gebhart/patrepeval huggingface dataset:
Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie (1996)

Both infectivity and TSE-specific amyloid protein (also referred to as protease resistant- or prion protein, PrP) are pathognomonic markers for transmissible spongiform encephalopathies (TSE). This paper presents a new densitometric method for the quantification of TSE-specific amyloid protein and its application to studying the pathogenesis of scrapie in Syrian hamsters after infection with scrapie strain 263K. A first study established a close correlation between infectivity and TSE-specific amyloid protein with a doubling time of 2-2.6 days in the brain and cervical spinal cord for both markers. The ratio of infectivity and TSE-specific amyloid protein was relatively constant at a mean value of about 10(6) protein molecules per infectious unit during the course of infection. A subsequent study addressed the temporal-spatial spread of infection in the central nervous system by tracing the accumulation of the pathological protein. The pathogenetic process was first detected in the spinal cord between vertebrae T4 and T9, and then showed an anterograde and retrograde spread with a rate of 0.8-1.0 mm/day. There were also some indications for a possible alternative route of spread of infection from the periphery to the brain, other than via the spinal cord. Involvement of the spleen did not appear essential for the early pathogenesis in hamsters orally infected with the 263K strain of scrapie.
Design of a 300-mV 2.4-GHz Receiver Using Transformer-Coupled Techniques (2013)

This paper presents a 1.6-mW 2.4-GHz receiver that operates from a single supply of 300 mV allowing direct powering from various energy harvesting sources. We extensively utilize transformer coupling between stages to reduce headroom requirements. We forward-bias bulk-source junctions to lower threshold voltages where appropriate. A single-ended 2.4 GHz RF input is amplified and converted to a differential signal before down-converting to a low IF of 1 to 10 MHz. A chain of IF amplifiers and narrowband filters are interleaved to perform programmable channel selection. The chip is fabricated in a 65-nm CMOS process. The receiver achieves -91.5-dBm sensitivity for a BER of 10e-3.
Molecular quantitative genetics (2014)

Abstract Recent development of high-throughput genomics tools has made it possible and affordable to examine the molecular basis of variation in quantitative traits in studies of non-model species in the wild. High-density single nucleotide polymorphism data and genome sequences provide promising methodological advances complementing and strengthening traditional quantitative genetic analyses from long-term pedigrees. This chapter, discusses how high-density genomic data can be used to determine the actual or realised genetic relationship between relatives, which then can be accounted for in further analyses to improve estimates of quantitative genetic parameters, perhaps even without the need to construct a pedigree. Furthermore, this chapter suggests how combining long-term field data with high-density genomic data, to carry out genome-wide association studies or genomic predictions of phenotypes, can provide important insight into the genetic architecture and evolutionary dynamics of fitness-related traits. Empirical results thus far provide good support for the notion that most quantitative genetic traits studied in wild populations have a highly polygenic basis; a key assumption of quantitative genetic analyses. This chapter also discusses how high-density genomic data can be used to identify past signatures of selection in genetic data that can be further compared to loci currently responsible for variation in individual fitness. Finally, this chapter presents some important issues to consider when sampling, storing and preparing DNA for high-throughput genomics analyses. The application of high-throughput genomics tools in quantitative genetic studies of non-model species in the wild shows great promise to increase understanding of ecological and evolutionary processes in natural populations.
Bias of Selection on Human Copy-Number Variants (2006)

