Miracle-dz/UniFAR-FTUs huggingface dataset:
Bovine Immature Oocytes Acquire Developmental Competence During Meiotic Arrest In Vitro1

Abstract To test the hypothesis that oocytes require time to acquire developmental competence during meiotic arrest, we investigated the effects of butyrolactone I (BL I), a potent and specific inhibitor of cyclin-dependent kinase, on the developmental competence of bovine oocytes after in vitro fertilization (IVF) following release from meiotic arrest. In the present study, 4 culture conditions were used: addition of BSA or fetal bovine serum (FBS) under 2 oxygen tensions (5% vs. 20%) during meiotic arrest with 100-μM BL I. The developmental competence to the blastocyst stage was higher (P < 0.01) in oocytes that were arrested in FBS-supplemented medium under 5% O2 (37%) than in oocytes that were arrested under other conditions (5%–24%) or that matured directly following follicle aspiration (23%). The time course of nuclear maturation of BL I-treated oocytes was also examined. The results demonstrated that oocytes treated with BL I start germinal vesicle (GV) breakdown and reach the metaphase II stage 5.5–6.0 h earlier than nonarrested oocytes. The developmental rates to the blastocyst stage of BL I-treated oocytes matured for 15.5 and 21 h were higher (P < 0.05) than those of nontreated oocytes matured for 21 and 26.5 h, respectively. These results demonstrate that bovine immature oocytes, which were arrested at the GV stage with BL I in FBS-supplemented medium under low oxygen tension, acquire higher developmental competence during meiotic arrest.
13.1 A 940MHz-bandwidth 28.8µs-period 8.9GHz chirp frequency synthesizer PLL in 65nm CMOS for X-band FMCW radar applications

To obtain a 20cm-resolution image within a 15m distance using an X-band FMCW radar, an agile chirp frequency synthesizer phase-locked loop (FSPLL) with a wide chirp bandwidth (BW) greater than 750MHz and a short chirp period (Tm) less than 100μs is necessary. Challenges arise as one tries to realize a triangular chirp profile in Fig. 13.1. 1 with a fast chirp slope (=BW/Tm) and precise linearity. In particular, many FMCW FSPLLs exhibit increased frequency errors around the turn-around points (TAPs), degrading the effective resolution achievable. For instance, for FSPLLs modulating either the reference or feedback clock frequency [1-3], the finite loop bandwidth of the PLL limits the maximum chirp slope as well as the linearity of the chirp profile. Moreover, many of these PLLs use a multi-modulus frequency divider (FD) and delta-sigma modulation (DSM) [2], which put further constraints on the maximum PLL bandwidth to filter the quantization noise. While a two-point modulation (TPM) scheme can decouple the conflicting requirements on the PLL bandwidth [4-6], the gain or timing mismatch between the two modulation paths and limited resolution of the DSM-based FD can still limit the chirp linearity, especially when one tries to push the chirp slope faster.
Thermo-mechanical study of a 2.5D passive silicon interposer technology: Experimental, numerical and In-Situ stress sensors developments

Thermo-mechanical stresses have proven to be a critical issue in a typical interposer integration and assembly flow. However the nature of passive interposer makes the integration of MOS-based stress sensors impossible. New methods are required. Using a coupling strategy between 3D Finite Element Models (FEM) and physical characterization, a method based on electrical measurement of passive stress sensors is presented here to assess stress at die- and wafer-level. Innovative combination of passive stress sensors based on rosettes of serpentine resistors have been developed and embedded to quantify local strain states in a typical interposer die. Their principle and implementation at a copper interconnect level of interposer are presented in this paper. Preliminary results are depicted, including first electrical measurements of these sensors. Electrical characterization has been performed after the back-side interconnection fabrication of the interposer. A local sensibility of each copper serpentine is highlighted. Discrepancies in the resistance values of orthogonal resistors could indicate local deformations to the environment of sensors, such as TSV's and bump pads. However, the order of magnitude of relative variation of resistance values is unexpectedly high and requires further investigations.
Beyond Dichotomy: The Curvilinear Relationship between Social Responsibility and Financial Performance

