An In Vivo and Histological Study (2016)

The PEG sealant may become an effective option for closing vitrectomy incisions including pediatric cases.
Expression and Purification of Native Human Granulocyte-Macrophage Colony-Stimulating Factor from an Escherichia coli Secretion Vector (1987)

The human granulocyte-macrophage colony stimulating factor (GM-CSF) was expressed and purified from a high-level Escherichia coli secretion vector. A cDNA fragment encoding mature GM-CSF was fused with the aid of a synthetic oligonucleotide to the E. coli outer membrane signal peptide (ompA) of the secretion expression vector pIN-III-ompA3. The primary construction, designated pLB5001, is under transcriptional control of the tandem lipoprotein promoter (lppP) lactose promoter-operator (lacPO), and is regulated by the lactose repressor. Upon induction, a polypeptide of MW = 14,600 was produced which had GM-CSF activity in a human bone marrow colony assay. The linker sequence between the ompA signal peptide and the amino terminus of the mature GM-CSF was removed by oligonucleotide-directed site-specific mutagenesis to produce GM-CSF with an authentic amino terminus. The resulting construct, designated pLB5001-4, expressed authentic GM-CSF with a specific activity similar to that observed for the pLB5001 specified GM-CSF. Both versions of GM-CSF were associated with the membrane fraction after osmotic shock, and were purified to homogeneity by DEAE-Sephacel chromatography, followed by reversed-phase HPLC. Amino acid sequencing from the amino terminus of the purified GM-CSF established that the ompA signal peptide was cleaved at its normal processing site in both cases.
Assembly site of bacteriophage f1 corresponds to adhesion zones between the inner and outer membranes of the host cell (1985)

Morphogenesis of the filamentous bacteriophage f1 occurred at adhesion zones between the inner and outer membranes of the host cell. Quantitation of adhesion zones in cells infected with mutant phage strains suggested that the phage gene I protein may be involved in the formation of adhesion zones for phage assembly.
Ultrathin gate oxide CMOS on [111] surface-oriented Si substrate (2002)

The properties of ultrathin gate oxides in the direct-tunneling regime and the characteristics of the related CMOS transistors on a [111] surface-oriented Si substrate were investigated and compared with those on a [100] substrate for the first time. It was confirmed that low field mobility of n-MOSFETs on the [111] substrate is smaller than that on the [100] substrate and that of p-MOSFETs on [111] is larger than that on [100] until the direct-tunneling gate oxide regime. It has been found that most of the electrical properties of MOSFETs, with the notable exception of mobility, become almost identical for [100] and [111] substrates when the oxide thickness is reduced to less than 2.0 nm. Some of the properties are quite different between the two substrates for the thicker oxide case. It has been found that the reliability of hot carrier injection and time-dependent dielectric breakdown (TDDB) of the oxides and MOSFETs on the [111] substrate is slightly better than that on the [100] substrate. In addition, the characteristics and reliability of oxides and MOSFETs on a wafer tilted 4/spl deg/ from [100] axis were investigated. It was found that there are few differences in the mobility between [100] and [100] 4/spl deg/ off substrates for both n- and p-MOSFET cases. The reliability of oxides or MOSFETs on the wafer was identical to that on normal [100] substrate. These results suggest that ultrathin gate oxide MOSFETs on Si surfaces with various orientations are likely to have practical applications. This is good news for possible future new structures of MOSFETs such as vertical or three-dimensional (3-D) MOSFETs.
Routes to High Energy Cathodes of Sodium‐Ion Batteries (2015)

Sodium‐ion batteries (SIBs) are now being actively developed as low cost and sustainable alternatives to lithium‐ion batteries (LIBs) for large‐scale electric energy storage applications. In recent years, various inorganic and organic Na compounds, mostly mimicked from their Li counterparts, have been synthesized and tested for SIBs, and some of them indeed demonstrate comparable specific capacity to the presently developed LIB electrodes. However, the lack of suitable cathode materials is still a major obstacle to the commercial development of SIBs. Here, we present a brief review on the recent developments of SIB cathodes, with a focus on low cost and high energy density materials (&gt; 450 Wh kg −1 vs Na) together with discussion of their Na‐storage mechanisms. The considerable differences in the structural requirements for Li‐ and Na‐storage reactions mean that it is not sufficient to design SIB cathode materials by simply mimicking LIB materials, and therefore great efforts are needed to discover new materials and reaction mechanisms to further develop variable cathodes for advanced SIB technology. Some directions for future research and possible strategies for building advanced cathode materials are also proposed here.
Lipid Internal Dynamics Probed in Nanodiscs (2017)

