gebhart/patrepeval huggingface dataset:
Identifying the Molecular Phenotype of Renal Progenitor Cells (2004)

Although many of the molecular interactions in kidney development are now well understood, the molecules involved in the specification of the metanephric mesenchyme from surrounding intermediate mesoderm and, hence, the formation of the renal progenitor population are poorly characterized. In this study, cDNA microarrays were used to identify genes enriched in the murine embryonic day 10.5 (E10.5) uninduced metanephric mesenchyme, the renal progenitor population, in comparison with more rostral derivatives of the intermediate mesoderm. Microarray data were analyzed using R statistical software to determine accurately genes differentially expressed between these populations. Microarray outliers were biologically verified, and the spatial expression pattern of these genes at E10.5 and subsequent stages of early kidney development was determined by RNA in situ hybridization. This approach identified 21 genes preferentially expressed by the E10.5 metanephric mesenchyme, including Ewing sarcoma homolog, 14-3-3 theta, retinoic acid receptor-alpha, stearoyl-CoA desaturase 2, CD24, and cadherin-11, that may be important in formation of renal progenitor cells. Cell surface proteins such as CD24 and cadherin-11 that were strongly and specifically expressed in the uninduced metanephric mesenchyme and mark the renal progenitor population may prove useful in the purification of renal progenitor cells by FACS. These findings may assist in the isolation and characterization of potential renal stem cells for use in cellular therapies for kidney disease.
A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy (2003)

5q spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and the leading genetic cause of infantile death. Patients lack a functional survival of motor neurons (SMN1) gene, but carry one or more copies of the highly homologous SMN2 gene. A homozygous knockout of the single murine Smn gene is embryonic lethal. Here we report that in the absence of the SMN2 gene, a mutant SMN A2G transgene is unable to rescue the embryonic lethality. In its presence, the A2G transgene delays the onset of motor neuron loss, resulting in mice with mild SMA. We suggest that only in the presence of low levels of full-length SMN is the A2G transgene able to form partially functional higher order SMN complexes essential for its functions. Mild SMA mice exhibit motor neuron degeneration, muscle atrophy, and abnormal EMGs. Animals homozygous for the mutant transgene are less severely affected than heterozygotes. This demonstrates the importance of SMN levels in SMA even if the protein is expressed from a mutant allele. Our mild SMA mice will be useful in (a) determining the effect of missense mutations in vivo and in motor neurons and (b) testing potential therapies in SMA.
A paired-image radiation transport model for skeletal dosimetry. (2005)

The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton, thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high beta-emitters.
Spectroscopic studies of single‐stranded DNA ligands and oxazole yellow dyes (1998)

Interactions between short single-stranded DNA ligands and fluorescent DNA indicator dyes were used to investigate binding selectivity of the ligands. Conformational differences among four DNA ligands of different sequence and structure, including two that form a G-quartet and two that do not, were confirmed by circular dichroism spectroscopy. Their interactions with indicator dyes YO-pro-1 iodide (YO) and YOYO-1 iodide (YOYO) were probed using measurements of dye absorbance; induced circular dichroism; and fluorescence spectra, anisotropy, and lifetime. Equilibrium binding constants and stoichiometry were determined as well. Results indicate significant differences among the dye interactions and binding stoichiometries of the four ligands. One of the G-quartet forming ligands, a 20-mer of sequence 5′-GGTTTT-GGTTTTGGTTTTGG-3′, shows distinctly different interactions from the other three ligands, all of which are 15-mers. These studies illustrate the importance of sequence and conformation in determining the binding interactions of short single-stranded DNA. © 1998 John Wiley & Sons, Inc. Biospectroscopy 4: 27–35, 1998
The urine output definition of acute kidney injury is too liberal (2013)

A 6-hour urine output threshold of 0.3 ml/kg/hour best associated with mortality and dialysis, and was independently predictive of both hospital mortality and 1-year mortality. This suggests that the current AKI urine output definition is too liberally defined. Shorter urine collection intervals may be used to define AKI using lower urine output thresholds.
Quantification of intracompartmental pressure and volume under plaster casts. (1981)

