gebhart/patrepeval huggingface dataset:
Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen (2008)

The 60 cell lines of the National Cancer Institute Anticancer Drug Screen (NCI-60) constitute the most extensively characterized in vitro cancer cell model. They have been tested for sensitivity to more than 100,000 potential chemotherapy agents and have been profiled extensively at the DNA, RNA, protein, functional, and pharmacologic levels. We have used the NCI-60 cell lines and three additional lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis, and gene expression response by microarray. Although several studies have profiled relative basal gene expression in the NCI-60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. Twenty-two genes were differentially regulated in cells with low survival after 2-Gy gamma-rays; 14 genes identified lines more sensitive to 8 Gy. Unlike reported basal gene expression patterns, changes in expression in response to radiation showed little tissue-of-origin effect, except for differentiating the lymphoblastoid cell lines from other cell types. Basal expression patterns, however, discriminated well between radiosensitive and more resistant lines, possibly being more informative than radiation response signatures. The most striking patterns in the radiation data were a set of genes up-regulated preferentially in the p53 wild-type lines and a set of cell cycle regulatory genes down-regulated across the entire NCI-60 panel. The response of those genes to gamma-rays seems to be unaffected by the myriad of genetic differences across this diverse cell set; it represents the most penetrant gene expression response to ionizing radiation yet observed.
Pulse cyclophosphamide therapy for refractory autoimmune thrombocytopenic purpura [see comments] (1995)

Autoimmune thrombocytopenic purpura (AITP) is generally a chronic disorder in affected adults. Twenty-five percent of these patients will become refractory to routine therapy (corticosteroids and splenectomy), as well as most other available agents. Intravenous pulse cyclophosphamide therapy was used to treat 20 patients with severe refractory AITP who had previously failed to achieve a sustained remission with a mean of 4.8 agents (range 2 to 8). Patients received 1 to 4 doses (mean 2.0) of 1.0 to 1.5 g/m2 intravenous cyclophosphamide per course. Of the 20 patients treated with pulse cyclophosphamide therapy, 13 patients (65%) achieved a complete response (CR), four (20%) a partial response (PR), and three patients (15%) failed to respond. Of the 13 complete responders, eight have remained in remission with stable platelet counts during followup intervals of 7 months to 7 years (median 2.5 years). Five patients developed recurrent AITP 4 months to 3 years following a CR. Of these, two patients responded to subsequent courses of pulse cyclophosphamide therapy with current remissions of 1 and 4 years. Of the four patients who obtained a PR, two remain in partial remission after 10 months and 4 years; one relapsed after 18 months and, after retreatment, is still in remission at 6 months. Of the patient characteristics examined, duration of disease was most strongly associated with response to pulse cyclophosphamide. Side-effects of treatment included neutropenia (three patients, one of whom developed staphylococcal sepsis), acute deep venous thrombosis (two patients), and psoas abscess (one patient). Intravenous pulse cyclophosphamide should be strongly considered in the treatment of patients with refractory AITP. There is a relatively low incidence of side-effects, and it can be administered easily on an out- patient basis.
Glutamic protease distribution is limited to filamentous fungi (2004)

Glutamic proteases are a distinct, and recently re-classified, group of peptidases that are thought to be found only in fungi. We have identified and analysed the distribution of over 20 putative glutamic proteases from all fungal species whose genomes have been sequenced so far. Although absent from the Saccharomycetales class, glutamic proteases appear to be present in all other ascomycetes species examined. A large number of coding regions for glutamic proteases were also found clustered together in the Phanerochaete chrysosporium genome, despite apparently being absent from three other species of Basidiomycota.
Gigaohm resistance membrane seals with stealth probe electrodes (2010)

Direct electrical access into the cell interior is required for low-noise recording of ion channel activity, yet conventional patch clamp techniques are destructive, leading to rapid cell death, while on-chip devices have poor seal resistances. Here we report chip-based nanoscale electrodes that nondestructively incorporate into biological membranes. These consist of a metallic post with a hydrophobic band that mimics transmembrane proteins, driving insertion into the lipid membrane and forming a tight seal at the electrode-membrane interface. We demonstrate spontaneous gigaohm seals with an average seal resistance of 3.8±1.9 GΩ using red blood cells, and show the nanoband is the key attribute for high resistances.
Degradation of the BAF Complex Factor BRD9 by Heterobifunctional Ligands (2017)

The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex. Degraders of BRD9 exhibit markedly enhanced potency compared to parental ligands (10- to 100-fold). Parallel study of degraders with divergent BRD9-binding chemotypes in models of acute myeloid leukemia resolves bromodomain polypharmacology in this emerging drug class. Together, these findings reveal the tractability of non-BET bromodomain containing proteins to chemical degradation, and highlight lead compound dBRD9 as a tool for the study of BRD9.
Extent and Kinetics of Genetic Change in the omp1 Gene of Chlamydia trachomatis in Two Villages with Endemic Trachoma (1995)

