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We show that infrared telescopes can be constructed at low cost using consumer-grade thermal infrared imagers and commercially available germanium lenses. Using these telescopes in the laboratory, introductory astronomy students can image nearby celestial objects to observe properties that are not seen in the visible region, in particular, variations in temperature across the surface.

Supplementary Figures 1-6 from Tissue Inhibitor of Metalloproteinase-3 via Oncolytic Herpesvirus Inhibits Tumor Growth and Vascular Progenitors

Malignant solid tumors remain a significant clinical challenge, necessitating innovative therapeutic approaches. Oncolytic viral therapy is a nonmutagenic, biological anticancer therapeutic shown to be effective against human cancer in early studies. Because matrix metalloproteinases (MMP) play important roles in the pathogenesis and progression of cancer, we sought to determine if “arming” an oncolytic herpes simplex virus (oHSV) with an MMP-antagonizing transgene would increase virus-mediated antitumor efficacy. We generated oHSVs that express human tissue inhibitor of metalloproteinases 3 (TIMP3) or firefly luciferase and designated them rQT3 and rQLuc, respectively. We evaluated the antitumor efficacy of these viruses against neuroblastoma and malignant peripheral nerve sheath tumor (MPNST) xenografts. Relative to rQLuc, rQT3-infected primary human MPNST and neuroblastoma cells exhibited equivalent virus replication but increased cytotoxicity and reduced MMP activity. In vivo, rQT3-treated tumors showed delayed tumor growth, increased peak levels of infectious virus, immature collagen extracellular matrix, and reduced tumor vascular density. Remarkably, rQT3 treatment reduced circulating endothelial progenitors, suggesting virus-mediated antivasculogenesis. We conclude that rQT3 enhanced antitumor efficacy through multiple mechanisms, including direct cytotoxicity, elevated virus titer, and reduced tumor neovascularization. These findings support the further development of combined TIMP-3 and oncolytic virotherapy for cancer. [Cancer Res 2008;68(4):1170–9]

The United States’ Global Positioning System (GPS), and similar geolocation systems such as Galileo, GLONASS, and Beidou are used by people all over the globe. Modern receivers of these global navigation satellite systems can track multiple satellites from different constellations. Casual, non-technical users are probably aware that the positional information provided is typically accurate to within a few meters. We could expect physics students to infer that, because these systems rely on the travel time of radio signals, this implies time measurement accuracy on the scale of tens of nanoseconds. This feature has led to GPS-enabled Internet time servers providing stratum 1 accuracy for under $1000. In this paper, we will show that we can couple a GPS unit to a field programmable gate array (FPGA) to determine the temperature in a room. The more serious application of this GPS-FPGA pairing is to provide precise time-stamping of events, thereby synchronizing data collection between stations across a room or across the globe.

Although we may consider the power outlets in our homes to be nearly ideal voltage sources, a variety of influences in and around the home can cause departures from the nominal 60 Hz, 110–120 V root-mean-square (rms) of the North American grid. Even without instrumentation, we can see that a large motor starting from rest can be sufficient to cause lights to dim momentarily (voltage sag). This dimming is due to the inrush current drawn by a stationary motor, which may be several times the current drawn at operating speed. We prepared a voltage monitoring system using a voltage divider, the construction details of which we omit in the interest of safety.

Using the Sun to tell time is an ancient idea, but we can take advantage of modern technology to bring it into the 21st century for students in astronomy, physics, or physical science classes. We have employed smartphones, Google Earth, and 3D printing to find the moment of local noon at two widely separated locations. By reviewing GPS time-stamped photos from each place, we are able to illustrate that local noon is longitude-dependent and therefore explain the need for time zones.

Google Earth has made a wealth of aerial imagery available online at no cost to users. We examine some of the potential uses of that data in illustrating basic physics and astronomy, such as finding the local magnetic declination, using landmarks such as the Washington Monument and Luxor Obelisk as gnomons, and showing how airport runways get their numbers. Close inspection of the images provided by Google Earth reveals that most of them are actually obtained via camera-equipped planes rather than satellites.

Some of the results from the electrostatics portion of introductory physics are particularly difficult for students to understand and/or believe. For students who have yet to take vector calculus, Gauss's law is far from obvious and may seem more difficult than Coulomb's. When these same students are told that the minimum potential energy for charges added to a conductor is realized when all charges are on the surface, they may have a hard time believing that the energy would not be lowered if just one of those charges were moved from the surface to the interior of a conductor. Investigating these ideas using Coulomb's law and/or the formula for the potential energy of a system of discrete charges might be tempting, but as the number of charges climbs past a few the calculations become tedious. A spreadsheet enables students to perform these for a hundred or more charges and confirm the familiar results.

