Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity of rostral trigeminal sensory neurons in the cat during wakefulness and sleep.

1. Relatively little is known about the activity of trigeminal sensory neurons during naturally occurring behavioral states of sleep and wakefulness. Accordingly, experiments were performed in chronic unanesthetized behaving cats in which neuronal activity in the rostral trigeminal sensory nuclear complex (TSNC) was recorded extracellularly in response to low-intensity stimulation of mandibular and maxillary divisions of cranial V nerve. The peripheral responses of TSNC neurons were evaluated during naturally occurring episodes of wakefulness, quiet sleep, and active sleep. 2. The location of the rostral TSNC was confirmed by recording characteristic orthodromic field potentials generated in response to afferent volleys from tooth pulp and inferior alveolar (IAN) nerve stimuli. Antidromic fields from the trigeminal (MotV) and facial (MotVII) motor pools were used to demarcate the anterior and posterior limits of the rostral TSNC (i.e., main sensory nucleus and nucleus oralis pars gamma). 3. In the absence of peripherally applied stimuli, individual rostral TSNC neurons recorded in the chronic, unanesthetized cat during the behavioral state of wakefulness did not display ongoing spike activity. 4. The response characteristics of individual TSNC neurons to low-intensity stimuli delivered to V afferents emanating from the canine tooth pulps during the behavioral state of drowsy wakefulness consisted of a short train of action potentials characterized by a short latency-to-onset (7.2 +/- 0.4 ms, mean +/- SE, n = 51). TSNC neurons fell into two categories on the basis of their response to graded intensities of tooth pulp stimuli. "Stimulus intensity-dependent" neurons demonstrated evoked responses that had a response profile that increased with stimulus intensity. In contrast, the response profile of "stimulus intensity-independent" neurons remained stable irrespective of the stimulus intensity used. 5. During episodes of wakefulness and quiet sleep, IAN-evoked orthodromic fields did not differ in their amplitude or other waveform parameters. However, during active sleep, the IAN-evoked orthodromic field potential was suppressed by an average of 28% as compared with wakefulness. 6. The number of action potentials evoked by consecutive presentation of low-intensity tooth pulp stimuli were compared during sleep and wakefulness. The evoked responses were suppressed during active sleep (29%, n = 42). Suppression observed during active sleep occurred in both ("stimulus-dependent" and "stimulus-independent") groups of TSNC neurons. During the phasic rapid-eye-movement (REM) episodes of active sleep, both the orthodromic field potentials and unitary action potentials were further suppressed or abolished. 7. The conclusion is reached that synaptic transmission through the rostral trigeminal sensory nucleus is dependent on the behavioral state of the animal. (ABSTRACT TRUNCATED AT 400 WORDS)
Defining Negative Margins in DCIS Patients Treated with Breast Conservation Therapy: The University of Chicago Experience

Abstract: Management of ductal carcinoma in situ (DCIS) has been evolving and the majority of women are now being treated with breast‐conserving surgery and radiation therapy (i.e. breast conservation therapy [BCT]). Controversies still exist regarding the histologic features and margin status that are associated with local recurrence. The goal of this study was to review our institution's experience in patients diagnosed with DCIS and treated with BCT to determine pathologic features that can predict local recurrence, with particular emphasis on the final surgical margin status. We analyzed 103 consecutive patients with DCIS who were treated with BCT between 1986 and 2000. The slides were reviewed to determine the final margin status, type of DCIS, size of DCIS, nuclear grade, presence of necrosis and calcification, and volume of excised specimen. Margins were considered positive when DCIS touched or was transected at an inked margin. Negative margins were further categorized as close (less than 1 mm), 1–5 mm, and more than 5 mm. The size of the DCIS was determined based on either the maximal dimension on a slide or from the number of consecutive slides containing DCIS. Morphology and immunohistochemical profiles of the recurrent DCIS cases were compared with original DCIS. All patients were treated uniformly with external beam radiation therapy to the entire breast (median dose 46 Gy) with a boost to the tumor bed (median dose 14 Gy). The median follow‐up was 63 months (range 7–191 months). The actuarial 5‐year local control rate was 89%. The median time to local recurrence was 55 months. There were 13 local recurrences, of which 9 recurred as pure DCIS and 4 as invasive ductal carcinomas. Univariate analysis showed a significant association with local recurrence for positive margin (p = 0.008), high nuclear grade (p = 0.02), and young age at diagnosis (p = 0.03). If margins were negative, the 5‐year local control was 93%, as compared to 69% if margins were positive. A multivariate analysis showed that early age at diagnosis, positive margin status, and high nuclear grade were independently associated with local recurrence. The morphology and immunohistochemical stains of all nine recurrent DCIS were similar to those of the original DCIS. Breast conservation can be achieved with excellent local control by obtaining microscopically negative margins as strictly defined by DCIS not touching the inked surgical margins, and postoperative radiation that includes boost therapy to the tumor bed.
Multiple sclerosis in children; a clinical study of 40 cases with onset in childhood.

