gebhart/patrepeval huggingface dataset:
Genetic protection of repopulating hematopoietic cells with an improved MDR1‐retrovirus allows administration of intensified chemotherapy following stem cell transplantation in mice (2002)

This study was undertaken to analyze the hematotoxicity of paclitaxel (Taxol) and to test whether transduction of repopulating hematopoietic cells with a retroviral vector (SF1m) expressing the human multidrug resistance 1 gene (MDR1) would permit dose intensification following bone marrow transplantation (BMT). While the regimen chosen (8 x 20 mg/kg i.p. within 12 days) produced a non-lethal, reversible hematotoxicity in mice with steady-state hematopoiesis, only 35.3% (6/17) of control mice survived when treated starting 14 days post BMT. In contrast, 83.3% (15/18) of mice transplanted with SF1m-transduced cells survived, owing to a significant protection against severe acute myelotoxicity (as determined by neutrophil counts, white and red blood cell counts and values for hemoglobin and hematocrit). After recovery from chemotherapy, an increase of myeloid cells that were resistant to colchicine and effluxed the fluorochrome Rhodamine 123 was observed in SF1m-mice, but not in controls. These results reveal that the lethal, dose-limiting hematotoxicity of an intensified post-transplantation chemotherapy with paclitaxel can be prevented by retroviral transfer of the MDR1 gene to a minor proportion of repopulating cells. Our mouse model, mimicking clinically achievable gene transfer rates, thus suggests that bone marrow chemoprotection may widen the therapeutic window and permit an earlier onset of post-transplantation chemotherapy.
Stepwise refinement and verification in box-structured systems (1988)

The author proposes that the formality of specifications and designs be developed together in box structures with many sponsor and user interfaces. Box structures of data abstractions allow the stepwise refinement and verification of hierarchical system designs from their specifications at formal and informal levels. He discusses the features and advantages of the approach. He used a navigation and weather buoy case study and gives a detailed, step-by-step application of the method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Multiprocessor experiments for high-speed ray tracing (1988)

New single- and multiprocessor models for ray tracing are presented. Important features are (1) the use of custom VLSI building blocks, (2) the use of a modified hierarchical data-structure-based ray tracing algorithm with three disjoint data sets, and (3) scene access through adaptive information broadcasting. A modular design is presented that permits incremental performance enhancement up to two orders of magnitude over conventional minicomputers or workstations. Ray tracing is a surprisingly good application for a shared bus architecture because of the computational complexity of intersecting light rays with graphics objects.
RF Energy Harvesting and Transport for Wireless Sensor Network Applications: Principles and Requirements (2013)

This paper presents an overview of principles and requirements for powering wireless sensors by radio-frequency (RF) energy harvesting or transport. The feasibility of harvesting is discussed, leading to the conclusion that RF energy transport is preferred for powering small sized sensors. These sensors are foreseen in future Smart Buildings. Transmitting in the ISM frequency bands, respecting the transmit power limits ensures that the International Commission on Non-Ionizing Radiation Protection (ICNIRP) exposure limits are not exceeded. With the transmit side limitations being explored, the propagation channel is next discussed, leading to the observation that a better than free-space attenuation may be achieved in indoors line-of-sight environments. Then, the components of the rectifying antenna (rectenna) are being discussed: rectifier, dc-dc boost converter, and antenna. The power efficiencies of all these rectenna subcomponents are being analyzed and finally some examples are shown. To make RF energy transport a feasible powering technology for low-power sensors, a number of precautions need to be taken. The propagation channel characteristics need to be taken into account by creating an appropriate transmit antenna radiation pattern. All subcomponents of the rectenna need to be impedance matched, and the power transfer efficiencies of the rectifier and the boost converter need to be optimized.
On the accuracy of RFID-based localization in a mobile wireless network testbed (2009)

