gebhart/patrepeval huggingface dataset:
Optimization of VDD and VTH for low-power and high speed applications (2000)

Closed-form formulas are presented for optimum supply voltage (VDD) and threshold voltage (VTH) that minimize power dissipation when technology parameters and required speed are given. The formulas take into account short-channel effects and the variation of VTH and temperature. Using typical device parameters, it is shown that a simple guideline to optimize the power consumption is to set the ratio of maximum leakage power to total power about 30%. Extending the analysis, the future VLSI design trend is discussed. The optimum VDD coincides with the SIA roadmap and the optimum VTH for logic blocks at the highest temperature and at the lowest process variation corner is in the range of 0V~0.1V over generations.
Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications (2004)

PREFACE TO THE SECOND EDITION PREFACE TO THE FIRST EDITION INTRODUCTION Why Organofluorine Chemistry? History The Basic Materials The Unique Properties of Organofluorine Compounds PART I: Synthesis of Complex Organofluorine Compounds INTRODUCTION OF FLUORINE Perfluorination and Selective Direct Fluorination Electrochemical Fluorination (ECF) Nucleophilic Fluorination Synthesis and Reactivity of Fluoroaromatic Compounds Transformations of Functional Groups Fluorination PERFLUOROALKYLATION Radical Perfluoroalkylation Nucleophilic Perfluoroalkylation Perfluoroalkylation Difluorocarbene and Fluorinated Cyclopropanes SELECTED FLUORINATED STRUCTURES AND REACTION TYPES Difluoromethylation and Halodifluoromethylation The Perfluoroalkoxy Group The Perfluoroalkylthio Group and Sulfur-Based Super-Electron-Withdrawing Groups The Pentafluorosulfanyl Group and Related Structures THE CHEMISTRY OF HIGHLY FLUORINATED OLEFINS Fluorinated Polymethines Fluorinated Enol Ethers as Synthetic Building Blocks PART II: Fluorous Chemistry FLUOROUS CHEMISTRY Fluorous Biphase Catalysis FLUOROUS SYNTHESIS AND COMBINATORIAL CHEMISTRY Fluorous Synthesis Separation on Fluorous Stationary Phases Fluorous Concepts in Combinatorial Chemistry PART III: Applications of Organofluorine Compounds HALOFLUOROCARBONS, HYDROFLUOROCARBONS, AND RELATED COMPOUNDS Polymers and Lubricants Applications in the Electronics Industry Fluorinated Dyes Liquid Crystals for Active Matrix Liquid Crystal Displays Fluorine in Organic Electronics PHARMACEUTICALS AND OTHER BIOMEDICAL APPLICATIONS Why Fluorinated Pharmaceuticals? Lipophilicity and Substituent Effects Hydrogen Bonding and Electrostatic Interactions Stereoelectronic Effects and Conformation Metabolic Stabilization and Modulation of Reaction Centers Bioisosteric Mimicking Mechanism-Based Suicide Inhibition Fluorinated Radiopharmaceuticals Inhalation Anesthetics Blood Substitutes and Respiratory Fluids Contrast Media and Medical Diagnostics Agricultural Chemistry APPENDIX A: TYPICAL SYNTHETIC PROCEDURES Selective Direct Fluorination Hydrofluorination and Halofluorination Electrophilic Fluorination with F-TEDA - BF4 (Selectfluor) Fluorinations with DAST and BAST (Deoxofluor) Fluorination of a Carboxylic Acid with Sulfur Tetrafluoride Generation of a Trifluoromethoxy Group by Oxidative Fluorodesulfuration of a Xanthogenate Oxidative Alkoxydifluorodesulfuration of Dithianylium Salts Electrophilic Trifluoromethylation with Umemoto's Reagents Nucleophilic Trifluoromethylation with Me3SiCF3 Transition Metal-Mediated Aromatic Perfluoroalkylation Copper-Mediated Introduction of the Trifluoromethylthio Group Substitution Reactions on Fluoroolefins and Fluoroarenes Reactions with Difluoroenolates APPENDIX B: INDEX OF SYNTHETIC CONVERSIONS INDEX
The diploid genome sequence of Candida albicans (2004)

We present the diploid genome sequence of the fungal pathogen Candida albicans. Because C. albicans has no known haploid or homozygous form, sequencing was performed as a whole-genome shotgun of the heterozygous diploid genome in strain SC5314, a clinical isolate that is the parent of strains widely used for molecular analysis. We developed computational methods to assemble a diploid genome sequence in good agreement with available physical mapping data. We provide a whole-genome description of heterozygosity in the organism. Comparative genomic analyses provide important clues about the evolution of the species and its mechanisms of pathogenesis.
Nitrogen bridgehead compounds. Part88. Synthesis of 3H, 7H‐[1,4]diazepino[3,4‐b]quinazoline‐3,7‐diones (1997)

