gebhart/patrepeval huggingface dataset:
Physiological and pathological consequences of identification of very small embryonic like (VSEL) stem cells in adult bone marrow. (2006)

Bone marrow (BM) contains a population of self-renewing hematopoietic stem cells (HSC) that give rise to cells from all hemato-lymphopoietic lineages. The concept that HSC could also be plastic and be able to transdifferentiate into stem/progenitor cells for different non-hematopoietic tissues became one of the most controversial issues of modern stem cell biology. Accumulating experimental evidence suggests that contribution of BM-derived stem cells to organ/tissue regeneration could be explained not by plasticity (transdifferentiation) of HSC but rather by the presence of non-hematopoietic stem cells in BM. In this review new evidence will be presented, that adult BM contains a small population of pluripotent very small embryonic-like (VSEL) stem cells. These cells are deposited in BM early during ontogenesis and could be mobilized from BM and circulate in peripheral blood during tissue/organ injury in an attempt to regenerate damaged organs. However, if these cells are mobilized at the wrong time and migrate to the wrong place they may contribute to the development of several pathologies, including tumor formation.
Bimetallic nanoparticles—novel materials for chemical and physical applications (1998)

A new class of materials for catalysis have been intensively investigated, that is, ‘bimetallic nanoparticles’. Extensive studies of non-supported bimetallic nanoparticle dispersions, stabilized by polymers or ligands, started only about 10 years ago. Many preparative procedures have been proposed, and detailed characterizations have been carried out on bimetallic nanoparticles, thanks to the rapid improvement of analytical technology on surface and nanoscale materials. In this review, we focus on the preparation, characterization and application to catalysis of polymer- or ligand-stabilized bimetallic nanoparticles in dispersion, emphasizing our own work and introducing recent progress of this area.
Entangled Macroscopic Quantum States in Two Superconducting Qubits (2003)

We present spectroscopic evidence for the creation of entangled macroscopic quantum states in two current-biased Josephson-junction qubits coupled by a capacitor. The individual junction bias currents are used to control the interaction between the qubits by tuning the energy level spacings of the junctions in and out of resonance with each other. Microwave spectroscopy in the 4 to 6 gigahertzrange at 20 millikelvin reveals energy levels that agree well with theoretical results for entangled states. The single qubits are spatially separate, and the entangled states extend over the 0.7-millimeter distance between the two qubits.
Loss-of-Function of HtrA1 Abrogates All- Trans Retinoic Acid-Induced Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells Through Deficiencies in p70S6K Activation (2016)

All-trans retinoic acid (ATRA) is a potent inducer of osteogenic differentiation in mouse adipose-derived stromal cells (mASCs), although the underlying mechanisms responsible for its mode of action have yet to be completely elucidated. High temperature requirement protease A1 (HtrA1) is a newly recognized modulator of human multipotent stromal cell (MSC) osteogenesis and as such, may play a role in regulating ATRA-dependent osteogenic differentiation of mASCs. In this study, we assessed the influence of small interfering RNA (siRNA)-induced repression of HtrA1 production on mASC osteogenesis and examined its effects on ATRA-mediated mammalian target of rapamycin (mTOR) signaling. Inhibition of HtrA1 production in osteogenic mASCs resulted in a significant reduction of alkaline phosphatase activity and mineralized matrix formation. Western blot analyses revealed the rapid activation of Akt (Ser473) and p70S6K (Thr389) in ATRA-treated mASCs, and that levels of phosphorylated p70S6K were noticeably reduced in HtrA1-deficient mASCs. Further studies using mTOR inhibitor rapamycin and siRNA specific for the p70S6K gene Rps6kb1 confirmed ATRA-mediated mASC osteogenesis as being dependent on p70S6K activation. Finally, transfection of cells with a constitutively active rapamycin-resistant p70S6K mutant could restore the mineralizing capacity of HtrA1-deficient mASCs. These findings therefore lend further support for HtrA1 as a positive mediator of MSC osteogenesis and provide new insights into the molecular mode of action of ATRA in regulating mASC lineage commitment.
Gene therapy for inherited retinal degeneration (1997)

