gebhart/patrepeval huggingface dataset:
Yeast Genes That Enhance the Toxicity of a Mutant Huntingtin Fragment or α-Synuclein (2003)

Genome-wide screens were performed in yeast to identify genes that enhance the toxicity of a mutant huntingtin fragment or of alpha-synuclein. Of 4850 haploid mutants containing deletions of nonessential genes, 52 were identified that were sensitive to a mutant huntingtin fragment, 86 that were sensitive to alpha-synuclein, and only one mutant that was sensitive to both. Genes that enhanced toxicity of the mutant huntingtin fragment clustered in the functionally related cellular processes of response to stress, protein folding, and ubiquitin-dependent protein catabolism, whereas genes that modified alpha-synuclein toxicity clustered in the processes of lipid metabolism and vesicle-mediated transport. Genes with human orthologs were overrepresented in our screens, suggesting that we may have discovered conserved and nonoverlapping sets of cell-autonomous genes and pathways that are relevant to Huntington's disease and Parkinson's disease.
Reduced Complexity and Improved Performance for Short Regular LDPC Codes Based on Select Updating Schedule (2007)

In this paper, we present a modified BP decoding algorithm based on select updating schedule by analyzing the properties of message-passing through cycles, we also proposed a concrete scheme to obtain the select updating schedule, the simulations prove that we could improve performance and reduce complexity at the same time for short regular LDPC codes which have a small difference between the maximal and minimal single bit node girths by select updating schedule compared with the conventional BP decoding algorithm.
The Relation of Plasma Androgen Levels to Sexual Behaviors and Attitudes of Women1 (1982)

Four androgens: dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and dihydrotestosterone (DHT), a variety of sexual behaviors and attitudes, and several moods were determined regularly in two groups of healthy, married women who differed by three decades in age. The younger women exhibited significantly higher levels of each androgen, the differences being almost entirely attributable to ovarian failure in the older group. Although the older women reported the same levels of sexual desire and sexual arousal as the younger women, their intercourse frequencies and self-rated sexual gratification scores were significantly lower than the values obtained for the younger wives. One or more of the androgen levels related significantly and in the expected direction to each stage of the four-stage sexual response process. Global measures of so-called "sexual adjustment" and estimates of anxiety, depression, and hostility feelings experienced by these women did not relate significantly to any of the four androgen levels.
Survivin mRNA expression in patients with breast cancer. (2002)

We measured survivin mRNA expression in breast cancers using a fluorogenically detected reverse transcription-polymerase chain reaction, seeking relationships between expression and clinical and histological variables. The mean relative expression of survivin mRNA was 0.347+/-0.466 in breast cancers and 0.017+/-0.023 in noncancerous breast tissue resected with the tumors. A cut-off value for positivity was set at the mean + SD for expression in the noncancerous tissues; positivity for survivin mRNA expression was 90.2% (37 out of 41 cases) in breast cancers and 23% (3 out of 13) in adjacent noncancerous breast tissues. Expression in tumors varied independently of clinicopathological factors except for lymphatic invasion. As measured by our sensitive detection system, survivin mRNA is a useful diagnostic marker for breast cancer.
Scleral Plug of Biodegradable Polymers for Controlled Drug Release in the Vitreous (1994)

We designed a new device, a scleral plug, that releases drugs into the vitreous after being implanted and fixed at the pars plana. Use of the plug for provision of doxorubicin hydrochloride was evaluated in rabbits. The scleral plug (8.5 mg) was made of poly(lactic-glycolic acid) (molecular weight, 40,000 daltons) containing 1% doxorubicin. Vitreous concentrations of doxorubicin were measured after the implantation. In vitro studies showed that the plug released 26% of the drug during 4 weeks. In vivo studies demonstrated that the concentration in the vitreous humor was maintained at a therapeutic range for longer than 4 weeks. No substantial toxic reactions were observed by electroretinographic and histopathologic evaluations. Our findings suggested that a scleral plug made of biodegradable polymers is a promising device for a controlled drug-release system in the vitreous.
A facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid–base neutralization reactions (2008)