Forty cases of disease of the central nervous system, characterized by several episodes and disseminated lesions, with onset in childhood and clinically typical of multiple sclerosis, were studied. The disease as it occurs in children does not appear to differ clinically from the disease as observed in adults, in respect to mode of onset, symptoms, physical findings, and changes in the spinal fluid. In the Mayo Clinic series, however, almost twice as many girls as boys were affected. A pediatrician confronted with a child showing evidence of scattered neurologic deficits that remit, particularly a disturbance of vision and co-ordination, should consider the possibility of multiple sclerosis.
Optic atrophy in association with cobalamin C (cblC) disease

Purpose: To report the association of optic atrophy with cobalamin C (cblC) disease. Methods: Descriptive case reports on three patients, two of whom were siblings. Results: All three patients with cblC disease exhibited bilateral optic atrophy with decreased visual acuity. Of the two siblings, the younger sister had received cobalamin supplements from birth and the mother had been given cobalamin supplements prenatally. Conclusion: These three cases confirm the association of optic atrophy with cblC disease. Early treatment with cobalamin supplements does not appear to prevent the development of optic atrophy.
Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear‐induced c‐fos expression

Intracellular reactive oxygen species (ROS) may participate in cellular responses to various stimuli including hemodynamic forces and act as signal transduction messengers. Human umbilical vein endothelial cells (ECs) were subjected to laminar shear flow with shear stress of 15, 25, or 40 dynes/cm2 in a parallel plate flow chamber to demonstrate the potential role of ROS in shear‐induced cellular response. The use of 2′,7′‐dichlorofluorescin diacetate (DCFH‐DA) to measure ROS levels in ECs indicated that shear flow for 15 minutes resulted in a 0.5‐ to 1.5‐fold increase in intracellular ROS. The levels remained elevated under shear flow conditions for 2 hours when compared to unsheared controls. The shear‐induced elevation of ROS was blocked by either antioxidant N‐acetyl‐cysteine (NAC) or catalase. An iron chelator, deferoxamine mesylate, also significantly reduced the ROS elevation. A similar inhibitory effect was seen with a hydroxyl radical (·OH) scavenger, 1,3‐dimethyl‐2‐thiourea (DMTU), suggesting that hydrogen peroxide (H2O2), ·OH, and possibly other ROS molecules in ECs were modulated by shear flow. Concomitantly, a 1.3‐fold increase of decomposition of exogenously added H2O2 was observed in extracts from ECs sheared for 60 minutes. This antioxidant activity, abolished by a catalase inhibitor (3‐amino‐1,2,4‐triazole), was primarily due to the catalase. The effect of ROS on intracellular events was examined in c‐fos gene expression which was previously shown to be shear inducible. Decreasing ROS levels by antioxidant (NAC or catalase) significantly reduced the induction of c‐fos expression in sheared ECs. We demonstrate for the first time that shear force can modulate intracellular ROS levels and antioxidant activity in ECs. Furthermore, the ROS generation is involved in mediating shear‐induced c‐fos expression. Our study illustrates the importance of ROS in the response and adaptation of ECs to shear flow. J. Cell. Physiol. 175:156–162, 1998. © 1998 Wiley‐Liss, Inc.
Estradiol Negatively Modulates the Pleiotropic Actions of Orphanin FQ/Nociceptin at Proopiomelanocortin Synapses

