gebhart/patrepeval huggingface dataset:
Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL (2003)

Heterogeneity in the clinical behavior of patients with chronic lymphocytic leukemia (CLL) makes it difficult for physicians to accurately identify which patients may benefit from an early or more aggressive treatment strategy and to provide patients with relevant prognostic information. Given the potential efficacy of newer therapies and the desire to treat patients at "optimum" times, it is more important than ever to develop sensitive stratification parameters to identify patients with poor prognosis. The evolution of risk stratification models has advanced from clinical staging and use of basic laboratory parameters to include relevant biologic and genetic features. This article will review the dramatic progress in prognostication for CLL and will propose statistical modeling techniques to evaluate the utility of these new measures in predictive models to help determine the optimal combination of markers to improve prognostication for individual patients. This discussion will also elaborate which markers and tools should be used in current clinical practice and evaluated in ongoing clinical trials.
Intraband transitions in semiconductor nanocrystals (1998)

Intraband spectra of CdSe nanocrystal colloids are observed. The photoexcited nanocrystals, of average diameters 31.5, 38, and 43 Å, exhibit an isolated and strong infrared-induced absorption with peak energy between 0.5 and 0.3 eV. The energies and cross sections of the resonance are consistent with a one-electron transition between the delocalized 1Se and 1Pe states of the strongly confined quantum dots.
Joining of Short DNA Oligonucleotides with Base Pair Mismatches by T4 DNA Ligase (2001)

Oligonucleotide-directed mutagenesis is a widely used method for studying enzymes and improving their properties. The number of mutants that can be obtained with this method is limited by the number of synthetic 25-30mer oligonucleotides containing the mutation mismatch, becoming impracticably large with increasing size of a mutant library. To make this approach more practical, shorter mismatching oligonucleotides (7-12mer) might be employed. However, the introduction of these oligonucleotides in dsDNA poses the problem of sealing a DNA nick containing 5'-terminal base pair mismatches. In the present work we studied the ability of T4 DNA ligase to catalyze this reaction. It was found that T4 DNA ligase effectively joins short oligonucleotides, yielding dsDNA containing up to five adjacent mismatches. The end-joining rate of mismatching oligonucleotides is limited by the formation of the phosphodiester bond, decreasing with an increase in the number of mismatching base pairs at the 5'-end of the oligonucleotide substrate. However, in the case of a 3 bp mismatch, the rate is higher than that obtained with a 2 bp mismatch. Increasing the matching length with the number of mismatching base pairs fixed, or moving the mismatching motif downstream with respect to the joining site increases the rate of ligation. The ligation rate increases with the molar ratio [oligonucleotide:dsDNA]; however, at high excess of the oligonucleotide, inhibition of joining was observed. In conclusion, 9mer oligonucleotides containing a 3 bp mismatch are found optimal substrates to introduce mutations in dsDNA, opening perspectives for the application of T4 DNA ligase in mutagenesis protocols.
Frequent display of human papillomavirus type 16 E6-specific memory t-Helper cells in the healthy population as witness of previous viral encounter. (2003)

Genital human papillomavirus (HPV) infection is common and the majority of infected individuals successfully deal with this virus. Clearance of HPV is presumably mediated by T cells but HPV-16-specific T-cell memory was usually detected in patients with progressive disease and not in healthy subjects, suggesting that HPV-immunity comes too late. We now show the presence of HPV-16 E6-specific memory T-helper (Th) responses in a major fraction (12 of 20) of healthy individuals by application of the IFN-gamma-ELISPOT assay. Although nearly all E6-peptides were recognized, the majority of the responders targeted peptide sequences of the COOH-terminal half (E6(81-158)) of HPV-16 E6. In a direct comparison, the presence of HPV-16 E6-specific T cells coincided with HPV-16 E2-specific T-cell reactivity in healthy individuals, whereas hardly any HPV-16 E7-specific Th immunity was found. This indicates that the induction of T-cell reactivity against HPV-16 E7 is suboptimal during infection when compared with that against HPV-16 E2 and HPV-16 E6. In conclusion, the presence of HPV-16 E6-specific Th memory in the healthy population demonstrates that HPV infection leads to T-cell immunity against immediate early proteins expressed during infection. Because this HPV-16 E6-specific T-cell immunity was frequently detected in healthy subjects, our data suggest that the observed IFN-gamma-producing proliferating T cells circulating in the peripheral blood play a role in protection against persistent HPV infection and associated development of malignancies.
Clarification and application of an ion parametric resonance model for magnetic field interactions with biological systems (1994)