Although large-scale copy-number variation is an important contributor to conspecific genomic diversity, whether these variants frequently contribute to human phenotype differences remains unknown. If they have few functional consequences, then copy-number variants (CNVs) might be expected both to be distributed uniformly throughout the human genome and to encode genes that are characteristic of the genome as a whole. We find that human CNVs are significantly overrepresented close to telomeres and centromeres and in simple tandem repeat sequences. Additionally, human CNVs were observed to be unusually enriched in those protein-coding genes that have experienced significantly elevated synonymous and nonsynonymous nucleotide substitution rates, estimated between single human and mouse orthologues. CNV genes encode disproportionately large numbers of secreted, olfactory, and immunity proteins, although they contain fewer than expected genes associated with Mendelian disease. Despite mouse CNVs also exhibiting a significant elevation in synonymous substitution rates, in most other respects they do not differ significantly from the genomic background. Nevertheless, they encode proteins that are depleted in olfactory function, and they exhibit significantly decreased amino acid sequence divergence. Natural selection appears to have acted discriminately among human CNV genes. The significant overabundance, within human CNVs, of genes associated with olfaction, immunity, protein secretion, and elevated coding sequence divergence, indicates that a subset may have been retained in the human population due to the adaptive benefit of increased gene dosage. By contrast, the functional characteristics of mouse CNVs either suggest that advantageous gene copies have been depleted during recent selective breeding of laboratory mouse strains or suggest that they were preferentially fixed as a consequence of the larger effective population size of wild mice. It thus appears that CNV differences among mouse strains do not provide an appropriate model for large-scale sequence variations in the human population.
Patellar dislocation following total knee replacement. (1985)

The reported incidence of patellar problems after total knee replacement has ranged from 5 to 30 per cent. Patellar dislocation is infrequent but can cause disabling symptoms. Between January 1974 and May 1982, eleven patients (twelve knees) with symptomatic lateral dislocation of the patella after total knee replacement were treated at The Hospital for Special Surgery by realignment of the extensor mechanism. All of the patients were women. Their average age was sixty-two years and average weight, eighty-seven kilograms. The diagnosis was osteoarthritis in seven knees and rheumatoid arthritis in five. Most of the patients had had preoperative valgus deformity (average, 18 degrees). The cause of dislocation was trauma in three knees, incorrect tracking of the patella after replacement in six, and malrotation of the tibial component in three. Four different prosthetic designs had been used. The design of the implant did not appear to be a factor causing dislocation in this group. The patellar dislocation was treated by proximal realignment of the quadriceps in ten knees, lateral retinacular release alone in one, and revision of the tibial and femoral components combined with proximal realignment in one. After an average follow-up of thirty-four months (range, twenty-four to fifty-seven months), the results according to The Hospital for Special Surgery knee-rating scale were excellent in ten knees and good in two, and there had been no redislocations.
Leishmania mexicana Cysteine Proteinase-Deficient Mutants Have Attenuated Virulence for Mice and Potentiate a Th1 Response (1998)

Leishmania mexicana mutants lacking cysteine proteinase genes cpa (delta cpa), cpb (delta cpb), or both cpa and cpb (delta cpa/cpb) have been generated by targeted gene disruption. Delta cpa mutants produce a disease phenotype in BALB/c mice close to that of wild-type L. mexicana, but delta cpb mutants are much less infective, producing very slowly growing small lesions, and delta cpa/cpb double mutants do not induce lesion growth. Immunologic analysis of Ab isotype during infection and splenocyte IFN-gamma, IL-2, and IL-4 production following stimulation with Leishmania Ag or Con A indicates that there was a significant shift from a predominantly Th2-associated immune response in mice infected with wild-type L. mexicana to a Th1-associated response in mice inoculated with delta cpb or delta cpa/cpb. Significantly, delta cpa altered the balance of the immunologic response to a lesser extent than did the other mutants. Similar disease outcomes and switches in the Th1/Th2 balance were also observed when other L. mexicana-susceptible mouse strains were infected with the mutants. BALB/c and C57BL/6 mice vaccinated with delta cpa/cpb and CBA/Ca mice vaccinated with delta cpb or delta cpa/cpb were subsequently more resistant, to varying degrees, than were untreated mice to infection with wild-type parasites, as measured by development of lesions and parasite burden. These data implicate leishmanial cysteine proteinases not only as parasite virulence factors but also in modulation of the immune response and provide strong encouragement that cysteine proteinase-deficient L. mexicana mutants are candidate attenuated live vaccines.
Characterization of hyaluronan–methylcellulose hydrogels for cell delivery to the injured spinal cord (2012)

