Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Compressive Force Applied to the Intervertebral Disc in Vivo: A Study of Proteoglycans and Collagen

Study Design. Coil springs were stretched and attached to produce a compressive force across the lumbar intervertebral discs of dogs for up to 27 weeks. Objective. To test the hypothesis that a high compressive force applied over a period of time affects the production of proteoglycans and collagen by the intervertebral disc cells. Summary of Background Data. It is a commonly held belief that high forces applied to the intervertebral disc, and to joints in general, play a role in causing degeneration. Methods. Pairs of stainless steel coil springs were stretched and attached to produce a compressive force across the lumbar intervertebral discs (L1‐L2 and L3‐L4) of 16 dogs. Dogs were killed between 13 and 27 weeks after the springs were attached. The discs (L1‐L2 and L3‐L4) were excised and assessed using immunohistochemical analyses and enzyme‐linked immunosorbent assay; T13‐L1 and L4‐L5 were used as controls. Results. The main result relates to a group effect in the six dogs, assessed using enzyme‐linked immunosorbent assay, that were generally at the highest values of force for the greatest number of weeks. For the nucleus, but not the anulus, Spearman rank correlations revealed a strong correlation between increases in force and force‐weeks (force multiplied by number of weeks) and increases in collagen type I accompanied by decreases in proteoglycans, chondroitin sulfate, and collagen type II for both experimental discs (L1‐L2 and L3‐L4), as compared with corresponding values in the controls (T13‐L1 and L4‐L5). In other words, as either the force or the force‐weeks increased, the effect on the nucleus became greater. Conclusion. A high compressive force applied to the disc over a period of time initiates changes in proteoglycans and collagen.
Interactions of temperature and steroids on larval growth, development, and metamorphosis in a toad (Bufo boreas).

The effects of temperature and steroids [testosterone (T), estradiol (E2), and corticosterone (B)] on premetamorphic growth and development were investigated in the toad (Bufo boreas). The effects of steroids were both temperature and age dependent. In the first experiment, steroids (1.1-1.4 microM) were administered by dissolving them in the water beginning 1 day after hatching at 22 degrees C or 27 degrees C. At 22 degrees C, B inhibited growth (P < 0.001) but had no significant effect on development. Forelegs never emerged in B-treated animals and all died before complete tail resorption. Discontinuation of B treatment allowed normal growth and metamorphosis, but the resulting post-metamorphic animals were significantly shorter (snout-vent length, P < 0.001) than after other treatments. At 22 degrees C, T and E2 had no effect on larval growth and development or size at metamorphosis (P > 0.05), but T induced early foreleg emergence (FLE) (P < 0.005). At 27 degrees C, B was fatal after 2 weeks of treatment, and T and E2 inhibited growth (P < 0.001) and development (P < 0.001), but did not affect time to FLE. In a second experiment at 27 degrees C, treatment with 1.1 microM B starting 15 days after hatching induced early metamorphic events (P < 0.001), such as tail resorption and emergence of the left foreleg (but not the right), but jaw and head restructuring failed to occur. All B-treated animals died before complete tail resorption. In a third experiment, 0.275 and 1.11 microM B, starting at day 43 (stage 43), induced early FLE (P < 0.05) and decreased snout-vent length at tail resorption (P < 0.005) without a dose effect. A higher dose of B (4.44 microM) decreased snout-vent length at tail resorption and time to FLE (P < 0.05) but did not affect body weight at metamorphosis (P > 0.05). Animals in this experiment survived to complete tail resorption and transformed normally. The actions of B in these experiments closely resemble those observed with administration of thyroid hormones, suggesting that steroids may interact with endogenous thyroid hormones.
Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma.