This study demonstrates the need in clinical practice for continued evaluation and monitoring of a limb even after the cast has been completely removed because of signs and symptoms of a compartmental syndrome.
Fast Multiplication: Algorithms and Implementations (1994)

This thesis investigates methods of implementing binary multiplication with the smallest possible latency. The principle area of concentration is on multipliers with lengths of 53 bits, which makes the results suitable for IEEE-754 double precision multiplication.
Low latency demands high performance circuitry, and small physical size to limit propagation delays. VLSI implementations are the only available means for meeting these two requirements, but efficient algorithms are also crucial. An extension to Booth's algorithm for multiplication (redundant Booth) has been developed, which represents partial products in a partially redundant form. This redundant representation can reduce or eliminate the time required to produce hard multiples (multiples that require a carry propagate addition) required by the traditional higher order Booth algorithms. This extension reduces the area and power requirements of fully parallel implementations, but is also as fast as any multiplication method yet reported.
In order to evaluate various multiplication algorithms, a software tool has been developed which automates the layout and optimization of parallel multiplier trees. The tool takes into consideration wire and asymmetric input delays, as well as gate delays, as the tree is built. The tool is used to design multipliers based upon various algorithms, using both Booth encoded, non-Booth encoded and the new extended Booth algorithms. The designs are then compared on the basis of delay, power, and area.
For maximum speed, the designs are based upon a 0.6$\mu$ BiCMOS process using emitter coupled logic (ECL). The algorithms developed in this thesis make possible 53 x 53 multipliers with a latency of less than 2.6 nanoseconds @ 10.5 Watts and a layout area of 13mm$\sp2$. Smaller and lower power designs are also possible, as illustrated by an example with a latency of 3.6 nanoseconds @ 5.8 W, and an area of 8.9mm$\sp2$. The conclusions based upon ECL designs are extended where possible to other technologies (CMOS).
Crucial to the performance of multipliers are high speed carry propagate adders. A number of high speed adder designs have been developed, and the algorithms and design of these adders are discussed.
The implementations developed for this study indicate that traditional Booth encoded multipliers are superior in layout area, power, and delay to non-Booth encoded multipliers. Redundant Booth encoding further reduces the area and power requirements. Finally, only half of the total multiplier delay was found to be due to the summation of the partial products. The remaining delay was due to wires and carry propagate adder delays.
26.3: Multicolor Pixel Patterning of Light‐Emitting Polymers by Ink‐Jet Printing (1999)

Abstract In order to realize a multicolor display, we tried to pattern three different colors to make pixels by using ink‐jet technology. Light emitting polymer, poly( p ‐phenylene vinylene) (PPV), was successfully formulated into inks for ink‐jet printing. Those inks showed a good ink‐jetting behavior and became a good light emitting film. By combining the ink‐jet printing with the self‐patterning ability of the substrate, in which the hydrophilic and hydrophobic region is alternately constructed, an ink droplet can be patterned into the narrow pixel gap of 10 μm with precision of 1 μm order. We developed stacked structures combining PPV with Polyfluorene. It was confirmed that energy conversion from the wider gap layer to the smaller one occurred. As a result, we demonstrated the three color electroluminescence from the small pixels. This is the first demonstration of the fine pixel patterning of the multicolor light emitting polymers by ink‐jet technology.
Calcitonin gene-related peptide as a regulator of neuronal CaMKII–CREB, microglial p38–NFκB and astroglial ERK–Stat1/3 cascades mediating the development of tolerance to morphine-induced analgesia (2010)