Nanonization strategies have been used to enhance the oral availability of numerous drugs that are poorly soluble in water. Exploring a facile nanonization strategy with highly practical potential is an attractive focus. Here, we report a novel facile nanoaggregation strategy for constructing drug nanoparticles of poorly soluble drugs with pH-dependent solubility by utilizing acid-base neutralization in aqueous solution, thus facilitating the exploration of nanonization in oral delivery for general applicability. We demonstrate that hydrophobic itraconazole dissolved in acid solution formed a growing core and aggregated into nanoparticles in the presence of stabilizers. The nanoparticles, with an average diameter of 279.3 nm and polydispersity index of 0.116, showed a higher dissolution rate when compared with the marketed formulation; the average dissolution was about 91.3%. The in vivo pharmacokinetic studies revealed that the nanoparticles had a rapid absorption and enhanced oral availability. The diet state also showed insignificant impact on the absorption of itraconazole from nanoparticles. This nanoaggregation strategy is a promising nanonization method with a facile process and avoidance of toxic organic solvents for oral delivery of poorly soluble drugs with pH-dependent solubility and reveals a highly practical potential in the pharmaceutical and chemical industries.
Transposable Elements and Genome Organization: A Comprehensive Survey of Retrotransposons Revealed by the Complete Saccharomyces cerevisiae Genome Sequence (1998)

We conducted a genome-wide survey of Saccharomyces cerevisiae retrotransposons and identified a total of 331 insertions, including 217 Ty1, 34 Ty2, 41 Ty3, 32 Ty4, and 7 Ty5 elements. Eighty-five percent of insertions were solo long terminal repeats (LTRs) or LTR fragments. Overall, retrotransposon sequences constitute >377 kb or 3.1% of the genome. Independent evolution of retrotransposon sequences was evidenced by the identification of a single-base pair insertion/deletion that distinguishes the highly similar Ty1 and Ty2 LTRs and the identification of a distinct Ty1 subfamily (Ty1'). Whereas Ty1, Ty2, and Ty5 LTRs displayed a broad range of sequence diversity (typically ranging from 70%-99% identity), Ty3 and Ty4 LTRs were highly similar within each element family (most sharing >96% nucleotide identity). Therefore, Ty3 and Ty4 may be more recent additions to the S. cerevisiae genome and perhaps entered through horizontal transfer or past polyploidization events. Distribution of Ty elements is distinctly nonrandom: 90% of Ty1, 82% of Ty2, 95% of Ty3, and 88% of Ty4 insertions were found within 750 bases of tRNA genes or other genes transcribed by RNA polymerase III. tRNA genes are the principle determinant of retrotransposon distribution, and there is, on average, 1.2 insertions per tRNA gene. Evidence for recombination was found near many Ty elements, particularly those not associated with tRNA gene targets. For these insertions, 5'- and 3'-flanking sequences were often duplicated and rearranged among multiple chromosomes, indicating that recombination between retrotransposons can influence genome organization. S. cerevisiae offers the first opportunity to view organizational and evolutionary trends among retrotransposons at the genome level, and we hope our compiled data will serve as a starting point for further investigation and for comparison to other, more complex genomes.
Glossary of Terms Used in Combinatorial Chemistry (1999)

