gebhart/patrepeval huggingface dataset:
Azobenzene Photoswitching without Ultraviolet Light (2011)

Most azobenzene-based photoswitches use UV light for photoisomerization. This can limit their application in biological systems, where UV light can trigger unwanted responses, including cellular apoptosis. We have found that substitution of all four ortho positions with methoxy groups in an amidoazobenzene derivative leads to a substantial (~35 nm) red shift of the n-π* band of the trans isomer, separating it from the cis n-π* transition. This red shift makes trans-to-cis photoswitching possible using green light (530-560 nm). The cis state is thermally stable with a half-life of ~2.4 days in the dark in aqueous solution. Reverse (cis-to-trans) photoswitching can be accomplished with blue light (460 nm), so bidirectional photoswitching between thermally stable isomers is possible without using UV light at all.
Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease (2005)

MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO2 values. Long-term studies in females are warranted.
The combining DAG: a technique for parallel data flow analysis (1994)

As the number of available multiprocessors increases, so does the importance of providing software support for these systems, including parallel compilers. Data flow analysis, an important component of software tools, may be computed many times during the compilation of a program, especially when compiling for a multiprocessor. Although converting a sequential data flow algorithm to a parallel algorithm can present some opportunities for computing data flow in parallel, more parallelism can be exposed by the development of new parallel data flow algorithms. We present a technique that computes rapid data flow problems in parallel and thus is applicable for commonly used classical data flow problems, including reaching definitions, reachable uses, available expressions, and very busy expressions. Unlike previous techniques, our technique exploits the inherent parallelism in the data flow computation that occurs across independent paths, within linear paths, and in paths through loops of a control flow graph. The technique first changes cyclic structures in a control flow graph to acyclic structures and then builds a combining directed acyclic graph (DAG) that represents the paths through the control flow graph needed to compute data flow. Data flow is then computed using two passes over the DAG by computing the data flow for the nodes on each level of the DAG in parallel. We also present experimental results comparing the performance of our algorithm with a sequential algorithm and a parallelized sequential algorithm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Developmental changes in neural progenitor cell lineage commitment do not depend on epidermal growth factor receptor signaling (2000)

Multipotent neural progenitor cells become progressively more biased towards a glial fate during development coincident with an increase in expression of the epidermal growth factor receptor (EGFR). To determine whether differences in lineage commitment of neural progenitor cells from different stages are causally related to expression of the EGFR and whether generation of glia is EGFR-dependent, we used an EGFR-specific tyrosine kinase inhibitor, PD158780, to block the activation of EGFR in progenitor cells. Treatment of cultured neonatal progenitor cells with PD158780 completely blocked EGF-induced proliferation of the cells but did not affect bFGF-induced proliferation. Nevertheless, treatment with the inhibitor failed to inhibit the generation of astroglia in the presence of either EGF or bFGF. Treatment with bone morphogenetic protein-2 (BMP2) enhanced astroglial differentiation and suppressed oligodendroglial (OL) differentiation. PD158780 treatment had no effect on the BMP2-induced astroglial differentiation or OL suppression. These observations suggest that the generation of astroglia is not dependent on EGFR activation. Because it was still possible that the progenitor cell responses reflected a prior history of EGFR signaling, rat forebrain cells were cultured in the presence of PD158780 from a time (E12.5) preceding expression of the EGFR. After time in culture, the E12.5 cells expressed EGFR by Western analysis both in the presence and in the absence of PD158780, but activation of EGFR kinase (receptor autophosphorylation) was undetectable in the presence of PD158780 and the cells did not proliferate in response to EGF. Nevertheless, astroglial differentiation was normal in PD158780-treated cells both in the absence and in the presence of BMPs or CNTF. Furthermore, the propensity towards glial differentiation increased with time in culture even in the absence of EGFR signaling. This suggests that the increased bias towards glial differentiation during development does not depend on EGFR signaling. J. Neurosci. Res. 59:312–320, 2000 © 2000 Wiley-Liss, Inc.
Conjunctive Therapy of Cisplatin With the OCT2 Inhibitor Cimetidine: Influence on Antitumor Efficacy and Systemic Clearance (2013)

