gebhart/patrepeval huggingface dataset:
Nonlinear-Least-Squares Analysis of Slow-Motion EPR Spectra in One and Two Dimensions Using a Modified Levenberg–Marquardt Algorithm (1996)

The application of the “model trust region” modification of the Levenberg–Marquardt minimization algorithm to the analysis of one-dimensional CW EPR and multidimensional Fourier-transform (FT) EPR spectra especially in the slow-motion regime is described. The dynamic parameters describing the slow motion are obtained from least-squares fitting of model calculations based on the stochastic Liouville equation (SLE) to experimental spectra. The trust-region approach is inherently more efficient than the standard Levenberg–Marquardt algorithm, and the efficiency of the procedure may be further increased by a separation-of-variables method in which a subset of fitting parameters is independently minimized at each iteration, thus reducing the number of parameters to be fitted by nonlinear least squares. A particularly useful application of this method occurs in the fitting of multicomponent spectra, for which it is possible to obtain the relative population of each component by the separation-of-variables method. These advantages, combined with recent improvements in the computational methods used to solve the SLE, have led to an order-of-magnitude reduction in computing time, and have made it possible to carry out interactive, real-time fitting on a laboratory workstation with a graphical interface. Examples of fits to experimental data will be given, including multicomponent CW EPR spectra as well as two- and three-dimensional FT EPR spectra. Emphasis is placed on the analytic information available from the partial derivatives utilized in the algorithm, and how it may be used to estimate the condition and uniqueness of the fit, as well as to estimate confidence limits for the parameters in certain cases.
Analysis of the Structure and Stability of a Backbone-Modified Oligonucleotide:  Implications for Avoiding Product Inhibition in Catalytic Template-Directed Synthesis (1998)

The structural and thermodynamic origins of the destabilization of a backbone-modified DNA duplex 1, formed between d(CpGpTNTpGpC), containing a single aminoethyl group (−CH2−CH2−NH2+−) in place of the phosphodiester (−O−PO2-−O−) linkage of the central TT dimer, and d(GpCpApApCpG) are investigated. Analyses for the corresponding native duplex and two other related structural analogues of duplex 1 have been compared. Duplex 1 shows a cooperative thermal melting transition that is consistent with a two-state process. At a 2 mM concentration, the melting temperature of duplex 1 is reduced by 17 °C from the native duplex, and this decrease in stability is further assigned to an unfavorable decrease in enthalpy of 7 kcal mol-1 and a favorable increase in entropy of 15 eu mol-1. NMR structural analysis shows that the modified duplex 1 still adopts a canonical B-DNA conformation with Watson−Crick base pairing preserved; however, the CH2 group that replaces the native PO2- group in the modified backbone is flexible and free to collapse onto a hydrophobic core formed by the base edges and sugar rings of the flanking TT/AA nucleosides of the duplex. This conformation is significantly different from the maximally solvent-exposed orientation of the native phosphate in DNA. The entropic origin of the 15 eu mol-1 difference between the native and the modified duplex 1 is attributed to the hydrophobic interaction between the collapsed ethylamine linkage with the hydrophobic core of duplex 1. This assignment is further supported by a favorable comparison between the observed change in entropy and the estimated value for the hydrophobic interaction around the modified region. This estimated value is based on recent experimental measurement of the hydrophobic interaction between aliphatic groups and nucleic acids as well as ethylamine solvent transfer data. The overall decrease in the stability of duplex 1 results from a decrease in base stacking and hydrogen-bonding interactions between the base pairs. A model is, therefore, proposed to explain how the change in the local backbone conformation could disrupt the long-range cooperativity of DNA duplex formation upon backbone modifications. These studies provide an approach for identifying the factors that control the stability of the nucleic acid duplex structures containing backbone modifications, with direct implication for designing antisense oligonucleotides and template-directed reactions containing non-native phosphodiester linkages.
Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs (1993)

Mild, resuscitative cerebral hypothermia induced immediately with reperfusion after cardiac arrest improves cerebral functional and morphologic outcome, whereas a delay of 15 mins in initiation of cooling after reperfusion may not improve functional outcome, although it may slightly decrease tissue damage.
Into the heart of darkness: large-scale clustering of human non-coding DNA (2004)

Supplementary material to this work is available at http://www.soe.ucsc.edu/~jill/dark.html
Cyclooxygenases in hepatocellular carcinoma (2006)

