gebhart/patrepeval huggingface dataset:
Phase I and pharmacologic study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors. (1997)

The DLT in this phase I study for chronic oral topotecan for 21 days was diarrhea. The recommended dose for phase II studies is 0.5 mg/m2 twice daily.
Complexes of HIV-1 Reverse Transcriptase with Inhibitors of the HEPT Series Reveal Conformational Changes Relevant to the Design of Potent Non-Nucleoside Inhibitors (1996)

Crystal structures of HIV-1 reverse transcriptase (RT) complexed with a range of chemically diverse non-nucleoside inhibitors (NNIs) have shown a single pocket in which the inhibitors bind and details of the inhibitor-protein interactions. To delineate the structural requirements for an effective inhibitor, we have determined the structures of three closely related NNIs which vary widely in their potencies. Crystal structures of HIV-1 RT complexed with two very potent inhibitors, MKC-442 and TNK-651, at 2.55 angstroms resolution complement our previous analysis of the complex with the less effective inhibitor, HEPT. These structures reveal conformational changes which correlate with changes in potency. We suggest that a major determinant of increased potency in the analogues of HEPT is an improved interaction between residue Tyr181 in the protein and the 6-benzyl ring of the inhibitors which stabilizes the structure of the complex. This arises through a conformational switching of the protein structure triggered by the steric bulk of the 5-substituent of the inhibitor pyrimidine ring.
The Radon Transform and Related Transforms (1986)

In this chapter we introduce and study various integral transforms from a theoretical point of view. As general reference we recommend Helgason (1980). The material of this chapter serves as the theoretical basis for the rest of the book. It contains complete proofs, referring only to Chapter VII.
An Indirect Chaotropic Mechanism for the Stabilization of Helix Conformation of Peptides in Aqueous Trifluoroethanol and Hexafluoro-2-propanol (1998)

A revised indirect mechanism is proposed for the effect of 2,2,2-trifluoroethanol on peptide conformation (TFE effect) that suggests tighter solvent shells in pure water for helical states than random coil states. The alcoholic cosolvent stabilizes the helical state preferentially by disrupting the solvent shell, which causes unfavorable enthalpic and favorable entropic contributions to the free energy of helix formation. This revised mechanism was adopted because it best explained the solvent-dependent thermodynamic behavior of the coil/helix transition. To define the TFE effect, solvent-dependent physicochemical behaviors of two molecular probes for solvent character were monitored and compared with the solvent dependence of peptide helix formation. The rate of decarboxylation of 6-nitro-3-carboxybenzisoxazole was determined in aqueous mixtures as a function of concentration for DMSO, EtOH, MeOH, iPrOH, HFIP, and TFE. To relate these rate studies to the cosolvent-dependent thermodynamics of helix formation, ΔH⧧ and ΔS⧧ as a function of concentration for EtOH and TFE were determined and interpreted. The mixed solvent dependence of the UV spectrum of a solvatochromic ketone was also monitored to correlate the behavior of the mixed solvent systems with a microscopic polarity index.
Synthetic nucleosides and nucleotides. XIII. Stannic chloride catalyzed ribosylation of several 6-substituted purines. (1979)

Condensation of adenine (1a) with 1-O-acetyl-2, 3, 5-tri-O-benzoyl-β-D-ribofuranose (2a) in acetonitrile in the presence of stannic chloride at room temperature gave blocked nucleoside. After removal of the benzoyl group, adenosine (4a) was obtained in 78% overall yield. When 1, 2, 3, 5-tetra-O-acetyl-β-D-ribofuranose (2b) was used instead of 2a in the same reaction, 2', 3', 5'-tri-O-acetyladenosine (3b) was obtained in 77% yield. In both cases, the α-isomer or 1-, 3- or 7-riboside could not be detected in the reaction. In an application of this reaction, 6-chloropurine (1b) and purin-6-yl benzyl disulfide (1c) were coupled with 2a or 2b followed by reaction with thiourea or β-mercaptoethanol to give 2', 3', 5'-tri-O-acyl-6-thioinosine (3c). Coupling of 6-methylthiopurine (1d) with 3a after deblocking of the acyl group yielded 9-β-D-ribofuranosyl-6-methylthiopurine in 75% yield. In addition, 2, 6-dichloropurine (1e) coupled with 2b under the same conditions to give 9-β-D-ribofuranosyl-2, 6-dichlororopurine tri-O-acetate in 81% yield.
Analyzing Herbicide Interactions: A Statistical Treatment of Colby's Method (1988)