No effective clinical treatment currently exists for traumatic spinal cord injury. Cell replacement therapy holds promise for attaining functional repair. Cells may be delivered directly or near the injury site; however, this strategy requires a delivery vehicle to maintain cell viability. We have identified an injectable, biocompatible, and biodegradable hydrogel scaffold composed of hyaluronan (HA) and methylcellulose (MC) that may be an effective scaffold for therapeutic cell delivery. The purpose of the present study was to determine the effects of polymer concentration on HAMC mechanical strength, gelation time, and cell viability. The yield stress of HAMC, a measure of mechanical stiffness, was tunable via manipulation of MC and HA content. Measurement of the elastic and storage moduli as functions of time revealed that HAMC gels in less than 5 min at physiological temperatures. Human umbilical tissue-derived cells encapsulated in HAMC were homogenously and stably distributed over 3 days in culture and extended processes into the scaffold. Cell viability was stable over this period in all but the most concentrated HAMC formulation. Because of its strength-tunability, rapid gelation, and ability to maintain cell viability, HAMC is a promising vehicle for cell delivery and is being tested in ongoing in vivo studies.
Role of dynamical screening in excitation kinetics of biased quantum wells: Nonlinear absorption and ultrabroadband terahertz emission (2006)

In this work we describe the ultrafast excitation kinetics of a biased quantum well, arising from the optically induced dynamical screening of a bias electric field. The initial bias electric field inside the quantum well is screened by the optically excited polarized electron-hole pairs. This leads to a dynamical modification of the properties of the system within an excitation pulse duration. We calculate the excitation kinetics of a biased quantum well and the dependency of resulting electronic and optical properties on the excitation pulse fluence, quantum well width, and initial bias field strength. Our calculations, in particular, predict the strongly nonlinear dependency of the effective optical absorption coefficient on the excitation pulse fluence, and ultrabroadband terahertz emission. Our theoretical model is free of fitting parameters. Calculations performed for internally biased InGaN∕GaN quantum wells are in good agreement with our experimental observations [Turchinovich et al., Phys. Rev. B 68, 241307(R) (2003)], as well as in perfect compliance with qualitative considerations.
Mechanism of Action of 2-Aminobenzamide HDAC Inhibitors in Reversing Gene Silencing in Friedreichâ€™s Ataxia (2015)

The genetic defect in Friedreich's ataxia (FRDA) is the hyperexpansion of a GAA•TTC triplet in the first intron of the FXN gene, encoding the essential mitochondrial protein frataxin. Histone post-translational modifications near the expanded repeats are consistent with heterochromatin formation and consequent FXN gene silencing. Using a newly developed human neuronal cell model, derived from patient-induced pluripotent stem cells, we find that 2-aminobenzamide histone deacetylase (HDAC) inhibitors increase FXN mRNA levels and frataxin protein in FRDA neuronal cells. However, only compounds targeting the class I HDACs 1 and 3 are active in increasing FXN mRNA in these cells. Structural analogs of the active HDAC inhibitors that selectively target either HDAC1 or HDAC3 do not show similar increases in FXN mRNA levels. To understand the mechanism of action of these compounds, we probed the kinetic properties of the active and inactive inhibitors, and found that only compounds that target HDACs 1 and 3 exhibited a slow-on/slow-off mechanism of action for the HDAC enzymes. HDAC1- and HDAC3-selective compounds did not show this activity. Using siRNA methods in the FRDA neuronal cells, we show increases in FXN mRNA upon silencing of either HDACs 1 or 3, suggesting the possibility that inhibition of each of these class I HDACs is necessary for activation of FXN mRNA synthesis, as there appears to be redundancy in the silencing mechanism caused by the GAA•TTC repeats. Moreover, inhibitors must have a long residence time on their target enzymes for this activity. By interrogating microarray data from neuronal cells treated with inhibitors of different specificity, we selected two genes encoding histone macroH2A (H2AFY2) and Polycomb group ring finger 2 (PCGF2) that were specifically down-regulated by the inhibitors targeting HDACs1 and 3 versus the more selective inhibitors for further investigation. Both genes are involved in transcriptional repression and we speculate their involvement in FXN gene silencing. Our results shed light on the mechanism whereby HDAC inhibitors increase FXN mRNA levels in FRDA neuronal cells.
Asymmetry in Flp-mediated cleavage (1997)

