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Six cases of cartilage hair hypoplasia from five kindreds are described. They demonstrate variation in the expression of clinical features such as sparsity of hair, hair calibre, radiological changes, short stature and the extent of the disproportion between sitting height and stature.
Urogenital infections in postmenopausal women remain problematic. The use of estrogen replacement therapy has been shown to lower these infection rates, corresponding to increasing colonization by Lactobacillus species. Despite the gut's 500 microbial species and the proximity of the anus to the vagina, only a relatively few microbial strains appear to be able to colonize the urogenital area. In the present study, the sparsity of microbes in the vagina was confirmed by denaturing gradient gel electrophoresis analysis of swabs taken at time zero and monthly for 3 months from 40 postmenopausal subjects receiving Premarin (conjugated equine estrogen in combination with progesterone) hormone replacement therapy (HRT) and 20 who were not on HRT. Lactobacilli were recovered from the vagina of 95% or more women in both groups, but in the HRT group, Lactobacillus were more often the dominant and only colonizers and significantly fewer bacteria with pathogenic potential were found. The incidence of bacterial vaginosis was significantly lower in the HRT group than in the non-HRT-treated women (5.6% versus 31%). The use of HRTs has recently come under criticism. The ability of drugs such as Premarin to help recover the lactobacilli vaginal microbiota appears to be at least one benefit of HRT use. In women not using HRTs, use of probiotics may be the only way to restore a nonpathogen-dominated flora.
This work presents a new class of neural network models constrained by biological levels of sparsity and weight-precision, and employing only local weight updates. Concept learning is accomplished through the rapid recruitment of existing network knowledge - complex knowledge being realised as a combination of existing basis concepts. Prior network knowledge is here obtained through the random generation of feedforward networks, with the resulting concept library tailored through distributional bias to suit a particular target class. Learning is exclusively local - through supervised Hebbian and Winnow updates - avoiding the necessity for backpropagation of error and allowing remarkably rapid learning. The approach is demonstrated upon concepts of varying difficulty, culminating in the well-known Monks and LED benchmark problems.
There is a sparsity of data on energy expenditure in young children. We therefore examined the components of daily energy expenditure in a group of 30 children (16 boys, 14 girls; age 4-6 yr) characterized for body weight, height, heart rate, and body composition from bioelectrical resistance. Total energy expenditure (TEE) was measured over 14 days under free living conditions by doubly labeled water, resting energy expenditure (REE) from indirect calorimetry, and activity energy expenditure was estimated from the difference between TEE and REE. Mean TEE was 1,379 +/- 290 kcal/day, which was 475 +/- 202 kcal/day lower than energy intake recommendations for this age group. Activity-related energy expenditure was estimated to be 267 +/- 203 kcal/day. TEE was most significantly related to fat-free mass (FFM; r = 0.86; P < 0.001), body weight (r = 0.83; P < 0.001), and REE (r = 0.80; P < 0.001). When TEE was adjusted for FFM, a significant correlation with heart rate was observed (partial r = 0.54; P = 0.002). Collectively, 86% of interindividual variation in TEE was accounted for by FFM, heart rate, and REE. We conclude that, in young 4- to 6-yr-old children, 1) TEE is approximately 25% lower than current recommendations for energy intake and 2) combined measurement of FFM, heart rate, and REE explain 86% of interindividual variation in TEE, thus providing a possible alternative method to estimate TEE in young children.