Research into the molecular and genetic basis of disease is continually expanding and improving the prospects for rational treatments. Of these, gene therapy (here defined as the introduction of genetic material into human cells) may ultimately oVer the greatest scope. Of the inherited forms of retinal degeneration, retinitis pigmentosa (RP) is the best characterised (see Bird 2 for review). Seven diVerent non-syndromic RP genes have been identified to date, five of which However, photoreceptors and retinal pigment epithelial (RPE) cells are in close proximity and are interdependent. Defects in genes expressed in the RPE may also result in retinal degeneration. Delivery to these tissues of either normal copies of the defective genes or genes which enhance cell survival may arrest the degenerative process and thus preserve vision.
An industrial-strength audio search algorithm (2004)

We have developed and commercially deployed a flexible audio search engine. The algorithm is noise and distortion resistant, computationally efficient, and massively scalable, capable of quickly identifying a short segment of music captured through a cellphone microphone in the presence of foreground voices and other dominant noise, and through voice codec compression, out of a database of over a million tracks. The algorithm uses a combinatorially hashed time-frequency constellation analysis of the audio, yielding unusual properties such as transparency, in which multiple tracks mixed together may each be identified. Furthermore, for applications such as radio monitoring, search times on the order of a few milliseconds per query are attained, even on a massive music database.
Telomerase activity in the regenerative basal layer of the epidermis inhuman skin and in immortal and carcinoma-derived skin keratinocytes. (1996)

Cellular senescence is defined by the limited proliferative capacity of normal cultured cells. Immortal cells overcome this regulation and proliferate indefinitively. One step in the immortalization process may be reactivation of telomerase activity, a ribonucleoprotein complex, which, by de novo synthesized telomeric TTAGGG repeats, can prevent shortening of the telomeres. Here we show that immortal human skin keratinocytes, irrespective of whether they were immortalized by simian virus 40, human papillomavirus 16, or spontaneously, as well as cell lines established from human skin squamous cell carcinomas exhibit telomerase activity. Unexpectedly, four of nine samples of intact human skin also were telomerase positive. By dissecting the skin we could show that the dermis and cultured dermal fibroblasts were telomerase negative. The epidermis and cultured skin keratinocytes, however, reproducibly exhibited enzyme activity. By separating different cell layers of the epidermis this telomerase activity could be assigned to the proliferative basal cells. Thus, in addition to hematopoietic cells, the epidermis, another example of a permanently regenerating human tissue, provides a further exception of the hypothesis that all normal human somatic tissues are telomerase deficient. Instead, these data suggest that in addition to contributing to the permanent proliferation capacity of immortal and tumor-derived keratinocytes, telomerase activity may also play a similar role in the lifetime regenerative capacity of normal epidermis in vivo.
Comparison of technetium-99m-ll-EC isomers in rats and humans. (1997)

Technetium-99m-DD-EC has excellent imaging properties and the data suggest that its clearance may approach that of OIH more closely than any other 99mTc renal agent. A potential limitation is the fact that both 99mTc-DD and LL-EC exist in dianionic (80%) and monoanionic (20%) forms at physiological pH and it is unlikely that these two forms have the same clearance or protein binding affinity.
Enfuvirtide, an HIV-1 Fusion Inhibitor, for Drug-Resistant HIV Infection in North and South America (2003)

The addition of enfuvirtide to an optimized antiretroviral regimen provided significant antiretroviral and immunologic benefit through 24 weeks in patients who had previously received multiple antiretroviral drugs and had multidrug-resistant HIV-1 infection.
Plasmonic photoconductive detectors for enhanced terahertz detection sensitivity (2013)

A photoconductive terahertz detector based on plasmonic contact electrodes is presented. The use of plasmonic electrodes mitigates the inherent tradeoff between high quantum efficiency and ultrafast operation of the employed photoconductor, enabling significantly higher detection sensitivities compared to conventional photoconductive terahertz detectors. Prototypes of comparable photoconductive detectors with and without plasmonic contact electrode gratings were fabricated and characterized in a time-domain terahertz spectroscopy setup under the same operation conditions. The experimental results show that the plasmonic photoconductive detector offers more than 30 times higher terahertz detection sensitivities compared to the comparable conventional photoconductive detector without plasmonic contact electrodes over 0.1-1.5 THz frequency band.
A Novel Investigational Fc-Modified Humanized Monoclonal Antibody, Motavizumab-YTE, Has an Extended Half-Life in Healthy Adults (2013)