A model and a proposed method for testing herbicide interactions were modified from an analysis of variance (ANOVA) model for a 2 by 2 factorial experiment. Statistical tests for either synergism, antagonism, or additivity of herbicide combinations were developed through transforming growth data to logarithms followed by significance tests of 2 by 2 contrasts of the form μ ii - μ i0 - μ 0i + μ 00 with respect to the log-transformed data. Using actual experimental data, heterogeneity of variance was less severe on the log scale compared to the original measurement scale. An expedient SAS (R) program for obtaining the desired significance tests was developed.
A Facile Method for Oxidation of Primary Alcohols to Carboxylic Acids and Its Application in Glycosaminoglycan Syntheses (2006)

A convenient two-step, one-pot procedure was developed for the conversion of primary alcohols to carboxylic acids. The alcohol was first treated with NaOCl and TEMPO under phase-transfer conditions, followed by NaClO2 oxidation in one pot. This reaction is applicable to a wide range of alcohols and the mild reaction conditions are compatible with many sensitive functional groups, including electron-rich aromatic rings, acid-labile isopropylidene ketal and glycosidic linkages, and oxidation-prone thioacetal, p-methoxybenzyl, and allyl moieties. Several glycosaminoglycans such as heparin, chondroitin, and hyaluronic acid oligosaccharides have been synthesized in high yields by using this new oxidation protocol.
cGANs with Projection Discriminator (2018)

We propose a novel, projection based way to incorporate the conditional information into the discriminator of GANs that respects the role of the conditional information in the underlining probabilistic model. This approach is in contrast with most frameworks of conditional GANs used in application today, which use the conditional information by concatenating the (embedded) conditional vector to the feature vectors. With this modification, we were able to significantly improve the quality of the class conditional image generation on ILSVRC2012 (ImageNet) 1000-class image dataset from the current state-of-the-art result, and we achieved this with a single pair of a discriminator and a generator. We were also able to extend the application to super-resolution and succeeded in producing highly discriminative super-resolution images. This new structure also enabled high quality category transformation based on parametric functional transformation of conditional batch normalization layers in the generator.
Molecular oxygen and the state of geometric isomerism of intermediates are essential in the carotene desaturation and cyclization reactions in daffodil chromoplasts (1989)

The membrane-bound carotenogenic reaction sequence in daffodil chromoplasts can be subdivided in vitro into three reaction segments by varying the incubation parameters O2 and light. In the first segment, 15-cis-phytoene is desaturated to 15-cis-zeta-carotene (trans elimination of hydrogen) in the dark and in the presence of O2 as an essential cofactor. A photoisomerization of the 15-cis double bond of the accumulated zeta-carotene to trans is the prerequisite for the function of the second segment, the desaturation to 7,9,9',7'-tetra-cis-lycopene (prolycopene, cis elimination of hydrogen). The role of O2 as an electron acceptor is discussed and evidence for an oxidoreductase acting as a redox mediator between the desaturase (forming the polyene chromophore) and O2 is presented. A certain analogy to the desaturation of stearoyl-carrier protein, which also occurs in plastids, is proposed. The third segment, the cyclization of prolycopene, is active only in the absence of O2 and involves additional cis-trans isomerization reactions.
ACT-enabled 100 MHz channel equalizer (for magnetic recording application) (1991)

An acoustic charge transport (ACT) equalizer with 128 taps and a 180-MHz tap sampling rate is demonstrated with a variety of head responses. The standard programmable transversal filter (PTF) product has been modified for magnetic recording applications by the addition of an instrumentation interface and specialized analog circuitry for low-frequency equalization. The resulting module, when combined with controlling software is known as a filter/equalizer development station (FEDS). A laboratory system employing two such FEDS modules for separate amplitude and zero-crossing equalization in a digital saturated magnetic recording peak detection channel is modeled and demonstrated. Equalizer impacts on system speed, packing density, and error rates are predicted with a channel model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cutting Edge: CpG Oligonucleotides Induce Splenic CD19+ Dendritic Cells to Acquire Potent Indoleamine 2,3-Dioxygenase-Dependent T Cell Regulatory Functions via IFN Type 1 Signaling (2005)

