gebhart/patrepeval huggingface dataset:
A phase I study of combination therapy with immunotoxins IgG-HD37-deglycosylated ricin A chain (dgA) and IgG-RFB4-dgA (Combotox) in patients with refractory CD19(+), CD22(+) B cell lymphoma. (2000)

This study used an 8-day continuous infusion regimen of a 1:1 mixture of two immunotoxins (ITs) prepared from deglycosylated ricin A chain (dgA) conjugated to monoclonal antibodies directed against CD22 (RFB4-dgA) and CD19 (HD37-dgA; Combotox) in a Phase I trial involving 22 patients with refractory B cell lymphoma to determine the maximum tolerated dose, clinical pharmacology, and toxicity profile and to characterize any clinical responses. Adult patients received a continuous infusion of Combotox at 10, 20, or 30 mg/m2/192 h. No intrapatient dose escalation was permitted. Patients with > or =50 circulating tumor cells (CTCs)/mm3 in peripheral blood tolerated all doses without major toxicity. The maximum level of serum IT (Cmax) achieved in this group was 345 ng/ml of RFB4-dgA and 660 ng/ml of HD37-dgA (1005 ng/ml of Combotox). In contrast, patients without CTCs (<50/mm3) had unpredictable clinical courses that included two deaths probably related to the IT. Additionally, patients exhibited a significant potential for association between mortality and a history of either autologous bone marrow or peripheral blood stem cell transplants (P2 = 0.003) and between mortality and a history of radiation therapy (P2 = 0.036). In patients with CTCs, prior therapies appeared to have little impact on toxicity. Subsequent evaluation of the ITs revealed biochemical heterogeneity between two lots of HD37-dgA. In addition, HD37-dgA thawed at the study site tended to contain significant particulates, which were not apparent in matched controls stored at the originating site. This suggests that a tendency to aggregate may have resulted from shipping, storage, and handling of the IT that occurred prior to preparation for administration. It is not clear to what extent, if any, the aggregation of HD37-dgA IT was related to the encountered clinical toxicities; however, the potential to aggregate does suggest one possible basis for problems in our clinical experience with HD37-dgA and leads us to the conclusion that non-aggregate-forming formulations for these ITs should be pursued prior to future clinical trials.
Patterns of integration of DNA microinjected into cultured mammalian cells: evidence for homologous recombination between injected plasmid DNA molecules. (1982)

We examined the fate of DNA microinjected into nuclei of cultured mammalian cells. The sequence composition and the physical form of the vector carrying the selectable gene affected the efficiency of DNA-mediated transformation. Introduction of sequences near the simian virus 40 origin of DNA replication or in the long terminal repeat of avian sarcoma provirus into a recombinant plasmid containing the herpes simplex virus thymidine kinase gene. (pBR322/HSV-tk) enhanced the frequency of transformation of LMtk- and RAT-2tk- cells to the TK+ phenotype 20- to 40-fold. In cells receiving injections of only a few plasmid DNA molecules, the transformation frequency was 40-fold higher after injection of linear molecules than after injection of supercoiled molecules. By controlling the number of gene copies injected into a recipient cell, we could obtain transformants containing a single copy or as many as 50 to 100 copies of the selectable gene. Multiple copies of the transforming gene were not scattered throughout the host genome but were integrated as a concatemer at one or a very few sites in the host chromosome. Independent transformants contained the donated genes in different chromosomes. The orientation of the gene copies within the concatemer was not random; rather, the copies were organized as tandem head-to-tail arrays. By analyzing transformants obtained by coinjecting two vectors which were identical except that in one a portion of the vector was inverted, we were able to conclude that the head-to-tail concatemers were generated predominantly by homologous recombination. Surprisingly, these head-to-tail concatemers were found in transformants obtained by injecting either supercoiled or linear plasmid DNA. Even though we demonstrated that cultured mammalian cells contain the enzymes for ligating two DNA molecules very efficiently irrespective of the sequences or topology at their ends, we found that even linear plasmid DNA was recruited into the concatemer by homologous recombination.
A 24 GHz short range radar network for automotive applications (2002)