Flp is a member of the integrase family of site-specific recombinases. Members of the integrase family mediate DNA strand cleavage via a transesterification reaction involving an active site tyrosine residue. The first step of the reaction results in covalent linkage of the protein to the 3'-phosphoryl DNA terminus, leaving a 5'-hydroxyl group at the site of the nick. We have used Flp recognition target (FRT) sites containing a 5'-bridging phosphorothioate linkage at the site of Flp cleavage to accumulate intermediates in which Flp is covalently bound at a cleavage site. We have probed these intermediates with dimethylsulfate using methylation protection and find that Flp-mediated cleavage is associated with protection of two adenine residues that are opposite the sites of cleavage and covalent attachment by Flp. Methylation interference studies showed that cleavage and covalent attachment are also accompanied by differences in the contacts of Flp with each of the two cleavage sites and with the surrounding symmetry elements. Therefore, we provide evidence that Flp-mediated cleavage and covalent attachment result in changes to the conformation of the Flp-FRT complex. These changes may be required for Flp-mediated strand exchange activity.
“Synthetic Metals”: A Novel Role for Organic Polymers (Nobel Lecture) (2001)

Since the initial discovery in 1977, that polyacetylene (CH)x, now commonly known as the prototype conducting polymer, could be p- or n-doped either chemically or electrochemically to the metallic state, the development of the field of conducting polymers has continued to accelerate at an unexpectedly rapid rate and a variety of other conducting polymers and their derivatives have been discovered. Other types of doping are also possible, such as “photo-doping” and “charge-injection doping” in which no counter dopant ion is involved. One exciting challenge is the development of low-cost disposable plastic/paper electronic devices. Conventional inorganic conductors, such as metals, and semiconductors, such as silicon, commonly require multiple etching and lithographic steps in fabricating them for use in electronic devices. The number of processing and etching steps involved limits the minimum price. On the other hand, conducting polymers combine many advantages of plastics, for example, flexibility and processing from solution, with the additional advantage of conductivity in the metallic or semiconducting regimes; however, the lack of simple methods to obtain inexpensive conductive polymer shapes/patterns limit many applications. Herein is described a novel, simple, and cheap method to prepare patterns of conducting polymers by a process which we term, “Line Patterning”.
A genomewide survey of basic helix–loop–helix factors in Drosophila (2000)

The basic helix-loop-helix (bHLH) transcription factors play important roles in the specification of tissue type during the development of animals. We have used the information contained in the recently published genomic sequence of Drosophila melanogaster to identify 12 additional bHLH proteins. By sequence analysis we have assigned these proteins to families defined by Atonal, Hairy-Enhancer of Split, Hand, p48, Mesp, MYC/USF, and the bHLH-Per, Arnt, Sim (PAS) domain. In addition, one single protein represents a unique family of bHLH proteins. mRNA in situ analysis demonstrates that the genes encoding these proteins are expressed in several tissue types but are particularly concentrated in the developing nervous system and mesoderm.
Symptom features of postpartum depression: are they distinct? (2006)

The clinical features of postpartum depression and depression occurring outside of the postpartum period have rarely been compared. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)) provides a means to assess core depressive symptoms. Item response theory and classical test theory analyses were conducted to examine differences between postpartum (n=95) and nonpostpartum (n=50) women using the QIDS-SR(16). The two groups of females were matched on the basis of age. All met DSM-IV criteria for nonpsychotic major depressive disorder. Low energy level and restlessness/agitation were major characteristics of depression in both groups. The nonpostpartum group reported more sad mood, more suicidal ideation, and more reduced interest. In contrast, for postpartum depression sad mood was less prominent, while psychomotor symptoms (restlessness/agitation) and impaired concentration/decision-making were most prominent. These symptomatic differences between postpartum and other depressives suggest the need to include agitation/restlessness and impaired concentration/decision-making among screening questions for postpartum depression.
Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis (2009)