A central and contentious debate in many literatures concerns the relationship between financial and social performance. We advance this debate by measuring the financial–social performance link mutual funds that practice socially responsible investing (SRI). SRI fund managers have an array of social screening strategies from which to choose. Prior studies have not addressed this heterogeneity within SRI funds. Combining modern portfolio and stakeholder theories, we hypothesize that the financial loss borne by an SRI fund due to poor diversification is offset as social screening intensifies because better-managed and more stable firms are selected into its portfolio. We find support for this hypothesis through an empirical test on a panel of 61 SRI funds from 1972 to 2000. The results show that as the number of social screens used by an SRI fund increases, financial returns decline at first, but then rebound as the number of screens reaches a maximum. That is, we find a curvilinear relationship, suggesting that two long-competing viewpoints may be complementary. Furthermore, we find that financial performance varies with the types of social screens used. Community relations screening increased financial performance, but environmental and labor relations screening decreased financial performance. Based on our results, we suggest that literatures addressing the link between financial and social performance move toward in-depth examination of the merits of different social screening strategies, and away from the continuing debate on the financial merits of either being socially responsible or not.
Selenocysteine derivative overcomes TRAIL resistance in melanoma cells: evidence for ROS-dependent synergism and signaling crosstalk

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), as one of the most promising targeted drug for new cancer therapeutics, is limited in clinical application by the evolution of resistance in many cancer cell lines, especially in malignant melanoma. Thus, it is urgently needed to identify chemosensitizers to enhance the apoptotic inducing efficacy of TRAIL and overcome resistance of malignant melanoma cells. Herein, we reported that 3,3′-diselenodipropionic acid (DSeA), a Selenocysteine derivative, could synergistically enhance the growth inhibitory effect of TRAIL on A375 melanoma cells though induction of ROS-dependent apoptosis with involvement of PTEN-mediated Akt inactivation and DNA damage-mediated p53 phosphorylation, which subsequently activated mitochondrial and death receptor apoptotic pathways. Moreover, silencing of p53 down-regulated the expression levels of p53-inducible genes, and effectively blocked the cell apoptosis. Suppression of PI3K significantly increased the apoptotic cell death. In contrast, antioxidants effectively reversed the cell apoptosis through regulation of Akt and p53 signaling pathways. Taken together, the combination of DSeA and TRAIL could be a novel strategy to overcome TRAIL resistance in malignant melanoma, and DSeA may be candidates for further evaluation as a chemosensitizer in clinical trails.
Directed Functional Brain Connectivity Based on EEG Source Imaging: Methodology and Application to Temporal Lobe Epilepsy

Objective: The importance of functional brain connectivity to study physiological and pathological brain activity has been widely recognized. Here, we aimed to 1) review a methodological pipeline to investigate directed functional connectivity between brain regions using source signals derived from high-density EEG; 2) elaborate on some methodological challenges; and 3) apply this pipeline to temporal lobe epilepsy (TLE) patients and healthy controls to investigate directed functional connectivity differences in the theta and beta frequency bands during EEG epochs without visible pathological activity. Methods: The methodological pipeline includes: EEG acquisition and preprocessing, electrical-source imaging (ESI) using individual head models and distributed inverse solutions, parcellation of the gray matter in regions of interest, fixation of the dipole orientation for each region, computation of the spectral power in the source space, and directed functional connectivity estimation using Granger-causal modeling. We specifically analyzed how the signal-to-noise ratio (SNR) changes using different approaches for the dipole orientation fixation. We applied this pipeline to 20 left TLE patients, 20 right TLE patients, and 20 healthy controls. Results: Projecting each dipole to the predominant dipole orientation leads to a threefold SNR increase as compared to the norm of the dipoles. By comparing connectivity in TLE versus controls, we found significant frequency-specific outflow differences in physiologically plausible regions. Conclusion: The results suggest that directed functional connectivity derived from ESI can help better understand frequency-specific resting-state network alterations underlying focal epilepsy. Significance: EEG-based directed functional connectivity could contribute to the search of new biomarkers of this disorder.
Induction of Intracellular Superoxide Radical Formation by Arachidonic Acid and by Polyunsaturated Fatty Acids in Primary Astrocytic Cultures