BACKGROUND Lenalidomide is a structural analogue of thalidomide with similar but more potent biologic activity. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide plus dexamethasone in the treatment of relapsed or refractory multiple myeloma. METHODS Of 351 patients who had received at least one previous antimyeloma therapy, 176 were randomly assigned to receive 25 mg of oral lenalidomide and 175 to receive placebo on days 1 to 21 of a 28-day cycle. In addition, all patients received 40 mg of oral dexamethasone on days 1 to 4, 9 to 12, and 17 to 20 for the first four cycles and subsequently, after the fourth cycle, only on days 1 to 4. Patients continued in the study until the occurrence of disease progression or unacceptable toxic effects. The primary end point was time to progression. RESULTS The time to progression was significantly longer in the patients who received lenalidomide plus dexamethasone (lenalidomide group) than in those who received placebo plus dexamethasone (placebo group) (median, 11.3 months vs. 4.7 months; P<0.001). A complete or partial response occurred in 106 patients in the lenalidomide group (60.2%) and in 42 patients in the placebo group (24.0%, P<0.001), with a complete response in 15.9% and 3.4% of patients, respectively (P<0.001). Overall survival was significantly improved in the lenalidomide group (hazard ratio for death, 0.66; P=0.03). Grade 3 or 4 adverse events that occurred in more than 10% of patients in the lenalidomide group were neutropenia (29.5%, vs. 2.3% in the placebo group), thrombocytopenia (11.4% vs. 5.7%), and venous thromboembolism (11.4% vs. 4.6%). CONCLUSIONS Lenalidomide plus dexamethasone is more effective than high-dose dexamethasone alone in relapsed or refractory multiple myeloma. (ClinicalTrials.gov number, NCT00424047 [ClinicalTrials.gov].).
Ethanol acutely impairs glycogen repletion in skeletal muscle following high intensity short duration exercise in the rat

Ethanol is recognized to affect adversely carbohydrate metabolism in skeletal muscle. This paper seeks to establish whether ethanol acutely impairs glycogen repletion during recovery from high intensity short duration exercise in the rat. High intensity exercise caused the massive mobilization of glycogen stores in muscles rich in type IIa and IIb fibres and marked increases in plasma and muscle lactate levels. During the 30‐minute recovery period, there was substantial glycogen repletion in these muscles in both the ethanol‐treated and control rats. Ethanol, however, was associated with reduced glycogen resynthesis in both the tibialis anterior (by 22%) and red gastrocnemius (by 31%) muscles but not in the white gastrocnemius muscle. This reduction in post‐exercise glycogen deposition was accompanied by decreased lactate disposal and elevated plasma glucose levels. These effects of ethanol on glycogen repletion may involve interactions with hepatic gluconeogenesis, glucose uptake and utilization in muscle, muscle glycogen synthesis and lactate glyconeogenesis. The ethanol‐mediated impairment in post‐exercise glycogen repletion may have important implications for the pathogenesis of chronic alcoholic skeletal myopathy.
Clinical features of bipolar depression versus major depressive disorder in large multicenter trials.

OBJECTIVE Failure to recognize bipolar disorder in patients who experience a major depressive episode may lead to inappropriate treatment and poorer outcomes. Clinical features that could distinguish bipolar from unipolar depression would facilitate more appropriate treatment selection. METHOD The authors used data from nonpsychotic outpatients participating in three large multicenter clinical trials conducted in the United States for the treatment of major depressive episodes to compare 477 subjects with a diagnosis of bipolar disorder and 1,074 with major depressive disorder. RESULTS Bipolar depression was associated with family history of bipolar disorder, an earlier age at onset, a greater previous number of depressive episodes, and eight individual symptom items on the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale. Fears were more common in patients with bipolar disorder, whereas sadness; insomnia; intellectual (cognitive), somatic (muscular), respiratory, genitourinary complaints; and depressed behavior were more common in patients with unipolar depression. A logistic regression model correctly classified 86.9% of the subjects. CONCLUSIONS Bipolar depression and major depressive disorder exhibit subtle differences in presentation, which may help guide the initial diagnosis.
Diurnal variations in scrotal temperature of normal men and patients with varicocele before and after treatment.