Variants of Chlamydia trachomatis in two Gambian villages with hyperendemic trachoma were analyzed by omp1-based polymerase chain reaction and sequencing from conjunctival swabs. Samples collected over a 22-month period included a complete cross-sectional study of each village. Overall, 4 genovar A and 4 B variants were characterized by point mutations in the omp1 gene, resulting in changes in the inferred amino acid sequence. Two genovar A and 2 B variants accounted for 87% of the total ocular chlamydial infection in both villages. Although some flux in the prevalence of individual variants was observed overtime, their overall distribution remained remarkably stable. There was no evidence of major antigenic shift arising from recombination events at the omp1 locus as described for genital tract infection. These results indicate that omp1 variation in these two trachoma-hyperendemic communities is limited and unlikely to hamper development of trachoma vaccines based on the major outer membrane protein.
Phosphorescent C∧C* Cyclometalated PtII Dibenzofuranyl‐NHC Complexes – An Auxiliary Ligand Study (2013)

Abstract Neutral C ∧ C* cyclometalated Pt II NHC complexes have recently emerged as a new class of phosphorescent emitters with high quantum efficiencies, short decay lifetimes and high thermal stability, which makes them promising candidates for OLED applications. Herein, we report investigations on the photophysical properties of seven new Pt II complexes containing a chelating NHC dibenzofuranyl ligand (3‐methyl‐1‐dibenzo[ b , d ]furan‐4‐ylimidazole) and a bidentate monoanionic auxiliary ligand. All complexes have been fully characterized including extensive NMR studies (COSY, HSQC, HMBC, NOESY, 195 Pt NMR), three of them also by solid‐state structures. The extraordinary influence of the auxiliary ligands on the photoluminescence properties is demonstrated by quantum yields ranging from 0 % to 91 % in amorphous PMMA films at room temperature. DFT calculations were performed in order to investigate the nature of the emissive states in more detail.
RISC is a 5′ phosphomonoester-producing RNA endonuclease (2004)

Gene silencing in the process of RNA interference is mediated by a ribonucleoprotein complex referred to as RNA-induced silencing complex (RISC). Here we describe the molecular mechanism of target RNA cleavage using affinity-purified minimal RISC from human cells. Cleavage proceeds via hydrolysis and the release of a 3'-hydroxyl and a 5'-phosphate terminus. Substitution of the 2'-hydroxyl group at the cleavage site by 2'-deoxy had no significant effect, suggesting that product release and/or a conformational transition rather than a chemical step is rate-limiting. Substitution by 2'-O-methyl at the cleavage site substantially reduced cleavage, which is presumably due to steric interference. Mutational analysis of the target RNA revealed that mismatches across from the 5' or the 3' end of the siRNA had little effect and that substrate RNAs as short as 15 nucleotides were cleaved by RISC.
A Double-Blind Provocative Study Chocolate as A Trigger of Headache (1997)

A provocative double-blind study of headache was performed using chocolate as the active agent and carob as the placebo. The chocolate and carob samples were formulated to duplicate products used in an earlier study (1) in which strong differential effects between the ability of chocolate and carob to trigger headache in migraine were shown. Sixty-three women with chronic headache (50% migraine, 37.5% tension-type, 12.5% combined migraine and tension-type) participated in the study. After 2 weeks of following a diet that restricted vasoactive amine-rich foods, each subject underwent double-blinded provocative trials with two samples of chocolate and two of carob presented in random order. Diaries were maintained by the subjects throughout the study, monitoring diet and headache. The results demonstrated that chocolate was not more likely to provoke headache than was carob in any of the headache diagnostic groups (chi2(2)=0.36, p=0.83). Interestingly, these results were independent of subjects' beliefs regarding the role of chocolate in the instigation of headache (chi2(1)=0.73, p=0.39). Headache diagnosis and the concomitant use of additional vasoactive amine-containing foods were also not associated with chocolate acting as a headache trigger. Thus, contrary to the commonly held belief of patients and physicians, chocolate does not appear to play a significant role in triggering headaches in typical migraine, tension-type, or combined headache sufferers.
Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli (2016)

Significance This work presents the genome-wide replacement of all rare AGR (AGA and AGG) arginine codons in the essential genes of Escherichia coli with synonymous CGN alternatives. Synonymous codon substitutions can lethally impact noncoding function by disrupting mRNA secondary structure and ribosomal binding site-like motifs. Here we quantitatively define the range of tolerable deviation in these metrics and use this relationship to provide critical insight into codon choice in recoded genomes. This work demonstrates that genome-wide removal of AGR is likely to be possible and provides a framework for designing genomes with radically altered genetic codes.
Cellular Senescence in Yeast Caused by Carbon-Source Starvation (1972)