The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody (ADA), and safety of motavizumab-YTE (motavizumab with amino acid substitutions M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV) monoclonal antibody. Healthy adults (n = 31) were randomized to receive a single intravenous (i.v.) dose of motavizumab-YTE or motavizumab (0.3, 3, 15, or 30 mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly lower (71% to 86%) and the half-life (t1/2) was 2- to 4-fold longer than with motavizumab. However, similar peak concentrations and volume-of-distribution values, indicative of similar distribution properties, were seen at all dose levels. The sustained serum concentrations of motavizumab-YTE were fully functional, as shown by RSV neutralizing activity that persisted for 240 days with motavizumab-YTE versus 90 days postdose for motavizumab. Safety and incidence of ADA were comparable between groups. In this first study of an Fc-modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and exhibited an extended half-life of up to 100 days. (This study has been registered at ClinicalTrials.gov under registration no. NCT00578682.).
Down-Regulation of Regulatory Subunit Type 1A of Protein Kinase A Leads to Endocrine and Other Tumors (2004)

Mutations of the human type Ialpha regulatory subunit (RIalpha) of cyclic AMP-dependent protein kinase (PKA; PRKAR1A) lead to altered kinase activity, primary pigmented nodular adrenocortical disease, and tumors of the thyroid and other tissues. To bypass the early embryonic lethality of Prkar1a(-/-) mice, we established transgenic mice carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline-responsive promoter. Down-regulation of Prkar1a by up to 70% was achieved in transgenic mouse tissues and embryonic fibroblasts, with concomitant changes in kinase activity and increased cell proliferation, respectively. Mice developed thyroid follicular hyperplasia and adenomas, adrenocortical hyperplasia, and other features reminiscent of primary pigmented nodular adrenocortical disease, histiocytic and epithelial hyperplasias, lymphomas, and other mesenchymal tumors. These were associated with allelic losses of the mouse chromosome 11 Prkar1a locus, an increase in total type II PKA activity, and higher RIIbeta protein levels. This mouse provides a novel, useful tool for the investigation of cyclic AMP, RIalpha, and PKA functions and confirms the critical role of Prkar1a in tumorigenesis in endocrine and other tissues.
DCD – a novel plant specific domain in proteins involved in development and programmed cell death (2005)

It is tempting to speculate, that the DCD domain mediates signaling in plant development and programmed cell death and could thus be used to identify interacting proteins to gain further molecular insights into these processes.
Applications of automatic speech recognition to speech and language development in young children (2002)

Since 1990, the DRA Speech Research Unit has conducted research into applications of speech recognition technology to speech and language development for young children. This has been done in collaboration with the Hereford and Worcester County Council (HWCC) Education Department and, more recently, with Sherston Software Ltd. (an educational software publisher). An initial project, known as STAR (Speech Training Aid Research), was prompted by HWCC's awareness of a requirement by teachers for a computerised 'speech training aid' tool to aid young children in the development of a range of communications and language skills. The goal was to develop a computer-based system which was able to distinguish between 'good' and 'poor' pronunciations of a word, spoken by a child in response to a textual, pictorial or verbal prompt, from a 1,000-word children's vocabulary. The same speech recognition technology has subsequently been integrated into Sherston Software's commercially successful range of animated 'Talking Books', which use stored digitised speech to enable the computer to read words out-loud to a child. This converts them into 'Talking & Listening Books' which, in addition to the existing functions, are able to 'listen' to a child reading and indicate words which have been read incorrectly.
Oral Polio Vaccination During Pregnancy: Lack of Impact on Fetal Development and Perinatal Outcome (1994)