Tolerance to morphine-induced analgesia is an intractable phenomenon, often hindering its prolonged applications in the clinics. The enhanced pronociceptive actions of spinal pain-related molecules such as calcitonin gene-related peptide (CGRP) may underlie this phenomenon and could be a promising target for intervention. We demonstrate here how CGRP regulates the development of morphine analgesic tolerance at the spinal level. A 7-day treatment with morphine led to tolerance to its analgesic effects and enhanced expression of CGRP and its receptor subunits calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1). Activation of several cell-type-specific kinase transcription factor cascades is required to mediate this tolerance, including calcium/calmodulin-dependent protein kinase II (CaMKII) and cAMP response element-binding protein (CREB) in neurons, p38 and nuclear factor kappa B (NFκB) in microglia and extracellular signal-regulated protein kinase (ERK) and signal transducer and activator of transcription 1 and 3 (Stat1/3) in astrocytes, because inhibitors of CaMKII, p38 and ERK pathways correspondingly reduced the increases in phosphorylated CREB, acetylated-NFκB and phosphorylated Stat1/3 levels and attenuated the development of tolerance. Interestingly, these cascades were linked to the regulation of glutamatergic N-methyl-d-aspartate (NMDA) receptor expression. Chronic morphine-induced behavioural responses and biochemical events were all subjugated to modulation by disrupting CGRP receptor signaling. Together, these data suggest that CGRP contributes to the development of tolerance to morphine-induced analgesia by regulating the activation of the neuronal CaMKII-CREB, microglial p38-NFκB and astroglial ERK-Stat1/3 cascades. Targeting CGRP-associated signaling molecules may prolong or restore morphine's analgesic properties upon a chronic exposure.
Fluorometric measurements of conformational changes in glutamate transporters (2004)

Glutamate transporters remove glutamate from the synaptic cleft to maintain efficient synaptic communication between neurons and to prevent extracellular glutamate concentrations from reaching neurotoxic levels (1). It is thought that glutamate transporters mediate glutamate transport through a reaction cycle with conformational changes between the two major access states that alternatively expose glutamate-binding sites to the extracellular or to the intracellular solution. However, there is no direct real-time evidence for the conformational changes predicted to occur during the transport cycle. In the present study, we used voltage-clamp fluorometry to measure conformational changes in the neuronal excitatory amino acid transporter (EAAT) 3 glutamate transporter covalently labeled with a fluorescent reporter group. Alterations in glutamate and cotransported ion concentrations or in the membrane voltage induced changes in the fluorescence that allowed detection of conformational rearrangements occurring during forward and reverse transport. In addition to the transition between the two major access states, our results show that there are significant Na(+)-dependent conformational changes preceding glutamate binding. We furthermore show that Na(+) and H(+) are cotransported with glutamate in the forward part of the transport cycle. The data further suggest that an increase in proton concentrations slows the reverse transport of glutamate, which may play a neuro-protective role during ischemia.
Transmembrane Molecular Pump Activity of Niemann-Pick C1 Protein (2000)

Niemann-Pick C1 (NPC1) disease is characterized by cholesterol accumulation in lysosomes and aberrant feedback regulation of cellular cholesterol homeostasis. We provide evidence that the NPC1 protein has homology with the resistance-nodulation-division (RND) family of prokaryotic permeases and may normally function as a transmembrane efflux pump. Studies of acriflavine loading in normal and NPC1 fibroblasts indicated that NPC1 uses a proton motive force to remove accumulated acriflavine from the endosomal/lysosomal system. Expression of NPC1 in Escherichia coli (i) facilitated the transport of acriflavine across the plasma membrane, causing cytosolic accumulation, and (ii) resulted in transport of oleic acid but not cholesterol or cholesterol-oleate across the plasma membrane. These studies establish NPC1 as a eukaryotic member of the RND permease family.
Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene (2000)