Abstract Introduction : The development of combinatorial chemistry has generated a wide variety of new concepts and much associated terminology. In addition, the nature of research in this area has brought together scientists from diverse backgrounds: statisticians may discuss their work with biologists and heterocyclic chemists; medicinal chemists are talking to engineers, analytical chemists, and polymer scientists. In recognition of the potential for confusion and lack of communication in this field, the International Union of Pure and Applied Chemistry (IUPAC) convened a working party (within the Division of Human Health, Medicinal Chemistry Section) to attempt to capture and define the terminology at the interface of these endeavours. The following Glossary is the result of their efforts. It is hoped that it will provide a resource for those new to the area encountering terms for the first time, and, perhaps, to increase the clarity of communication between more experienced workers in the field. The Glossary is not intended as a comprehensive review or encyclopaedia of combinatorial chemistry, although occasional attempts have been made to broaden the scope beyond a strict dictionary-type definition of terms by providing illustrative examples of some terms, and directing readers to literature sources where appropriate. These references have not necessarily been chosen to attribute credit for the discovery or invention of a term; rather they should provide the most pertinent information for the topic. Ideally this will be an article or review with the Glossary term as its central theme, in which proper accreditation for the seminal contributions to that area may be found. Because of the intrinsic interdisciplinary nature of this area of research, it has not been possible to provide a comprehensive coverage of each of the sub-fields, neither has this been the intent. Rather it has been attempted to identify those elements which are particularly pertinent to combinatorial chemistry. Thus, in the analytical sciences "magic angle spinning" gains an entry whereas "mass spectrometry" does not. The interested reader will readily be able to find more detailed treatments of these specialized areas. Trademarks have been included where, in the judgement of the authors, their use has become sufficiently widespread that they often do not receive appropriate citation; the implicit assumption being that the reader will understand what is meant. This criterion has been adopted over one of inclusiveness, which would rapidly become extreme in many areas. In a field which is developing as rapidly as combinatorial chemistry a document such as this Glossary may soon require revision. The authors welcome suggestions for new terms, clarifications, references, and other comments which will aid in the development of this resource.
Frequent p53 overexpression in therapy related myelodysplastic syndromes and acute myeloid leukemias: an immunohistochemical study of bone marrow biopsies. (1993)

p53 overexpression was studied immunohistochemically in paraffin-embedded bone marrow biopsies using a recently described technique for antigen retrieval based on microwave oven heating of paraffin sections. Using a monoclonal antibody (PAb1801) that reacts with human cellular p53, nuclear staining was detected in 7/11 (63%) therapy-related myelodysplastic syndromes and in 3/4 (75%) therapy-related acute myeloid leukemias. Conversely, staining for p53 was seen only in 9/40 (22%) cases of "primary" hematologic conditions (P < 0.007); these included myelodysplastic syndromes [#2], acute myeloid leukemia [#4], and chronic granulocytic leukemia in accelerated phase or blast crisis [#3]. Biopsies of normal controls and of chronic granulocytic leukemia in stable phase were consistently p53(-). Nine of the 10 karyotyped p53(+) acute myeloid leukemia/myelodysplastic syndrome cases showed complex cytogenetic findings with frequent involvement of chromosome 5 and/or 7. Only four of the 33 karyotyped p53(-) cases showed similar cytogenetic changes. Chromosome 17 involvement was present in four of 13 (31%) cytogenetically assessed p53+ cases, but in none of the p53(-). In univariate analysis, p53 expression in both MDS and AML was significantly associated with shorter survival. The frequent overexpression of p53 in therapy-related myelodysplastic syndromes, therapy-related acute myeloid leukemias and in accelerated phase/blast crisis, chronic granulocytic leukemia and its strong association with complex karyotypes suggests an important role of this gene in the pathogenesis of these leukemic conditions.
Mid-infrared doping tunable transmission through subwavelength metal hole arrays on InSb (2009)

Doping-tunable mid-infrared extraordinary transmission is demonstrated from a periodic metal hole array patterned on n-InSb. The polarization-dependent transmission was measured at room temperature and 77 K. In addition, the extraordinary transmission was measured for incident angles from 0 degrees to 35 degrees in 5 degrees steps. A fundamental resonance shift of approximately 123 cm-1 (1.4 microm) is observed by varying the doping from 1 x 10(16) to 2 x 10(18) cm(-3). The calculated transmission resonances were in good agreement with the experimental results. This suggests that InSb semiconductor-based plasmonic structures may be suitable for a variety of tunable mid-infrared device applications.
Application of signature-tagged mutagenesis to the study of virulence ofErwinia amylovora (2006)