Prompted by a nascent epidemic of poliomyelitis in Finland, a mass vaccination program with live oral poliovirus vaccine (OPV) was implemented in February and March 1985. The final rate of coverage was approximately 94%. Pregnant women were included, and a cohort study was launched to evaluate any harmful effects of OPV on the developing embryo. All records of births to mothers who were pregnant during the period of vaccination and whose infants were delivered at the three major hospitals in the Helsinki area were reviewed. Within the study cohort, mothers were grouped into three categories according to their trimester of pregnancy during the program. In addition, two reference cohorts were evaluated; these cohorts consisted of infants delivered at the same hospitals during the second half of 1984 and of 1986, respectively. Each of the three categories in the study cohort included approximately 3,000 children, while each reference cohort included approximately 6,000 children. Data were analyzed on the rate of intrauterine growth and the prevalences of stillbirth, neonatal death, congenital malformation, premature birth, perinatal infection, and neurological aberration. No differences were documented among the study and reference cohorts or among the three categories within the study cohort. Thus, under the conditions described here, the inclusion of pregnant women in programs of mass vaccination with OPV appears to be safe.
Suppression of pyrimidine biosynthesis by targeting DHODH enzyme robustly inhibits rotavirus replication (2019)

Rotavirus infection remains a great health burden worldwide especially in some developing countries. It causes severe dehydrating diarrhea in infants, young children, as well as immunocompromised and organ transplanted patients. Viral replication heavily relies on the host to supply nucleosides. Thus, host enzymes involved in nucleotide biosynthesis represent potential targets for antiviral development. Dihydroorotate dehydrogenase (DHODH) is the rate-limiting enzyme in the de novo biosynthesis pathway of pyrimidines. In this study, we demonstrated that two specific DHODH enzyme inhibitors, brequinar (BQR) and leflunomide (LFM) robustly inhibited rotavirus replication in conventional human intestinal Caco2 cell line as well as in human primary intestinal organoids. The antiviral effect is conserved in both laboratory strain SA11 and rotavirus strain 2011K isolated from clinical sample. Mechanistic study indicated that BQR and LFM exerted their anti-rotavirus effect through targeting DHODH to deplete pyrimidine nucleotide pool. Therefore, targeting pyrimidine biosynthesis represents a potential approach for developing antiviral strategies against rotavirus.
Spectroelectrochemical and Photovoltaic Characterization of a Solution‐Processable n‐and‐p Type Dopable Pyrrole‐Bearing Conjugated Polymer (2010)

Abstract D‐A‐D‐type polymers are of high interest in the field of photovoltaics and electrochromism. In this study we report the synthesis and electrochemical properties of PPyBT along with its photophysical properties and photovoltaic performance. PPyBT is soluble in common organic solvents and both n‐ and p‐type dopable, which is a desired property for conjugated polymers. During electrochemistry studies, the onset potentials of the polymer were determined as +0.2 V for oxidation and −1.4 V for reduction. Using these values, HOMO and LUMO energy levels were calculated. The photovoltaic properties of PPyBT were also studied. PL studies showed that there is a charge transfer between PPyBT (donor) and PCBM (acceptor). magnified image
Targeted disruption of the human LIT1 locus defines a putative imprinting control element playing an essential role in Beckwith-Wiedemann syndrome (2000)

Human chromosome 11p15.5 harbors an intriguing imprinted gene cluster of 1 Mb. This imprinted domain is implicated in a wide variety of malignancies and Beckwith-Wiedemann syndrome (BWS). Recently, several lines of evidence have suggested that the BWS-associated imprinting cluster consists of separate chromosomal domains. We have previously identified LIT1, a paternally expressed antisense RNA within the KvLQT1 locus through a positional screening approach using human monochromosomal hybrids. KvLQT1 encompasses the translocation breakpoint cluster in BWS and patients exhibit frequent loss of maternal methylation at the LIT1 CpG island, implying a regulatory role for the LIT1 locus in coordinate control of the imprinting cluster. Here we generated modified human chromosomes carrying a targeted deletion of the LIT1 CpG island using recombination-proficient chicken DT40 cells. Consistent with the prediction, this mutation abolished LIT1 expression on the paternal chromosome, accompanied by activation of the normally silent paternal alleles of multiple imprinted loci at the centromeric domain including KvLQT1 and p57(KIP2). The deletion had no effect on imprinting of H19 located at the telomeric end of the cluster. Our findings demonstrate that the LIT1 CpG island can act as a negative regulator in cis for coordinate imprinting at the centromeric domain, thereby suggesting a role for the LIT1 locus in a BWS pathway leading to functional inactivation of p57(KIP2). Thus, the targeting and precise modification of human chromosomal alleles using the DT40 cell shuttle system can be used to define regulatory elements that confer long-range control of gene activity within chromosomal domains.
Building an effective software deployment process (2012)