Understanding the host response to oncolytic viruses is important to maximize their antitumor efficacy. Despite robust cytotoxicity and high virus production of an oncolytic herpes simplex virus (oHSV) in cultured human sarcoma cells, intratumoral (ITu) virus injection resulted in only mild antitumor effects in some xenograft models, prompting us to characterize the host inflammatory response. Virotherapy induced an acute neutrophilic infiltrate, a relative decrease of ITu macrophages, and a myeloid cell-dependent upregulation of host-derived vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, bevacizumab and r84, the latter of which binds VEGF and selectively inhibits binding to VEGF receptor-2 (VEGFR2) but not VEGFR1, enhanced the antitumor effects of virotherapy, in part due to decreased angiogenesis but not increased virus production. Neither antibody affected neutrophilic infiltration but both partially mitigated virus-induced depletion of macrophages. Enhancement of virotherapy-mediated antitumor effects by anti-VEGF antibodies could largely be recapitulated by systemic depletion of CD11b(+) cells. These data suggest the combined effect of oHSV virotherapy and anti-VEGF antibodies is in part due to modulation of a host inflammatory reaction to virus. Our data provide strong preclinical support for combined oHSV and anti-VEGF antibody therapy and suggest that understanding and counteracting the innate host response may help enable the full antitumor potential of oncolytic virotherapy.

Alight‐emitting diode (LED) and operational amplifier can be used as an affordable method to provide a digital output indicating detection of an intense light source such as a laser beam or high‐output LED.1 When coupled with a microcontroller, the combination can be used as a multiple photogate and timer for under $50. A similar circuit is used as a data logging system for a mirror galvanometer, providing a record of changes in the Earth's magnetic field as small as a few nanotesla (nT).

It is a fundamental result of introductory optics that a plane mirror must be at least one half of your height if you want to see your entire body. Students are commonly confused about whether this is still true as you back very far away from the mirror. An interesting student question proposed that we observe the Moon's image in a small makeup mirror. If someone on the Moon had a telescope large enough to see you and your surroundings clearly, would that person also be able to peer over your shoulder and see the entire Moon in your mirror, as you do? The answer provides a useful 'view' on mirror reflections.

Experimentation with polyphasic voltages is greatly simplified when microcontrollers are used to generate multiple square waves with fixed phase offsets. Each square wave is sent through a simple second-order Sallen–Key filter to produce an approximately sinusoidal voltage signal. The microcontroller allows the reproduction of split-phase and three-phase voltage relationships, mirroring those commonly distributed on the North American power grid, at safe voltage levels.

In most introductory physics courses, the first equations encountered are the kinematic equations. Though the emphasis at this level tends to be on cases of constant acceleration, many real-world examples of motion are not so simple. We describe the use of inexpensive hobbyist-grade accelerometers and spreadsheet software to explore inertial navigation via numerical integration of the measured acceleration.

Student-constructed magnetometers and commonly available software illustrate the use of autocorrelation functions to extract low-amplitude signals from background noise. The magnetometers are later used to measure forces at sampling rates over 50Hz, providing data for an introduction to numerical integration.

Malignant solid tumors remain a significant clinical challenge, necessitating innovative therapeutic approaches. Oncolytic viral therapy is a nonmutagenic, biological anticancer therapeutic shown to be effective against human cancer in early studies. Because matrix metalloproteinases (MMP) play important roles in the pathogenesis and progression of cancer, we sought to determine if “arming” an oncolytic herpes simplex virus (oHSV) with an MMP-antagonizing transgene would increase virus-mediated antitumor efficacy. We generated oHSVs that express human tissue inhibitor of metalloproteinases 3 (TIMP3) or firefly luciferase and designated them rQT3 and rQLuc, respectively. We evaluated the antitumor efficacy of these viruses against neuroblastoma and malignant peripheral nerve sheath tumor (MPNST) xenografts. Relative to rQLuc, rQT3-infected primary human MPNST and neuroblastoma cells exhibited equivalent virus replication but increased cytotoxicity and reduced MMP activity. In vivo, rQT3-treated tumors showed delayed tumor growth, increased peak levels of infectious virus, immature collagen extracellular matrix, and reduced tumor vascular density. Remarkably, rQT3 treatment reduced circulating endothelial progenitors, suggesting virus-mediated antivasculogenesis. We conclude that rQT3 enhanced antitumor efficacy through multiple mechanisms, including direct cytotoxicity, elevated virus titer, and reduced tumor neovascularization. These findings support the further development of combined TIMP-3 and oncolytic virotherapy for cancer. [Cancer Res 2008;68(4):1170–9]

The speed of sound is a physical property that can be measured easily in the lab. However, finding an inexpensive and intuitive way for students to determine this speed has been more involved. The introduction of affordable consumer-grade high-speed cameras (such as the Exilim EX-FC100) makes conceptually simple experiments feasible. Since the Exilim can capture 1000 frames a second, it provides an easy way for students to calculate the speed of sound by counting video frames from a sound-triggered event they can see. For our experiment, we popped a balloon at a measured distance from a sound-activated high-output LED while recording high-speed video for later analysis. The beauty of using this as the method for calculating the speed of sound is that the software required for frame-by-frame analysis is free and the idea itself (slow motion) is simple. This allows even middle school students to measure the speed of sound with assistance, but the ability to independently verify such a basic result is invaluable for high school or college students.