Abstract 3 H ,7 H ‐[1,4]Diazepino[3,4‐ b ]quinazolone‐3,7‐diones 9, 11 were synthesized starting from 2‐(1‐bromo‐ethyl)quinazolin‐4(3 H )‐ones 3 and 17 via 2‐[1‐(4‐methoxyphenylamino)ethyl]quinazolin‐4(3 H )‐ones 4 and 18. Cyclization of 3‐[2‐(1‐bromoethyl)‐4‐oxo‐3,4‐dihydroquinazolin‐3‐yl)propionic acid 14 by the action of triethylamine provided the first representative of the tricyclic 7 H ‐[1,4]oxazepino[3,4‐ b ]quinazoline‐3,7‐dione system, compound 15. The new tricyclic derivatives 9, 11 and 15 are characterized by uv, ir and 1 H nmr spectroscopy.
Tolerance to thymus-independent antigens. Characteristics of induction of tolerance to thymus-independent synthetic polypeptides. (1974)

The conditions have been studied for induction of tolerance in mice to two thymus-independent multichain synthetic polypeptides, poly(DTyr,DGlu)-polyDPro--polyDLys, and poly(DTyr,DGlu)-polyLPro--polyLLys. The antigens are of very similar structure, differing only in the optical configuration of proline and lysine residues. The tolerance thresholds were established by giving a single injection of antigen in solution in saline, followed later by challenge of antigen in adjuvant. For both antigens it was possible to induce high dose tolerance, which was preceded by a zone of priming at lower doses. In neither case was low zone tolerance observed. The induction of high zone tolerance was accompanied by a passing phase of antibody production in the case of poly(DTyr,DGlu)-polyDPro--polyDLys, but not in the case of poly(DTyr,DGlu)-polyLPro--polyLLys. Furthermore, the threshold doses for high zone tolerance for the two antigens differed by two orders of magnitude, being at about 100 μg per mouse for the former and at 1 μg per mouse for the latter. It appears that thymus-independent antigens, even if very similar structurally, can differ very markedly in the characteristics of their interaction with B cells.
Software visualization in the large (1996)

The invisible nature of software hides system complexity, particularly for large team-oriented projects. The authors have evolved four innovative visual representations of code to help solve this problem: line representation; pixel representation; file summary representation; and hierarchical representation. We first describe these four visual code representations and then discuss the interaction techniques for manipulating them. We illustrate our software visualization techniques through five case studies. The first three focus on software history and static software characteristics; the last two discuss execution behavior. The software library and its implementation are then described. Finally, we briefly review some related work and compare and contrast our different techniques for visualizing software.
Fused Protein Domains Inhibit DNA Binding by LexA (1992)

Many studies of transcription activation employ fusions of activation domains to DNA binding domains derived from the bacterial repressor LexA and the yeast activator GAL4. Such studies often implicitly assume that DNA binding by the chimeric proteins is equivalent to that of the protein donating the DNA binding moiety. To directly investigate this issue, we compared operator binding by a series of LexA-derivative proteins to operator binding by native LexA, by using both in vivo and in vitro assays. We show that operator binding by many proteins such as LexA-Myc, LexA-Fos, and LexA-Bicoid is severely impaired, while binding of other LexA-derivative proteins, such as those that carry bacterially encoded acidic sequences ("acid blobs"), is not. Our results also show that DNA binding by LexA derivatives that contain the LexA carboxy-terminal dimerization domain (amino acids 88 to 202) is considerably stronger than binding by fusions that lack it and that heterologous dimerization motifs cannot substitute for the LexA88-202 function. These results suggest the need to reevaluate some previous studies of activation that employed LexA derivatives and modifications to recent experimental approaches that use LexA and GAL4 derivatives to detect and study protein-protein interactions.
Study of thrombus from thrombosed hemodialysis access grafts. (1995)

Clot volume in thrombosed dialysis grafts is much less (approximately equal to 25%) than would be expected if the graft were completely filled with thrombus, a finding of significance to mechanical thrombolytic techniques. Resistance of the arterial plug to pulse-spray thrombolysis is likely due to compaction.
Molecular analysis of the structural gene for yeast transaldolase (1990)