Many epidemiological studies demonstrate that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase (COX) enzymes are well-known targets of NSAIDs. However, conventional NSAIDs non-selectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by pro-inflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpressed in many premalignant, malignant, and metastastic cancers, including hepatocellular carcinoma (HCC). Overexpression of COX-2 in patients with HCC is generally higher in well-differentiated HCCs compared with less-differentiated HCCs or histologically normal liver, suggesting that COX-2 may be involved in the early stages of hepatocarcinogenesis, and increased expression of COX-2 in noncancerous liver tissue has been significantly associated with shorter disease-free survival in patients with HCC. In tumors, overexpression of COX-2 leads to an increase in prostaglandin (PG) levels, which affect many mechanisms involved in carcinogenesis, such as angiogenesis, inhibition of apoptosis, stimulation of cell growth as well as the invasiveness and metastatic potential of tumor cells. The availability of novel agents that selectively inhibit COX-2 (COXIB), has contributed to shedding light on the role of this molecule. Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects. However, the key mechanism by which COX-2 inhibitors affect HCC cell growth is as yet not fully understood. Increasing evidence suggests the involvement of molecular targets other than COX-2 in the anti-proliferative effects of COX-2 selective inhibitors. Therefore, COX-inhibitors may use both COX-2-dependent and COX-2-independent mechanisms to mediate their antitumor properties, although their relative contributions toward the in vivo effects remain less clear. Here we review the features of COX enzymes, the role of the expression of COX isoforms in hepatocarcinogenesis and the mechanisms by which they may contribute to HCC growth, the pharmacological properties of COX-2 selective inhibitors, the antitumor effects of COX inhibitors, and the rationale and feasibility of COX-2 inhibitors for the treatment of HCC.
93rd Annual Meeting of the American Association for Cancer Research, San Francisco, CA, USA, 6-10 April 2002 (2002)

The 93rd Annual Meeting of the American Association for Cancer Research (AACR) was held in the vast underground complex of the Moscone Convention Center in downtown San Francisco, through mostly beautiful early summer weather during 6–10 April 2002.

This diverse meeting, attended by more than 14,000 people, was dedicated to all methods of cancer research, from basic cell biology to advanced clinical trials. The meeting was presented in a multitude of formats: interactive 'meet the expert' sessions (at 07:00 a.m.!), plenary lectures, symposia, minisymposia, poster sessions, educational workshops, and panel discussions. Despite the scope of the meeting, many of the presentations had an intimate feel. This was in part because of the quantity and quality of not-yet-published data that was presented, and in part because of the atmosphere of discussion, even in the largest lecture halls.

The present report will cover many of the topics that were presented. Because of the scope of the conference, however, the summaries that follow are only a representative sampling.
Fabry disease, do we think enough about this multisystemic disorder?: A presentation of three cases in a Serbian family (2012)

Although most symptoms begin in childhood, various manifestations often lead to misdiagnosis and clinical diagnosis is frequently delayed for many years, even decades. Enzyme replacement therapy has become available, pointing out the importance of early diagnosis so that treatment can be initiated before irreversible organ damage.
Expression of the Yersinia pestis capsular antigen (F1 antigen) on the surface of an aroA mutant of Salmonella typhimurium induces high levels of protection against plague (1997)

The caf operon from Yersinia pestis encoding the structural subunit (caf1), the molecular chaperone (caf1M), the outer membrane anchor (caf1A), and the regulatory protein (caf1R) was cloned into Salmonella typhimurium SL3261 aroA. The recombinant Salmonella organisms were encapsulated when cultured at 37 degrees C but not when cultured at 28 degrees C. Oral inoculation of mice with the recombinant Salmonella induced predominantly an immunoglobulin G2a response to F1 antigen, and isolated T cells showed a recall response to soluble or Salmonella-associated F1 antigen. Mice immunized with S. typhimurium SL3261 aroA expressing F1 antigen intracellularly developed lower antibody responses to F1 antigen and showed a T-cell recall response only to Salmonella-associated F1 antigen. Mice immunized orally with two doses of the recombinant Salmonella which expressed F1 antigen on the surface were protected against 10(7) 50% lethal doses (LD50) of virulent Y. pestis given by the subcutaneous route of challenge, whereas mice immunized with the recombinant Salmonella expressing F1 antigen intracellularly were only partially protected against 10(5) LD50 of Y. pestis.
Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling (2004)

We analyzed global gene expression patterns of 91 human hepatocellular carcinomas (HCCs) to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with patient survival. This association was validated via 5 independent supervised learning methods. We also identified the genes most strongly associated with survival by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification, suggesting an etiological involvement of these processes in accelerating the progression of HCC. In conclusion, the biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g., HIF1a) for selective treatment of HCC patients. Supplementary material for this article can be found on the HEPATOLOGY Web site (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html)
Selective chemical vapor deposition of copper on AZ 5214™-patterned silicon substrates (2001)