To identify genes that contribute to the virulence of Erwinia amylovora in plants, 1892 mutants were created and screened in pools of < or =96 mutants using signature-tagged mutagenesis. Nineteen mutants were not recovered from apple shoots following inoculation, which suggested that the insertions in these mutants affected genes important for bacterial survival in planta. DNA flanking the Tn5 insertions in the 19 mutants was sequenced and analysed by blast. One mutant had a Tn5 insertion in amsE, a gene involved in the biosynthesis of exopolysaccaride (EPS). Fourteen mutants had insertions in loci that were implicated in biosynthesis or transport of particular amino acids or nucleotides, a site-specific recombinase active during cell division and several putative proteins of unknown function; the flanking DNA of the remaining four mutants lacked significant homology with any DNA in the database. When inoculated individually to hosts, 10 of the 19 mutants caused significantly less disease and multiplied less, as compared with the wild-type strain.
High-precision division and square root (1997)

We present division and square root algorithm for calculations with more bits than are handled by the floating-point hardware. These algorithms avoid the need to multiply two high-precision numbers, speeding up the last iteration by as much as a factor of 10. We also show how to produce the floating-point number closest to the exact result with relatively few additional operations.
Potentiating antitumor effects of a combination therapy with lovastatin and butyrate in the Lewis lung carcinoma model in mice (2001)

Lovastatin, the drug used for the treatment of hypercholesterolemia, has previously been reported to exert antitumor activity in experimental murine models. Butyrate and butyric acid derivatives are well known to induce differentiation and apoptosis of tumour cells and also have recently gained acceptance as potential anticancer agents. In this study, we examined the antitumor effects of the combination of lovastatin and butyrate or its prodrug tributyrin in vitro and in vivo against a murine Lewis lung carcinoma (3LL). This combination therapy showed synergistic antitumor activity against 3LL cells in vitro. These effects were at least in part due to apoptosis induction that occurred after 12 hr of incubation with lovastatin and butyrate and was preceded by changes in cell cycle distribution of treated cells and expression of p21, p53 and cyclin D1. Remarkably, a systemic treatment of syngeneic mice inoculated with 3LL cells with both drugs resulted in significant tumour growth retardation.
Malassezin, a Novel Agonist of the Aryl Hydrocarbon Receptor from the Yeast Malassezia furfur, Induces Apoptosis in Primary Human Melanocytes (2005)

Pityriasis versicolor is the most common skin mycosis in humans worldwide. Yeasts of the genus Malassezia, particularly M. furfur, a saprophyte occurring widely on human skin, are generally regarded as the causative agents. Pityriasis versicolor is often accompanied by a long-lasting depigmentation that persists even after successful antimycotic therapy. M. furfur is able to convert tryptophan into a variety of indole alkaloids, some of them showing biological properties that correlate well with certain clinical features of pityriasis versicolor. This suggests a possible role for these compounds in the depigmentation process. We now report that human melanocytes undergo apoptosis when exposed to the crude mixture of tryptophan metabolites from M. furfur. The active compound was identified as malassezin, previously isolated by us from the same source and characterized as an agonist of the aryl hydrocarbon (Ah) receptor. The compound could, therefore, contribute to the marked depigmentation observed during the course of pityriasis versicolor.
Evaluation of Nanomechanical Properties of (Styrene–Methyl Methacrylate) Copolymer Composites Containing Graphene Sheets (2013)

The nanomechanical properties of polymers that contained (styrene–methyl methacrylate) copolymer (PS-PMMA) composites with reduced graphene oxide sheets (RGO) prepared by (i) in situ bulk polymerization and (ii) a microwave irradiation (MWI) method were compared. The nanomechanical properties such as the hardness and elastic modulus of these copolymers were analyzed using Berkovich nanoindentation. The results indicate that the composite obtained using the MWI method exhibited a better morphology and increased dispersion with enhanced thermal stability. As a result, the mechanical properties also improved due to increased mechanical interlocking between the graphene oxide (GO) nanofillers and the PS-PMMA matrix, which improved the mechanical strength. An average increase of 136% in hardness and 76% in elastic modulus were achieved through the addition of only 2.0 wt % of RGO composite obtained via the MWI method.
Hammerhead Ribozyme-Mediated Cleavage of the Human Insulin-Like Growth Factor-II Ribonucleic Acid in Vitro and in Prostate Cancer Cells (1999)