Scrotal temperature was monitored using a portable data recorder for periods of 24 h in six normal volunteers and 48 infertile patients with unilateral varicocele while subjects pursued their regular daily activities. Temperatures during sleep (TS) were generally higher than daytime values (TD), probably as a consequence of thermal insulation in bed. These diurnal variations were found to be less pronounced in the infertile patients than in volunteers (TS - TD = 0.29 degrees C +/- 0.06 degrees C vs 0.88 degrees C +/- 0.12 degrees C; P < 0.01). Moreover, scrotal temperatures at night of patients and volunteers were indistinguishable statistically, but were different during daytime hours. After successful ligation or embolization of the spermatic-vein in 16 patients, no change in scrotal temperature was observed. Although sperm counts were higher after treatment, this difference was not significant (67.4 +/- 17.2 x 10(6) vs 105.8 +/- 25.5 x 10(6); P > 0.05). The data support the view that varicocele-related damage to the testis results from a lack of adequate cooling, and that treatment does not normalize the temperature pattern.
Effects of cyclothiazide on GluR 1 AMPA receptors

*Istituto Pasteur–Fondazione Cenci Bolognetti, Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza BEMM, Universita’ di Roma ‘‘La Sapienza,’’ Piazzale Aldo Moro 5, I00185 Rome, Italy; ‡Laboratory of Cellular and Molecular Neurobiology, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550; and §Neuromed Instituto di Ricovero e Cura a Carattere Scientifico, Via Atinese 18, I86077 Isernia, Italy
SMART designs in cancer research: Past, present, and future

Background Cancer affects millions of people worldwide each year. Patients require sequences of treatment based on their response to previous treatments to combat cancer and fight metastases. Physicians provide treatment based on clinical characteristics, changing over time. Guidelines for these individualized sequences of treatments are known as dynamic treatment regimens (DTRs) where the initial treatment and subsequent modifications depend on the response to previous treatments, disease progression, and other patient characteristics or behaviors. To provide evidence-based DTRs, the Sequential Multiple Assignment Randomized Trial (SMART) has emerged over the past few decades. Purpose To examine and learn from past SMARTs investigating cancer treatment options, to discuss potential limitations preventing the widespread use of SMARTs in cancer research, and to describe courses of action to increase the implementation of SMARTs and collaboration between statisticians and clinicians. Conclusion There have been SMARTs investigating treatment questions in areas of cancer, but the novelty and perceived complexity has limited its use. By building bridges between statisticians and clinicians, clarifying research objectives, and furthering methods work, there should be an increase in SMARTs addressing relevant cancer treatment questions. Within any area of cancer, SMARTs develop DTRs that can guide treatment decisions over the disease history and improve patient outcomes.
An In Vitro RNA Synthesis Assay for Rabies Virus Defines Ribonucleoprotein Interactions Critical for Polymerase Activity