Copper features with dimensions down to 0.5 μm were fabricated on silicon substrates by selective chemical vapor deposition. For the fabrication, oxidized (100) silicon substrates were used, covered with a film grown by low-pressure chemical vapor deposition at 0.1 Torr and 550 °C, from W(CO)6 decomposition. These substrates were subsequently covered with AZ 5214™ photosensitive polymer, which has been developed as both positive and negative tone resist. Copper was then chemically vapor deposited on the patterned substrates by 1, 5-cyclooctadiene Cu(I) hexafluoroacetylacetonate decomposition, at 1 Torr and temperatures of 110 and 140 °C. A vertical, cold-wall reactor was used, equipped with an UV lamp permitting photon-assisted deposition. Under UV illumination, copper was deposited on resist covered and uncovered parts of the substrate. In the absence of illumination, the metal was selectively grown on the tungsten film only at relatively slow rates (1 and 3.5 nm/min at 110 and 140 °C, respectively). Copper films had a granular form with a grain size increasing with temperature (150 and 550 nm at 110 and 140 °C, respectively). After depositions, the resist was removed in oxygen plasma leading to the formation of fine copper features.
A Simple Method for the Synthesis of Unsymmetrical Ureas (2000)

Abstract A simple one pot procedure for the synthesis of N,N'-unsymmetrical ureas using phenyl chloroformate in THF is described.
Characterization of C-reactive protein and the complement subcomponent C1t as homologous proteins displaying cyclic pentameric symmetry (pentraxins). (1977)

Partial amino acid sequences of rabbit C-reactive protein, a peptide derived from human C-reactive protein by cyanogen bromide cleavage, and the C1t subcomponent of the human complement component C1 have been determined. Extensive sequence homology between these proteins establish their evolutionary relationships. In addition, examination of C-reactive proteins by negative-stain electron microscopy revealed that the protein is composed of five subunits arranged in cyclic symmetry. This structure is similar to that reported for both C1t and the amyloid P-component. The extensive structural relationship suggests similar or overlapping functions and the term pentraxin is proposed to describe these homologous proteins.
Controlled conversion of an immortalized mesodermal progenitor cell towards osteogenic, chondrogenic, or adipogenic pathways. (1995)

The teratocarcinoma-derived C1 clone behaves as a mesodermal tripotential progenitor cell whose choice of fate, either osteoblast, chondroblast, or adipoblast, is strictly dependent on the spatial organization of the cells and the nature of the induction. In the absence of cell contact before the addition of inducers, the C1 cells maintain a stable undifferentiated phenotype while expressing potential regulators of embryonic mesodermal stem cell fate such a M-twist and Id1. Upon establishment of cell contacts before the induction of differentiation, the early genes characteristic of the three fates become expressed. In the presence of beta glycerophosphate and ascorbate, provided the cells have formed aggregates, 95% of the C1 cells mineralize with a kinetics of gene expression close to that of osteoblasts (Poliard, A., D. Lamblin, P. J. Marie, M. H. Buc, and O. Kellerman. 1993. J. Cell Sci. 106:503-512). With 10(-6)M dexamethasone, 80% of the same aggregates differentiate into foci of chondroblast-like cells. The kinetics of expression of the genes encoding type II, IX, X, and XI collagens, aggrecan and link protein during the conversion toward cartilage hypertrophy resembles that accompanying in vivo chondrogenesis. The synergistic action of dexamethasone and insulin convert most confluent C1 cells into functional adipocytes and induce a pattern of gene expression close to that reported for adipoblast cell lines. The C1 clone with its capacity to differentiate along three alternative pathways with high frequency, therefore appears as a valid in vitro model for deciphering the molecular basis of mesoblast ontogeny.
T-cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived versus thymic-independent progeny (1993)

Abstract To study the source of regenerated T cells after bone marrow transplantation (BMT), lethally irradiated thymectomized and thymus- bearing C57BL/6 (Thy 1.2+) mice were injected with syngeneic T-cell depleted bone marrow (TCD BM) cells and graded numbers of congenic B6/Thy 1.1+ lymph node (LN) cells. LN cell expansion was the predominant source for T-cell regeneration in thymectomized hosts but was minimal in thymus-bearing hosts. Analysis of T-cell receptor (TCR) expression on LN progeny showed a diverse V beta repertoire. Therefore, peripheral T-cell progenitors exist within V beta families, but expansion of these progenitors after BMT is downregulated in the presence of a functional thymus. CD4+ cells derived from BM versus LN in thymus-bearing hosts displayed differential CD44 and CD45 isoform expression. BM-derived cells were primarily CD45RB+CD44lo and LN derived cells were nearly exclusively CD45RB- CD44hi. In thymectomized hosts, BM, host, and LN CD4+ progeny were CD45RB- CD44hi. We conclude that T-cell regeneration via peripheral T-cell progenitors predominates in hosts lacking thymic function and gives rise to T cells that display a “memory” phenotype. In contrast, the ability to generate sizable populations of “naive” type T cells after BMT appears limited to the prethymic progenitor pool and could serve as a marker for thymic regenerative capacity.
Virtual humanoid robot platform to develop controllers of real humanoid robots without porting (2002)

