Miracle-dz/UniFAR-FTUs huggingface dataset:
LAPAROSCOPIC VASECTOMY IN AFRICAN SAVANNAH ELEPHANT (LOXODONTA AFRICANA); SURGICAL TECHNIQUE AND RESULTS

Abstract: Several small, enclosed reserves in southern Africa are experiencing significant elephant population growth, which has resulted in associated environmental damage and changes in biodiversity. Although several techniques exist to control elephant populations, e.g., culling, relocation, and immunocontraception, the technique of laparoscopic vasectomy of free-ranging bull elephants was investigated. Bilateral vasectomies were performed in 45 elephants. Of these elephants, one died within 24 hr of recovery and two had complications during surgery but recovered uneventfully. Histologic examination confirmed the resected tissue as ductus deferens in all the bulls. Most animals recovered uneventfully and showed no abnormal behavior after surgery. Complications recorded included incisional dehiscence, 1 full-thickness and 2 partial-thickness lacerations of the large intestine, and initial sling-associated complications, for example, deep radial nerve paresis. One bull was found dead 6 weeks after surgery without showing any prior abnormal signs. Vasectomy in free-ranging African bull elephants may be effectively performed in their normal environment. The surgical procedure can be used as a realistic population management tool in free-ranging elephants without major anesthetic, surgical, or postoperative complications.
Poly(ADP-Ribose) Polymerase 1 Modulates the Lethality of CHK1 Inhibitors in Carcinoma Cells

Prior studies have demonstrated that inhibition of CHK1 can promote the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and phosphorylation of histone H2AX and that inhibition of poly(ADP-ribose) polymerase 1 (PARP1) can affect growth factor-induced ERK1/2 activation. The present studies were initiated to determine whether CHK1 inhibitors interacted with PARP1 inhibition to facilitate apoptosis. Transient expression of dominant-negative CHK1 raised basal ERK1/2 activity and prevented CHK1 inhibitors from activating ERK1/2. CHK1 inhibitors modestly increased the levels of PARP1 ADP ribosylation and molecular or small-molecule inhibition of PARP1 blocked CHK1 inhibitor-stimulated histone H2AX phosphorylation and activation of ERK1/2. Stimulated histone H2AX phosphorylation was ataxia telangiectasia-mutated protein-dependent. Multiple CHK1 inhibitors interacted in a greater than additive fashion with multiple PARP1 inhibitors to cause transformed cell-killing in short-term viability assays and synergistically killed tumor cells in colony-formation assays. Overexpression of BCL-xL or loss of BAX/BAK function, but not the function of BID, suppressed CHK1 inhibitor + PARP1 inhibitor lethality. Inhibition of BCL-2 family protein function enhanced CHK1 inhibitor + PARP1 inhibitor lethality and restored drug-induced cell-killing in cells overexpressing BCL-xL. Thus, PARP1 plays an important role in regulating the ability of CHK1 inhibitors to activate ERK1/2 and the DNA damage response. An inability of PARP1 to modulate this response results in transformed cell death mediated through the intrinsic apoptosis pathway.
Gambling with your life: The process of breast cancer treatment decision making in Chinese women

Treatment decision making (TDM) studies have primarily focused on assessing TDM quality and predominantly presume rational analytic processes as the gold standard. In a grounded theory study of 22 Hong Kong Chinese women following breast surgery who completed an in‐depth interview exploring the process of TDM in breast cancer (BC), narrative data showed that discovery of a breast abnormality and emotional responses to BC diagnosis influence the TDM process. Lack of guidance from surgeons impaired TDM. Decisions were, for the most part, made using intuitive, pragmatic and emotionally driven criteria in the absence of complete information. The experience of TDM, which was likened to gambling, did not end once the decision was made but unfolded while waiting for surgery and the post‐operative report. In this waiting period, women were emotionally overwhelmed by fear of death and the uncertainty of the surgical outcome, and equivocated over whether they had made the ‘right’ choice. This suggests that Chinese women feel they are gambling with their lives during TDM. These women are particularly emotionally vulnerable whilst waiting for their surgery and the post‐surgical clinical pathology results. Providing emotional support is particularly important at this time when these women are overwhelmed by uncertainty. Copyright © 2004 John Wiley & Sons, Ltd.
A Novel Tumor Suppressor Function of Glycine N-Methyltransferase Is Independent of Its Catalytic Activity but Requires Nuclear Localization