Theoretical models proposed to date have been unable to clearly predict biological results from exposure to low-intensity electric and magnetic fields (EMF). Recently a predictive ionic resonance model was proposed by Lednev, based on an earlier atomic spectroscopy theory described by Podgoretskii and Podgoretskii and Khrustalev. The ion parametric resonance (IPR) model developed in this paper corrects mathematical errors in the earlier Lednev model and extends that model to give explicit predictions of biological responses to parallel AC and DC magnetic fields caused by field-induced changes in combinations of ions within the biological system. Distinct response forms predicted by the IPR model depend explicitly on the experimentally controlled variables: magnetic flux densities of the AC and DC magnetic fields (Bac and Bdc, respectively); AC frequency (fac); and, implicitly, charge to mass ratio of target-ions. After clarifying the IPR model and extending it to combinations of different resonant ions, this paper proposes a basic set of experiments to test the IPR model directly which do not rely on the choice of a particular specimen or endpoint. While the fundamental bases of the model are supported by a variety of other studies, the IPR model is necessarily heuristic when applied to biological systems, because it is based on the premise that the magnitude and form of magnetic field interactions with unhydrated resonant ions in critical biological structures alter ion-associated biological activities that may in turn be correlated with observable effects in living systems.
Pentavalent Antimony-Mannan Conjugate Therapy of Experimental Visceral Leishmaniasis (1996)

Pentavalent antimony-mannan (Sb[V]-mannan) was 10-fold more potent than sodium stibogluconate in a murine model of visceral leishmaniasis. Liver antimony concentrations were six-fold higher after Sb[V]-mannan therapy compared with a dose of sodium stibogluconate that was equipotent in reducing liver parasite burdens. Murine toxicity of Sb[V]-mannan was variable, with a 50% lethal dose (LD50) for one preparation that was well above the concentration that killed 90% of the parasites, and for another preparation was only modestly higher than the concentration that killed 90% of the parasites.
A 15 amino acid fragment of influenza nucleoprotein synthesized in the cytoplasm is presented to class I-restricted cytotoxic T lymphocytes. (1989)

A recombinant vaccinia has been designed to express amino acids 366-379 of influenza nucleoprotein, previously shown to be the minimal epitope recognized by a class I-restricted cytotoxic T cell clone. Target cells infected with the recombinant vaccinia virus expressing this peptide are recognized by CTL as efficiently as target cells expressing the complete nucleoprotein. The results imply the existence of a peptide transport system that constitutively passes the products of degraded proteins from the cytoplasm into a membrane-bound compartment of the cell.
Immunogenicity of recombinant GA733-2E antigen (CO17-1A, EGP, KS1-4, KSA, Ep-CAM) in gastro-intestinal carcinoma patients (2001)

Targeting the GA733 antigen (also known as CO17-1A, EGP, KS1-4, KSA, Ep-CAM) by monoclonal antibody CO17-1A or anti-idiotypic antibodies mimicking the CO17-1A or GA733 epitope has induced prolonged survival and specific immune responses to the antigen, respectively, in colorectal cancer (CRC) patients. In pre-clinical studies in mice and rabbits, recombinant baculovirus-derived GA733-2E antigen was superior to anti-idiotypic antibodies at modulating specific immune responses. Our aim was to evaluate the immunogenicity and potential toxicity of alum-precipitated GA733-2E in a phase I trial in patients with resected CRC or pancreatic cancer. Six patients with advanced pancreatic carcinoma and 6 with CRC Dukes' stage A, B or C received between 4 and 7 doses of alum-precipitated GA733-2E at 50, 200 or 800 microg/dose at monthly intervals. Antibody binding to GA733-2E or antigen-positive CRC cells was determined, as were antigen-specific proliferative, cytolytic T-lymphocyte and delayed-type hypersensitivity responses. Six of the 12 patients developed antigen-specific humoral immune responses after immunotherapy, and 8 developed cellular immune responses. The overall immune response rate, including patients with humoral and/or cellular immune responses, was 83%. Median overall survival of the CRC and pancreatic cancer patients was 39.8 and 11.2 months, respectively. Following 18 years of single-epitope targeting of the GA733 antigen, immunization of patients against multiple epitopes of the antigen frequently induces an immune response in the absence of significant toxicity, despite relatively widespread expression of this antigen on normal epithelial cells.
A double blind, placebo‐controlled study to assess the effect of famciclovir on virus replication in patients with chronic hepatitis B virus infection (1996)

