gebhart/patrepeval huggingface dataset:
Reversing cognitive–motor impairments in Parkinson’s disease patients using a computational modelling approach to deep brain stimulation programming (2010)

Deep brain stimulation in the subthalamic nucleus is an effective and safe surgical procedure that has been shown to reduce the motor dysfunction of patients with advanced Parkinson's disease. Bilateral subthalamic nucleus deep brain stimulation, however, has been associated with declines in cognitive and cognitive-motor functioning. It has been hypothesized that spread of current to nonmotor areas of the subthalamic nucleus may be responsible for declines in cognitive and cognitive-motor functioning. The aim of this study was to assess the cognitive-motor performance in advanced Parkinson's disease patients with subthalamic nucleus deep brain stimulation parameters determined clinically (Clinical) to settings derived from a patient-specific computational model (Model). Data were collected from 10 patients with advanced Parkinson's disease bilaterally implanted with subthalamic nucleus deep brain stimulation systems. These patients were assessed off medication and under three deep brain stimulation conditions: Off, Clinical or Model based stimulation. Clinical stimulation parameters had been determined based on clinical evaluations and were stable for at least 6 months prior to study participation. Model-based parameters were selected to minimize the spread of current to nonmotor portions of the subthalamic nucleus using Cicerone Deep Brain Stimulation software. For each stimulation condition, participants performed a working memory (n-back task) and motor task (force tracking) under single- and dual-task settings. During the dual-task, participants performed the n-back and force-tracking tasks simultaneously. Clinical and Model parameters were equally effective in improving the Unified Parkinson's disease Rating Scale III scores relative to Off deep brain stimulation scores. Single-task working memory declines, in the 2-back condition, were significantly less under Model compared with Clinical deep brain stimulation settings. Under dual-task conditions, force tracking was significantly better with Model compared with Clinical deep brain stimulation. In addition to better overall cognitive-motor performance associated with Model parameters, the amount of power consumed was on average less than half that used with the Clinical settings. These results indicate that the cognitive and cognitive-motor declines associated with bilateral subthalamic nucleus deep brain stimulation may be reversed, without compromising motor benefits, by using model-based stimulation parameters that minimize current spread into nonmotor regions of the subthalamic nucleus.
Shot-noise limited localization of single 20 nm gold particles with nanometer spatial precision within microseconds (2014)

Single-particle tracking (SPT) is a powerful approach to investigate dynamics without ensemble average. Continuing effort has been made to track smaller particles with better spatial precision at higher speed. In this work, we demonstrate SPT of 20 nm gold nanoparticle (GNP) with 2 nm spatial precision up to 500 kHz by using microsecond interferometric scattering (μs-iSCAT) microscopy. The linear scattering signal from single GNPs is detected by a high-speed CMOS camera via interference. Through this homodyne detection, shot-noise limited sensitivity, and therefore optimal localization precision are achieved at high speed where considerable electronic noise is present. Using μs-iSCAT microscopy, we observe anomalous diffusion of GNPs labeled to lipid molecules in a supported bilayer membrane prepared on a glass substrate. The combination of nanometer spatial precision and microsecond temporal resolution provides the opportunity to study rapid motions of nano-objects on molecular scale with unprecedented clarity.
Suppression of delayed-type hypersensitivity reactions and lymphokine production by cyclosporin A in the mouse. (1983)

Two consecutive daily i.m. injections of cyclosporin A (Cs A) (greater than 50 mg/kg) inhibited delayed type hypersensitivity (DTH) responses in mice immunized with SRBC. Maximal suppression was observed when Cs A was administered 24 and 48 h after sensitization. Culture of spleen cells from these animals with antigen, insoluble concanavalin A (iCon A) or PHA revealed inhibition of the production of two lymphokines: that inducing macrophage procoagulant activity (MPCA) and macrophage chemotactic factor (LDCF). The inhibitory effect on lymphokine production was not due to depletion of T cells. In vitro, 25 ng/ml Cs A suppressed T cell proliferative responses to antigen and mitogen but much higher doses were required to impair the response to LPS. Similar doses of Cs A also suppressed lymphokine production, but the responses of macrophages to these lymphokines was unaffected, even at doses which totally inhibited lymphokine production. Production of interleukin 1 by LPS stimulated macrophages was inhibited by Cs A only at concentrations much greater than those required to suppress lymphokine production.
Mantle cell lymphomas express a distinct genetic signature affecting lymphocyte trafficking and growth regulation as compared with subpopulations of normal human B cells. (2002)