Software defines the functionality and availability of computer systems, particularly those in higher education. Often, though, installing the appropriate applications in a multi-platform environment can be time-consuming, unorganized, and altogether onerous. A common approach to this problem is to create a thick image with all of the software pre-installed; especially with computer labs, however, these images can quickly become large and difficult to maintain and update. This paper presents best practices for building a phased-installation software deployment paradigm. When combined with thin imaging techniques, software installations on both academic and administrative machines become more organized, flexible, and discreet. While examples are implemented using IBM Tivoli Endpoint Manager and Active Directory/Group Policy, IT professionals can easily extend these core concepts into their own environments regardless of infrastructure.
Structural analysis of the phase‐variable lipooligosaccharide from Haemophilus somnus strain 738 (1998)

The structure of the phase variable lipooligosaccharide (LOS) from Haemophilus somnus strain 738 was elucidated. The LOS was subjected to a variety of degradative procedures. The structures of the purified products were established by monosaccharide and methylation analyses, NMR spectroscopy and mass spectrometry. The following structures for the two major components were determined on the basis of the combined data from these experiments. Kdo P Cho 2 P ∣∣∣ 6 4 4 β‐Gal‐1‐3‐β‐GlcNAc‐1‐3‐β‐Gal‐1‐4‐β‐Glc‐1‐4‐α‐Hep‐1‐5‐α‐Kdo‐2‐6‐β‐GlcN‐1‐6‐α‐GlcN‐1‐ P 3 ∣ 1 α‐Hep‐6‐ P Etn Kdo P Cho 2 P ∣∣∣ 6 4 4 β‐Gal‐1‐3‐β‐GlcNAc‐1‐3‐β‐Gal‐1‐3‐β‐Glc‐1‐4‐β‐Glc‐1‐4‐α‐Hep‐1‐5‐α‐Kdo‐2‐6‐β‐GlcN‐1‐6‐α‐GlcN‐1‐ P 3 ∣ 1 α‐Hep‐6‐ P Etn In the structures Kdo is 3‐deoxy‐ D ‐ manno ‐octulosonic acid, P Etn is phosphoethanolamine, P Cho is phosphocholine, Hep is L ‐ glycero ‐ D ‐ manno ‐heptose, and the remaining glucose units have the D configuration. The elucidation of these structures has increased our understanding of the relationship between the phase‐variable LOS and the pathogenic potential of this organism.
Binding and diffusion of a Si adatom around the type A step on Si(001) c(4×2) (1995)

The results of a simulation are described, using a density functional method, of the diffusion of adatoms on a flat Si(001)c(4×2) surface and around one type of surface step (the SA step). These indicate that there is a moderate additional energy barrier (0.2±0.1 eV) to cross the SA step as compared to the energy for diffusion on a flat surface. The dimer-top lattice site on the lower terrace adjacent to the step edge is stabilized (by 0.15±0.1 eV) with respect to the flat surface result although the most stable binding sites near the step are unaffected. This behavior can be understood based on the disruption of dimer tilt near the step. The results suggest that adatoms are more likely to stop on lattice sites at the SA step edge than on lattice sites on the open surface. This may affect the relative dimer formation rate near the step with respect to the behavior on the flat surface even in the absence of a clear change in binding energy. The effect of the SA step terrace edge on adatom behavior is very short ranged and weak. This is consistent with the relatively small strain field and lack of change in dangling bond density associated with the step edge.