Abstract: The effects of arachidonic acid and other polyunsaturated fatty acids (PUFAs) on both oxidative and metabolic perturbation were studied in primary cultures of rat cerebral cortical astrocytes. In the presence of 0.1 mM arachidonic acid, the rate of the reduction of nitroblue tetrazoiium (NBT) to nitroblue formazan (NBF) was stimulated from 0.65 ± 0.10 to 1.43 ± 0.15 and from 0.092 ± 0.006 to 0.162 ± 0.009 nmol/min/mg protein in intact and broken cell preparations, respectively. The rate of superoxide radical formation, as measured by the superoxide dismutase (SOD)‐inhibitable NBT reduction was 0.042 nmol/mg protein in broken cells and was negligible in intact cells. The latter is due to the impermeability of SOD into the intact cell preparation. NBF formation in intact astrocytes stimulated by arachidonic acid was both time‐ and dosedependent. Other PUFAs, including linoleic acid, linolenic acid, and docosahexaenoic acid, were also effective in stimulating NBF formation in astrocytes, whereas saturated palmitic acid and monounsaturated oleic acid were ineffective. Similar effects of these PUFAs were observed in ma‐londialdehyde formation in cells and lactic acid accumulation in incubation medium. These data indicate that both membrane integrity and cellular metabolism were perturbed by arachidonic acid and by other PUFAs. The sites of superoxide radical formation appeared to be intracellular and may be associated with membrane phospholipid domains, because liposome‐entrapped SOD, which was taken up by intact astrocytes, reduced the level of superoxide radicals and lactic acid content, whereas free SOD was not effective.
The Effects of Twelve Weeks of Tai Chi Practice on Anxiety in Stressed But Healthy People Compared to Exercise and Wait-List Groups-A Randomized Controlled Trial.

OBJECTIVE This randomized controlled trial was undertaken to determine whether 12 weeks of Tai Chi (TC) practice can reduce anxiety in healthy but stressed people. METHOD Fifty participants were randomized into TC (n=17), exercise (n=17), and wait-list (WL) groups (n=16). Outcome measures used were State Trait Anxiety Inventory, Perceived Stress Scale 14 (PSS14), blood pressure and heart rate variability, visual analogue scale (VAS), and Short Form 36. RESULTS Significant improvements were observed from baseline for both TC and exercise groups for both state (p <0.01) and trait (p <0.01) anxiety, PSS14 (p <0.01), VAS (p <0.01), mental health domain (p <0.01), and vitality domain (p <0.01). Superior outcomes were also observed for TC when compared with WL for state and trait anxiety (p <0.01) and mental health domain (p <0.05). CONCLUSION TC reduces stress levels in healthy individuals and provides a safer, cost effective, and less physically vigorous alternative to exercise.
Is Anterior Cruciate Reconstruction Superior to Conservative Treatment?

Abstract Not all patients who have a rupture of the anterior cruciate ligament (ACL) elect to have surgical reconstruction. The aim of this study was to assess the short-to-medium-term results of patients who chose conservative management in comparison to patients who had reconstructive surgery within the same time period. Sixty-three patients with an ACL injury were retrospectively studied. Forty patients were managed, according to patient choice, with ACL reconstruction and 23 conservatively. Four validated questionnaires were used to assess general and knee-specific function in a cohort with a median age of 32 years and a median follow-up period of 38 months. Patients were matched on demographic variables except for gender. There were no statistically significant differences in the outcome measures, and the majority of patients would proceed with the same treatment in the event the control leg became injured. Patients who elect to have conservative management of an ACL rupture can achieve similar function and satisfaction to those who elect to have reconstruction. Until a large randomized controlled trial is conducted, patients need to be made aware of the merits of both management strategies and the lack of evidence of superiority of one over the other.
A structured and scalable test access architecture for TSV-based 3D stacked ICs