Differential gene expression analysis, using high-density microarray chips, demonstrated 300-400 genes to be deregulated in mantle cell lymphomas (MCLs) compared with normal B-cell populations. To investigate the significance of this genetic signature in lymphoma etiology and diagnostics, we selected 90 annotated genes involved in a number of cellular functions for further analysis. Our findings demonstrated a normal gene expression of CCR7, which indicated a normal homing to primary follicles, which was in contrast to other receptors for B-cell trafficking, such as a significant down-regulation for CXCR5 and CCR6, as well as down-regulation of IL4R involved in differentiation. This indicated that the malignant transformation of a normal B cell could have appeared during the transition of a primary follicle to a germinal center, i.e., after an initial B-cell activation. Genes involved in blockage of antiproliferative signals in normal cells were also deregulated, e.g., gene expression of TGF beta 2 and Smad3 was suppressed in MCLs. Furthermore, lymphoproliferative signal pathways were active in MCLs compared with normal B cells, because genes encoding, e.g., IL10R alpha and IL18 were up-regulated, as were oncogenes like Bcl-2 and MERTK. Genes encoding receptors for different neurotransmitters mediating B-cell stimulation, such as norepinephrine and cannabinoids were also up-regulated, again illustrating deregulation of a complex network of genes involved in growth and differentiation. Furthermore, hierarchical cluster analysis revealed two subpopulations of MCLs, which indicates that despite the homogeneous and strong overexpression of cyclin D1, further subtyping might be possible.
An Approach to Catalyst Design:  Cyclopentadienyl-Titanium Phosphinimide Complexes in Ethylene Polymerization (2003)

A strategy for polymerization catalyst design has been developed based on the steric and electronic analogy of bulky phosphinimides to cyclopentadienyl ligands. To this end, the family of complexes of the form (Cp†)TiCl2(NPR3) has been prepared and characterized. Alkyl and aryl derivatives of these species have also been synthesized, and a number have been evaluated for use as catalyst precursors in olefin polymerization. The polymerization of ethylene has been examined employing several types of cocatalyst activators. Trends and patterns in the structure−activity relationship are discussed, and the implications for catalyst design are evaluated.
Effect of a New FunctionalCYP3A4Polymorphism on Calcineurin Inhibitors‘ Dose Requirements and Trough Blood Levels in Stable Renal Transplant Patients (2011)

The CYP3A4 intron 6 C>T polymorphism is associated with altered Tac and CsA metabolism. CYP3A4 intron 6 C>T along with CYP3A5*3 (especially for Tac) pharmacogenetic testing performed just before transplantation may help identifying patients at risk of CNI overexposure and contribute to limit CNI-related nephrotoxicity by refining the starting dose according to their genotype. Original submitted 5 May 2011; Revision submitted 29 June 2011.
Metamorphic GaAs/AlAs Bragg mirrors deposited on InP for 1.3/1.55 μm vertical cavity losers (2002)

Long wavelength (1.3/1.5 /spl mu/m) GaAs-GaAlAs vertical cavity surface emitting lasers (VCSEL) with Bragg mirror (GaAs/AlAs) wafer fused on InP substrate exhibits low threshold current and cw operation at room temperature. However the wafer fusion technique requires additional substrate, epitaxy and technological steps. Furthermore the wafer fusion is difficult to achieve on a full 2 inches substrate. A new approach is proposed which consists in the metamorphic growth of GaAs-AlAs Bragg mirrors on InP by gas source molecular beam epitaxy.
Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development (1996)