This study evaluated the importance of ATP-dependent potassium channels (KATP) for ischemic preconditioning (IP) in swine. Swine were studied because due to the sparsity of their innate collateral circulation infarct size (IS) development closely resembles that observed in humans. Ninety minutes of ischemia at a blood flow reduction sufficient to reduce regional myocardial work by 90% caused 13.2 +/- 8.9% (SD) IS of the area at risk. A single cycle of 10-min preconditioning ischemia followed by 15-min reperfusion reduced IS after 90 min of ischemia to 2.8 +/- 2.7%. The epicardial monophasic action potential duration at 50% repolarization (MAP50) was decreased more markedly during the initial 10 min of the prolonged ischemia than during the first 10 min of the preconditioning ischemic period (84 +/- 4 vs. 89 +/- 2%). Transmural myocardial adenosine (ADO) uptake was reversed to net release during both ischemic periods and during the initial phase of reperfusion. Glibenclamide (0.5 mg/kg, followed by 50 micrograms/min i.v.) abolished the reduction in MAP50 without altering ADO release. Glibenclamide did not alter IS per se (13.0 +/- 7.6%) but abolished the beneficial effect of IP (IS: 13.6 +/- 6.2%). Thus blockade of KATP with glibenclamide abolishes the IS-reducing effect of IP in swine but does not reduce ADO release.
1. Continuous segments of synaptic noise were recorded, in 12 experiments, from the voltage-clamped goldfish Mauthner (M-)-cell soma during depolarizations beyond the Cl- equilibrium potential so that spontaneous inhibitory postsynaptic currents (IPSCs) were outward going, i.e., opposite in polarity to excitatory transients. Inhibitory components constituting the noise were detected with a program based on their expected waveforms, and their amplitude distributions were analyzed according to a quantal model to determine whether these responses, presumably because of asynchronous impulses in a population of presynaptic cells, were integral multiples of the same minimal unit. 2. Synaptic noise in the M-cell is predominantly inhibitory, as it is abolished by the glycine antagonist strychnine. IPSC amplitudes varied by 20-fold or more and about one-third were grouped in bursts, with one or several components often occurring during the falling phase of a preceding one. To measure individual amplitudes, a base-line correction procedure was designed to extrapolate the decay of the leading IPSC, on the assumption that it was exponential with a time constant, tau, equal to that obtained by fitting averaged waveforms of distinct IPSCs recorded in quiet periods. Currents were expressed in nanoamperes and, for comparison between experiments, as percentages of the full-sized IPSC evoked by activation of the collateral network. 3. The probability distribution functions (PDFs) of inhibitory events generated with such an analysis had from 5 to 12 clear and equally spaced peaks, larger transients not being included because of their sparsity. These PDFs were fit with a sum of Gaussians, on the assumption that all peaks were integral multiples of the smallest unit and had the same standard deviation, sigma. The fits were statistically satisfactory, according to a chi 2 test, and mean quantal size was 0.63 +/- 0.17% (SD; range, 0.42-1.0%) of the collateral IPSC. 4. In eight experiments, tetrodotoxin (TTX) was subsequently applied topically to block presynaptic impulses and isolate "miniature" responses because of single exocytotic events. It had no apparent nonspecific effects, as indicated by the constancy of M-cell input conductance (8.01 +/- 3.11 microS vs. 7.90 +/- 2.89 microS). Amplitude distributions of residual IPSCs were unimodal and Gaussian, with their mean size (0.60 +/- 0.19%) and average rise time (0.548 +/- 0.128 ms) the same as those of the first peaks of control histograms. The latter parameter was also comparable with that of unitary IPSCs studied previously. These results thus confirmed that spontaneous and evoked events are due to transmitter release from the same afferent population.(ABSTRACT TRUNCATED AT 400 WORDS)
Evidence on the relationship between the infiltration of dendritic cells (DCs) and prognosis in head and neck tumors exists. Interestingly, only limited information is available regarding the maturation state and distribution of DCs in parotid gland tumors. The purpose of our study was therefore to extend these observations and to investigate in more detail the density and distribution of mature DCs and Langerhans cells (LCs) in parotid gland tumors. We present immunohistochemical evidence of characterization and distribution of DCs and LCs in parotid gland tumors, enclosed pleomorphic adenomas and malignant parotid tumors. Two populations of mature DCs could be identified, P55(+)-DCs and DC-LAMP(+)-DCs, whereas LCs could be identified as Langerin(+)-LCs. The overall impression was that parotid gland tumors contained only few mature DCs and LCs. Considering the sparsity of mature DCs in the malignant tissues, anti-tumor response can be only limited. On the basis of our data, we imply that the application of DC vaccination in combination with other modalities for treatment of parotid gland carcinoma should be taken into account. In this regard, the utilization of DC immunotherapy for management of minimal residual disease after resection of primary tumor can be promising. Putative targets expressed in this type of tumors have to be defined.