The electrostatic potential is a key element of the second semester of introductory physics. Teaching about its gravitational analog in the first semester allows students to make more connections between the two courses. The use of a simple thought experiment with an unexpected outcome provides a method for introducing gravitational potential in a way students may remember.

Purpose This study examined the influence of body fatness on body core temperature and heat loss responses during moderate-intensity exercise. Methods Nine men with lower body fat and eight men with higher body fat, matched for aerobic fitness, completed 1 h of recumbent cycling at the same absolute intensity in a warm environment (30 degrees C, 40% RH). Percent body fat was measured by hydrostatic weighing, using oxygen dilution to determine residual volume. Esophageal temperature (T(es)), mean skin temperature (T(sk)), and local sweat rate (m(sw)) were measured at rest and continuously during exercise while forearm blood flow (FBF) was measured at rest and every 10 min during exercise. Results The lower body fat and higher body fat groups were successfully matched for aerobic fitness, removing the influence of body fatness, given that V/O2(peak) was 50.72 +/- 7.34 and 50.43 +/- 5.01 ml x kg LBM(-1) x min(-1), respectively. When compared to lower body fat individuals, % body fat, body surface area (A(D)), and body mass were higher and A(D)/ mass was lower in higher body fat individuals. T(es), T(sk), FBF, m(sw), and the slope of m(sw):T(es) were not different between groups. Metabolic heat production was similar between the lower body fat (299.7 +/- 40.5 W x m(-2)) and higher body fat (288.1 +/- 30.6 W x m(-2)) subjects, respectively. Dry and evaporative heat loss, as well as heat storage during exercise, were not different between groups. Conclusion These data suggest that there is no effect of body fatness on body core temperature or heat loss responses during moderate-intensity exercise in a warm environment.

Effective therapies for metastatic sarcomas remain elusive. Oncolytic viruses have shown promise as anticancer agents, but their access to metastatic sites following systemic delivery is low. As systemic delivery of small-molecule chemotherapy is enhanced by previous treatment with antiangiogenic agents because of changes in intravascular-to-tumor interstitial pressure, we sought to determine whether antiangiogenic pretreatment increases the antitumor efficacy of systemic virotherapy by increasing virus uptake into tumor. Virus biodistribution and antitumor effects were monitored in tumor-bearing mice given antihuman vascular endothelial growth factor (VEGF) or antimouse VEGFR2 before or after an intravenous (i.v.) injection of virus. Without pretreatment, the average virus titers in the tumor samples amplified 1700-fold over 48 h but were undetectable in other organs. After antiangiogenic treatment, average virus titers in the tumor samples were unchanged or in some cases decreased up to 100-fold. Thus, antiangiogenic pretreatment failed to improve the tumor uptake of systemic oncolytic herpes simplex virus (oHSV), in contrast to previously reported enhanced uptake of small molecules. Superior tumor control because of the combined effects of virus and anti-VEGF was seen most dramatically when anti-VEGF was given after virus. Our data suggest that i.v. oHSV can treat distant sites of disease and can be enhanced by antiangiogenic therapy, but only when given in the proper sequence.

Background Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers. Methodology/Principal Findings Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice. Conclusions/Significance These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

Students commonly find the second semester of introductory physics to be more challenging than the first, probably due to the mechanical intuition we acquire just by moving around. For most students, there is no similar comfort with electricity or magnetism. In an effort to combat this confusion, we decided to examine simple electric circuits with either a high-speed camera or a thermal imager in an effort to make things like current and voltage as familiar as slow motion or temperature.

Extending the usefulness of the instruments we have has never been more important. The current economic crisis has prompted all of us to re-examine how money is spent and to try to minimize our expenditures because of future uncertainties. We have been able to breathe new life into an aging 60 MHz NMR spectrometer used by hundreds of undergraduates each year in the second-year organic chemistry sequence. Minor repairs have been necessary over the years but the recent loss of the plotter necessitated a more extensive “repair”. With the help of a physicist, the instrument output is now routed through a two-channel data acquisition device to a laptop. The data gathered is saved as a comma-delimited text file, and an Excel spreadsheet is used for analysis of the data. Not only does the new system allow faster data collection and processing, it also allows students to save data to a thumb drive. With minimal expense, the 20-year-old spectrometer has been modernized and continues to be an essential part of the organic laboratory.