Symmetry breaking in the female germline cyst.

In mammals and flies, only one cell in a multicellular female germline cyst becomes an oocyte, but how symmetry is broken to select the oocyte is unknown. Here, we show that the microtubule (MT) minus end-stabilizing protein Patronin/CAMSAP marks the future Drosophila oocyte and is required for oocyte specification. The spectraplakin Shot recruits Patronin to the fusome, a branched structure extending into all cyst cells. Patronin stabilizes more MTs in the cell with the most fusome material. Our data suggest that this weak asymmetry is amplified by Dynein-dependent transport of Patronin-stabilized MTs. This forms a polarized MT network, along which Dynein transports oocyte determinants into the presumptive oocyte. Thus, Patronin amplifies a weak fusome anisotropy to break symmetry and select one cell to become the oocyte.

Inhibition of turbulence in inertial-confinement-fusion hot spots by viscous dissipation.

Achieving ignition in inertial confinement fusion (ICF) requires the formation of a high-temperature (>10 keV) central hot spot. Turbulence has been suggested as a mechanism for degrading the hot-spot conditions by altering transport properties, introducing colder, mixed material, or reducing the conversion of radially directed kinetic energy to hot-spot heating. We show, however, that the hot spot is very viscous, and the assumption of turbulent conditions in the hot spot is incorrect. This work presents the first high-resolution, three-dimensional simulations of National Ignition Facility (NIF) implosion experiments using detailed knowledge of implosion dynamics and instability seeds and including an accurate model of physical viscosity. We find that when viscous effects are neglected, the hot spot can exhibit a turbulent kinetic energy cascade. Viscous effects, however, are significant and strongly damp small-scale velocity structures, with a hot-spot Reynolds number in the range of only 10-100.

Excessive anticoagulation in patients with mild renal insufficiency receiving long-term therapeutic enoxaparin.

Low-molecular-weight heparins, such as enoxaparin, are increasingly being used for treatment of venous thromboembolism. We describe two patients who received therapeutic enoxaparin for several months. Although their serum creatinine values were normal, both had mild renal insufficiency (creatinine clearance 60-70 ml/min), and both accumulated the drug abnormally and experienced clinical bleeding. These results suggest that patients receiving enoxaparin (or other low-molecular-weight heparins) in therapeutic doses for periods of more than 4 weeks should be considered for laboratory monitoring to avoid bleeding.

A study of library use in problem-based and traditional medical curricula.

A key question for librarians and medical educators who are planning for curriculum change is whether students and faculty in problem-based learning (PBL) programs use the library and its resources differently than do participants in traditional programs. During 1991, this research question was explored at three medical schools in the province of Ontario, Canada. At the time of the study, McMaster University medical school was totally problem-based, the University of Western Ontario had one PBL day each week for first-year medical students, and the University of Toronto, although planning for medical curriculum change, had not yet initiated PBL. Data collected in the study suggest that more medical students in the problem-based curriculum than in the more traditional programs use the library and that, when the PBL students use the library, they do so more frequently, for longer periods of time, and as a source of a greater proportion of their study materials. PBL students also use the library more than their counterparts as a place to study and meet other students. Students in the problem-based curriculum use the following resources more extensively: end-user MEDLINE searching, library journals, reserve or short-term loan materials, photocopy services, and audiovisual materials. PBL students also report purchasing more textbooks. In contrast to the differences found among medical students, however, patterns of library and resource use by medical faculty at the three schools were quite similar.

Evaluation of treatment with single-dose ampicillin/sulbactam with probenecid or ceftriaxone in patients with uncomplicated gonorrhea.

This study compared ampicillin/sulbactam plus probenecid with ceftriaxone for treatment of uncomplicated gonorrhea. Of the 297 men and women who were enrolled and randomized to receive either ampicillin/sulbactam (1.0 g/0.5 g) with probenecid (1 g) or ceftriaxone (0.25 g), 274 patients were evaluable. Both ampicillin/sulbactam and ceftriaxone were administered by intramuscular injections. Patients were gonococcal contacts, had positive culture results for Neisseria gonorrhoeae, or had clinical evidence of gonorrhea. Specimens for gonococcal cultures were collected from the cervix (female patients), urethra, rectum, and pharynx at pretreatment and test-of-cure visits. The presence of N. gonorrhoeae and a test-of-cure visit were required for drug efficacy analysis. Of the 274 evaluable patients, 195 (71.2%) had positive culture results for N. gonorrhoeae. Cure was achieved in 93 (94.9%) of 98 patients receiving ampicillin/sulbactam with probenecid and in 96 (99.0%) of 97 patients receiving ceftriaxone. Penicillinase-producing N. gonorrhoeae strains were found in 21 (10.8%) patients; these were eradicated by either ampicillin/sulbactam with probenecid (N = 9) or ceftriaxone (N = 12). Overall, the two drug regimens were very well tolerated and no serious adverse effects were noted. Ampicillin/sulbactam with probenecid may be useful as single-dose therapy in patients with uncomplicated genitorectal gonorrhea.