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and life-threatening cardiomyopathy with conduction blocks. We recently identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be implicated in the autosomal dominant form of EDMD. Here, we report on the variability of the phenotype and spectrum of LMNA mutations in 53 autosomal dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve of the 53 patients showed cardiac involvement exclusively, although the remaining 41 all showed muscle weakness and contractures. We were able to identify a common phenotype among the patients with skeletal muscle involvement, consisting of humeroperoneal wasting and weakness, scapular winging, rigidity of the spine, and elbow and Achilles tendon contractures. The disease course was generally slow, but we observed either a milder phenotype characterized by late onset and a mild degree of weakness and contractures or a more severe phenotype with early presentation and a rapidly progressive course in a few cases. Mutation analysis identified 18 mutations in LMNA (i.e., 1 nonsense mutation, 2 deletions of a codon, and 15 missense mutations). All the mutations were distributed between exons 1 and 9 in the region of LMNA that is common to lamins A and C. LMNA mutations arose de novo in 76% of the cases; 2 of these de novo mutations were typical hot spots, and 2 others were identified in 2 unrelated cases. There was no clear correlation between the phenotype and type or localization of the mutations within the gene. Moreover, a marked inter- and intra-familial variability in the clinical expression of LMNA mutations exists, ranging from patients expressing the full clinical picture of EDMD to those characterized only by cardiac involvement, which points toward a significant role of possible modifier genes in the course of this disease. In conclusion, the high proportion of de novo mutations together with the large spectrum of both LMNA mutations and the expression of the disease should now prompt screening for LMNA in familial and sporadic cases of both EDMD and dilated cardiomyopathy associated with conduction system disease.
Drug Discovery Today (2003)

In recent years, tools for the development of new drugs have been dramatically improved. These include genomic and proteomic research, numerous biophysical methods, combinatorial chemistry and screening technologies. In addition, early ADMET studies are employed in order to significantly reduce the failure rate in the development of drug candidates. As a consequence, the lead finding, lead optimization and development process has gained marked enhancement in speed and efficiency. In parallel to this development, major pharma companies are increasingly outsourcing many components of drug discovery research to biotech companies. All these measures are designed to address the need for a faster time to market. New screening methodologies have contributed significantly to the efficiency of the drug discovery process. The conventional screening of single compounds or compound libraries has been dramatically accelerated by high throughput screening methods. In addition, in silico screening methods allow the evaluation of virtual compounds. A wide range of new lead finding and lead optimization opportunities result from novel screening methods by NMR, which are the topic of this review article.
Endoplasmic Reticulum Stress and the Unfolded Protein Response in Cellular Models of Parkinson's Disease (2002)

6-hydroxydopamine, 1-methyl-4-phenyl-pyridinium (MPP+), and rotenone cause the death of dopaminergic neurons in vitro and in vivo and are widely used to model Parkinson's disease. To identify regulated genes in such models, we performed serial analysis of gene expression on neuronal PC12 cells exposed to 6-hydroxydopamine. This revealed a striking increase in transcripts associated with the unfolded protein response. Immunoblotting confirmed phosphorylation of the key endoplasmic reticulum stress kinases IRE1alpha and PERK (PKR-like ER kinase) and induction of their downstream targets. There was a similar response to MPP+ and rotenone, but not to other apoptotic initiators. As evidence that endoplasmic reticulum stress contributes to neuronal death, sympathetic neurons from PERK null mice in which the capacity to respond to endoplasmic reticulum stress is compromised were more sensitive to 6-hydroxydopamine. Our findings, coupled with evidence from familial forms of Parkinson's disease, raise the possibility of widespread involvement of endoplasmic reticulum stress and the unfolded protein response in the pathophysiology of this disease.
Prolonged radioprotective activity of WR-2721 linked to dextran. (1990)

The radioprotective agent WR-2721 was linked to dextran and poly(glutamic acid) respectively, to obtain a prolonged radioprotective ability. Male mice were administered these water soluble polymer conjugates one to 72 hours prior to a whole body irradiation with X-rays. A prolongation of radioprotective efficiency was achieved with two dextran-(WR-2721)-conjugates. For a period of 24 hours between administration, and irradiation dose reduction factors of 1.14 +/- 0.04 and 1.10 +/- 0.03 respectively were found. After 72 hours, no protective effect was observed. Histopathological investigations of the liver for formation of tumors 200 to 600 days after irradiation seems to indicate that a protective effect is not produced by the dextran-(WR-2721)-conjugates.
High-Level Penicillin Resistance among Isolates of Enterococci (1989)