CpG oligodeoxynucleotides (CpG-ODNs) stimulate innate and adaptive immunity by binding to TLR9 molecules. Paradoxically, expression of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is induced following i.v. CpG-ODN administration to mice. CpG-ODNs induced selective IDO expression by a minor population of splenic CD19+ dendritic cells (DCs) that did not express the plasmacytoid DC marker 120G8. Following CpG-ODN treatment, CD19+ DCs acquired potent IDO-dependent T cell suppressive functions. Signaling through IFN type I receptors was essential for IDO up-regulation, and CpG-ODNs induced selective activation of STAT-1 in CD19+ DCs. Thus, CpG-ODNs delivered systemically at relatively high doses elicited potent T cell regulatory responses by acting on a discrete, minor population of splenic DCs. The ability of CpG-ODNs to induce both stimulatory and regulatory responses offers novel opportunities for using them as immunomodulatory reagents but may complicate therapeutic use of CpG-ODNs to stimulate antitumor immunity in cancer patients.
An interaction of β‐amyloid with aluminium in vitro (1993)

We have used circular dichroism spectroscopy to confirm that, in a membrane-mimicking solvent, A beta P(1-40) adopts a partially helical conformation and we have demonstrated the loss of this structure in the presence of physiologically relevant concentrations of aluminium. This is the first evidence of a direct biochemical interaction between aluminium and beta-amyloid and may have important implications for the pathogenesis of Alzheimer's disease.
Evidence for the Existence of Ca2+/calmodulin-Dependent Protein Kinase IV Kinase Isoforms in Rat Brain (1996)

Calmodulin-dependent protein kinase IV (CaM-kinase IV), which plays crucial roles in the functioning of Ca2+ in the central nervous system and immune system, is markedly activated upon phosphorylation by the action of CaM-kinase IV kinase. Northern and Western blot analyses of CaM-kinase IV kinase showed relatively weak reactions in the rat cerebellum, where the activity of CaM-kinase IV kinase has been demonstrated to exist, indicating that CaM-kinase IV kinase isoforms distinct from the enzyme cloned from the cerebral cortex may exist in the cerebellum. When the crude extracts of rat cerebral cortex, brain stem, and cerebellum were immunotitrated with antibody against the cloned enzyme, only approximately 46, 56, and 25% of the enzyme activity of the respective extracts were immunoprecipitated. Thus, at least two distinct isoforms of CaM-kinase IV kinase appear to exist in the brain.
Climacteric obesity: from genesis to clinic (2006)

The etiology of obesity is multifactorial and still unclear. Genetic factors play a significant role and include several gene candidates: polymorphisms of genes for β2-adrenoreceptor, resistin, estrogen receptor-α and peroxisome proliferator-activated receptor-γ. Moreover, peptides regulating hunger and satiety, e.g. leptin, galanin, cholecystokinin and neuropeptide Y, and altered nutritional patterns have been implicated. Also, factors associated with aging, e.g. decreased levels of growth hormone and dehydroepiandrosterone, and the activity of the sympathetic nervous system (resting metabolism and thermogenesis) cannot be disregarded. Participation of the sex steroids and inflammatory factors has also been postulated in the etiology of obesity. Three phenotypes of obesity are postulated; however, the visceral (abdominal) phenotype is typical of postmenopausal women and is characterized by several metabolic disorders with high risks of diabetes mellitus type 2 and cardiovascular disease. On the basis of personal experience and data from evidence-based medicine, diagnostic–therapeutic algorithms of climacteric obesity are presented.
Sustained in vivo regression of Dunning H rat prostate cancers treated with combinations of androgen ablation and Trk tyrosine kinase inhibitors, CEP-751 (KT-6587) or CEP-701 (KT-5555). (1999)