This is the first double-blind controlled study of famciclovir, an oral antiviral agent, as potential therapy for chronic hepatitis B virus (HBV) carries. A fall of more than 90% in HBV DNA levels was noted in six of 11 evaluable patients treated with a 10 day course of oral famciclovir. Further studies with more prolonged therapy are ongoing.
Investigation into the growth of gold nanoparticles immobilized on a mica surface due to tetrachloroauric acid reduction by hydrogen peroxide (2011)

The growth of gold nanoparticles 10 nm in size immobilized on the mica surface under the effect of tetrachloroauric acid and different hydrogen peroxide concentrations in the range from 2 × 10−6 M to 2 × 10−2 M has been studied. An investigation into the kinetics of this process by atomic force microscopy has shown that the position of the maximum in histograms of the particle height distribution depends on the hydrogen peroxide concentration and the process duration. The number of particles does not substantially change during this process. The growth of the particles stops 30 min after the reaction starts.
Distributed algorithm for optimal power flow on a radial network (2014)

The optimal power flow (OPF) problem is fundamental in power system operations and planning. Large-scale renewable penetration calls for real-time feedback control, and hence the need for fast and distributed solutions for OPF. This is difficult because OPF is nonconvex and Kirchhoff's laws are global. In this paper we propose a solution for radial networks. It exploits recent results that suggest solving for a globally optimal solution of OPF over a radial network through the second-order cone program (SOCP) relaxation. Our distributed algorithm is based on alternating direction method of multiplier (ADMM), but unlike standard ADMM algorithms that often require iteratively solving optimization subproblems in each ADMM iteration, our decomposition allows us to derive closed form solutions for these subproblems, greatly speeding up each ADMM iteration. We present simulations on a real-world 2,065-bus distribution network to illustrate the scalability and optimality of the proposed algorithm.
Voltage-dependent Anion-selective Channels VDAC2 and VDAC3 Are Abundant Proteins in Bovine Outer Dense Fibers, a Cytoskeletal Component of the Sperm Flagellum (2004)

Outer dense fibers (ODF) are specific subcellular components of the sperm flagellum. The functions of ODF have not yet been clearly elucidated. We have investigated the protein composition of purified ODF from bovine spermatozoa and found that one of the most abundant proteins is a 30-32-kDa polypeptide. This protein was analyzed by sequencing peptides derived following limited proteolysis. Peptide sequences were found to match VDAC2 and VDAC3. VDACs (voltage-dependent, anion-selective channels) or eukaryotic porins are a group of proteins first identified in the mitochondrial outer membrane that are able to form hydrophilic pore structures in membranes. In mammals, three VDAC isoforms (VDAC1, -2, -3) have been identified by cDNA cloning and sequencing. Antibodies against synthetic peptides specific for the three mammal VDAC isoforms were generated in rabbits. Their specificity was demonstrated by immunoblotting using recombinant VDAC1, -2, and -3. In protein extracts of bovine spermatozoa, VDAC1, -2, and -3 were detected by specific antibodies, while only VDAC2 and -3 were found as solubilized proteins derived from purified bovine ODFs. Immunofluorescence microscopy of spermatozoa revealed that anti-VDAC2 and anti-VDAC3 antibodies clearly bound to the sperm flagellum, in particular to the ODF. Transmission electron immunomicroscopy supported the finding that VDAC2 protein is abundant in the ODF. Since the ODF does not have any known membranous structure, it is tempting to speculate that VDAC2 and VDAC3 might have an alternative structural organization and different functions in ODF than in mitochondria.
Power and energy reduction via pipeline balancing (2001)