The organic cation transporter 2 (OCT2) regulates uptake of cisplatin in proximal tubules, and inhibition of OCT2 protects against severe cisplatin-induced nephrotoxicity. However, it remains uncertain whether potent OCT2 inhibitors, such as cimetidine, can influence the antitumor properties and/or disposition of cisplatin. Using an array of preclinical assays, we found that cimetidine had no effect on the uptake and cytotoxicity of cisplatin in ovarian cancer cells with high OCT2 mRNA levels (IGROV-1 cells). Moreover, the antitumor efficacy of cisplatin in mice bearing luciferase-tagged IGROV-1 xenografts was unaffected by cimetidine (P = 0.39). Data obtained in 18 patients receiving cisplatin (100 mg/m(2)) in a randomized crossover fashion with or without cimetidine (800 mg × 2) revealed that cimetidine did not alter exposure to unbound cisplatin, a marker of antitumor efficacy (4.37 vs. 4.38 µg·h/ml; P = 0.86). These results support the future clinical exploration of OCT2 inhibitors as specific modifiers of cisplatin-induced nephrotoxicity.
Narrowband laser produced extreme ultraviolet sources adapted to silicon/molybdenum multilayer optics (1998)

The extreme ultraviolet radiation emitted from a plasma generated by a pulsed Nd:yttrium aluminum garnet laser is investigated around 13 nm wavelength for several low Z elements (lithium, nitrogen, oxygen, fluorine). A narrowband EUV source can be designed by using the narrowband line emission of low Z elements in combination with the broadband reflection characteristic of silicon/molybdenum (Si/Mo) multilayer mirrors. Experimental results are discussed within a theoretical model, which allows a deduction of an optimization criterion for a maximum conversion efficiency. The Lyman-α line of hydrogenlike lithium ions fulfills the demands for high intense, free-standing narrowband emission at the long wavelength side of the silicon absorption L edge.
Atomic resolution crystal structures of HIV‐1 protease and mutants V82A and I84V with saquinavir (2007)

Saquinavir (SQV), the first antiviral HIV-1 protease (PR) inhibitor approved for AIDS therapy, has been studied in complexes with PR and the variants PR(I) (84V) and PR(V) (82A) containing the single mutations I84V and V82A that provide resistance to all the clinical inhibitors. Atomic resolution crystal structures (0.97-1.25 A) of the SQV complexes were analyzed in comparison to the protease complexes with darunavir, a new drug that targets resistant HIV, in order to understand the molecular basis of drug resistance. PR(I) (84V) and PR(V) (82A) complexes were obtained in both the space groups P2(1)2(1)2 and P2(1)2(1)2(1), which provided experimental limits for the conformational flexibility. The SQV interactions with PR were very similar in the mutant complexes, consistent with the similar inhibition constants. The mutation from bigger to smaller amino acids allows more space to accommodate the large group at P1' of SQV, unlike the reduced interactions observed in darunavir complexes. The residues 79-82 have adjusted to accommodate the large hydrophobic groups of SQV, suggesting that these residues are intrinsically flexible and their conformation depends more on the nature of the inhibitor than on the mutations in this region. This analysis will assist with development of more effective antiviral inhibitors.
Vasodilation to acetylcholine in primary and secondary forms of human hypertension. (1993)

Endothelium-dependent vasodilatation to acetylcholine is reduced in the forearm of essential hypertensive patients. To investigate whether endothelium-dependent vasodilatation is reduced also in secondary hypertension, we evaluated the effects of an intrabrachial infusion of acetylcholine on forearm blood flow (strain-gauge venous plethysmography) in essential hypertensive (n = 12), primary aldosteronism hypertensive (n = 8), and renovascular hypertensive (n = 8) patients and normotensive control subjects (n = 12). To further evaluate the role of a cyclooxygenase-dependent endothelium-derived vasoconstrictor substance, we repeated the infusion of acetylcholine in the presence of indomethacin. The effect of the direct vasodilator sodium nitroprusside was also examined. The vasodilatation to acetylcholine was reduced in essential, primary aldosteronism, and renovascular hypertensive patients compared with normotensive subjects. In contrast, the vasodilatation induced by sodium nitroprusside was similar in all groups of patients and control subjects. In the presence of indomethacin, the vasodilator effect of acetylcholine was increased in essential hypertensive patients but not in normotensive or in secondary hypertensive individuals. These data demonstrate an impairment of endothelium-dependent vasodilation in renovascular and primary aldosteronism hypertensive patients and indicate that a cyclooxygenase-dependent vasoconstrictor mechanism participates in the blunting of endothelium-dependent vasodilation in essential hypertensive patients.
Hepatitis B virus X gene can transactivate heterologous viral sequences. (1989)