The indolocarbazole analogue CEP-751 is a potent and selective tyrosine kinase inhibitor of the neurotrophin-specific trk receptors that has demonstrated antitumor activity in nine different models of prostate cancer growth in vivo. In the slow-growing, androgen-sensitive Dunning H prostate cancers, which express trk receptors, CEP-751 induced transient regressions independent of effects on cell cycle. Because androgen ablation is the most commonly used treatment for prostate cancer, we examined whether the combination treatment of CEP-751 with castration would lead to better antitumor efficacy than either treatment alone. For a 60-day period, H tumor-bearing rats received treatment with either castration, CEP-751 (10 mg/kg once a day s.c. for 5 days every 2 weeks), a combination of both, or vehicle. Castration caused tumor regression, followed by tumor regrowth in 4-6 weeks, whereas intermittent CEP-751 treatments resulted in tumor regressions during each treatment, which were followed by a period of regrowth between intermittent drug treatment cycles. Overall, both monotherapies significantly inhibited tumor growth compared with the vehicle-treated control group. However, the combination of castration and concomitant CEP-751 produced the most dramatic results: sigificantly greater tumor regression than either therapy alone, with no signs of regrowth. A related experiment using an orally administered CEP-751 analogue (CEP-701), as the trk inhibitor, and a gonadotrophin-releasing hormone agonist, Leuprolide, to induce androgen ablation demonstrated similar results, indicating that these effects could be generalized to other forms of androgen ablation and other trk inhibitors within this class. In addition, when CEP-701 was given sequentially to rats bearing H tumors, which were progressing in the presence of continuous androgen ablation induced by Leuprolide, regression of the androgen-independent tumors occurred. In summary, these data demonstrate that CEP-751 or CEP-701, when combined with surgically or chemically induced androgen ablation, offer better antitumor efficacy than either monotherapy and suggest that each therapy produces prostate cancer cell death through complementary mechanisms.
Wave phase conjugation of ultrasonic beams (1998)

The current state of the acoustic wave phase conjugation (PC) problem is reviewed. The generation of phase conjugate ultrasonic waves is discussed with emphasis on the parametric method using electromagnetic pumping in solids. The giant-amplification supercritical parametric PC mode is considered in detail. Ultrasonic PC with a gain in excess of 80 dB is demonstrated for a soft magnetic ceramics-based amplifier. The high quality of supercritical parametric PC sound is confirmed by acoustic-optical visualization. Acoustic PC effects, such as anomalous sound reflection at the PC mirror and the autofocusing and self-targeting of phase conjugate sound beams incident on a scatterer in a liquid, are shown. Recent experimental results demonstrating the potential of PC for applications are presented.
Generic text summarization using relevance measure and latent semantic analysis (2001)

In this paper, we propose two generic text summarization methods that create text summaries by ranking and extracting sentences from the original documents. The first method uses standard IR methods to rank sentence relevances, while the second method uses the latent semantic analysis technique to identify semantically important sentences, for summary creations. Both methods strive to select sentences that are highly ranked and different from each other. This is an attempt to create a summary with a wider coverage of the document's main content and less redundancy. Performance evaluations on the two summarization methods are conducted by comparing their summarization outputs with the manual summaries generated by three independent human evaluators. The evaluations also study the influence of different VSM weighting schemes on the text summarization performances. Finally, the causes of the large disparities in the evaluators' manual summarization results are investigated, and discussions on human text summarization patterns are presented.
TCR signaling thresholds regulating T cell development and activation are dependent upon SHP-1. (1999)

An examination of thymocytes and peripheral T cells from SHP-1-deficient motheaten mice possessing a transgenic MHC class I-restricted TCR has implicated SHP-1 in regulating TCR signaling thresholds at three checkpoints in T cell development and activation. First, in the population of CD4-CD8- double negative thymocytes, SHP-1 appears capable of regulating signals from TCR complexes that control the maturation and proliferation of double negative thymocytes. Second, the loss of SHP-1 increased the number of CD4+CD8+ double positive thymocytes capable of maturing as TCRhigh single positive thymocytes. Third, the loss of SHP-1 altered the basal level of activation of naive lymph node T cells. Accordingly, SHP-1-deficient lymph node T cells bearing the transgenic TCR demonstrated a hyperresponsiveness to stimulation with cognate peptide. However, the loss of SHP-1 did not alter the cytolytic ability of mature effector cytotoxic T lymphocytes. Together these results suggest that SHP-1 contributes to establishing thresholds for TCR signaling in thymocytes and naive peripheral T cells.
An efficient profile-analysis framework for data-layout optimizations (2002)