The extensive recent research in protocols development for wireless networks must be complemented with simple yet efficient prototyping and evaluation mechanism. MiNT-2 is a miniaturized multi-hop wireless network testbed that addresses this challenge by combining the benefits of existing protocol evaluations strategies: simulations and custom built large scale wireless network testbeds. A key component of MiNT-2 is the ability of testbed nodes to move around in the testbed space, whether to reconfigure the network topology or to emulate node mobility patterns. Consequently, we need to devise accurate mechanisms for node localization - the ability of a node to be aware of its exact location in the testbed space. This paper presents the details of the current RFID-based node localization mechanism in MiNT-2. We describe the sources of inaccuracy encountered when using RFID tags due to the error margin associated with the reading range of tags. We then present the implementation and evaluation of two approaches which can be combined to improve the overall accuracy of the RFID-based localization system. Through our experimental evaluation, we show that the proposed approaches improve the accuracy of RFID-based localization mechanisms by up to 58.22% for dense deployment of RFID tags. Though described in the context of the MiNT-2 testbed, our localization techniques are also applicable in more general settings where accurate and inexpensive positioning of mobile nodes is important.
Coin flipping by telephone a protocol for solving impossible problems (1983)

Alice and Bob want to flip a coin by telephone. (They have just divorced, live in different cities, want to decide who gets the car.) Bob would not like to tell Alice HEADS and hear Alice (at the other end of the line) say "Here goes . . . I'm flipping the coin. . . . You lost!"Coin-flipping in the SPECIAL way done here has a serious purpose. Indeed, it should prove an INDISPENSABLE TOOL of the protocol designer. Whenever a protocol requires one of two adversaries, say Alice, to pick a sequence of bits at random, and whenever it serves Alice's interests best NOT to pick her sequence of bits at random, then coin-flipping (Bob flipping coins to Alice) as defined here achieves the desired goal:1. It GUARANTEES to Bob that Alice will pick her sequence of bits at random. Her bit is 1 if Bob flips heads to her, O otherwise.2. It GUARANTEES to Alice that Bob will not know WHAT sequence of bits he flipped to her.Coin-flipping has already proved useful in solving a number of problems once thought impossible: mental poker, certified mail, and exchange of secrets. It will certainly prove a useful tool in solving other problems as well.
Effects of thiols, sugars, and proteins on nitric oxide activation of guanylate cyclase. (1979)

Purification of soluble guanylate cyclase from rat liver resulted in an apparent loss of enzyme activation by nitric oxide that could be restored by dithiothreitol. methemoglobin, bovine serum albumin, or sucrose. Although hemoglobin also permitted some activation with nitric oxide, the effect of other agents to restore enzyme activation was prevented with hemoglobin. As a result of enzyme purification, there is an alteration of the dose-response relationship for nitric oxide activation. After partial enzyme purification, relatively high concentrations of nitric oxide that were stimulatory in crude enzyme preparations had no effect on enzyme activity. However, partially purified or homogeneous enzyme was activated by lower concentrations of nitric oxide. The bell-shaped dose-response curve for nitric oxide was shifted to the left with guanylate cyclase purification. The addition of dithiothreitol, methemoglobin, bovine serum albumin, or sucrose to enzyme markedly broadens the dose-response curve for nitric oxide. Thus, the apparent loss of responsiveness to nitric oxide with purification is a function of increased sensitivity of guanylate cyclase to nitric oxide. Increased sensitivity to nitric oxide with enzyme purification probably results from the removal of heme, proteins, and small molecules that can serve as scavengers or sinks for nitric oxide and prevent excessive oxidation of the enzyme.
Negative log-likelihood and statistical hypothesis testing as the basis of model selection in IDEAs (2000)

In this paper, we analyze the most prominent features in model selection criteria that have been used so far in iterated density estimation evolutionary algorithms (IDEAs, EDAs, PMBGAs). These algorithms build probabilistic models and estimate probability densities based upon a selection of available points. We show that the negative log{likelihood is a basis of the inference features when the Kullback{Leibler divergence is used. We show how previously found to be problematic issues in the case of continuous random variables can be resolved by starting from the derived basics. By doing so, we have a probabilistic model search metric that can be justied through the use of statistical hypothesis tests. This in turn reduces the need for additional complexity penalties.
Functional interactions of HslV (ClpQ) with the ATPase HslU (ClpY) (2002)