The smallest open reading frame of hepatitis B virus (HBV) has been designated the X gene and its biological function during HBV infection and replication is not known. Experiments described here demonstrate that expression of the HBV X gene in HepG2 cells containing a plasmid with the chloramphenicol acetyltransferase (CAT) gene under control of the human immunodeficiency virus (HIV-1) long terminal repeat (LTR) sequence leads to a marked increase in CAT gene transcription as well as expression of the gene product (CAT). The HIV-1 tatIII gene and the HBV X gene together increased HIV-1 LTR-regulated CAT expression above that observed with either gene alone, suggesting a synergistic effect of the X gene and tat. HBV X gene also stimulated expression of the CAT gene under control of the simian virus 40 enhancer and early promoter but not the visna virus LTR or the human T-cell lymphotropic virus type I (HTLV-I) LTR, indicating that the HBV X gene can transactivate some but not other heterologous viral sequences. Transactivation of the HIV-1 LTR by the HBV X gene varied in different cell lines, suggesting that it may be mediated by a cellular factor(s).
Predicting the efficacy of short oligonucleotides in antisense and RNAi experiments with boosted genetic programming (2004)

We develop a genetic programming based prediction system that shows promising results on both antisense and siRNA efficacy prediction. We train and evaluate our system on a previously published database of antisense efficacies and our own database of siRNA efficacies collected from the literature. The best models gave an overall correlation between predicted and observed efficacy of 0.46 on both antisense and siRNA data. As a comparison, the best correlations of support vector machine classifiers trained on the same data were 0.40 and 0.30, respectively.
From Distributed Resources to Limited Slots in Multiple-Item Working Memory: A Spiking Network Model with Normalization (2012)

Recent behavioral studies have given rise to two contrasting models for limited working memory capacity: a "discrete-slot" model in which memory items are stored in a limited number of slots, and a "shared-resource" model in which the neural representation of items is distributed across a limited pool of resources. To elucidate the underlying neural processes, we investigated a continuous network model for working memory of an analog feature. Our model network fundamentally operates with a shared resource mechanism, and stimuli in cue arrays are encoded by a distributed neural population. On the other hand, the network dynamics and performance are also consistent with the discrete-slot model, because multiple objects are maintained by distinct localized population persistent activity patterns (bump attractors). We identified two phenomena of recurrent circuit dynamics that give rise to limited working memory capacity. As the working memory load increases, a localized persistent activity bump may either fade out (so the memory of the corresponding item is lost) or merge with another nearby bump (hence the resolution of mnemonic representation for the merged items becomes blurred). We identified specific dependences of these two phenomena on the strength and tuning of recurrent synaptic excitation, as well as network normalization: the overall population activity is invariant to set size and delay duration; therefore, a constant neural resource is shared by and dynamically allocated to the memorized items. We demonstrate that the model reproduces salient observations predicted by both discrete-slot and shared-resource models, and propose testable predictions of the merging phenomenon.
Thread-level speculation on off-the-shelf hardware transactional memory (2014)