Orphanin FQ/nociceptin (OFQ/N) inhibits the activity of proopiomelanocortin (POMC) neurons located in the hypothalamic arcuate nucleus (ARH) that regulate female sexual behavior and energy balance. We tested the hypothesis that estradiol modulates the ability of OFQ/N to pre- and postsynaptically decrease the excitability of these cells. To this end, whole-cell patch-clamp recordings were performed in hypothalamic slices prepared from ovariectomized rats, including some that were injected with the retrograde tracer Fluorogold in the medial preoptic nucleus (MPN) to label the POMC neurons regulating sexual receptivity. OFQ/N (1 µM) evoked a robust outward current in ARH neurons from vehicle-treated animals that was blocked by the opioid receptor-like (ORL)1 receptor antagonist UFP-101 (100 nM) and the G protein-gated, inwardly rectifying K+ (GIRK-1) channel blocker tertiapin (10 nM). OFQ/N also produced a decrease in the frequency of glutamatergic, miniature excitatory postsynaptic currents (mEPSCs), which was also antagonized by UFP-101. Estradiol benzoate (2 µg) increased basal mEPSC frequency and markedly diminished both the OFQ/N-induced activation of postsynaptic GIRK-1 channel currents and the presynaptic inhibition of glutamatergic neurotransmission. These effects were observed in identified POMC neurons, including eight that projected to the MPN. Taken together, these data reveal that estradiol attenuates the pleiotropic inhibitory actions of OFQ/N on POMC neurons: presynaptically through reducing the OFQ/N inhibition of glutamate release and postsynaptically by reducing ORL1 signaling through GIRK channels. As such, they impart critical insight into a mechanism for estradiol to increase the activity of POMC neurons that inhibit sexual receptivity.
HLA Class I Molecules Partner with Integrin β4 to Stimulate Endothelial Cell Proliferation and Migration

Interactions between human leukocyte antigen I and the integrin β4 subunit may contribute to transplant rejection. Integrating Rejection Human leukocyte antigens (HLAs), major histocompatibility complexes in humans, are best known for presenting antigens to immune cells; however, they also mediate other processes. For example, antibody-mediated cross-linking of HLA class I (HLA-I) on the surface of endothelial cells triggers proliferation, involving the activation of the kinases PI3K, Akt, and ERK. HLA-I molecules have no kinase activity, so it is thought that they must associate with other proteins to mediate such signaling. In the context of organ transplantation, the development of recipient antibodies against donor HLA molecules leads to an increased risk of tissue rejection, which is associated with endothelial cell proliferation and migration. Zhang et al. found that cross-linking with antibody against HLA-I triggered a physical and functional association between HLA-I and the integrin β4 subunit in human endothelial cells. Knockdown of HLA-I impaired integrin β4 signaling and the migration of endothelial cells, whereas knockdown of integrin β4 prevented the proliferation of cells in response to antibody-induced cross-linking of HLA-I. Discovery of the interaction between integrin β4 and HLA-I may lead to the development of therapeutic strategies to prevent antibody-mediated transplant rejection and other pathologies. Among transplant recipients, those who produce antibodies against the donor’s human leukocyte antigens (HLAs) are at higher risk for antibody-mediated rejection and transplant vasculopathy, which is a progressive, vasculo-occlusive disease that results in ischemic injury and deterioration of organ function. Antibodies against HLA class I (HLA-I) molecules are thought to contribute to transplant vasculopathy by triggering signals that elicit the activation and proliferation of endothelial cells. Here, we demonstrate a molecular association between HLA-I and the integrin β4 subunit after the stimulation of endothelial cells with HLA-I–specific antibodies. Knockdown of integrin β4 in these cells abrogated the ability of HLA-I to stimulate the phosphorylation of the kinases Akt, extracellular signal–regulated kinase (ERK), and Src, as well as cellular proliferation. Similarly, reducing the abundance of HLA-I suppressed integrin β4–mediated phosphorylation of ERK and the migration of endothelial cells on laminin-5, a component of the extracellular matrix. These results indicate a mutual dependency between HLA-I and the integrin β4 subunit to stimulate the proliferation and migration of endothelial cells, which may be important in promoting transplant vasculopathy and tumor angiogenesis.
Towards Next Generation Bug Tracking Systems