HslVU is a bacterial homolog of the proteasome, where HslV is the protease that is activated by HslU, an ATPase and chaperone. Structures of singly and doubly capped HslVU particles have been reported, and different binding modes have been observed. Even among HslVU structures with I-domains distal to HslV, no consensus mode of activation has emerged. A feature in the Haemophilus influenzae HslVU structure, insertion of the C termini of HslU into pockets in HslV, was not seen in all other structures of the enzyme. Here we report site-directed mutagenesis, peptide activation, and fluorescence experiments that strongly support the functional relevance of the C terminus insertion mechanism: we find that mutations in HslV that disrupt the interaction with the C termini of HslU invariably lead to inactive enzyme. Conversely, synthetic peptides derived from the C terminus of HslU bind to HslV with 10(-5) M affinity and can functionally replace full HslU particles for both peptide and casein degradation but fail to support degradation of a folded substrate. Thus, the data can be taken as evidence for separate substrate unfoldase and protease stimulation activities in HslU. Enhanced HslV proteolysis could be due to the opening of a gated channel or allosteric activation of the active sites. To distinguish between these possibilities, we have mutated a series of residues that line the entrance channel into the HslV particle. Our mutational and fluorescence experiments demonstrate that allosteric activation of the catalytic sites is required in HslV, but they do not exclude the possibility of channel opening taking place as well. The present data support the conclusion that the H. influenzae structure with I-domains distal to HslV captures the active species and point to significant differences in the activation mechanism of HslV, ClpP, and the proteasome.
Transforming water: Water efficiency as stimulus and long‐term investment (2008)

Water Efficiency programs have an established track record as cost‐effective long‐term public resource investments. Less well understood are the short‐term economic impacts of these rapidly scalable and adaptable programs, and the ability of these programs to quickly deliver economic benefit as well as sustainable solutions. This paper quantitatively examines the short‐term economic growth impacts of water/energy efficiency investments, specifically in terms of job creation, income, GDP, national output, water savings, and other benefits.\nOur consultant team modeled a wide range of water/energy efficiency program possibilities, across all water‐using sectors and involving indoor, outdoor, and water system efficiencies. This modeling clearly confirms that economic stimulus benefits could be broadly distributed throughout the national economy:\n1. The economic output benefits range between $2.5 and $2.8 million per million dollars of direct investment.\n2. GDP benefits range between $1.3 and $1.5 million per million dollars of direct investment.\n3. Employment potential ranges between 15 and 22 jobs per million dollars of direct investment.
NY‐CO‐58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer (2009)

NY-CO-58/KIF2C has been identified as a tumor antigen by screening antibody responses in patients with colorectal cancer. However, expression had not consequently been examined, and nothing was known about its ability to induce spontaneous T cell responses, which have been suggested to play a role in the development of colorectal cancer. We analyzed 5 colorectal cancer cell lines, and tumor samples and adjacent healthy tissues from 176 patients with epithelial cancers for the expression of NY-CO-58/KIF2C by RT-PCR and Western Blot. T cell responses of 43 colorectal cancer patients and 35 healthy donors were evaluated by ELISpot following stimulation with 30mer peptides or full-length protein. All cell lines and tumor samples from colorectal cancer patients expressed NY-CO-58/KIF2C on the protein and RNA level, and expression levels correlated strongly with Ki-67 expression (r = 0.69; p = 0.0003). Investigating NY-CO-58/KIF2C-specific T cell responses, CD8(+) T cells directed against 1 or more peptides were found in less than 10% of patients, whereas specific CD4(+) T cells were detected in close to 50% of patients. These T cells were of high avidity, recognized the naturally processed antigen and secreted IFN-gamma and TNF-alpha. Depletion of CD4(+)CD25(+) T cells before stimulation significantly increased the intensity of the preexisting response. NY-CO-58/KIF2C is significantly overexpressed in colorectal and other epithelial cancers and expression levels correlate with the proliferative activity of the tumor. Importantly, NY-CO-58/KIF2C was able to induce spontaneous CD4(+) T cell responses of the Th1-type, which were tightly controlled by peripheral T regulatory cells.
Integrated plasmonic lens photodetector (2009)