Thread-level speculation can speed up a single-thread application by splitting its execution into multiple tasks and speculatively executing those tasks in multiple threads. Efficient thread-level speculation requires hardware support for memory conflict detection, store buffering, and execution rollback, and in addition, previous research has also proposed advanced optimization facilities, such as ordered transactions and data forwarding. Recently, implementations of hardware transactional memory (HTM) are coming into the market with minimal hardware support for thread-level speculation. However, few implementations offer advanced optimization facilities. Thus, it is important to determine how well thread-level speculation can be realized on the current HTM implementations, and what optimization facilities should be implemented in the future. In our research, we studied thread-level speculation on the off-the-shelf HTM implementation in Intel TSX. We manually modified potentially parallel benchmarks in SPEC CPU2006 for thread-level speculation. Our experimental results showed that thread-level speculation resulted in up to an 11% speed-up even without the advanced optimization facilities, but actually degraded the performance in most cases. In contrast to our expectations, the main reason for the performance loss was not the lack of hardware support for ordered transactions but the transaction aborts due to memory conflicts. Our investigation suggests that future hardware should support not only ordered transactions but also memory data forwarding, data synchronization, multi-version cache, and word-level conflict detection for thread-level speculation.
Expression of the Salmonella virulence plasmid gene spvB in cultured macrophages and nonphagocytic cells (1993)

Certain serotypes of salmonellae carry virulence plasmids that greatly enhance the pathogenicity of these bacteria in experimentally infected mice. This phenotype is largely attributable to the 8-kb spv regulon. However, spv genes are not expressed while bacteria grow in vitro. We now show that spvB, which is required for virulence, is expressed rapidly after Salmonella dublin is ingested by cultured J774 and murine peritoneal macrophages and that expression is not affected by the alkalinization of intracellular vesicles. The level of induction of spvB is reduced when macrophages are pretreated with gamma interferon. spvB is also expressed in human and canine epithelial cell lines and a human hepatoma cell line. In all cases, spvB expression is dependent on the spvR gene, just as it is in stationary-phase cultures in vitro. These data suggest that spv virulence genes are expressed by intracellular salmonellae in vivo in response to a signal that is common to the intracellular compartments of cells that are invaded by salmonellae.
Identification of the Minimal Lysosomal Enzyme Recognition Domain in Cathepsin D (2005)

Specific recognition of lysosomal hydrolases by UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, the initial enzyme in the biosynthesis of mannose 6-phosphate residues, is governed by a common protein determinant. Previously, we generated a lysosomal enzyme recognition domain in the secretory protein glycopepsinogen by substituting in two regions (lysine 203 and amino acids 265-293 of the beta loop) from cathepsin D, a highly related lysosomal protease. Here we show that substitution of just two lysines (Lys-203 and Lys-267) stimulates mannose phosphorylation 116-fold. Substitution of additional residues in the beta loop, particularly lysines, increased phosphorylation 4-fold further, approaching the level obtained with intact cathepsin D. All the phosphorylation occurred at the carboxyl lobe glycan, indicating that additional elements are required for phosphorylation of the amino lobe glycan. These data support the proposal that as few as two lysines in the correct orientation to each other and to the glycan can serve as the minimal elements of the lysosomal enzyme recognition domain. However, our findings show that the spacing between lysines is flexible and other residues contribute to the recognition marker.
Phase 1 Trial of Intranodal Injection of a Melan-A/MART-1 DNA Plasmid Vaccine in Patients With Stage IV Melanoma (2008)

Nineteen patients with stage IV melanoma were treated in an escalating dose, phase 1 trial of a DNA plasmid vaccine pSEM. The plasmid encoded T-cell epitopes from differentiation antigens Melan-A/melanoma antigen recognized by T cells (MART)-1 and tyrosinase, encompassing amino acids 26-35 and 31-70 from Melan-A/MART-1, and 1-9 as well as 369-377 from tyrosinase. End points of the trial were safety, tolerability, and melanoma antigen-specific immunity by tetramer assay. Intralymph nodal infusions of the vaccine were given 4 times, every 2 weeks over 96 hours each to groin lymph nodes. Vaccine doses were 500, 1000, and 1500 microg of DNA per infusion. Disease evaluation was performed 8 weeks after treatment initiation. The vaccine was well tolerated, with only grade I/II toxicity observed and no dose limiting toxicity at the highest dose of 1500 microg per infusion. Immune response defined prospectively was seen in 4/19 patients, and 5/19 had evidence of preexisting immunity to Melan-A/MART-1. No immune responses to tyrosinase was seen. There was a correlation between time to progression (TTP) and Melan-A/MART-1 immunity (preexisting or induced) for all patients. There was no association between TTP and immune competence assayed by ex vivo polyclonal stimulation of peripheral blood mononuclear cells. No clinical responses were seen. DNA plasmid pSEM vaccine was well tolerated when administered intranodally by 96-hour infusion to patients with stage IV melanoma, and was immunogenic, but did not induce regression of established disease. The association of TTP with preexisting or induced Melan-A immunity supports future attempts to induce potent immunity to this antigen.
Mapping the Intercellular Adhesion Molecule-1 and -2 Binding Site on the Inserted Domain of Leukocyte Function-associated Antigen-1 (1998)