Although bug tracking systems are fundamental to support virtually any software development process, they are currently suboptimal to support the needs and complexities of large communities. This dissertation first presents a study showing empirical evidence that the traditional interface used by current bug tracking systems invites much noise— unreliable, unuseful, and disorganized information—into the ecosystem. We find that noise comes from, not only low-quality contributions posted by inexperienced users or from conflicts that naturally arise in such ecosystems, but also from the difficulty of fitting the complex bug resolution process and knowledge into the linear sequence of comments that current bug tracking systems use to collect and organize information. Since productivity in bug tracking systems relies on bug reports with accessible and realible information, this leaves contributors struggling to work on and to make sense of the dumps of data submitted to bug reports and, thus, impacting productivity. Next generation bug tracking systems should be more than a tool for exchanging unstructured textual comments. They should be an ecosystem that is tailored for collaborative knowledge building, leveraging the power of the masses to collect reliable and useful information about bugs, providing mechanisms and incentives to verify the validity of such information and mechanisms to organize such information, thus, facilitating comprehension and reasoning. To bring bug tracking systems towards this vision, we present three orthogonal approaches aiming at increasing the usefulness and realiability of contributions and organizing information to improve understanding and reasoning. To improve the usefulness and realibility of contributions we propose the addition of game mechanisms to bug tracking systems, with the objective of motivating contributors to post higher-quality content. Through an empirical investigation of Stack Overflow we evaluate the effects of the mechanisms in such a collaborative software development ecosystem and map a promissing approach to use game mechanisms in bug tracking systems. To improve data organization, we propose two complementary approaches. The first is an automated approach to data organization, creating bug report summaries that make reading and working with bug reports easier, by highlighting the portions of bug reports that expert developers would focus on, if reading the bug report in a hurry. The second approach to improve data organization is a fundamental change on how data is collected and organized, eliminating comments as the main component of bug reports. Instead of comments, users contribute informational posts about bug diagnostics or solutions, allowing users to post contextual comments for each of the different diagnostic
A Fifteen-Amino-Acid Peptide Inhibits Human Papillomavirus E1-E2 Interaction and Human Papillomavirus DNA Replication In Vitro

ABSTRACT Mutation of the conserved glutamic acid residue at position 39 of human papillomavirus type 16 (HPV-16) E2 to alanine (E39A) disrupts its E1 interaction activity and its replication function in transient replication assays but does not affect E2 transcriptional activation. This E39A mutation also disrupts replication activity of HPV-16 E2 in HPV-16 in vitro DNA replication. On this basis, we designed 23- and 15-amino-acid peptides derived from HPV-16 E2 sequences flanking the E39 residue and tested the ability of these peptides to inhibit interaction between HPV-16 E1 and E2 in vitro. The inhibitory activity of these peptides was specific, since analogous peptides in which alanine was substituted for the E39 residue did not inhibit interaction. The 15-amino-acid peptide E2N-WP15 was the smallest peptide tested that effectively inhibited HPV-16 E1-E2 interaction. This peptide also inhibited in vitro replication of HPV-16 DNA. The efficacy of E2N-WP15 was not exclusive to HPV-16: this peptide also inhibited interaction of HPV-11 E1 with the E2 proteins of both HPV-11 and HPV-16 and inhibited in vitro replication with these same combinations of E1 and E2 proteins. These results provide further evidence that E1-E2 interaction is required for papillomavirus DNA replication and constitute the first demonstration that inhibition of this interaction is sufficient to prevent HPV DNA replication in vitro.
[A clinical study of hyperhomocysteinemia in rheumatological diseases].