Cells of Saccharomyces cerevisiae survived for 14 days after the cessation of growth caused by the consumption of lactate, and they began to die exponentially. In the long lasting stationary phase, respiratory activity of yeast cells decreased stepwise: the first step occurred while cells were still viable and the second step almost con-comitantly with the loss of viability. The inactivations of respiratory enzymes, such as succinate-cytochrome c reductase system and cytochrome oxidase [EC 1. 9. 3. 1], started between the two impairment steps of respiration. The involvement of lipid peroxidation reaction in the first-step decrease in respiratory activity is suggested. The activity of this reaction, which required the presence of NADPH, increased markedly from the late log phase to the early stationary phase. In vitro experiments showed that succinate oxidase activity of yeast mitochondria was partially inactivated by lipid peroxidation system extracted from yeast.
Visual Notes and the Acquisition of Architectural Knowledge (1986)

This article discusses the value and purpose of drawing in its relationship to the design process and understanding architecture. The authors base much of their discussion on their own experiences in teaching both drawing and architectural design to undergraduates. These experiences however are informed and supported both by architectural history and theory and theories of perception and art. The authors discuss the importance of visual notes to architects of the past, note both the decline of the usage of visual notes in the twentieth century as well as their continued use by important architects of our time. This article stresses the analytical and critical value of such drawing as opposed to its pictorial purposes.
Youth, slang, and pragmatic expressions: Examples from Brazilian Portuguese1 (2007)

This article draws on an ethnographic study of the stigmatized speech style of poor black male youth in Rio de Janeiro, Brazil. These youth are said to speak gíria (‘slang’), and their speech is often described as incomprehensible to the Brazilian middle class. Speakers and listeners point to a wide range of pragmatic expressions as some of the most salient linguistic features associated with this speech style. This article presents examples from Brazilian Portuguese slang, in which youth draw on sound words, obscenities, address forms, and addressee‐oriented tags to create new pragmatic markers and forms of indefinite reference. It is argued that these pragmatic expressions offer multiple opportunities for speakers to convey stance, novelty, and style, social goals long associated with slang. This data suggests that we broaden the purview of slang beyond the lexicon to investigate the ways in which speakers actively innovate within the area of pragmatics.
Triple-negative, basal-like, and quintuple-negative breast cancers: better prediction model for survival (2010)

The QNBC/5NP subtype is a worse prognostic subgroup of TNBCs, especially in higher stage and this result may be related to adjuvant chemotherapy benefit of BLBCs, calling for caution in the identification of subgroups of patients for therapeutic classification.
Heritable pathologic cardiac hypertrophy in adulthood is preceded by neonatal cardiac growth restriction (2009)

The identification of genetic factors influencing cardiac growth independently of increased load is crucial to an understanding of the molecular and cellular basis of pathological cardiac hypertrophy. The central aim of this investigation was to determine how pathological hypertrophy in the adult can be linked with disturbances in cardiomyocyte growth and viability in early neonatal development. The hypertrophic heart rat (HHR) model is derived from the spontaneously hypertensive rat and exhibits marked cardiac hypertrophy, in the absence of a pressure load at maturity. Hearts were harvested from male HHR, and control strain normal heart rats (NHR), at different stages of postnatal development [neonatal (P2), 4 wk, 6 wk, 8 wk, 12 wk, 20 wk]. Isolated neonatal cardiomyocytes were prepared to evaluate cell size, number, and binucleation. At postnatal day 2, HHR hearts were considerably smaller than control NHR (4.3 +/- 0.2 vs. 5.0 +/- 0.1 mg/g, P < 0.05). Cardiac growth restriction in the neonatal HHR was associated with reduced myocyte size (length and width) and an increased proportion of binucleated cardiomyocytes. Furthermore, the number of cardiomyocytes isolated from HHR neonatal hearts was significantly less ( approximately 29%) than NHR. We also observe that growth stress in the neonate is associated with accentuated PI3K and suppressed MAPK activation, although these signaling pathways are normalized in the adult heart exhibiting established hypertrophy. Thus, using the HHR model, we identified novel molecular and cellular mechanisms involving premature exit from the cell cycle, reduced cardiomyocyte endowment, and dysregulated trophic signaling during early development, which are implicated in the etiology of heritable cardiac hypertrophy in the adult.
Vision-based ACC with a single camera: bounds on range and range rate accuracy (2004)