New process technology developments enable the creation of three-dimensional stacked ICs (3D-SICs) interconnected by means of Through-Silicon Vias (TSVs). This paper presents a DfT test access architecture for such 3D-SICs that allows for both pre-bond die testing and post-bond stack testing. The DfT architecture is based on a modular test approach, in which the various dies, their embedded IP cores, the inter-die TSV-based interconnects, and the external I/Os can be tested as separate units to allow optimization of the 3D-SIC test flow. The architecture builds on and reuses existing DfT hardware at the core, die, and product level. It adds a die-level wrapper, which is based on IEEE 1500, with the following novel features: (1) dedicated probe pads on the non-bottom dies to facilitate pre-bond die testing, (2) TestElevators that transport test control and data signals up and down during post-bond stack testing, and (3) a hierarchical Wrapper Instruction Register (WIR) chain. The paper also hints at opportunities for optimization and standardization of this architecture.
Pharmacokinetics of lansoprazole, amoxicillin and clarithromycin after simultaneous and single administration.

In a randomized, double-blind, placebo-controlled, four-way crossover study, possible influences of the triple therapy with amoxicillin, clarithromycin and the proton pump inhibitor lansoprazole on the pharmacokinetics of each of the drugs and the active 14-OH-clarithromycin metabolite were assessed. Twelve Helicobacter pylori-negative healthy male volunteers (age 27 +/- 4.3 years; creatinine clearance 7.0 +/- 2.0 L/h) were given lansoprazole 30 mg, amoxicillin 1 g and clarithromycin 500 mg, alone and in triple combination. Drug elimination intervals were at least 9 days between the dosing periods. The study medication was administered twice daily for 4 days. On the fifth day of each period, drugs were only given once in the morning, and blood and urine samples were collected for 12 h. The concentrations of the three substances administered, and 14-OH-clarithromycin, were determined by validated HPLC methods. Alterations in the serum kinetics were found for lansoprazole and the active 14-OH-clarithromycin metabolite (all data expressed as mean +/- S.D.). For lansoprazole, the elimination half-life (t(1/2)) was significantly prolonged (1.46 versus 1.7 h, P < 0.05) and the area under the concentration-time curve from 0 to 8 h (AUC(0-8)) was significantly increased (3.65 versus 4.59 mg.h/L, P < 0.05) by combination of the drugs. For 14-OH-clarithromycin, the peak concentration (C(max)) was 0.95 versus 1.18 mg/L and the AUC from 0 to 12 h (AUC(0-12)) was 8.3 versus 10.5 mg.h/L (augmented significantly, P < 0.05). The amoxicillin concentrations were slightly elevated by concomitant administration of lansoprazole and clarithromycin but without statistical significance (11.1 versus 12.6 mg/L). For clarithromycin, the time to maximum concentration of drug in serum (T(max)) was increased (2.73 versus 3.31 h, P < 0.05), whereas AUC and C(max) remained unchanged. Simultaneous administration of lansoprazole, amoxicillin and clarithromycin increases the serum concentrations of lansoprazole and the active 14-OH-clarithromycin metabolite significantly. These effects were not so pronounced as to have any therapeutic influence, making dosage adjustment unnecessary.
Epidermal stem cells: practical perspectives and potential uses

Throughout adult life, the epidermis and the hair follicle undergo a perpetual cycle of growth, regression and rest. Stem cells in the epidermis not only ensure the maintenance of epidermal homeostasis and hair regeneration, but also contribute to repair of the epidermis after injury. These stem cells lie within specific niches in the hair follicle and the epidermis. The availability of monoclonal antibodies that can be used on formalin‐fixed paraffin‐embedded tissue has greatly facilitated the use of this methodology as an adjunct to uncovering stem cell niches. In this review, we attempt to provide an overview of the potential markers available to identify and study stem cells in an effort to providing a better understanding of the pathogenesis of skin diseases including disorders of hair loss and malignancies. The potential uses of these markers in prognosis and in expanding the therapeutic options in several disorders will also be addressed.
In vitro microvessels for the study of angiogenesis and thrombosis