Glycine N-methyltransferase (GNMT), an abundant cytosolic enzyme, catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to glycine generating S-adenosylhomocysteine and sarcosine (N-methylglycine). This reaction is regulated by 5-methyltetrahydrofolate, which inhibits the enzyme catalysis. In the present study, we observed that GNMT is strongly down regulated in human cancers and is undetectable in cancer cell lines while the transient expression of the protein in cancer cells induces apoptosis and results in the activation of ERK1/2 as an early pro-survival response. The antiproliferative effect of GNMT can be partially reversed by treatment with the pan-caspase inhibitor zVAD-fmk but not by supplementation with high folate or SAM. GNMT exerts the suppressor effect primarily in cells originated from malignant tumors: transformed cell line of non-cancer origin, HEK293, was insensitive to GNMT. Of note, high levels of GNMT, detected in regenerating liver and in NIH3T3 mouse fibroblasts, do not produce cytotoxic effects. Importantly, GNMT, a predominantly cytoplasmic protein, was translocated into nuclei upon transfection of cancer cells. The presence of GNMT in the nuclei was also observed in normal human tissues by immunohistochemical staining. We further demonstrated that the induction of apoptosis is associated with the GNMT nuclear localization but is independent of its catalytic activity or folate binding. GNMT targeted to nuclei, through the fusion with nuclear localization signal, still exerts strong antiproliferative effects while its restriction to cytoplasm, through the fusion with nuclear export signal, prevents these effects (in each case the protein was excluded from cytosol or nuclei, respectively). Overall, our study indicates that GNMT has a secondary function, as a regulator of cellular proliferation, which is independent of its catalytic role.
Retinol/Ethanol Drug Interaction during Acute Alcohol Intoxication in Mice Involves Inhibition of Retinol Metabolism to Retinoic Acid by Alcohol Dehydrogenase*

Substantial evidence indicates that one consequence of alcohol intoxication is a reduction in retinoic acid (RA) levels. Studies on the mechanism have shown that chronic ethanol consumption induces P450 enzymes that increase RA degradation, thus accounting for much but not all of the observed decrease in RA. A reduction in RA synthesis may also be involved as ethanol competitively inhibits retinol oxidation catalyzed by alcohol dehydrogenase (ADH)in vitro. This may be important during acute ethanol intoxication and may contribute to adverse retinol/ethanol drug interactions. Here we have examined mice for the effect of either acute ethanol intoxication or Adh1 gene disruption on RA synthesis and degradation. RA produced following a dose of retinol (50 mg/kg) was reduced 87% by pretreatment with an intoxicating dose of ethanol (3.5 g/kg). RA produced inAdh1-null mutant mice following a 50-mg/kg dose of retinol was reduced 82% relative to wild-type mice, thus similar to wild-type mice pretreated with ethanol. Reduced RA production was associated with increased retinol levels in both ethanol-treated wild-type mice andAdh1-null mutant mice, indicating reduced clearance of the retinol dose. RA degradation following a dose of RA (10 mg/kg) was increased only 42% by ethanol pretreatment (3.5 g/kg) and only 26% inAdh1-null mutant mice relative to wild-type mice. These findings demonstrate that the reduced RA levels observed during acute retinol/ethanol drug interaction are due primarily to a decrease in ADH-catalyzed RA synthesis and secondarily to an increase in RA degradation.
Early results of surgery in patients with nonfunctioning pituitary adenoma and analysis of the risk of tumor recurrence.