This paper presents a virtual humanoid robot platform (V-HRP for short) on which we can develop the identical controller for a virtual humanoid robot and its real counterpart. The unification of the controllers for the virtual and real robot has been realized by introducing software adapters for two robots respectively and employing ART-Linux on which real-time processing is available at the user level. Thanks to the unification, the controllers can share softwares with the dynamics simulator of V-HRP, including the parameter parser, kinematics and dynamics computations and the collision detector. This feature can make the development of the controllers more efficient and the developed controllers more reliable.
Shrinkage estimation of dispersion in Negative Binomial models for RNA-seq experiments with small sample size (2013)

Abstract Motivation: RNA-seq experiments produce digital counts of reads that are affected by both biological and technical variation. To distinguish the systematic changes in expression between conditions from noise, the counts are frequently modeled by the Negative Binomial distribution. However, in experiments with small sample size, the per-gene estimates of the dispersion parameter are unreliable. Method: We propose a simple and effective approach for estimating the dispersions. First, we obtain the initial estimates for each gene using the method of moments. Second, the estimates are regularized, i.e. shrunk towards a common value that minimizes the average squared difference between the initial estimates and the shrinkage estimates. The approach does not require extra modeling assumptions, is easy to compute and is compatible with the exact test of differential expression. Results: We evaluated the proposed approach using 10 simulated and experimental datasets and compared its performance with that of currently popular packages edgeR, DESeq, baySeq, BBSeq and SAMseq. For these datasets, sSeq performed favorably for experiments with small sample size in sensitivity, specificity and computational time. Availability: http://www.stat.purdue.edu/∼ovitek/Software.html and Bioconductor. Contact: ovitek@purdue.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Dietary Protein Restriction Decreases Insulin-Like Growth Factor I Independent of Insulin and Liver Growth Hormone Binding* (1989)

To determine the role of hypoinsulinemia and liver somatogenic (GH) receptors in growth retardation and decreased serum insulin-like growth factor I (IGF-I) levels during protein restriction, we have used a rat model where the effects of a low protein intake on body weight (BW), serum IGF-I concentration, and liver GH binding could be evaluated in the presence of low or high insulin concentrations. Two days after being made diabetic with streptozotocin (60 mg/kg BW), 6-week-old female rats (nine per group) were begun on a low (5%) or normal (15%) protein diet, without or with insulin supplementation (3 U lente daily). Nondiabetic rats fed both diets were used as controls (nine per group). In the nondiabetic animals, 7 days of protein restriction reduced BW gain by 50% (P less than 0.001), serum insulin by 44% (P less than 0.025), and serum IGF-I concentrations by 28% (P less than 0.001) without significantly changing liver GH binding. By day 9, BW was decreased in the diabetic animals by 12%, serum insulin by 80%, serum IGF-I by 55%, and liver GH binding by 62%; these effects were similar in the 5% and 15% protein-fed rats (P less than 0.001 vs. the corresponding controls). In the diabetes fed the normal diet, insulin treatment restored BW gain, serum IGF-I, and liver GH binding to normal values. In contrast, in the diabetics fed a protein-restricted diet and treated with insulin, BW gain and serum IGF-I concentrations remained low, similar to those in the malnourished controls. This diet-induced growth attenuation was observed despite high circulating insulin (2-3 times normal values), appropriate glucose control (63 +/- 9 mg/dl), and near restoration of liver GH binding. We conclude that while both protein restriction and diabetes attenuate growth and reduce IGF-I concentrations, the effects of protein restriction are independent of the effects of insulin and probably act by alteration of postreceptor mechanisms.
Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study (2008)

Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 microg kg(-1) (lower-dose) ghrelin; 11 received 8 microg kg(-1) (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4-5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml(-1) with lower-dose and 42 ng ml(-1) with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (P<0.05) for upper-dose patients at end of study (3580 pg ml(-1)) than at baseline (990 pg ml(-1)). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower- and upper-dose group.