Nanodiscs offer a very promising tool to incorporate membrane proteins into native-like lipid bilayers and an alternative to liposomes to maintain protein functions and protein-lipid interactions in a soluble nanoscale object. The activity of the incorporated membrane protein appears to be correlated to its dynamics in the lipid bilayer and by protein-lipid interactions. These two parameters depend on the lipid internal dynamics surrounded by the lipid-encircling discoidal scaffold protein that might differ from more unrestricted lipid bilayers observed in vesicles or cellular extracts. A solid-state NMR spectroscopy investigation of lipid internal dynamics and thermotropism in nanodiscs is reported. The gel-to-fluid phase transition is almost abolished for nanodiscs, which maintain lipid fluid properties for a large temperature range. The addition of cholesterol allows fine-tuning of the internal bilayer dynamics by increasing chain ordering. Increased site-specific order parameters along the acyl chain reflect a higher internal ordering in nanodiscs compared with liposomes at room temperature; this is induced by the scaffold protein, which restricts lipid diffusion in the nanodisc area.
Synaptic Targeting by Alzheimer's-Related Amyloid β Oligomers (2004)

The cognitive hallmark of early Alzheimer's disease (AD) is an extraordinary inability to form new memories. For many years, this dementia was attributed to nerve-cell death induced by deposits of fibrillar amyloid beta (Abeta). A newer hypothesis has emerged, however, in which early memory loss is considered a synapse failure caused by soluble Abeta oligomers. Such oligomers rapidly block long-term potentiation, a classic experimental paradigm for synaptic plasticity, and they are strikingly elevated in AD brain tissue and transgenic-mouse AD models. The current work characterizes the manner in which Abeta oligomers attack neurons. Antibodies raised against synthetic oligomers applied to AD brain sections were found to give diffuse stain around neuronal cell bodies, suggestive of a dendritic pattern, whereas soluble brain extracts showed robust AD-dependent reactivity in dot immunoblots. Antigens in unfractionated AD extracts attached with specificity to cultured rat hippocampal neurons, binding within dendritic arbors at discrete puncta. Crude fractionation showed ligand size to be between 10 and 100 kDa. Synthetic Abeta oligomers of the same size gave identical punctate binding, which was highly selective for particular neurons. Image analysis by confocal double-label immunofluorescence established that >90% of the punctate oligomer binding sites colocalized with the synaptic marker PSD-95 (postsynaptic density protein 95). Synaptic binding was accompanied by ectopic induction of Arc, a synaptic immediate-early gene, the overexpression of which has been linked to dysfunctional learning. Results suggest the hypothesis that targeting and functional disruption of particular synapses by Abeta oligomers may provide a molecular basis for the specific loss of memory function in early AD.
Characterization of DC-SIGN/R Interaction with Human Immunodeficiency Virus Type 1 gp120 and ICAM Molecules Favors the Receptor's Role as an Antigen-Capturing Rather than an Adhesion Receptor (2005)

The dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin binding receptor (DC-SIGN) was shown to bind human immunodeficiency virus type 1 (HIV-1) viral envelope protein gp120 and proposed to function as a Trojan horse to enhance trans-virus infection to host T cells. To better understand the mechanism by which DC-SIGN and DC-SIGNR selectively bind HIV-1 gp120, we constructed a series of deletion mutations in the repeat regions of both receptors. Different truncated receptors exist in different oligomeric forms. The carbohydrate binding domain without any repeats was monomeric, whereas the full extracellular receptors existed as tetramers. All reconstituted receptors retained their ability to bind gp120. The dissociation constant, however, differed drastically from micromolar values for the monomeric receptors to nanomolar values for the tetrameric receptors, suggesting that the repeat region of these receptors contributes to the avidity of gp120 binding. Such oligomerization may provide a mechanism for the receptor to selectively recognize pathogens containing multiple high-mannose-concentration carbohydrates. In contrast, the receptors bound to ICAMs with submicromolar affinities that are similar to those of two nonspecific cell surface glycoproteins, FcgammaRIIb and FcgammaRIII, and the oligomerization of DC-SIGNR resulted in no increase in binding affinity to ICAM-3. These findings suggest that DC-SIGN may not discriminate other cell surface glycoproteins from ICAM-3 binding. The pH dependence in DC-SIGN binding to gp120 showed that the receptor retained high-affinity gp120 binding at neutral pH but lost gp120 binding at pH 5, suggesting a release mechanism of HIV in the acidic endosomal compartment by DC-SIGN. Our work contradicts the function of DC-SIGN as a Trojan horse to facilitate HIV-1 infection; rather, it supports the function of DC-SIGN/R (a designation referring to both DC-SIGN and DC-SIGNR) as an antigen-capturing receptor.
Reaching into the Major Groove of B-DNA:  Synthesis and Nucleic Acid Binding of a Neomycin−Hoechst 33258 Conjugate (2003)

Synthesis of a neomycin-Hoechst 33258 conjugate is reported. The conjugate combines the ligands known to selectively bind in the duplex and the triplex groove. The conjugate stabilizes DNA duplex over DNA triplex. The conjugate selectively stabilizes the DNA duplex (in the presence of salt), with as little as 2 muM of the ligand leading to a DeltaTm of 25 degrees C.
Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury (2015)

The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.
Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage (2000)

The mRNA upregulation of these proteins indicates that activation of rho A/rho kinase-related signal transduction pathways is involved in the development of long-lasting contraction of cerebral arteries after SAH.
Nitric oxide and TNF-α trigger colonic inflammation and carcinogenesis inHelicobacter hepaticus-infected,Rag2-deficient mice (2009)