For automotive short range applications, i.e. for distances up to 20 m, at the Technical University of Hamburg a radar network based on cheap 24 GHz high range resolution pulse radar technology was integrated into an experimental vehicle and tested in a real street environment. This paper presents a description of the network design, the individual pulse radar sensors, the network signal processing and possible automotive applications of the radar network, respectively. Object position estimation is accomplished by the very precise range measurement of each individual sensor and additional multilateration procedures. This radar network has been integrated into the front bumper of an experimental car for detailed measurement campaign in normal street and traffic situations. The paper concludes with a few results measured with the experimental vehicle in realistic traffic conditions.
Characterization of bovine cellular and serum antibody responses during infection by Cryptosporidium parvum (1991)

Cellular and serum antibody responses of calves were monitored for 23 days after oral inoculation of the calves with oocysts of Cryptosporidium parvum. In vitro blastogenic responses of peripheral blood lymphocytes were assessed after stimulation with a C. parvum preparation. Specific lymphocyte blastogenic responses to the parasite were detected 2 days after inoculation. Parasite-specific antibody titers were demonstrable 7 days after inoculation with oocysts and achieved peak levels 9 days after inoculation, coinciding with oocyst shedding at 5 to 10 days after inoculation. Both lymphocyte and antibody responses remained elevated until the termination of the experiment. Immunoblotting the C. parvum preparation with serum from an infected calf revealed six major parasite antigens. Five of these antigens reacted on immunoblots from 7 to 14 days after inoculation with oocysts. A parasite antigen of approximately 11,000 molecular weight demonstrated intense reactivity on immunoblots from 7 to 23 days after inoculation. The 11,000-molecular-weight antigen also reacted on immunoblots with parenterally raised antioocyst and antisporozoite rabbit sera. These results indicate that cell-mediated as well as humoral immune responses are initiated by cryptosporidial infection in calves and that the 11,000-molecular-weight parasite antigen is immunodominant.
The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2 (1997)

The inhibition of new blood vessel formation (angiogenesis) is an effective means of limiting both the size and metastasis of solid tumors. The leading anti-angiogenic compound, TNP-470, has proven to be effective in in vitro and in animal model studies, and is currently being tested in phase III antitumor clinical trials. Despite many detailed pharmacological studies, little is known of the molecular mode of action of TNP-470. Using a derivative of the TNP-470 parent compound, the fungal metabolite, fumagillin, we have purified a mammalian protein that is selectively and covalently bound by this natural product. This fumagillin binding protein was found to be a metalloprotease, methionine aminopeptidase (MetAP-2), that is highly conserved between human and Saccharomyces cerevisiae. In the absence of MetAP-1, a distantly related methionine aminopeptidase, MetAP-2 function is essential for vegetative growth in yeast. We demonstrate that fumagillin selectively inhibits the S. cerevisiae MetAP-2 protein in vivo. The binding is highly specific as judged by the failure of fumagillin to inhibit MetAP-1 in vivo. Hence, these results identify MetAP-2 as an important target of study in the analysis of the potent biological activities of fumagillin.
Identification of Autonomously Replicating Circular Subtelomeric Y' Elements in Saccharomyces cerevisiae (1985)

We marked a large number of yeast telomeres within their Y' regions by transforming strains with a fragment of Y' DNA into which the URA3 gene had been inserted. A few of the Ura+ transformants obtained were very unstable and were found to contain autonomously replicating URA3-marked circular Y' elements in high copy number. These marked extrachromosomal circles were capable of reintegrating into the chromosome at other telomeric locations. In contrast, most of the Ura+ transformants obtained were quite stable mitotically and were marked at bona fide chromosomal ends. These stable transformants gave rise to mitotically unstable URA3-marked circular Y' elements at a low frequency (up to 2.5%). The likelihood that such excisions and integrations represent a natural process in Saccharomyces cerevisiae is supported by our identification of putative Y' circles in untransformed strains. The transfer of Y' information among telomeres via a circular intermediate may be important for homogenizing the sequences at the ends of yeast chromosomes and for generating the frequent telomeric rearrangements that have been observed in S. cerevisiae.
Physiopathogenesis of subdural hematomas (1976)