To address the function of bone morphogenetic protein-2 (BMP2) in mammalian development, mice with a targeted deletion of the Bmp2 mature region were generated using embryonic stem cell technology. This mutation caused embryonic lethality when homozygous. Mutant embryos failed to close the proamniotic canal, which caused the malformation of the amnion/chorion. BMP2-deficient embryos also exhibited a defect in cardiac development, manifested by the abnormal development of the heart in the exocoelomic cavity. These defects are consistent with the expression of Bmp2 in the extraembryonic mesoderm cells and promyocardium. Thus BMP2 is a critical factor for both extraembryonic and embryonic development.
Herbicide seed treatment for weed control in wet‐seeded rice (1992)

Abstract One laboratory and two field experiments were conducted at the International Rice Research Institute (IRRI) to determine the effect of herbicides applied as seed treatments on crop safety and weed control in wet‐seeded rice (Oryza sativa L.). In the laboratory experiment all the herbicides tested, except butachlor‐2,4‐D, did not affect rice seed germination. Butachlor‐2,4‐D reduced root growth the most, while thiobencarb caused the greatest reduction in shoot growth. In the first field experiment all the seed treatments except bensulfuron reduced crop stand. The same herbicides poured directly onto flooded fields several days after sowing did not decrease plant stand significantly. Plant heights were reduced significantly by seed treatments with both butachlor formulations and pretilachlor + fenclorim. The best weed control was observed with pretilachlor + fenclorim applied either as a seed treatment or poured onto water. In the second field experiment, pretilachlor + fenclorim at 0.45 kg a.i./ha reduced crop stand and slightly stunted plant height when applied to the seed. Weed weights were generally less, and crop yields were increased, in the herbicide‐treated plots compared with the untreated plots, regardless of application method. Seed treatment with herbicides appears to be a promising technique for controlling weeds in wet‐seeded rice.
Zirconium Complexes with Cyclopentadienyl Ligands Involving Fused a Thiophene Fragment (2002)

The following cyclopentadienes (Cp‘H) with fused thiophene and benzothiophene fragments were synthesized: 4,5-dimethyl-6H-cyclopenta[b]thiophene (2), 5,6-dimethyl-4H-cyclopenta[b]thiophene (4), 1,3,5-trimethyl-4H-cyclopenta[c]thiophene (6), 2-methyl-1(and 3)H-cyclopenta[b][1]thiophenes (9), 2,3-dimethyl-1H-cyclopenta[b][1]benzothiophene (11), 1,2-dimethyl-3H-cyclopenta[b][1]benzothiophene (14). After a deprotonation of 2, 4, 11, and 14 with n-BuLi, followed by treatment of the resulting lithium salts with (η5-C5Me5)ZrCl3, complexes (η5-Cp‘)(η5-C5Me5)ZrCl2 were obtained. The ligand 6 gave a mixture of undesirable products instead of the respective metallocene. Two of them were isolated and turned out to be the polynuclear hydride complex {(Cp*Zr)(μ-H)(μ-Cl)2(Cp*ZrCl)}2(μ-Cl)6Li2 and a binuclear complex containing an unusual bridged bis[1,5-dimethyl-3-methylene-1,3-dihydro-η5-cyclopenta[c]thien-1-yl] ligand. Starting from the cyclopentadienes 2, 4, 11, and 14, several bis(cyclopentadienyl)dimethylsilanes were obtained and further used for the synthesis of the respective ansa-zirconocenes, which were isolated and unambiguously characterized either as pure diastereomeres or as rac/meso mixtures. Unbridged complex Cp‘2ZrCl2 was prepared in a similar manner from the ligand 9.
Multiplex quantitative PCR using self-quenched primers labeled with a single fluorophore (2002)