These findings suggest that PRF1 mutations play a role in the development of MAS in SoJIA patients.
Hypoglycemic effect of liposome-entrapped insulin administered by various routes into normal rats. (1990)

We entrapped insulin into liposomes using one combination of lipids comprising egg lecithin-cholesterol-stearylamine (7:2:1 molar ratio). The efficiency of entrapment was about 20% with unsonicated liposomes (LMV), and around 5% with sonicated liposomes (SUV). LMV-, SUV- and free-insulins were administered via different routes into male, non-diabetic Wistar rats in order to change the glycemia. When administered parenterally all preparations acted in a similar manner, reducing the glycemia after 2 h in the range of 75% to 85% in case of iv administration, and 43% to 67%--after sc administration. Only liposome insulin acted via intragastric route, and SUV-insulin-via buccal--or nasal route.
Clonal growth of colorectal-carcinoma cell lines transplanted to nude mice (1997)

It is generally assumed that tumor progression is a micro-evolutionary process in which increasingly aggressive clones, generated through genetic instability, emerge in an initially monoclonal lesion. The present study was undertaken to determine how rapidly a dominant clone will emerge from an initial polyclonal situation, and whether dominance of these clones is a prerequisite for the onset of metastasis. To this end, colon-carcinoma cells were infected in culture with an amphotropic retroviral vector containing the neomycin-phosphotransferase gene, which makes cells resistant to neomycin. A heterogeneous population of neomycin-resistant cells carrying random retroviral integrations was xenografted to the subcutis and to the cecum of nude mice. The xenografts obtained, as well as the available metastases, were analyzed as to viral integrations by Southern blotting. The results show that, (i) clonal selection already takes place during growth of the primary tumor; (ii) dominant clones also generate metastases. The retroviral integration pattern of metastases turned out to be identical to that found in the primary xenografts. This pattern remained unchanged in tumors obtained after serial transplantations of cells cultured from metastases. Int. J. Cancer 72:1137–1141, 1997. © 1997 Wiley-Liss, Inc.
Synthesis, Characterization, and Remarkable Biological Properties of Cyclodextrins Bearing Guanidinoalkylamino and Aminoalkylamino Groups on Their Primary Side (2008)

The introduction of aminoalkylamino and guanidinoalkylamino substituents on the primary side of beta- and gamma-cyclodextrin (CDs) resulted in a series of novel compounds that were extensively characterized by NMR spectroscopy and mass spectrometry. Bromination of the primary side of beta- and gamma-CD, and reaction with neat alkylene diamines at a pressure of 7 atm afforded aminoalkylamino derivatives that were then guanylated at the primary amino group to give the corresponding guanidinoalkylamino-CDs. These compounds are water soluble and display pK(a) values that allow them to be mostly protonated at neutral pH; for example, pK(a(1)) approximately 6.4 and pK(a(2)) approximately 9.5 for the aminoethylamino-beta-CD and pK(a(1)) approximately 7.8 and pK(a(2)) approximately 11.0 for the guanidinoethylamino-beta-CD. The title CDs are rigid, cyclic alpha-D-glucopyranose oligomers (heptamers or octamers) with branches that resemble lysine and arginine side chains that enable multiple interactions with suitable substrates. Thus, they bear similarities to known cell-penetrating peptides. Indeed, the compounds were found to cross the membranes of HeLa cells and penetrate inside the cytoplasm quickly, the guadinylated ones within 15 min, as shown by fluorescence microscopy using fluorescein-labeled derivatives. The toxicity of the compounds, measured by performing MTT tests, ranged from 50 to 300 microM. Furthermore, some of the aminated CDs could facilitate the transfection of DNA expressing the green fluorescent protein (GFP) in HEK 293T cells, with effectiveness comparable to the commercial agent Lipofectamine 2000. Circular dichroism, atomic force microscopy and electrophoresis experiments confirmed the strong interaction of the compounds with DNA. Because of their carbohydrate, non-peptide nature the title compounds are not anticipated to be enzymatically labile or immunogenic, and thus they fulfill many of the criteria for non-hazardous transport vectors in biological and pharmaceutical applications.