A black girl with the Rothmund-Thomson syndrome is presented. Immunophenotyping of subpopulations of immunocompetent cells in a biopsy of an atrophic hyperpigmented skin lesion revealed sparsity and unusual distribution of epidermal Langerhans cells. These cells were mainly located in the basal layer of the epidermis and did not show the usual dendritic pattern. Impressive immunoreactivity of the dermal infiltrate was observed by anti-HLA-DR staining. The changes in Langerhans cell morphology and distribution may indicate functional impairment of the up-regulating arm of skin immunity.
In this letter, we analyze a two-stage cluster-then-l(1)-optimization approach for sparse representation of a data matrix, which is also a promising approach for blind source separation (BSS) in which fewer sensors than sources are present. First, sparse representation (factorization) of a data matrix is discussed. For a given overcomplete basis matrix, the corresponding sparse solution (coefficient matrix) with minimum l(1) norm is unique with probability one, which can be obtained using a standard linear programming algorithm. The equivalence of the l(1)-norm solution and the l(0)-norm solution is also analyzed according to a probabilistic framework. If the obtained l(1)-norm solution is sufficiently sparse, then it is equal to the l(0)-norm solution with a high probability. Furthermore, the l(1)- norm solution is robust to noise, but the l(0)-norm solution is not, showing that the l(1)-norm is a good sparsity measure. These results can be used as a recoverability analysis of BSS, as discussed. The basis matrix in this article is estimated using a clustering algorithm followed by normalization, in which the matrix columns are the cluster centers of normalized data column vectors. Zibulevsky, Pearlmutter, Boll, and Kisilev (2000) used this kind of two-stage approach in underdetermined BSS. Our recoverability analysis shows that this approach can deal with the situation in which the sources are overlapped to some degree in the analyzed domain and with the case in which the source number is unknown. It is also robust to additive noise and estimation error in the mixing matrix. Finally, four simulation examples and an EEG data analysis example are presented to illustrate the algorithm's utility and demonstrate its performance.
The sparsity of photons at very low light levels necessitates a nonlinear synaptic transfer function between the rod photoreceptors and the rod-bipolar cells. We examine different ways to characterize the performance of the pathway: the error rate, two variants of the mutual information, and the signal-to-noise ratio. Simulation of the pathway shows that these approaches yield substantially different performance at very low light levels and that maximizing the signal-to-noise ratio yields the best performance when judged from simulated images. The results are compared to recent data.
We derive a new general representation for a function as a linear combination of local correlation kernels at optimal sparse locations (and scales) and characterize its relation to principal component analysis, regularization, sparsity principles, and support vector machines.
Influenza virus attaches primarily to ciliated cells in mature airways epithelium. This process is mediated by a viral envelope glycoprotein (hemagglutinin) that binds to sialic acid-containing receptors in the apical membrane of host cells. The purpose of this study was to determine the cellular distribution of these receptors as a function of tracheal epithelial maturation in the ferret, which is susceptible to influenza virus infection at all ages and undergoes postnatal ciliation. To assay for virus attachment, tracheal strips from ferrets at ages 0, 7, 14, and 28 d were incubated at 4 degrees C for 1 h with a concentrated suspension of influenza A virus. Transmission electron microscopy demonstrated virus attachment to the apical surface of 77 to 87% of ciliated cells, but only to 1 to 9% of nonciliated surface epithelial cells at all ages, including the newborn, which has few ciliated cells (less than 10% of total cells). Virions also attached to most of the preciliated cells identified. Pretreatment of tracheal strips with neuraminidase virtually eliminated viral attachment. These findings demonstrate preferential influenza virus binding to sialylated receptors on ciliated cells and their immediate precursors. The sparsity of ciliated cells with no evidence for increased influenza virus binding per cell in newborn ferret tracheas suggests that the previously demonstrated high risk of death from influenza infection in newborn ferrets is due to factors other than increased susceptibility to virus attachment. Influenza virus receptors appear to be selective membrane markers for ciliated cells and may be particularly useful for the identification of preciliated cells.