Monovision contact lens wear and occupational task performance.

The effects of monovision (MV) contact lens wear on the performance of occupational-type nearpoint tasks was evaluated on 18 presbyopic subjects (ages 44 to 67 years) by comparing MV performance (MV condition) to that with distance contact lenses with reading glasses (BV condition). Each subject had correctable distance visual acuity of 6/6 (20/20) in each eye, at least 60 sec arc of near stereopsis, good ocular health, and no previous MV experience. Time performance and error performance for 3 nearpoint occupational tasks (pointers and straws, card filing, and letter editing) were measured with the MV correction and BV correction. Measurements were taken at dispensing and at 2 weeks and 8 weeks after dispensing. Subjects were instructed to wear the MV soft spherical contact lenses at least 8 h per day. We measured BV time performance to be better than MV time performance by 2.8 to 5.7% and also measured an increased number of errors with MV.

Fast ballistic arm movements triggered by visual, auditory, and somesthetic stimuli in the monkey. I. Activity of precentral cortical neurons.

Single-unit recordings from motor cortex (area 4) were obtained in two monkeys trained to perform simple flexion and extension movements of the arm in response to somesthetic, visual, and auditory signals. All neurons tested showed movement-related responses that were identical for equivalent movements irrespective of the modality of the triggering stimulus. Progressively longer reaction times were always associated with progressively longer latencies of unit responses. When visual and auditory stimuli were presented simultaneously, the intensity and the duration of both motor and unitary responses remained unchanged as if only one stimulus (auditory) had been given. When the auditory stimulus was appropriately delayed with respect to the visual one, shortening of motor reaction time was observed with a corresponding shortening of the latency of unit responses. In addition to movement-related responses, some neurons showed sensory-related responses mainly to the somesthetic stimulus (37%) and more rarely to the auditory (11%) and visual stimuli (3%). These "sensory" responses preceded and were independent of the movement-related responses; they showed no obvious correlation with the reaction time. Whenever tested, the somatosensory responses persisted after extinction of the motor responses. These findings suggest that, in our experimental conditions, area 4 neurons of the monkey are not involved in the early processing of sensory information required for the initiation of simple, triggered movements. Rather, they appear to generate signals that are mainly related to the characteristics of the motor responses.

Fast ballistic arm movements triggered by visual, auditory, and somesthetic stimuli in the monkey. II. Effects of unilateral dentate lesion on discharge of precentral cortical neurons and reaction time.

Single-unit recordings from motor cortex (area 4) were obtained before and after dentate lesion in two monkeys executing fast elbow flexions and extensions in response to randomly presented visual, auditory, and somesthetic stimuli. There were no starting or ending reference points or preparatory signals. Monkeys were trained to perform movements larger than 15 degrees within 500 ms of the stimulus presentation. After electrolytic lesion of the dentate nucleus ipsilateral to the trained arm, changes in reaction time (RT) were observed. Mean daily RTs of movements triggered by light and sound were lengthened by 50-70 ms. RTs of movements triggered by somesthetic stimuli were not changed in one monkey, whereas a small increase of only 20 ms was observed in the other animal. Spontaneous firing of precentral neurons was about the same before and after dentate lesion. However, movement-related responses of cortical neurons were affected by the lesion. Whenever there was an increase in RT according to the triggering stimuli, a corresponding increase in the response time of neurons (RS) appeared. Both RS and RT increased by the same amount when movements were triggered by visual and auditory stimuli, whereas they remained about the same when somesthetic stimuli were used to trigger movements. In contrast, the time interval between the appearance of the change of neuronal firing and onset of arm displacement (RM) was not modified after the lesion. Gating of sensory conditioning inputs and modification of RT by the presentation of more than one stimulus were not abolished by dentate lesion. As a whole, the effects of dentate lesion on motor cortical neurons are consistent with the hypothesis that the neocerebellum controls the initiation of simple ballistic limb movements by controlling the discharge of motor cortex neurons. The effects could be attributed to the withdrawal of a facilitatory influence of dentate neurons on the motor cortical cells, particularly for movements triggered by teleceptive inputs.

Biochemical selection systems for mammalian cells: the essential amino acids.

The essential amino acid requirement of cultured mammalian cells can be satisfied by 19 amino acid derivatives. This finding (a) confirms the results of animal nutritional studies and (b) identifies 19 essential amino acid derivatives and should permit the isolation of a new class of auxotrophic mutants. Five naturally occurring auxotrophic markers have been detected in this survey; namely, inability to utilize cystathionine and citrulline in Chinese hamster ovary (CHO) cells, inability to metabolize citrulline by HTC+hepatoma cells, and confirmation of Eagle's observation that KB cells can utilize homocystine in place of methionine or cystine and D-cystine in place of L-cystine.