By extensive mutagenic analysis of the inserted domain (I-domain) of the alpha-chain (CD11a) of the leukocyte function-associated antigen-1 (LFA-1), we have defined a putative binding surface for intercellular adhesion molecules 1 and 2 (ICAM-1 and -2). This analysis showed that individually mutating Leu-205 or Glu-241 to alanine completely abolished LFA-1 binding to ICAM-1 or -2 without affecting I-domain structure, as assayed by antibody binding. Mutating Thr-243 to alanine also had a profound effect on LFA-1 binding to ICAM-1 and -2, as seen by complete loss of binding to ICAM-1 and a significant reduction (70% decrease) in binding to ICAM-2. Mutating Glu-146 to alanine reduced LFA-1 binding to ICAM-1 or -2 by 70%, and mutating His-264 or Glu-293 to alanine reduced binding to ICAM-1 or -2 by about 30-40%. Mutating Thr-175 to alanine reduced binding to ICAM-1 by about 30% and binding to ICAM-2 by about 70%. Interestingly, mutating Lys-263 to alanine preferentially abolished LFA-1 binding to ICAM-2. Using these data, we have generated a model of the interface between the LFA-1 I-domain and residues in the first domain of ICAM-1 that have been shown to be critical for this interaction. In addition, this model, together with the ICAM-2 crystal structure, has been used to map residues that are likely to mediate LFA-1 I-domain binding to ICAM-2.
Prevalence of Bacterial Vaginosis and Vaginal Flora Changes in Peri- and Postmenopausal Women (2002)

Our aim was to evaluate the prevalence of bacterial vaginosis and decrease in lactobacillus colonization in women 40 years old or older in relation to menopausal status by evaluation of Gram-stained smears. A total of 1,486 smears from Italian Caucasian women aged 40 to 79 years were examined. Women were classified as follows: fertile (regular cycles) (n = 328), perimenopausal (irregular cycles) (n = 237), and postmenopausal (n = 921), including 331 women on estroprogestinic hormone replacement therapy (HRT). The prevalences of bacterial vaginosis (assessed as a Nugent score of >or=7) in fertile (9.8%) and perimenopausal (11.0%) women were not statistically different, whereas the prevalence was significantly lower overall in postmenopausal women (6.0%) (P = 0.02). Specifically, 6.3% of postmenopausal women without HRT and 5.4% of postmenopausal women with HRT were positive for bacterial vaginosis. The Nugent score system was not adequate for evaluating the normal and intermediate vaginal flora in women over the age of 40 years. High numbers of peri- and postmenopausal women had no lactobacilli and no bacterial-vaginosis-associated microorganisms. This nonpathological absence of lactobacilli in women with a Nugent score of 4 was scored as 4*, and this group was considered separately from the intermediate flora group. A score of 4* was obtained for 2.1% of fertile women, 11.4% of perimenopausal women, 44.1% of postmenopausal women without HRT, and 6.9% of postmenopausal women with HRT. The physiological reduction in lactobacillus colonization of the vagina in postmenopausal women does not cause an increase in bacterial-vaginosis prevalence. Reversion of lactobacillus flora to premenopausal levels due to HRT does not increase the prevalence of bacterial vaginosis in postmenopausal women.