This paper describes a vision-based adaptive cruise control (ACC) system which uses a single camera as input. In particular, we discuss how to compute the range and range-rate from a single camera and discuss how the imaging geometry affects the range and range rate accuracy. We determine the bound on the accuracy given a particular configuration. These bounds in turn determine what steps must be made to achieve good performance. The system has been implemented on a test vehicle and driven on various highways over thousands of miles.
Porothramycin, a new antibiotic of the anthramycin group: Production, isolation, structure and biological activity. (1988)

A new antitumor antibiotic porothramycin was produced by a new strain of Streptomyces albus. The antibiotic was isolated in two active forms, the natural free hydroxyl form (porothramycin A) or the crystalline methyl ether form (porothramycin B) depending upon the isolation process used. Structural studies established that porothramycin is a new member of the pyrrolo[1,4]benzodiazepine group antibiotics having only one substituent on the benzene ring. The antibiotic exhibited antimicrobial activity against Gram-positive bacteria and anaerobes and significantly prolonged the survival times of mice implanted with experimental tumors.
Synthesis of substituted pyrenes by indirect methods (2013)

The pyrene nucleus is a valuable component for materials, supramolecular and biological chemistry, due to its photophysical/electronic properties and extended rigid structure. However, its exploitation is hindered by the limited range of methods and outcomes for the direct substitution of pyrene itself. In response to this problem, a variety of indirect methods have been developed for preparing pyrenes with less usual substitution patterns. Herein we review these approaches, covering methods which involve reduced pyrenes, transannular ring closures and cyclisations of biphenyl intermediates. We also showcase the diverse range of substituted pyrenes which have been reported in the literature, and can serve as building blocks for new molecular architectures.
Pseudorandom construction of low-density parity-check codes using linear congruential sequences (2002)

We consider maximal-length linear congruential sequences generated using a simple recursion to generate the bipartite graph of a low-density parity-check (LDPC) code. The main advantage is that the graph structure of the codes (edge connections) can be generated using a recursion, rather than having to store the graph connections in memory, which facilitates hardware implementation of the decoder. For this class of codes, sufficient conditions on the recursion parameters are derived, such that regular LDPC codes can be constructed with no cycles of length four or less. Simulation results show that these codes provide almost the same performance of a constrained pseudorandom construction that explicitly avoids cycles of length less than or equal to four.
Selectin Ligands Promote Ultrasound Contrast Agent Adhesion under Shear Flow (2006)

Contrast-enhanced ultrasound imaging has shown promise in the field of molecular imaging. This technique relies upon the adhesion of ultrasound contrast agent (UCA) to targeted molecular markers of disease. This is accomplished by coating the surface of the contrast agent with a ligand that specifically binds to the intended molecular marker. Most UCA particles remain in the blood space, and their retention is influenced by the forces imposed by blood flow. For a UCA bound to a molecular target on the vascular endothelium, blood flow imposes a dislodging force that counteracts retention. Additionally, contrast agent adhesion to the molecular marker requires rapid binding kinetics, especially in rapid blood flow. The ability of a ligand:target bond complex to mediate fast adhesion and withstand dislodging force is necessary for efficient ultrasound-based molecular imaging. In the current study, we describe a flow-based adhesion assay which, combined with a novel automated tracking algorithm, enables quick determination of the ability of a targeting ligand to mediate effective contrast agent adhesion. This system was used to explore the adhesion of UCA targeted to the proinflammatory endothelial protein P-selectin via four targeting ligands, which revealed several interesting adhesive behaviors. Contrast agents targeted with glycoconjugate ligands modeled on P-selectin glycoprotein ligand 1 exhibited primarily unstable or transient adhesion, while UCA targeted with an anti-P-selectin monoclonal antibody exhibited primarily firm adhesion, although the efficiency with which these agents were recruited to the target surface was relatively low.
RNA fingerprinting of respiratory syncytial virus using ribonuclease protection. Application to molecular epidemiology. (1989)

We have used the technique of ribonuclease protection to define genomic variation among circulating isolates of subgroup A respiratory syncytial (RS) virus. RNAs extracted from HEp-2 cells infected with strains to be analyzed were hybridized with a 32P-labeled RNA probe corresponding to the RS virus G glycoprotein (A2 strain). Areas of nonhomology were detected by cleavage with ribonuclease A. Using this technique, multiple distinct RNA cleavage patterns could be distinguished among viral isolates recovered from infants residing in the same metropolitan area and infected during the same epidemic season. Epidemiologically related isolates (from coinfected twins, from infants infected during a nosocomial outbreak at an extended care facility, and from institutionalized adults infected during an outbreak) yielded identical patterns. In two separate outbreaks, differences in cleavage patterns among certain isolates corresponded to epidemiologically significant differences among the individuals from whom the isolates were recovered. We conclude that substantial genomic heterogeneity exists among circulating isolates of subgroup A RS virus. Ribonuclease protection can be used as a molecular fingerprinting tool for expanded studies of the molecular epidemiology of this virus.