Specimens from 17 head and neck tumor patients were immunohistochemically stained with monoclonal antibodies against HLA-DR, CD1a, RFD1, LAG, CD3, CD4, CD8, CD45RO, CD68, and cytokeratin to identify the nature and distribution of dendritic cells (DCs), T cells, and macrophages. Small numbers of DCs were present in all but 2 specimens. They were located between the tumor cells and in the stroma, especially in areas of inflammatory cell infiltration. Variable numbers of T lymphocytes (cytotoxic and memory type) occurred in the same locations. Numerous macrophages were found in the epithelium, in the stroma, and in the vicinity of tumor cells. The presence of DCs in head and neck tumors indicates that the organism has activated the immune surveillance system and is trying to present tumor antigens. Considering the sparsity of DCs in the malignant tissues, the T cell response can be only limited.
We sought to describe the clinical presentation and consequences of meningitis among 64 very-low-birth-weight (VLBW <1.5 kg) infants who had 67 culture-proven episodes of meningitis over an 18-year period, 1977 through 1995. Demographic and neonatal descriptors of meningitis and later outcomes were retrospectively examined and neurodevelopmental outcomes of 39 of 45 (87%) meningitis survivors were compared to those of nonmeningitis survivors followed up to 20 months corrected age. Causes of meningitis included coagulase-negative Staphylococcus in 43% of episodes, other gram-positive bacteria in 19%, gram-negative bacteria in 17%, and Candida species in 20% of episodes. Spinal fluid abnormalities were sparse, regardless of etiologic organism. Of 38 nonbloody spinal fluid taps (<1,000 erythrocytes/mm3), 6 had >30 leukocytes/mm3, 5 protein >150 mg/dL%, and 6 glucose <30 mg/dL (1.67 mmol/L). Only 10 infants (26%) had 1 or more of these spinal fluid abnormalities. Meningitis survivors had a higher rate of major neurologic abnormality (41% vs 11%, p<0.001) and subnormal (<70) Mental Development Index (38% vs 14%, p<0.001) than nonmeningitis survivors. Impairment rates did not differ by etiologic organism. The effect of meningitis on neurologic outcome persisted even after controlling for birth weight, intraventricular hemorrhage, chronic lung disease, and social risk factors (odds ratio 2.27 [95% CI 1.02, 5.05]). We conclude that despite a sparsity of abnormal spinal fluid findings, culture-proven neonatal meningitis among VLBW infants has a detrimental effect on neurologic outcome, which persists even after controlling for other risk factors.
The hypermetabolic state observed in thermally injured patients warrants aggressive nutritional management. Enteral support is the preferred route of nutrient delivery, however diarrhea is reported to be a persistent complication of continuous nasogastric or nasoduodenal hyperalimentation. Diarrhea adds to problems in patient care, disturbs fluid and electrolyte balance, and worsens nutritional status. There has been the impression that tube feeding hyperosmolality, antibiotics, and low serum albumin induce diarrhea. However, in view of the sparsity of published work, a prospective study was undertaken to determine the incidence of diarrhea and to define factors associated with its cause. Of the 50 patients studied, 16 (32%) developed diarrhea. Stool cultures were negative for pathogenic organisms. Although the risk of diarrhea was associated with antibiotics (p less than 0.005), several nutrients also had an impact. Results demonstrated a significant relationship between dietary lipid content (p less than 0.05) or vitamin A intake (p less than 0.001) and diarrhea. Implementation of tube feeding within 48 hrs postburn was also associated with a decreased incidence of diarrhea (p less than 0.001). This paper describes a modular tube feeding program in which diarrheal frequency is lessened (p less than 0.0001). Surprisingly, tube feeding osmolality, drugs used to prevent stress ulcers, or hypoalbuminemia did not have an adverse effect on intestinal absorption. The cause of diarrhea in burn patients is obviously multifactorial. It is concluded that a low fat (less than 20% of caloric intake), vitamin A enriched (greater than 10,000 IU/day), early enteral support program maximizes conditions which promote tube feeding tolerance while minimizing nutrient malabsorption during the nutritional rehabilitation of thermal injury.