Insulin-like growth factor (IGF)-II plays an important role in fetal growth and development. IGFs are potent mitogens for a variety of cancer cells. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. To test the role of IGF-II in cancer cell growth, hammerhead ribozymes targeted to human IGF-II RNA were constructed. Single (R)- and double (RR)-ribozymes were catalytically active in vitro whereas mutant ribozymes (M or MM) did not cleave IGF-II RNA. RR was more active than R. In human prostate cancer PC-3 cells, both R and RR similarly suppressed IGF-II messenger RNA (mRNA) levels (∼40%) compared with the level in parental or M-expressing PC-3 cells. Polymerase II and III promoter-driven R similarly suppressed IGF-II mRNA levels. Suppression of IGF-II mRNA levels by R was associated with suppression of IGF-II protein levels. R- (or RR-) expressing PC-3 cells did not grow under serum-starved conditions and showed prolonged doubling times in the presence of 10% FCS compared with those of parental or M-expressing cells. These results substantiated that IGF-II plays a critical role in prostate cancer cell growth.
Conjugation of plasminogen activators and fibrin-specific antibodies to improve thrombolytic therapeutic agents (1991)

Here we have reviewed chemical and recombinant approaches to the construction of hybrid molecules that combine a "targeting" antibody and an "effector" enzyme activity. There are advantages and disadvantages to both chemical and recombinant methods, and one goal of this review has been to elucidate these so that the appropriate method can be used by those interested in using hybrid molecules to study questions of basic or therapeutic importance. The system studied in greatest detail has as its goal the targeting of a plasminogen activator to an occlusive intravascular thrombus. We have, therefore, used this system as an example of currently available approaches. Now that these methodologies have been studied and put into use, it is anticipated that this principle will be generalized both to other therapeutic applications, as well as to the design and construction of molecules that will allow more basic questions to be addressed.
Use of serum free light chain analysis and urine protein electrophoresis for detection of monoclonal gammopathies (2010)

Using FLC alongside or in place of UPE can give clinical benefit through earlier diagnosis and hence treatment earlier in the patients' disease.
Analysis of the SlyA‐controlled expression, subcellular localization and pore‐forming activity of a 34 kDa haemolysin (ClyA) from Escherichia coli K‐12 (1999)

Escherichia coli K-12 harbours a chromosomal gene, clyA (sheA, hlyE), that encodes a haemolytic 34 kDa protein. Recombinant E. coli overexpressing the cloned clyA gene accumulated this haemolysin in the periplasm and released only very small amounts of it into the external medium. The secretion of ClyA was confined to the log phase and paralleled by the partial release of several other periplasmic proteins. Sequencing of ClyA revealed the translational start point of the clyA gene and demonstrated that the clyA gene product is not N-terminally processed during transport. The transcription of clyA from its native promoter region was positively controlled by SlyA, a regulatory protein found in E. coli, Salmonella typhimurium and other Enterobacteriaceae. SlyA-controlled transcription started predominantly 72 bp upstream from clyA, as shown by primer extension. The corresponding putative promoter contains an unusual -10 sequence (TATGAAT) that is separated from a conventional -35 sequence by a GC-rich spacer. Site-directed deletion of the G in the -10 sequence abrogated the SlyA requirement for strong ClyA production, whereas a reduction in the G + C content of the spacer diminished the capability of SlyA to activate the clyA expression. Osmotic protection assays and lipid bilayer experiments suggested that ClyA forms stable, moderately cation-selective transmembrane pores that have a diameter of about 2.5-3 nm.