✓ A previously described experimental hematoma model, achieved by the subcutaneous injection of 12 ml of autologous hemolyzed blood clotted in situ, was made in 33 rats. Seventeen animals served as controls; the other 16 received daily intramuscular injections of dexamethasone. After an initial decrease in size, 47% of the lesions in the control animals enlarged to a mean weight of 12.1 ± 2.5 gm, while the lesions in the 16 steroid-treated rats weighed 3.2 ± 0.70 gm (p &lt; 0.01). Histologically, lesions from the steroid group showed absence of neomembrane formation. These data offer further support to the theory that the neomembrane development and subsequent enlargement of subdural hematomas is due to inflammatory reactions of tissues in contact with large blood clots.
USE OF LIMESTONE QUARRY BY-PRODUCTS FOR DEVELOPING ECONOMICAL SELF-COMPACTING CONCRETE (2005)

The scope of this research was to determine the usefulness of limestone-quarry by-product material in the development of economical self-compacting concrete (SCC). Class C fly ash was also used and it was received from a power plant in Wisconsin. The main objective of this project was to evaluate the possibility for using these materials to reduce costs of expensive chemical admixtures needed for the manufacturing of self-compacting concrete. Use of quarry fines and Class C fly ash in self-compacting concrete is expected to provide significant economic benefits to quarries, coal-fired power plants, and concrete producers. Based on the extensive laboratory work, it was concluded that the limestone-quarry fines and Class C fly ash have high potential for utilization in the manufacturing of self-compacting concrete (SCC). The test data collected indicate that these materials can be used in the manufacturing of economical SCC in several different ways. When quarry fine material was used for the substitute of natural sand, it reduced the requirement of chemical admixtures, high-range water-reducing admixture (HRWRA) and viscosity-modifying admixture (VMA), without affecting the strength of SCC. The 28-day compressive strength of the mixtures made with sand replaced with quarry fines was in the range of 7,500 psi and 9,000 psi, qualifying the mixtures to be classified as high-strength SCC (≥ 6500 psi). Also by using Class C fly ash for the replacement of up to 55% of total cement by mass, high-strength SCC with the 28-day strength in the range of 9,000 psi and 10,000 psi was produced in an economical way. In conclusion, the use of quarry fines and Class C fly ash significantly reduced the amount of expensive chemical admixtures such as HRWRA and VMA in producing SCC. Professor of Structural Engineering and Academic Program Director, UWM Center for ByProducts Utilization, Department of Civil Engineering and Mechanics, University of WisconsinMilwaukee, Milwaukee, WI, USA. Assistant Director, Center for By-Products Utilization, Univ. of Wisconsin–Milwaukee, P.O. Box 784, Milwaukee, WI 53201, USA. Postdoctoral Fellow, Center for By-Products Utilization, Univ. of Wisconsin–Milwaukee, P.O. Box 784, Milwaukee, WI 53201,USA Manager of Land-Quality, We Energies Environmental Department, 333 W. Everett Street, Milwaukee, WI 53203, USA.
Principles of protein targeting to the nucleolus (2015)

The nucleolus is the hallmark of nuclear compartmentalization and has been shown to exert multiple roles in cellular metabolism besides its main function as the place of rRNA synthesis and assembly of ribosomes. Nucleolar proteins dynamically localize and accumulate in this nuclear compartment relative to the surrounding nucleoplasm. In this study, we have assessed the molecular requirements that are necessary and sufficient for the localization and accumulation of peptides and proteins inside the nucleoli of living cells. The data showed that positively charged peptide entities composed of arginines alone and with an isoelectric point at and above 12.6 are necessary and sufficient for mediating significant nucleolar accumulation. A threshold of 6 arginines is necessary for peptides to accumulate in nucleoli, but already 4 arginines are sufficient when fused within 15 amino acid residues of a nuclear localization signal of a protein. Using a pH sensitive dye, we found that the nucleolar compartment is particularly acidic when compared to the surrounding nucleoplasm and, hence, provides the ideal electrochemical environment to bind poly-arginine containing proteins. In fact, we found that oligo-arginine peptides and GFP fusions bind RNA in vitro. Consistent with RNA being the main binding partner for arginines in the nucleolus, we found that the same principles apply to cells from insects to man, indicating that this mechanism is highly conserved throughout evolution.
A bottom–up model of spatial attention predicts human error patterns in rapid scene recognition (2007)