Data-layout optimizations rearrange fields within objects, objects within objects, and objects within the heap, with the goal of increasing spatial locality. While the importance of data-layout optimizations has been growing, their deployment has been limited, partly because they lack a unifying framework. We propose a parameterizable framework for data-layout optimization of general-purpose applications. Acknowledging that finding an optimal layout is not only NP-hard, but also poorly approximable, our framework finds a good layout by searching the space of possible layouts, with the help of profile feedback. The search process iteratively prototypes candidate data layouts, evaluating them by "simulating" the program on a representative trace of memory accesses. To make the search process practical, we develop space-reduction heuristics and optimize the expensive simulation via memoization. Equipped with this iterative approach, we can synthesize layouts that outperform existing non-iterative heuristics, tune application-specific memory allocators, as well as compose multiple data-layout optimizations.
SCCmecin staphylococci: genes on the move (2006)

Staphylococcal cassette chromosome (SCC) elements are, so far, the only vectors described for the mecA gene encoding methicillin resistance in staphylococci. SCCmec elements are classified according to the type of recombinase they carry and their general genetic composition. SCCmec types I-V have been described, and SCC elements lacking mecA have also been reported. In this review, we summarize the current knowledge about SCC structure and distribution, including genetic variants and rudiments of the elements. Its origin is still unknown, but one assumes that staphylococcal cassette chromosome is transferred between staphylococci, and mecA-positive coagulase-negative staphylococci may be a potential reservoir for these elements. Staphylococcal genomes seem to change continuously as genetic elements move in and out, but no mechanism of transfer has been found responsible for moving SCC elements between different staphylococcal species. Observations suggesting de novo production of methicillin-resistant staphylococci and horizontal gene transfer of SCCmec will be discussed.
Fuzzy Controller Design for a Automotive Air Suspension (2012)

본 연구의 목적은 에어 서스펜션 시스템의 제어 특성을 분석하는 것이다. 우선 에어 서스펜션 시스템의 수학적 모델을 구하였다. 그리고 퍼지 제어 알고리즘을 적용하여 반능동식 하이브리드 제어 에어 서스펜션을 구하였다. 차체 가속도에 따라 퍼지 제어기는 오리피스 개도를 변경하여 특정 영역에서 에어 스프링의 강도를 조정한다. 동시에 서스펜션 운동 상태에 따라 서스펜션 댐핑이 제어된다. 시뮬레이션 결과는 반능동식 하이브리드 제어 에어 서스펜션이 노면 접지능력의 상실이나 서스펜션 작동 공간의 증가 없이 최고의 승차감을 제공할 수 있음을 보여준다.
Macrophage Microbicidal Mechanisms In Vivo: Reactive Nitrogen versus Oxygen Intermediates in the Killing of Intracellular Visceral Leishmania donovani (1999)

To determine the relative contributions of respiratory burst-derived reactive oxygen intermediates (ROI) versus reactive nitrogen intermediates (RNI) to macrophage-mediated intracellular host defense, mice genetically deficient in these mechanisms were challenged with Leishmania donovani, a protozoan that selectively parasitizes visceral tissue macrophages. During the early stage of liver infection at wk 2, both respiratory burst-deficient gp91(phox)-/- (X-linked chronic granulomatous disease [X-CGD]) mice and inducible nitric oxide synthase (iNOS) knockout (KO) mice displayed comparably increased susceptibility. Thereafter, infection was unrestrained in mice lacking iNOS but was fully controlled in X-CGD mice. Mononuclear cell influx into infected liver foci in X-CGD and iNOS KO mice was also overtly impaired at wk 2. However, granuloma assembly in parasitized tissue eventually developed in both hosts but with divergent effects: mature granulomas were functionally active (leishmanicidal) in X-CGD mice but inert in iNOS-deficient animals. These results suggest that (a) ROI and RNI probably act together in the early stage of intracellular infection to regulate both tissue recruitment of mononuclear inflammatory cells and the initial extent of microbial replication, (b) RNI alone are necessary and sufficient for eventual control of visceral infection, and (c) although mature granulomas have traditionally been associated with control of such infections, these structures fail to limit intracellular parasite replication in the absence of iNOS.