A 34-year-old female orangutan (Pongo pygmaeus) developed renal failure and became uremic. At necropsy, large gastric masses were present around the cardia and in the corpus. Abdominal metastases occurred in the liver, pancreas, and right ovary. Light microscopic examination of the tumor revealed polygonal cells with vesicular nuclei and prominent nucleoli. The growth pattern was predominantly solid. Focal areas contained excentric cytoplasmic intermediate filament inclusions, as identified by immunohistochemistry and electron microscopy. Immunohistochemical procedures demonstrated mainly the vimentin type of intermediate filaments. Except for occasional cytokeratin, other intermediate filament markers and neural, lymphocytic, and histiocytic markers stained negative. The morphologic and ultrastructural characteristics are typical for a malignant rhabdoid tumor, a term used in human pathology to describe a rare and extremely aggressive malignancy of uncertain histogenesis. Although usually located in the infant kidney, a few reports have documented the occurrence of similar lesions in extrarenal sites of adults. In human tumors, vimentin is often combined with the expression of cytokeratins. The sparsity of the cytokeratin filaments in this case might be due to species-specific variations and/or may reflect the hypothesis of a phenotypic concept encompassing a spectrum of histogenetic diversity.
The burgeoning field of lymphatic research, and the applications of surgical and microsurgical techniques to the problem of lymphedema have been briefly reviewed. The chronicity of this symptom complex and the relative sparsity of cases in developed countries make controlled clinical trials of treatment unfeasable and comparisons of present regimens difficult. However, continued investigation will undoubtedly be fruitful.
BACKGROUND: Single-cell RNA sequencing (scRNA-seq) enables cellular characterization at single-cell resolution. However, its high dimensionality, sparsity, and noise make clustering challenging. Approaches utilizing contrastive learning and data augmentation have been introduced to improve representation quality for scRNA-seq clustering. In particular, dual contrastive frameworks combining instance- and cluster-level objectives can capture both cell-cell similarities and inter-cluster variations. However, existing dual contrastive frameworks focus primarily on discrete cluster boundaries, neglecting the biological continuity inherent in scRNA-seq data. METHODS: We propose scFANCL, a dual contrastive framework designed to capture biological continuity in scRNA data. Rather than treating all non-augmented samples as negatives, scFANCL applies a cosine-similarity-based threshold to exclude cells of the same type from the negative pool, preserving continuous transcriptional relationships among them while maintaining inter-cluster separation. RESULTS: Extensive experiments across seven publicly available scRNA-seq datasets demonstrated that scFANCL achieves competitive clustering performance compared with existing baseline methods, consistently yielding high ARI and NMI scores across datasets of varying size and complexity. Ablation studies further confirmed the contribution of the false negative filtering component, showing measurable improvements over variants without filtering. Downstream analyses further suggest that the learned embeddings may reflect biologically meaningful transcriptional transitions, including continuous differentiation trajectories within related cell types. The source code is available at https://github.com/mjuailab/scFANCL . CONCLUSIONS: scFANCL addresses a key limitation of conventional contrastive learning by applying a cosine-similarity-based threshold to exclude cells of the same type from the negative pool, thereby preserving biological continuity within cell types while maintaining inter-cluster separation. Evaluations across seven benchmark scRNA-seq datasets demonstrate competitive clustering performance, with learned embeddings capturing biologically meaningful transcriptional structure and characteristics of rare cell populations.