We have cloned the structural gene for yeast transaldolase. Transformants carrying the TAL1 gene on a multicopy plasmid over-produced transaldolase. A deletion mutant which was constructed using the cloned gene did not show any detectable transaldolase activity in vitro. Furthermore, both transaldolase isoenzymes which were detected in wild-type crude extracts by immunoblotting were missing in the deletion mutants. Thus, TAL1 is the only transaldolase structural gene in yeast. TAL1 is not an essential gene. Deletion of the transaldolase gene did not affect growth on complete media with different carbon sources or on synthetic media. However, the transaldolase-deficient strains accumulated sedoheptulose 7-phosphate, an intermediate of the pentose-phosphate pathway. Mutants lacking both transaldolase and phosphoglucose isomerase grew more slowly than the single mutants. They accumulated more sedoheptulose 7-phosphate on medium containing fructose than on glucose medium. This shows that fructose 6-phosphate and glyceraldehyde 3-phosphate, metabolites of glycolysis, can enter the nonoxidative part of the pentose-phosphate pathway.
Enhanced Protein Thermostability by Ala → Aib Replacement (1998)

The introduction into peptide chains of alpha-aminoisobutyric acid (Aib) has proven to stabilize the helical structure in short peptides by restricting the available range of polypeptide backbone conformations. In order to evaluate the potential stabilizing effect of Aib at the protein level, we have studied the conformational and stability properties of Aib-containing analogs of the carboxy-terminal subdomain 255-316 of thermolysin. Previous NMR studies have shown that this disulfide-free 62-residue fragment forms a dimer in solution and that the global 3D structure of each monomer (3 alpha-helices encompassing residues 260-274, 281-295, and 301-311) is largely coincident with that of the corresponding region in the X-ray structure of intact thermolysin. The Aib analogs of fragment 255-316 were prepared by a semisynthetic approach in which the natural fragment 255-316 was coupled to synthetic analogs of peptide 303-316 using V8-protease in 50% (v/v) aqueous glycerol [De Filippis, V., and Fontana, A. (1990) Int. J. Pept. Protein Res. 35, 219-227]. The Ala residue in position 304, 309, or 312 of fragment 255-316 was replaced by Aib, leading to the singly substituted fragments Ala304Aib, Ala309Aib, and Ala312Aib. Moreover, fragment Ala304Aib/Ala309Aib with a double Ala-->Aib exchange in positions 304 and 309 was produced. Far- and near-UV circular dichroism measurements demonstrated that both secondary and tertiary structures of the natural fragment 255-316 are fully retained upon Ala-->Aib substitution(s). Thermal unfolding measurements, carried out by recording the ellipticity at 222 nm upon heating, showed that the melting temperatures (Tm) of analogs Ala304Aib and Ala309Aib were 2.2 and 5.4 degrees C higher than that of the Ala-containing natural species (Tm = 63.5 degrees C), respectively, whereas the Tm of the Ala312Aib analog was lowered by -0.6 degree C. The enhanced stability of the Ala304Aib analog can be quantitatively explained on the basis of a reduced backbone entropy of unfolding due to the restriction of the conformational space allowed to Aib in respect to Ala, while the larger stabilization observed for the Ala309Aib analog can be accounted for by both entropic and hydrophobic effects. In fact, whereas Ala304 is a surface residue, Ala309 is shielded from the solvent, and thus the enhanced stability of fragment Ala309Aib is also due to the burial of an additional -CH3 group with respect to the natural fragment. The slightly destabilizing effect of the Ala-->Aib exchange in position 312 appears to derive from unfavorable strain energy effects, since phi and psi values for Ala312 are out of the allowed angles for Aib. Of interest, the simultaneous incorporation of Aib at positions 304 and 309 leads to a significant and additive increase of +8 degrees C in Tm. The results of this study indicate that the rational incorporation of Aib into a polypeptide chain can be a general procedure to significantly stabilize proteins.
Human Monoclonal Antibodies Isolated from Spontaneous Epstein‐Barr Virus–Transformed Tumors of Hu‐SPL‐SCID Mice and Specific for Fusion Protein Display Broad Neutralizing Activity Toward Respiratory Syncytial Virus (1999)