Multiplex quantitative PCR based on novel design of fluorescent primers is described. Fluorogenic primers are labeled with a single fluorophore on a base close to the 3' end with no quencher required. A tail of 5-7 nt is added to the 5' end of the primer to form a blunt-end hairpin when the primer is not incorporated into a PCR product. This design provides a low initial fluorescence of the primers that increases up to 8-fold upon formation of the PCR product. The hairpin oligonucleotides (DeltaG from -1.6 to -5.8 kcal/mol) may be as efficient as linear primers and provide additional specificity to the PCR by preventing primer-dimers and mispriming. Multiple fluorogenic primers were designed by specialized software and used for real-time quantitation of c-myc and IL-4 cDNAs in the presence of reference genes such as beta-actin, GAPDH and 18S rRNA. Targets of 10-10(7) copies were detected with precision in PCR using FAM-labeled primers for variable genes and JOE-labeled primers for the reference genes. This method was also used to detect single nucleotide polymorphism of the human retinal degeneration gene by allele-specific PCR with end-point detection using a fluorescent plate reader or a UV-transilluminator. We conclude that fluorogenic mono-labeled primers are an efficient and cost-effective alternative to FRET-labeled oligonucleotides.
Antisense inhibition of acetylcholinesterase gene expression causes transient hematopoietic alterations in vivo. (1994)

Hematopoietic acetylcholinesterase (ACHE) gene expression and its implication for development were studied by in vivo administration to mice of an antisense phosphorothioate oligonucleotide targetted toward ACHE (AS-ACHE). Hematopoietic alterations were observed by differential cell counts and ACHE mRNA levels determined by quantified RNA polymerase chain reaction (RNA-PCR) and in situ hybridization analyses. In control mice, injected with phosphate-buffered saline and untreated, ACHE mRNA labeling with ACHE [35S]cRNA was about 10-fold higher on megakaryocytes (MK) compared with all other bone marrow cells and increased by 20-fold during MK development, similar to reports for MK actin mRNA. Drastic reductions occurred in the bone marrow lymphocyte and erythroid fractions 12 days following intraperitoneal injection of AS-ACHE (5 micrograms/g weight) into groups of four mice. RNA-PCR revealed over 1000-fold decreases in ACHE mRNA levels in lymph nodes and bone marrow at this time, while actin mRNA levels dropped by 10 and 100-fold in lymph nodes and bone marrow of AS-ACHE treated mice compared with controls. In view of the developmental increase in MK actin, this suggested arrest in MK development as well. By 20 days postinjection, bone marrow actin mRNA was fully restored and the sensitive in situ hybridization technique revealed that ACHE mRNA levels were also restored and reached levels only 2-3-fold lower than in controls in all bone marrow cells of AS-ACHE treated mice. Moreover, lymphocytes and erythroid cells repopulated to levels 25% above normal, and promegakaryocyte and mature MK fractions of the total MK were 3 and 2-fold higher, respectively, than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Potential and constraints of Unmanned Aerial Vehicle technology for the characterization of Mediterranean riparian forest (2009)

Unmanned Aerial Vehicle (UAV) technology provides potential for very high spatial resolution (<25 cm) mapping of relatively large areas at a user-defined re-survey frequency. In a riparian context, UAV technology provides a mechanism for riparian managers to (a) quantify riparian terrain and vegetation units and (b) identify standing dead wood and canopy mortality. In this study a paraglider UAV was used to survey 174 ha at 6.8–21.8 cm ground resolution. Pixel-based and object-oriented classification approaches were used at the scale of a single image and a channel mosaic. Significant potential was demonstrated: vegetation units were classified with an accuracy of kappa = 0.79 and standing dead wood units were identified with an average accuracy with respect to omission and commission errors of 80% and 65%, respectively. Work across multiple images identified that major constraints currently result from factors such as illumination conditions and sensor movement during flight, which create variations in spatial resolution and radiometry. It is expected that with further methodological refinement and more complex methods of automated radiometric correction UAV technology can provide the flexibility to rapidly produce very high resolution map products to aid riparian management.
Microcin E492 antibacterial activity: evidence for a TonB‐dependent inner membrane permeabilization on Escherichia coli (2003)