OBJECT Nonfunctioning pituitary adenomas (NFPAs) are benign tumors of the pituitary gland that typically cause visual and/or hormonal dysfunction. Surgery is the treatment of choice, but patients remain at risk for tumor recurrence for several years afterwards. The authors evaluate the early results of surgery and the long-term risk of tumor recurrence in patients with NFPAs. METHODS Between 1990 and 2005, 491 previously untreated patients with NFPA underwent surgery at the Università Vita-Salute. Determinations of recurrence or growth of the residual tumor tissue during the follow-up period were based on neuroradiological criteria. RESULTS Residual tumor after surgery was detected in 173 patients (36.4%). Multivariate analysis showed that invasion of the cavernous sinus, maximum tumor diameter, and absence of tumor apoplexy were associated with an unfavorable surgical outcome. At least 2 sets of follow-up neuroimaging studies were obtained in 436 patients (median follow-up 53 months). Tumors recurred in 83 patients (19.0%). When tumor removal appeared complete, younger age at surgery was associated with a risk of tumor recurrence. In patients with incomplete tumor removal, adjunctive postoperative radiotherapy had a marked protective effect against growth of residual tumor. CONCLUSIONS Complete surgical removal of NFPAs can be safely achieved in > 50% of cases. Visual symptoms and, less frequently, pituitary function may improve after surgery. However, tumor can recur in patients after apparently complete surgical removal. In patients with incomplete tumor removal, radiation therapy is the most effective adjuvant therapy for preventing residual tumor growth.
Building extraction and change detection in multitemporal remotely sensed images with multiple birth and death dynamics

In this paper we introduce a new probabilistic method which integrates building extraction with change detection in remotely sensed image pairs. A global optimization process attempts to find the optimal configuration of buildings, considering the observed data, prior knowledge, and interactions between the neighboring building parts. The accuracy is ensured by a Bayesian object model verification, meanwhile the computational cost is significantly decreased by a non-uniform stochastic object birth process, which proposes relevant objects with higher probability based on low-level image features.
Lottery and stride scheduling: flexible proportional-share resource management

This thesis presents flexible abstractions for specifying resource management policies, together with efficient mechanisms for implementing those abstractions. Several novel scheduling techniques are introduced, including both randomized and deterministic algorithms that provide proportional-share control over resource consumption rates. Such control is beyond the capabilities of conventional schedulers, and is desirable across a broad spectrum of systems that service clients of varying importance. Proportional-share scheduling is examined for several diverse resources, including processor time, memory, access to locks, and disk bandwidth. Resource rights are encapsulated by abstract, first-class objects called tickets. An active client consumes resources at a rate proportional to the number of tickets that it holds. Tickets can be issued in different amounts and may be transferred between clients. A modular currency abstraction is also introduced to flexibly name, share, and protect sets of tickets. Currencies can be used to isolate or group sets of clients, enabling the modular composition of arbitrary resource management policies. Two different underlying mechanisms are introduced to support these abstractions. Lottery scheduling is a novel randomized resource allocation mechanism. An allocation is performed by holding a lottery, and the resource is granted to the client with the winning ticket. Stride scheduling is a deterministic resource allocation mechanism that computes a representation of the time interval, or stride, that each client must wait between successive allocations. Stride scheduling cross-applies and generalizes elements of rate-based flow control algorithms designed for networks to dynamically schedule other resources such as processor time. A novel hierarchical stride algorithm is also introduced that achieves better throughput accuracy than prior schemes, and can reduce response-time variability for some workloads. The proposed techniques are compared and evaluated using a variety of quantitative experiments. Simulation results and prototype implementations for operating system kernels demonstrate flexible control over a wide range of resources and applications.
Family-Centered Rounds