Two human monoclonal antibodies, RF-1 and RF-2, specifically recognize the fusion protein of the human respiratory syncytial virus (RSV). These were isolated from spontaneous tumors in SCID mice reconstituted with human splenocytes and boosted with fusion protein. The tumors consisted of Epstein-Barr virus-transformed human B cells in animals with antigen-specific antibody titers>105. The binding affinity of RF-1 and RF-2 to the fusion protein is 1010 and 109 M-1, respectively. The antibodies bind specifically to a conformational epitope of the fusion protein on RSV-infected HEp-2 cells. Both antibodies display virus-neutralizing properties in vitro at concentrations varying between 8 and 1000 ng/mL. Virus neutralization applies to a broad variety of wild and laboratory-adapted virus strains belonging to both virus types A and B. These antibodies are potential candidates for passive immunotherapy of severe RSV infections.
Molecular Cloning and Functional Expression of a New Human CC-Chemokine Receptor Gene (1996)

The cloning of several receptors activated by either CC or CXC chemokines and belonging to the G protein-coupled family of receptors has been reported recently. In the present work, we describe the cloning of a human gene, named ChemR13, encoding a new CC-chemokine receptor. The gene encodes a protein of 352 amino acids with a calculated molecular mass of 40 600 Da and displaying a single potential site for N-linked glycosylation. Using a set of overlapping lambda clones, the genomic organisation of the locus was investigated, demonstrating that the ChemR13 gene is physically linked, and in the same orientation, as the CC-CKR2 gene that encodes a receptor for the monocyte chemoattractant protein-1 (MCP-1). A distance of 17.5 kb separates the two coding regions, which share 75% identity in nucleic acid and amino acid sequences. Human ChemR13 was functionally expressed in a stably transfected CHO-K1 cell line. Physiological responses to chemokines were monitored using a microphysiometer. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) was the most potent agonist. MIP-1 beta and RANTES were also active at physiological concentrations. The other CC-chemokines, MCP-1, MCP-2 and MCP-3, as well as CXC-chemokines (IL-8, GRO alpha) had no effect. ChemR13 receptor transcripts were detected by Northern blotting in the promyeloblastic cell line KG-1A, suggesting a potential role in the control of granulocytic lineage proliferation or differentiation. ChemR13 is thus a new member of the growing family of chemokine receptors that mediate the recruitment of cells involved in immune and inflammatory processes. Being the fifth functionally identified receptor in his class, this new CC-chemokine receptor (CC-CKR) is tentatively designated CC-CKR5.
Copper Promoted Aryl/Saturated Heterocyclic C-N Bond Cross-Coupling with Arylboronic Acid and Arylstannane (2000)

Arylboronic acid/cupric acetate arylation of N-H containing saturated heterocycles has been explored and found to give good yields of the cross-coupled products. Phenyltrimethylstannane is also found to arylate N-H containing heterocycles.
Role of Endothelin in Mediating the Attenuated Renal Hemodynamics in Dahl Salt-Sensitive Hypertension (1997)

The aim of this study was to evaluate the role of endothelin (ET) in the hypertension associated with giving a high sodium diet in Dahl salt-sensitive (DS) rats. To achieve this goal, we examined the effects of intravenous infusion of the nonspecific ET(A)-ET(B) antagonist on arterial pressure and renal function in conscious, chronically instrumented DS and Dahl salt-resistant (DR) rats. After 3 weeks on a high sodium (8%) diet, mean arterial pressure (MAP) in DS rats (166+/-3 mm Hg) was significantly higher than in DR rats (124+/-3 mm Hg). Baseline glomerular filtration rate (GFR) and renal plasma flow (RPF) in DS rats (1.92+/-0.25 mL/min and 7.07+/-0.80 mL/min) were lower than in DR rats (2.52+/-0.21 mL/min and 7.98+/-0.85 mL/min), respectively. Renal vascular resistance was significantly higher in DS rats (32.78+/-5.88 mm Hg x mL(-1) x min(-1)) than in DR rats (24.60+/-5.04 mm Hg x mL(-1) x min(-1)). Intravenous infusion of the ET antagonist SB 209670 at a dose of 30 microg x kg(-1) x min(-1) for 75 minutes caused a significant decrease in MAP in DS rats (from 166+/-3 to 144+/-4 mm Hg). In contrast, the effect of the ET antagonism on MAP in DR rats was not significant. ET-antagonist infusion tended to improve GFR and RPF in DS but not in DR rats. To determine the renal effects of ET antagonism independent of the systemic hemodynamic responses, we examined the effects of the same ET antagonist in rats chronically implanted with a renal interstitial catheter. Arterial pressure in DS rats (181+/-5 mm Hg) was significantly higher than in DR rats (135+/-3 mm Hg). Renal interstitial infusion of SB 209670 at a dose of 200 ng x kg(-1) x min(-1) for 60 minutes caused no change in MAP in DS or DR rats. Intrarenal ET antagonism significantly increased GFR (25%), RPF (30%), urine flow (32%), and urinary sodium excretion (25%) in DS rats, while it had no significant effect in DR rats. Fractional excretion of sodium was not significantly changed by renal interstitial infusion of the ET antagonist in DS rats, indicating that improved renal excretory function in DS rats is most likely due to the associated improvement in renal hemodynamics. We conclude that ET may play a role in the attenuated renal hemodynamics and possibly the development of Dahl salt-sensitive hypertension.
Attenuated amyloid-β aggregation and neurotoxicity owing to methionine oxidation (2007)