Humans demonstrate a peculiar ability to detect complex targets in rapidly presented natural scenes. Recent studies suggest that (nearly) no focal attention is required for overall performance in such tasks. Little is known, however, of how detection performance varies from trial to trial and which stages in the processing hierarchy limit performance: bottom-up visual processing (attentional selection and/or recognition) or top-down factors (e.g., decision-making, memory, or alertness fluctuations)? To investigate the relative contribution of these factors, eight human observers performed an animal detection task in natural scenes presented at 20 Hz. Trial-by-trial performance was highly consistent across observers, far exceeding the prediction of independent errors. This consistency demonstrates that performance is not primarily limited by idiosyncratic factors but by visual processing. Two statistical stimulus properties, contrast variation in the target image and the information-theoretical measure of "surprise" in adjacent images, predict performance on a trial-by-trial basis. These measures are tightly related to spatial attention, demonstrating that spatial attention and rapid target detection share common mechanisms. To isolate the causal contribution of the surprise measure, eight additional observers performed the animal detection task in sequences that were reordered versions of those all subjects had correctly recognized in the first experiment. Reordering increased surprise before and/or after the target while keeping the target and distractors themselves unchanged. Surprise enhancement impaired target detection in all observers. Consequently, and contrary to several previously published findings, our results demonstrate that attentional limitations, rather than target recognition alone, affect the detection of targets in rapidly presented visual sequences.
Calibration Research on Fish-eye lens (2010)

A novel calibration method for fisheye lens camera is proposed in this paper. The method is based on equidistance projection model of fisheye lens. The inner structure of the fisheye lens which consists of many pieces of lens is so complex that it is very difficult and unnecessary to construct its physical model. The optical center of the fisheye lens (u <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> ,v <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> ), the virtual focal of the fish-eye lens l and the ration of the distortion in x coordinate Kx and the Ky in y coordinate should be calibrate in the mathematical mode proposed by us. Some special calibration patterns have been designed for calibrating them. Here, the optical center is the precondition for other parameters precise calibration. Therefore, we discuss four different methods to get it. The experiment results show that the methods we present are accurate and stable.
Proteomic Analysis of Early Melanosomes:  Identification of Novel Melanosomal Proteins (2002)

Melanin is a heterogeneous biopolymer produced only by specific cells termed melanocytes, which synthesize and deposit the pigment in specialized membrane-bound organelles known as melanosomes. Although melanosomes have been suspected of being closely related to lysosomes and platelets, the total number of melanosomal proteins is still unknown. Thus far, six melanosome-specific proteins have been identified, and the challenge is to characterize the complete proteome of the melanosome to further understand its mechanism of biogenesis. In this report, we used mass spectrometry and subcellular fractionation to identify protein components of early melanosomes. Using this approach, we have identified all 6 of the known melanosome-specific proteins, 56 proteins that are shared with other organelles, and confirmed the presence of 6 novel melanosomal proteins using western blotting and by immunohistochemistry. Keywords: melanoma • proteomics • melanosome
The Relationship between Body and Ambient Temperature and Corneal Temperature (2010)

Corneal temperature is estimated to reach the maximum of 36.5°C to 37.0°C at ambient temperatures between 32.0°C and 34.5°C. If there is a causal relationship between elevated eye temperature, cataract, and presbyopia, the incidence of these eye diseases is predicted to increase with global warming. Importantly, the strong association between corneal temperature and body core temperature indicates that frequent infections could also be considered a risk factor for age-related lens disorders.
A Relationship Between Sequence and Statechart Diagrams. (2000)