ABSTRACT We report an in vitro RNA synthesis assay for the RNA-dependent RNA polymerase (RdRP) of rabies virus (RABV). We expressed RABV large polymerase protein (L) in insect cells from a recombinant baculovirus vector and the phosphoprotein cofactor (P) in Escherichia coli and purified the resulting proteins by affinity and size exclusion chromatography. Using chemically synthesized short RNA corresponding to the first 19 nucleotides (nt) of the rabies virus genome, we demonstrate that L alone initiates synthesis on naked RNA and that P serves to enhance the initiation and processivity of the RdRP. The L-P complex lacks full processivity, which we interpret to reflect the lack of the viral nucleocapsid protein (N) on the template. Using this assay, we define the requirements in P for stimulation of RdRP activity as residues 11 to 50 of P and formally demonstrate that ribavirin triphosphate (RTP) inhibits the RdRP. By comparing the properties of RABV RdRP with those of the related rhabdovirus, vesicular stomatitis virus (VSV), we demonstrate that both polymerases can copy the heterologous promoter sequence. The requirements for engagement of the N-RNA template of VSV by its polymerase are provided by the C-terminal domain (CTD) of P. A chimeric RABV P protein in which the oligomerization domain (OD) and the CTD were replaced by those of VSV P stimulated RABV RdRP activity on naked RNA but was insufficient to permit initiation on the VSV N-RNA template. This result implies that interactions between L and the template N are also required for initiation of RNA synthesis, extending our knowledge of ribonucleoprotein interactions that are critical for gene expression. IMPORTANCE The current understanding of the structural and functional significance of the components of the rabies virus replication machinery is incomplete. Although structures are available for the nucleocapsid protein in complex with RNA, and also for portions of P, information on both the structure and function of the L protein is lacking. This study reports the expression and purification of the full-length L protein of RABV and the characterization of its RdRP activity in vitro. The study provides a new assay that has utility for screening inhibitors and understanding their mechanisms of action, as well as defining new interactions that are required for RdRP activity.
Social Media for Promoting Grassroots Political Movements and Social Change

In light of many recent Internet-led revolutions, the Internet and its tools of social media have been heralded as instrumental in facilitating the uprisings. This chapter provides a close examination of the social media role in grass roots political and social change movements. The chapter discusses the ways activists have used social media tools for organizing and generating awareness of political mobilization and the characteristics of social networking that can be harnessed in a particular cultural and historical context to achieve collective political actions. The chapter also discusses long-established theories of communication to explain how social networking tools became appealing to the activists in these Internet-led movements. The chapter will look at various Internet-led political movements around the globe to demonstrate the enormous potential of social networking tools to facilitate and expedite political mobilization.
Correction of Caporin and Paruolo (2015)

In a recent working paper, Bacchiocchi and Lucchetti (2015) describe counterexamples to the applicability of the structure condition of Lucchetti (2006); this conditionwas used in Eq. (21) in Theorem 5 in our paper, Caporin andParuolo (2015). Hence, Eq. (21) in Theorem5 inCaporin andParuolo (2015) is not a necessary and su cient condition for identi cation of speci cation (18) under restrictions (19) there. To check identi cation in Eq. (18) under restrictions (19) in Caporin and Paruolo (2015), one can still use the rank condition for identi cation of the A-B model given on page 57 in Amisano and Giannini (1997), given that this speci cation is a special case of the A-B model, as shown in Caporin and Paruolo (2015) on page 591. The rank condition in Amisano and Giannini (1997) involves parameter values. As shown in Lucchetti (2006), this rank condition can be checked numerically for some value of the parameters, generated drawing from any given probability density function; if this condition holds for this value of the parameters, then it holds for all values of the parameters except for a set of Lebesgue measure 0.
Collaborative system to investigate mental models: The information architecture automatic tool (IAAT)

A software product that has been developed according to user centered design principles takes into account knowledge of the future user and guarantees a user friendly human-computer interaction through interfaces that enable to effectively and efficiently accomplish tasks. Therefore, the user's mental and conceptual model should match to achieve interfaces consistent with the user's system expectations, and consequently with the representation of how a system should work. To investigate mental models and extend the knowledge and understanding of human interaction with technical systems, we describe a collaborative system that relies on the user configuration of the information architecture of an In-Vehicle Information System (IVIS) that reflect the users' mental models. Each user generates the content of predefined information structures that compete in efficiency with structures from other users, thereby expanding the number of “lead users” and the test subjects' sample.
Disclosure of Relevant Acts or Facts: A Study of Brazilian Companies Issuing American Deposit Receipts – Adrs at American Stock Exchanges