We present a fabricated metal-semiconductor-metal (MSM) photodetector exhibiting an enhanced photocurrent by integrating a nanoscale metallic grating into its contacts. This serves to increase the incident photon flux about the aperture of the device by guiding incident photons as surface plasmon polaritons. High speed time response data shows that the device responsivity may be increased without sacrificing speed. We demonstrate both a photocurrent enhancement and responsivity increase of about 90% at the design wavelength in comparison to otherwise identical MSM photodetectors without integrated nanoscale gratings. The device retains the MSM advantages of simplicity, planarity, and monolithic integrability.
Urinary excretion of cathepsin B and cystatins as parameters of tubular damage. (1994)

The urinary excretion of the lysosomal hydrolases cathepsin B and beta-N-acetylglucosaminidase (beta-NAG) was compared with the tubular activities of these enzymes in remnant kidneys 16 weeks after subtotal nephrectomy (5/6 NX) or unilateral nephrectomy (UNX), as well as in kidneys from diabetic rats. In addition, the urinary excretion of the low-molecular weight protein cystatins, inhibitors of lysosomal cathepsins, was also followed in these animals. The urinary excretion of cathepsin B and beta-NAG was significantly enhanced in all three models of renal disease. The highest excretion rates for these enzymes were found in diabetic animals (cathepsin B: 4-fold; beta-NAG: more than a 10-fold increase over respective controls). In terms of tubular enzyme activities, tissue activities of both hydrolases were reduced in the remnant kidney after 5/6 NX, while in UNX and diabetes only cathepsin B activity was decreased. The urinary excretion of cystatins was enhanced in all three animal models, particularly in 5/6 nephrectomized rats, where a 40-fold increment over control animals was observed. Taken together, these findings indicate that there was severe tubular damage in the remnant kidney after 5/6 NX (reduced tubular enzyme activities, enzymuria and severely compromised tubular protein reabsorption). Furthermore, considerable enzymuria and disturbed protein reabsorption in early diabetes suggest tubular dysfunction before signs of glomerular damage become evident.
Restitution of myocardial adenine nucleotides: acceleration by administration of ribose. (1980)

In the present study, the influence of ribose on the biosynthesis of myocardial adenine nucleotides was examined in rats in vivo utilizing two experimental models which are characterized by a reduction in the adenine nucleotide content; recovery from oxygen deficiency and application of isoproterenol. 1. The biosynthesis (= de novo synthesis) of cardiac adenine nucleotides was enhanced by 90% during the first 60 min of recovery from five intermittent periods of asphyxia of 4.5 min duration (Table I). 2. Isoproterenol induced a stimulation of myocardial adenine nucleotide synthesis in a dose-dependent manner amounting to 640% three hours after s.c. administration of 25 mg/kg (Fig. 1). 3. Ribose which bypasses the hexose monophosphate shunt in the myocardium and which leads to an elevation of the available pool of 5-phosphoribosyl-1-pyrophosphate (PRPP), stimulated the biosynthesis of adenine nucleotides in the heart, but not in liver and kidney, of rats one hour after i.v. application of a single dose of 100 mg/kg from 6 nmoles/g/h to 27 nmoles/g/h (Fig. 2). 4. When ribose was constantly infused during the first 60 min of recovery from asphyxia, the enhancement of cardiac adenine nucleotide biosynthesis was further stimulated from 12.6 nmoles/g/h to 20.5 nmoles/g/h (with 500 mg ribose/kg/h) and to 43.4 nmoles/g/h (with 1 000 mg ribose/kg/h) (Fig. 3). 5. Continuous I.V. infusion of ribose (200 mg/kg/h) for 24 hours in isoproterenol-treated rats during a 13-fold increase in myocardial adenine nucleotide biosynthesis compared with the control (Fig. 4). In this condition, the isoproterenol-induced decline in the adenine nucleotide level did not occur (Table II).
Incorporation of CpG into a Liposomal Vaccine Formulation Increases the Maturation of Antigen-Loaded Dendritic Cells and Monocytes To Improve Local and Systemic Immunity (2014)