The mechanism of action of microcin E492 (MccE492) was investigated for the first time in live bacteria. MccE492 was expressed and purified to homogeneity through an optimized large-scale procedure. Highly purified MccE492 showed potent antibacterial activity at minimal inhibitory concentrations in the range of 0.02-1.2 microM. The microcin bactericidal spectrum of activity was found to be restricted to Enterobacteriaceae and specifically directed against Escherichia and Salmonella species. Isogenic bacteria that possessed mutations in membrane proteins, particularly of the TonB-ExbB-ExbD complex, were assayed. The microcin bactericidal activity was shown to be TonB- and energy-dependent, supporting the hypothesis that the mechanism of action is receptor mediated. In addition, MccE492 depolarized and permeabilized the E. coli cytoplasmic membrane. The membrane depolarization was TonB dependent. From this study, we propose that MccE492 is recognized by iron-siderophore receptors, including FepA, which promote its import across the outer membrane via a TonB- and energy-dependent pathway. MccE492 then inserts into the inner membrane, whereupon the potential becomes destabilized by pore formation. Because cytoplasmic membrane permeabilization of MccE492 occurs beneath the threshold of the bactericidal concentration and does not result in cell lysis, the cytoplasmic membrane is not hypothesized to be the sole target of MccE492.
Rapid Systemic Delivery of Zolmitriptan Using an Adhesive Dermally Applied Microarray (2017)

Adhesive Dermally-Applied Microarray (ADAM) is a device for intracutaneous drug administration consisting of a 3 cm<sup>2</sup> disposable array of drug-coated titanium microprojections on an adhesive backing. It is applied using a low cost, reusable, handheld applicator. Microprojections penetrate the stratum corneum, delivering drug proximal to capillaries with limited likelihood of pain. The pharmacokinetics of zolmitriptan delivery using ADAM was evaluated in 20 healthy volunteers. Median t<sub>max</sub> was <20 min, comparable to subcutaneous sumatriptan. Absorption was faster than for oral zolmitriptan, with higher exposure in the first 2 h. Most adverse events were consistent with those seen in previous triptan trials. Application site reactions were generally mild and resolved within 24 h. ADAM zolmitriptan shows a promising pharmacokinetic profile for migraine treatment.
SDF-1 and CXCR4 in normal and malignant hematopoiesis. (2004)

Over recent years it has become apparent that the chemokine SDF-1 and its receptor CXCR4 play pivotal roles in normal hematopoiesis. They are essential for the normal ontogeny of hematopoiesis during embryogenesis and continue to play a key role in retaining hematopoietic progenitors within the bone marrow microenvironment in the adult. As a result of this role disruption of SDF-1/CXCR4 interactions results in mobilization of hematopoietic progenitors and standard mobilization protocols disrupt this axis. Similarly SDF-1/CXCR4 interactions are required for homing and engraftment of hematopoietic stem cells during transplantation. SDF-1 regulates the localisation of leukemic cells and like their normal counterparts most leukemic cells respond to SDF-1 with increased adhesion, survival and proliferation. However in some instances leukemic cell responses to SDF-1 can be disregulated, the impact of which on the progression of disease in not known. In this review we discuss the pleiotropic roles of SDF-1/CXCR4 interactions in human hematopoietic stem cell ontogeny, bone marrow homing and engraftment, mobilization and how these interactions impact on malignant hematopoiesis.
Control of spectral dynamics in concatenative speech synthesis (2001)

Current speech synthesis methods based on the concatenation of waveform units can produce highly intelligible speech capturing the identity of a particular speaker. However, the quality of concatenated speech often suffers from discontinuities between the acoustic units, due to contextual differences and variations in speaking style across the database. In this paper, we present methods to spectrally modify speech units in a concatenative synthesizer to correspond more closely to the acoustic transitions observed in natural speech. First, a technique called "unit fusion" is proposed to reduce spectral mismatch between units. In addition to concatenation units, a second, independent tier of units is selected that defines the desired spectral dynamics at concatenation points. Both unit tiers are "fused" to obtain natural transitions throughout the synthesized utterance. The unit fusion method is further extended to control the perceived degree of articulation of concatenated units. A signal processing technique based on sinusoidal modeling is also presented that enables high-quality resynthesis of units with a modified spectral shape.