Enterococcus faecium accounts for a notable proportion of clinical enterococcal isolates. Many strains from patients at our institution, as well as from patients at other institutions throughout the country, are highly resistant to penicillin. Because high-level penicillin resistance has important therapeutic implications, periodic surveillance and MIC testing of significant enterococcal isolates, especially E. faecium, are suggested.
Neurocognitive effects of adjunctive levetiracetam in children with partial‐onset seizures: A randomized, double‐blind, placebo‐controlled, noninferiority trial (2009)

Neurocognitive effects were no different in pediatric patients with POS treated with adjunctive levetiracetam or placebo. Levetiracetam was effective and well tolerated.
Synthetic Ribonucleotide Analogues for RNA Structure-Function Studies (1995)

Abstract The use of synthetic ribonucleotide analogues in structure-function analysis of RNA is reviewed with particular reference to the roles of specific RNA functional groups in hammerhead ribozyme cleavage and in the interactions of the HIV-1 gene regulatory proteins tat and rev with their respective RNA targets TAR and RRE.
Extradural Sensory Rhizotomy in the Management of Chronic Lumbar Radiculopathy (1997)

The results of the rhizotomy procedures deteriorated over time. Possible reasons for the failure, other than temporal deterioration, were anatomic factors and lack of specificity of diagnostic techniques, specifically selective nerve root sheath injection. At this point rhizotomy cannot be recommended with any confidence whatsoever in the setting of chronic lumbar radiculopathy after lumbar surgery.
Protein Binding and the Electronic Properties of Iron(II) Complexes: An Electrochemical and Optical Investigation of Outer Sphere Effects (2009)

Metalloenzymes and electron transfer proteins influence the electrochemical properties of metal cofactors by controlling the second-sphere environment of the protein active site. Properties that tune this environment include the dielectric constant, templated charge structure, van der Waals interactions, and hydrogen bonds. By systematically varying the binding of a redox-active ligand with a protein, we can evaluate how these noncovalent interactions alter the electronic structure of the bound metal complex. For this study, we employ the well-characterized avidin−biotin conjugate as the protein−ligand system, and have synthesized solvatochromic biotinylated and desthiobiotinylated iron(II) bipyridine tetracyano complexes ([Fe(BMB)(CN)4]2− (1) and [Fe(DMB)(CN)4]2− (2)). The binding affinities of 1 and 2 with avidin are 3.5 × 107 M−1 and 1.5 × 106 M−1, respectively. The redox potentials of 1 and 2 (333 mV and 330 mV) shift to 193 mV and 203 mV vs Ag/AgCl when the complex is bound to avidin and adsorbed to a monolayer-coated gold electrode. Upon binding to avidin, the MLCT1 band red-shifts 20 nm for 1 and 10 nm for 2. Similarly, the MLCT2 band for 1 red-shifts 7 nm and the band for 2 red-shifts 6 nm. For comparison, the electronic properties of 1 and 2 were investigated in organic solvents, and similar shifts in the MLCT bands and redox potentials were observed. An X-ray crystal structure of 1 bound to avidin was obtained, and molecular dynamics simulations were performed to analyze the protein environment of the protein-bound transition metal complexes. Our studies demonstrate that changes in the binding affinity of a ligand-receptor pair influence the outer-sphere coordination of the ligand, which in turn affects the electronic properties of the bound complex.
Imaging of RNA in Bacteria with Self-Ligating Quenched Probes (2002)

We report on the application of a new class of oligonucleotide reporter probes, QUAL probes, that "light up" when a nucleophilic phosphorothioate probe binds adjacent to a dabsyl-quenched probe. These self-ligating DNA probes were used for sequence-specific detection of 16S rRNA in Escherichia coli cells. Strong fluorescence was observed only when the phosphorothioate and quenched dabsyl probes bind side-by-side on a 16S rRNA target. The results demonstrate the use of QUAL probes to detect specific RNA sequences in bacterial cells without enzymes and without washing steps.