Objective. To study the impact of family-centered rounds for general pediatrics inpatients. Methods. An observation tool and participant surveys was developed. The authors analyzed rounding time and rounds participants. Associations between family presence and participants’ satisfaction were analyzed. Results. Data were collected on 295 patients and from 257 staff members. Average rounding time was reduced with increased family and nurse presence (8.7 minutes with both, 12.7 minutes without family, P = .0001). Families reported high satisfaction regardless of participants. Families present on rounds reported increased knowledge of team members’ roles (54% vs 35%, P = .04). Attending physicians more often reported ease in managing rounds with families present. Senior residents perceived decreased autonomy with high family participation (11%) versus low family participation (70%; P = .02). Improved nurse satisfaction was associated with increased family and nurse participation. Conclusion. Family participation may shorten inpatient rounds. Families and staff were satisfied with family-centered rounds, though senior resident autonomy requires attention.
Telaprevir for previously treated chronic HCV infection.

BACKGROUND Patients with genotype 1 hepatitis C virus (HCV) who do not have a sustained response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment. METHODS We randomly assigned patients with HCV genotype 1 who had not had a sustained virologic response after peginterferon alfa-ribavirin therapy to one of four treatment groups: 115 patients to the T12PR24 group, receiving telaprevir (1125-mg loading dose, then 750 mg every 8 hours) for 12 weeks and peginterferon alfa-2a (180 microg per week) and ribavirin (1000 or 1200 mg per day, according to body weight) for 24 weeks; 113 patients to the T24PR48 group, receiving telaprevir for 24 weeks and peginterferon alfa-2a and ribavirin for 48 weeks (at the same doses as in the T12PR24 group); 111 patients to the T24P24 group, receiving telaprevir and peginterferon alfa-2a for 24 weeks (at the same doses as in the T12PR24 group); and 114 patients to the PR48 (or control) group, receiving peginterferon alfa-2a and ribavirin for 48 weeks (at the same doses as in the T12PR24 group). The primary end point was sustained virologic response (undetectable HCV RNA levels 24 weeks after the last dose of study drugs). RESULTS The rates of sustained virologic response in the three telaprevir groups--51% in the T12PR24 group, 53% in the T24PR48 group, and 24% in the T24P24 group--were significantly higher than the rate in the control group (14%; P<0.001, P<0.001, and P=0.02, respectively). Response rates were higher among patients who had previously had relapses than among nonresponders. One of the most common adverse events in the telaprevir groups was rash (overall, occurring in 51% of patients, with severe rash in 5%). Discontinuation of study drugs because of adverse events was more frequent in the telaprevir groups than in the control group (15% vs. 4%). CONCLUSIONS In HCV-infected patients in whom initial peginterferon alfa and ribavirin treatment failed, retreatment with telaprevir in combination with peginterferon alfa-2a and ribavirin was more effective than retreatment with peginterferon alfa-2a and ribavirin alone. (ClinicalTrials.gov number, NCT00420784.)
Synthesis of output feedback controllers for a class of nonlinear parameter-varying discrete-time systems subject to actuators limitations

We present a methodology for computing output feedback control laws for a class of nonlinear systems subject to input saturations. This class of systems consists of a L'ure type nonlinear system with some time-varying parameters which are assumed to be real-time available. Based on some tools from the absolute stability theory, on a modified sector condition to take into account input saturation effects, and on the concept of contractive sets applied to a level set obtained from a particular parameter dependent Lyapunov function, an LMI framework is proposed to design dynamic output feedback compensators. Two local stabilization strategies are considered: (i) with saturation avoidance, and (ii) with saturating actuators. In both cases, convex optimization problems are proposed to compute the controllers matrices aiming at the maximization of the basin of attraction.
A Study into the Correlation between Narcissism and Facebook Communication Patterns

Despite the usage of Facebook data by researchers for various types of personality analyses there has been no investigation into the "comment-liking" feature of Facebook. Two studies are performed which analyse the link between narcissism and users' interactions on Facebook. Firstly, comment-liking activity is measured and this is compared to narcissism scores. Secondly, measures of promotional self-worth derived from the content analysis of users' posts are also compared to narcissism scores. The results of the comparisons show that narcissistic behaviour is observable in the tendency of Facebook users to selectively respond to their Facebook friends' comments while at the same time indulging in conversations lacking diversity and for the most part focusing on self-promotion.
Clinical and Subclinical Macrovascular Disease as Predictors of Cognitive Decline in Older Patients With Type 2 Diabetes