Microvascular networks support metabolic activity and define microenvironmental conditions within tissues in health and pathology. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of complex vascular phenomena, including angiogenesis and thrombosis. We have engineered living microvascular networks in three-dimensional tissue scaffolds and demonstrated their biofunctionality in vitro. We describe the lithographic technique used to form endothelialized microfluidic vessels within a native collagen matrix; we characterize the morphology, mass transfer processes, and long-term stability of the endothelium; we elucidate the angiogenic activities of the endothelia and differential interactions with perivascular cells seeded in the collagen bulk; and we demonstrate the nonthrombotic nature of the vascular endothelium and its transition to a prothrombotic state during an inflammatory response. The success of these microvascular networks in recapitulating these phenomena points to the broad potential of this platform for the study of cardiovascular biology and pathophysiology.
Mental illness and the late Victorians: a study of patients admitted to three asylums in York, 1880–1884

Synopsis The case histories of the patients newly admitted to the Retreat Asylum in York between 1880–1884 were examined. Most patients were aged under 50 years, single and non-Quaker, and a majority satisfied the Research Diagnostic Criteria for a diagnosis of schizophrenia or affective disorder. It was found that 72·9% of the patients were deluded, the most common delusions being of persecution, grandeur and guilt; in 34·9% of the deluded patients, the delusion had a religious content. Suicidal ideation was recorded in the case records of 31·4% of the patients. Drug therapy was commonly prescribed, a history of assault on other patients or asylum staff was recorded in 38·1% of the patients, and 11% of patients were force fed at some stage during their illness. Within a year of admission 49·1% of the patients were discharged, the prognosis being better for patients with an affective illness than for schizophrenia, but 31·4% remained in the asylum for five or more years. The characteristics, alleged causes of mental illness, and treatment and outcome of the Retreat patients were compared with those of patients admitted during the same period to the two other York asylums which served different socio-economic groups of the population. Mortality rates were higher in the asylum admitting mainly pauper patients, and possible reasons for this are explored.
Prefabrication of Mucosa‐Lined Flaps: A Preliminary Study in the Pig Model

&NA; There is a need in reconstructive surgery for flaps lined by nonkeratizing stratified squamous epithelium or mucous membrane. Applications could be found in nasal, oral, genital, and esophageal reconstruction and even in reconstruction of hollow intra‐abdominal tubes. Prefabrication of lined flaps has so far been limited to a pretransfer grafting of split‐thickness skin. However, in certain situations this does not satisfy’ the primary requirement of replacing “like with like. ” Also, the availability of donor sites for harvesting mucosa is limited. The present study involves prefabrication of mucosa‐lined flaps without causing donor site morbidity. The study was carried out on six mini‐Hartford pigs. Buccal mucosa was harvested from the cheeks; the sheet was divided into several smaller graft pieces of 1 to 2 cm2 area. These graft pieces were then applied to the deep fascia at a distance of 5 to 15 mm from one another, also to galea, and to the undersurface of skin flaps. The grafted area was isolated from the opposing surface with a silicone sheet or Marlex mesh. The grafts were allowed to take and, it was hoped, merge together to form a sheet graft of dimensions greater than those of the original. Two to 7 weeks after the initial grafting, the skin flap was elevated; the mucosal grafts were observed macroscopically for take and surface area and microscopically to confirm that the lining was indeed mucosa. The mucosa took well on both the fascia and galea and also on the undersurface of the skin; it enlarged in size, and the small pieces became confluent to form a single sheet. The increase in surface area varied from 33 percent at 11 days postgrafting to a maximum of 238 percent after 7 weeks. All pigs had positive cultures from the mucosa before implantation but only one developed gross infection leading to partial graft loss.