This paper is an introduction to an easy way to formalise sequence diagrams and verify coherence with the statechart diagrams, with the pi-calculus that is a process algebra where processes interact by sending communication links to each other.
Wandering: A Significant Problem among Community Residing Individuals with Alzheimer's Disease (1998)

This study evaluated the frequency, predictors, and effects of wandering in a population-based sample of 193 individuals with Alzheimer's disease (AD). Although wandering occurred in subjects at all levels of cognitive impairment, analysis of variance indicated that for the group as a whole, greater frequency of wandering was associated with significantly more impairment in cognition, day-to-day functioning, and behavior. Caregiver distress also increased significantly with increased frequency of wandering. Logistic regression modeling identified functional impairment and disruptive behavior problems as the strongest independent predictors of wandering occurring within the past week. Cluster analysis revealed four characteristic groups of wanderers that represented a continuum of wandering frequency, each having a unique pattern of other behavioral disturbances. Based on this analysis, we recommend further evaluation and the development of possible treatment strategies that address the individual differences found among AD patients who wander.
Pharmacokinetics and Pharmacodynamics of AJW200, a Humanized Monoclonal Antibody to von Willebrand Factor, in Monkeys (2002)

The interaction between platelet glycoprotein Ib and von Willebrand factor (vWF) plays a crucial role in platelet-mediated thrombus formation under high-shear-stress conditions. The aim of this study was to investigate the antiplatelet profile of a humanized anti-vWF monoclonal antibody, AJW200. In vitro studies were performed with a modified cone-and-plate viscometer and human platelets. AJW200 inhibited high-shear-stress-induced platelet adhesion, aggregation, and thrombin generation, but it did not have such effects under low-shear-stress conditions. Although abciximab inhibited platelet aggregation under both shear stress conditions, it did not inhibit platelet adhesion and thrombin generation. In addition, the pharmacokinetics and pharmacodynamics of AJW200 were evaluated in cynomolgus monkeys. Sustained inhibition of ristocetin-induced platelet aggregation was observed over 24 hours, 6 days, and 2 weeks after a single bolus injection of 0.3, 1, and 3 mg/kg, respectively. Moderate prolongation of the bleeding time was observed at the doses of 1 and 3 mg/kg. Abciximab markedly prolonged the bleeding time at 0.4 mg/kg, at which concentration complete inhibition of ADP-induced platelet aggregation was observed. These results suggest that glycoprotein Ib-vWF blockade with AJW200 results in a sustained antiplatelet effect without extensive prolongation of the bleeding time, probably due to a shear-stress-dependent inhibitory action.
“Reagentless” Micropatterning of Organics on Silicon Surfaces:  Control of Hydrophobic/Hydrophilic Domains1 (2001)

NRC publication: Yes
Pancreatic cancer, treatment options, and GI-4000 (2014)

Although pancreatic cancer is but the eleventh most prevalent cancer in the US, it is predicted that of all the patients newly diagnosed with this disease in 2014, only 27% will still be alive at the end of the first year, which is reduced to 6% after 5 years. The choice of chemotherapy in the treatment of pancreatic cancer is dependent on disease stage and patient performance status but, in general, the most widely used approved regimens include 5-fluorouracil (5-FU) combinations and gemcitabine combinations. Recent therapeutic strategies have resulted in an improvement in survival of patients with pancreatic cancer but the magnitude of change is disappointing and vast improvements are still needed. The goal of immunotherapy is to enhance and guide the body's immune system to recognize tumor-specific antigens and mount an attack against the disease. Among newer immune therapies, GI-4000 consists of 4 different targeted molecular immunogens, each containing a different Ras protein (antigen) encoded by the most commonly found mutant RAS genes in solid tumors-RAS mutations exist in over 90% of pancreatic ductal adenocarcinomas. We will review pancreatic cancer epidemiology and its current treatment options, and consider the prospects of immunotherapy, focusing on GI-4000. We discuss the potential mechanism of action of GI-4000, and the performance of this vaccination series thus far in early phase clinical trials.