OBJECTIVE Macrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes. We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes. RESEARCH DESIGN AND METHODS Eight hundred thirty-one men and women (aged 60–75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS). At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP). Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g). Adjustment of follow-up g for baseline g assessed 4-year cognitive change. Adjustment for vocabulary (estimated premorbid ability) was used to estimate lifetime cognitive change. RESULTS Measures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. The association of stroke with increased estimated lifetime cognitive decline (standardized β, −0.12) and of subclinical markers with actual 4-year decline (standardized β, −0.12, 0.12, and −0.15 for NT-proBNP, ABI, and cIMT, respectively) reached the Bonferroni-adjusted level of statistical significance (P < 0.006). Results altered only slightly on adjustment for vascular risk factors. CONCLUSIONS Stroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes. Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted.
Protein supplementation may enhance the spontaneous recovery of neurological alterations in patients with ischaemic stroke

Objective: To determine whether protein supplementation could enhance neurological recovery in subacute patients with ischaemic stroke. Design: Alimentation-independent patients with ischaemic stroke were randomly allocated to either 21 days of protein supplementation (protein-supplemented group; n=20) or to a spontaneous diet only (control group; n=21) in order to investigate the recovery of neurological changes (measured using the National Institute of Health (NIH) Stroke Scale). Setting: Tertiary care rehabilitation in Italy. Participants: Forty-two patients (27 male and 15 female; 66.4 ± 11 years) 16 ±2 days after the acute event. Intervention: Supplementation with a hyperproteic nutritional formula (10% protein). Main outcome measures: NIH Stroke Scale and protein intake. Results: At admission to rehabilitation, both groups of patients were homogeneous for demographic, clinical and functional characteristics. After 21 days from the start of the protocol, the NIH Stroke Scale was found to be enhanced in the group with supplemental proteins (-4.4 ± 1.5 score versus -3 ± 1.4 of control group; P<0.01). When expressed as difference (▵) between baseline and 21 days, the NIH Stroke Scale correlated negatively with change in protein intake (g/day) (r=-0.50, P= 0.001) and positively with change in carbohydrate/protein ratio (r=+0.40, P=0.01) Conclusions: Protein supplementation may enhance neurological recovery in subacute patients with ischaemic stroke.
Topography of the Euryarchaeal Transcription Initiation Complex*

Transcription in the Archaea is carried out by RNA polymerases and transcription factors that are highly homologous to their eukaryotic counterparts, but little is known about the structural organization of the archaeal transcription complex. To address this, transcription initiation complexes have been formed with Pyrococcus furiosus transcription factors (TBP and TFB1), RNA polymerase, and a linear DNA fragment containing a strong promoter. The arrangement of proteins from base pair -35 to +20 (relative to the transcriptional start site) has been analyzed by photochemical protein-DNA cross-linking. TBP cross-links to the TATA box and TFB1 cross-links both upstream and downstream of the TATA box, as expected, but the sites of most prominent TFB1 cross-linking are located well downstream of the TATA box, reaching as far as the start site of transcription, suggesting a role for TFB1 in initiation of transcription that extends beyond polymerase recruitment. These cross-links indicate the transcription factor orientation in the initiation complex. The pattern of cross-linking of four RNA polymerase subunits (B, A′, A″, and H) to the promoter suggests a path for promoter DNA relative to the RNA polymerase surface in this archaeal transcription initiation complex. In addition, an unidentified protein approximately the size of TBP cross-links to the non-transcribed DNA strand near the upstream edge of the transcription bubble. Cross-linking is specific to the polymerase-containing initiation complex and requires the gdh promoter TATA box. The location of this protein suggests that it, like TFB1, could also have a role in transcription initiation following RNA polymerase recruitment.