The aim of this article identifies, evaluates and describes relevant facts and acts' occurrences disclosed by Brazilian companies issuing ADRs - American Depositary Receipts. The analysis was made based on 1,125 information extracted from the Comissao de Valores Imobiliarios – CVM’s website, the regulatory commission organization empowered to regulate, standardize and supervise the activities of trade agents of public securities in Brazil. The research used information that was carried out from January 2006 to April 2012. It was evidenced that companies whose trade their depositary receipts in markets with high standards of corporate governance practices do not disclose a larger amount of information than the lower one governance practices. This research expands the knowledge about the content, frequency and timing of disclosure of relevant information by Brazilian organizations in international equity markets.
Evolution of the transcription complex during sporulation of Bacillus subtilis

Ribonucleic acid polymerase activity in partially purified extract of cells of Bacillus subtilis harvested at different times (t-1, to, t1, and t2) was studied by zone centrifugation. During the course of sporulation, vegetative sigma-factor activity decreased and the transcription complex lost some of its affinity for active sigma factor. The complex underwent a two-stage change in sedimentation value, from 14.5S in vegetative growth phase to a 13S species very early in sporulation to a 16S species at later times. Two SpoO mutants have been studied by zone centrifugation. One strain, a rifampin-resistant (RfmR) mutant, failed to show any modification of the transcription complex, whereas the other, a Rfms strain, underwent a partial evolution of the transcription complex after to.
The experimental study of miRNA in pituitary adenomas.

AIM We investigated the differential miRNA expression in pituitary adenomas (both non-functioning and gonadotropin-secreting) and normal pituitaries. MATERIAL AND METHODS RNA was extracted and purified from pituitary adenomas (10 non-functioning and 10 gonadotropin-secreting) and from two normal pituitary tissue samples. The samples were analyzed by miRNA microarray. Gene expression was measured using realtime RT-PCR with SYBR GREEN I. RESULTS In non-functioning pituitary adenomas, 25 miRNA genes were up-regulated (six by over 5-fold) and 15 were down-regulated (six by more than 10-fold). miR-124a was the most up-regulated gene (38.58-fold), and miR-31 the most down-regulated gene (21.5-fold). In gonadotropin-secreting pituitary adenomas, 16 miRNA genes were up-regulated (six by over 4-fold) and 13 were down-regulated (seven by more than 10-fold). miR-10b was the most up-regulated gene (48.73-fold), and miR-503 the most down-regulated gene (39.8-fold). Five genes were up-regulated in both subtypes: miR-523, miR-10b, miR-520b, miR-422a, and miR-422b. The RT-PCR results were consistent with those of the gene chips. CONCLUSION We established miRNA expression maps of non-functioning and gonadotropin-secreting pituitary adenomas. The most strongly differentially expressed genes were miR-124a and miR-31 in non-functioning pituitary adenomas, and miR-10b and miR-503 in gonadotropin-secreting pituitary adenomas.
Comparison of community and government preferences in prioritizing suitable lands for sustainable tree plantations

ABSTRACT The objective of the research was to compare the community and government preferences in prioritizing suitable lands for sustainable tree plantations in production forest areas. In selecting planting locations, a number of physical and spatial analyses have been conducted using a geographical information system. Physical criteria consist of land cover/land uses, slopes, soils, and rainfall, while spatial criteria encompass proximity of land units to the roads, villages, and industries. In determining the most suitable locations for sustainable tree plantations, the community and government stakeholders were involved in ranking the characteristics within each criterion and weighting the criterion through the point allocation method. The results showed that the community and government had different preferences in selecting locations for tree plantations. The community gave higher ranks to criterion characteristics that have large areas; conversely, the government assigned higher ranks to criterion characteristics that have small and moderate areas. Based on the community’s preferences, most prioritized land units followed the roads and were located in and around the villages, whereas the land units prioritized by the government mostly scattered all over the production forest areas. However, the two groups preferred the slopes of 8–15% for tree plantation locations. These results should supplement the Minister of Forestry Regulation No. P.23/Menhut-II/2007 stating that locations of people’s plantations should be close to industries, and the Minister of Forestry Decree No.21/Kpts-II/2001 stating that tree plantations should be established in the lands with slopes ≤25%.