Minimizing power dissipation is an important design requirement for both portable and non-portable systems. In this work, we propose an architectural solution to the power problem that retains performance while reducing power. The technique, known as Pipeline Balancing (PLB), dynamically tunes the resources of a general purpose processor to the needs of the program by monitoring performance within each program. We analyze metrics for triggering PLB, and detail instruction queue design and energy savings based on an extension of the Alpha 21264 processor. Using a detailed simulator, we present component and full chip power and energy savings for single and multi-threaded execution. Results show an issue queue and execution unit power reduction of up to 23% and 13%, respectively, with an average performance loss of 1% to 2%.
Effect of Brain-Derived Neurotrophic Factor Treatment and Forced Arm Use on Functional Motor Recovery After Small Cortical Ischemia (2004)

Postischemic intravenous BDNF treatment improves functional motor recovery after photothrombotic stroke and induces widespread neuronal remodeling. Early FAU treatment after stroke does not increase infarct size, impairs sensorimotor function, but leaves motor function unchanged. Postischemic astrogliosis was reduced by both treatments.
Half-Duplex Estimate-and-Forward Relaying: Bounds and Code Design (2006)

We propose a practical coding scheme for half-duplex estimate-and-forward relaying. The proposed construction is guided by the information theoretic coding scheme for the estimate-and-forward relay protocol. Our construction incorporates several design features to reduce receiver complexity without compromising performance. Observing that the relaying gain is significant only at low SNRs, we use binary LDPC codes in the source broadcast phase of relaying. Estimation is performed by entropy constrained scalar quantization of the received signal at the relay. Finally, a procedure similar to maximal ratio combining is used to aggregate direct and relayed signals at the destination. An important practical advantage of our scheme is that it does not require source-relay symbol synchronization. The codes outperform direct and two-hop channel capacities, as well as decode-and-forward relaying when the relay-destination link is strong
Molecular determinants in the plasma clearance and tissue distribution of ribonucleases of the ribonuclease A superfamily. (1996)

The similarities and differences among members of the RNase A superfamily provide an ideal opportunity to examine the molecular basis for differences in their pharmacokinetics and biodistribution. Plasma clearances in BALB/c mice are similar among the five RNases studied: human pancreatic RNase, angiogenin, eosinophil-derived neurotoxin, onconase, and bovine seminal RNase. The average clearance is 0.13 ml/min or 60% of the glomerular filtration rate (measured by [14C]inulin clearance during continuous infusion from an i.p. implanted osmotic pump). Angiogenin has a higher volume of distribution and plasma-to-muscle transport rate than the other RNases, suggestive of binding to endothelial cells. Organ distribution differs dramatically among these RNases. The RNase most toxic to tumor cells, onconase, exhibits the longest retention in the kidneys: at 180 min, 50% of the injected dose is found in the kidneys, whereas only 1% or less of the other RNases is retained in the kidneys. Slower elimination of onconase from the kidneys may be due to a higher degree of binding in the kidney or a resistance to proteolytic degradation. To elucidate the molecular determinants involved in tissue uptake, we examined the biodistribution of recombinant onconase and two onconasepancreatic RNase chimeric proteins. The tissue retention property of onconase appears to be located in at least two regions, one of which is in the NH2-terminal 9-amino acid alpha-helix. The NH2-terminal pyroglutamate of onconase, a residue essential for ribonucleolytic activity and cytotoxicity, does not play a role in kidney retention.
Inverse Scattering Solutions by a Sinc Basis, Multiple Source, Moment Method -- Part I: Theory (1983)