Liposomal vaccine formulations incorporating stimulants that target innate immune receptors have been shown to significantly increase vaccine immunity. Following vaccination, innate cell populations respond to immune stimuli, phagocytose and process Ag, and migrate from the injection site, via the afferent lymphatic vessels, into the local lymph node. In this study, the signals received in the periphery promote and sculpt the adaptive immune response. Effector lymphocytes then leave the lymph node via the efferent lymphatic vessel to perform their systemic function. We have directly cannulated the ovine lymphatic vessels to detail the in vivo innate and adaptive immune responses occurring in the local draining lymphatic network following vaccination with a liposome-based delivery system incorporating CpG. We show that CpG induces the rapid recruitment of neutrophils, enhances dendritic cell-associated Ag transport, and influences the maturation of innate cells entering the afferent lymph. This translated into an extended period of lymph node shutdown, the induction of IFN-γ-positive T cells, and enhanced production of Ag-specific Abs. Taken together, the results of this study quantify the real-time in vivo kinetics of the immune response in a large animal model after vaccination of a dose comparable to that administered to humans. This study details enhancement of numerous immune mechanisms that provide an explanation for the immunogenic function of CpG when employed as an adjuvant within vaccines.
Generalized Additive Models (2006)

Now in widespread use, generalized additive models (GAMs) have evolved into a standard statistical methodology of considerable flexibility. While Hastie and Tibshirani's outstanding 1990 research monograph on GAMs is largely responsible for this, there has been a long-standing need for an accessible introductory treatment of the subject that also e
New Compounds Related to Podophyllotoxin and Congeners: Synthesis, Structure Elucidation and Biological Testing. (1993)

4-Azido, 4-amino, 4-amido and 4-alkoxy compounds related to the lignans podophyllotoxin and 4'-demethylepipodophyllotoxin have been synthesized, and their structures elucidated. The Ritter reaction was shown to be useful in the preparation of the 4-amido compounds with the required stereochemistry. A preparative method for 4-chloro-4-deoxypicrophyllotoxin, for which all earlier synthetic attempts resulted in the two dehydrated compounds, alpha- and beta-apopicropodophyllotoxin, was developed. Supplementary preliminary studies of the biological activities of some of the compounds were performed. All compounds had pronounced inhibitory effect on the in vitro growth of human cervical cancer cells and TC-mouse cells with 4-amino-4-deoxypodophyllotoxin and 4-azido-4-deoxypodophyllotoxin showing the highest activity. Alkaline elution studies indicate that the toxicity of the 4'-demethoxy derivatives is due to protein-mediated DNA nicking. None of the compounds were found to have antiviral effect against herpes simplex type 2 (HSV-2), human immunodeficiency (HIV), and cytomegalovirus (CMV) in doses not toxic to the cells.
The development of anti-hepatitis C virus agents (1995)

We have built a model of the specificity pocket of the protease of hepatitis C virus on the basis of the known structures of trypsin-like serine proteases and of the conservation pattern of the protease sequences among various hepatitis C strains. The model allowed us to predict that the substrate of this protease should have a cysteine residue in position P1. This hypothesis was subsequently proved by N-terminal sequencing of two products of the protease. The success of this “blind” test increases our confidence in the overall correctness of our proposed alignment of the enzyme sequence with those of other proteases of known structure and constitutes a first step in the construction of a complete model of the viral protease domain.
Identification of Patients with Increased Risk of Infection with Herpes Simplex Virus after Renal Transplantation (1979)

Forty-nine recipients of renal allografts were studied for infection with herpes simplex virus (HSV) before and at sequential intervals after transplantation. Forty-four (90%) of the patients studied were initially seropositive for neutralizing antibody to HSV type 1. HSV was not shed prior to transplantation nor by any of the five seronegative recipients after transplantation. Twenty-nine (66%) of the 44 seropositive patients shed virus postoperatively: 23 in saliva, three in urine, and three in both sites. Twenty (63%) of 32 seropositive patients examined developed herpetic mucocutaneous lesions. Both viral shedding and lesions were most prevalent during the first four weeks after transplantation. Twenty-nine (85%) of 34 patients with antibody titers of 1:256-1:4,096 and zero of 10 with titers of 1:8-1:128 shed HSV postoperatively (P less than 0.0001). The group with high antibody titers before transplantation were also more likely to develop lesions after transplantation (P = 0.002) as were those with a positive history (P = 0.017). The ability to predict symptomatic HSV recurrences in renal transplant patients could be a valuable aid in identifying individuals with which to evaluate antiviral compounds.