Recombinase-activating gene-2-deficient (Rag2(-/-)) mice lacking functional lymphocytes provide a useful model of chronic inflammatory bowel disease-emulating events in human colon cancer. Infection of Rag2(-/-) mice with Helicobacter hepaticus led to accumulation of macrophages and neutrophils in the colon, a process temporally related to up-regulation of tissue inducible nitric oxide synthase (iNOS) expression at the site of infection and increased nitric oxide (NO) production, as evidenced by urinary excretion of nitrate. Progressive development of increasingly severe inflammation, hyperplasia, dysplasia, and cancer accompanied these changes. Concurrent administration of an iNOS inhibitor prevented NO production and abrogated epithelial pathology and inhibited the onset of cancer. The presence of Gr-1(+) neutrophils and elevated tumor necrosis factor-alpha (TNF-alpha) expression in colon were required for increased iNOS expression and cancer, whereas interleukin-10 (IL-10) down-regulated TNF-alpha and iNOS expression and suppressed cancer. Anti-inflammatory CD4(+) regulatory lymphocytes also down-regulated iNOS and reduced cancer formation. Collectively, these results confirm essential roles for inflammation, increased TNF-alpha expression, and elevated NO production in colon carcinogenesis.
Overproduction of polyomavirus middle T antigen in mammalian cells through the use of an adenovirus vector (1987)

To overproduce biologically active polyomavirus middle T antigen, we used an adenovirus vector and human 293 cells as hosts. Two helper-independent recombinant adenoviruses were isolated that contain a hybrid transcription unit, in differing orientations, at a site in the adenovirus genome from which the E1a and most of the E1b transcription units have been deleted. The hybrid transcription unit consists of the adenovirus type 2 major late promoter and tripartite leader and a cDNA segment capable of encoding polyomavirus middle T antigen and accompanying 3' RNA-processing signals. Both recombinant viruses were stable and replicated to high titers in human 293 cells. The polyomavirus sequences were expressed, predominantly at late times after infection of 293 cells, to yield mRNAs that encoded middle T antigen. One of the recombinant viruses also expressed a middle T antigen-related protein in 293 cells. The latter was translated from one of several novel mRNA species that resulted from aberrant splicing and incomplete RNA processing of precursor RNA transcripts. Comparison of the amount of middle T antigen produced in 3T6 cells infected with polyomavirus with that in 293 cells infected with either of the recombinant adenoviruses, under optimal conditions for each system, revealed at least a 10-fold greater yield of the protein on a per-cell basis in the latter system than in the former. The recombinant-virus-encoded middle T antigen was biologically active, as evidenced by its ability to associate with and serve as a substrate for human pp60c-src. The functionality of the middle T antigen was further confirmed by demonstrating that both recombinant viruses efficiently transformed Rat-1 cells. These recombinant viruses will be useful to overproduce middle T antigen and to introduce the polyomavirus oncogene into a wide variety of mammalian cells.
Pituitary Adenylate Cyclase-Activating Polypeptide Is Required for the Development of Spinal Sensitization and Induction of Neuropathic Pain (2004)

The prolonged sensitization of pain transmission after nerve injury by increasing excitability of spinal neurons and thereby promoting repair is an adaptive response of the body. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the nervous system and implicated in neurotransmission, neural plasticity, and neurotrophic actions. Although PACAP is distributed in the spinal cord and dorsal root ganglia, a role of PACAP in pain responses remains essentially unknown. Here we show that mice lacking the PACAP gene (PACAP-/-) did not exhibit inflammatory pain induced by intraplantar injection of carrageenan or neuropathic pain induced by L5 spinal nerve transection, whereas they did retain normal nociceptive responses. Intrathecal administration of NMDA induced mechanical allodynia in wild-type mice, but not in PACAP-/- mice. The NMDA-induced allodynia in PACAP-/- mice was reproduced by simultaneous intrathecal injection of PACAP with NMDA. Concomitant with the increase in PACAP immunoreactivity after nerve injury, NADPH-dependent nitric oxide synthase (NOS) activity visualized by NADPH diaphorase histochemistry markedly increased in the superficial layer of the spinal cord of wild-type mice, which was not observed in PACAP-/- mice. Simultaneous addition of PACAP and NMDA caused translocation of neuronal NOS from the cytosol to the membrane and stimulated NO production in vitro. These results demonstrate that PACAP might promote the functional coupling of neuronal NOS to NMDA receptors for both inflammatory and neuropathic pain to occur.
Exploiting deferred destruction an analysis of read-copy-update techniques in operating system kernels (2004)

Marked differences in cases of stage I cervical carcinoma, dependent on the extent of tissue involvement, are demonstrated by retrospective, prognostic as well als by prospective, immunological investigations. It seems recommendable to separate cases of a newly-defried stage Ib from stage Ic. The prognosis of these stage Ic cases is even worse than of stage IIa cases. As this subgrouping can be carried out only post-operatively, the preoperative assignment of cases to different stages should not be used for assessing the operative results.