The disease xeroderma pigmentosum is characterized by deficient repair of damaged DNA. Fusions of cells from different patients have defined nine genetic complementation groups (A through I), implying that DNA repair in humans involves multiple gene products. In this report, an extension of the gel electrophoresis binding assay was used to identify at least one nuclear factor that (i) bound to DNA damaged by ultraviolet radiation or the antitumor drug cisplatin, but (ii) was notably absent in cells from complementation group E. Therefore, the factor appears to participate in a versatile DNA repair pathway at the stage of binding and recognition.

Since the Wright Flyer, engineers have strived to develop flying machines with morphing wings that can control flight as deftly as birds. Birds morph their wing planform parameters simultaneously—including sweep, span, and area—in a way that has proven to be particularly challenging to embody robotically. Previous solutions have primarily centered around the classical aerospace paradigm of controlling every degree of freedom to ensure predictable performance, but underperform compared with birds. To understand how birds accomplish wing morphing, we measured the kinematics of wing flexion and extension in common pigeons, Columba livia. The skeletal and feather kinematics show that the 20 primary and 20 secondary feathers are coordinated via approximately linear transfer functions controlled by wrist and finger motion. To replicate this control principle in a robot, we developed a biohybrid morphing wing with real feathers to understand the underlying design principles. The outcome, PigeonBot, embodies 42 degrees of freedom that control the position of 40 elastically connected feathers via four servo-actuated wrist and finger joints. Our flight tests demonstrate that the soft feathered wings morph rapidly and robustly under aerodynamic loading. They not only enable wing morphing but also make robot interactions safer, the wing more robust to crashing, and the wing reparable via “preening.” In flight tests, we found that both asymmetric wrist and finger motion can initiate turn maneuvers—evidence that birds may use their fingers to steer in flight.

Variable feather overlap enables birds to morph their wings, unlike aircraft. They accomplish this feat by means of elastic compliance of connective tissue, which passively redistributes the overlapping flight feathers when the skeleton moves to morph the wing planform. Distinctive microstructures form “directional Velcro,” such that when adjacent feathers slide apart during extension, thousands of lobate cilia on the underlapping feathers lock probabilistically with hooked rami of overlapping feathers to prevent gaps. These structures unlock automatically during flexion. Using a feathered biohybrid aerial robot, we demonstrate how both passive mechanisms make morphing wings robust to turbulence. We found that the hooked microstructures fasten feathers across bird species except silent fliers, whose feathers also lack the associated Velcro-like noise. These findings could inspire innovative directional fasteners and morphing aircraft.

Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, we identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair.Drugs used in cancer chemotherapy may be extremely effective in killing tumor cells, but relapses occur all too often due to the subsequent development of drug resistance in the tumor cells. One model for this phenomenon is the development of methotrexate resistance in vitro. The level of resistance may increase 100-to 1000-fold when cells are grown in the presence of methotrexate and can be due to many mechanisms, including amplification or mutations of the gene for dihydrofolate reductase (dhfr) (1). A second model is the simultaneous development of resistance to multiple drugs, including adriamycin, actinomycin D, vinca alkaloids, and podophyllotoxins (2). Again the level of resistance may be very high and has been shown to arise from amplification or mutations of multidrug resistance (mdr) genes that code for membrane glycoproteins involved in drug efflux (3,4).However, neither the dhfr nor mdr gene is involved in the development of resistance to a number of therapeutically important drugs that form DNA adducts, including agents such as nitrogen mustard, cyclophosphamide, mitomycin C, and cisplatin. Tissue culture models indicate that the level of resistance to such agents is limited. For example, cell lines grown in cisplatin exhibit only 5-to 50-fold increased resistance (5). There has been indirect evidence that resistance is mediated at least in part by DNA repair (6), but evidence for the increased expression of specific DNA repair proteins has been lacking because the biochemistry of DNA repair in humans has been poorly understood.To study resistance to cisplatin, we reasoned that the repair of damaged DNA must depend on cellular factors that are capable of recognizing the site of damage. Such factors can be identified by an extension of the gel electrophoresis binding assay utilizing damaged DNA as the probe for analyzing cell extracts (7).This report describes two independent cellular factors that recognize cisplatin-damaged DNA. One was detected by a cisplatin-damaged DNA probe, appeared to recognize only that form of damaged DNA, and was designated as cisplatincrosslinked DNA (CCD) binding factor. The other was detected by a UV-damaged DNA probe, also bound to cisplatindamaged and single-stranded DNA in competit...