A new method for solving the inverse scattering problem for the scalar, inhomogeneous, exact, Helmholtz wave equation is presented. No perturbation approximations are used and the method is applicable even for many cases where weak to moderate attenuation and moderate to strong refraction of incident fields occur. The ill-posed nature of the inverse scattering problem for a single monochromatic source is known. However, the use of multiple sources, the collection of redundant (i.e., overdetermined) data, and the constraining of the fields and complex refractive index to be spatially band limited constitutes a new problem. The cases we have tested by computer simulation indicate that the new problem is well posed, a unique solution, and is stable with noisy data. The method is an application of the well-known method of moments with sinc basis and delta testing functions to discretize the problem. The inverse scattering solution may be obtained by solving the resulting set of simultaneous, quadratic, multivariate equations. Several algorithms for solving these equations are given.
Tuning Pharmacokinetics and Biodistribution of a Targeted Drug Delivery System Through Incorporation of a Passive Targeting Component (2014)

Major challenges in the development of drug delivery systems (DDSs) have been the short half-life, poor bioavailability, insufficient accumulation and penetration of the DDSs into the tumor tissue. Understanding the pharmacokinetic (PK) parameters of the DDS is essential to overcome these challenges. Herein we investigate how surface chemistry affects the PK profile and organ distribution of a gold nanoparticle-based DDS containing both a passive and active targeting moiety via two common routes of administration: intravenous and intraperitoneal injections. Using LC/MS/MS, ELISA and INAA we report the half-life, peak plasma concentrations, area under the curve, ability to cross the peritoneal barrier and biodistribution of the nanoconjugates. The results highlight the design criteria for fine-tuning the PK parameters of a targeted drug delivery system that exploits the benefits of both active and passive targeting.
Designing for Responsiveness with Computational Sprinting (2013)

The tight thermal constraints of mobile devices, which limit sustainable performance, and the bursty nature of interactive mobile applications call for a new design focus: enhancing user responsiveness rather than sustained throughput. To that end, this article explores computational sprinting, wherein a mobile device temporarily exceeds sustainable thermal limits to provide a brief, intense burst of computation in response to user input. By enabling tenfold more computation within the timescale of human patience, sprinting has the potential to fundamentally change the user experience that an interactive application can provide.
Predicting Zika virus structural biology: Challenges and opportunities for intervention (2015)

Lead candidates for Zika virus can likely be established using NS3 and NS5 inhibitors from other flaviviruses, and the structures presented can provide opportunities for Zika virus intervention strategies.
Cyclic Nucleotide Phosphodiesterase 3B Is a Downstream Target of Protein Kinase B and May Be Involved in Regulation of Effects of Protein Kinase B on Thymidine Incorporation in FDCP2 Cells (2000)

Wild-type (F/B), constitutively active (F/B*), and three kinase-inactive (F/Ba-, F/Bb-, F/Bc-) forms of Akt/protein kinase B (PKB) were permanently overexpressed in FDCP2 cells. In the absence of insulin-like growth factor-1 (IGF-1), activities of PKB, cyclic nucleotide phosphodiesterase 3B (PDE3B), and PDE4 were similar in nontransfected FDCP2 cells, mock-transfected (F/V) cells, and F/B and F/B- cells. In F/V cells, IGF-1 increased PKB, PDE3B, and PDE4 activities approximately 2-fold. In F/B cells, IGF-1, in a wortmannin-sensitive manner, increased PKB activity approximately 10-fold and PDE3B phosphorylation and activity ( approximately 4-fold), but increased PDE4 to the same extent as in F/V cells. In F/B* cells, in the absence of IGF-1, PKB activity was markedly increased ( approximately 10-fold) and PDE3B was phosphorylated and activated (3- to 4-fold); wortmannin inhibited these effects. In F/B* cells, IGF-1 had little further effect on PKB and activation/phosphorylation of PDE3B. In F/B- cells, IGF-1 activated PDE4, not PDE3B, suggesting that kinase-inactive PKB behaved as a dominant negative with respect to PDE3B activation. Thymidine incorporation was greater in F/B* cells than in F/V cells and was inhibited to a greater extent by PDE3 inhibitors than by rolipram, a PDE4 inhibitor. In F/B cells, IGF-1-induced phosphorylation of the apoptotic protein BAD was inhibited by the PDE3 inhibitor cilostamide. Activated PKB phosphorylated and activated rPDE3B in vitro. These results suggest that PDE3B, not PDE4, is a target of PKB and that activated PDE3B may regulate cAMP pools that modulate effects of PKB on thymidine incorporation and BAD phosphorylation in FDCP2 cells.