OBJECTIVE To analysis plasma homocysteine (Hcy) level and some relative factors in some rheumatological diseases. METHODS 54 cases with systemic lupus erythematosus (SLE), 48 cases with rheumatoid arthritis (RA), 60 cases with ankylosing spondylitis (AS), 30 cases with undifferentiated spondyloarthropathy (uSpA) and 62 controls were recruited to participate the study. Plasma Hcy, vitamin B(12), folate and the MTHFR gene C677T polymorphism were measured in all patients and controls. RESULTS (1) Plasma Hcy levels were higher significantly in all disease groups than in the controls, the mean plasma Hcy level was (19.04 +/- 6.86) micromol/L for SLE, (19.07 +/- 7.43) micromol/L for RA, (16.47 +/- 6.50) micromol/L for AS, (16.59 +/- 6.72) micromol/L for uSpA and (12.24 +/- 3.58) micromol/L for controls (P < 0.01). (2) Significant inverse correlation was found between plasma Hcy level and vitamin B(12), folate (r = -0.701, -0.443, respectively; P < 0.01). (3) The MTHFR gene mutation make Hcy level dramatically rise, CC genotype (13.41 +/- 5.78) micromol/L, CT genotype (16.81 +/- 4.22) micromol/L, TT genotype (20.88 +/- 6.60) micromol/L (P < 0.05). TT genotype is susceptible for hyperhomocysteinemia and SLE (OR = 84.46, 7.56 respectively; P < 0.05). CONCLUSIONS (1) Hyperhomocysteinemia is found in most SLE, RA, AS and uSpA patients. (2) There are lots of factors associated with Hcy concentration, such as folate, vitamin B12 and MTHFR gene mutation. (3) TT genotype of MTHFR is susceptible for hyperhomocysteinemia and SLE.
Towards Physical Understanding of Molecular Recognition in the Cell: Recent Evolution of Molecular Dynamics Techniques and Free Energy Theories

In cells, molecules do not arbitrarily interact with others; interact only with molecules of a particular type. This molecular recognition is a very important molecular function as one of the molecular bases on which the cells sustain their lives. Recently, it has been found that molecular recognition, which occurs not only between protein and protein but also between RNA and protein, plays important roles in the cell. Understanding of the molecular recognition at the atomic level is one of the challenging problems in the field of molecular biology and biochemistry. In this review, we address the theoretical and practical aspects of molecular dynamics simulation, which has become an important tool for studying the molecular recognition. From the theoretical viewpoint, many free energy calculation methods based on statistical mechanics have been developed. As for the practical aspects, it is important that the evolution of the computing technique not only enabled long-time simulations, but also enhanced prediction accuracy of simulations with developing new reliable force fields. By the recent development of theory and technology, the challenging tasks such as analysis and prediction of conformational distribution, structural change, and free energy of protein and/or nucleic acid systems are becoming possible.
Cost‐Effectiveness of Physics Journals

The rapid increase in the prices of physics journals has forced many physics libraries, in the face of static budgets, to cancel some of their subscriptions. Decisions on cancellations are usually based on the research interests of the users of the library, but the decision‐making process can be improved if a quantitative measure of the cost‐effectiveness of the journals is available. An often‐used measure is the cost per printed character; another is the frequency with which articles in the journal are cited, often referred to as the “impact. ” The ratio of these two measures is perhaps the best indicator of a journal's cost‐effectiveness.
Seasonality, body condition, and timing of reproduction in Propithecus verreauxi verreauxi in the Kirindy Forest

Mammals that live in seasonal environments may adjust their reproductive cycles to cope with fluctuations in food availability. Because lemurs in Madagascar experience highly seasonal variation in food availability, we examined the effects of fluctuating food availability on body condition and reproduction in one of the larger living species, Verreaux's sifaka (Propithecus verreauxi verreauxi), in the Kirindy Forest of western Madagascar. Seven years of demographic data were combined with an intensive study of 25 individuals over the course of 18 months. In contrast to other populations of Verreaux's sifaka, females were found to have greater body mass than males. Both male and female sifaka exhibited significant losses of body mass and fat during the dry season. Females were more likely to give birth and successfully wean an infant when they had higher body mass during the mating season. They mated during the periods of high and declining food availability, gave birth during the lean season, and then timed mid/late lactation with the period of increasing food availability. Thus, we conclude that sifaka follow the “classic” reproductive strategy (sensu van Schaik and van Noordwijk [Journal of Zoology (London) 206:533–549, 1985]). Am. J. Primatol. 63:347–364, 2005. © 2005 Wiley‐Liss, Inc.
Frequency of Isolation of Staphylococcus lugdunensisamong Staphylococcal Isolates Causing Endocarditis: a 20-Year Experience

ABSTRACT Eighty-nine staphylococcal isolates recovered from patients with bacterial endocarditis at the Mayo Clinic from 1980 to 1999 were studied to determine the prevalence of Staphylococcus lugdunensis among clinical isolates of staphylococci causing endocarditis. Four isolates, all from patients with native mitral valve endocarditis, were identified as S. lugdunensis.