A novel technique is presented for estimating the various transport quantities in two-phase materials of random structure by extending, in an approximate manner, the effective continuum description of such systems. The method is then applied to three representative examples and is found to give results in excellent agreement with those obtained from exact calculations.

Angiotensinogen is regulated by both hormones and changes in cardiovascular and electrolyte status. We have used the Reuber H35 (H4IIE) rat hepatoma cell line to study the regulation of angiotensinogen mRNA levels by dexamethasone, aldosterone, L-T3, and 17 beta-estradiol. Using the Acc I (1097 basepairs) fragment of our angiotensinogen cDNA clone, we have studied, by Northern and slot blot analysis, the accumulation of angiotensinogen mRNA in this cell culture system. Angiotensinogen mRNA of approximately 1800 bases was identified in these cells. It was identical in size to angiotensinogen mRNA from rat liver. Cells grown in medium containing serum depleted of thyroid and steroid hormones for up to 72 h showed a progressive decrease in angiotensinogen mRNA. Dexamethasone treatment resulted in a time- and dose-dependent increase in angiotensinogen mRNA. The half-maximal response occurred at 10(-9) M dexamethasone, with a maximal response of approximately 4-fold (serum-free conditions). Aldosterone induced a dose-dependent increase in mRNA. Half-maximal levels were obtained at 5 X 10(-8) M. Competition studies using the glucocorticoid antagonist RU38486 (Roussel-UCLAF) confirmed that dexamethasone was acting through the glucocorticoid receptor and suggested that aldosterone was acting through the same receptor. L-T3 treatment caused a dose and time-dependent increase in angiotensinogen mRNA levels. The half-maximal response occurred at 5 X 10(-8) M, and the maximal response was a 2-fold increase. Combined treatment with dexamethasone and L-T3 triiodothyronine resulted in a synergistic increase in angiotensinogen mRNA levels. 17 beta-Estradiol failed to elicit a change in angiotensinogen mRNA levels consistent with the observation that these cells lack estrogen receptors. Our results indicate that hepatic angiotensinogen mRNA levels are regulated in a complex fashion by several hormones. These cells provide a useful system for studying the hormonal regulation of the angiotensinogen gene.

Flying birds maneuver effectively through lateral gusts, even when gust speeds are as high as flight speeds. What information birds use to sense gusts and how they compensate is largely unknown. We found that lovebirds can maneuver through 45° lateral gusts similarly well in forest-, lake-, and cave-like visual environments. Despite being diurnal and raised in captivity, the birds fly to their goal perch with only a dim point light source as a beacon, showing that they do not need optic flow or a visual horizon to maneuver. To accomplish this feat, lovebirds primarily yaw their bodies into the gust while fixating their head on the goal using neck angles of up to 30°. Our corroborated model for proportional yaw reorientation and speed control shows how lovebirds can compensate for lateral gusts informed by muscle proprioceptive cues from neck twist. The neck muscles not only stabilize the lovebirds’ visual and inertial head orientations by compensating low-frequency body maneuvers, but also attenuate faster 3D wingbeat-induced perturbations. This head stabilization enables the vestibular system to sense the direction of gravity. Apparently, the visual horizon can be replaced by a gravitational horizon to inform the observed horizontal gust compensation maneuvers in the dark. Our scaling analysis shows how this minimal sensorimotor solution scales favorably for bigger birds, offering local wind angle feedback within a wingbeat. The way lovebirds glean wind orientation may thus inform minimal control algorithms that enable aerial robots to maneuver in similar windy and dark environments.

We consider the problem of heat conduction near an isothermal wall in contact with a composite consisting of a matrix containing a random dispersion of spheres having a different thermal conductivity than the matrix. Far away from the wall, i.e., on the macroscopic length scale, the average bulk temperature field is composed of a uniform gradient term plus a constant offset. If the temperature of the wall is set equal to zero, this offset temperature, which would vanish if the composite were replaced everywhere with an effective continuum, provides a measure of the degree to which the continuum hypothesis is inapplicable in describing the heat transfer process near the wall. To this end, we estimate this offset temperature via an effective continuum method to all orders in the inclusion volume fraction c of the composite, as well as find its exact value when c is small. Finally, we illustrate how these results may be applied to other problems in which the continuum assumption becomes invalid using, as an example, the problem of finding the rate of heat conduction from a heated sphere surrounded by a composite.