Aggregation of the amyloid-beta (Abeta) peptide into amyloid plaques is a characteristic feature of Alzheimer's disease neuropathogenesis. We and others have previously demonstrated delayed Abeta aggregation as a consequence of oxidizing a single methionine residue at position 35 (Met-35). Here, we examined the consequences of Met-35 oxidation on the extremely aggregation-prone peptides Abeta1-42 and Abeta1-40Arctic with respect to protofibril and oligomer formation as well as neurotoxicity. Size exclusion chromatography and mass spectrometry demonstrated that monomer/dimers prevailed over larger oligomers after oxidizing Met-35, and consequently protofibril formation and aggregation of both Abeta1-42 and Abeta1-40Arctic were delayed. The oxidized peptides completely lacked neurotoxic effects in cortical neuronal cultures under these conditions, in contrast to the neurotoxic properties of the unoxidized peptides. We conclude that oxidation of Met-35 significantly attenuates aggregation of Abeta1-42 and Abeta1-40Arctic, and thereby reduces neurotoxicity.
Tumor suppressor activity of RB and p53 genes in human breast carcinoma cells. (1993)

Breast cancer is the most common cancer of women in Western countries. Various genetic alterations have been implicated in its development. Two tumor suppressor genes, the retinoblastoma susceptibility gene (RB) and the gene encoding the p53 protein, are frequently found to be deleted or mutated in breast cancer cell lines and primary tumor samples. Breast carcinoma cell lines MDA-MB468 and BT549 both harbor partial RB gene deletions as well as point mutations of their p53 genes, thus providing an excellent model system for testing the roles played by these two genes in the oncogenesis of breast cancer. Single copies of wild-type RB or p53 were delivered to these cells by retrovirus-mediated gene transfer. Restoration of RB expression in cells reduced their ability to grow in soft agar and their tumorigenicity in nude mice, although no significant alteration of growth rate in culture could be detected. Introduction of wild-type p53 into these cells exerted a similar effect on the neoplastic phenotypes. This effect occurred even in the presence of their endogenous mutated p53 alleles, which argues for the phenotypical dominance of the wild-type p53 over mutated p53 during human oncogenesis. The ability of RB and p53 genes to suppress the tumorigenicity of breast carcinoma cells provides functional evidence that deletion or mutational inactivation of tumor suppressor genes represents an important step in the genesis of breast cancer.
Intracellular generation of single-stranded DNA for chromosomal triplex formation and induced recombination (2001)

Synthetic triple helix-forming oligodeoxyribonucleotides (TFOs) have been used to alter gene expression and to induce targeted genome modification in cells and animals. However, the efficacy of such oligodeoxyribonucleotides (ODNs) depends on efficient intracellular delivery. A novel vector system was tested for the production of single-stranded DNA (ssDNA) to serve as a TFO in mouse cells. Mouse cells carrying a substrate that can report triplex-stimulated intrachromosomal recombination were transfected with a series of ssDNA vectors, and induced recombination was assayed. Transfection with a vector set designed to generate a 34 nt G-rich ssDNA capable of triplex formation at a 30 bp polypurine target site within the reporter substrate yielded recombinants at a frequency of 196 x 10(-6), versus a background frequency of 45 x 10(-6) in mock transfected cells. No induction was seen when a vector set lacking the TFO sequence insert was tested or when the component vectors were transfected individually. Vectors engineered to express a C-rich 34 nt sequence (not expected to form triplex under physiological conditions) had no effect over background. Primer extension analyses on lysates from transfected cells confirmed the production of the intended ssDNAs. These results suggest that ssDNA molecules of a defined sequence can be generated intracellularly using a novel vector system and that such molecules are active in mediating triplex-dependent chromosomal events. The ability to produce active TFOs within cells may provide a new foundation for triplex-based gene targeting strategies.